Samarium-Doped Indium-Tin-Oxide Electrode for Organic Light-Emitting Devices.

Here in, properties of samarium-doped indium-tin-oxide (ITO:Sm) films deposited by DC-magnetron sputtering, and organic light-emitting devices (OLEDs) using an ITO:Sm film as an anode were investigated. The electrical resistivity of the ITO:Sm films increased with Sm doping. The work function of each ITO:Sm film (5.2-5.7 eV) was higher than that of an ITO film (4.8 eV). The crystal structure of the ITO:Sm films was In2O3-type when the doping ratio of Sm in the film was up to 5 at.%, and the structure was amorphous in more strongly samarium-doped films. The properties of the OLEDs were varied by the doping ratio of samarium in the ITO:Sm electrodes. The OLEDs with the ITO:Sm electrode exhibited higher efficiency than that of an ITO-based control device at the same current density.

The fibrosis of ketamine, a noncompetitive N-methyl-d-aspartic acid receptor antagonist dose-dependent change in a ketamine-induced cystitis rat model.

Ketamine abusers have greatly increased in number worldwide during recent years. The consumption of ketamine has increased, as have the number of published accounts of devastating urological sequelae. However, the mechanism of ketamine-associated urinary tract dysfunction remains unclear. This study was to evaluate the ketamine dose-dependency of ketamine-induced cystitis (KC) in a rat model. A total of 42 Sprague-Dawley rats (female, 10-week-old) were used. Each of the 7 KC rat models were induced by 1, 5, 10, 25 and 50 mg/kg ketamine intravenous injection for two weeks. For the sham group (n = 7), a phosphate-buffered saline (PBS) vehicle was used rather than ketamine hydrochloride. The cystometric parameters, histological examinations, staining for Masson's trichome, cytokeratin, toluidine blue and quantitative PCR were measured at two weeks following the intervention. The voiding interval gradually decreased depending upon the ketamine dose of 1, 5, 10, 25, or 50 mg/kg, respectively, and was decreased compared with Sham. Bladder capacity was decreased as ketamine dose increased. In particular, the increase of fibrosis and submucosal apoptosis were found according to the increase of the ketamine dose. The bladder apoptosis in the KC rat model makes the fibrotic bladder change, and led us to hypothesize that fibrosis could contribute to the lower urinary-tract symptoms. We suggest that according to the pathophysiology evidence, fibrosis induced by apoptosis plays a key role in KC.

Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway.

Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague-Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC+MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC+MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology.

A prospective, observational study to assess the association between dry mouth and solifenacin treatment in patients with overactive bladder syndrome.

PURPOSE: Dry mouth is among the most common side effects of antimuscarinic therapy. This study evaluated the drug-related change in dry mouth after the solifenacin treatment and the impact of dry mouth on the drug efficacy against overactive bladder syndrome (OAB). MATERIALS AND METHODS: OAB patients (n = 331) were enrolled in a prospective, multicenter, 8-week observational study of solifenacin treatment. Participants were >20 years of age and presented with OAB symptoms for ≥3 months, a total overactive bladder symptom score (OABSS) of ≥3, and an urgency score of ≥2. Primary endpoints were changes in dry mouth according to baseline dry mouth status using Xerostomia Inventory (XI) and the effect of dry mouth to the drug efficacy according to improvements in the OABSS. RESULTS AND CONCLUSIONS: Three hundred and thirty-three patients were initially screened for the study, with 331 actually enrolled. One hundred and ninety-four patients completed the study. Mean total XI scores increased by 2.8 points in the entire patient population, with larger increases for patients stratified into the non-dry mouth group (NDG) versus the dry mouth group (DG) (4.0 vs. 1.9, p = 0.015) at study baseline. Mean total OABSSs decreased by 3.2 points, with no significant differences between the NDG and the DG (-3.4 vs. -3.0 points, p = 0.578). The dry mouth aggravated in 71 patients (29.2 %) (NDG 30.1 % and DG 27.1 %), but only 10/331 individuals (3.0 %) stopped medication due to xerostomia. Dry mouth progressed in approximately 30 % of the OAB patients, regardless of its presence before solifenacin treatment. However, OAB symptoms were well relieved by solifenacin, and the adverse influence of dry mouth on drug persistence was low.

Comparing Argus sling and artificial urinary sphincter in patients with moderate post-prostatectomy incontinence.

Post-prostatectomy incontinence (PPI) is a main complication of radical prostatectomy. The purpose of this study was to compare the efficacy and safety of the Argus male sling (Argus) with that of artificial urinary sphincters (AUS) in patients with moderate PPI. A total of 33 moderate PPI patients underwent AUS or Argus implantation from January 2009 to June 2013 (13 AUS, 20 Argus). We defined moderate PPI as the use of 2-4 pads per day. To compare efficacy, we assessed the success rate between the two groups. Success was defined as the daily need for no pads or one small safety pad that remained dry most of the day. The mean patient age was 73.5±6.3 yr in the AUS group and 70.9±5.1 yr in the Argus group, and the mean follow-up period was 29.8±14.9 months in the AUS group and 24.7±11.8 months in the Argus group. The success rate was 72.7% in the AUS group and 85.0% in the Argus group (P=0.557). Abnormal postoperative pain persisted in more patients in the Argus group (6/20, 30%) than in the AUS group (1/13, 7.7%) (P=0.126). However, the rate of other complications was not different between the two groups (7.7% and 15.0% for AUS and Argus, respectively, P=0.822). Argus surgery showed similar success and complication rates to those of AUS in moderate PPI patients, indicating that it could be an alternative surgical option for the treatment of moderate PPI.

Clinical factors associated with dose escalation of solifenacin for the treatment of overactive bladder in real life practice.

PURPOSE: To determine the baseline clinical characteristics associated with dose escalation of solifenacin in patients with overactive bladder (OAB). METHODS: We analyzed the data of patients with OAB (micturition frequency ≥8/day and urgency ≥1/day) who were treated with solifenacin and followed up for 24 weeks. According to our department protocol, all the patients kept voiding diaries, and OAB symptom scores (OABSS) were monitored at baseline and after 4, 12, and 24 weeks of solifenacin treatment. RESULTS: In total, 68 patients (mean age, 60.8±10.0 years) were recruited. The dose escalation rate by the end of the study was 41.2%, from 23.5% at 4 weeks and 17.6% at 12 weeks. At baseline, the dose escalator group had significantly more OAB wet patients (53.6% vs. 20.0%) and higher total OABSS (10.2±2.4 vs. 7.9±3.5, P=0.032) than the nonescalator group. OAB wet (odds ratio [OR], 4.615; 95% confidence interval [CI], 1.578-13.499; P<0.05) and total OABSS (OR, 1.398; 95% CI, 1.046-1.869; P<0.05) were found to be independently associated with dose escalation. CONCLUSIONS: Patients who have urgency urinary incontinence and high total OABSS have a tendency for dose escalation of solifenacin.

Safety and efficacy of desmopressin for the treatment of nocturia in elderly patients: a cohort study.

PURPOSE: Desmopressin is used widely to treat nocturnal polyuria (NP), but there is concern of hyponatremia especially in elderly patients. This study aimed to evaluate the safety and efficacy of long-term desmopressin treatment in elderly patients with NP. METHODS: Patients who were ≥65 years old with NP were analyzed. All patients were started on 0.1 mg desmopressin, and the dose was escalated to 0.2 mg depending on patient symptoms. All patients were educated the mechanism of desmopressin. The voiding diary and serum sodium levels were evaluated at baseline, 3-7 days after starting treatment and every 3-6 months. Safety was evaluated by hyponatremia, hyponatremic symptoms and other adverse drug events. The mean changes in number of nocturia and nocturnal urine volume (NUV) were evaluated for efficacy. RESULTS: A total of 68 patients were included. The mean age was 72.6 (66-85) years. The mean night-time frequency was 3.0 ± 1.8 day, and the mean serum sodium level was 141.2 ± 2.1 mEq/L at baseline. The mean follow-up period was 27.9 months. The mean decrease in serum sodium level was 1.3 ± 3.4 mEq/L at the last follow-up (p = 0.003). Hyponatremia incidence was 4.4 %, and all patients recovered by stopping medication. Severe adverse events were not observed. The mean night-time frequency had decreased by 2.1, and the NUV had decreased by 374.2 ± 261.3 mL at the last follow-up (p < 0.001). CONCLUSIONS: Desmopressin at doses below 0.2 mg is safe and effective in elderly patients with NP if patients are well informed and are closely followed up.

A Comparative Study of Outside-In and Inside-Out Transobturator Tape Procedures for Female Stress Urinary Incontinence: 7-Year Outcomes.

OBJECTIVES: The aim of this study was to compare the long-term surgical outcomes of the "inside-out" (TVT-O) and "outside-in" (TOT) transobturator tape procedures for treating female stress urinary incontinence (SUI). METHODS: This was a retrospective analysis of women who underwent a transobturator tape procedure and were followed for at least 7 years. Patients' baseline characteristics and urodynamic parameters were compared between the two groups and analyzed to identify factors related to failure of therapy. RESULTS: A total of 215 patients were followed for > 7 years (TOT, n = 129; TVT-O, n = 86), with a median follow-up period of 7.1 years. No significant differences were observed in the baseline characteristics or urodynamic parameters between the groups, except incontinence type (TOT 33.3% vs. TVT-O 52.3% with mixed urinary incontinence, P < 0.05). The TOT group had significantly higher cure rate, satisfaction with surgery, willingness to undergo the procedure to others, and willingness to receive the same procedure than those of the TVT-O group (87.1 vs. 66.7%, 87.6 vs. 64.0%, 89.1 vs. 77.9%, and 77.5 vs. 57.0%, all P-values < 0.05), respectively. A Univariate analysis identified maximum urethral closure pressure (MUCP) (odds ratio, 0.980; 95% confidence interval, 0.960-1.000; P = 0.046) as a risk factor for surgical failure. CONCLUSIONS: TOT and TVT-O procedures are safe and effective for the treatment of SUI in women over a 7-year follow-up period. The TOT procedure had higher cure rate and satisfaction rates than TVT-O. MUCP may be associated with surgical outcome.

Correlation of the Overactive Bladder Symptom Score, and the Voiding Diary and Urodynamic Parameters in Patients with Overactive Bladder Syndrome.

OBJECTIVES: To investigate correlations between the overactive bladder symptom score (OABSS), the voiding diary, and urodynamic parameters in women with overactive bladder syndrome (OAB). METHODS: A data analysis was performed on 164 women who presented with OAB between January 2006 and December 2011. All patients completed a 3-day voiding diary, OABSS (frequency [Q-F], nocturia [Q-N], urgency [Q-U], urgency incontinence [Q-UI]), and a urodynamic study. The relationships of the OABSS, voiding diary variables, and urodynamic parameters, such as detrusor overactivity (DO) and maximal cystometric capacity (MCC), were analyzed. We used univariate and multivariate regression analysis to compare the bladder diary and OABSS. Detrusor overactivity and other variables were compared using logistic regression analysis. RESULTS: The 24-h frequency, voided volume, and presence of urgency in the voiding diary were 9.8 ± 3.2 events/day, 176.6 ± 5.8 mL, and 70.7%. The 24-h frequency and the voided volume recorded were significantly associated with Q-F (P < 0.001, P < 0.001) and Q-N (P = 0.008, P = 0.005). The presence of urgency recorded was associated with Q-U in multivariate analysis (P = 0.012). The predictive factors related to DO was Q-U in multivariate analysis. The MCC was found to correlate with the voided volume, urgency episode, Q-F. CONCLUSIONS: The OABSS correlate well with the voiding diary and urodynamic parameters and could be a useful tool to diagnose OAB when there is an absence of voiding diary and to later monitor OAB symptoms and treatment interventions.

The paracrine effects of mesenchymal stem cells stimulate the regeneration capacity of endogenous stem cells in the repair of a bladder-outlet-obstruction-induced overactive bladder.

Overactive bladder (OAB), which is characterized by the sudden and uncomfortable need to urinate with or without urinary leakage, is a challenging urological condition. The insufficient efficacy of current pharmacotherapies that uses antimuscarinic agents has increased the demand for novel long-term/stable therapeutic strategies. Here, we report the superior therapeutic efficacy of using mesenchymal stem cells (MSCs) for the treatment of OAB and a novel therapeutic mechanism that activates endogenous Oct4(+) primitive stem cells. We induced OAB using bladder-outlet-obstruction (BOO) in a rat model and either administered a single transplantation of human adipose-derived MSCs or daily intravenous injections of solifenacin, an antimuscarinic agent, for 2 weeks. Within 2 weeks, both the MSC- and solifenacin-treated groups similarly demonstrated relief from BOO-induced detrusor overactivity, hypertrophic smooth muscle, and neurological injuries. In contrast with the solifenacin-treated groups, a single transplantation of MSCs improved most OAB parameters to normal levels within 4 weeks. Although the transplanted human MSCs were hardly engrafted into the damaged bladders, the bladder tissues transplanted with MSCs increased rat sequence-specific transcription of Oct4, Sox2, and Stella, which are surrogate markers for primitive pluripotent stem cells. In addition, MSCs enhanced the expression of several genes, responsible for stem cell trafficking, including SDF-1/CXCR4, HGF/cMet, PDGF/PDGFR, and VEGF/VEGFR signaling axis. These changes in gene expression were not observed in the solifenacin-treated group. Therefore, we suggest the novel mechanisms for the paracrine effect of MSCs as unleashing/mobilizing primitive endogenous stem cells, which could not only explain the long-term/stable therapeutic efficacy of MSCs, but also provide promising new therapies for the treatment of OAB.

Effect of combined systematized behavioral modification education program with desmopressin in patients with nocturia: a prospective, multicenter, randomized, and parallel study.

PURPOSE: The aims of this study were to investigate the efficacy of combining the systematized behavioral modification program (SBMP) with desmopressin therapy and to compare this with desmopressin monotherapy in the treatment of nocturnal polyuria (NPU). METHODS: Patients were randomized at 8 centers to receive desmopressin monotherapy (group A) or combination therapy, comprising desmopressin and the SBMP (group B). Nocturia was defined as an average of 2 or more nightly voids. The primary endpoint was a change in the mean number of nocturnal voids from baseline during the 3-month treatment period. The secondary endpoints were changes in the bladder diary parameters and questionnaires scores, and improvements in self-perception for nocturia. RESULTS: A total of 200 patients were screened and 76 were excluded from the study, because they failed the screening process. A total of 124 patients were randomized to receive treatment, with group A comprising 68 patients and group B comprising 56 patients. The patients' characteristics were similar between the groups. Nocturnal voids showed a greater decline in group B (-1.5) compared with group A (-1.2), a difference that was not statistically significant. Significant differences were observed between groups A and B with respect to the NPU index (0.37 vs. 0.29, P=0.028), the change in the maximal bladder capacity (-41.3 mL vs. 13.3 mL, P<0.001), and the rate of patients lost to follow up (10.3% [7/68] vs. 0% [0/56], P=0.016). Self-perception for nocturia significantly improved in both groups. CONCLUSIONS: Combination treatment did not have any additional benefits in relation to reducing nocturnal voids in patients with NPU; however, combination therapy is helpful because it increases the maximal bladder capacity and decreases the NPI. Furthermore, combination therapy increased the persistence of desmopressin in patients with NPU.

Elimination of Hunner's Ulcers by Fulguration in Patients With Interstitial Cystitis: Is It Effective and Long Lasting?

PURPOSE: To evaluate the outcome of fulguration of Hunner's ulcers (HUs) in painful bladder syndrome/interstitial cystitis (PBS/IC) that is refractory to conservative treatment. MATERIALS AND METHODS: Patients diagnosed with refractory PBS/IC and treated with fulguration between 2011 and 2013 were identified through screening of medical records. To evaluate treatment outcomes, voiding diaries, the visual analogue scale (VAS) for pain, and two IC symptom questionnaires (pelvic pain and urgency/frequency scale [PUF] and O'Leary-Sant IC symptom index and IC problem index [OS]) were used. Fulguration was deemed to be successful if the VAS score was <2 or less than half of the preoperative VAS score. RESULTS: In total, 27 patients with PBS/IC in whom conservative treatments had failed were enrolled. Two months after fulguration, decreases were observed in the mean 24-hour urinary frequency (from 16.0 to 10.2), 24-hour urgency episodes (8.0 to 1.8), and the VAS (5.8 to 1.2), PUF symptom (15.1 to 7.0), PUF bother (8.4 to 2.7), OS symptom (15.1 to 7.2), and OS problem (13.8 to 6.0) scores. At 5 and 10 months, all variables had worsened. At 2, 5, and 10 months, the success rates were 94.1%, 70.0%, and 33.3%, respectively. Four patients underwent one repeat fulguration on average 11.3 months after the first fulguration. Repeat fulguration was not significantly associated with any clinical characteristics. CONCLUSIONS: In PBS/IC that was refractory to medication or other conservative treatments, HU elimination by fulguration effectively improved symptoms. However, this effect decreased gradually over time.

A study assessing the quality of life related to voiding symptoms and sexual functions in menopausal women.

PURPOSE: To investigate the impact of menopause on the quality of life (QoL) of middle-aged and older women, including their general well-being, voiding-related symptoms, and sexual distress. MATERIALS AND METHODS: To assess QoL, we administered a questionnaire that included questions about voiding-related symptoms and female sexual distress and part of the Women's Health Questionnaire. The self-administered questionnaires were completed by 1,679 women in the Korea. Data for 1,262 women were available for analysis, including premenopausal (n=307), perimenopausal (n=240), and postmenopausal (n=715) groups. RESULTS: Voiding-related discomfort increased significantly in perimenopausal and postmenopausal women compared with premenopausal women (p<0.001). General well-being worsened as menopause progressed (p<0.001). Menopausal women who were older (p=0.014), had a hysterectomy (p=0.005), or had urinary incontinence (p=0.001) had more voiding-related symptoms. Hypertension (p=0.026), cardiac disease (p=0.013), and arthritis (p=0.001) resulted in significantly decreased general well-being. Women with a hysterectomy (p=0.017) and those with arthritis (p=0.004) had high sexual distress. In the menopausal group, employed women had better general well-being than did unemployed women. CONCLUSIONS: Menopause negatively affected the QoL of middle-aged and older women because of decreased general well-being and increased voiding-related symptoms. General health, even in menopausal women, was important to maintain a better QoL. To preserve the QoL of women undergoing menopause, control of menopause and underlying disease should be considered.