Sang-Kuk Yang

Does phosphorylation of cofilin affect the progression of human bladder cancer

BackgroundWe 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.MethodsWe 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.ResultsThe 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.ConclusionsThese 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.

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.

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.

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.

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.

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 Alzheimers disease in this population. We determined whether oxybutynin altered plaque formation, amyloid beta peptide expression and behavior in a transgenic mouse model of Alzheimers 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 Alzheimers 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 Alzheimers disease in this model.

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 patients 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.

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.

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

This study aims to examine whether care management has an effect on adherence to depression treatment in a psychiatric clinic in Korea.