Leak Point Pressure Research Articles

Effectiveness of physiotherapy for lower urinary tract symptoms in postpartum women: systematic review and meta-analysis.

The efficacy of physiotherapy for postpartum lower urinary tract symptoms (LUTS) has attracted considerable research interest. In the current study we evaluated the efficacy and safety of pelvic floor muscle training (PFMT) combined with biofeedback (BF), electrical stimulation (ES) therapy, or both for postpartum LUTS. PUBMED, EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technique Journals Database, and Wanfang databases were searched from inception to December 2020. Eligible randomized controlled trials on postpartum LUTS comparing PFMT plus BF, ES, or both with PFMT alone were included. The Cochrane handbook was used to evaluate the quality of the studies. Seventeen studies were included. The results of the meta-analysis showed that PFMT plus ES with or without BF was more effective than PFMT alone. Patients receiving PFMT plus ES and BF achieved greater improvement than controls receiving PFMT alone in incontinence quality of life scores (mean difference: 15.33, 95% confidence interval [CI]: 11.70-18.97, P < 0.00001), pelvic floor muscle strength (risk ratio: 2.29, 95% CI: 1.53-3.43, P < 0.0001), and urodynamic parameters (maximum urethral closure pressure, abdominal leak point pressure, and maximum urinary flow rate), and 1-h urine leakage (standardized mean difference: -0.70, 95% CI: -1.23 to -0.17, P = 0.010) also decreased. PFMT plus ES with or without BF exhibited better efficacy and safety for early postpartum LUTS than PFMT alone.

Transurethral versus suprapubic catheterization to test urethral function in rats

Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization. There was no significant difference in peak bladder pressure during LPP testing whether measured with a transurethral or suprapubic catheter. There was no significant difference in peak bladder pressure between the first and second catheter insertions. However, peak EMG firing rate, as well as peak EMG amplitude and EMG amplitude difference between peak and baseline were significantly higher after the first catheter insertion compared to the second insertion, regardless of the catheter method. Our results suggest that route of catheterization does not alter urethral function, e.g. create a functional partial outlet obstruction. Either catheterization method could be used for LPP and/or EUS EMG testing in rats.

The effect of testosterone replacement therapy on bladder functions, histology, apoptosis, and Rho-kinase expression in bladder outlet obstruction and hypogonadism rat model

Background/aimThe effect of testosterone replacement therapy was investigated on bladder functions, histology, apoptosis as well as Rho-kinase expression in the rat bladder outlet obstruction (BOO) and hypogonadism models. Materials and methods30 mature male rats divided into 4 groups: sham group (n = 8), BOO group (n = 8), BOO + orchiectomy group (n = 7), BOO + orchiectomy + testosterone (T) treatment group (n = 7). Cystometric findings, apoptosis index, Rho-kinase (ROCK-2) expression, and smooth muscle/collagen ratio were compared. Results BOO did not change ROCK-2 expression level, compared to sham group (P > 0.05). However, when compared to BOO group (P < 0.01), BOO + orchiectomy led ROCK-2 increase. The testosterone treatment failed to reverse the up-regulation of ROCK-2 induced by orchiectomy although it tended to lower ROCK-2 level. Compared to sham group (P = 0.002), changes in maximal bladder capacity and leak point pressure were higher (P = 0.026, P = 0.001), and bladder compliance was lower in BOO group. Also, the apoptosis index was different between the two groups (P = 0.380). Smooth muscle/collagen ratio was higher in BOO + orchiectomy + T group than in BOO + orchiectomy group (P = 0.010).ConclusionsThe research draws attention to alternating treatment approaches in case of the presence of hypogonadism and BOO.

Brain derived neurotrophic factor mediates accelerated recovery of regenerative electrical stimulation in an animal model of stress urinary incontinence

ObjectiveStress urinary incontinence (SUI) is prevalent among older women and can result from insufficient regeneration of the pudendal nerve (PN). Electrical stimulation (ES) of the PN upregulates brain derived neurotrophic factor (BDNF) and accelerates regeneration. Using tyrosine kinase B (TrkB) to reduce the availability of free BDNF, the aim of this study was to determine if BDNF is necessary for accelerated recovery via ES in a model of SUI. MethodsOur SUI model consists of Female Sprague-Dawley rats, whose PNs were crushed bilaterally twice for 30 s, followed by insertion of a modified Foley catheter into the vagina with balloon inflation for 4 h. These rats were divided into 4 groups: 1) Sham PN crush and sham vaginal distension without electrode implantation and with saline treatment (sham injury); 2) SUI with sham stimulation and saline treatment (SUI); 3) SUI and ES with saline treatment (SUI&ES); and 4) SUI and ES with TrkB treatment (SUI&ES&TrkB). Animals underwent ES or sham stimulation four times a week for two weeks. Four weeks after injury, animals underwent functional testing consisting of leak point pressure (LPP) with simultaneous external urethral sphincter (EUS) electromyography (EMG) and pudendal nerve recordings. Data was analyzed using ANOVA with Holm-Sidak posthoc test (p < 0.05). EUS and PN specimen were sectioned and stained to semi-quantitatively evaluate morphology, regeneration, and reinnervation. ResultsLPP and EUS EMG firing rate were significantly increased in the sham injury and SUI&ES groups compared to the SUI and SUI&ES&TrkB groups. EUS of SUI rats showed few innervated neuromuscular junctions compared to sham injured rats, while both treatment groups showed an increase in reinnervated neuromuscular junctions. ConclusionES accelerates functional recovery via a BDNF-mediated pathway in a model of SUI. These findings suggest ES could be used as a potential regenerative therapy for women with SUI.

Immunochemical and urodynamic outcomes after polypropylene mesh explant from the pelvic wall of rats.

To analyze the immunochemical and urodynamic outcomes after partial versus complete excision of transvaginal polypropylene mesh (PPM) from pelvic walls of rats. Forty-eight female Sprague-Dawley (SD) rats were randomly distributed into seven groups: control, mesh total removal 60days (M-T 60D), mesh total removal 180days (M-T 180D), mesh partial removal 60days (M-H 60D), mesh partial removal 180days (M-H 180D), sham 60days (Sham 60D), and sham 180days (Sham 180D). In the mesh groups, PPM was inserted and partially (0.3 × 0.3cm) or completely removed 30days later. In the Sham group, the space between the vagina and bladder was dissected without placing or removing the synthetic mesh at day 1 and day 30 later. Urodynamic studies, immunochemical analysis, and Western blot were done at days 60 and 180. The M-T 60D voiding pressure was significantly decreased compared to the Sham 60D and M-H 60D. The voiding interval of M-T 60D was significantly shorter than that of M-H 60D. In the M-T 60D and M-T 180D groups, the leak point pressure was significantly less than in their corresponding sham groups. IL-1 and TNF-α were significantly more intense in M-T 60D compared to M-H 60D and Sham 60D. NGF was significantly greater in M-T 60D compared to Sham 60D. There were no significant differences in MMP-2 and CD-31s throughout the group. Total mesh excision incites a host inflammatory response and transitory lower urinary tract dysfunction. Despite the good outcomes after total excision, the invasiveness and surgical risk associated with repeated procedures should not be underestimateded.

Regenerative Medicine in Urogynecological Services: Opportunities in Cases of Stress Urinary Incontinence

Stress urinary incontinence (SUI) is a case that often occurs in women. The handling of this case is not yet fully effective, even though the challenge of health care is to provide quality services and adjust to the needs of the patient. The purpose of this study was to examine the effectiveness of regenerative medicine applied in urogynecology especially in stress urinary incontinence cases as a preliminary study. A selective database search of PubMed, and Google Scholar was conducted to validate the effectiveness of regenerative medicine in urogynecology especially urinary stress incontinence. The search included experimental research, written in English, and has Leak Point Pressure assessment data in the results analysis. Research involves both animals and humans. The search used the following keywords in various combinations: 'stem cell therapy', 'cell-based therapy for SUI', 'regenerative medicine for SUI', and 'tissue engineering'. LPP is an assessor of the success of SUI's services. Most of the studies explored the success and potential of stem cell utilization in cases of stress urinary incontinence even with different types of stem cells. Future studies need to test or experiment the manufacture of stem cell products that can be applied more easily and in the long term.&#x0D; Keywords: Stress urinary incontinence, stem cell, regenerative medicine

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

ObjectiveTo report the clinical data in a large population of patients affected by inflammatory encephalomyelopathy. Material and methodsWe 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. ResultsThe 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. ConclusionPersistent 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.

Impact of preoperative factors on recovery of continence after artificial urinary sphincter implantation in postprostatectomy incontinence.

BackgroundThe purpose of this study was to determine the influence of preoperative factors on the recovery of continence after artificial urinary sphincter (AUS) implantation in postprostatectomy incontinence.Materials and methodsSeventy-two patients who underwent AUS implantation between April 2006 and March 2020 were analyzed. The clinical features and preoperative urodynamic parameters were correlated with the postoperative continence rate using linear and logistic regression analysis. The recovery of continence was defined by the patient requiring no use of a protective urine pad during the 24 hours.ResultsOf the 72 patients, 57 (79.2%) recovered continence (dry group), while 15 (20.8%) were wearing more than 1 pad per day (wet group) on the last follow-up visit. In the clinical characteristics, only the interval between radical prostatectomy and AUS (in months) showed a statistically significant difference (35.4 ± 26.2 in the dry group, 22.7 ± 12.2 in the wet group, p = 0.009). Other preoperative clinical features such as the underlying disease, surgical methods, size of prostate, tumor stage, and radio nor hormonal therapy did not present statistically significant differences.Of the preoperative urodynamic parameters, only the abdominal leak point pressure (ALPP) showed statistical significance when related to surgical outcomes by 88.6 ± 33.6 in the dry group and 66.1 ± 29.6 in wet the group (P = 0.024). The number of patients for whom ALPP was higher than 80 cm H2O was 61.4% in the dry group and 20% in the wet group (95% confidence interval: 1.612-25.11). Other preoperative UDS features including detrusor underactivity, maximum urethral closure pressure, and others were not statistically significant.ConclusionsThe interval between RP and AUS, as well as the preoperative ALPP, can be possible predictive factors for the surgical outcomes of AUS implantation. In addition, an ALPP of >80 cm H2O has a high degree of predictability for success of AUS surgical outcomes in post-RP incontinence.

Is coital incontinence a manifestation of urodynamic stress incontinence or detrusor overactivity?

Coital incontinence (CI) is an underreported symptom among sexually active women. It has been assumed that incontinence at penetration (CIAP) is due to urodynamic stress incontinence (USI), while coital incontinence at orgasm (CIAO) is thought to be due to detrusor overactivity (DO). To evaluate demographic and urodynamic findings associated with coital incontinence (CI) and to confirm the hypotheses 'CIAP is associated with USI' and 'CIAO is associated with DO we performed a retrospective study of 661 sexually active women attending a tertiary clinic between January 2017 and December 2019 for pelvic floor dysfunction. All patients filled in a standardized questionnaire and had a clinical examination and multichannel urodynamic testing. Women were asked if they experienced urine leakage during intercourse and the timing of such leakage. Of 661 sexually active women, one third (n = 220) reported coital incontinence. While 121 (18%) women experienced CIAP, 172 (26%) had CIAO and 76 (11.5%) suffered both. For women with pure USI, the prevalence of CIAP (61.7%) and CIAO (69.5%) was significantly higher than for women with pure DO, where only 12.3% had CIAP and 8.6% had CIAO. Factors significantly associated with CI were body mass index, mid-urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP). When only women with pure USI or DO were included, USI remained associated with CI while DO was not. CI is clearly associated with SUI and USI and is likely to share etio-pathogenetic mechanisms. CI seems to be a manifestation of USI, even when it occurs during orgasm.

Secretomes of human pluripotent stem cell-derived smooth muscle cell progenitors upregulate extracellular matrix metabolism in the lower urinary tract and vagina

BackgroundAdult mesenchymal stem cells (MSCs) have been studied extensively for regenerative medicine; however, they have limited proliferation in vitro, and the long culture time induces cell senescence. MSCs also contribute to tissue repair through their paracrine function. In this study, we sought to examine the paracrine effects of human smooth muscle cell progenitors (pSMC) on the urethra and adjacent vagina of stress urinary incontinence rodents. We use human pluripotent stem cell (PSC) lines to derive pSMCs to overcome the issue of decreased proliferation in tissue culture and to obtain a homogenous cell population.MethodThree human PSC lines were differentiated into pSMCs. The conditioned medium (CM) from pSMC culture, which contain pSMC secretomes, was harvested. To examine the effect of the CM on the extracellular matrix of the lower urinary tract, human bladder smooth muscle cells (bSMCs) and vaginal fibroblasts were treated with pSMC-CM in vitro. Stress urinary incontinence (SUI) was induced in rats by surgical injury of the urethra and adjacent vagina. SUI rats were treated with pSMC-CM and monitored for 5 weeks. Urethral pressure testing was performed prior to euthanasia, and tissues were harvested for PCR, Western blot, and histological staining. Kruskal-Wallis one-way ANOVA test and Student t test were used for statistical comparisons.ResultspSMC-CM upregulated MMP-2, TIMP-2, collagen, and elastin gene expression, and MMP-9 activity in the human bladder and vaginal cells consistent with elastin metabolism modulation. pSMC-CM treatment in the SUI rat improved urethral pressure (increase in leak point pressure compared to intact controls, p < 0.05) and increased collagen and elastin expression in the urethra and the adjacent vagina.ConclusionConditioned media from smooth muscle cell progenitors derived from human pluripotent stem cells improved urethral leak point pressure and collagen and elastin content in the SUI rat. These findings suggest a novel therapeutic potential for PSC-based treatments for SUI and pelvic floor disorders where tissues are affected by collagen, elastin, and smooth muscle loss.

Bone marrow stem cells secretome accelerates simulated birth trauma-induced stress urinary incontinence recovery in rats.

Stress urinary incontinence (SUI) is defined as involuntary urine leakage during physical activities that increase the intra-abdominal pressure on the bladder. We studied bone marrow stem cell (BMSC) secretome-induced activation of anterior vaginal wall (AVW) fibroblasts and its ability to accelerate SUI recovery following vaginal distention (VD) in a rat model of birth trauma using BMSC-conditioned medium (BMSC-CM) and concentrated conditioned medium (CCM). BMSC-CM enhanced the proliferation, migration, and collagen synthesizing abilities of fibroblasts. Differentially expressed genes in BMSC-CM-induced fibroblasts were mainly enriched for cell adhesion, extracellular fibril organization and angiogenesis. Treatment with the JAK2 inhibitor AG490 reversed BMSC-CM-induced activation of the JAK2/STAT4 pathway. Periurethral injection with BMSC-CCM markedly enhanced the abdominal leak point pressure (LPP) in rats after VD. Histological analysis revealed increased numbers of fibroblasts, improved collagen fibers arrangement and elevated collagens content in the AVW of rats receiving BMSC-CCM. These findings suggest the BMSC secretome activates AVW fibroblasts and contributes to the functional and anatomic recovery of simulated birth trauma-induced SUI in rats.

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.

Clinical features of neurogenic bladder with vesicoureteral reflux in children

OBJECTIVE To study the clinical features of vesicoureteral reflux (VUR) in children with neurogenic bladder (NB), and to provide a reference for its early diagnosis and treatment. METHODS Clinical data were collected from 26 children with NB and urinary tract infection who were admitted to the Department of Pediatric Nephrology from January 2014 to December 2019. According to the presence or absence of VUR, the children were divided into a VUR group with 11 children and a non-VUR group with 15 children. Clinical features were compared between the two groups. RESULTS Compared with the non-VUR group, the VUR group had a significantly higher proportion of children with non-Escherichia coli urinary tract infection, hydronephrosis (the severity of hydronephrosis increased with the grade of VUR), abnormal 99mTc-DMSA renal scanning findings, elevated ratios of urinary albumin, urinary IgG and urinary transferrin to creatinine, increased residual urine volume, and increased detrusor leak point pressure (P < 0.05). CONCLUSIONS When NB children have the clinical manifestations of non-Escherichia coli urinary tract infection, hydronephrosis, abnormal 99mTc-DMSA renal scanning findings, glomerular proteinuria, increased bladder residual urine volume, and high detrusor leak point pressure, such children may already have VUR, and so diagnosis and intervention should be performed as early as possible.

Urodynamic effectiveness of a beta-3 adrenoreceptor agonist (vibegron) for a pediatric patient with anticholinergic-resistant neurogenic detrusor overactivity: a case report

BackgroundMyelomeningocele, which causes a neurogenic bladder, is usually treated with anticholinergics in children with neurogenic detrusor overactivity (NDO); however, anticholinergics cause side effects such as dry mouth, constipation, attention deficit, and inadequate reduction in detrusor leak point pressure. Vibegron, a novel selective beta-3 adrenoreceptor agonist, is a well-established alternative to anticholinergics in adults with an overactive bladder. It remains unknown whether this agent can be used for pediatric patients. We report the case of a girl with anticholinergic-resistant NDO due to tethered cord syndrome after myelomeningocele repair, who was treated with vibegron.Case presentationA 4-year-old Filipino girl had increased frequency of daytime urinary incontinence and foul-smelling urine since the age of 3. Clinical examination revealed constipation, and urinalysis revealed bacteriuria. Voiding cystourethrography revealed an enlarged and trabeculated bladder without vesicoureteral reflux. On the urodynamic study (UDS), she was found to have detrusor overactivity (DO) and low bladder compliance. She could not void and was diagnosed with overflow incontinence. Clean intermittent catheterization (CIC) and orally administered propiverine (0.8 mg/kg/day) were initiated, and urinary incontinence was resolved. She underwent a UDS annually; the UDS at 6 years of age still revealed DO and low bladder compliance in spite of receiving propiverine. The treatment was switched from propiverine to vibegron (1.4 mg/kg/day). On the UDS after a 5-week treatment schedule of vibegron, the DO disappeared and the bladder compliance improved. CIC and orally administered vibegron have been continued for 7 months so far, and she has had no urinary tract infection with no drug-related adverse events.Conclusions Vibegron was effective and well tolerated in the treatment of a pediatric patient with NDO. Vibegron improved the urodynamic parameters for anticholinergic-resistant neurogenic bladder. This agent can be a beneficial and preferable alternative therapeutic agent to anticholinergics in patients with anticholinergic-resistant NDO.

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.

Therapeutic Efficacy of Urethral Sphincter Injections of Platelet-Rich Plasma for the Treatment of Stress Urinary Incontinence due to Intrinsic Sphincter Deficiency: A Proof-of-Concept Clinical Trial.

PurposeThe aim of this study was to investigate the efficacy of autologous platelet-rich plasma (PRP) in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD) refractory to medical treatment.MethodsThirty-five patients with SUI due to urodynamically proven ISD were prospectively enrolled. Five milliliters of PRP (2.5–5 times the platelet concentration in peripheral blood) was injected into the external sphincter at 5 sites; all patients received 4 injections at monthly intervals. The primary end-point was the change in SUI severity as assessed by a visual analogue scale (VAS of SUI). The secondary-endpoints were the Global Response Assessment score and changes in urodynamic parameters from baseline to 3 months after treatment.ResultsThe mean age of patients was 68.7±12 years; the median duration of SUI was 4 years. Five patients had neurogenic SUI, while 30 had nonneurogenic SUI (21 with postprostatectomy incontinence, 6 with previous radical cystectomy, and 3 with other etiologies). Complete dryness was achieved in 7 patients (20.0%) while moderate improvement was observed in 14 (40.0%). The mean VAS of SUI score decreased significantly from 6.57±1.89 to 3.77±2.41 after treatment. The abdominal leak point pressure (ALPP) increased significantly from 98.3±55.8 to 157.3±79.3 cm H2O. There was no increase of ALPP in neurogenic SUI and less increase of ALPP in patients with failed treatment outcomes. No perioperative adverse events or severe complications occurred.ConclusionsUrethral PRP injection is safe and effective in increasing urethral resistance and improving SUI. PRP could be an alternative treatment modality for male and female patients with moderate SUI due to nonneurogenic causes.

Transplantation of bone marrow-derived mesenchymal stem cells with silencing of microRNA-138 relieves pelvic organ prolapse through the FBLN5/IL-1β/elastin pathway.

Nondegradable transvaginal polypropylene meshes for treating pelvic organ prolapse (POP) are now generally unavailable or banned due to serious adverse events. New tissue engineering approaches combine degradable scaffolds with mesenchymal stem/stromal cells from human endometrium (eMSC). In this study, we investigate effect of microRNA-138 (miR-138) regulation on bone marrow-derived mesenchymal stem cells (BMSCs) and the efficacy of BMSC transplantation therapy in a rat POP model. We first identified FBLN5 as a target of miR-138. miR-138, fibulin-5 (FBLN5), interleukin-1β (IL-1β), and elastin expression in uterosacral ligament of POP patients and controls were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. After isolation and identification, BMSCs were treated to alter their expression of miR-138 or FBLN5. Proliferation of BMSCs was analyzed by CCK-8. After establishing the rat pelvic floor dysfunction (PFD) model, we evaluated efficacy of BMSC injection by applying leak point pressure (LPP) and the conscious cystometry (CMG) tests. miR-138 inhibition resulted in increased viability of BMSCs and elevated their secretion of elastin, while downregulating IL-1β expression. BMSCs with inhibited miR-138 improved LPP and conscious CMG results in vivo. Taken together, miR-138 could be a potential therapeutic target for treating POP in conjunction with tissue engineering.

MicroRNA-124-3p affects myogenic differentiation of adipose-derived stem cells by targeting Caveolin-1 during pelvic floor dysfunction in Sprague Dawley rats.

BackgroundThe aim of this study was to investigate using myogenic differentiation of adipose stem cells for the treatment of female pelvic floor dysfunction (PFD) and aimed to further study the influences of microRNA-124-3p (miR-124-3p) in the process of myogenic differentiation of adipose-derived stem cells (ADSCs) through targeting Caveolin-1 (Cav1) during PFD in Sprague Dawley (SD) rats.MethodsThe ADSCs were separated from 6–8-week-old female SD rats (n=25) and were cultivated. Then, we observed the cell status and conducted fat and osteogenic experiments. We then constructed an ADSC-green fluorescent protein (GFP) stable transfer strain. Flow cytometry was used to identify the positive rates of CD44, CD90, and CD45 in ADSCs and ADSC-GFP. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were used to mRNA and protein expression levels. Myogenic differentiation of ADSCs was measured with immunofluorescence methods. A dual-luciferase reporter assay was executed to affirm whether Cav1 was a target of miR-124-3p.ResultsThe isolated ADSCs cells were in good condition under the microscope. The results of flow cytometry showed that the positive rate of CD44 and CD90 was high, and the positive rate of CD45 was low in ADSCs and ADSC-GFP. Under normal culture conditions, ADSCs-GFP cells can be massively adipated and osteogenic. After 5-Aza induced ADSC-GFP myogenic differentiation, the level of miR-124-3p was significantly increased. We found that MiR-124-3p mimics promoted the myogenic differentiation of ADSCs. Moreover, we discovered that Cav1 was a target gene of miR-124-3p and was negatively regulated by miR-124-3p. The results of leak point pressure (LPP), hematoxylin and eosin (HE), and Masson showed that the collagen fiber content of the PFD group was lower than that of the control group; the collagen fiber content of ADSC-GFP, 5-Aza, or miR-124-3p mimics were increased after intervention. Furthermore, the outcomes qRT-PCR, western blotting, and immunofluorescence suggested that miR-124-3p facilitated the survival ADSC-GFP fat transplantation by regulating many key factors in vivo.ConclusionsThese results proofed that miR-124-3p could accelerate myogenic differentiation of ADSCs by down-regulating Cav1 to improve PFD in SD rats, which will pave the way for therapeutic delivery of miRNA targeting PFD disease.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model.Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies.Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder.Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

Adjustment of tension applied in transobturator tapes in females with intrinsic sphincteric deficiency: Two centers' prospective, comparative, randomized surgical trial.

Objectives:Stress incontinence is the most common type of urinary incontinence in females. Recently, the gold standard treatment is mid-urethral tapes, however their efficacy is questioned in intrinsic sphincter deficiency (ISD). In our study, we try to adjust the tension applied during transobturator tapes (TOT) to evaluate its effectiveness in ISD, in order to prevent obstruction or failure and persistence of stress urinary incontinence.Materials and Methods:This study was prospectively conducted on eighty female patients having ISD, presenting at the Urology Departments in Alexandria and Minia University Hospitals. The patients were randomly assigned to two groups, with Group I including forty patients, who underwent TOT using tension-free technique, and Group II including forty patients using our new tension adjustment technique under saddle anesthesia. Patients filled the International Continence Questionnaire and Urinary Distress Inventory and did pressure flow study pre- and postoperatively. Postoperatively, the patients filled Patient Global Impression of Improvement and underwent translabial ultrasound (U/S) to estimate the distance between the tape and the urethra.Results:In Group I, 70% of the patients were cured with mean Valsalva leak point pressure (VLPP) of 51.43 ± 3.39 preoperatively, 20% were not improved, and 10% were improved with a mean VLPP of 44.5 ± 3.54 preoperatively, which increased to 86 ± 4.24 postoperatively. In Group II, 95% of the patients were cured with a mean VLPP of 50.74 cmH2O ± 6.56 preoperatively and 5% improved but not cured with a mean VLPP of 31 cmH2O preoperatively, which increased to 127 cmH2O at a bladder capacity of 400 ml. All patients in both groups underwent translabial U/S 6 months postoperatively. The distance between the mid-tape and the outer urethra measured by translabial US showed no significant difference between the two studied groups.Conclusion:Performing TOT using our tensioned proposed technique in ISD seems to be effective and with low morbidity. Intraoperative adjustment of tension using Valsalva maneuver under saddle anesthesia gives better outcomes than the conventional tension-free technique. The concept of tension-free vaginal tape should be challenged.