A Simple and Nonenzymatic Method to Isolate Human Corpus Cavernosum Endothelial Cells and Pericytes for the Study of Erectile Dysfunction

A Method to Isolate Pericytes From the Mouse Urinary Bladder for the Study of Diabetic Bladder Dysfunction / 대한배뇨장애요실금학회지

Purpose@#Pericytes surround the endothelial cells in microvessels and play a distinct role in controlling vascular permeability and maturation. The loss of pericyte function is known to be associated with diabetic retinopathy and erectile dysfunction. This study aimed to establish a technique for the isolation of pericytes from the mouse urinary bladder and an in vitro model that mimics in vivo diabetic bladder dysfunction. @*Methods@#To avoid contamination with epithelial cells, the urothelial layer was meticulously removed from the underlying submucosa and detrusor muscle layer. The tissues were cut into multiple pieces, and the fragmented tissues were settled by gravity into collagen I-coated culture plates. The cells were cultured under normal-glucose (5 mmol/L) or high-glucose (30 mmol/L) conditions, and tube formation, cell proliferation, and TUNEL assays were performed. We also performed hydroethidine staining to measure superoxide anion production. @*Results@#We successfully isolated high-purity pericytes from the mouse urinary bladder. The cells were positively stained for platelet-derived growth factor receptor-β and NG2 and negatively stained for smooth muscle cell markers (desmin and myosin) and an endothelial cell marker (CD31). The number of tubes formed and the number of proliferating cells were significantly lower when the pericytes were exposed to high-glucose conditions compared with normal-glucose conditions. In addition, there were significant increases in superoxide anion production and the number of apoptotic cells when the pericytes were cultured under high-glucose conditions. @*Conclusions@#To the best of our knowledge, this is the first study to isolate and culture pericytes from the mouse urinary bladder. Our model would be a useful tool for screening the efficacy of therapeutic candidates targeting pericyte function in diabetic bladder dysfunction and exploring the functional role of specific targets at the cellular level.

A Method to Isolate Pericytes From the Mouse Urinary Bladder for the Study of Diabetic Bladder Dysfunction / 대한배뇨장애요실금학회지

Purpose@#Pericytes surround the endothelial cells in microvessels and play a distinct role in controlling vascular permeability and maturation. The loss of pericyte function is known to be associated with diabetic retinopathy and erectile dysfunction. This study aimed to establish a technique for the isolation of pericytes from the mouse urinary bladder and an in vitro model that mimics in vivo diabetic bladder dysfunction. @*Methods@#To avoid contamination with epithelial cells, the urothelial layer was meticulously removed from the underlying submucosa and detrusor muscle layer. The tissues were cut into multiple pieces, and the fragmented tissues were settled by gravity into collagen I-coated culture plates. The cells were cultured under normal-glucose (5 mmol/L) or high-glucose (30 mmol/L) conditions, and tube formation, cell proliferation, and TUNEL assays were performed. We also performed hydroethidine staining to measure superoxide anion production. @*Results@#We successfully isolated high-purity pericytes from the mouse urinary bladder. The cells were positively stained for platelet-derived growth factor receptor-β and NG2 and negatively stained for smooth muscle cell markers (desmin and myosin) and an endothelial cell marker (CD31). The number of tubes formed and the number of proliferating cells were significantly lower when the pericytes were exposed to high-glucose conditions compared with normal-glucose conditions. In addition, there were significant increases in superoxide anion production and the number of apoptotic cells when the pericytes were cultured under high-glucose conditions. @*Conclusions@#To the best of our knowledge, this is the first study to isolate and culture pericytes from the mouse urinary bladder. Our model would be a useful tool for screening the efficacy of therapeutic candidates targeting pericyte function in diabetic bladder dysfunction and exploring the functional role of specific targets at the cellular level.

Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque

PURPOSE: Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque. MATERIALS AND METHODS: For differential gene expression study, we performed reverse-transcriptase polymerase chain reaction for HDAC isoforms (1–11) in fibroblasts isolated from PD plaque or normal TA. Fibroblasts isolated from PD plaque were pretreated with HDAC7 siRNA (100 pmol) and then stimulated with transforming growth factor-β1 (TGF-β1, 10 ng/mL). Protein was extracted from treated fibroblasts for Western blotting. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-β1-induced nuclear translocation of Smad2/3 and myofibroblastic differentiation. RESULTS: The mRNA expression of HDAC2, 3, 4, 5, 7, 8, 10, and 11 was higher in fibroblasts isolated from PD plaque than in fibroblasts isolated from normal TA tissue. Knockdown of HDAC7 in PD fibroblasts inhibited TGF-β1-induced nuclear shuttle of Smad2 and Smad3, transdifferentiation of fibroblasts into myofibroblasts, and abrogated TGF-β1-induced production of extracellular matrix protein. CONCLUSIONS: These findings suggest that specific inhibition of HDAC7 with RNA interference may represent a promising epigenetic therapy for PD.

Combination of stromal vascular fraction and Ad-COMP-Ang1 gene therapy improves long-term therapeutic efficacy for diabetes-induced erectile dysfunction / 亚洲男科学杂志(英文版)

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Ang1 notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice. In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED.

Optimizing in vivo gene transfer into mouse corpus cavernosum by use of surface electroporation

PURPOSE: Electroporation is known to enhance the efficiency of gene transfer through a transient increase in cell membrane permeability. The aim of this study was to determine the optimal conditions for in vivo electroporation-mediated gene delivery into mouse corpus cavernosum. MATERIALS AND METHODS: Diabetes was induced in C57BL/6 mice by intraperitoneal injections of streptozotocin. After intracavernous injection of pCMV-Luc (100 microg/40 microL), different electroporation settings (5-50 V, 8-16 pulses with a duration of 40-100 ms) were applied to the penis to establish the optimal conditions for electroporation. Gene expression was evaluated by luciferase assay. We also assessed the undesired consequences of electroporation by visual inspection and hematoxylin-eosin staining of penile tissue. RESULTS: Electroporation profoundly induced gene expression in the corpus cavernosum tissue of normal mice in a voltage-dependent manner. We observed electrical burn scars in the penis of normal mice who received electroporation with eight 40-ms pulses at a voltage of 50 V and sixteen 40-ms pulses, eight 100-ms pulses, and sixteen 100-ms pulses at a voltage of 30 V. No detectable burn scars were noted in normal mice stimulated with eight 40-ms pulses at a voltage of 30 V. Electroporation also significantly induced gene expression in diabetic mice stimulated with 40-ms pulse at a voltage of 30 V without injury to the penis. CONCLUSIONS: We have established the optimal electroporation conditions for maximizing gene transfer into the corpus cavernosum of mice while avoiding damage to the erectile tissue. The electroporation-mediated gene delivery technique will be a valuable tool for gene therapy in the field of erectile dysfunction.

Therapeutic Angiogenesis as a Potential Future Treatment Strategy for Erectile Dysfunction

The cavernous endothelium plays a crucial role in regulating the tone of the underlying smooth muscle and physiologic penile erection. Recently, the link between erectile dysfunction (ED) and cardiovascular disease was unveiled, and the main etiology of ED was found to be vasculogenic. Although oral phosphodiesterase-5 inhibitors are generally effective for men with ED, such therapies do not cure underlying vasculopathy in the corpus cavernosum tissue. This review addresses current preclinical protein, gene, and cell or stem cell therapies for enhancing cavernous endothelial regeneration and restoring erectile function.

Activin Receptor-Like Kinase 5 Inhibitor Attenuates Fibrosis in Fibroblasts Derived from Peyronie's Plaque

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is the key fibrogenic cytokine associated with Peyronie's disease (PD). The aim of this study was to determine the antifibrotic effect of 3-((5-(6-Methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl) methyl)benzamide (IN-1130), a small-molecule inhibitor of the TGF-beta type I receptor activin receptor-like kinase 5 (ALK5), in fibroblasts isolated from human PD plaque. MATERIALS AND METHODS: Plaque tissue from a patient with PD was used for primary fibroblast culture, and we then characterized primary cultured cells. Fibroblasts were pretreated with IN-1130 (10 microM) and then stimulated with TGF-beta1 protein (10 ng/ml). We determined the inhibitory effect of IN-1130 on TGF-beta1-induced phosphorylation of Smad2 and Smad3 or the nuclear translocation of Smad proteins in fibroblasts. Western blot analyses for plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV were performed to evaluate effect of IN-1130 on the production of extracellular matrix proteins. RESULTS: The treatment of fibroblasts with TGF-beta1 significantly increased phosphorylation of Smad2 and Smad3 and induced translocation of Smad proteins from the cytoplasm to the nucleus. Pretreatment with IN-1130 substantially inhibited TGF-beta1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins. The TGF-beta1-induced production of extracellular matrix proteins was also significantly inhibited by treatment with IN-1130 and returned to basal levels. CONCLUSIONS: Overexpression of TGF-beta and activation of Smad transcriptional factors are known to play a crucial role in the pathogenesis of PD. Thus, inhibition of the TGF-beta signaling pathway by ALK5 inhibitor may represent a promising therapeutic strategy for treating PD.

Differential Expression of Nerve Injury-Induced Protein 1 (Ninjurin 1) in In Vivo and In Vitro Models for Diabetic Erectile Dysfunction

PURPOSE: Endothelial dysfunction and peripheral neuropathy are important mechanisms responsible for diabetes-induced erectile dysfunction (ED). Nerve injury-induced protein 1 (Ninjurin 1) is known to be related to neuroinflammatory processes and is also reported to induce vascular regression during the developmental period. In the present study, we determined the differential expression of Ninjurin 1 in penile tissue of streptozotocin (STZ)-induced diabetic mice with ED. MATERIALS AND METHODS: Diabetes was induced in 8-week-old C57BL/6J mice by intraperitoneal injections of STZ (50 mg/kg for 5 days). Eight weeks later, erectile function was measured by electrical stimulation of the cavernous nerve (n=6 per group). The penis was then harvested for immunohistochemical analysis and Western blot analysis for Ninjurin 1 (n=4 per group). We also determined Ninjurin 1 expression in primary cultured mouse cavernous endothelial cells (MCECs) incubated under the following conditions: normal glucose condition (5 mM), high-glucose condition (30 mM), and high-glucose condition (30 mM)+insulin (1 nM). RESULTS: The expression of Ninjurin 1 protein was significantly higher in both cavernous endothelial cells and the dorsal nerve bundle of diabetic mice than in those of controls. In the in vitro study in MCECs, Ninjurin 1 expression was also significantly increased by the high-glucose condition and was returned to baseline levels by treatment with insulin. CONCLUSIONS: Regarding the role of Ninjurin 1 in neuropathy and vascular regression, it would be interesting to examine the effects of inhibition of Ninjurin 1 on erectile function in animal models of ED with a vascular or neurogenic cause.

Transforming Growth Factor-beta Type I Receptor Inhibitor Induces Functional and Morphologic Recovery in a Rat Model of Erectile Dysfunction and Cavernous Fibrosis / 대한남성과학회지

PURPOSE: To examine the effectiveness of small-molecule inhibitor of transforming growth factor-beta (TGF-beta) type I receptor, an activin receptor-like kinase 5 (ALK5), on erectile dysfunction (ED) in a rat model of cavernous fibrosis, in which fibrosis was induced by intracavernous injection of adenovirus expressing TGF-beta1 (Ad-TGF-beta1). MATERIALS AND METHODS: Four-month-old Sprague-Dawley rats were divided into four groups (n=10 per group): age-matched controls without treatment, age-matched controls receiving intracavernous injection of LacZ adenovirus, and cavernous fibrosis rats receiving an intracavernous injection of saline or ALK5 inhibitor (5 mg/kg). ALK5 inhibitor or saline was administered on day 5 after injection of Ad-TGF-beta1. On day 30, erectile function was assessed by electrical stimulation of the cavernous nerve and the penis was then harvested for histologic studies (n=6 per group) and for the measurement of the hydroxyproline level (n=4 per group). RESULTS: Ad-TGF-beta1-induced cavernous fibrosis rats treated with saline showed a significant decrease in cavernous smooth muscle and endothelial content, and an increase in collagen deposition, which resulted in profound deterioration of all erectile function parameters, such as the ratios of maximal intracavernous pressure (ICP), total ICP, and slope to mean arterial pressure. ALK5 inhibitor significantly restored erectile function in a rat model of cavernous fibrosis by increasing cavernous smooth muscle and endothelial content, and by blocking cavernous fibrosis. CONCLUSIONS: The results suggest that inhibition of the TGF-beta pathway is a promising therapeutic strategy for the treatment of ED related to cavernous fibrosis from various causes.

Establishment of a Cavernous Fibrosis Model in a Rat Using Adenovirus Expressing Transforming Growth Factor-beta1 / 대한남성과학회지

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) has been implicated in cavernous fibrosis due to a variety of causes of erectile dysfunction (ED), such as diabetes mellitus and post-radical prostatectomy. To examine the role of the TGF-beta signaling pathway in cavernous fibrosis, we established a rat model of cavernous fibrosis by using adenovirus expressing TGF-beta1 (ad-TGF-beta1). MATERIALS AND METHODS: Four-month-old male Sprague-Dawley rats received intracavernous injection of ad-TGF-beta1 (1x10(8), 1x10(9), or 1x10(10) virus particles [vp] in 100 microliter of PBS) and the penis was harvested for histologic examination at 10, 20, or 30 days after injection (n=4 per group and per time point). Based on the initial findings, the animals were divided into three groups (n=6 per group): Group 1, age-matched control; Group 2, intracavernous injection of ad-LacZ (1x10(10) vp/100 microliter); and Group 3, intracavernous injection of ad-TGF-beta1 (1x10(10) vp/100 microliter). At 30 days after injection, erectile function was evaluated during electrical stimulation of the cavernous nerve. The penis was then harvested and stained with Masson's trichrome and antibody to smooth muscle alpha-actin. RESULTS: Masson's trichrome staining revealed that intracavernous delivery of ad-TGF-beta1 sufficiently induced cavernous fibrosis in a dose-dependent manner. The fibrotic scars persisted up to 30 days after injection at the highest dosage (1x10(10) vp/100 microliter), whereas no histologic evidence of cavernous fibrosis was found in the control rats or the ad-LacZ-injected rats. The rats receiving ad-TGF-beta1 showed a higher cavernous collagen content and less smooth muscle content than the control rats or ad-LacZ-injected rats. Erectile function was significantly decreased in rats receiving ad-TGF-beta1 compared with that in controls or rats receiving ad-LacZ. CONCLUSIONS: This model induced by ad-TGF-beta1 may play an important role in understanding the pathophysiologic mechanisms of cavernous fibrosis-associated TGF-beta signaling and the development of new therapeutics targeting this pathway.

Effect of IN-1130, a Novel Transforming Growth Factor-beta Type I Receptor Kinase (ALK5) Inhibitor, on a Rat Model of Peyronie's Disease Induced by Repeated Intratunical Injections of Fibrin / 대한남성과학회지

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) has been known to be involved in the pathogenesis of Peyronie's disease (PD). In the present study, we investigated the therapeutic effect of IN-1130, a novel small molecule inhibitor of activin receptor-like kinase (ALK)5, a type I receptor of TGF-beta, in an animal model of PD induced by fibrin. MATERIALS AND METHODS: Four-month-old male Sprague-Dawley rats were divided into three groups (n=4 per group): group 1, age-matched control; group 2, PD rats without treatment; group 3, PD rats receiving an intratunical injection of IN-1130 (on day 20, 5 mg/kg in 0.1 ml saline) into the lesion. PD was induced in rats through repeated injections of fibrin (50 microliter each of human fibrin and thrombin solutions, days 0, 3, and 6, respectively) into the tunica albuginea. Penile curvature was evaluated by use of an artificialerection test on day 30. The penis was then harvested and stained with Masson trichrome, hematoxylin- eosin, and antibody to vimentin and phospho-Smad2. RESULTS: PD rats receiving repeated intratunical injections of fibrin revealed an infiltration of inflammatory cells, including lymphocytes, plasma cells, and fibroblasts, and an increase in transnuclear expression of phospho-Smad2 in the fibrotic plaque. However, repeated intratunical injections of fibrin did not induce penile curvature. IN-1130 induced significant regression of fibrotic plaque through reduced infiltration of inflammatory cells and reduced transnuclear expression of phospho-Smad2. CONCLUSIONS: Inhibition of TGF-beta pathway through the use of ALK5 inhibitors may be a curative local treatment modality for PD.

Peyronie's Disease: Current Medical Treatment and Future Perspectives

PURPOSE: Because of our incomplete understanding of the pathogenesis of Peyronie's disease (PD), management of PD remains a therapeutic dilemma in the field of sexual medicine. Most currently available medical treatments have not demonstrated conclusive effects. The present review addresses the current status of nonsurgical treatment and emerging new therapeutic targets for PD. MATERIALS AND METHODS: A systematic review of clinical or preclinical results of nonsurgical treatment for PD published as original articles in peer-reviewed journals is provided. RESULTS: Although many studies regarding nonsurgical treatment of PD showed positive outcomes, the majority of these studies were not placebo-controlled approaches. Currently available randomized controlled trials on the use of oral, intralesional injection, and topical agents have not showed conclusive effects, with minor or little effect. However, the outcomes of recent preclinical studies targeting the TGF-beta pathway or NO-cGMP pathway are promising. CONCLUSIONS: There is no viable therapeutic option for PD between watchful waiting and surgical manipulation. With further research into the pathologic cascade of cellular and molecular events and an increase in our understanding of the pathophysiology of PD using animal models, the development of novel and effective medical therapies will become a realistic objective.

Establishment of Peyronie's Disease Model in a Rat with Repeated Injections of Fibrin into Tunica Albuginea / 대한남성과학회지

PURPOSE: This study was undertaken to establish a Peyronie's disease model by using local injection of fibrin into the tunica albuginea. MATERIALS AND METHODS: Four-month-old male Sprague-Dawley rats were divided into three groups (n=12 per group): Gr I, age-matched control; Gr II, a single injection of fibrin (50 microliter each of human fibrin and thrombin solutions); and Gr III, repeated injections of fibrin (50 microliter each of human fibrin and thrombin solutions, days 0, 3, and 6, respectively) into the tunica albuginea. We evaluated penile curvature by the use of an artificial erection test with intracavernous injection of saline and erectile function by cavernous nerve electrical stimulation 30, 45, and 60 days (n=4 per time point) after treatment. The penis was then harvested and stained with Masson trichrome, hematoxylin-eosin, and antibody to phospho-Smad2. RESULTS: Whereas a single intratunical injection of fibrin induced fibrous scar in the tunica, which lasted up to 45 days and disappeared 60 days after injection, repeated injections of fibrin induced more pronounced tunical fibrosis, which lasted up to 60 days after injection. However, a single or repeated intratunical injection of fibrin did not induce significant penile curvature. The peculiar histological findings in group receiving a single or repeated intratunical injection of fibrin were infiltration of inflammatory cells, and increase of transnuclear expression of phospho-Smad2. CONCLUSIONS: Although a single or repeated administration of fibrin did not induce penile curvature, this model may contribute to further investigation of pathogenesis and development of potential therapeutics in Peyronie's disease.

The Relationship between Inflammation or Bacterial Infection according to the Traditional 4-glass Tests or Tc-99m Ciprofloxacin Imaging and the Scores of the National Institute of Health-Chronic Prostatitis Symptom Index in Men with Chronic Prostatitis / 대한비뇨기과학회지

PURPOSE: We wanted to determine whether inflammation and bacterial infection, as tested for by the traditional 4-glass test or Tc-99m ciprofloxacin imaging, correlate with the symptom severity in men with chronic prostatitis. MATERIALS AND METHODS: The study included 256 patients with symptoms of prostatitis. The Korean version of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was used to measure the symptoms of each patient. To diagnose bacterial infection, four-glass tests were performed that included culture for general bacteria, Mycoplasma hominis and Ureaplasma urealyticum, and polymerase chain reaction was performed for Chlamydia trachomatis. The patients with established uropathogens localized to the expressed prostatic secretion or the voided urine 3 were classified as having chronic bacterial prostatitis (CBP). To further localize the infection, the single photon emission computerized tomography images were obtained 3 hours after intravenous injection of Tc-99m ciprofloxacin. Associations between the symptoms and the inflammation and infection were evaluated. RESULTS: Based on the 4-glass tests, the patients were classified as CBP (n=16) or as chronic pelvis pain syndrome (CCPS) (the inflammatory type, n=94; non-inflammatory type, n=146). The CBP patients had a higher pain score than did the CPPS patients and there were no significant differences in the subscores for voiding symptoms and the quality of life between the groups. No significant differences were found in the total score or the subscores of the NIH-CPSI based on the presence or location of infection on the Tc-99m ciprofloxacin imaging. CONCLUSIONS: These findings suggest that bacterial infection, not inflammation, as determined by traditional laboratory tests contribute to the symptoms, especially pain, in men with chronic prostatitis.

Comparison of the Efficacy of Transperineal Intraprostatic Injection and Oral Administration of Fluoroquinolone in Men with Chronic Bacterial Prostatitis-Seminal Vesiculitis / 대한비뇨기과학회지

Purpose: Although oral antibiotic therapy remains the most common treatment modality for chronic bacterial prostatitis (CBP), it is known to have problems, such as potential adverse effects and the development of bacterial resistance. We compared the effects of oral and local injection therapies, with fluoroquinolones, in patients diagnosed as having chronic bacterial prostatitis/seminal vesiculitis, from Tc-99m ciprofloxacin imaging. Materials and Methods: The study randomly included 79 patients with symptom of prostatitis, who also showed hot uptake in the prostate or seminal vesicle on Tc-99m ciprofloxacin imaging. A total of 53 patients received oral antibiotics for 3 months. In 26 patients, a local injection of ciprofloxacin into the prostate and/or seminal vesicle was performed via the transperineal route, with transrectal ultrasonography guidance. Four- glass tests and Tc-99m ciprofloxacin imaging were performed, and the patients were asked to complete National institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaires at the baseline and 3 months after the initiation of therapy. Results: The total score or subscores from the NIH-CPSI and bacteriological study after treatment was significantly decreased in both groups compared to that before treatment. The complete cure rate, based on the Tc-99m ciprofloxacin imaging findings, was significantly higher in the local injection (23.1%) than the oral therapy group (16.9%, p<0.024). In the local injection group, 15 men (57.7%) showed transient hematuria and/or bloody ejaculation, but without any serious side effects. Conclusions: A transperineal lesional injection of fluoroquinolone will be a valuable therapeutic alternative in men with chronic bacterial prostatitis/ seminal vesiculitis; although a long term outcome study will be required.

Xanthogranulomatous Epididymitis / 대한비뇨기과학회지

Xanthogranulomatous epididymitis is extremely uncommon inflammatory disease of the epididymis that may result in massive destruction of the organ. It's clinical manifestation mimics epididymal tumor or abscess, which does not allow easy discrimination between theses diseases. We report here on a case of xanthogranulomatous epididymitis in a 69 years old man that, did not respond to antibiotic therapy.

Gene Therapy for Erectile Dysfunction / 대한남성과학회지

It is now well known that vascular diseases, including hypercholesterolemia, atherosclerotic vascular disease, and diabetes mellitus are major causes for erectile dysfunction(ED). Despite the introduction of oral phosphodiesterase-5 inhibitors in the treatment of ED, new therapeutic strategies are warranted. Current therapies have two shortcomings. First, every currently approved non-surgical treatment option for ED requires planning prior to intercourse. Second, there is a need for increased treatment efficacy for patients with moderate to severe ED. Gene therapy may well address both of these areas, as the ultimate goal of the therapy is the restoration of physiologic erections following normal endogenous signals, in the absence of the any other form of therapy. The penis is a convenient organ for local gene therapy because of its external location, ubiquity of endothelial-lined spaces, slow circulation in the flaccid state, and gap junctions between smooth muscles, which ensure wide distribution of injected genes inside the penis. Many gene therapy approaches have focused on the NO/cGMP pathway, angiogenic factors, neurotrophic factors, potassium channels, the RhoA/Rho-kinase system, etc. Various viral and nonviral vectors as well as genetically engineered cells have been used as gene delivery vehicles for the transfer of genetic material to the target cell or tissues. In contrast to its use in cancer, the application of gene therapy for a non-life threatening disease, such as ED, requires a higher safety level and more knowledge of secure and efficacious vectors for gene transfer. The preclinical data from recent studies in several ED models are quite impressive and encouraging. Gene therapy interventions to restore erectile function may represent an exciting new therapeutic strategy for the future treatment of ED.

Clinical Outcome of Acute Bacterial Prostatitis, a Multicenter Study / 대한비뇨기과학회지

PURPOSE: Few studies have examined acute prostatitis in Korea. To initiate the investigation of this topic, a multi-center retrospective analysis of acute prostatitis was conducted. MATERIALS AND METHODS: The clinical records of 335 patients from 13 hospitals, diagnosed with acute prostatitis, between January of 1994 and October of 2004, were reviewed. For each patient, the urine culture, changes in the PSA (prostate-specific antigen) value and the prostate volume, the incidence of prostate abscess, the use of antibiotics, and whether the disease went into remission or progressed to chronic prostatitis were analyzed. RESULTS: The mean age of the patients, time from the onset of symptom to admission and number of days of admitted were 54.9+/-15.1 (16-85) years, 2.4+/-3.4 (16-85) days and 7.5+/-3.9 (1-25) days, respectively. The chief symptoms of the patients were high fever, dysuria and urinary frequency. Routine urinalysis found pyuria in 82% and hematuria in 70% of patients. The causative organisms of 43.0% of the patients were cultured, with the chief organisms found to be E. coli (67%) and P. aeruginosa (13%), et al. The mean PSA and prostate volume on initial diagnosis were 24.6+/-30.2ng/ml and 45.8 +/-17.4ml, respectively, and a prostate abscess was found in 4 patients (3.1%). The antibiotics injected during patient admission were: cephalosporin family (68%), aminoglycosides (70%) and quinolone family (43%). An additional alpha blocker was used in 49% of cases. Oral quinolone (91%), cephalosporin (9%) and alpha blocker (44%) were prescribed for a mean 32.5 (2-180) days after discharge. 259 (77%) of the patients were available for follow-up. Of these, 21% took antibiotics over an 8 week treatment period, and 8% over a 12 week period. The disappearance of pyuria after treatment was observed in a mean of 13 days after the end of treatment. After 13 weeks of treatment, 11 (50%) of the 22 patients who received prostate massage (4.2% of all follow up patients) were found to have chronic prostatitis. The mean PSA and prostate volume declined during follow up, to 6.13+/-10.38ng/ml and 37.5+/-13.5ml, respectively. CONCLUSIONS: In our study, the most common chief symptom of acute prostatitis was a high fever, with the most common causative organism being E. coli. Patients were admitted for approximately one week, and treated with antibiotic for about one month, after which time PSA elevation was observed in 80% of patients. Although all acute prostatitis patients were treated with proper antibiotics, progression to chronic prostatitis was observed in 4.2% of patients.

Plasma transforming growth factor-beta1 levels in patients with erectile dysfunction / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To evaluate the plasma TGF-beta1 level in erectile dysfunction (ED) patients of various causes.</p><p><b>METHODS</b>Sixty-two patients with ED and 26 potent men were subjected to the study. Based on multidisciplinary work-ups, including medical history, physical examinations, blood tests with lipid profile and hormones, penile duplex Doppler ultrasonogram and neurophysiological tests, causes for ED were classified as psychogenic (n=15), neurogenic (n=16) and vasculogenic (n=31). The plasma TGF-beta1 level was measured by the ELISA method.</p><p><b>RESULTS</b>The plasma TGF-beta1 level was significantly increased in the ED group (6.7+/-4.9 ng/mL), compared to the control (4.0 +/-2.1 ng/mL) (P<0.01). In the ED groups, there was a significant increase in the vasculogenic group (9.0 +/-5.5 ng/mL), compared to the psychogenic (3.8 +/-1.8 ng/mL) and neurogenic groups (4.8+/-3.2 ng/mL) (P<0.01). Of the vascular risk factors, both the smoking (7.5 +/-4.7 ng/mL) and dyslipidemia groups (7.4+/-4.4 ng/mL) showed significantly increased plasma TGF-beta1 levels, compared to the non-smokers (5.5+/-2.8 ng/mL), and those without dyslipidemia (4.8+/-2.8 ng/mL) (P<0.05).</p><p><b>CONCLUSION</b>Vascular risk factors are associated with an elevated plasma TGF-beta1 level, which may contribute to cavernous fibrosis and ED.</p>