Efficacy and Safety of Mirodenafil Oro-Dispersible Film in Korean Patients with Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter, Phase IV Study.

PURPOSE: To investigate the efficacy, safety, and tolerability of oro-dispersible film (ODF) formulation of mirodenafil 50 mg and 100 mg for the treatment of patients with erectile dysfunction (ED) in Korea. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 129 subjects was performed. Subjects were randomized to either placebo or mirodenafil ODF 50 mg or 100 mg to be taken in an "on demand" manner for 8 weeks. The primary efficacy variable was the International Index of Erectile Dysfunction (IIEF)-5 questionnaire. The secondary efficacy variables comprised Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). RESULTS: IIEF-5 was significantly increased in all groups after treatment. However, compared to the placebo group, only the mirodenafil ODF 100 mg group showed a significant difference. SEP2 and SEP3 were increased in both mirodenafil groups; however, the increase was not statistically significant for SEP2. In terms of GAQ and LSC, the mirodenafil ODF groups showed significant increases compared with the baseline. Most treatment-associated adverse events were mild and resolved spontaneously. CONCLUSIONS: Mirodenafil ODF is an effective and well-tolerated agent for the treatment of patients with ED in Korea.

Effect of combined solifenacin and aclatonium in preventing dry mouth in patients with overactive bladder.

OBJECTIVE: The aim of the present study was to prospectively evaluate the effect of aclatonium on dry mouth in patients with overactive bladder (OAB) after treatment with solifenacin. METHODS: A multicenter randomized double-blind controlled trial was conducted. The study subjects were men and women who had been diagnosed with OAB for ≥3 months and presented with a total Overactive Bladder Symptom Score (OABSS) ≥3. Eligible subjects were randomized to receive 5 mg solifenacin with placebo or 5 mg solifenacin with 150 mg aclatonium once daily for 8 weeks. Subjects rated dry mouth using a visual analog scale (VAS) and completed the OAB-questionnaire (OAB-q) short form (SF) and OABSS questionnaires at baseline and after 8 weeks treatment. Dry mouth was defined as a VAS score >30 points (range 0-100). RESULTS: Overall, 92 patients (49 and 43 in the placebo and aclatonium groups, respectively) completed the 8-week treatment. In patients who had dry mouth at baseline, no differences were detected in changes in the dry mouth VAS, OABSS, or OAB-q SF scores between the 2 groups. However, in patients who had no dry mouth at baseline, the change in dry mouth VAS score was significantly lower in the aclatonium- than placebo-treated group: the VAS score increased 20 points in the placebo group compared with 9 points in the aclatonium group (P = .03). However, there were no significant differences in changes in the OABSS and OAB-q SF scores between the 2 groups. CONCLUSIONS: Aclatonium decreased dry mouth without disturbing treatment efficacy in patients who did not have dry mouth before treatment.

Is It Worth Treating Non-Bothering Nocturia? Results of a Multicenter Prospective Observational Study.

PURPOSE: The purpose of this study was to evaluate the efficacy of treatment in patients with non-bothering nocturia. MATERIALS AND METHODS: In this prospective multicenter study, patients who visited hospitals for treatment of voiding symptoms were enrolled. Inclusion criteria were: 1) men >45 years, and 2) nocturia ≥2 confirmed by a three-day voiding diary. Subjects were divided into non-bothering and bothering groups based on International Consultation on Incontinence Questionnaire Nocturia (ICIQ-N) question 2b. Changes in voiding symptoms, frequency of nocturia, and bothersomeness were evaluated with international prostate symptom score (IPSS), ICIQ-N, and three-day voiding diary at 4 and 12 weeks after treatment. RESULTS: A total of 48 patients in the non-bothering nocturia group and 50 patients in the bothering nocturia group who completed the 12-week treatment were analyzed. The total IPSS was decreased by 5.8 in the non-bothering group and 5.2 in the bothering group. There was no significant difference in decrease of IPSS between the two groups. Both groups showed significant reduction in discomfort of nocturia. The ICIQ-N 2b score decreased from 3.9 to 2.7 (p=0.01) in the non-bothering group and from 6.9 to 4.6 (p=0.02) in the bothering group. The number of nocturia episodes was significantly decreased in both groups. CONCLUSIONS: Regardless of discomfort associated with nocturia, both groups showed significant improvement in nocturia-related discomfort and voiding symptoms. These results suggest that patients with nocturia who were unaware of its discomfort benefited from treatment.

Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial.

BACKGROUND: Phosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). AIMS: To assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED. METHODS: A randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg. OUTCOMES: The primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24. RESULTS: The mean changes in total IPSS and IIEF-EF scores were -9.46 and 9.17 for FDC 0.4/5 mg and -8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period. CLINICAL IMPLICATIONS: The FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED. STRENGTHS AND LIMITATIONS: The study clearly demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower incidence of side effects, and the simplification and convenience of therapy, which led to better overall patient compliance. However, the lack of a tamsulosin monotherapy control group was a limitation of this study. CONCLUSION: The FDC 0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that combination therapy could provide clinical benefits for patients with BPH-associated LUTS complaints and ameliorate the comorbidity of ED. Kim SW, Park NC, Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. J Sex Med 2017;14:1018-1027.

Diagnosis and Treatment of Premature Ejaculation by Urologists in South Korea.

PURPOSE: This study discusses the treatment of premature ejaculation (PE) using various approaches with the goal of evaluating the methods of diagnosis and treatment of PE in clinical practice in 2014 in South Korea. MATERIALS AND METHODS: We surveyed 200 urologists and andrologists who treated patients with PE from July 1, 2014 to July 29, 2014 using an online questionnaire. The questionnaire was composed of 4 parts: disease, comorbidities, diagnosis, and treatment. Using the answers to this survey, current trends in the diagnosis and treatment of PE were investigated using weighted averages. RESULTS: The median number per month of patients who were diagnosed with PE was 14 patients (interquartile range, 7~24). The time to ejaculation necessary for a diagnosis of PE was considered to be <1 minute by 12% of respondents, <2 minutes by 27%, <3 minutes by 28%, <5 minutes by 13%, and 20% stated that diagnosis was based on a patient's subjective complaint. The treatment methods preferred by PE patients were reported to be pharmacological treatment (87%), surgical treatment (9.5%), and behavioral management (3.5%). The treatment methods used by respondents were pharmacological treatment (77%), surgical treatment (15%), and behavioral management (14%). The most commonly used pharmacological treatment was the oral administration of dapoxetine (97%). CONCLUSIONS: In 2014 in South Korea, various methods were used to diagnose and treat PE. The most commonly used treatment for PE was the oral administration of dapoxetine. It was also found that surgical treatment was applied in some cases.

Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications.

BACKGROUND: The objective of this study was to assess the efficacy and safety of alfuzosin 10 mg monotherapy or combined antihypertensive medication on blood pressure (BP) in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS) with or without antihypertensive medication. METHODS: This was a 3-month, multicenter, randomized, open-label study in 335 patients aged ≥45 years with a clinical diagnosis of BPH/LUTS by medical history and clinical examination, a total International Prostatic Symptom Score (IPSS) ≥8 points, a maximum flow rate >5 mL/sec and ≤15 mL/sec, and a voided volume ≥120 mL. Eligible subjects were randomized to receive alfuzosin 10 mg as monotherapy (group 1) or alfuzosin 10 mg + antihypertensive combination therapy (group 2). Based on baseline BP and hypertensive history with or without antihypertensive medications at first medical examination, group 1 was divided into two subgroups of normotensive and untreated hypertensive patients, and group 2 into two subgroups of controlled hypertensive and uncontrolled hypertensive patients. The primary study outcomes were change in IPSS, BP, and heart rate from baseline. Secondary outcomes were change in IPSS-quality of life score, maximum flow rate, average flow rate, voided volume, and post-voided volume. RESULTS: The overall BP change was not significantly different between groups 1 and 2 (systolic BP, P=0.825; diastolic BP, P>0.999). In patients with uncontrolled or untreated hypertension, alfuzosin 10 mg alone or combined with antihypertensive therapy significantly decreased systolic and diastolic BP. The mean difference in total IPSS and IPSS-quality of life scores from baseline between groups 1 and 2 was 0.45 (95% CI: -1.26, 2.16) and 0.12 (95% CI: -0.21, 0.45), respectively (both P>0.05). Maximum flow rate, average flow rate, voided volume, and post-voided volume at endpoint were numerically, but not significantly, changed from baseline (all P>0.05). CONCLUSION: This study shows that alfuzosin 10 mg is effective and well tolerated in patients with BPH/LUTS with or without antihypertensive medications. However, in patients with uncontrolled or untreated hypertension, alfuzosin 10 mg alone or in combination with antihypertensive medication appears to decrease systolic and diastolic BP, and these patients should be warned about a decrease in BP on initiation of therapy.

Safety and efficacy of 8-mg once-daily vs 4-mg twice-daily silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (SILVER Study): a 12-week, double-blind, randomized, parallel, multicenter study.

OBJECTIVE: To show the noninferiority of silodosin 8-mg once-daily (QD) to 4-mg twice-daily (BID) in efficacy and safety in patients with lower urinary tract symptoms or benign prostatic hyperplasia in the Korean population. METHODS: A prospective, multicenter, double-blind, randomized, comparative study was conducted. A total of 532 male patients aged ≥50 years with lower urinary tract symptoms or benign prostatic hyperplasia were included. All patients received silodosin QD or BID for 12 weeks. The primary end point was the change from baseline in total International Prostate Symptom Score (IPSS) at 12 weeks. Adverse drug reactions, vital signs, and laboratory tests were recorded. RESULTS: A total of 424 patients were randomized to the silodosin QD or BID groups. These groups were not significantly different in baseline characteristics. The mean total IPSS change in QD group was not inferior to that in BID group (-6.70 and -6.94, respectively; 95% confidence interval, -0.88 to 1.36). The QD and BID groups did not significantly differ in the following: percentages of patients with ≥25% (63.41% and 67.82%, respectively; P = .349) or ≥4-point improvement in total IPSS (65.85% and 69.31%, respectively; P = .457), maximum urinary flow rate improvement ≥30% (47.32% and 40.59%, respectively; P = .172), changes in IPSS voiding subscore (-4.42 ± 4.93 and -4.65 ± 4.77; P = .641), IPSS storage subscore (-2.05 ± 3.07 and -2.52 ± 2.97; P = .117), quality of life (-1.19 ± 1.49 and -1.40 ± 1.42; P = .136), maximum urinary flow rate (3.55 ± 5.93 and 3.74 ± 6.79 mL/s; P = .768), International Continence Society male questionnaire score, Patient Goal Achievement Score, or Treatment Satisfaction Question. The 2 groups had similar frequencies of adverse drug reactions. CONCLUSION: QD administration of silodosin was not inferior to BID in efficacy. The 2 groups had similar adverse drug reaction profiles.

Does phosphorylation of cofilin affect the progression of human bladder cancer?

BACKGROUND: We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. METHODS: We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. RESULTS: The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. CONCLUSIONS: These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.

Effect of Intravesical Prostatic Protrusion on the Characteristics of Lower Urinary Tract Symptom Change after 12-Week Drug Medication: A Prospective Analysis.

OBJECTIVES: The aim of this study was to identify whether intravesical prostatic protrusion (IPP) is related to the characteristics of voiding symptoms improvement after drug treatment in benign prostatic hyperplasia patients. METHODS: Ninety male patients with more than 30 g prostate volume were prospectively enrolled. All patients were evaluated with International Prostate Symptoms Score (IPSS), uroflowmetry, postvoid residual urine (PVR), prostate volume and IPP measurement by transrectal ultrasound. Treatment response was evaluated again by IPSS after 12 weeks of medication. We evaluated the correlation of IPP and IPSS, quality of life (QoL) score, maximum urinary flow rate (Qmax) and PVR, and compared IPPS and IPSS subscale score change between the IPP and non-IPP groups. RESULTS: IPP was significantly correlated with total IPSS, voiding/storage symptom subscore and PVR. IPP was inversely correlated with Qmax. IPP showed a significant correlation with storage symptoms after an adjustment of prostate volume. After 12 weeks of medication, the IPP group showed persistently high storage symptoms than the non-IPP group. CONCLUSION: BPH patients with IPP showed less improvement of storage symptoms after 12 weeks of medication. This study suggests that IPP may be a possible cause of intractable storage symptoms in early treatment.

Urologist's Practice Patterns Including Surgical Treatment in the Management of Premature Ejaculation: A Korean Nationwide Survey.

PURPOSE: According to previous studies, the prevalence of premature ejaculation (PE) in Korea ranges from 11.3% to 33%. However, the actual practice patterns in managing patients with PE is not well known. In this study, we have endeavored to determine how contemporary urologists in Korea manage patients with PE. MATERIALS AND METHODS: The e-mailing list was obtained from the Korean Urological Association Registry of Physicians. A specifically designed questionnaire was e-mailed to the 2,421 urologists in Korea from May 2012 to August 2012. RESULTS: UROLOGISTS IN KOREA DIAGNOSED PE USING VARIOUS CRITERIA: the definition of the International Society for Sexual Medicine (63.4%), Diagnostic and Statistical Manual of Mental Disorders (43.8%), International Statistical Classification of Disease, 10th edition (61.7%), or perceptional self-diagnosis by the patient himself (23.5%). A brief self-administered questionnaire, the Premature Ejaculation Diagnostic Tool, was used by only 42.5% of the urologists. Selective-serotonin reuptake inhibitor (SSRI) therapy was the main treatment modality (91.5%) for PE patients. 40.2% of the urologists used phosphodiesterase type 5 inhibitors, 47.6% behavior therapy, and 53.7% local anesthetics. Further, 286 (54.3%) urologists managed PE patients with a surgical modality such as selective dorsal neurotomy (SDN). CONCLUSIONS: A majority of Korean urologists diagnose PE by a multidimensional approach using various diagnostic tools. Most urologists believe that medical treatment with an SSRI is effective in the management of PE. At the same time, surgical treatment such as SDN also investigated as one of major treatment modality despite the lack of scientific evidence.

The effects of care management on depression treatment in a psychiatric clinic: a randomized controlled trial.

OBJECTIVE: This study aims to examine whether care management has an effect on adherence to depression treatment in a psychiatric clinic in Korea. METHODS: Fifty-seven patients with depression aged 60 years or over participated in the study. They were all low-income patients screened in the community and treated in a psychiatric clinic. The study design was a double-blind randomized controlled trial. The patients were randomly assigned to intervention (n = 29) or usual care (n = 28) groups. Intervention patients received depression care management for 6 months. Primary endpoint was an increase in remission rate as assessed using the 17-item Hamilton Depression Rating Scale score at 6 months. Secondary endpoints included improvement in treatment adherence, improvement in health-related quality of life, and a reduction in feelings of hopelessness. RESULTS: Patients in the care management intervention group showed a higher remission rate than those in the usual care group (55% vs. 29%, p = 0.0421). Intervention patients were significantly more likely to adhere to the treatment (59% vs. 18%, p = 0.0016). The hopelessness score at the 6-month assessment was significantly lower in the intervention group than the usual care group (23.5 vs. 25.7, p = 0.0443). However, there was not a significant group difference in the quality of life. CONCLUSIONS: We found that care management not only contributed to reducing depressive symptoms in geriatric patients suffering from depression but also increased the treatment adherence rate, which in turn increased the remission rate. Care management intervention is both feasible and effective in psychiatric clinics in Korea.

Isolation and characterization of smooth muscle cells from rat corpus cavernosum tissue for the study of erectile dysfunction.

PURPOSE: Primary culture of the cavernous smooth muscle cells from corpus cavernous tissues is known to be difficult, mainly because of contamination with fibroblasts. We applied a new method for better isolation of rat penile smooth muscle cells (RPSMCs) from rat corpus cavernosum tissue for reliable ex vivo research on erectile dysfunction. MATERIALS AND METHODS: With the use of 8-week-old adult male Sprague-Dawley rats, ex vivo migrations of rat cavernous tissue were measured by penis and aortic ring assay by use of a Matrigel-based D-valine-modified culture method. The expression of α-smooth muscle actin (α-SMA) and platelet/endothelial cell adhesion molecule (PECAM)-1 in the RPSMCs was determined by standard immunofluorescent staining and immunoblotting. The expression patterns of phosphodiesterase (PDE) family mRNA in RPSMCs were compared with patterns in rat aortic smooth muscle cells (RASMCs) by use of quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Immunocytochemical staining showed greater α-SMA-positive and PCAM-1-negative fluorescence. Moreover, whereas the expression of α-SMA was detected in the RPSMCs, that of PECAM-1 was not. The levels of PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, and PDE5A mRNA in the RPSMCs were about 3.2-, 4.4-, 3.4-, 29.0-, 3.5-, 2.8-, 2.9-, 6.1-, 45.0-, and 6.0-fold the corresponding expression in RASMCs. CONCLUSIONS: We developed a two-stage tissue culture method utilizing a Matrigel-based sprouting culture system to facilitate stromal cell sprouting and an adherent culture system using D-valine to eliminate the contamination of fibroblasts into the smooth muscle cells.

Prevalence of premature ejaculation in young and middle-aged men in Korea: a multicenter internet-based survey from the Korean Andrological Society.

In this study, we aimed to investigate the prevalence and perception of premature ejaculation (PE) in young and middle-aged Korean men. The study was conducted using an Internet-assisted questionnaire. A total of 2 037 Korean male adults, aged 20 years or older, were randomly sampled based on age and residency. The questionnaire developed by the PE Study Group of the Korean Andrological Society includes four categories (overall sexual function, symptoms, distress and treatment) with a total of 16 questions. For each question, symptoms were evaluated by a scale ranging from 0 to 10. Intravaginal ejaculation latency time was '5-10 min' in 38.6%, followed by 'longer than 10 min' in 29.9%, '2-5 min' in 23.6%, '1-2 min' in 5.4% and 'shorter than 1 min' in 2.5%. In our series, 27.5% of respondents reported having PE. Control over ejaculation within a recent 3-month period was 6.2 points on average. Respondent complaints of PE-related stress averaged 7.1 points and stress-related complaints from sexual partners averaged 7.1 points. The effect of PE on sexual life was 6.8 points. Of the respondents determined as having PE, 42.6% responded that they were inclined to receive treatment. Results from this study suggest that the prevalence of PE diagnosed by the respondent on his own was approximately 27.5% in young and middle-aged men in Korea. PE-related stress had a significant effect on the stress, sexual activity and quality of life of the respondent and his sexual partner.

Does oxybutynin alter plaques, amyloid beta peptides and behavior in a mouse model of Alzheimer's disease?

PURPOSE: In elderly patients oxybutynin (Sigma-Aldrich) is commonly used to treat overactive bladder despite increased prevalence of Alzheimer's disease in this population. We determined whether oxybutynin altered plaque formation, amyloid beta peptide expression and behavior in a transgenic mouse model of Alzheimer's disease expressing the mutant human presenilin 1 (deltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe). MATERIALS AND METHODS: Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid beta peptide expression was tested using enzyme-linked immunosorbent assay for amyloid beta peptides 1-40 and 1-42. RESULTS: Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean +/- SEM 2.2 +/- 0.4 vs 4.1 +/- 0.9 plaques, p <0.05) and cortex (5.8 +/- 0.7 vs 11.6 +/- 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid beta 1-42 (82.8 +/- 9.0 etag/ml vs 105.6 +/- 5.5 etag/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimer's disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9% +/- 1.6% vs 35.6% +/- 18.9%, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle. CONCLUSIONS: These results suggest that oxybutynin may slow the progression of Alzheimer's disease in this model.

Tadalafil increases Akt and extracellular signal-regulated kinase 1/2 activation, and prevents apoptotic cell death in the penis following denervation.

PURPOSE: Despite techniques to preserve the cavernous nerves during radical prostatectomy erectile dysfunction remains a complication. We determined whether bilateral cavernous nerve resection induces apoptosis in the penis. We also determined whether treatment with the phosphodiesterase-5 inhibitor tadalafil prevents apoptosis as well as the specific mechanisms involved. MATERIALS AND METHODS: Mice were subjected to cavernous nerve resection or sham surgery. Penises were processed for the identification of apoptotic cells, changes in phosphorylation of several protein kinases and immunolocalization of specific kinases. Mice were also placed on tadalafil or vehicle after cavernous nerve resection and the penises were processed as described. Statistical analysis was performed with the Mann-Whitney U test for comparisons among groups or Student's t test. RESULTS: An increase in apoptotic cavernous smooth muscle and endothelial cells was evident by 2 weeks, which further increased 4 and 6 weeks after cavernous nerve resection. Apoptosis coincided with an increase in the phosphorylation of c-jun N-terminal kinase and p38 mitogen activated protein kinase. Phospho-c-jun N-terminal kinase was immunolocalized to endothelial and smooth muscle cells. Treatment with tadalafil decreased the number of apoptotic cells and increased the phosphorylation of the 2 survival associated kinases Akt and extracellular signal-regulated kinase 1/2. CONCLUSIONS: These results provide a rationale for the early use of phosphodiesterase-5 inhibition following radical prostatectomy or extensive pelvic surgery, during which there may be injury to the cavernous nerves, to aid in the return of erectile function.

Increased expression of heat shock protein 20 and decreased contractile stress in obstructed rat bladder.

PURPOSE: Bladder outlet obstruction induces detrusor hypertrophy and it can eventually lead to decreased bladder smooth muscle contractility. Heat shock protein 20 is the proposed mediator of force suppression in vascular smooth muscle. We investigated whether heat shock protein 20 could also mediate the decreased contractility observed in partially obstructed rat bladders. MATERIALS AND METHODS: Female Wistar rats (Harlan Laboratories, Indianapolis, Indiana) were randomized to partial urethral ligation or sham ligation. After 3 weeks the rats were sacrificed, and the bladders were harvested, frozen, homogenized and analyzed for heat shock protein 20 content by Western blot immunoreactivity. The content of myosin regulatory light chain, a constitutively expressed protein, was determined as a control. Bladder smooth muscle strips were dissected from some rats and mounted for force generation measurement. RESULTS: At cystectomy obstructed bladders were significantly heavier and had more residual urine compared to sham operated bladders. Heat shock protein 20 immunoreactivity was significantly increased a mean +/- 1 SEM of 1.9 +/- 0.3-fold in obstructed vs sham operated bladders. Control protein myosin regulatory light chain immunoreactivity did not significantly differ in obstructed and sham operated bladders. Maximal stress, that is force per cross-sectional area, was significantly decreased in obstructed vs sham operated bladders. Human bladder was found to express immunoreactive heat shock protein 20. CONCLUSIONS: We noted that partially obstructed rat bladders 1) express higher levels of heat shock protein 20 and 2) generate less stress than sham operated bladders. These data suggest the possibility that heat shock protein 20 over expression could at least partially mediate the decreased contractile activity observed with partial bladder outlet obstruction. The mechanism for increased heat shock protein 20 expression is unknown but it may involve increased mechanical stress or hypoxia from urethral obstruction. Human bladder expressed immunoreactive heat shock protein 20, suggesting that a similar mechanism could potentially occur in humans. If confirmed in humans, patients with clinical conditions that result in detrusor hypocontractility could potentially benefit from pharmacological interventions aimed at inhibiting heat shock protein 20.

In vivo detection of apoptotic cells in the testis using fluorescence labeled annexin V in a mouse model of testicular torsion.

PURPOSE: It is well established that experimental testicular torsion induces germ cell specific apoptosis. Annexin V (BD Pharmingentrade mark) binds phosphatidylserine that becomes exposed on the cell membrane in apoptotic cells. In vivo detection of apoptotic cells with fluorescently labeled annexin V is an emerging technique that we evaluated for detecting apoptotic germ cells in a mouse model of testicular torsion. MATERIALS AND METHODS: Annexin V labeled with an indocyanine fluorophore (bisfunctional succinimidyl ester of cyanine 5.5) (Amersham, Little Chalfont, United Kingdom) was injected intravenously in mice 18 hours after the repair of unilateral 720-degree testicular torsion for 2 hours. Serial fluorescence images were obtained 21, 24, 28 and 42 hours after torsion repair. Relative fluorophore localization was visualized in vivo using an optical small animal imaging system mounted with a filter in near infrared light. Average fluorescence intensity in torsed and sham testes was quantified in images of testes in situ exposed through an abdominal incision and in ex vivo testes. RESULTS: A significant increase in fluorescence intensity was found in images of torsed vs sham operated testes. This was seen in ex vivo, exposed and in vivo testes (215%, 250% and 161%, respectively, p <0.05). Bisfunctional succinimidyl ester of cyanine 5.5 conjugated to dehydrogenase, a protein with a size similar to that of annexin V, was used to assess for capillary leakage. It was also more localized to the torsed testis relative to its contralateral sham control whether exposed or ex vivo (174% and 176%, respectively). CONCLUSIONS: To our knowledge this study demonstrates for the first time the possibility of in vivo near infrared fluorescence imaging of apoptotic germ cells after testicular torsion in mice. It shows important confounding factors that must be considered as this new imaging technique is developed for detecting apoptotic cells in vivo in testes or in any other organ.

Laparoscopic management of complicated urachal remnant in a child.

A few cases of laparoscopic surgery for urachal remnant in children has been reported in English literature. With recent developments in minimal invasive surgery, laparoscopic approach for urachal remnant in adulthood is recommended by some laparoscopic surgeons because of its technical feasibility and safety as well as cosmesis. Recently we experienced a case of complicated urachal remnant in a 14-month-old girl, who was managed by laparoscopic approach. At presentation, she complained of high fever and lower urinary tract symptoms. After 6 weeks of antibiotics therapy, laparoscopic surgery was performed transperitoneally via 3 ports. Our experience suggests that laparoscopic excision of urachal remnant can be performed easily and safely in children.