Perineal ultrasound to assess the urethral spatial movement in stress urinary incontinence in women.

BACKGROUND: Perineal ultrasound as a non-invasive method for the diagnosis of female stress urinary incontinence has attracted more and more attention. However, the criteria for stress urinary incontinence in women using perineal ultrasound have not been fully established. Our study aimed to evaluate characteristics of the urethral spatial movement with perineal ultrasonography. METHODS: A total of 136 female patients with stress urinary incontinence and 44 controls were enrolled. Stress urinary incontinence was diagnosed using the International Consultation on Incontinence Questionnaire Short Form, medical history and physical examination, and severity was assessed using a 1 h pad test. We described the mobility of four equidistant points (A-D) located along the urethra length. The retrovesical and urethral rotation angles were measured using perineal ultrasonography at rest and during the maximal Valsalva maneuver. RESULTS: Patients with stress urinary incontinence showed a more significant vertical movement at Points A, B and C than controls. The mean variations in the retrovesical angle were significantly larger in patients with stress urinary incontinence at rest and during the Valsalva maneuver than in controls (21.0 ± 16.5° vs. 14.7 ± 20.1°, respectively). The cut-off value for the retrovesical angle variation was 10.7° with 72% sensitivity and 54% specificity. There was a receiver-operating characteristic curve area of 0.73 and 0.72 for Points A and B, respectively. A cut-off of 10.8 mm, and 9.4 mm provided 71% sensitivity and 68% specificity and 67% sensitivity and 75% specificity, respectively. CONCLUSIONS: The spatial movement of the bladder neck and proximal urethra, and variations in the retrovesical angle may be correlated with clinical symptoms and facilitate to the assessment of SUI.

The potential involvement of MRP5 pump in urethral dysfunction in streptozotocin-induced diabetic rats.

PURPOSE: To examine the effects of i.v. administration of MK-571, a MRP4/5 pump inhibitor, on urethral function in the urethane-anesthetized rat, and the changes of urethral multidrug resistance protein 5 (MRP5) pump in streptozotocin (STZ)-induced diabetes mellitus (DM) rats. METHODS: Isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were carried out in normal control (NC) group and 8week DM groups under urethane anesthesia. When stable rhythmic bladder contractions were showed, UPP parameters were recorded after successive administration of various dose of MK-571. Additionally, urethral cyclic guanosine monophosphate (cGMP) protein level was evaluated by ELISA, and changes of MRP5 pump and neurogenic nitric oxide synthase (nNOs) in the urethra were examined with immunohistochemical staining and Western blot analysis. RESULTS: In NC group, UPPnadir was significantly decreased but UPP change increased after administration of MK-571, while no significant differences in UPP parameters were observed in 8-week DM group. Furthermore, urethral MRP5 protein level was up-regulated, whereas urethral cGMP and nNOS protein levels were down-regulated in 8-week DM group. CONCLUSIONS: MK-571 could not restore NO-mediated urethral relaxation dysfunction in DM rats, which may be attributed to the up-regulation of urethral MRP5 pump, and thus decrease of intracellular cGMP concentration in the urethra. These novel results would be useful for a better understanding of DM-related lower urinary tract dysfunction LUT (LUTD). Also, they could be helpful to study the importance of MRP pumps in the control of urethral relaxation mechanisms under physiological and pathological states.

Improvement of urethral dysfunction by 5-HT1A receptor agonist NLX-112 in diabetic rats.

OBJECTIVE: To examine the effects of the selective 5-HT1A receptor agonist, NLX-112, on urethral function in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Female Sprague-Dawley rats (n = 32) were divided into two groups: rats with type 1 diabetes mellitus (T1DM) and age-matched normal control rats (NC). T1DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Isovolumetric cystometry and urethral perfusion pressure (UPP) were evaluated 10 weeks postinjection in rats (n = 9 per group). The selective 5-HT1A receptor antagonist, WAY-100635 maleate salt, was administered after NLX-112 hydrochloride dose-response curve was generated (intravenously). The remaining rats were used for immunofluorescence and Western blot assays. RESULTS: Compared to controls, type 1 diabetic rats (T1D rats) had lower maximal intravesical pressure (IP max) and UPP changes. In T1D rats, NLX-112 hydrochloride (0.003-1.0 mg/kg) induced dose-dependent decreases in UPP nadir, IP max, high-frequency oscillations (HFOs) rate; and increases in UPP change and HFOs amplitude. WAY-100635 maleate salt (0.3 mg/kg) partially or completely reversed the NLX-112-induced changes. Immunofluorescence revealed that 5-HT1A receptors were found in the L6-S1 spinal cord dorsolateral nucleus, but the expression was significantly higher in the T1D rats. Additionally, Western blot showed there were significantly more 5-HT1A receptors in the ventral L6-S1 spinal cord of T1D rats. CONCLUSIONS: Urethral dysfunction in T1D rats was improved by NLX-112. 5-HT1A receptors were upregulated in the dorsolateral nucleus of L6-S1 spinal cord in T1D rats. These findings suggest that NLX-112 may constitute a novel therapeutic strategy to treat diabetic urethral dysfunction.

Numerical investigation of urethra flow characteristics in benign prostatic hyperplasia.

BACKGROUND AND OBJECTIVE: Conventional practice includes a limited depiction of urethral pressure and flows based on fragmented gross clinical observations. However, with technological advancements in simulations, computational fluid dynamics (CFD) can provide an alternative approach to predict the bladder pressure with a concordant quantitative flow field in the urethra. Thus, this study aims to comprehensively analyze the urine flow characteristics in various urethra models using simulations. METHODS: Three-dimensional urethra models were constructed for seven specific subjects based on clinical radiographs. Simulations with Reynolds averaged Navier-Stokes model were performed to quantitatively investigate the urine flow under various volume flow rate of voided urine. RESULTS: Under benign prostatic hyperplasia, the spindle shape of the prostatic urethra (PRU) generates wake flow. The wake flow was also observed in several regions downstream of the PRU, depending on the urethra shape. This wake flow resulted in total pressure loss and urinary tract dysfunction. When comparing pre- and post-operative urethra models, the bladder pressure decreased by 14.98% in P04 and 4.67% in P06. Thus, we identified variability between surgical results of patients. The bladder pressure according to the volume flow rate of voided urine was investigated using simulations and the theoretical consideration based on hydrodynamics. In theoretical consideration, the bladder pressure was expressed as a second-order polynomial for volume flow rate. These results concur with the simulation results. CONCLUSION: Numerical simulation can describe the urine flow field in the urethra, providing the possibility to predict the bladder pressure without requiring painful, invasive interventions, such as cystoscopy. Furthermore, effective treatments to improve urination function can be formulated to be patient-specific, by detecting causes and problem regions based on quantitative analysis and predicting post-surgical outcomes.

Pressure transmission theory-The Rasputin of incontinence.

BACKGROUND: Enhorning's pressure transmission theory (PTT), though mortally wounded by multiple invalidations from the 1990 Integral Theory of female urinary incontinence (IT), like Rasputin, continues to survive as a theory for continence and incontinence. AIM: To examine the questions: How has the PTT survived? What is its contribution to knowledge? METHODS: Eleven different invalidations are presented based on images, pressure readings, clinical examples, experiments by the author, and others, for example, flow mechanics, finite element models, and surgical operations. RESULTS: Each of the 11 invalidations prima facie invalidate the PTTs of enhorning and others. CONCLUSIONS: "How has the PTT survived?" Having provided a plausible explanation for all abdominal stress urinary incontinence operations since 100 years, PTT, unsurprisingly, like climate change today, had become an entrenched convention which abdicated the need for midurethral sling (MUS) surgeons to learn the very different functional surgical anatomy underlying the MUS. "Has the PTT progressed knowledge, or retarded it?" This lack of knowledge by the surgeons of how and why the MUS works could be held responsible for the large number of major complications reported by the TVT: including, transected urethras, obturator nerve damage, perforation of external iliac vessels, more than 20 deaths. The role of the sling is to strengthen the pubourethral neoligament to prevent the urethra opening out under stress, not to elevate it. Elevating the sling remains the major cause of the most frequent complication of the MUS today, postoperative urinary retention.

Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia.

Pathogenic variation in the X-linked gene FLNA causes a wide range of human developmental phenotypes. Loss-of-function is usually male embryonic-lethal, and most commonly results in a neuronal migration disorder in affected females. Gain-of-function variants cause a spectrum of skeletal dysplasias that present with variable additional, often distinctive, soft-tissue anomalies in males and females. Here we present two, unrelated, male individuals with novel, intronic variants in FLNA that are predicted to be pathogenic. Their phenotypes are reminiscent of the gain-of-function spectrum without the skeletal manifestations. Most strikingly, they manifest urethral anomalies, cardiac malformations, and keloid scarring, all commonly encountered features of frontometaphyseal dysplasia. Both variants prevent inclusion of exon 40 into the FLNA transcript, predicting the in-frame deletion of 42 amino acids, however the abundance of FLNA protein was equivalent to that observed in healthy individuals. Loss of these 42 amino acids removes sites that mediate key FLNA functions, including binding of some ligands and phosphorylation. This phenotype further expands the spectrum of the FLNA filaminopathies.

Therapeutic efficacy of biofeedback pelvic floor muscle exercise in women with dysfunctional voiding.

Dysfunctional voiding (DV), a voiding dysfunction due to hyperactivity of the external urethral sphincter or pelvic floor muscles leading involuntary intermittent contractions during voiding, is not uncommon in neurologically normal women with lower urinary tract symptoms (LUTS). We aimed to investigate the therapeutic efficacy of biofeedback pelvic floor muscle training (PFMT) in female patients with DV and to identify the therapeutic efficacy. Thirty-one patients diagnosed with DV. All participates completed the 3-month biofeedback PFMT program, which was conducted by one experienced physiotherapist. At 3 months after treatment, the assessment of treatment outcomes included global response assessment (GRA), and the changes of clinical symptoms, quality of life index, and uroflowmetry parameters. 25 (80.6%) patients had successful outcomes (GRA ≥ 2), and clinical symptoms and quality of life index significantly improved after PFMT. Additionally, uroflowmetry parameters including maximum flow rate, voided volume, voiding efficiency, total bladder capacity, voiding time, and time to maximum flow rate significantly improved after PFMT treatment. Patients with the history of recurrent urinary tract infection in recent 1 year were found to have unsatisfied therapeutic outcomes. In conclusion, biofeedback PFMT is effective in female patients with DV with significant improvements in clinical symptoms, quality of life, and uroflowmetry parameters. The history of urinary tract infection in recent 1 year is a negative predictor of successful outcome.

Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence.

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.

Therapeutic Effects of Urethral Sphincter Botulinum Toxin A Injection on Dysfunctional Voiding with Different Videourodynamic Characteristics in Non-Neurogenic Women.

Although female dysfunctional voiding (DV) is common in urological practice, it is difficult to treat. This study evaluated the therapeutic efficacy of urethral botulinum toxin A (BoNT-A) on non-neurogenic female DV. Based on the videourodynamic study (VUDS), the DV was classified into three subgroups according to the obstructive site. A successful treatment outcome was defined as an improvement of voiding efficiency by 10% and reported global response assessment by ≥1. The study compared therapeutic efficacy, baseline urodynamic parameters, and changes in urodynamic parameters between the treatment success and failure groups and among three DV subgroups. Predictive factors for successful treatment were also investigated. A total of 81 women with DV were categorized into three groups: 55 (67.9%) had mid-urethral DV, 19 (23.5%) had distal urethral DV, and 7 (8.6%) had combined BN dysfunction and mid-urethral DV after BN transurethral incision. The treatment outcome was successful for 55 (67.9%) patients and failed for 26 (32.1%). Successfully treated patients had a significant decrease of detrusor pressure, post-void residual volume, and bladder outlet obstruction index, as well as an increase in voiding efficiency at follow-up versus the treatment failure group. The logistic regression of urodynamic parameters and clinical variables revealed that a greater volume of first sensation of filling predicts a successful BoNT-A treatment outcome (p = 0.047). The urethral BoNT-A injection is effective in treating non-neurogenic women with DV, with a success rate of 67.9%. The videourodynamic characteristics of DV may differ among patients but does not affect the treatment outcome.

Absceso recurrente de la glándula de Skene en paciente joven: reporte de caso / Recurrent abscess of Skene's gland in a young patient: case report

Las glándulas de Skene se encuentran localizadas en la región lateral de la uretra distal, por lo general son asintomáticas sin embargo en ciertas ocasiones pueden obstruirse creando acumulación de líquido en su interior, el cual provoca síntomas, abscesos o quistes que pueden ser tratados con tratamiento médico o quirúrgico. En este caso se presenta una mujer que consulta en múltiples ocasiones por salida de secreción purulenta de la glándula de skene, ya tratada con esquemas antibióticos en 3 ocasiones, sin embargo al persistir con recurrencia de absceso a pesar de antibioterapia se realiza abordaje quirúrgico para resección de la misma (AU)

Skene's glands are located in the lateral region of the distal urethra, are usually asymptomatic however on certain occasions they can become clogged creating accumulation of fluid inside, which causes symptoms, abscesses or cysts They can be treated with medical or surgical treatment. In this case, a woman is presented who consults in multiple sometimes due to discharge of purulent secretion from the skene's gland, she already treated with antibiotic regimens on 3 occasions, however When abscess recurrence persists despite antibiotic therapy, performs surgical approach for its resection

Long-term functional outcomes of artificial urinary sphincter (AMS 800™) implantation in women aged over 75 years and suffering from stress urinary incontinence caused by intrinsic sphincter deficiency.

PURPOSE: To assess the outcomes after artificial urinary sphincter (AUS) implantation in older women aged over 75 years. METHODS: A monocentric retrospective study included all non-neurological women aged over 75 years suffering from stress urinary incontinence (SUI) due to intrinsic sphincter deficiency and undergoing an AUS placement between 1991 and 2015. Early postoperative complications were reported according to Clavien-Dindo classification. Continence, defined as no pad use, was assessed at the end of follow-up. Explantation, revision and deactivation rates of the AUS were reported. A Kaplan-Meier survival curve was generated to evaluate the survival rate of the device without revision or explantation. RESULTS: Among 393 AUS implantations, a total of 45 patients, median age 77 years (IQR 75-79), were included. Twenty-six early postoperative complications occurred in 18 patients (40%) patients. All were minor Clavien grades (I-II) except one (grade IVa). Median follow-up was 36 months (IQR 16-96). Overall, 32 women (71.1%) still had their AUS in place at the end of the follow-up, without revision or explantation. The AUS was definitively removed in four (8.9%). The AUS required revisions in nine (20%) women. The 5- and 10-year survival rates of the device without revision or explantation were 78 and 50%, respectively. Three patients (6.7%) had their AUS deactivated. At last follow-up, in an intention-to-treat analysis, the continence rate was 68.9%. CONCLUSION: In women aged over 75-years-old, suffering from SUI, the AUS provides satisfactory functional results comparable to the general population.

Lower Urinary Tract Function in Patients with Inflammatory Encephalomyelopathy: Characteristics of Urodynamics, Neurological Deficits and Magnetic Resonance Imaging.

OBJECTIVE: To report the clinical data in a large population of patients affected by inflammatory encephalomyelopathy. MATERIAL AND METHODS: We retrospectively reviewed the medical history, imaging studies and urodynamic findings in a series of 87 consecutive patients with inflammatory encephalomyelopathy. Age at disease onset ranged from 3 to 76 years with an average of 35.4 years. The type of bladder dysfunction, neurological impairment and spinal magnetic resonance imaging were assessed. Upper urinary tract was evaluated. The urological complications and subsequent management were reported. RESULTS: The mean follow-up was 3.0 years (range from 0.5 to 6.6 yrs). Initial evaluation revealed detrusor overactivity in 53 patients (61.1%), detrusor underactivity in 34 patients (39.1%), detrusor leak point pressure greater than 40 cm water and decreased compliance in 29.9% of patients. At the latest follow-up, a total of 64 patients (73.6%) had persistent bladder dysfunction requiring treatment, mainly presenting as urinary incontinence and incomplete bladder emptying. Around 18.8% patients (13/69) experienced upper urinary tract changes. The location of spinal lesions may correspond with the type of bladder dysfunction. Higher abnormal sensory levels are associated with poor bladder recovery. CONCLUSION: Persistent bladder dysfunction is common in inflammatory encephalomyelopathy and tend to change with the progression of disease. Evaluation must be instituted at early onset of the disease and ongoing surveillance should be offered through the entire disease process. Management can be tailored individually to the urodynamic findings for optimal preservation of bladder and renal function.

Effect of aging on lower urinary tract symptoms and urodynamic parameters in women.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are common in women. However, due to multifactorial etiologies, it is difficult to determine the prevalence, and functional changes with age. The aim of this study is to assess the effect of age on female LUTS, urethral and bladder function after their midlife. MATERIALS AND METHODS: This was an observational cohort study conducted at a tertiary referral medical center. Women who visited for bothersome LUTS, valid quality of life questionnaires, and urodynamic tests were recruited into the this study. Patients The patients were divided into four groups (<50, 50-59, 60-69, and >69 years). All LUTS, and urodynamic parameters were reviewed, and compared between groups. RESULTS: A total of 364 women were enrolled and analyzed. The urodynamic tests showed the that maximal cystometric bladder capacity, the average and maximal urine flow rate, and pressure of detrusor contractility at maximal urine flow rate were all significantly decreased with age. Besides, the voiding time, and post-voiding residual urine volume significantly increased with age. For urethral competence, the maximal urethral closure pressure deteriorated with age. All storage symptoms did not change with age, except for nocturnal enuresis. However, the effect of age on some voiding symptoms significantly increased with age, including straining to void, hesitancy, and intermittency. CONCLUSIONS: Lower urinary tract symptoms, bladder and urethral functions change with age, particularly voiding function. Physicians should be aware of the aging process when counseling and before implementing management strategies, particularly for older people.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model.

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity and the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4, and 6 wk post-SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, nonvoiding contractions were confirmed at 2 wk post-SCI and did not increase over time to 6 wk. In 2-wk SCI mice, EUS-EMG measurements revealed detrusor sphincter dyssynergia, but periodic EMG reductions during bladder contraction were hardly observed. At 4 wk, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency. At 6 wk, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of transient receptor potential vanilloid 1 and acid-sensing ion channels (ASIC1-ASIC3) in SCI mice with a decrease of ASIC2 and ASIC3 at 6 wk compared with 4 wk, whereas Piezo2 showed a slow increase at 6 wk. Protein assay showed SCI-induced overexpression of bladder brain-derived neurotrophic factor with a time-dependent decrease post-SCI. These results indicate that detrusor overactivity is established in the early phase, whereas detrusor sphincter dyssynergia is completed later at 4 wk with an improvement at 6 wk post-SCI, and that mechanosensitive channels may be involved in the time-dependent changes.NEW & NOTEWORTHY This is the first paper to evaluate the time-course changes of bladder dysfunction associated with mechanosensitive channels in a mouse model.

On Structure-Function Relationships in the Female Human Urethra: A Finite Element Model Approach.

Remarkably little is known about urethral striated and smooth muscle and vascular plexus contributions to maintaining continence or initiating micturition. We therefore developed a 3-D, multiphysics, finite element model, based on sequential MR images from a 23-year-old nulliparous heathy woman, to examine the effect of contracting one or more individual muscle layers on the urethral closure pressure (UCP). The lofted urethra turned out to be both curved and asymmetric. The model results led us to reject the current hypothesis that the striated and smooth muscles contribute equally to UCP. While a simulated contraction of the outer (circular) striated muscle increased closure pressure, a similar contraction of the large inner longitudinal smooth muscle both reduced closure pressure and shortened urethral length, suggesting a role in initiating micturition. When age-related atrophy of the posterior striated muscle was simulated, a reduced and asymmetric UCP distribution developed in the transverse plane. Lastly, a simple 2D axisymmetric model of the vascular plexus and lumen suggests arteriovenous pressure plays and important role in helping to maintain luminal closure in the proximal urethra and thereby functional urethral length. More work is needed to examine interindividual differences and validate such models in vivo.

The extracellular matrix molecules versican and hyaluronan in urethral and vaginal tissues in stress urinary incontinence.

PURPOSE: Abnormal extracellular matrix (ECM) changes are correlated with stress urinary incontinence (SUI). The ECM components versican (Vcan) and hyaluronan (HA) play key roles in regulating tissue inflammation and maintaining connective tissue homeostasis. We analyzed the localization and expression of these ECM components in urethral and vaginal tissues from a rat model of urinary incontinence and from human clinical specimens. METHODS: Nulliparous rats underwent vaginal distension (VD), a rodent model of SUI, or a sham procedure. Tissues were harvested from six rats per group at days 1, 4, and 21 for immunohistochemistry and RNA expression analysis of ECM components. Periurethral vaginal samples from female patients with SUI were also examined. RESULTS: High-intensity staining for Vcan was observed 1 day after procedure in both control and VD animals. This level of abundance persisted at day 4 in VD compared to control, with concurrent reduced messenger RNA (mRNA) expression of the Vcan-degrading enzymes ADAMTS5 and ADAMTS9 and reduced staining for the Vcan cleavage epitope DPEAAE. Abundance of HA was not different between VD and control, however mRNA expression of the HA synthase Has2 was significantly reduced in VD tissues at day 4. Abundant Vcan staining was observed in 60% of SUI patient samples, which was strongest in regions of disrupted elastin. CONCLUSION: Reduction of Vcan-degrading enzymes and HA synthases at day 4 postsurgery indicates a potential delay in ECM turnover associated with SUI. Abundant Vcan is associated with inflammation and elastin fiber network disruption, warranting further investigation to determine its role in SUI pathogenesis.

A novel management for postprostatectomy urinary incontinence: platelet-rich plasma urethral sphincter injection.

Platelet-rich plasma (PRP) is the most innovative blood-derived product used in regenerative medicine. We aimed to investigate the therapeutic efficacy of PRP urethral sphincter injection for the management of postprostatectomy incontinence (PPI). In total, 28 PPI patients with a mean age of 71.8 ± 8.9 years were prospectively enrolled. They received four PRP urethral sphincter injections each month. The clinical outcomes were assessed 3 months after the fourth injection as posttreatment Global Response Assessment (GRA) score, the newly designed visual analogue scale of stress urinary incontinence (VAS of SUI), and in urodynamic parameters. After injections, the posttreatment median GRA with quartiles was 2.0 (1.0, 2.0). Overall, six (21.4%) patients achieved complete continence and pad-free status, 20 (71.4%) achieved successful outcome (GRA score ≥ 2), and 26 (92.9%) showed clinical improvement (GRA score ≥ 1). The VAS of SUI significantly improved from 6.5 (5.0, 8.0) to 3.5 (2.0-5.8) (p < 0.001) as well as abdominal leak point pressure, from 57.5 (50.0, 115.0) to 126.0 (68.3, 150.0), (p = 0.004). After repeated PRP urethral sphincter injections, the SUI severity reduced significantly with high success rates. There was no major adverse event, except three patients with mild hematuria and micturition pain. In conclusion, PRP urethral sphincter injection is safe and effective as a novel management of PPI.

Deletion of the lysyl oxidase-like 1 gene induces impaired elastin fiber synthesis and inefficient urethral closure in rats.

We investigated the bladder and urethral function in a rat model lacking the protein lysyl oxidase-like 1 (Loxl1). Female nulliparous rats of Loxl1-/- or age-matched wild type (WT) rats had leak-point pressure testing, cystometry, histopathological analyses of lower urinary tract, and contractile response of isolated detrusor strips to carbachol and electric field stimulation. The Loxl1-/- rats showed increased looseness and redundancy of the skin, the decreased intercontraction interval and voided volume in cystometry, the lower leak-point pressure, thinner elastic fibers of the mesentery, bladder, urethra and vagina, and smaller contractile response of detrusor strips to carbachol when compared to the WT rats. Thus, the insufficient hydrostatic mechanism of urethra via submucosal impaired elastin synthesis might reduce the resting urethral closure pressure and the diminished cholinergic contractile response of detrusor smooth muscle might be involved in bladder activity in the Loxl1-/- rats.

A general framework for automatic closed-loop control of bladder voiding induced by intraspinal microstimulation in rats.

Individuals with spinal cord injury or neurological disorders have problems in voiding function due to the dyssynergic contraction of the urethral sphincter. Here, we introduce a closed-loop control of intraspinal microstimulation (ISMS) for efficient bladder voiding. The strategy is based on asynchronous two-electrode ISMS with combined pulse-amplitude and pulse-frequency modulation without requiring rhizotomy, neurotomy, or high-frequency blocking. Intermittent stimulation is alternately applied to the two electrodes that are implanted in the S2 lateral ventral horn and S1 dorsal gray commissure, to excite the bladder motoneurons and to inhibit the urethral sphincter motoneurons. Asynchronous stimulation would lead to reduce the net electric field and to maximize the selective stimulation. The proposed closed-loop system attains a highly voiding efficiency of 77.2-100%, with an average of 91.28 ± 8.4%. This work represents a promising approach to the development of a natural and robust motor neuroprosthesis device for restoring bladder functions.