Development of a Multiparametric Magnetic Resonance Imaging-Based Nomogram for Clinically Insignificant Prostate Cancer

Purpose@#Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. @*Materials and Methods@#We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. @*Results@#Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. @*Conclusions@#We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker.

Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge / 中国结合医学杂志

OBJECTIVE@#To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo.@*METHODS@#Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells. Molecular mechanism was investigated by Western blot analysis of p53, Bcl-2, prostate specific antigen (PSA), and androgen receptor (AR). Six-week-old male BALB/c nude mice were randomly divided into normal control group (n=101) and treated group (n=101) which administered 500 mg/kg SM for 2 weeks. Tumor volumes were measured.@*RESULTS@#Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1. DNA laddering analysis indicated the apoptosis of DU-145 cells. Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins. The levels of PSA were considerably reduced in SM-treated group compared to the controls, and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA. In the tumour xenograft study, SM given once a day for 2 weeks significantly inhibited tumour growth.@*CONCLUSION@#SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

Development of a Multiparametric Magnetic Resonance Imaging-Based Nomogram for Clinically Insignificant Prostate Cancer

Purpose@#Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. @*Materials and Methods@#We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. @*Results@#Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. @*Conclusions@#We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker.

Electromagnetic Low-Intensity Extracorporeal Shock Wave Therapy in Patients with Erectile Dysfunction: A Sham-Controlled, Double-Blind, Randomized Prospective Study

PURPOSE: The aim of the present study was to evaluate the efficacy and safety of the electromagnetic-type low-intensity extracorporeal shock wave therapy (Li-ESWT) in patients with erectile dysfunction (ED).MATERIALS AND METHODS: The randomized, sham-controlled, double-blind prospective study was performed at two referral hospitals. Participants were randomized in a 1:1 ratio to receive sham or Li-ESWT for 6 weeks. ED was evaluated at screening and at 4 and 7 weeks after treatment. Participants were asked to complete the international index of erectile function-erectile function (IIEF-EF) domain questionnaire, erection hardness scale (EHS), and sexual encounter profile questionnaire (SEPQ 2 and 3). The development of complications was investigated.RESULTS: Eighty-one of 96 patients completed the study. The median change in the IIEF-EF score in the Li-ESWT and sham groups was 5.1 and −2.2 (p<0.001), respectively, at the 7-week follow-up; 47.4% (18/38) patients had EHS <3, of which 77.8% (14/18) showed significant improvement in virtue of Li-ESWT treatment (p=0.001). A significant improvement was observed in the percentage of “Yes” responses to SEPQ 2 and 3 in the Li-ESWT group vs. sham group from baseline to 7-week follow-up (91.3% vs. 69.4%; p=0.008 and 50.0% vs. 14.3%; p=0.002, respectively). No patients reported pain or other adverse events during treatment or follow-up.CONCLUSIONS: Thus, Li-ESWT could have a role in improving erectile function. Furthermore, it is safe. We believe that Li-ESWT is an attractive new treatment modality for patients with ED.

Adipose Tissue-Derived Stem Cell Therapy for Cavernous Nerve Injury-Induced Erectile Dysfunction in the Rat Model: A Systematic Review and Meta-Analysis Using Methodological Quality Assessment

BACKGROUND AND OBJECTIVES: Few studies were evaluated the effect of blindness on outcome in animal models, though a potential effect of blinding has been reported in clinical trials. We evaluated the effects of adipose tissue-derived stem cells (ADSCs) on cavernous nerve injury (CNI)-induced erectile dysfunction (ED) in the rat and examined how proper blinding of the outcome assessor affected treatment effect. METHODS AND RESULTS: We searched in Pubmed, EMBASE, Cochrane and Web of Science databases from inception to January 2019. We included CNI animal model, randomized controlled experiments, and ADSC intervention. Erectile function and structural changes were assessed by intracavernous pressure and mean arterial pressure (ICP/MAP) ratios, neuronal nitric oxide synthase (nNOS) levels, cavernous smooth muscle and collagen (CSM/collagen) ratios, and cyclic guanosine monophosphate (cGMP). RESULTS: Nineteen studies were included in the final meta-analysis. The ICP/MAP ratio of the ADSC treatment group increased compared to the control group (SMD=1.33, 95%CI: 1.11~1.56, I²=72%). The nNOS level (SMD=2.29, 95%CI: 1.74~2.84, I²=75%), CSM/collagen (SMD=2.57, 95%CI: 1.62~3.52; I²=85%), and cGMP (SMD=2.96, 95%CI: 1.82~4.10, I²=62%) were also increased in the ADSC treatment group. Preplanned subgroup analysis was conducted to explore the source of heterogeneity. Five studies with blinded outcome assessment were significantly less effective than the unblinded studies (SMD=1.33, 95%CI: 0.86~1.80; SMD=1.81, 95%CI: 1.17~2.46, respectively). CONCLUSIONS: ADSCs might be effective in improving erectile function and structural change in CNI-induced ED. However, non-blinded outcome assessors might cause detection bias and overestimate treatment efficacy. Therefore, the ADSC efficacy must be further evaluated with a rigorous study design to avoid bias.

The Treatment of Metastatic and Castration-Resistant Prostate Cancer Patients in Korea

The treatment of advanced prostate cancer has rapidly evolved. Androgen deprivation therapy is recognized as the first-line therapy for metastatic disease; however, a substantial proportion of patients will eventually progress to develop castration-resistance. For the past several years, docetaxel-based chemotherapy has shown significant therapeutic benefit in castration-resistant prostate cancer. Over the last 5 years, several new agents such as the enzalutamide, abiraterone, cabazitaxel, and 223radium have been developed which have all been associated with improved quality of life, pain palliation, and an increase in survival. Unfortunately, there are no Korean treatment guideline for metastatic prostate cancer and/or castration-resistant prostate cancer which has been developed based on adequate review and assessment of evidences. Thus, a guideline adequate for domestic circumstances is eagerly needed. The Korean Association for Clinical Oncology, the Korean Prostate Society, the Korean Urological Oncology Society, and the Korean Society of Pathologists reviewed and endorsed the guidelines.

Effect of Korean Herbal Formula (Modified Ojayeonjonghwan) on Androgen Receptor Expression in an Aging Rat Model of Late Onset Hypogonadism

PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.

Capsaicin-Induced Apoptosis in MBT-2 Murine Bladder Tumor Cells and Bladder Wall Penetration Effect of the Nano-Encapsulated Capsaicin in Rabbit

PURPOSE@#In this study, we attempted to characterize capsaicin's effects with regard to the apoptosis of murine bladder cancer cells (MBT-2) as well as the pharmacodynamics of nano-encapsulated capsaicin formulation for intravesical instillation.@*MATERIALS AND METHODS@#We assessed the viability of the MBT-2 cells via MTT staining, agarose gel electrophoresis, and flow cytometric apoptosis analysis. Intravesical reagents were instilled into 3 groups of male white New Zealand rabbits. Instillation agents were nano-encapsulated capsaicin dissolved in saline, capsaicin dissolved in saline, and capsaicin dissolved in dimethyl sulfoxide (DMSO). We also determined the pharmacokinetics of urine, plasma, and bladder tissue after intravesical capsaicin instillation.@*RESULTS@#Capsaicin treatment was determined to reduce cell viability in a time- and dose-dependent manner. The capsaicin concentrations in the urine of the rabbits decreased in each of the treatment groups, but we noted a more profound reduction of capsaicin concentration in the nano-encapsulated capsaicin group. Plasma concentrations were definitely lower as compared with the levels measured in the bladder tissue and urine. We noted distinctive differences in patterns of concentration change between the capsaicin with normal saline solution (NSS) or DMSO and the nano-encapsulated capsaicin groups. The concentration of nano-encapsulated capsaicin in the tissue appeared to increase directly with tissue depth.@*CONCLUSIONS@#Our results show that capsaicin can induce apoptosis in MBT-2 cells, as well as the excellent permeation properties of nano-encapsulated capsaicin. Treatment with intravesical capsaicin may be a promising alternative therapeutic modality for the treatment of bladder cancer.

Efficacy and Safety of Incontinence Surgery According to the Surgeon’s Specialty and Performance of a Preoperative Urodynamic Study / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to analyze the efficacy and to estimate the complication rate of incontinence surgery according to the surgeon's specialty and whether a preoperative urodynamic study (UDS) was performed, using a nationally representative dataset. METHODS: We enrolled 356,155 women over 20 years old who had undergone surgery for stress urinary incontinence between 2006 and 2015. Patients were followed for up to 3 years to analyze the reoperation and complication rates. Data were obtained from the National Health Claims Database of the National Health Insurance Service (NHIS) of Korea. Multiple Cox regression analysis was conducted to examine the efficacy and safety of incontinence surgery according to the surgeon’s specialty and whether a preoperative UDS was performed. RESULTS: The hazard ratio (HR) for reoperation was significantly higher for procedures performed by nonurologists than for procedures performed by urologists (HR, 1.174; 95% confidence interval [CI], 1.103–1.249). Acute urinary retention, postoperative infections, procedure-associated pain, and other complications were also more common in procedures performed by nonurologists than in those performed by urologists. When stratified by whether a preoperative UDS was performed, the HR for reoperation according to the surgeon’s specialty varied by performance of a preoperative UDS. While the reoperation rate was significantly higher in procedures performed by non-urologists when a preoperative UDS was performed (HR, 1.208; 95% CI, 1.122–1.3), there was no significant difference in the HRs for reoperation according to specialty when a preoperative UDS was not performed. CONCLUSIONS: This population-based study showed that the postoperative outcomes of incontinence surgery were dependent upon the surgeon’s specialty and that the reoperation rate according to the surgeon’s specialty varied based on whether a preoperative UDS was performed.

Suppression of Oxidative Stress of Modified Gongjin-Dan (WSY-1075) in Detrusor Underactivity Rat Model Bladder Outlet Induced by Obstruction / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model.</p><p><b>METHODS</b>Rats were randomly allocated to three groups: shamoperated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders.</p><p><b>RESULTS</b>Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05).</p><p><b>CONCLUSION</b>WSY-1075 had beneficial effect on prevention of BOO-DU.</p>

Clinical Practice Guidelines for the Antibiotic Treatment of Community-Acquired Urinary Tract Infections

Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.

Clinical Practice Guidelines for the Antibiotic Treatment of Community-Acquired Urinary Tract Infections

Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.

Anti-inflammatory and Antimicrobial Effects of Anthocyanin Extracted from Black Soybean on Chronic Bacterial Prostatitis Rat Model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis (CBP) rat model.</p><p><b>METHODS</b>The Sprague-Dawley rats were divided into 4 groups, including control, ciprofloxacin, anthocyanins and anthocyanins with ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial suspension (Escherichia coli Z17 O:K:H) into Sprague-Dawley rats was conducted to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and histological analysis on the prostate were analyzed for each group.</p><p><b>RESULTS</b>The use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05).</p><p><b>CONCLUSIONS</b>These results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.</p>

Corrigendum: Improvement of Persistent Detrusor Overactivity through Treatment with a Phytotherapeutic Agent (WSY-1075) after Relief of Bladder Outlet Obstruction

Current affiliation of Su Jin Kim has been changed, but it was not reflected in the process of publishing. The publishing office and editorial office would like to apologize for any inconvenience caused.

Improvement of Persistent Detrusor Overactivity through Treatment with a Phytotherapeutic Agent (WSY-1075) after Relief of Bladder Outlet Obstruction

PURPOSE: Many patients with benign prostatic hyperplasia need treatment for remaining storage symptoms after surgery. Therefore, we evaluated the effect of the phytotherapeutic agent WSY-1075 on persistent detrusor overactivity (DO) after the relief of bladder outlet obstruction (BOO). MATERIALS AND METHODS: Rats were assigned to 3 groups: control (n=6), persistent DO (n=6), and persistent DO treated with the phytotherapeutic agent WSY-1075 (n=6). Persistent DO after relief of partial BOO was generated in the rat model, and 6 of the rats with this condition were orally administered WSY-1075. After 4 weeks of administration, cystometry was performed. Additionally, 8-hydroxy-2-deoxyguanosine and superoxide dismutase were measured to evaluate oxidative stress in the bladder. Pro-inflammatory cytokines, such as interleukin-8 and tumor necrosis factor-α, were analyzed, as were the M2 and M3 muscarinic receptors of the bladder. RESULTS: Significantly increased contraction pressure and a decreased contraction interval were observed in the persistent DO group after relief of BOO. Moreover, oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors were significantly increased. After treatment with WSY-1075, significantly reduced DO was observed by cystometry in comparison with the persistent DO group. Additionally, significantly decreased levels of oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors in the bladder were observed after treatment with WSY-1075. CONCLUSIONS: Treatment with WSY-1075 improved persistent DO after the relief of BOO mediated by antioxidative and anti-inflammatory effects. Further studies are necessary to identify the exact mechanism of the treatment effect of WSY-1075.

Administration of Goji (Lycium chinense Mill.) Extracts Improves Erectile Function in Old Aged Rat Model

PURPOSE: This study investigated the effect of goji (Lycium chinense Mill.) on erectile dysfunction in old-aged rats. MATERIALS AND METHODS: Twenty-four 18-month-old male Sprague-Dawley rats (defined as old-aged rats) were used. Treatment groups contained eight rats each: a control group, goji extract of 150 mg/kg/day group, and goji extract of 300 mg/kg/day group. Treatment was by orogastric tube once daily for 6 weeks. After 6 weeks of treatment, testes weight, serum testosterone, superoxide dismutase, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, intracavernous pressure/mean arterial pressure, and histological changes were examined. RESULTS: Treatments with goji extracts increased serum testosterone level, increased the expression of endothelial NO synthase, neuronal NO synthase, and cGMP, improved the oxidative stress marker, and decreased corporal fibrosis. CONCLUSIONS: Our results indicate that goji extract may have a positive effect on erectile dysfunction via its antioxidant effects.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

PURPOSE: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. MATERIALS AND METHODS: Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. RESULTS: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p < 0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p < 0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p < 0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p < 0.05). CONCLUSIONS: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Anti-Inflammatory and Antimicrobial Effects of a Novel Herbal Formulation (WSY-1075) in a Chronic Bacterial Prostatitis Rat Model

PURPOSE: The aim of this study was to investigate the anti-inflammatory and anti-oxidative effects of a multi-herbal formula known as WSY-1075 in the treatment of chronic bacterial prostatitis in a rat model. MATERIALS AND METHODS: Experimental chronic bacterial prostatitis was induced in 32 Wistar rats by instillation of a bacterial suspension (Escherichia coli, 10⁸ colony-forming units [CFU]/mL) into the prostatic urethra. After the induction of prostatitis, the rats were randomly divided into one of 4 treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg)+ciprofloxacin (n=8). After 4 weeks of treatment, microbiological data from prostate tissue cultures, level of prostatic pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-8), anti-oxidant effects (superoxide dismutase [SOD]), and histological findings were noted. RESULTS: The WSY-1075, ciprofloxacin, and WSY-1075+ciprofloxacin groups showed fewer CFUs in prostate tissue cultures than the control group. The WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups showed statistically significantly lower levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 than the control group. SOD levels in the WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups were significantly higher than in the control group. CONCLUSIONS: This study found that WSY-1075 had anti-microbial effects, anti-inflammatory effects, and anti-oxidative effects in a chronic bacterial prostatitis rat model. We expect the WSY-1075 may be useful for the clinical treatment of chronic bacterial prostatitis.

Development of an Improved Animal Model of Overactive Bladder: Transperineal Ligation versus Transperitoneal Ligation in Male Rats

PURPOSE: We compared a transperineal ligation model and a transperitoneal ligation model in male rats to determine which animal model of overactive bladder (OAB) was more useful based on cystometrography, estimations of oxidative stress, and measurements of pro-inflammatory cytokine levels. MATERIALS AND METHODS: Male rats were randomly divided into three groups (n=15 in each): the control group, the transperineal ligation group, and the transperitoneal ligation group. Four weeks after the ligation procedure, cystometrography was performed and oxidative stress, pro-inflammatory cytokine levels, and histologic changes were evaluated. Oxidative stress was assessed by measuring 8-hydroxy-20-deoxyguanosine and superoxide dismutase, and pro-inflammatory cytokine activity was investigated by measuring levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α. RESULTS: The transperineal model led to results similar to those observed for the transperitoneal model, namely (1) increased voiding frequency and reductions in the non-voiding contraction interval and the maximal vesical pressure, (2) increased levels of oxidative stress markers, (3) increased pro-inflammatory cytokine levels, and (4) fibrotic changes in the bladder tissue. CONCLUSIONS: We suggest that the transperineal procedure can be used as an alternative OAB model in male rats.

Anthocyanin Induces Apoptosis of DU-145 Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer

PURPOSE: To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). MATERIALS AND METHODS: The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2x106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. RESULTS: Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. CONCLUSION: This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.