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.
Angiogenesis Inducing Agents ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Diabetes Mellitus ; Erectile Dysfunction* ; Gap Junctions ; Genetic Therapy* ; Humans ; Hypercholesterolemia ; Male ; Muscle, Smooth ; Nerve Growth Factors ; Penis ; Potassium Channels ; Treatment Outcome ; Vascular Diseases

Conventional laparoscopic surgery requires definite leaming curve, and must be converted to an open procedure in the event of a large vessel injury. The usage of carbon dioxide gas for securing operative field is generally accepted, but such field rapidly disappears when air pressure decreases. To overcome these shortcomings without sacrificing advantages of excellent cosmetic results and reduced wound pain of laparoscopy without using the gas insufflation, various urologic operations utilizing incisions 2 to 5 cm long were made without cutting abdominal musculature with the help of specially designed retractors and video systems used in conventional laparoscopic surgery. It can be performed in familiar anatomical settings and all the surgical skills of open procedures can be utilized. We have performed 3 living donor nephrectomies, 6 simple nephrectomies, 2 partial nephrectomies, 9 pyeloplasties, 16 ureterolithotomies, 1 ureteroureterostomy, and 2 renal cyst marsupializations. Mean operative time and hospital stay were 185 minutes and 7 days for living donor nephrectomies, 150 minutes and 6.7 days for simple nephrectomies, 255 minutes and 7.5 days for partial nephrectomies, 130 minutes and 4.8 days for pyeloplasties, 85 minutes and 4.1 days for ureterolithotomies, 90 minutes and 5 days for ureteroureterostomy, and 75 minutes and 5.5 days for renal cyst marsupializations, respectively. Immediate wound pain was severe probably due to intense traction of abdominal musculature, but the recovery of such pain was remarkably rapid. No postoperative wound paresthesia was seen and early discharge was possible. In conclusion, the gasless retroperitoneoscopically assisted surgery can take advantage of both conventional open and laparoscopic surgery, and it can be a valid option to conventional open surgery for any surgical procedures in retroperitoneum, including kidney, ureter, and bladder.
Air Pressure ; Carbon Dioxide ; Humans ; Insufflation ; Kidney ; Laparoscopy ; Length of Stay ; Living Donors ; Nephrectomy ; Operative Time ; Paresthesia ; Traction ; Ureter ; Urinary Bladder ; Wounds and Injuries

Peyronie's disease(PD) is an inflammatory condition characterized by the formation of fibrous, noncompliant nodules in the tunica albuginea leading to penile deformity and bending. Repetitive microtrauma of the penis during sexual intercourse is thought to incite a local autoimmune reaction in genetically susceptible individuals. The fibrotic plaques are most likely produced by tunical fibroblasts in response to cytokine stimulation, such as by transforming growth factor-beta1. In the acute inflammatory phase, pain during erection and penile deviation are the main symptom. In later stages, PD is often associated with erectile dysfunction(ED), distal flaccidity, or both. The causes of ED include psychological factors (performance anxiety), penile pain and deformity, flail penis, and vascular disease. Conservative treatment is useful during the early inflammatory stage. Despite myriad proposed medical therapies, including numerous oral agents and local injection regimens, there have been limited advances. Surgery is typically reserved for patients who fail to respond to conservative treatment and have had no disease progression for at least several months. Penile lengthening procedures with different grafting materials have, to a great extent, replaced conventional procedures with penile plication or its modifications. Prosthesis insertion is reserved for patients with severe ED that does not respond to medical management. As the molecular mechanism of inflammation and wound healing is elucidated, new approaches for medical intervention, such as modification of fibroblast function, growth factor activity, and cytokine action, will no doubt be available for therapy of PD.
Coitus ; Congenital Abnormalities ; Disease Progression ; Fibroblasts ; Humans ; Inflammation ; Male ; Penile Induration* ; Penis ; Prostheses and Implants ; Psychology ; Transplants ; Vascular Diseases ; Wound Healing

PURPOSE: We compared the clinical efficacy of Therasonic LTS (piezoelectric type) with that of SDS-5000 (spark gap type) for the management of urinary stones. MATERIALS AND METHODS: We evaluated 516 patients treated with Therasonic LTS, between June 1996 and April 2001, and 314 treated with SDS-5000 between September 2001 and January 2003. We compared the average success rates and shock wave sessions according to the stone sizes and locations, and also verified the complications related to the therapies. RESULTS: The total success rates of Therasonic LTS and SDS-5000 were similar (92.6 and 94.6%, respectively), with no difference according to stone location and size. However, the average shock wave sessions were significantly lower in the group treated with SDS-5000 (2.5 1.8 sessions) compared to the group treated with Therasonic LTS (3.1 1.9 sessions) (p<0.05). The cumulative success rates were 64.3 and 77.1%, respectively, at the completion of session 3, and 82.2 and 88.2%, respectively, at the completion of session 5. The complication rates associated with the therapies were 8.9 and 6.9%, respectively, consisting of pain, gross hematuria, steinstrasse and acute pyelonephritis, most of which were successfully controlled by conservative treatment. CONCLUSIONS: SDS-5000 lithotripsy is more efficient than Therasonic LTS in terms of shock wave sessions.
Calculi ; Hematuria ; Humans ; Lithotripsy ; Pyelonephritis ; Shock ; Urinary Calculi* ; Urinary Tract

PURPOSE: The aim of this study was to evaluate the effectiveness of external sphincter relaxant and biofeedback with electrical stimulation therapy (EST) in patients who did not respond well to antibiotics. MATERIALS AND METHODS: One hundred-five patients with a diagnosis of female urethral syndrome were entered in this study. Antibiotics were given as first-line therapy for about 3 months. In cases of recurrent or persistent urethral syndrome, antibiotic therapy combined with external sphincter relaxant or biofeedback with EST were performed. According to video-urodynamic analysis, 31 patients (29.5%) were external sphincter relaxant group who showed functional urethral obstruction and 41 patients (39.5%) were biofeedback with EST group who had severe pain or discomfort with irritative voiding symptoms. Subjective symptom was measured before and after therapy using the Bristol Female Lower Urinary Tract Symptoms questionnaire. RESULTS: Thirty-three patients (31.4%) of all patients (n=105) were terminated with antibiotic therapy alone and 7 (21.2%) patients were recurred. The symptom score changed 10.51 to 2.85. In antibiotics with external sphincter relaxant, the symptom score changed 12.39 to 3.96. In five (16.1%) of them symptoms were recurred and 3 of 5 patients underwent urethral dilatation. In antibiotics with biofeedback, average frequency changed from 12.2 to 7.7 times a day and nocturia changed 2.4 to 0.6 time a night. The symptom score improved from 15.22 to 4.69 and the overall satisfaction rate was 87.8% (41.5%: very satisfied, 46.3%: satisfied, 12.2%: no response). CONCLUSIONS: Biofeedback and external sphincter relaxant therapy as an alternative therapeutic option are effective and appropriate for the treatment of female urethral syndrome especially in patients who did not respond well to antibiotics. For the better outcomes, selection of the most appropriate therapeutic modality with the diagnostic work up is warranted.
Anti-Bacterial Agents* ; Biofeedback, Psychology ; Diagnosis ; Dilatation ; Electric Stimulation Therapy ; Female* ; Humans ; Lower Urinary Tract Symptoms ; Nocturia ; Surveys and Questionnaires ; Urethral Obstruction

PURPOSE: With traditional laboratory tests it is often difficult to differentiate chronic bacterial prostatitis (CBP) from chronic pelvic pain syndrome (CPPS), resulting in inappropriate antibiotic therapy, without definite evidence of infection. Tc-99m Ciprofloxacin imaging was developed to discriminate an infection from inflammation. The value of this imaging for differential diagnosis of CBP was investigated. MATERIALS AND METHODS: The study included 104 patients diagnosed as CBP or CPPS by traditional laboratory tests and 4 normal subjects and 2 patients with acute prostatitis or cystourethritis as positive and negative controls, respectively. Patients that had received antibiotic therapy within the previous 6 weeks were excluded. Single photon emission computerized tomography (SPECT) images were obtained 3 hours after an injection of Tc-99m Ciprofloxacin. The results of the imaging were compared with those of the 4-glass test for identification of microorganism. RESULTS: On the images, negative uptake was shown in all normal subjects, while strong hot uptake was shown in the entire prostate of the patient with acute prostatitis and the entire urethra of the patient with acute cystourethritis. Based on traditional laboratory tests, 104 patients were classified as CBP (n=32) and CPPS (n=72). Nine of the 32 CBP patients (28%) showed negative uptake in the prostate, and 47 (65%) of the 72 CPPS patients showed hot uptake in the prostate. CONCLUSIONS: Tc-99m Ciprofloxacin imaging may have potential as a diagnostic technique for the discrimination of chronic bacterial prostatitis that cannot be identified by traditional laboratory tests.
Ciprofloxacin* ; Diagnosis* ; Diagnosis, Differential ; Discrimination (Psychology) ; Humans ; Inflammation ; Pelvic Pain ; Prostate ; Prostatitis* ; Radioisotopes ; Tomography, Emission-Computed, Single-Photon ; Urethra

The use of conventional laparoscopic technique in surgeries of kidney, ureter, and bladder requires unnecessary manipulations in the peritoneal cavity. Despite such disadvantages, the inevitable advantages of laparoscopic surgery such as reduced wound pain and scar along with reduced hospital stay, and the difficulties in securing sufficient operative space in retroperitoneum, the urologists had to resort to the conventional laparoscopic surgeries. Recently to avoid unnecessary intraperitoneal manipulations thereby reducing postoperative complications such as bowel injury and adhesion, balloon dissectors were introduced. We have performed 9 renal cystectomy in symptomatic or obstructive renal cysts, and 6 bladder neck suspensions(Burch) in females with stress urinary incontinence. Mean operative time and hospital stay were 120 minutes(range: 90-210 minutes) and 3 days(range: 2-4 days) for bladder neck suspensions and 70 minutes(range: 45-120 minutes) and 2 days(range: 1-3 days) for renal cystectomy, respectively Few problems were encountered during pelvic procedures, but for renal cystectomy it was difficult to secure operative field in case of peritoneal perforations. The need for development or improvement of appropriate operative equipments required for these cases.
Cicatrix ; Cystectomy ; Female ; Health Resorts ; Humans ; Kidney ; Laparoscopy* ; Length of Stay ; Neck ; Operative Time ; Peritoneal Cavity ; Postoperative Complications ; Suspensions ; Ureter ; Urinary Bladder ; Urinary Incontinence ; Wounds and Injuries

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.
Animals ; Blotting, Western ; Caves ; Diabetes Mellitus ; Electric Stimulation ; Endothelial Cells ; Endothelium ; Erectile Dysfunction ; Glucose ; Injections, Intraperitoneal ; Male ; Mice ; Models, Animal ; Penis ; Peripheral Nervous System Diseases ; Streptozocin

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.
Activin Receptors ; Activins ; Blotting, Western ; Cells, Cultured ; Collagen ; Cytoplasm ; Extracellular Matrix ; Extracellular Matrix Proteins ; Fibroblasts ; Fibronectins ; Fibrosis ; Humans ; Imidazoles ; Male ; Penile Induration ; Phosphorylation ; Plasminogen Activators ; Protein-Serine-Threonine Kinases ; Quinoxalines ; Receptors, Transforming Growth Factor beta ; Smad Proteins ; Transforming Growth Factor beta ; Transforming Growth Factor beta1

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.
Fibrosis ; Injections, Intralesional ; Male ; Models, Animal ; Penile Induration ; Protein-Serine-Threonine Kinases ; Receptors, Transforming Growth Factor beta ; Transforming Growth Factor beta ; Watchful Waiting