Successful robot-assisted partial nephrectomy for giant renal hilum angiomyolipoma through the retroperitoneal approach: A case report.

BACKGROUND: Giant renal angiomyolipomas (AMLs) may lead to complications including flank pain, hematuria, hypertension, retroperitoneal hemorrhage and even death. Giant AMLs which grow around renal hilar vessels and the ureter are rare. Most previous reports on the treatment of giant renal AMLs have focused on open surgery or a transperitoneal approach, with few studies on the retroperitoneal approach for large AMLs. We here report a case of giant renal hilum AML successfully treated with robot-assisted laparoscopic nephron sparing surgery the retroperitoneal approach, with a one-year follow-up. CASE SUMMARY: A 34-year-old female patient was diagnosed with renal AML 11 years ago and showed no discomfort. The tumor gradually increased in size to a giant AML over the years, which measured 63 mm × 47 mm ×90 mm and was wrapped around the right hilum. Therefore, a robotic laparoscopic partial nephrectomy (LPN) via the retroperitoneal approach was performed. The patient had no serious postoperative complications and was discharged soon after the operation. At the one-year follow-up, the patient's right kidney had recovered well. CONCLUSION: Despite insufficient operating space via the retroperitoneal approach, LPN for giant central renal AMLs can be completed using a well-designed procedure with the assistance of a robotic system.

Effects of plication procedures in special cases of Peyronie's disease: a single-center retrospective study of 72 patients.

General recommendations regarding surgical techniques are not always appropriate for all Peyronie's disease (PD) patients. Therefore, the purpose of this study was to investigate the effects of plication procedures in PD patients with severe penile curvature and the effects of early surgical correction in patients who no longer have progressive deformities. The clinical data from 72 patients who underwent plication procedures were analyzed in this study. Patients were divided into Groups A and B according to the curvature severity (≤60° or >60°) and Groups 1 and 2 according to the duration of disease stabilization (≥3 months or <3 months). At the 1-year follow-up, 90.0% (36/40) and 90.6% (29/32) patients reported complete penile straightening, and 60.0% (24/40) and 100.0% (32/32) patients reported penile shortening in Groups A and B, respectively. No curvature recurrence occurred in any patient, and no significant differences were observed in postoperative International Index of Erectile Function-Erectile Function domain (IIEF-EF), erectile pain, sensitivity, or suture knots on the penis whether such outcomes were grouped according to the curvature severity or the duration of stabilization. However, the duration from symptom onset to surgical management in Group 1 was significantly longer than that in Group 2 (mean ± standard deviation [s.d.]: 20.9 ± 2.0 months and 14.3 ± 1.2 months, respectively, P < 0.001). The present study showed that the plication procedures seemed to be an effective choice for the surgical treatment of PD patients with severe penile curvature. In addition, the early surgical treatment seemed to benefit those patients who already had no erectile pain and no longer exhibited progressive deformity.

[Suprapubic lipectomy with a "Ω" incision for buried penis in obese adult men].

Objective: To investigate the application of suprapubic lipectomy with a "Ω" incision to removal of the prepubic fat pad for the management of buried penis in obese adult patients. METHODS: We retrospectively analyzed the clinical data on 20 obese adult patients with buried penis treated by suprapubic lipectomy via a "Ω" incision between August 2016 and September 2019. RESULTS: The operations were successfully completed in all the cases, with a mean operation time of 3.7 ± 0.6 hours and an average hospital stay of 8.3 ± 3.3 days. There were no such severe surgery-related complications as hematoma, urethral injury, or fat embolism in any of the cases. Fat liquefaction-related superficial wound infection developed in 1 patient postoperatively, which was cured by combined topical and systemic antibiotic therapy. A 3-month follow-up showed a 95% satisfaction of the patients with the postoperative appearance of the penis and suprapubic incision, but no complications such as ED, abnormal penile sensation, or penile retraction. CONCLUSIONS: Suprapubic lipectomy with a "Ω" incision to remove the prepubic fat pad is an effective surgical approach to the management of buried penis in obese adult males, which is an anatomy-based surgical correction and has the advantages of slight injury, rapid recovery and few complications./.

Effects of patients' understanding and choice of surgical types on postoperative outcomes of Peyronie's disease: a single-center retrospective study of 108 patients.

Surgical correction can be considered for treating patients with a chronic phase of Peyronie's disease (PD) and persistent penile curvature. In clinical practice, some patients pay too much attention to surgical complications and refuse the recommended feasible surgical types. Meanwhile, they require operations according to their preferences. This study aimed to evaluate the effects of patients' own choice of surgical type on postoperative satisfaction. This retrospective study analyzed data from 108 patients with PD who underwent surgical correction according to doctors' recommendations or patients' own demands. The objective and subjective surgical outcomes were assessed. Patients' understanding of the disease was analyzed using a questionnaire survey. Objective measurements of surgical outcomes, including penile straightening, penile length, and sexual function, in patients who received the recommended surgery, were similar to those in patients who did not accept the recommended surgery. However, subjective evaluations, including erectile pain, discomfort because of nodules on the penis, and decreased sensitivity in the penis, were more obvious in patients who did not follow doctors' recommendations. In addition, a questionnaire survey showed that understanding PD and the purpose of surgery of patients who did not follow doctors' advice were inappropriate, as they did not conform to the principle of treatment. The present study showed that surgical correction seemed to be an objectively effective option in the management of patients in the stable chronic phase of PD. Low patient satisfaction might be related to patients' lack of correct understanding of the disease and its treatment strategy as well as unrealistic expectations.

Treatments of Peyronie's disease with Scutellaria baicalensis and surgery according to the disease course: a single-center retrospective study of 261 patients.

BACKGROUND: Oral medication therapies are more conventional than other non-surgical therapies in the acute phase of Peyronie's disease (PD). Although the commonly used oral drugs for PD have shown poor or indeterminate outcomes, most patients prefer oral medications. The aim of this study was to evaluate the efficacy and safety of Scutellaria baicalensis extract for treating acute-phase PD patients and examine the practicality of treatment strategies for PD according to the disease course. METHODS: This retrospective study was performed at our institution from 2005 to 2015 and analyzed the data of 261 patients with PD. The acute-phase PD patients received Scutellaria baicalensis extract for 6 months. After oral treatment, the patients with persistent curvature underwent surgical correction during the stable phase. RESULTS: During this study period, 183 patients received oral treatment with Scutellaria baicalensis, and 78 patients did not. Compared to the untreated patients, treatment with Scutellaria baicalensis had a significant effect in improving the symptoms of acute-phase PD. The mean time required for stabilization also showed a significant statistical difference. Treatment with Scutellaria baicalensis was safe and well-tolerated. After the disease stabilized, 70 and 31 patients with significant penile curvature underwent surgical correction by 16- dot plication and great saphenous vein grafting procedures, respectively. At the one-year follow-up, complete penile straightening and penile length shortening were observed in 92.86% and 41.43% of the patients after 16-dot plication and in 87.10% and 25.81% of the patients after grafting procedures, respectively. The postoperative Erectile Function domain of the International Index of Erectile Function scales were maintained in all patients after the 16-dot plication procedure and decreased in 54.84% of the patients after the grafting procedure. Overall, 92.86% and 83.87% of the patients who received 16-dot plication and grafting procedures, respectively, were satisfied with the final surgical results. CONCLUSIONS: Treatment with extract of Scutellaria baicalensis seems to be beneficial for improvements in symptoms of acute phase PD and acceleration of the disease stabilization. The 16-dot plication and great saphenous vein grafting procedure seem effective options in the surgical management of the stable phase after Scutellaria baicalensis administration in the acute phase of PD.

Staged male genital reconstruction with a local flap and free oral graft: a case report and literature review.

BACKGROUND: Male genital skin loss is a common disease in urology. However, male genital skin loss accompanying a penile urethra defect is rarely reported. Herein, we describe a novel surgical technique using a composite local flap and oral mucosal graft to reconstruct the penis, which may provide a new solution for patients with similar conditions. CASE PRESENTATION: A 36-year-old male with a penile urethra defect and a large area of genital skin loss required urethral reconstruction. The meatus had descended to the penoscrotal junction. This procedure was divided into three stages. The first stage of the surgery involved burying the nude penile shaft beneath the skin of the left anteromedial thigh for coverage of the skin defect. The second stage consisted of releasing the penis and expanding the size of the urethral plate for further urethroplasty. The third stage consisted of reconstruction of the anterior urethra 6 months later. Postoperatively, the patient reported satisfactory voiding. The maximal flow rate (MFR) was 22.2 ml/s with no postvoiding residual urine at the 24-month follow-up visit. No edema, infection, hemorrhage, or cicatricial retraction were observed. The patient's erectile function was satisfactory, and his international index of erectile function-5 score (IIEF-5 score) was 23 at the 24-month follow-up visit. Additionally, the presence of nocturnal penile tumescence demonstrated that he had normal erectile function. CONCLUSIONS: This procedure is an effective surgical option for men with complete foreskin and penile urethra defects. It could also be extended as a treatment strategy when composite local or pedicle transposition flaps and free grafts are needed for specific patients.

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats.

BACKGROUND/AIMS: Transforming growth factor-ß1 (TGF-ß1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-ß in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. METHODS: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. RESULTS: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-ß1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-ß1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. CONCLUSION: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

[Effects of different medications with tadalafil on erectile dysfunction in males with primary sexual failure].

OBJECTIVE: To evaluate the effects of three different medications with tadalafil on erectile dysfunction (ED) in young men with primary sexual failure. METHODS: This study included 76 male ED patients aged 21－35 years who had primary sexual failure but normal nocturnal penile tumescence and rigidity and failed to respond to psychotherapy. We randomly assigned them to receive oral tadalafil once daily, on demand, or once-daily + on-demand. After 2－3 months of treatment, we evaluated the effects based on the scores of the patients in the five domains of the International Index of Erectile Function (IIEF-5). RESULTS: After medication, all the patients showed significantly increased scores in the four domains of IIEF-5, namely, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction. The on-demand group achieved even higher scores in erectile and orgasmic functions but a lower score in sexual desire than the once-daily group. However, the patients in the once-daily + on-demand group exhibited more significant improvement than those in the other two in all the five domains. CONCLUSIONS: Once-daily + on-demand medication with tadalafil can significantly enhance the therapeutic effect on psychogenic ED in young men with primary sexual failure.

[Surgical repair and reconstruction of male external genitals].

One of the challenges in andrology nowadays is the diagnosis and treatment of external genital abnormalities and defects along with the consequent voiding, sexual, and reproductive dysfunctions, for which no guidelines are yet available. Hitherto, surgical repair and reconstruction are efficient for these diseases. The key to these operations is to individualize surgical strategies according to the specific local lesion and dysfunction, usually involving flap and graft techniques. This article presents our experience in the surgical treatment of penile and scrotal abnormalities and defects with urological and andrological techniques and microsurgical strategies, focusing on the external repair and functional reconstruction. Satisfactory treatment outcomes pivot on a precise evaluation of the disease, a rational design of surgical procedures, and an earnest communication with the patient. Some cases are rather complicated and challenging, usually with complications, and therefore deserve further researches for more effective treatment strategies in clinical practice.

Differential effects of peripheral and transitional prostatic stromal cells on tumorigenesis.

The human prostate contains two types of stromal cells, peripheral stromal cells (PSCs) and transitional stromal cells (TSCs). Here, we demonstrate the effects of PSCs and TSCs on tumorigenesis in prostate cancer (PCa) and identify the mechanisms underlying these effects. Using microarray analysis, we identified 3,643 differentially expressed genes in cocultures of TSCs, PSCs, and DU145 cells, a human prostate cancer cell line. Expression of cell division cycle 25 homolog A (CDC25A) was lower and that of tumor-associated calcium signal transducer 2 (TACSTD2) was higher in TSCs than in PSCs. Additionally, increased CDC25A expression or decreased TACSTD2 expression modulated the survival, growth, and migration of DU145 cells. These data suggest that PSCs promote and TSCs inhibit tumorigenesis by regulating the expression of CDC25A and TACSTD2.

P144, A TGF-ß1 antagonist peptide, synergizes with sildenafil and enhances erectile response via amelioration of cavernosal fibrosis in diabetic rats.

INTRODUCTION: Patients with diabetes exhibit more severe erectile dysfunction (ED) and are less responsive to first-line oral phosphodiesterase type 5 inhibitor (PDE5i). It has been suggested that increased collagen deposition and reduced smooth muscle content in the corpus cavernosum are important mechanisms for diabetes-associated ED and that transforming growth factor-ß1 (TGF-ß1) is a potent fibrotic factor responsible for the structural alterations in the corpus cavernosum. AIMS: The aims of this study are to determine whether activation of TGF-ß1 and its downstream pathways is responsible for the reduced efficacy of the PDE5is in diabetic ED via abnormalities in cavernosal structures and to investigate the synergistic effects of the TGF-ß1 antagonist P144 and sildenafil on erectile response. METHODS: Six weeks after inducting diabetes with streptozotocin in male Sprague-Dawley rats, age-matched control and diabetic rats were treated with vehicle, sildenafil, or P144 alone or in combination for 4 weeks, respectively. MAIN OUTCOME MEASURES: Intracavernous pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were analyzed. RESULTS: Diabetic rats exhibited a decreased erectile response, severe corporal veno-occlusive dysfunction (CVOD), and structural alterations including cavernosal fibrosis and decreased smooth muscle content. Expression and activation of TGF-ß1 and its downstream Smad and non-Smad pathways increased in diabetic rats. Treatment with sildenafil showed modest effect on erectile response and a less suppressive effect on CVOD, cavernosal fibrosis, and molecular alterations. Treatment with P144 had lower effect on erectile response, even greatly improved the histological and molecular alterations and CVOD than sildenafil. The combined treatment with P144 and sildenafil effectively restored erectile response, CVOD, and histological and molecular alterations. CONCLUSION: An insufficient suppressive effect of sildenafil on cavernosal fibrosis, severe CVOD, and TGF-ß1 pathways was implicated in reduced efficacy of the PDE5i in diabetic ED. Treatment with P144 synergized sildenafil and significantly increased erectile response by the potential antifibrotic activity.

Surgical treatment of Peyronie's disease by modified 16-dot placation in China.

OBJECTIVE: To assess the long-term patient's satisfaction and functional results of surgical correction for Peyronie's disease (PD) patients with penile curvature by 16-dot minimal tension placation and its modification in Chinese population. PATIENTS AND METHODS: Between August 2004 and December 2008, 32 patients with PD underwent surgical correction of penile curvature by 16-dot minimal tension placation and its modification. Indications for operation included PD patients with penile curvature, adequate erectile capacity, difficulty or inability to vaginal penetration. Preoperative evaluation included International Index of Erectile Function 5 (IIEF-5) questionnaire score, pain on erection and physical examination. Patients were recommended daily low dose phosphodiesterase type 5 (PDE5) inhibitors two weeks after surgery and maintained for two months. At follow-up, patients and partner's satisfaction and erectile function were assessed by IIEF-5 questionnaire score. RESULTS: There were no surgery-related complications, and 94% of patients and 88% of partners reported overall satisfaction after the surgery. Complete penile straightening was achieved in 27 (84%) patients. Slight residual curvatures were observed in 4 patients, which did not affect their sexual intercourse. All patients were satisfied with postoperative penile length while shortening of the penis was noted in 13 patients (40%) with median penile length loss of 1.5 cm. In addition, no de novo erectile dysfunction was observed, and sexual function was significantly improved evidenced by the IIEF-5 scores, especially in the patients who have received PDE5 inhibitors for two months after two weeks surgery. CONCLUSIONS: Correction of penile curvature using 16-dot placation and its modification is a simple and safe method to achieve cosmetic and functional satisfaction in carefully selected PD patients.

A prospective, randomized clinical trial comparing plasmakinetic resection of the prostate with holmium laser enucleation of the prostate based on a 2-year followup.

PURPOSE: We compared plasmakinetic resection with holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia by analyzing 2-year followup data from a prospective randomized clinical trial. MATERIALS AND METHODS: A total of 280 patients were randomly treated with plasmakinetic resection or holmium laser enucleation of the prostate. Perioperative and postoperative outcome data were obtained during a 2-year followup. RESULTS: No significant differences between the 2 surgical groups were observed in the preoperative data. Both groups displayed significant improvements after surgery. However, we identified no significant differences between the 2 groups in the 2-year followup data for I-PSS (International Prostate Symptom Score), quality of life scores or maximum flow rate values. Patients in the holmium laser enucleation group displayed a lower risk of hemorrhage, shorter bladder irrigation and catheter times, and shorter hospital stays. A larger amount of prostate tissue was retrieved in the holmium laser enucleation group, but the operation time was longer for this group than for the plasmakinetic resection group. CONCLUSIONS: Plasmakinetic resection and holmium laser enucleation of the prostate are effective and safe treatments for benign prostatic hyperplasia. Holmium laser enucleation of the prostate can be applied to prostates of all sizes, and involves less risk of hemorrhage, decreased bladder irrigation and catheter times, as well as reduced hospital stay. Thus, we believe holmium laser enucleation of the prostate should be proposed as a potential new gold standard surgical therapy instead of transurethral resection of the prostate for patients with benign prostatic hyperplasia.

Management of lower urinary tract dysfunction in patients with neurological disorders.

The proper performance of the lower urinary tract is dependent on an intact neural innervation of the individual structures involved. Therefore, any congenital neurological anomalies, diseases, or lesions of the central, peripheral, or autonomic nervous systems can result in lower urinary tract symptoms. Lower urinary tract dysfunction (LUTD) secondary to neurological disorders can significantly reduce quality of life (QoL) and may also give rise to serious complications and psychological and social sequelae. The goals of management of LUTD in patients with neurological disorders are to prevent serious complications and to improve the patient's QoL. Understanding the physiology and pathophysiology of micturition is critical to selecting appropriate treatment options. This article provides an overview of the clinical characteristics, diagnosis, and management of LUTD in patients with certain central and peripheral neuropathies and common lesions.

An improved morcellation procedure for holmium laser enucleation of the prostate.

PURPOSE: We modified the conventional morcellation procedure for holmium laser enucleation of the prostate (HoLEP), and its outcomes are presented in this article. MATERIALS AND METHODS: As 395 patients were included, the conventional morcellation procedure was performed in the first 100 cases (group 1, cases 1-100), and an improved procedure was used in the last 100 cases (group 2, cases 296-395). The improved morcellation process has three steps to execute. The morcellation time, collected tissue weight, morcellation rate, and associated complications were recorded. RESULTS: The tissue-resected weight was similar between group 1 (60.7±33.9 g) and group 2 (62.4±36.8 g). The mean morcellation time in group 1 was greater than that in group 2 (11.3±7.1 and 8.3±4.1 minutes, respectively), and the mean morcellation rate was better in group 2 than in group 1 (5.75±1.7 g/minutes in group 1 v 7.3±1.1 g/minutes in group 2). Complications, such as bladder injury, were similar in both groups. CONCLUSION: The improved morcellation procedure described in this article can be used in various situations of suction and can be performed in a more fluent manner and with better efficiency.

Poly(ADP-ribose) polymerase inhibition improves erectile function by activation of nitric oxide/cyclic guanosine monophosphate pathway in diabetic rats.

INTRODUCTION: Endothelial dysfunction-induced abnormalities of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the corpus cavernosum are thought to be the main factors involved in the pathogenesis of diabetes-induced erectile dysfunction (ED). Recent studies have shown that the poly(adenosine diphosphate ribose) polymerase (PARP) pathway plays a critical role in diabetic endothelial dysfunction. AIM: The aim of this study is to determine whether activation of the PARP pathway is involved in diabetic cavernosal endothelial dysfunction and abnormalities of the NO/cGMP pathway. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: age-matched controls, diabetic controls (DM), and the 3-aminobenzamide (3-AB, a PARP inhibitor)-treated diabetic group (DM+3-AB). Diabetes was induced by intraperitoneal injection of streptozotocin. Eight weeks after inducing diabetes, the DM+3-AB group was treated with 3-AB for 4 weeks. MAIN OUTCOME MEASURES: Erectile function was assessed at 12 weeks after inducing diabetes by stimulating the cavernous nerve. Expression of poly(ADP-ribose), protein kinase B (Akt), phospho-Akt, endothelial nitric oxide synthase (eNOS), phospho-eNOS, and neuronal nitric oxide synthase (nNOS) were evaluated by Western blot. Cavernous NO generation and cGMP levels were also determined. RESULTS: The DM group showed impaired erectile function and significantly increased PARP activity. Expression of total eNOS and nNOS, phospho-Akt, and eNOS decreased significantly in the DM group compared with those in the control group. In addition, cavernous NO generation and cGMP levels decreased significantly in the DM group compared with those in the control group. Treatment with 3-AB restored erectile function and significantly reversed all molecular alterations except decreased nNOS expression. CONCLUSION: Overactivation of the PARP pathway in the corpus cavernosum of diabetic rats was involved in cavernosal endothelial dysfunction and abnormalities of the NO/cGMP pathway resulting in ED. These findings may be applied to develop novel therapies for patients with diabetic ED.

Effects of level of consciousness on urodynamic procedure in female cats.

Urodynamic evaluation is an invasive and uncomfortable procedure that can cause physical distress and is difficult to perform in uncooperative patients. The aim of this study was to evaluate the effects of consciousness on urodynamic evaluation in an animal model. Repeated cystometry, electromyogram, and measurement of serum cortisol concentrations were performed in female cats under conscious (CON), conscious sedation (CS) and deep anesthesia (DA) conditions. Urodynamic evaluation showed that there were no statistical differences in maximum detrusor pressure or bladder capacity observed among the three conditions. Under the DA condition, but not the CON and CS conditions, bladder contraction was accompanied by an un-relaxed anal sphincter. Residue urine volume significantly increased in the DA condition compared to the CON and CS conditions. The levels of serum cortisol significantly increased after performing urodynamic evaluation under the CON condition, whereas these levels were not significantly increased under the CS and DA conditions. This study showed that conscious sedation has no adverse effects on the urodynamic variables, and that it significantly reduces distress in cats undergoing the examination. These results may provide novel insights for performing urodynamic studies in uncooperative patients.

Poly(ADP-ribose) polymerase is involved in the development of diabetic cystopathy via regulation of nuclear factor kappa B.

OBJECTIVES: To investigate whether overactivated Poly (ADP-ribose) polymerase (PARP) and subsequent activation of nuclear factor kappa B (NF-κB) correlate with the development of diabetic cystopathy via induction of bladder apoptosis. Diabetic cystopathy as a common complication of diabetes is frequently associated with increased oxidative stress and apoptosis of the bladder. PARP is activated by hyperglycemia-induced oxidative stress and plays a critical role in cell apoptosis and the development of diabetic complications, such as retinopathy and nephropathy. METHODS: Sprague-Dawley rats were divided into 3 groups: control, diabetic, and diabetic treated with PARP inhibitor (DM+Vit-B3). Four weeks after induction of diabetes, the DM+Vit-B3 group was treated with PARP inhibitor (nicotinamide, 400 mg/kg/d) for 3 weeks. Bladder function was then assessed by conscious cystometry. The extent of oxidative stress and apoptosis, expression of poly(ADP-ribose) (PAR), NF-κB, phosphorylated inhibitor of NF-κB (IκB)-α, Bcl-2, and Bax in the bladder were also investigated. RESULTS: Bladder dysfunction was strongly associated with increased oxidative stress and bladder apoptosis. In addition, the amount of PAR, phosphorylated IκB-α, expression of NF-κB, and Bax were significantly increased in diabetic rat bladder. Inhibition of PARP significantly reduced PARP activation and expression of NF-κB and Bax. As a result, bladder apoptosis was attenuated and bladder function was improved. CONCLUSIONS: These results indicate that overactivated PARP and subsequent activation of NF-κB play important roles in the development of diabetic cystopathy via induction of bladder apoptosis. These findings may be applied in the development of novel therapies for patients with diabetic cystopathy.

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying.

It has been demonstrated that increases in poly(ADP-ribose) polymerase (PARP) activity causes damage to several organs under ischemia/reperfusion (I/R) conditions. The aims of this study were to investigate whether inhibition of PARP could suppress apoptosis in the bladder following acute urinary retention (AUR) and subsequent bladder emptying. Twelve-week-old male Sprague Dawley rats were divided into a control group, saline treated group, and 3-aminobenzamide (3-AB, a specific PARP inhibitor)-treated group. Sixty minutes after the administration of saline and 3-AB, the saline and 3-AB-treated groups had 60 min of over-distension and followed by 2 h of drainage. The degree of bladder apoptosis, levels of malondialdehyde (MDA), ATP and nicotinamide adenine dinucleotide (NAD+); expression of poly(ADP-ribose) (PAR), phosphorylation of protein kinase B (Akt); and levels of Bcl-2, Bax, and caspase 3 activity in the bladder were determined. Molecular and histological analyses showed that bladder apoptosis was associated with increases in the amount of PAR and decreases in ATP and NAD+ levels in the saline treated group. In addition, phosphorylated Akt and Bcl-2/Bax ratio were significantly decreased. The activity of caspase 3 was significantly increased in the saline treated group. Inhibition of PARP significantly increased the levels of ATP and NAD+, phosphorylation of Akt, and Bcl-2/Bax ratio, and significantly reduced the activation of caspase 3. As a result, apoptosis in the bladder was attenuated. These results indicate that PARP activation may be involved in apoptosis in the bladder induced by AUR and subsequent emptying via energy depletion and suppression of Akt activity.

PARP inhibition restores erectile function by suppressing corporal smooth muscle apoptosis in diabetic rats.

INTRODUCTION: An important mechanism suggested to be responsible for diabetes-associated erectile dysfunction (ED) involves increased apoptosis, increased collagen deposition, and reduced smooth muscle content in the corpus cavernosum. AIM: To determine whether the activation of the pro-apoptotic poly(adenosine diphosphate ribose) polymerase (PARP) pathway is involved in the induction of corporal apoptosis, and whether the administration of 3-aminobenzamide (3-AB), a specific PARP inhibitor, could ameliorate ED in diabetic rats. METHODS: Male Sprague-Dawley rats (8-weeks-old) were randomly divided into three groups: age-matched controls (C), diabetic controls (DM), and 3-AB-treated diabetic group (DM + 3-AB). Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50 mg/kg). Eight weeks after the induction of diabetes, DM + 3-AB group treated with 3-AB (30 mg/kg/day, ip) for 4 weeks. MAIN OUTCOME MEASURES: At 12 weeks after diabetes induction, erectile function was assessed by cavernous nerve stimulation. Penile tissue was assessed for apoptosis, Masson's trichrome stain and immunohistochemical analysis for smooth muscle alpha actin. Expression of poly(ADP-ribose), phospho-protein kinase B (Akt), phospho-Bcl-2-associated death promoter (Bad), B-cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X Protein (Bax), and apoptosis-inducing factor (AIF) were evaluated by Western blot. Caspase-3 activity and malondialdehyde (MDA), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NAD+) concentrations were also determined. RESULTS: DM group showed impaired erectile function, increased PARP activity and corporal apoptosis, and decreased smooth muscle contents. Expression of phospho-Akt, phospho-Bad, Bcl-2, and concentrations of ATP and NAD+ were decreased in the DM group, whereas concentrations of MDA, expression of Bax, nuclear translocation of AIF, and caspase-3 activity were increased. Treatment with 3-AB restored erectile function and significantly reversed all molecular and histological alterations except for the increased MDA. CONCLUSION: Over-activation of penile PARP pathway in diabetic rats enhances corporal apoptosis via energy depletion, suppression of Akt phosphorylation, and activation of the mitochondrial apoptotic pathway, which results in ED; these event could be prevented by treatment with 3-AB.