Niclosamide attenuates erectile dysfunction and corporal fibrosis via reversal of Smad signaling in diabetic rat model.

BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is a common urological complication of diabetes, and current drugs often fail to provide an effective treatment. Smad2/3 signaling-mediated corporal fibrosis has a critical role in the molecular basis of DMED. AIM: We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model. METHODS: Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75 mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10 mg·kg-1/day; i.p) or vehicle for 4 weeks. At week 12, erectile function was evaluated as intracavernous pressure (ICP) response to the electrical stimulation of the cavernous nerve (CN). Penile tissues were harvested for Masson's trichrome staining or western blotting to determine corporal fibrosis and Smad2/3 pathway-related protein expression, respectively. OUTCOMES: At the end of the experimental protocol, in vivo erectile function was assessed by measuring the ratio of ICP/ mean arterial pressure (MAP) and total ICP following CN stimulation. Smooth muscle content and collagen fibers were evaluated by Masson's trichrome staining of the penile tissues. The expressions of fibrosis-related proteins (Smad2, Smad3, fibronectin) were determined using western blotting in the penile tissues. RESULTS: Erectile function, as determined by the maximum ICP/MAP and total ICP/MAP ratios, was drastically decreased in diabetic rats. Corporal tissues of diabetic rats were severely fibrotic with a significant increase in collagen fibers and a marked reduction in smooth muscle content. Also, the protein expressions of phosphorylated (p-)Smad2, p-Smad3 and fibronectin were significantly increased in the penis of diabetic rats. Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration. CLINICAL IMPLICATIONS: Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects. STRENGTHS AND LIMITATIONS: The present study provides the first evidence that Nic has beneficial effect on erectile dysfunction by attenuating corporal fibrosis in a rat model of DMED. The effect of Nic on penile endothelial function and the other potential underlying mechanisms needs to be further elucidated. CONCLUSIONS: Nic improved erectile function in DMED rats possibly suppressing penile fibrosis by inhibiting Smad2/3 signaling. These results suggest a potential therapeutic repurposing of Nic as an adjuvant treatment in DMED.

Lightweight macroporous mesh can be used for corporal reconstruction during penile prosthesis surgery.

BACKGROUND: Options to reinforce or reconstruct the corpora cavernosa during penile prosthesis surgery are limited. Synthetic grafts may confer a higher infection risk. Lightweight macroporous mesh is a promising alternative due to better integration and tissue ingrowth. AIM: The study sought to report the first experience of using lightweight mesh to reinforce or reconstruct the corpora. METHODS: The medical records of all patients undergoing insertion or revision of penile prosthesis between May 2016 and May 2021 were reviewed retrospectively. Patient characteristics, management, and outcomes were extracted in which mesh was used for corporal reconstruction. Poliglecaprone-25/polypropylene mesh (UltraPro) was used in all cases. The surgical technique and alternatives were summarized. OUTCOMES: The outcomes were infection rate, postoperative complications by Clavien-Dindo classification, and patient-reported outcomes. RESULTS: Mesh was required during penile prosthesis surgery in 21 men (median age 56 [range, 18-74] years). Reasons for reconstruction were severe corporal fibrosis (n = 6), impending erosion (n = 6), crossover/perforation (n = 6), congenital corporal agenesis (n = 2), and excision of Peyronie's plaque. All but 2 patients (with corporal agenesis) presented for revision penile prosthesis surgery with a median number of previous revision attempts of 2 (range, 1-5). Two (10%) patients required explant after a mean follow-up of 23 ± 8.7 months. One man developed infection of the device 2 years after surgery, translating to an infection rate of 5% despite a high prevalence of diabetes (25%) in this cohort. Another required explantation due to debilitating chronic pain after 3 months. Further revision surgery for stiction syndrome was required in a third patient. Finally, another man was not satisfied with the position of the pump within the scrotum or the axial rigidity of the device, despite a second opinion suggesting no issues with the device. All men were sexually active following surgery. CLINICAL IMPLICATIONS: A lightweight mesh can be considered to reinforce or reconstruct the corpora cavernosa in complex cases in which there are no alternative techniques available. STRENGTHS AND LIMITATIONS: This is the first study using a lightweight macroporous mesh for revision penile prosthesis surgery. This was a well-characterized cohort of patients. A larger cohort with 5-year follow-up would be preferable. CONCLUSION: These early results suggest that a lightweight macroporous mesh may be an acceptable synthetic graft for corporal reconstruction. Poliglecaprone-25/polypropylene mesh may be ideal because it is partially absorbable, easy to handle, and not bulky.

Review of Ischemic and Non-ischemic Priapism.

PURPOSE OF REVIEW: Priapism is a rare condition that has different presentations, etiologies, pathophysiology, and treatment algorithms. It can be associated with significant patient distress and sexual dysfunction. We aim to examine the most up-to-date literature and guidelines in the management of this condition. RECENT FINDINGS: Priapism is a challenging condition to manage for urologists, since the etiology is often multi-factorial and the suggested treatment algorithms are based on small studies and expert anecdotal experience, perhaps due to the rarity of the disorder. Ischemic priapism of less than 24 h can be managed non-surgically in most cases with excellent results. Ischemic priapism of more than 36 h is frequently associated with permanent erectile dysfunction. Management of prolonged priapism with penile shunting still may result in poor erectile function, so penile prosthesis can be discussed in these scenarios.

Management of Disastrous Complications of Penile Implant Surgery.

RATIONALE: Penile Prosthesis Implantation (PPI) is the definitive treatment for Erectile Dysfunction not responsive to conservative management strategies. Furthermore, it is a staple of surgical treatment of severe Peyronie's Disease (PD) and phallic reconstruction. Expert implantologists occasionally face disastrous complications of penile implant surgery which can prove to be very challenging. In this article we present a selected number of case reports which exemplify this kind of situations and discuss management strategies while also commenting on plausible aetiologies. PATIENTS' CONCERNS: The first case describes a PPI performed in end-stage fibrotic corpora after multiple instances of implantation/explant. The second and third cases show two diametrically opposed approaches to the management of glans necrosis after PPI in post-radical cystectomy patients. The fourth case describes the history of a diabetic patient suffering from glandular, corporal and urethral necrosis after a complicated PPI procedure. The fifth case reports the surgical treatment of a case of recurring PD due to severe scarring and shrinking of a vascular Dacron patch applied in a previous operation. DIAGNOSIS: Complication diagnosis in all patient was mainly clinical, intra- and postoperative, with Penile Color Doppler Ultrasonography performed when needed in order to demonstrate penile blood flow. INTERVENTIONS: The patients underwent complex surgical procedures that addressed each specific complication. Complex penile implants with fibrosis-related complications, penile prosthesis explant with and without surgical debridement of necrotic areas, penile prosthesis explant with necrotic penile shaft and urethral amputation with perineostomy, and complex corporoplasty with scar tissue excision and patch application with PPI were performed in the five patients. OUTCOMES: Penile anatomy and erectile function with PPI was achieved in 4 out of 5 patients. 1 of 5 patient is scheduled to undergo a total phallic reconstruction procedure at the time of this writing. LESSONS: Management of disastrous complications of penile implant surgery can be very challenging even in expert hands. In-and-out knowledge of possible PPI and PD complications is required to achieve an acceptable outcome. Bettocchi C, Osmonov D, van Renterghem K, et al. Management of Disastrous Complications of Penile Implant Surgery. J Sex Med 2021;18:1145-1157.

Inflatable penile prosthesis implantation into scarred corporal bodies: timing may decrease postoperative problems.

OBJECTIVES: To compare the rates of intra- and postoperative complications between early (<4 months) or delayed (>4 months) inflatable penile prosthesis (IPP) re-implantation performed after a fibrosis-inducing event. PATIENTS AND METHODS: Cases of IPP re-implantation were performed by a single, high-volume prosthetic surgeon in hospitals domestically and abroad over a 15-year period (2001-2016). The time interval from the precipitating event to operation, intra-operative complications and postoperative complications for up to 1 year after implantation, were recorded. RESULTS: A total of 72 cases of IPP re-implantation were recorded. There were 16 (53%) intraoperative complications in patients who had surgery at <4 months (Group 1) and 23 (55%) in patients operated at >4 months (Group 2). There were four (13%) postoperative complications in Group 1 and 14 (33%) in Group 2. CONCLUSION: Re-implantation of an IPP into fibrotic corporal bodies is associated with less serious postoperative complications when performed within 4 months of the fibrosis-inducing event.

Androgen deficiency impairs erectile function in rats through promotion of corporal fibrosis.

The aim of this study was to investigate the underlying mechanism of androgen deficiency inducing corporal fibrosis, thereby causing erectile dysfunction (ED). Forty 12-week-old healthy male rats were divided randomly into four groups: normal control group (Control); castration group (Castration); the other 20 rats were castrated followed by testosterone (T) (orally) each day: castration + 10mg/kg T group (Castration + 10T) and castration + 20 mg/kg T group (Castration + 20T). After 8 weeks' treatment, the main outcome measures were the following: serum levels of T; the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP); histologic changes in penile smooth muscle cells; the Smad and non-Smad pathways; and extracellular matrix (ECM) protein deposition. Castration group showed lower level of T and ratio of ICP/MAP, reduced ratio of penile smooth muscle cells/collagen, increased extracellular matrix protein deposition, and a higher expression of the Smad and non-Smad pathways. Castration + 10T partially preserved erectile function and histology stabilisation. However, the Castration + 20T group showed significantly better erectile function and molecular changes. Better efficacy could be expected with ART of adequate dose. Androgen deficiency induces corporal fibrosis through activation of the Smad and non-Smad pathways, and accumulation of ECM proteins.

Successful Placement of Penile Prostheses in Men With Severe Corporal Fibrosis Following Vacuum Therapy Protocol.

INTRODUCTION: Penile prosthesis (PP) implantation in men with severe corporal fibrosis presents a significant surgical challenge. For the past 7 years, we have used a novel, preoperative protocol of daily vacuum therapy (VT) using a vacuum erection device for at least 3 months before PP placement for men with severe corporal fibrosis from PP infection or ischemic priapism. AIM: To evaluate this standardized preoperative regimen. METHODS: We retrospectively reviewed all patients who underwent three-piece PP placement at our institution from 2008 through 2015. Of these, 13 men had severe corporal fibrosis from prior PP infection (11 of 13) or prolonged ischemic priapism (2 of 13). Our protocol included VT for 10 to 15 minutes at least two times daily in all patients for at least 3 months (mean = 3.5 months). MAIN OUTCOME MEASURES: We report on our surgical experience and post-VT stretched flaccid penile length (SFPL) compared with baseline SFPL. RESULTS: All 13 men underwent successful three-piece PP placement with standard-size cylinders without additional surgical maneuvers. There was one infection and one erosion requiring revision. Daily average use of VT was 32.5 minutes. SFPL increased 0.92 cm (range = 0-2 cm, SD = 0.76 cm) after VT and three-piece PP placement compared with preoperative SFPL. These men also noted improved quality of life and sexuality as measured by postoperative office interviews. CONCLUSION: The use of VT before surgery appears to result in softening of corporal fibrosis and facilitates placement of a PP regardless of the period from developing corporal fibrosis to starting VT. We strongly recommend preoperative corporal tissue rehabilitation with VT to improve surgical outcomes and to decrease difficulty during PP implantation in men with severe corporal fibrosis.

FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis.

INTRODUCTION: Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis. AIM: To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED). METHODS: Forty male Sprague-Dawley rats (8 weeks old) were used for the experiment. Thirty-two had type 1 DM induced by streptozotocin and the other eight rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with FTY720 orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks. MAIN OUTCOME MEASURE: Metabolic parameters; erectile function; sphingosine-1-phosphate receptor 3 (S1P3), protein kinase B (Akt), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) signaling pathway; corporal fibrosis; apoptosis level; and Smad and non-Smad signaling pathways. RESULTS: There were no significant differences in the initial body weights and fasting glucose concentrations among the three groups. Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED + FTY720 group. The DMED group showed inhibited activity of the S1P3-Akt-NO-cGMP signaling pathway, and the inhibition was partly reversed in the DMED + FTY720 group. The DMED group showed serious corporal fibrosis, higher apoptosis level, higher ratio of Bax to Bcl-2, and higher expressions of the Smad pathway (transforming growth factor-ß1, Smad, and connective tissue growth factor) and the non-Smad pathway (transforming growth factor-ß1, rho-associated protein kinase, LIM domain kinase 2, and cofilin). However, FTY720 supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of Bax to Bcl-2, and inhibited activity of the Smad and non-Smad pathways. CONCLUSION: FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED. Cui K, Ruan Y, Wang T, et al. FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis. J Sex Med 2017;14:323-335.

Penile Prosthesis Surgery: Current Recommendations From the International Consultation on Sexual Medicine.

INTRODUCTION: Penile prosthesis implantation has emerged as a definitive treatment to restore sexual function to the motivated man with erectile dysfunction. Substantial improvements in the design of inflatable devices have been made since they first became available more than four decades ago. AIM: To review the history of the penile prosthesis, the indications, preoperative evaluation, and patient and partner satisfaction. The current approaches to addressing intra- and postoperative complications, provide an understanding of prosthesis infection, and placement of these devices will be reviewed. METHODS: A committee of worldwide experts in this field was assembled during the 2015 International Consultation on Sexual Medicine (ICSM) and performed a systematic review of the peer-reviewed published medical literature pertaining to penile prosthesis. Particular attention was given to higher level trials when available. Recommendations are based upon the Oxford Criteria. MAIN OUTCOME MEASURES: Unfortunately there is limited level 1 and 2 evidence, and where expert opinion was utilized, the decision was unanimous within the committee with a goal of presenting a clinically relevant guideline pertaining to penile prostheses. RESULTS: Penile prosthesis has undergone an evolution over the past 40 years resulting in a more effective and reliable treatment for advanced erectile dysfunction not responding to less invasive methods including oral treatment with PDE5 inhibitors, vacuum erection device, and intracorporal injection therapy. It should be considered an appropriate treatment option for the man who wishes to restore erectile function and who understands the potential risk of mechanical failure and infection, both of which are less common now as a result of improvements made in device design as well as surgical protocols adhered to in the operating room. Patients must be clearly informed of the risks associated with penile prosthesis including mechanical failure, infection, shortening of the penis, change in sensation and configuration of the penis, as well as injury to local structures. Intraoperative complications are unusual but do occur and can usually be addressed intraoperatively to allow placement of the device at the time of initial surgery. Postoperative complications may also be addressed when they occur but may require more advanced reconstructive surgical techniques. Men with Peyronie's disease, corporal fibrosis due to infection, trauma, prior prosthesis explantation, priapism, and men who have undergone construction of a neophallus may require additional advanced maneuvers to obtain optimum results with a penile prosthesis. CONCLUSION: Penile prosthesis remains as an important, viable, and effective treatment for male erectile dysfunction that does not respond to other less invasive approaches or when these approaches are contraindicated or not acceptable to the patient. These devices provide the patient with the ability to engage in penetrative sexual activity without interfering with urination, ejaculation, sensation, or orgasm. Although mechanical failure can occur, the current devices are more reliable as a result of design modifications. Infection remains the most dreaded complication but since the introduction of antibiotic and hydrophilic coatings, infection is less common. Overall, patient and partner satisfaction appear to be reasonably high when a penile prosthesis is used to restore erectile function.

Penile fibrosis-still scarring urologists today: a narrative review.

Background and Objective: Implantation of penile prosthesis (PP) into scarred and fibrotic corpora can be a difficult challenge. In this review article, we provide a review of penile fibrosis, discuss current medical and surgical management and summarize preventative strategies. Methods: In this study, we searched PubMed between the years 2000-2023 for publications with search strategy: "penile fibrosis" OR "scarred corpora" OR "fibrosed corpora". Key Content and Findings: This search returned a total of 137 articles. We examine the evidence for preoperative patient evaluation and penile ultrasound (US), oral phosphodiesterase-5 inhibitors, pentoxifylline, and L-arginine, vacuum device therapy and the use of surgical approaches and tools in the context of complex penile fibrosis cases. Severe penile fibrosis is most associated with priapism and infection. Estimating the degree of fibrosis via preoperative US may help set realistic patient expectations. Phosphodiesterase inhibitors and L-arginine reduce fibrosis in animal models however their impact in humans remains unclear despite theoretical advantage for their use. Vacuum device therapy may preserve penile length following priapism and infected PP cases. The use of Coloplast Narrow-Based or AMS-700 CXR implants are used primarily for severe fibrosis. Various surgical excisional/incisional techniques, the Carrion-Rossello, Mooreville Uramix cavernotomes and reverse cutting scissors are all options, and their use varies from case to case. Finally, prevention of penile fibrosis in patients with history of penile implant infection and the safety of early implantation of a penile implant in patients with refractory priapism is encouraged. Conclusions: The management of penile fibrosis remains a challenge but there are multiple options to assist clinicians. Complex cases should be managed and studied at high volume centers.

Distal penile shaft reconstruction and reinforcement: the "double-windsocks" technique.

INTRODUCTION: The management of penile prosthesis protrusion and the implantation of a prosthesis in fibrotic penile corporal bodies represents a challenging task even for experienced surgeons. AIM: To demonstrate the long-term efficacy and safety of a new technique for distal shaft reconstruction and reinforcement in cases of penile prosthesis protrusion or cases of penile prosthesis implantation in corporal fibrosis. METHODS: Between August 2007 and August 2012, 69 patients underwent surgery for penile prosthesis protrusion (45 patients) or severe distal corporal fibrosis (24 patients). The mean age at the time of surgery was 56 years (range 38-69). All patients underwent distal shaft reconstruction using our technique, involving the creation of two neocorpora ("double windsocks"). MAIN OUTCOME MEASURES: Functional outcome and patient satisfaction were evaluated with item numbers 1 and 7 of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Furthermore, clinical data concerning the early postoperative outcome were analyzed retrospectively. RESULTS: Mean follow-up time was 22.5 months (range 6-48). Based on answers to EDITS questionnaire item 1, 42 patients (60.9%) were very satisfied and 19 patients (27.5%) were somewhat satisfied with the outcome of the procedure. Furthermore, answers to the self-confidence domain question (EDITS item 7) revealed that 63 patients (91.3%) felt that the treatment had a positive effect with respect to their ability to engage in sexual activity. No patient exhibited device extrusion, postoperative infection, or skin dehiscence, and glans sensation as well as orgasmic ability were also preserved in all cases. Neuropraxia was reported in five cases (3.4%) immediately after the operation. The recovery of orgasmic ability was delayed in 17 (24.6%) patients. All patients were able to perform sexual intercourse postoperatively. CONCLUSION: The "double-windsocks" technique is an effective option for difficult cases of distal penile shaft reconstruction and reinforcement.

Losartan treatment significantly attenuates the fibrotic changes in the corpus cavernosum of castrated rats.

INTRODUCTION AND OBJECTIVES: The aim of this study is to evaluate the effects of castration and subsequent losartan administration on the fibrosis-related parameters in the corpora cavernosa of castrated rats. MATERIAL AND METHODS: Twenty-four male rats were divided into four equal groups. Group 1:sham surgery plus vehicle (0.9% NaCl) (control:con), group 2:sham surgery plus losartan (con+los), group 3: castration plus vehicle (castration:cast) and group 4:castration plus losartan (cast+los). After four weeks of oral losartan treatment, corporal levels of transforming growth factor-beta (TGF-ß), thrombospondin-1 (TSP-1), alpha-actin, beta-actin and fibronectin were investigated by ELISA kits. Changes in the collagen and smooth muscle content were evaluated by histological analysis with Masson trichrome staining. RESULTS: Initial and post-treatment body weights of rats were similar among groups. Castration significantly increased the expression of TGF-ß, TSP-1 and fibronectin and resulted in a significant decrease in alpha-actin levels in the corpora cavernosa. Administration of losartan reduced the levels of TGF-ß, TSP-1 and fibronectin in castrated rats. Alpha actin levels also increased after losartan treatment. Beta-actin levels were not significantly different among 4 groups. The levels of all markers were similar in group 1 and 2. Rate of fibrosis was significantly higher in castrated rats and treatment with losartan reduced this rate. CONCLUSION: Castration increased the expression of fibrosis-related markers in the corpora cavernosa of rats. Administration of losartan significantly attenuated those changes and exerted an antifibrotic effect.

Shaeer's Anti-Scarring Technique: A Preventive Measure Against Corporal Fibrosis Upon Explantation of Infected Penile Implants.

INTRODUCTION: In cases of explantation and delayed reimplantation of an infected penile prosthesis, the scarring that afflicts the corporal bodies renders reimplantation difficult and risky, with potential loss in penile size. AIM: Mitomycin C is an antitumor, antibiotic agent with a potent antifibrotic action that can be used to limit corporal scarring following explantation with the aim of achieving easy and safe subsequent reimplantation, in addition to preserving penile size. METHODS: This was a prospective study involving 5 patients with infected penile prostheses who were referred to our tertiary implantation center. The infected prostheses were explanted, followed by corporal washout with antiseptics and antibiotics. Patients were rescrubbed and redraped. Mitomycin C, 10 mg in 250 cc saline, was instilled into the corpora cavernosa (125 cc each), avoiding extracavernous spilling and contact with corporotomy and skin edges. Corporotomy and skin edges were freshened and closed. Reimplantation was performed 10 to 12 weeks later. MAIN OUTCOME MEASURE: We evaluated the ease of blunt dilatation upon reimplantation and success in implanting cylinders the same size as the ones explanted. RESULTS: We were able to dilate the corporal bodies with ease in all cases using blunt Hegar dilators. All cases received the same size implant as the one explanted, in terms of length and girth, with the exception of a case where the length was only 1 cm shorter. CONCLUSIONS: Irrigation of the cavernous spaces with mitomycin C upon explantation of an infected penile prosthesis appears to ameliorate corporal scarring and keep the cavernous spaces open. On a larger scale, this approach could render the most feared complication of penile prosthesis implantation surgery much more manageable. Shaeer O, Abdel Rahman IFS, Shaeer K. Shaeer's Anti-Scarring Technique: A Preventive Measure Against Corporal Fibrosis Upon Explantation of Infected Penile Implants. Sex Med 2019; 7:357-360.

Penile prosthetic surgery for the management of Peyronie's disease.

With the increased prevalence of Peyronie's disease (PD) among men, there is also an up-rise of associated erectile dysfunction (ED) which can be devastating psychologically and sexually to most men. A wide range of therapies including medical and surgical procedures are available to satisfactorily address this condition. However when ED coexists, the gold standard treatment is penile prosthetic prosthesis (PP) with or without additional straightening procedures. We herein systematically review the contemporary literature addressing the role of the PP in the management of PD with concomitant ED with particular emphasis on patient's satisfaction, outcomes and safety.

Treatment with a combination of ginger, L-citrulline, muira puama and Paullinia cupana can reverse the progression of corporal smooth muscle loss, fibrosis and veno-occlusive dysfunction in the aging rat.

AIMS: Aging associated erectile dysfunction is characterized within the corpora by a progressive apoptosis of the smooth muscle cells and their replacement by collagen. Nitric oxide from iNOS has been shown to inhibit these histological changes in the corpora while PDE5 inhibitors as well as certain nutraceuticals such as ginger, paullinia cupana, muira puama and L-citrulline are known to enhance the effects of NO. We evaluated whether the daily oral administration for 2 months with a combination of ginger, paullinia cupana, muira puama and L-citrulline (COMP-4) can effectively delay the ongoing corporal fibrosis, smooth muscle cell apoptosis and cavernosal veno-occlusive dysfunction (CVOD) seen in middle aged rats similar to that seen with tadalafil. METHODS: 10 Month old Fisher 344 rats were treated or not for two months with COMP-4, tadalafil or a combination of tadalafil plus COMP-4. CVOD was determined by dynamic infusion cavernosometry. Penile sections of the corpora cavernosa were subjected to Masson trichrome staining to evaluate fibrosis and immunohistochemistry for desmin as a marker of smooth muscle content and inducible nitric oxide synthase (iNOS) followed by image analysis. Oxidative stress levels were determined by GSH/GSSG ratio in whole blood. RESULTS: a decline in the non-treated rat's erectile function is evident by 10-12 months of age and is accompanied by a decrease in the corporal smooth muscle content determined by desmin expression and an increase in corporal fibrosis. The daily treatment for two months with COMP-4 reverses this process by reducing systemic oxidative stress and increasing desmin and iNOS expression, similar to that seen with tadalafil or the combination of COMP-4 plus tadalafil. CONCLUSION: An oral combination of ginger, muira puama, Paullinia cupana and L-citrulline seems to be as effective as daily PDE5 inhibitor therapy in either delaying or reversing the onset of the histological and functional characteristics of aging related erectile dysfunction.

Treatments for fibrosis of the corpora cavernosa.

INTRODUCTION: Corporal fibrosis usually occurs after explantation of an infected penile prosthesis, severe penile trauma, refractory low-flow priapism, Peyronie's disease, or the chronic intracavernous injection of vasoactive drugs. METHODS: We analysed current treatmentss for penile fibrosis. We searched PubMed using the keywords 'penile corporal fibrosis', 'treatment' and 'penile fibrosis', resulting in 63 matches, of which 19 articles met the inclusion criteria. RESULTS AND CONCLUSIONS: This review covers conservative medical therapy for corporal fibrosis and surgical therapeutic methods. The roles of phosphodiesterase- 5 inhibitors and pentoxifylline are analysed. Surgical therapy includes implantation of a penile prosthesis and corporal reconstruction, and these are reviewed. Corporal fibrosis is a major problem for patients, and is associated with severe erectile dysfunction. Conservative treatment options can be applicable in the early phase, but simultaneous corporal reconstruction procedures with concomitant implantation of a penile prosthesis should be attempted in severe cases of corporal fibrosis.