Evaluation of PTEN Inhibitor Following Spinal Cord Injury on Recovery of Voiding Efficiency and Motor Function Observed by Regeneration in Spinal Cord / 대한배뇨장애요실금학회지

Purpose@#Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Therefore, we investigated the effects of a tissue gene nerve (TGN), PTEN inhibitor, on voiding function, motor function, and the expression of growth factors after SCI. @*Methods@#In this experiment, female rats were randomly divided into 3 groups (n=10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and TGN-treated group. Cystometry; the Basso, Beattie, and Bresnahan (BBB) scale test; the ladder walking test; hematoxylin and eosin staining; and Western blotting for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) were performed to evaluate functional and molecular changes. @*Results@#After SCI, the rats exhibited decreased walking ability according to the BBB scale test and impaired coordinative function according to the ladder walking test. The PTEN inhibitor promoted enhanced walking ability and coordinative function. Cystometry showed voiding impairment after SCI and improved voiding function was observed after PTEN treatment. Overexpression of VEGF, BDNF, and NGF were observed after SCI. Administration of PTEN inhibitors significantly attenuated the overexpression of growth factors due to SCI. @*Conclusion@#PTEN inhibitor treatment diminished the overexpression of growth factors and promoted the repair of damaged tissue. PTEN inhibitor-treated rats also showed improved motor function and improved voiding function. Therefore, we suggest TGN as a new therapeutic agent that can be applied after SCI.

Stem Cell Therapy for Neurogenic Bladder After Spinal Cord Injury: Clinically Possible? / 대한배뇨장애요실금학회지

Neurogenic bladder (NB) after spinal cord injury (SCI) is a common complication that inhibits normal daily activities and reduces the quality of life. Regrettably, the current therapeutic methods for NB are inadequate. Therefore, numerous studies have been conducted to develop new treatments for NB associated with SCI. Moreover, a myriad of preclinical and clinical trials on the effects and safety of stem cell therapy in patients with SCI have been performed, and several studies have demonstrated improvements in urodynamic parameters, as well as in sensory and motor function, after stem cell therapy. These results are promising; however, further high-quality clinical studies are necessary to compensate for a lack of randomized trials, the modest number of participants, variation in the types of stem cells used, and inconsistency in routes of administration.

Influence of Circadian Disruption Associated With Artificial Light at Night on Micturition Patterns in Shift Workers / 대한배뇨장애요실금학회지

Shift workers often experience problems associated with circadian disruption associated with artificial light at night and nocturia is commonly noted in night-shift workers. Nocturia associated with circadian disruption is due to increased urine production of the kidney and decreased storage function of the bladder. A recent discovery of peripheral clock genes in the bladder and their role in contractile property of the bladder support that micturition is closely related to the circadian rhythm. Moreover, there are clinical studies showed that shift workers more often experienced nocturia due to circadian disruption. However, comparing with other health problems, concerns on nocturia and voiding dysfunction associated with circadian disruption are insufficient. Therefore, further studies about voiding dysfunction associated with the circadian disruption in shift workers are necessary.

Treatment of Prostate Disease and Cognitive Problems / 대한배뇨장애요실금학회지

No abstract available.

Treadmill Exercise Improves Motor Function by Suppressing Purkinje Cell Loss in Parkinson Disease Rats / 대한배뇨장애요실금학회지

PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.

Neonatal Bladder Irritation Is Associated With Vanilloid Receptor TRPV1 Expression in Adult Rats / 대한배뇨장애요실금학회지

PURPOSE: To evaluate whether mild chemical irritation of the bladder in neonatal rats is associated with persistent vanilloid receptor transient receptor potential vanilloid subfamily 1 (TRPV1) activity in adult rats. METHODS: Female Sprague-Dawley rats were used. Ten-day-old rat pups underwent bladder sensitization via intravesical infusion of 0.2% acetic acid in saline with or without prior bladder desensitization with capsaicin. After 8 weeks, 3 groups of rats (control [group 1], bladder sensitization [group 2], and bladder desensitization [group 3]) underwent cystometry. Inflammation of bladder tissue and the expression of TRPV1 in bladder tissue and dorsal root ganglia (DRG) were also evaluated. RESULTS: The bladder sensitization group showed more frequent voiding contractions. TRPV1 expression in adult bladder tissue was elevated in group 2. TRPV1 mRNA levels in the bladder and DRG were significantly higher in group 2 than in group 1. Moreover, group 2 had significantly more DRG neurons (identified by uptake of the retrograde label Fast Blue) that exhibited TRPV1 immunoreactivity. CONCLUSIONS: We found a significant association between neonatal bladder sensitization and persistent TRPV1 activity in adult rats. This is the first study to focus on the underlying pathogenesis of bladder overactivity from childhood to adulthood. Our findings could lead to the development of new strategies for the treatment and prevention of adult urinary symptoms arising from childhood urinary tract dysfunction.

Importance of Central Regulation for Lower Urinary Tract Functions / 대한배뇨장애요실금학회지

No abstract available.

Development and Evaluation of Hyaluronic Acid-Based Hybrid Bio-Ink for Tissue Regeneration

BACKGROUND: Bioprinting has recently appeared as a powerful tool for building complex tissue and organ structures. However, the application of bioprinting to regenerative medicine has limitations, due to the restricted choices of bio-ink for cytocompatible cell encapsulation and the integrity of the fabricated structures. METHODS: In this study, we developed hybrid bio-inks based on acrylated hyaluronic acid (HA) for immobilizing bioactive peptides and tyramine-conjugated hyaluronic acids for fast gelation. RESULTS: Conventional acrylated HA-based hydrogels have a gelation time of more than 30 min, whereas hybrid bioink has been rapidly gelated within 200 s. Fibroblast cells cultured in this hybrid bio-ink up to 7 days showed < 90% viability. As a guidance cue for stem cell differentiation, we immobilized four different bio-active peptides: BMP-7-derived peptides (BMP-7D) and osteopontin for osteogenesis, and substance-P (SP) and Ac-SDKP (SDKP) for angiogenesis. Mesenchymal stem cells cultured in these hybrid bio-inks showed the highest angiogenic and osteogenic activity cultured in bio-ink immobilized with a SP or BMP-7D peptide. This bio-ink was loaded in a three-dimensional (3D) bioprinting device showing reproducible printing features. CONCLUSION: We have developed bio-inks that combine biochemical and mechanical cues. Biochemical cues were able to regulate differentiation of cells, and mechanical cues enabled printing structuring. This multi-functional bio-ink can be used for complex tissue engineering and regenerative medicine.

Fabrication of Microchannels and Evaluation of Guided Vascularization in Biomimetic Hydrogels

BACKGROUND: The fabrication of microchannels in hydrogel can facilitate the perfusion of nutrients and oxygen, which leads to guidance cues for vasculogenesis. Microchannel patterning in biomimetic hydrogels is a challenging issue for tissue regeneration because of the inherent low formability of hydrogels in a complex configuration. We fabricated microchannels using wire network molding and immobilized the angiogenic factors in the hydrogel and evaluated the vasculogenesis in vitro and in vivo. METHODS: Microchannels were fabricated in a hyaluronic acid-based biomimetic hydrogel by using “wire network molding” technology. Substance P was immobilized in acrylated hyaluronic acid for angiogenic cues using Michael type addition reaction. In vitro and in vivo angiogenic activities of hydrogel with microchannels were evaluated. RESULTS: In vitro cell culture experiment shows that cell viability in two experimental biomimetic hydrogels (with microchannels and microchannels + SP) was higher than that of a biomimetic hydrogel without microchannels (bulk group). Evaluation on differentiation of human mesenchymal stem cells (hMSCs) in biomimetic hydrogels with fabricated microchannels shows that the differentiation of hMSC into endothelial cells was significantly increased compared with that of the bulk group. In vivo angiogenesis analysis shows that thin blood vessels of approximately 25–30 µm in diameter were observed in the microchannel group and microchannel + SP group, whereas not seen in the bulk group. CONCLUSION: The strategy of fabricating microchannels in a biomimetic hydrogel and simultaneously providing a chemical cue for angiogenesis is a promising formula for large-scale tissue regeneration.

Evidence Is Enough?: A Systematic Review and Network Meta-Analysis of the Efficacy of Tamsulosin 0.2 mg and Tamsulosin 0.4 mg as an Initial Therapeutic Dose in Asian Benign Prostatic Hyperplasia Patients / 대한배뇨장애요실금학회지

PURPOSE: We compared the efficacy of tamsulosin between 0.2 mg and 0.4 mg in Asian prostatic hyperplasia (BPH) patients using network meta-analysis due to lack of studies with direct comparison. METHODS: The literature search was conducted using the MEDLINE, Embase, and Cochrane Library. Keywords used were “BPH,”“tamsulosin,”“placebo.” Experimental groups were defined as tamsulosin 0.2 mg (Tam 0.2) and 0.4 mg (Tam 0.4) and common control group was defined as placebo for indirect treatment comparison. Mixed treatment comparison was performed including one direct comparison study. RESULTS: Seven studies met the eligible criteria. Indirect treatment comparison revealed that total International Prostate Symptoms Score (IPSS) and quality of life score of IPSS were not significantly different in Tam 0.2 and Tam 0.4 (P>0.05). There was no significant difference of maximal flow rate and postvoid residual urine volume in Tam 0.2 and Tam 0.4 (P>0.05). Mixed treatment comparison including one direct comparison study showed inconsistency (P<0.001). Therefore, analysis using direct treatment comparison effect sizes of Tam 0.2 vs. placebo and Tam 0.4 vs. placebo was done and there was no significant difference. CONCLUSIONS: Network meta-analysis showed no difference of efficacy between tamsulosin 0.2 mg and 0.4 mg and the evidence of tamsulosin 0.4 mg as initial dose for Asian BPH patient seems to be insufficient. Therefore, initial dose of tamsulosin for Asian BPH patient should be 0.2 mg.

Chronic Pelvic Pain and Neuropelveology / 대한배뇨장애요실금학회지

No abstract available.

The Authors Reply: Reply on “Evidence Is Enough?: A Systematic Review and Network Meta-Analysis of the Efficacy of Tamsulosin 0.2 mg and Tamsulosin 0.4 mg as an Initial Therapeutic Dose in Asian Benign Prostatic Hyperplasia Patients” / 대한배뇨장애요실금학회지

No abstract available.

Interstitial Cystitis/Bladder Pain Syndrome: A Urologic Mystery / 대한배뇨장애요실금학회지

No abstract available.

Acute Dose-Related Differential Effects of Methylphenidate on Murine Cystometric Parameters / 대한배뇨장애요실금학회지

PURPOSE: Methylphenidate is the most widely used central nervous system stimulant in patients with attention deficit hyperactivity disorder. However, few studies have assessed its effects on voiding. Various doses of methylphenidate were investigated for their effects on cystometric parameters in conscious mice. METHODS: Ten male C57BL/6 mice, weighing between 20 and 23 g, were used in this study. To compare the acute drug responses before and after the oral medication was administered in the awake condition, we injected the solution through a catheter inserted into the stomach. Methylphenidate (1.25, 2.5, and 5 mg/kg) in an injection volume of 0.05 mL was administered. RESULTS: Four mice that received high doses of methylphenidate (2.5 and 5 mg/kg) showed no voiding contraction, with urine leakage. Six mice that received a low dose of methylphenidate (1.25 mg/kg) showed typical micturition cycles before and after administration. The micturition pressure decreased and bladder capacity increased without an increased residual volume after administration. CONCLUSIONS: Methylphenidate has differential, dose-dependent effects on the function of the lower urinary tract, due to the dependent relationship between the brain and lower urinary tract. Especially at higher doses, this drug may interfere with normal micturition. Therefore, more detailed clinical or experimental studies are warranted in the future.

Impact of Treatment With Statins on Prostate-Specific Antigen and Prostate Volume in Patients With Benign Prostatic Hyperplasia

PURPOSE: We investigated the impact on prostate-specific antigen (PSA) and prostate volume (PV) of statin medication for 1 year in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We retrospectively investigated 791 patients in whom BPH was diagnosed. For analysis, the patients were divided into four groups according to their medications: group A, alpha-blocker; group B, alpha-blocker+statin; group C, alpha-blocker+dutasteride; group D, alpha-blockers+statin+dutasteride. To investigate changes in serum PSA, PV, and total cholesterol, we analyzed the data at the time of initial treatment and after 1 year of medication. RESULTS: After 1 year, group A showed a 1.3% increase in PSA and a 1.0% increase in PV. Group B showed a 4.3% decrease in PSA and a 1.8% decrease in PV. The difference in PV reduction between groups A and B was statistically significant (p<0.001). Group C showed a 49.1% reduction in PSA and a 22.9% reduction in PV. Group D showed a 51.6% reduction in PSA and a 24.5% reduction in PV. The difference in PV reduction between groups C and D was not statistically significant (p=0.762). By use of a multivariate logistic regression model, we found that the probability of PV reduction after 1 year was more than 14.8 times in statin users than in statin nonusers (95% confidence interval, 5.8% to 37.6%; p<0.001). CONCLUSIONS: Statin administration reduced PSA and PV in BPH patients. This finding may imply the improvement of lower urinary tract symptoms and prevention of cardiovascular disease and chemoprevention of prostate cancer with statin treatment.

Wilms' Tumor in a Horseshoe Kidney

The incidence of horseshoe kidney is about 1 in 400 cases. The presence of Wilms' tumor with a horseshoe kidney is unusual, and the occurrence of Wilms' tumor in a horseshoe kidney is estimated at 0.4 to 0.9% of all Wilms' tumors. We report the case of a 5-year-old boy who presented with a stage IV Wilms' tumor in a horseshoe kidney. The patient was treated with preoperative chemotherapy followed by surgical resection and adjuvant chemotherapy. This case illustrates the role of preoperative chemotherapy for preserving renal function and aims to highlight the multimodality treatment of Wilms' tumor.

Tumor Establishment Features of Orthotopic Murine Bladder Cancer Models

PURPOSE: Animal tumor models are important for the evaluation of novel therapeutic modalities. Since the initial report of an orthotopic bladder tumor model, several modifications have been proposed to improve the tumor take rate. Here we compared the HCl-pretreated and electrocauterization-pretreated orthotopic murine bladder tumor models. MATERIALS AND METHODS: MBT-2 murine bladder cancer cells were transurethrally implanted in the bladder of syngeneic C3H/He mice. The mice were divided into three groups according to pretreatment methods (electrocautery, HCl, and control group) and were subjected to pretreatment before instillation of MBT-2 tumor cells into the bladder. Mice were sacrificed on day 21, and bladders were harvested, weighed, and examined histopathologically. RESULTS: The tumor take rate of the control, electrocautery, and HCl groups was 0%, 54%, and 100%, respectively. The tumor take rate of the HCl group was significantly higher than that of the control group (p<0.01) and the electrocautery group (p=0.01). Pathologic reports revealed that all established bladder tumors were high-grade papillary urothelial carcinomas. CONCLUSIONS: The HCl pretreatment model was a preferable murine bladder tumor model for evaluating further therapeutic interventions.

Relationship between Metabolic Syndrome and Prostate Volume in Korean Men under 50 Years of Age

PURPOSE: The metabolic syndrome (MS) has been accepted as an important cause of benign prostatic hyperplasia (BPH) in old age. However, there are no studies of the influence of MS on prostate volume in relatively young adults. We evaluated the relationship between parameters of MS and prostate volume in men under 50 years of age who visited our health promotion center. MATERIALS AND METHODS: A total of 968 men aged 30 to 49 years were enrolled from March 2009 to June 2010. Prostate volume by transrectal ultrasonography of the prostate, serum prostate-specific antigen, digital rectal examination, urinalysis, and MS-related parameters were investigated. We evaluated the correlations of prostate volume with MS and MS-related parameters. RESULTS: Prostate volume was not significantly larger in the MS group (18.4 cc; range: 14.3-23.1 cc) than in the non-MS group (17.8 cc; range, 13.6-21.6 cc). The prostate volumes in subjects with abnormal fasting plasma glucose (FPG) (18.9 cc; range, 14.3-22.7 cc) and abnormal waist circumference (WC) (19.5 cc; range, 15.6-23.7 cc) were significantly larger than those of subjects with normal parameters (16.9 [range, 12.7-20.4] cc and 17.5 [range, 13.3-21.2] cc, respectively; p=0.001). The logistic regression analysis showed the FPG level and WC to have a significantly positive correlation with the prostate volume (odds ratios: 1.441 [95% CI: 1.303-1.643] and 2.305 [95% CI: 1.470-3.614], respectively). CONCLUSIONS: Groups with abnormal FPG and WC had larger prostate volumes than did normal groups. The abnormal FPG and WC could be more important factors than MS in prostate volume enlargement in relatively young adults.

Association of Prostate Specific Antigen (PSA) Velocity with Age and Initial PSA in Healthy Korean Men / 대한남성과학회지

PURPOSE: Prostate specific antigen (PSA) is a test with relatively low specificity used for determination of risk for prostate cancer. PSA velocity (PSAV) has been used as a complimentary test. We investigated the association of PSAV with age and an initial PSA. MATERIALS AND METHODS: We enrolled 989 healthy men with initial PSA of 4.0ng/ml or lower. The PSA levels were measured at intervals of at least 12 months. We analyzed the influence of age and initial PSA on the PSAV. RESULTS: PSAV was directly correlated with age and the initial PSA. The initial PSA was not correlated with the PSAV when adjusted by age (r=0.009, p=0.773); age was correlated with PSAV when adjusted by initial PSA level (r=0.276, p<0.001). The mean PSAV in cases with initial PSA of 2.1-4.0 ng/ml was significantly greater compared to the cases with an initial PSA of 0-2.0 ng/ml (p<0.01). The ratio of the men with a PSAV greater than 0.75 ng/ml/year was significantly higher in cases with an initial PSA of 2.1-4.0 ng/ml (p<0.05). CONCLUSIONS: PSAV is associated with age and an initial PSA level in healthy Korean men. Men with initial PSA of 2.1-4.0 ng/ml had an abnormal PSAV in high proportion, and therefore annual follow up PSA would be useful for the early detection of prostate cancer in these cases.

Potassium-Titanyl-Phosphate Laser Photoselective Vaporization of the Prostate in Patients with Benign Prostatic Hyperplasia with Detrusor Underactivity: Influence on Detrusor Pressure

PURPOSE: Potassium-titanyl-phosphate laser photoselective vaporization of the prostate (PVP) is a safe and effective treatment for patients with symptomatic benign prostatic hyperplasia (BPH). The aim of this study was to assess the influence and the effect of PVP in BPH patients with detrusor underactivity. MATERIALS AND METHODS: We evaluated 21 patients with detrusor under-activity treated with PVP for BPH from January 2006 to December 2007. Detrusor underactivity was defined as detrusor pressure at maximal flow rate (Qmax) of less than 30 cmH2O and Qmax of less than 15 ml/s. Urodynamic studies were performed and international prostate symptom score (IPSS) and quality of life (QoL) scores were assessed preoperatively and at 6 months postoperatively. RESULTS: There were significant improvements in Qmax, voiding urine volume, post-void residual urine volume, IPSS, and QoL scores at 6 months after PVP treatment. However, patients did not show significant changes in maximal bladder capacity, bladder compliance, or detrusor pressure at Qmax. CONCLUSIONS: Even though BPH patients had detrusor underactivity, PVP was an effective surgical procedure. However, PVP did not make any significant difference on detrusor pressure at Qmax in 6 months.