Point Pressure Measurements Research Articles

Microenergy acoustic pulse therapy restores urethral wall integrity and continence in a rat model of female stress incontinence.

To determine the outcomes and mechanisms of microenergy acoustic pulse (MAP) therapy in an irreversible rat model of female stress urinary incontinence. Twenty-four female Sprague-Dawley rats were randomly assigned into four groups: sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + β-aminopropionitrile (BAPN), and VBDO + β-aminopropionitrile treated with MAP (MAP). MAP therapy was administered twice per week for 4 weeks. After a 1-week washout period, all 24 rats were evaluated with functional and histological studies. The urethral vascular plexus was examined by immunofluorescence staining with antibodies against collagen IV and von Willebrand factor (vWF). The urethral smooth muscle stem/progenitor cells (uSMPCs) were isolated and functionally studied in vivo and in vitro. Functional study with leak point pressure (LPP) measurement showed that the MAP group had significantly higher LPPs compared to VBDO and BAPN groups. MAP ameliorated the decline in urethral wall thickness and increased the amount of extracellular matrix within the urethral wall, especially in the urethral and vaginal elastic fibers. MAP also improved the disruption of the urethral vascular plexus in the treated animals. In addition, MAP enhanced the regeneration of urethral and vaginal smooth muscle, and uSMPCs could be induced by MAP to differentiate into smooth muscle and neuron-like cells in vitro. MAP appears to restore urethral wall integrity by increasing muscle content in the urethra and the vagina and by improving the urethral vascular plexus and the extracellular matrix.

Optimization of Kiel geometry for better recovery factor in high temperature measurement in aero gas turbine engine

Abstract During gas turbine engine testing, steady-state gas-path stagnation temperatures and pressures are measured in order to calculate the adiabatic efficiencies of the major turbomachinery components. These measurements are carried out using fixed intrusive probes, which are installed at the inlet and outlet of each component. The overall uncertainty in calculated component efficiency depends on the accuracy of discrete point pressure and temperature measurement. High accuracy in measurement and prediction of measurement errors has become increasingly important if small gains in component performance needs to be achieved. The recent trend is to predict component efficiencies within ±1–2%. The present work covers different Kiel designs that have been developed in a response to this demand based on a MATLAB code and experimental evaluation. A parametric study has been carried out by varying the two most critical parameters viz. Ae/Ab ratio and L/D ratio to optimize the Kiel design. These design changes will allow measurements to be made with minimum possible errors and efficiencies to be calculated more accurately over a wider range of conditions inside a low bypass turbofan gas turbine engine.

Simulation of the Schiaparelli Entry and Comparison to Aerosciences Flight Data

The European Space Agency flew an entry, descent, and landing demonstrator module called Schiaparelli that entered the atmosphere of Mars on 19 October 2016. The entry and descent instrumentation suite had sensors on both the heat shield and backshell and included forebody pressure transducers and thermocouples (Atmospheric Mars Entry and Landing Investigations and Analysis, or AMELIA), along with aftbody pressure transducers and heat flux (COMbined Aerothermal and Radiometer Sensors instrument package, or COMARS) and narrowband radiative heatflux sensors (Infrared CO Two Measurement, or ICOTOM). Because of the failed landing attempt, only a subset of the flight data was transmitted before and after plasma blackout. The goal of this paper is to present comparisons of the flight data with calculations using NASA’s aerodynamic and aeroheating simulation tools. Simulations were conducted at various angles of attack to compare against forebody pressure data and to infer the angle of attack used in full three-dimensional simulations to calculate the total heat flux at the sensor locations. Comparisons with the COMARS total heat flux data and backshell pressure data are presented. Furthermore, due to the sparse dataset, results are also compared with the reconstructed heat flux, which was calculated from an inverse analysis of the AMELIA thermocouple data. The simulations agree within 16% for both the total heat flux measured in flight and the heat flux reconstructed from the thermocouple data. A potential link between the Schiaparelli high spin rate observed during entry as documented in the anomaly report and the unexpected stagnation point pressure measurement is also discussed.

Retrograde Gas Condensate Reservoirs: Reliable Estimation of Dew Point Pressure by the Hybrid Neuro-Fuzzy Connectionist Paradigm

AbstractThe dew point pressure (DPP) is a crucial thermodynamic property for gas reservoir performance evaluation, gas/condensate characterization, reservoir development and management, and downstream facility design. However, dew point pressure measurement is an expensive and time-consuming task; its estimation using the thermodynamic approaches has convergency problems, and available empirical correlations often provide high uncertainty levels. In this paper, the hybrid neuro-fuzzy connectionist paradigm is developed using 390 literature measurements. The adaptive neuro-fuzzy inference system (ANFIS) topology, including the training algorithm and cluster radius (radii), was determined by combining trial-and-error and statistical analyses. The hybrid optimization algorithm and radii = 0.675 are distinguished as the best characteristics for the ANFIS model. A high value of observed R2 = 0.97948 confirms the excellent performance of the designed approach for calculating the DPP of retrograde gas condensate reservoirs. Furthermore, visual inspections and statistical indices are employed to compare the ANFIS reliability and available empirical correlations. The results showed that the ANFIS model is more accurate than the well-known empirical correlations and previous intelligent paradigms in the literature. The designed ANFIS model, the best empirical correlation, and the most accurate intelligent paradigm in the literature present the absolute average relative deviation (AARD) of 1.60%, 11.25%, and 2.10%, respectively.

Validation of a new rat model of urethral sphincter injury and leak point pressure measurements

Aims In vivo experiments were performed to establish and validate a rat model of urethral sphincter injury and to develop a method for leak point pressure (LPP) measurements performed repeatedly in the same animal. Methods Twenty-four Sprague-Dawley female rats underwent bladder and epidural catheter implantation. Five days later, cystometry was performed using continuous infusion. Anesthesia with isoflurane, ketamine-xylazine (KX) or fentanyl-fluanisone-midazolam (FFM) was used. After three micturition cycles, intrathecal bupivacaine was administered leading to the suppression of reflex bladder contractions. LPP measurements were performed using vertical tilt. After the initial LPP measurement, animals underwent partial resection of the striated urethral sphincter. The effect was evaluated 6 weeks after surgery, by repeating the LPP measurement in the same animal. Results Ten out of 19 animals showed full micturition cycles under isoflurane, and all 9 animals under KX anesthesia. No significant difference in micturition pressures (Mean ± SEM; 30.1 ± 2.3 vs. 26.8 ± 1.6 mmHg) and LPP (31.0 ± 2.4 vs. 28.0 ± 0.9 mmHg) was observed between isoflurane and KX groups, respectively. Reflex micturition was suppressed with FFM. Bupivacaine led to overflow incontinence in all cases. Sphincter injury caused fibrotic changes and a significant increase in LPP (26.4 ± 2.3 before vs. 46.9 ± 4.6 mmHg after injury, p < 0.05). Conclusions KX anesthesia preserves bladder contractions. Intrathecal bupivacaine eliminates reflex micturition, allowing for repeated LPP measurements in the same animal. Resection of striated sphincter resulted in increased LPP 6 weeks post injury. The site of urethral sphincter resection healed with fibrosis.

Urodynamic Studies for the Diagnosis of Lower Urinary Tract Symptoms: Experience in BSMMU

Objectives: The aim of urodynamic testing is to obtain objective information regarding urinary bladder storage and voiding function. This investigation provides information of the underlying causes depending on the individual situation and findings. Materials and Methods: This Retrospective study of the UDS was conducted at Urology department of Bangabandhu Sheikh Mujib Medical University, Dhaka from January 2012 to April 2017. A total of 403 cases of urodynamic studies done. Patient age range was 10-85 years. Female Patient was only 41 and post operative cases was only six. Bladder dairy, Ultrasonography of Kidney, ureter, bladder with maximum cystometric capacity (MCC)and post void residue (PVR), Urine culture were done for most of the patient. Patient with indwelling catheter was remove and clean intermittent catheterization was demonstrated. There was no patient with pace maker or valve replacement. We didn’t use routine prophylactic antibiotics, Patients was advice to contact to UDS room physically or over telephone if they feel fever, retention, and other complications. Urodynamic tests include uroflowmetry, postvoid residual measurement, cystometric test, leak point pressure measurement, pressure flow study, and few cases with electromyography. Results: Among them most cases are equivocal and obstructive cases are ranked second about 68 cases (16.87 These were Benign Prostatic Hyperplasia (BPH), stricture urethra, atonic bladder, and dysfunctional voiding. Only five patients had urinary tract infections (1.2%) with rise of temperature but only two had cultural positive and treated with sensitive antibiotics. Organism were streptococcus aureus and pseudomonus. One female and one male patient develop retention and relived by continuous catheterisation and after 7 days removed catheter. Conclusions: Urodynamics could help most diagnosis of LUTSs in most of the cases. We are not yet in using video urodynamics instead urethrocystoscopy may help in assessing the urethra and bladder neck. Bangladesh Journal of Urology, Vol. 21, No. 1, January 2018 p.8-13

Association of intrinsic sphincter deficiency with urine flow acceleration measurement.

Intrinsic sphincter deficiency (ISD) is associated with an inability to maintain mucosal coaptation either at rest or in the presence of stress resulting from damage to muscles or nerves that maintain tonus. The purpose of our trial was to determine the role of urodynamic measurements of flow such as maximum flow rate, flow time, and acceleration speed of flow to assess the urethral resistance on prediction of stress incontinence and ISD. Our study was based on a retrospective analysis of urodynamic records of female patients performed for urinary incontinence. Mean flow rate, maximum flow rate, detrusor pressure at maximum flow, vesical pressure at maximum flow, maximum detrusor pressure, and flow rate at maximum detrusor pressure measurements were extracted from the voiding phase of urodynamic charts. The slope of the maximum flow was used to calculate acceleration of flow (Qacc). The urodynamic records of 142 women were reviewed and Qacc was measured. The mean age of the ISD group was 53.3 ± 12.5 (24-78) and of the non-ISD group 53.7 ± 12.5 (35-74). The mean Qacc (30.3 ± 16.1° [mL/s2 ]) in the ISD group was significantly higher than in the non-ISD group (21.6 ±9.6° [mL/s2 ]). Urodynamic bladder capacity of the non-ISD group (432.3 ± 90.4 mL) was higher than the ISD group (389.2 ± 109) (P = .01). The Valsalva leak point pressure and maximum urethral closure pressure measurements in assessing urethral function are not useful for predicting incontinence surgery failure. We demonstrated that Qacc is higher in ISD stress incontinent women than stress incontinent women. Qacc may demonstrate urethral resistance and tonus in a more reliable manner.

Therapeutic new targets for stress urinary incontinence in the central nervous system

Stress urinary incontinence (SUI) is a common and bothersome problem among middle-aged women. However, there are few useful drugs for SUI. Urethral hypermobility and intrinsic sphincter deficiency are two main causes of SUI. Various animal models of SUI, such as vaginal distention, pudendal nerve injury, or ovariectomy, have been developed to study the pathophysiology of SUI. In addition, we have previously reported that cerebral infarction rats also induce SUI. Leak point pressure measurements are the most commonly used methods to evaluate the urethral dysfunction in SUI animal models. Originally, we have developed microtransducer-tipped catheter measurements of urethral activity during sneezing. Previous or our basic research has clarified potential strategies for pharmacotherapy of SUI in the central nervous system. Therapeutic targets include adrenergic and serotonergic (5-HT) receptors in the spinal cord, which stimulate pudendal nerve innervating the external urethral sphincter and/or sympathetic nerve innervating urethral smooth muscle. Activation of α1-adrenoceptors, 5-HT2C, or 5-HT7 receptors enhances the reflex at the spinal cord level whereas pre- or postsynaptic α2-adrenoceptors and/or 5-HT1A receptors inhibit the reflex. We have recently reported that stimulation of the spinal μ-opioid receptors by tramadol also enhances the reflex. Thus, we review the recent advances in basic SUI research and potential targets for pharmacotherapy of SUI in the central nervous system.

Influence of the urethral pressure transducer in measuring Valsalva leak point pressure in women undergoing multichannel urodynamic testing.

To determine if the air-charged urethral sensor balloon currently used in urodynamic testing (UDS) significantly impacts Valsalva leak point pressure (VLPP) measurements. This is a prospective cohort study of women undergoing UDS at an academic institution. VLPPs were obtained at 150 mL and urodynamic capacity with and without the urethral pressure sensor in the urethra. VLPP measurements were analyzed using a Wilcoxon signed-rank test. Median and interquartile range are presented. Sixty-three patients were enrolled in the study, 53 were included in the primary analysis. The mean age of the subjects was 56.2 ± 12.1 years. Nine patients (16%) solely leaked when the balloon was not present in the urethra either with cough or during VLPP measurement. At both 150 mL and urodynamic capacity, when VLPP testing was performed, there was a significant difference (cmH2 O) between the control and intervention values, (76.2 [55.0, 97.0] vs 68.8 [46.3, 93.3], P = .0012; 79.3 [53, 96.5] vs 72.5 [50.8, 92.3], P = .04). There was also a statistically significant difference between the control and intervention values for the lowest leak value at 150 mL and capacity (70.5 [51, 94.5] vs 60.0 [40, 88] P = .002; 73.5 [49.5, 91.5] vs 61 [45, 88], P = .017). The higher VLPPs obtained with the urethral balloon in place indicate that the balloon may be the cause of falsely elevated VLPPs during urodynamic testing. Additionally, the balloon may mask a diagnosis of stress urinary incontinence in some patients.

Effects of oligomers dissolved in CO2 or associated gas on IFT and miscibility pressure with a gas-light crude oil system

The solubility of an oligomer in a supercritical gas solvent (e.g. CO2 or associated gas (AG) mixture) and the subsequent effects on the phase behaviour, interfacial tension (IFT) and miscibility pressure of the in-situ oil/oligomer-thickened gas system at a molecular level are crucial to understanding and designing a thickened miscible gas injection (MGI) process. We have conducted cloud point pressure measurements, which revealed that the phase behaviour of P-1-D-thickened CO2 would follow a UCST (upper critical solution temperature) trend while P-1-D-thickened AG mixture would lie close to a LCST (lower critical solution temperature) behaviour. Moreover, our measured equilibrium IFTs of crude oil/P-1-D-thickened CO2 system and crude oil/PVEE-thickened CO2 system were found to be slightly lower than those of the crude oil/CO2 system. This results in a slight reduction in the MMP (minimum miscibility pressure) and considerable reduction in the first contact miscibility pressure (Pmax). We found the dissolution of P-1-D in the AG mixture to cause an increase in the equilibrium IFT for the crude oil/P-1-D-thickened AG mixture system, resulting in an increase in both of the MMP and Pmax. This indicates that the dissolution of an oligomer may have a considerable effect on the crude oil/thickened gas IFT behaviour at a pressure close to the cloud point pressure.

Fluid–Structure Interactions on a Tunable Store in Complex Cavity Flow

Fluid–structure interactions were studied on a store with tunable structural natural frequencies in complex cavity flow. Different leading-edge geometries, doors, and internal inserts generated cavity pressure fields more representative of an actual aircraft bay. The store loading and response was characterized using point pressure and accelerometer measurements, while high-frequency pressure-sensitive paint captured the distribution of surface pressure. In the complex cavity, the store responded to the cavity resonant tones not only in the streamwise and wall-normal directions but also in the spanwise direction. That spanwise response to cavity tones was not observed in a simple rectangular cavity because the flow in the spanwise direction was uniform and in phase. This different behavior highlights the importance of using a representative bay geometry and internal store for the prediction of the structural response in a flight environment.

An animal experimental study on pubourethral ligament restoration with platelet rich plasma for the treatment of stress urinary incontinence.

IntroductionMinimally invasive methods for injured ligament and tendon restoration have been developed and gained popularity in recent years. Injury and relaxation of the pubourethral ligament (PUL) can lead to stress urinary incontinence (SUI). The aim of this study was to investigate the impact of injecting platelet rich plasma (PRP) into the PUL following its surgical transection resulting in SUI, confirmed by leak point pressure (LPP) measurements pre- and post-intervention in an experimental animal model.Material and methodsTwenty female adult Sprague-Dawley rats were assigned in 2 groups: 1) treatment group with transection of the PUL and application of PRP at the time of transection and at one month follow-up and 2) a control group, with transection of the PUL only. Leak point pressures (LPPs) were measured prior to transection, immediately following the transection and at 1 and 2 months in both groups.ResultsThe median LPPs for the control group were: LPP – preT: 35.6 (29.8–44.8) cmH2O, LPP – postT: 14.6 (5.8–19.0) cmH2O, LPP – 1 month: 27.3 (19.2–33.8) cmH2O, LPP – 2 months: 29.0 (27.0–34.0) cmH2O, whereas for the PRP group were: LPP-preT: 40.5 (33.2–46.3) cmH2O, LPP – postT: 15.7 (3.0–24.0) cmH2O, LPP – 1month: 31.6 (24.8–37.4) cmH2O, LPP – 2 months: 36.8 (32.5–45.4) cmH2O. PRP injections on transected PULs significantly increased LPPs at one month follow-up [31.6 cmH2O vs. 27.3 cmH2O, p = .043]. This effect was confirmed at two months [36.8 cmH2O vs. 29.0 cmH2O, p <.001].ConclusionsInjection of PRP into transected PULs significantly improved LPPs at one and two months' follow-up. However, further experimental and clinical research is needed to evaluate the safety and efficacy of this treatment, in clinical practice.

Molecular simulation aided design of copolymer thickeners for supercritical CO2 as non-aqueous fracturing fluid

Molecular modeling of CO2-polymer system was established to study the molecular behaviors and intermolecular interaction of copolymers in supercritical carbon dioxide (SC-CO2) by all-atom molecular dynamics (MD) simulation. According to the simulation results, the correlations of the intermolecular interaction with the molecular structure and composition were explored. The effects of intermolecular interactions on the copolymer properties in SC-CO2 were identified. A series of copolymers were synthesized with CO2-philic monomer 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluorodecyl acrylate (HFDA) and CO2-phobic monomer vinyl n-Octanoate (VOc), vinyl acetate (VAc), vinyl pivalate (VPi), respectively. The solubility and viscosification of the copolymers in SC-CO2 were evaluated by cloud point pressure and relative viscosity measurements. It was found that P(HFDA0.49-co-VAc0.51), which is the most effective thickener among the copolymers, could enhance the viscosity of SC-CO2 by 62 times at 5 wt%. It was suggested that the thickening capability of the copolymers in SC-CO2 may originate from intermolecular cross-links generated by associative groups. Combining the molecular simulation and experiment results, the structure-activity relationships of the copolymers in SC-CO2 were revealed. It is believed that the molecular simulation aided design method for the SC-CO2 copolymer thickener is reliable.

Effect of monomer sequence distribution on the CO2-philicity of a well-defined ternary copolymer: Poly(vinyl acetate-co-vinyl butyrate-co-vinyl butyl ether)

The work aims to interpret the phase behavior of multi-polymers in super critical CO2 via a spatially dependent structural parameter, the monomer sequence distribution, rather than traditional statistical factors. Well-defined statistical copolymers based on three CO2-philic monomers, vinyl acetate, vinyl butyrate and vinyl butyl ether, were synthesized with reversible addition-fragmentation chain transfer free-radical polymerization by combining their kinetic behaviors and pairwise reactivity ratios into the Alfrey–Goldfinger–Skeist model. The corresponding cloud point pressures become nonlinear with the polymer composition and possess upper critical solution pressure behavior. Additionally, their diad and triad monomer sequence distributions were calculated by simple theoretical arithmetic. While analyzing the cloud point pressure measurements, we found that both the differences in composition and symmetrical structure of the monomer triads could impact the CO2-philicity of triads, which were close to the properties of the products, and thus, the variations in the triad sequence distribution could reasonably predict the phase behavior of the products.

Retrograde leak point pressure measurement improves outcomes of the Virtue male sling for postprostatectomy incontinence.

We aimed to compare the efficacy of two different sling tensioning approaches, and to report our experience, including safety and impact on quality of life (QoL) of the Virtue® male sling for the treatment of postprostatectomy incontinence (PPI). From our prospectively maintained database, we retrospectively identified all men treated with the Virtue male sling for PPI between March 2009 and February 2014 by two urologists in two institutions. Baseline demographic data and the sling tensioning method were abstracted from the database. Likewise, the Patient Global Impression of Improvement (PGI-I) scale, severity of incontinence, and clinical outcomes were also abstracted. 48 patients were treated with the Virtue quadratic male sling. Sling tensioning was done using cystoscopy in the first 18 patients (Group 1), while per-operative retrograde leak point pressure (RLPP) measurement was done in the last 30 patients (Group 2). The median (interquartile range [IQR]) followup from the day of surgery was 22 (15-41) months. At the last followup visit, 7 (39%) patients in Group 1 were cured or improved of their PPI, compared to 21 (70%) patients in Group 2 (p=0.03). The final median (IQR) RLPP in these patients was 41 (37-48) cm H2O. Transient pain was the most common adverse event, occurring in 23 (48%) of patients. Twenty-one (70%) patients in Group 2 were "much better" or "very much better" with their device, compared to 7 (39%) in Group 1 (p=0.0008). The Virtue male sling is a valuable treatment option for PPI. Per-operative RLPP measurement significantly improves cure and satisfaction rates.

Valsalva Leak Point Pressure Measurement in Women with Stress Urinary Incontinence: At what Bladder Volume?

Valsalva Leak Point Pressure Measurement in Women with Stress Urinary Incontinence: At what Bladder Volume?

Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) measurements.

The relationship between pelvic floor muscles and measurements of urethral function is not well studied. It is not known whether adjusting for clinical, demographic and urodynamic parameters would improve the association between MUCP and ALPP. Our hypothesis was that pelvic floor muscle strength (PFMS) influences the relationship between MUCP and ALPP. This was a retrospective study of women who underwent a complex urodynamic study with evaluation of MUCP and ALPP using ICD-9 codes with documentation of PFMS. Urodynamic stress incontinence was confirmed in 478 patients, of whom 323 had MUCP recorded and 263 had both MUCP and ALPP recorded. Women with higher PFMS had a higher MUCP. In regression analysis ALPP at 150mL and MUCP were weakly associated (coefficient 0.43, 95% CI 0.08-0.78; p=0.02), whereas ALPP at capacity and MUCP were moderately associated (coefficient 0.60, 95% CI 0.25-0.95; p<0.001). This study showed that MUCP and ALPP at 150mL were weakly associated and that this improved to a moderate association for ALPP at capacity. MUCP increased with increasing PFMS among women with stress urinary incontinence and decreased with increasing age. There was no evidence that ALPP was associated with PFMS or age. The relationship between MUCP and ALPP was unchanged when accounting for covariates of PFMS (age, parity, BMI, prior procedure, urethral mobility, bladder capacity, stage of cystocele, or stage of uterine or apical prolapse).

Using fluid-induced seismicity to infer permeability

For engineering applications involving fluid flow through porous rocks underground, the permeability of a rock mass is an important parameter. Imaging of the 3D permeability distribution is generally done by a history-matching approach: fluid pressure due to injection in a well with known pressure and flow rates is numerically simulated, and the rock permeability is adjusted so as to match predicted pressure values to measured observations. These pressure observations are made at producing wells. Because there will normally be few wells, the observations, while being dense in time, are spatially sparse. The idea of this paper is to augment these downhole pressure measurements by using microseismic data to infer pressure at seismic event locations.The mechanism of pressure-induced seismicity is the reduction of effective normal stress across a plane of weakness. The rock strength can be represented as a critical pressure - the pore pressure above which the rock will fail. The rock strength is highly heterogeneous, because of the existence of weaknesses such as joints, bedding planes, and clay bands, and stronger regions such as sandstone channels. So the rock strength will be random. We model the rock strength as a Weibull-distributed critical field. A microseismic event occurs where pressure exceeds this critical field, and so is effectively a point pressure measurement, with an uncertainty given by this Weibull distribution. The idea is to augment the well-pressure observations with these “virtual” pressure measurements at seismic event locations.We model pressure diffusion using a finite volume approach, and examine the inversion, for permeability, of two different types of data, (1) pressure measurements in boreholes, and (2) virtual pressure measurements at seismic event locations. We show that the two types of data provide complementary information.

MP65-02 EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A AND TESTOSTERONE ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II1 Apr 2016MP65-02 EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A AND TESTOSTERONE ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS Takahiro Shimizu, Katsumi Kadekawa, Naoki Kawamorita, Philip Turnbull, Alan Russell, and Naoki Yoshimura Takahiro ShimizuTakahiro Shimizu More articles by this author , Katsumi KadekawaKatsumi Kadekawa More articles by this author , Naoki KawamoritaNaoki Kawamorita More articles by this author , Philip TurnbullPhilip Turnbull More articles by this author , Alan RussellAlan Russell More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1213AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stress urinary incontinence (SUI) is common in post-menopausal women, indicating that estrogen deficiency is one of the major causes of SUI that induces atrophic and degenerative changes in urethral and pelvic floor muscles. Selective androgen receptor modulators (SARMs) selectively stimulate anabolic pathway of the androgen receptor (AR) in muscle and bone while sparing the androgenic effects. In this study, we examined effects of a SARM (GSK2849466A, GSK) and dihydrotestosterone (DHT) on urethral continence function in a bilateral ovariectomy (OVX)-induced rat SUI model. METHODS Female nulliparous Sprague-Dawley rats with bilateral OVX were used. Rats were divided into 5 groups; sham operated (S), vehicle-treated OVX (O-V), GSK-treated OVX (0.005 or 0.03 mg/kg/day, po, O-L or O-H, respectively), and DHT-treated OVX (1 mg/kg/day, sc, O-D) groups. At 2 or 3 weeks after OVX, GSK (or vehicle) or DHT treatment was started. Six weeks after OVX, rats were subjected to the evaluation of sneeze-induced continence reflex and sneeze-induced leak point pressure (SLPP) measurements, followed by histological analyses of urethral tissues. RESULTS Urethral baseline pressure (UBP) and the amplitude of urethral responses during sneezing (AURS) were significantly reduced in O-V rats (n=11) by 46% and 38%, compared to S rats (n=8). Compared to the O-V, UBP was significantly increased in the O-L (n=6) and O-H (n=9) by 123% and 86%, and AURS was significantly increased in the O-H and O-D (n=10) by 106% and 60%. Fluid leakage was observed during sneezing in all O-V rats (n=8, SLPP=59.9 ± 9.5 cmH2O) whereas sham rats (n=8) did not leak. The leakage was also observed in O-L (7 of 9 rats, SLPP=67.4 ± 3.0 cmH2O), O-H (1 of 8 rats, SLPP=82.9 cmH2O) and O-D rats (3 of 8 rats, SLPP=73.2 ± 12.8 cmH2O). O-H rats showed hypertrophy/reversal of atrophy of striated (ST) and smooth (SM) muscles in urethral transverse sections, compared to O-V rats. CONCLUSIONS These results indicate that OVX significantly impairs urethral continence function after 6 weeks, and that GSK dose-dependently restores the reductions in UBP, AURS and SLPP accompanied with urethral muscle hypertrophy, leading to the prevention of SUI. Based on our previous studies, UBP and AURS predominantly reflect urethral SM and ST activity in rats. Considering that DHT restores the reduction in AURS without affecting reduced UBP and partially prevents SUI in OVX rats, SARMs could be more effective for the treatment of SUI by enhancing both SM and ST-mediated urethral function under stress conditions such as sneezing. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e864 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Takahiro Shimizu More articles by this author Katsumi Kadekawa More articles by this author Naoki Kawamorita More articles by this author Philip Turnbull More articles by this author Alan Russell More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP65-01 STROMAL CELL DERIVED FACTOR-1 ACCELERATES RECOVERY OF CONTINENCE IN RAT MODEL OF VAGINAL DISTENSION INJURY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II1 Apr 2016MP65-01 STROMAL CELL DERIVED FACTOR-1 ACCELERATES RECOVERY OF CONTINENCE IN RAT MODEL OF VAGINAL DISTENSION INJURY Ahmad Khalifa, Amr Mahran, Michael Kavran, Juliana Woda, Marc Penn, and Adonis Hijaz Ahmad KhalifaAhmad Khalifa More articles by this author , Amr MahranAmr Mahran More articles by this author , Michael KavranMichael Kavran More articles by this author , Juliana WodaJuliana Woda More articles by this author , Marc PennMarc Penn More articles by this author , and Adonis HijazAdonis Hijaz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1212AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Vaginal distension (VD) in rats results in a reproducible injury to urethral continence mechanism that is recoverable in 2 weeks. VD injury has been shown to cause ischemia. Stromal cell derived factor-1 (SDF-1), is a known chemokine involved in angiogenesis and chemo attraction of stem cells into injury area. Previously in animal and human studies, delivery of non-viral human SDF-1 plasmid (pSDF-1), which expresses SDF-1 for 2-3 weeks, has shown safety, increased vessel density and improved patient status in ischemic heart and vascular diseases. In this experiment we examined the efficacy of pSDF-1 injection on continence recovery after VD & correlated the changes with histological changes. METHODS A total of 72 Sprague Dawley rats underwent VD and were randomly divided into 2 groups. Group 1 (42 rats) underwent SDF-1 injection followed by Leak point pressure (LPP) measurement at 4, 7, and 14 days (14 rats per time point). Group 2 (30 rats) were sham injected (5% dextrose) after VD and LPP was measured at same time points (10 rats per time point). VD was done as described with inflation of a 10 French modified Foley catheter intravaginal for 4 hours to create injury. SDF-1 and dextrose were injected peri-uretherally immediately after VD. Following LPP measurement, urogenital tissues were harvested for histological examination. Slides were stained with H&E and Masson’s trichrome. Vascularity and collagen content was determined using Adobe Photoshop and Image J software. Data analysis was done by IBM SPSS v.22. RESULTS As expected, the LPP decreased at 4 days in both groups. SDF-1 group exhibited a significant increase in LPP at 7 days compared to the sham (22.3 cmH2O vs 13.62 3 cmH2O, P value <0.001 respectively). The improvement in LPP continued in both groups at day 14, with the statistical difference approaching significance (36.38 cmH2O vs 25.82 cmH2O respectively, p=0.067). Histological evaluation and image analysis revealed no gross differences in the smooth and skeletal muscle thickness of the mid-urethra with no statistically significant difference in the collagen content and vascular density in the urethra at all-time points. CONCLUSIONS pSDF-1 plasmid injection at the time of VD accelerated the recovery of continence in the rat model of simulated birth trauma. The mechanism of improved recovery is not evident from the gross histological evaluation. Further research is needed to explain the mechanism of early improvement, possible hypothesizes are stem cell attraction and decrease in cellular injury or death. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e864 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ahmad Khalifa More articles by this author Amr Mahran More articles by this author Michael Kavran More articles by this author Juliana Woda More articles by this author Marc Penn More articles by this author Adonis Hijaz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...