A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Comparative Human Study to Verify the Functionality and Safety of the Lespedeza cuneata G. Don Extract for the Improvement of Aging Male Syndrome.

OBJECTIVE: Aging male syndrome is a clinical biochemical syndrome characterized by typical aging symptoms and serum testosterone deficiency. Although it is accompanied by various health problems, directly affects life satisfaction, and requires proper management, no clear prevention or treatment other than hormone replacement therapy is currently available for this syndrome. Here, we aimed to determine the efficacy and safety of the Lespedeza cuneata extract in the management of the aging male syndrome. METHODS: Males aged 43-70 years who provided consent for participation and had a total Aging Males' Symptom questionnaire score ≥ 37 and testosterone level ≤ 500 ng/dL were enrolled in this study. This study was conducted in a randomized, double-blind manner. Participants were randomly assigned to either the experimental or control groups and orally administered the assigned product twice a day. Efficacy was evaluated by measuring changes in Aging Males' Symptom score, Androgen Deficiency in the Aging Male questionnaire score, International Index of Erectile Function score, International Prostatic Symptom Score, blood test results, and body mass index at 8 weeks. RESULTS: After 8 weeks, the experimental group had significantly improved symptom scores compared to the control group on the Aging Males' Symptom and Androgen Deficiency in the Aging Male questionnaires. However, no significant differences in the International Index of Erectile Function score, International Prostatic Symptom Score score, blood test results, and body mass index were observed between the experimental and control groups. CONCLUSION: Lespedeza cuneata extract safely alleviates andropause symptoms without any significant side effects, suggesting its potential for the treatment of the aging male syndrome.

Adult-type granulosa cell tumor of the testis: A case report with immunohistochemical study.

We report that a case of adult testicular granulosa cell tumor in a 40-year-old man who presented with a palpable testicular mass. The sectioned surface of the testis revealed a well-circumscribed, yellowish tan, solid mass with hemorrhagic foci. Histologically, the tumor was arranged in solid nests, trabeculae, gyriform, pseudopapillae and macro-and microfollicles in a fibrocollagenous stroma. The tumor cells were ovoid or carrot-shaped with scant cytoplasm and nuclear grooves. Immunohistochemically, the tumor cells were diffusely strongly positive for estrogen receptor, progesterone receptor, androgen receptor, CD10, CD56, calretinin and vimentin, and multifocally positive for inhibin, synaptophysin and cytokeratin.

Changes in autonomic nervous system activity after treatment with alpha-blocker in men with lower urinary tract symptoms.

Purpose: To determine changes in autonomic nervous system activity after treatment in men with lower urinary tract symptoms (LUTS), we evaluated changes in patients' symptoms, uroflowmetry, and heart rate variability (HRV) after treatment with alpha-blockers for 12 weeks. Materials and Methods: Ninety-five men who had LUTS (International Prostate Symptom Score [IPSS] ≥8) were included in this study. We divided them into two groups on the basis of a low frequency/high frequency (LF/HF) ratio of 1.6. After treatment with Xatral XL (Handok Inc., Korea) 10 mg for 3 months, we rechecked their IPSS, uroflowmetry, HRV and compared these with the baseline measurements. Results: Fifty-four men were assigned to the low LF/HF group (group A: LF/HF ≤1.6) and 41 men to the high LF/HF group (group B: LF/HF >1.6). At baseline and 12 weeks, none of the parameters differed significantly between the groups except for HF, which is one of the parameters of HRV. IPSS, the IPSS-voiding subscore, and the IPSS-storage subscore decreased and maximal uroflow increased significantly after 12 weeks of treatment. Whereas the baseline LF/HF ratio increased from 0.89±0.407 to 1.80±1.804 after treatment in group A, it decreased from 3.93±5.471 to 1.79±1.153 in group B. Conclusions: The efficacies of Xatral XL were clear in both groups. We found that the LF/HF ratio in the two groups merged to a value of approximately 1.79 after treatment. We suggest that this could be a clue to the importance of balance in autonomic nervous system activity in men with LUTS.

Association Between Irritable Bowel Syndrome and Overactive Bladder: A Research Survey.

OBJECTIVE: To investigate the relationship between irritable bowel syndrome (IBS) and overactive bladder (OAB) in men and women using questionnaires. MATERIALS AND METHODS: This research survey was based on multicenter data (men and women older than 20 years). The Korean version of the Rome III criteria was used for the diagnosis of IBS, Overactive Bladder Symptom Score (OABSS) was used for screening OAB, Self-Rating Depression Scale was used for depressive symptoms, and International Prostate Symptom Score and Quality of Life were used to determine the degrees of lower urinary tract symptoms. RESULTS: A total of 609 (men: 257, women: 352) people answered the questionnaire. The prevalence of IBS and OAB was 31.9% (men vs women: 27.3% vs 39.2%) and 19.2% (men vs women: 25.3% vs 18.5%), respectively. The OABSS values of patients with IBS and non-IBS patients were 1.70 ± 2.48 and 2.48 ± 2.79 (P <.001). On the Self-Rating Depression Scale, individuals with IBS had a higher score than non-IBS individuals (n = 201) (44.92 ± 13.71 vs 39.19 ± 10.39, P <.001). In men, non-IBS (n = 56) had higher OABSS and OABSS question number 3 responses than patients with IBS (OABSS: 2.56 ± 2.69 vs 1.57 ± 2.43, P = .01, OABSS Q3: 0.92 ± 1.26 vs 0.66 ± 1.13, P = .17). Also, in women, non-IBS (n = 214) had higher OABSS and OABSS question number 3 responses than patients with IBS (n = 138) (OABSS: 2.40 ± 2.87 vs 1.76 ± 2.52, P = .03, OABSS Q3: 0.83 ± 1.25 vs 0.70 ± 1.18, P = .32). CONCLUSION: IBS in adults had no relationship with OAB in our study. These data suggest that more studies are needed to determine the relationship between IBS and OAB.

Alpha-Blocker Treatment Response in Men With Lower Urinary Tract Symptoms Based on Sympathetic Activity: Prospective, Multicenter, Open-Labeled, Observational Study.

PURPOSE: In this study, we compared the treatment outcomes for an α-blocker between 2 groups of men, one with high sympathetic activity (HSA) and another with low sympathetic activity (LSA) or normal sympathetic activity. METHODS: A total of 159 men (≥50 years of age) with lower urinary tract symptoms resulting from benign prostatic hyperplasia were analyzed. We assigned patients to groups according to their sympathetic activity, which was evaluated by heart ratevariability measurements. HSA was defined as a low frequency/high frequency ratio greater than 1.6. All patients received 10mg of alfuzosin once a day for 12 weeks. The primary end point was a change in the total International Prostate SymptomScore (IPSS) at 12 weeks from baseline. RESULTS: Sixty-seven men were assigned to the HSA group and 92 men were assigned to the LSA group. The baseline characteristics were not significantly different between the 2 groups, and the response to alfuzosin was good in both groups. Themean total IPSS change was not different between the groups. Both groups were not significantly different with respect to the changes in maximal flow rate, IPSS voiding or storage symptom subscores, quality of life, and rates of adverse drug events. TheHSA group showed a similar willingness to continue treatment compared to the LSA group, although their treatment satisfaction rating was lower. CONCLUSIONS: The therapeutic effects of alfuzosin did not differ in regards to the differences in sympathetic activity, but treatment satisfaction ratings were lower in the HSA group.

Analysis of female voiding dysfunction: a prospective, multi-center study.

PURPOSE: Female voiding dysfunction lacks clear definitions or objective data even to this day due to the relatively low prevalence and complex etiologies of voiding dysfunction in women compared to men. The prevalence varies widely from 2.7 to 23 % (Nitti et al. in J Urol 161(5):1535-1540, 1999; Rees et al. in Br J Urol 47(7):853-860, 1975; Groutz et al. in Neurourol Urodyn 19(3):213-220, 2000; Farrar et al. in Br J Urol 47(7):815-822, 1975; Massey and Abrams in Br J Urol 61(1):36-39, 1988; Chassagne et al. in Urology 51(3):408-411, 1998). Diagnostic criteria and management of female voiding dysfunction have not yet been established. We performed a prospective, multi-center study at nine hospitals to investigate the characteristics and prevalence of female voiding dysfunction. MATERIALS AND METHODS: A total of 1,415 women visited urology clinics in nine hospitals from September to December 2005. Among them, 792 patients presented with lower urinary tract symptoms (LUTS). We analyzed their urinary symptoms with an International Prostate Symptom Score (IPSS) and obtained objective data using uroflowmetry, residual urine volume, and urinalysis. The authors hereby define female voiding dysfunction as maximum flow rate (Q max) of 15 ml/s or less, which may be due to either bladder outlet obstruction (BOO) or bladder dysfunction caused by detrusor underactivity. BOO was defined as Q max <15 ml/s with detrusor pressure >20 cmH2O at Q max, and detrusor underactivity was defined as Q max <15 ml/s with detrusor pressure <20 cmH2O at Q max on pressure flow studies. RESULTS: Hundred and two patients (12.8 %) from a total of 792 LUTS patients complained of voiding difficulty. Mean total IPSS score, mean IPSS subscores for voiding and storage symptom was 19.5 ± 7.9, 12.0 ± 5.0, and 8.4 ± 3.4, respectively. Among the seven categories of IPSS, incomplete emptying was the most common symptom followed by weak stream. Eighty-nine patients (87.2 %) from a total of 102 voiding dysfunction patients showed BOO, while 13 patients (12.8 %) showed detrusor underactivity. Concomitant diseases observed with voiding dysfunctions were overactive bladder (32 patients), stress urinary incontinence (25), detrusor underactivity (13), previous stress urinary incontinence surgery (12), pelvic organ prolapse (4), and anatomical obstruction (3 patients). CONCLUSION: The prevalence of voiding difficulty in female urology patients who visit urologic office clinic was 7.2 and 12.8 % in female LUTS patients. Voiding symptoms were more common than storage symptoms, while functional BOO was more prevalent than detrusor underactivity in female voiding difficulty patients. We may expect alpha blockers to be an effective treatment option in female voiding difficulty due to functional BOO.

Efficacy of anticholinergics for chronic prostatitis/chronic pelvic pain syndrome in young and middle-aged patients: a single-blinded, prospective, multi-center study.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) exhibits variable lower urinary tract symptoms (LUTS). The aim of this study was to evaluate the incidence of LUTS and the efficacy of an anticholinergic agent in young and middle-aged CP/CPPS patients. METHODS: Ninety-six men with CP/CPPS were randomly assigned in a single-blind fashion and received either ciprofloxacin (group 1, 49 patients) or ciprofloxacin and solifenacin (5 mg/day; group 2, 47 patients) for 8 weeks. The National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), the International Prostate Symptom Score (IPSS), and the International Index of Erectile Function-5 (IIEF-5) were used to grade the patients' symptoms and the quality of life impact at the start of the study, and at 4 and 8 weeks from the initiation of the study. RESULTS: There was no significant difference between groups 1 and 2 with respect to age, duration of disease, or sub-domains of the IPSS, NIH-CPSI, or IIEF-5 at baseline. Of these patients, 67.4% had LUTS. Statistically significant differences were determined via the NIH-CPSI for total score and the pain and urinary domain scores. Statistically significant differences were determined via the IPSS for total score and the storage domain score. The total score of the IIEF-5 increased, but the change was not significant. There was no statistically significant difference in residual urine. CONCLUSIONS: Many CP/CPPS patients had LUTS. Solifenacin in CP/CPPS demonstrated improvements in the NIH-CPSI and the IPSS total score and storage score. Storage factors significantly improved via the NIH-CPSI and IPSS assessments in the solifenacin treatment group.

Changes in serum prostate-specific antigen after treatment with antibiotics in patients with lower urinary tract symptoms/benign prostatic hyperplasia with prostatitis.

PURPOSE: Many urologists have performed prostate biopsy in men with a high level of prostate-specific antigen (PSA) alone. However, high levels of PSA may be induced by infection. We studied the effects of antibiotics on serum total PSA and PSA density (PSAD) in men with total PSA between 4 and 10 ng/ml and normal digital rectal examination (DRE) and transrectal sonographic findings. MATERIALS AND METHODS: From January 2005 to October 2009, a total of 107 patients with complaints of lower urinary tract symptoms (LUTS) or benign prostatic hyperplasia (BPH) were evaluated. To be included in this study, patients had to be at least 50 years old, have a palpably normal DRE, have infection in the prostate, have a total serum PSA of 4 to 10 ng/ml, and have transrectal ultrasound findings that did not show a hypoechoic lesion in the prostate. Only patients in whom the PSA level was rechecked after short-term antibiotics administration (8 weeks) were included. Serum PSA and PSAD were measured before transrectal ultrasound or EPS and after 8 weeks of treatment with antibiotics (quinolone). Age, prostate volume, serum PSA, PSAD, and PSA rate of change were compared. RESULTS: The mean age of the patients was 66.3 years. The mean prostate size was 48.8±24.9 g. Forty patients had a high level of PSAD. Total PSA and PSAD significantly decreased after treatment (p<0.05). In 45 of the 107 men, total PSA after antibiotics treatment was normalized (less than 4 ng/ml). PSAD after treatment was normalized (less than 0.15 ng/ml/cm(3)) in 23 of the 40 patients with a high level of PSAD. CONCLUSION: Antibiotics treatment for at least 8 weeks in BPH patients with an increased PSA level (4-10 ng/ml), infection, and normal DRE and transrectal sonographic findings may decrease serum PSA significantly. However, because the PSA level was not decreased to the normal range (less than 4 ng/ml) in all patients, it seems that antibiotics therapy before prostatic biopsy is not necessary.

Cross-cultural differences for adapting overactive bladder symptoms: results of an epidemiologic survey in Korea.

The purpose of this study was to evaluate the prevalence of overactive bladder (OAB) in a Korean national community sample of adults aged 40-89 years. A national Korean telephone survey using quota sampling methods was conducted. A clinically validated computer-assisted telephone interview approach was used in the survey. In 2,005 subjects (1,005 women and 1,000 men) interviewed, the prevalence of OAB(wet) increased with age in both men and women but OAB(dry) did not. OAB(dry) of men and women was not different in each age decade but OAB(wet) was more common among women than men aged <70 years. Multivariate analysis indicated that sex, age and body mass index (BMI) were associated with OAB(dry). For OAB(wet), sex and age were independent risk factors but BMI was not. In multivariate analysis, urgency was not associated with an increased likelihood of the impact on sexual life in men. The likelihood of the impact on sexual life, quality of life (QOL) and willingness to seek medical consultation was not related to nocturia. In female subjects, odds ratios for the impact of daily living, sexual life, QOL, and willingness to seek help from a health professional were not increased for nocuria. The likelihood of the impact on sexual life and willingness to seek medical help was not related to urge incontinence. Our study provides a valuable insight into the need for tailored education to this population about OAB. These findings suggest that there are cross-cultural differences for adapting OAB symptoms.

Cytokeratin-20 and seminal vesicle secretory protein VI as possible marker proteins in urinary bladder preneoplastic lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

BACKGROUND: A simple and non-invasive methods for the diagnosis of transitional cell carcinoma of the bladder are needed for the prevention of invasive tumor. A proteomic technology has recently been developed to facilitate protein profiling of biological mixtures. We tried to detect the marker proteins by proteomic approach during the initiation stages on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in rats. METHODS: Ten rats in group A were given 0.05% BBN in drinking water for 12 weeks. Other 10 rats in group B with 10 rats were designated as a control group and were not given BBN. Whole urinary bladders of all rats were excised at 12 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-dimension gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. RESULTS: A comparison of urinary bladder hyperplasia tissue with control tissue showed that five proteins; actin gamma2 propeptide, cytokeratin-20 (CK-20), proapolipoprotein, alpha2 actin (alpha-cardiac actin) and heat shock 27 kDa protein-1 were over-expressed in hyperplastic tissues. Three proteins; transcription factor myocardin, seminal vesicle secretory protein VI (SVS-VI) precursor and hypothetical protein RMT-7 were under-expressed in hyperplastic tissues. CONCLUSION: In our animal mode, BBN-induced urinary bladder mucosal hyperplasia resulted in an increase in the expression of five proteins and a decrease in the expression of three proteins. Of these, CK-20 and SVS-VI seem to be of particular interest. However other method such as Western blotting seems to be needed for confirmation of these proteins and more information on human bladder tissue is needed for clinical application.

Investigation of early protein changes in the urinary bladder following partial bladder outlet obstruction by proteomic approach.

We investigated the pathophysiological mechanism by proteomic approach as a possible tool to detect the marker proteins to develop lower urinary tract symptoms following bladder outlet obstruction (BOO). Rats were randomized into 3 groups; control, sham operation and BOO groups. BOO group was divided into 1, 3, and 5 day-group. Conventional proteomics was performed with high resolution 2-D gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry using rat urinary bladders. A comparison of bladder of BOO group with control bladder showed that three proteins of optineurin, thioredoxin and preprohaptoglobin were over-expressed in the bladder of BOO group. In addition, four proteins, such as peroxiredoxin 2, transgelin, hippocampal cholinergic neurostimulating peptide (HCNP) and beta-galactoside-binding lectin, were under-expressed in the bladder of BOO group. These data supported that downregulation of HCNP might make detrusor muscle be supersensitive to acetylcholine, up-regulation of optineurin means the protection of nerve injury, and down-regulation of transgelin means the decreased contractility of detrusor muscle. Beside these proteins, other proteins are related to oxidative stress or have a nonspecific function in this study. However more information is needed in human bladder tissue for clinical usage.

Combination treatment with propiverine hydrochloride plus doxazosin controlled release gastrointestinal therapeutic system formulation for overactive bladder and coexisting benign prostatic obstruction: a prospective, randomized, controlled multicenter study.

PURPOSE: We evaluated the efficacy and safety of a therapeutic modality involving propiverine combined with doxazosin in patients with overactive bladder (OAB) and benign prostatic obstruction. MATERIALS AND METHODS: Men 50 years or older with OAB symptoms and urodynamically proven bladder outlet obstruction (Abrams-Griffith score greater than 20) were randomized (1:2) into 2 groups, namely group 1-doxazosin controlled release gastrointestinal therapeutic system formulation (4 mg once daily) only and group 2-propiverine hydrochloride (20 mg once daily) plus doxazosin controlled release gastrointestinal therapeutic system formulation for an 8-week treatment regimen. RESULTS: A total of 211 men, including 69 in group 1 and 142 in group 2, were treated and 198 (93.8%) completed the 8 weeks of treatment. Significant improvements were noted in each group after treatment in urinary frequency, maximum flow rate, average micturition volume and International Prostate Symptom Score. Compared with group 1 improvement rates with regard to urinary frequency (23.5% vs 14.3%, p = 0.004), average micturition volume (32.3% vs 19.2%, p = 0.004), and storage (41.3% vs 32.6%, p = 0.029) and urgency (p = 0.019) International Prostate Symptom Score symptoms were more significant in group 2. Post-void residual urine was found to be significantly increased only in group 2 but this was not accompanied by urinary retention. Patient satisfaction rates were found to be significantly higher in group 2 than in group 1 (p = 0.002). Overall adverse event rates were higher in group 2 (p = 0.002), although discontinuation rates and discontinuation rates due to adverse events were not different between the 2 groups. CONCLUSIONS: This study reveals that combination therapy consisting of alpha1-adrenoceptor antagonists with antimuscarinics represents an effective and relatively safe treatment modality in select patients with OAB coexisting with benign prostatic obstruction.

The proteomics approach to find biomarkers in gastric cancer.

Gastric cancer is a very serious disease and is naturally resistant to many anticancer drugs. To reduce the mortality and improve the effectiveness of therapy, many studies have tried to find key biomarkers. Proteomic technologies are providing the tools needed to discover and identify disease-associating biomarkers. The proteomic study of gastric cancer establishes any specific events that lead to cancer, and it provides a direct way to define the true function of genes. Using two dimensional (2-D) electrophoresis of the stomach cancer tissue, we have gained about 1,500 spots in each gel, and 140 protein spots also were identified. Among the identified proteins, there were seven over-expressed proteins in stomach cancer tissue: NSP3, transgelin, prohibitin, heat shock protein (hsp) 27 and variant, protein disulfide isomerase A3, unnamed protein product and glucose regulated protein. There were also seven under-expressed proteins in stomach cancer: Apolipoprotein A-1, p20, nucleoside diphosphate isomerase A, alpha 1 antitrypsin, desmin, serum albumin and serotransferrin.

Effects of ylang-ylang essential oil on the relaxation of rat bladder muscle in vitro and white rabbit bladder in vivo.

Current and primary treatment modality in overactive bladder includes the administration of anticholinergics. The demand for new agents has been rising since anticholinergics have proven to come with many side effects. This study was designed to investigate the effects of ylang-ylang essential oil (YYEO) on the relaxation of urinary bladder muscle in vitro and in vivo. Effects of YYEO were assessed on resting tension, and electrical field stimulation- and various drug-induced contraction in vitro by checking the isometric tension changes of muscle strips and same procedures were repeated in the presence of methylene blue, Nw-Nitro-L-arginine methyl ester hydrochloride (L-NAME), or N-ethylmaleimide, and in vivo. YYEO decreased significantly the contractility of strips. There was no statistically significant difference between the treated group only with YYEO and the pretreated group with YYEO and methylene blue or L-NAME. When N-ethylmaleimide was employed, there was a statistically significant decrease in the rate of contraction. In vivo studies showed the same results compared with in vitro study. The results of this study indicate that YYEO has a relaxing effect on the bladder, and such mechanism is thought to be brought about by a pathway mediated by c-AMP.