Penile Fibrosis Research Articles

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

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. We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model. Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10mg·kg-1/day; i.p) or vehicle for 4weeks. 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. 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. 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. Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects. 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. 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.

Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway.

To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus-induced erectile dysfunction (DMED). DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three groups: control group (n=8), DMED group (n=8) and DMED+Leu-Ser-Lys-Leu (LSKL) group (n=8). After eight weeks following the induction of diabetes mellitus, the DMED+LSKL group was subjected to intraperitoneal injections of LSKL twice weekly for four weeks. To measure intracavernous pressure (ICP), a 25-gauge needle connected to a PE tube containing heparin was inserted into the corpus cavernosum (CC). Additionally, a needle was inserted into the carotid artery to measure mean arterial pressure (MAP). Sirius red staining and Masson trichrome staining were utilized to assess CC fibrosis. Moreover, high glucose (HG)-induced CC smooth muscle cells (CCSMCs) and CC fibroblasts (CCFs) were treated with or without LSKL. Western blotting and immunofluorescence were utilized to assess the phosphorylation and expression of related proteins. Compared with those in the control group, the ratio of the maximum ICP to the MAP markedly decreased in the DMED group, as did the ratio of smooth muscle to collagen and the ratio of collagen I to collagen III. These ratios were greater in the DMED+LSKL group than in the DMED group. TSP1 was highly expressed in the CC of DMED rats. In vitro experiments indicated that TSP1 expression significantly increased in the medium of CCSMCs and CCFs cultured in HG media and that the TGF-β pathway was activated in CCSMCs. Collagen IV was overexpressed in CCSMCs, indicating severe fibrosis was severe. Adding LSKL or knocking TSP1 down can prevent the activation of TGF-β signaling, as well as the overexpression of collagen IV in CCSMCs promoted by TSP1 secreted from CCSMCs itself or CCFs. TSP1 expression is increased in the CC of DMED rats. HG-induced TSP1 secretion via autocrine signaling from CCSMCs and/or paracrine signaling from CCFs to accelerate penile fibrosis. LSKL, an antagonist of TSP1, could improve erectile dysfunction by inhibiting the TGF-β/SMAD pathway.

Targeting heme in sickle cell disease: new perspectives on priapism treatment.

Men with sickle cell disease (SCD) frequently experience priapism, defined as prolonged, painful erections occurring without sexual arousal or desire. This urological emergency can lead to penile fibrosis and permanent erectile dysfunction if not treated adequately. Due to its complex pathophysiology, there is currently no effective preventative treatment for this condition. Recent studies have highlighted the dysfunction of the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) pathway in erectile tissues as a critical mechanism in developing priapism in SCD. Additionally, further research indicates that intravascular hemolysis promotes increased smooth muscle relaxation in the corpus cavernosum and that excess heme may significantly contribute to priapism in SCD. Pharmacological treatments should ideally target the pathophysiological basis of the disease. Agents that reduce excess free heme in the plasma have emerged as potential therapeutic candidates. This review explores the molecular mechanisms underlying the excess of heme in SCD and its contribution to developing priapism. We discuss pharmacological approaches targeting the excess free heme in the plasma, highlighting it as a potential therapeutic target for future interventions in managing priapism.

Guilingji capsules enhances erectile function by promoting testosterone-dependent angiogenesis in the corpus cavernosum

Background and aimGuilingji capsules (GLJC) have the effect of treating erectile dysfunction (ED). This study aims to explore the potential mechanisms of GLJC in treating ED. Experimental procedureWe conducted network pharmacology analysis of ED-related targets with GLJC components reported in the TCMSP database and GLJC components reported in the literature, respectively. Molecular docking was employed to validate the binding affinity of these molecular targets. Animal experiments were conducted to validate the aforementioned results. The mechanism of GLJC in treating ED was studied using d-galactose-induced aging rats, and orchiectomized rats were used to investigate further whether the mechanism of GLJC in treating ED is related to androgen. Results and conclusionsTwo network pharmacology analyses indicated that Androgen receptor (AR) and fibroblast growth factor 2 (FGF2) are the candidate targets, suggesting that the mechanism of ED treatment by GLJC may be related to androgens and angiogenesis. Molecular docking further validated the effective binding of GLJC components to these two targets. In animal experiments, GLJC significantly increased the frequency of erections and elevated serum free testosterone levels and penile tissue AR expression in aged rats. GLJC also promoted angiogenesis and inhibited penile tissue fibrosis in aged rats by regulating the expression of FGF2, RICTOR/P-AKT/P-FOXO1. However, such regulation was not observed in orchiectomized rats. Therefore, GLJC increased testosterone utilization in d-galactose-induced aging rats and regulated FGF2, RICTOR/P-AKT/P-FOXO1 signaling pathway in a T-dependent manner, promoting corpus cavernosum survival and angiogenesis. This mechanism led to the inhibition of penile fibrosis.

Penile prosthesis in priapism: a systematic review of outcomes and complications.

Priapism is a rare condition characterized by persistent erection of the penis that lasts more than 4 hours in the absence of sexual stimulation and is associated with significant morbidity and complications, including erectile dysfunction and penile fibrosis. Surgical management of priapism can be extremely challenging. We herein provide a comprehensive review that aims to evaluate the role of penile prosthesis (PP) implantation in the management of priapism. A systematic literature search was performed using the following databases: PubMed, Embase, and Scopus to identify studies that evaluated the effectiveness of PP implantation in treating priapism and the long-term complications, outcomes, and patients' satisfaction rate. Out of 717 English-language studies published between 2002 and 2022, 17 were chosen for this review. Majority of patients had a malleable PP (MPP) implant, either early or delayed after the priapism episode. Early placement (EP) of PP is widely defined between studies ranging from less than 72 hours, within 1 week, and within 3 weeks. Most common causes of priapism were sickle cell anemia (SCA), medication-induced, and idiopathic. Studies show a higher satisfaction rate ranging between 80% and 100%, with sexual intercourse achievement ranging between 64.2% and 100%. Based on the GRADE system, included studies rated as very low quality of evidence. Commonly reported complications that arise after PP procedures, include device infection, erosion, curvature, and mechanical malfunction, such as auto-inflation. PP can be an effective treatment option for priapism, particularly in cases of ischemic priapism lasting more than 36 hours or recurrent priapism that is medically refractory. However, due to the very low quality of evidence, larger, well-designed studies are warranted where long-term outcomes, patients' satisfaction, and complications following priapism-related PP implantation are measured as endpoints.

(O-03) DORSAL VENOUS LEAK LIGATION IN PATIENTS WITH ERECTILE DYSFUNCTION. REPORT OF 60 PATIENTS WITH 12-MONTH FOLLOW-UP

Abstract Objective Penile dorsal venocclusive dysfunction is recognized as a cause of erectile dysfunction in some young patients with no other risk factors. The objective of this study is to report the results of a surgical technique in patients who presented ED before the age of 40, with follow-up up to 12 months after treatment. Materials and Methods A descriptive study was carried out in a retrospective cohort of medical records with 60 patients who met the inclusion criteria, evaluated, and underwent standardized ligature surgery by the same surgeon between 01/2014 and 04/2022. The group underwent a symptom score (International Index of Erectile Function-5), before surgery, 3, 6 and 12 months after. The results of the IIFE-5 before and after surgery were related to the different degrees of erectile dysfunction (severe, moderate, and mild); additionally they were divided into three groups according to criteria defined by the IIFE-5 as successful, moderate, and poor. The diagnosis of venous leaks was made by penile Doppler ultrasound, recording venous leaks and degree of penile fibrosis. The study protocol was approved by the Research Committee of the Pablo Tobon Uribe Hospital in Medellín. Results The age of onset of erectile dysfunction was between 14-39 years, mean 23.9; the mean age of the patients who consulted was 31.5 years. The time of evolution of the disease before attempting surgery varied between 2 months and 21 years (average 9.5 years). The result of the preoperative IIFE-5 was: Severe ED: n=6 (10%) and moderate ED: n=54 (90%), there were no preoperative mild ones. Postoperative outcomes at 12 months were: moderate ED n=13 (21.6%); mild ED n=25 (41.6%) and without ED n=22 (36.6%), after the intervention. Additionally, according to the internal analysis of IIFE-5: n=39 (65%) was successful; n=9 (15%) moderate and n=12 (20%) poor. Conclusions Ligation of penile dorsal venous leaks has good medium and long-term results in terms of erection quality and patient satisfaction. Financing No conflicto.

Unveiling the molecular Hallmarks of Peyronie's disease: a comprehensive narrative review.

Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within penile tissue, attributed to dysregulated fibrogenesis, is pathognomonic for this condition. The onset of fibrosis hinges on the perturbation of the equilibrium between matrix metalloproteinases (MMPs), crucial enzymes governing the extracellular matrix, and tissue inhibitors of MMPs (TIMPs). In the context of Peyronie's disease, there is an elevation in TIMP levels coupled with a decline in MMP levels, culminating in fibrogenesis. Despite the scant molecular insights into fibrotic pathologies, particularly in the context of Peyronie's disease, a comprehensive literature search spanning 1995 to 2023, utilizing PubMed Library, was conducted to elucidate these mechanisms. The findings underscore the involvement of growth factors such as FGF and PDGF, and cytokines like IL-1 and IL-6, alongside PAI-1, PTX-3, HIF, and IgG4 in the fibrotic cascade. Given the tissue-specific modulation of fibrosis, comprehending the molecular underpinnings of penile fibrosis becomes imperative for the innovation of novel and efficacious therapies targeting Peyronie's disease. This review stands as a valuable resource for researchers and clinicians engaged in investigating the molecular basis of fibrotic diseases, offering guidance for advancements in understanding Peyronie's disease.

(270) LISWT Before Penile Prosthesis Implantation Might Facilitate Dilation of Fibrotic Corpora

Abstract Introduction Severe corporeal fibrosis presents significant challenges in penile implant insertion. LISWT studies in rats and humans have suggested its ability to rejuvenate cavernous bodies through various mechanisms and growth factors. Objective This prompted our evaluation of LISWT's effectiveness in facilitating prosthesis implantation in patients with penile fibrosis, which are typically considered difficult cases. Methods A 34-year-old male smoker with a history of sickle cell disease, bilateral hip replacements, and splenectomy due to sickle cell crisis sought penile prosthesis implantation. He presented with severe erectile dysfunction and corporeal fibrosis following two ischemic priapism episodes caused by sickle cell disease, which were treated with distal shunts 4 and 1 years prior, respectively (Fig. 1). After obtaining consent, the patient underwent four cycles of LISWT, spaced one month apart. Each cycle consisted of four weekly sessions using the PiezoWave2 device from Richard WOLF with settings of 0.16mj/mm2 energy flux density, 6Hz frequency, and 10mm wave focus penetration depth. In each session, the patient received a total of 6000 shocks, distributed between the perineum, dorsum penis, and the lateral aspect of the penis. Results A month post-LISWT, the patient's Erection Hardness Score (EHS) improved from 0 to 1 following an intracavernous injection of 20 mcg of alprostadil (Fig. 2). Subsequently, he underwent a malleable penile implant procedure through the penoscrotal approach. Cavernosal dilation was successful up to 10mm using a Hegar dilator, with bilateral corporal measurements of 8cm proximally and 9cm distally. A Tactra malleable penile prosthesis (9.5mm girth and 17cm length) from Boston Scientific was implanted without complications (Fig. 3.A.B) Conclusions In cases of severe corporeal fibrosis, pre-treatment with LISWT may aid in the dilation of the corpora during penile prosthesis implantation, potentially reducing complications. Randomized studies are warranted to validate this indication Disclosure No.

(112) Penile Rehabilitation by Daily Intake of 5 mg Tadalafil for Erectile Dysfunction After Penile Fracture

Abstract Introduction Penile fracture is a rare complication to penile trauma, characterized by a sudden injury of the tunica albuginea of one or both corpora cavernosa of the penis. This commonly occurs during the erect state, when the tunica is thinner and under tension of fully engorged corpora cavernosa. Erectile dysfunction (ED) may occur in up to 12% of these patients due to organic and psychosexual factors including penile fibrosis. Objective This study aimed to assess the potential predictors of erectile dysfunction in patients who had penile fracture repair and the role of rehabilitation course of daily tadalafil 5 mg in management of ED following penile fracture. Methods From January 2022 to February 2023, 25 patients were included. Patients' baseline data as well as history including the time of presentation, the pattern and length of the tunical tear, and the presence of urethral injury, were obtained. After a week, all patients were followed up on and told to resume intercourse after at least two weeks if their wound had epithelialized. Only patients with a complaint of a weak erection, as determined by the Arabic validated version of the international index of erectile function (ArIIEF-5), were started on daily tadalafil 5 mg as a penile rehabilitation for at least one month, or until they regained their normal erection. The Hospital Anxiety and Depression Scale (HADS) was used for assessing patients. Patients with confounding disease as metabolic syndrome or mental illness were eliminated. Results Significant indicators predicting erectile dysfunction, according to the multiple logistic regression model, are the patients' age and the length of the tunical tear. A 1% increase in age was linked with a 73.6% rise in the probability of erectile dysfunction (p = 0.046), and a 1 cm increase in tunical tear length was associated with a 20.04 times increased risk of erectile dysfunction (p = 0.04). With a mean score of 20 on the Arabic-approved version of the internal index of erectile function, 5 of 9 patients with erectile dysfunction (55%) had improved erections after one month of penile rehabilitation, while only 4 of 9 patients (44%) required an additional month of treatment. Conclusions We propose that patients with penile fractur be counselled about erectile dysfunction and begin penile rehabilitation as soon as possible following repair to regain a normal erection. Disclosure No.

(065) Characterization of Cardiovascular Function, Metabolic Status and Erectile Function in Preclinical Model of Cardiometabolic Syndrome

Abstract Introduction Cardiometabolic syndrome is a widespread health issue and common cause of erectile dysfunction (ED). Cardiometabolic syndrome encompasses a group of indications including abdominal obesity, insulin-resistant glucose metabolism, dyslipidemia, and hypertension. To date, studies have looked at high fructose or high fat diets to induce cardiometabolic syndrome and ED in rodents, but these models do not closely model the clinical phenotype. Furthermore, the molecular basis of ED in cardiometabolic syndrome needs to be elucidated. Objective Our objective is to characterize the cardiovascular and erectile function, and metabolic status in the ZSF-1 obese rat. This hybrid rat is a cross between a Zucker diabetic fatty female and a spontaneously hypertensive heart failure male rat. We hypothesize that with age the ZSF-1 obese rats will demonstrate similar disease phenotype as seen clinically and develop ED. Methods We used male lean and obese ZSF-1 rats (n=8/group). We measured body weight weekly, and performed apomorphine erectile testing, MRI to assess body composition and glucose tolerance tests at 10, 20, 30 weeks. At 30 weeks, we assessed erectile function using ICP/MAP and vascular stiffness was measured via laser doppler pulse wave velocity (PWV). Additionally, acetylcholine (Ach)-mediated vasodilation, vasodilation to sodium nitroprusside (SNP), and contraction to phenylephrine (PE) was measured in thoracic and abdominal aortas. Aorta and penile segments were collected for histological analyses. Results On average, obese rats were 60% larger (230g) than controls, had greater percent body fat and had significantly impaired glucose tolerance at all time points (p<0.05). Over time, ZSF-1 obese rats developed ED as there was a significant decrease in apomorphine-induced erections by 30 weeks (p<0.05). ED was confirmed by significantly reduced ICP/MAP in ZSF-1 obese compared to lean rats (p<0.05). Obese rats were significantly more hypertensive compared to lean rats (MAP: 140.2 mmHg vs 99.6mmHg, p<0.05). Lean and obese rats had no difference in vascular stiffness indicated by PWV. In our tissue bath experiments, ACh-mediated vasodilation was significantly decreased in the thoracic aorta of obese rats (p<0.05) while the abdominal aorta was unchanged. SNP-mediated vasodilation was similar between groups in both thoracic and abdominal aortas. At high concentrations, PE-mediated vasoconstriction was significantly increased in the thoracic and decreased in the abdominal aortas of obese rats (p<0.05). Conclusions To our knowledge, this is the first report on the erectile function in the ZSF-1 rat model of cardiometabolic syndrome. The ZSF-1 obese rats had marked adiposity, hypertension, hyperglycemia and presented with aortic endothelial dysfunction and ED. We are currently assessing testosterone levels and penile fibrosis. We believe that the ZSF-1 rat is useful for studying ED as they gradually develop metabolic disease and ED over time like the human disease. Disclosure No.

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

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. In this study, we searched PubMed between the years 2000-2023 for publications with search strategy: "penile fibrosis" OR "scarred corpora" OR "fibrosed corpora". 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. 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.

The Role of Autophagy in Erectile Dysfunction.

Autophagy is a conservative lysosome-dependent material catabolic pathway, and exists in all eukaryotic cells. Autophagy controls cell quality and survival by eliminating intracellular dysfunction substances, and plays an important role in various pathophysiology processes. Erectile dysfunction (ED) is a common male disease. It is resulted from a variety of causes and pathologies, such as diabetes, hypertension, hyperlipidemia, aging, spinal cord injury, or cavernous nerve injury caused by radical prostatectomy, and others. In the past decade, autophagy has begun to be investigated in ED. Subsequently, an increasing number of studies have revealed the regulation of autophagy contributes to the recovery of ED, and which is mainly involved in improving endothelial function, smooth muscle cell apoptosis, penile fibrosis, and corpus cavernosum nerve injury. Therefore, in this review, we aim to summarize the possible role of autophagy in ED from a cellular perspective, and we look forward to providing a new idea for the pathogenesis investigation and clinical treatment of ED in the future.

Nrf2 enhances the therapeutic efficiency of adipose-derived stem cells in the treatment of neurogenic erectile dysfunction in a rat model

BackgroundErectile dysfunction (ED) caused by intraoperative nerve injury is a major complication of pelvic surgery. Adipose-derived stem cells (ADSCs) have presented therapeutic potential in a rat model of bilateral cavernous nerve injury (BCNI), while inadequate in vivo viability has largely limited their application. Nuclear factor-E2-related Factor (Nrf2) is a key transcription factor that regulates cellular anti-oxidative stress. In this work, we investigated the effect of Nrf2 expression regulation on the viability of ADSCs, and explore its repair potential in a BCNI rat model.ResultsThe survival time of tert-Butylhydroquinone (tBHQ)-ADSCs in BCNI model increased obviously. In addition, the tBHQ-ADSCs group presented better restoration of major pelvic ganglion (MPG) nerve contents and fibers, better improvement of erectile function, and less penile fibrosis than the other groups. Moreover, the expression of Nrf2 and superoxide dismutase 1 (SOD1) were higher than those of other groups.ConclusionNrf2 could enhance the anti-oxidative stress ability of ADSCs, so as to improve the therapeutic effect of ADSCs on BCNI rat model.

European Society of Sexual Medicine consensus statement on the use of animal models for studying Peyronie's disease.

Animal models are frequently used for translational research in Peyronie's disease (PD). However, due to lack of availability of guidelines, there is some heterogeneity in study design, data reporting, and outcome measures. This European Society for Sexual Medicine consensus statement aims to provide guidance in utilization of animal models in PD research in a standardized and uniform fashion. PubMed was searched for studies using animal models for PD. The following search terms were used: ("Peyronie's disease" OR "penile fibrosis" OR "penile curvature" OR "induration penis plastica" OR "erectile dysfunction") AND ("rodent" OR "mouse" OR "mice" OR "rat" OR "rabbit"). This European Society for Sexual Medicine statement describes best practice guidelines for utilization of animals in PD research: power calculation, details of available models, surgical procedures, and measurement techniques, while highlighting possible pitfalls and translational limitations of the models. In total, 2490 studies were retrieved and 2446 articles were excluded. A total of 44 studies were included, of which 40 studies used rats, 1 study used both rats and mice, 1 study used a genetic mouse model, and 2 studies used rabbits. A significant number of the studies (70.5%) used transforming growth factor β 1 for induction of fibrosis. Oxford 2011 Levels of Evidence criteria could not be applied due to the nature of the studies. Despite certain limitations of PD animal models presented, we aimed to provide guidance for their appropriate use in translational research, with the purpose of improving study quality and reproducibility as well as facilitating interpretation of reported results and conclusions.

MP27-09 OXYMATRINE IMPROVES ERECTILE FUNCTION THROUGH SUPPRESSION OF INFLAMMATION AND FIBROSIS IN DIABETIC RATS

You have accessJournal of UrologyCME1 Apr 2023MP27-09 OXYMATRINE IMPROVES ERECTILE FUNCTION THROUGH SUPPRESSION OF INFLAMMATION AND FIBROSIS IN DIABETIC RATS Wenchao Xu, Hao Li, Taotao Sun, Jiaxin Wang, Tao Wang, and Jihong Liu Wenchao XuWenchao Xu More articles by this author , Hao LiHao Li More articles by this author , Taotao SunTaotao Sun More articles by this author , Jiaxin WangJiaxin Wang More articles by this author , Tao WangTao Wang More articles by this author , and Jihong LiuJihong Liu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Diabetic mellitus-induced erectile dysfunction (DMED) responds poorly to phosphodiesterase type 5 inhibitors (PDE5i). Oxymatrine (OMT) has broad-spectrum anti-inflammatory and anti-fibrosis effects, but whether it improves the erectile function of diabetic populations through the above-mentioned mechanism is unclear. We intend to explore the role of OMT in the treatment of DMED. METHODS: A rat model of DMED was constructed by a single intraperitoneal injection of 1% streptozotocin solution. Thirty-two DMED rats were randomly divided into control group, DMED group, DMED + OMT-Low (50 mg/kg/day) group and DMED + OMT-High (100 mg/kg/day) group. Erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). The penile shafts were collected for subsequent molecular biological and histological analysis. RESULTS: ICP/MAP indicated that the erectile function of rats in the DMED model group was severely impaired, which was rescued in the DMED + OMT-Low and DMED + OMT-High groups. Rats in the DMED model group can highly express inflammatory indicators NF-kb, TNF-α and fibrosis-related proteins TGF-beta, CTGF, and Smad 2/3. The above-mentioned penile inflammation and fibrosis changes can be inhibited by OMT. Meanwhile, our results also showed that after OMT treatment, the NO/cGMP pathway was promoted and the RhoA/ROCK pathway was inhibited in the corpus cavernosum of DMED rats. CONCLUSIONS: OMT suppresses inflammation and fibrosis in the corpus cavernosum of diabetic rats to improve erectile function. OMT could improve penile erection by influencing endothelial and smooth muscle function. Our study provides new insight into the therapeutic effect of OMT and preclinical evidence for a potential treatment strategy for DMED. Source of Funding: This research was funded by grants from the National Natural Science Foundation of China (No. 82001536 and No.81873831) and the Fundamental Research Funds for the Central Universities (HUST: YCJJ202201021) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e365 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wenchao Xu More articles by this author Hao Li More articles by this author Taotao Sun More articles by this author Jiaxin Wang More articles by this author Tao Wang More articles by this author Jihong Liu More articles by this author Expand All Advertisement PDF downloadLoading ...

MP27-08 RADIAL TYPE LOW-INTENSITY EXTRACORPOREAL SHOCKWAVE THERAPY (LI-ESWT) AS NOVEL THERAPY TO ENHANCE MICROCIRCULATION IN AGING RAT PENIS

You have accessJournal of UrologyCME1 Apr 2023MP27-08 RADIAL TYPE LOW-INTENSITY EXTRACORPOREAL SHOCKWAVE THERAPY (LI-ESWT) AS NOVEL THERAPY TO ENHANCE MICROCIRCULATION IN AGING RAT PENIS Saager Chawla, Yong Sun Choi, Bae Woongjin, Samuel Sorkhi, Jae Hak Jeong, Tung-Chin Hsieh, and M. Raj Rajasekaran Saager ChawlaSaager Chawla More articles by this author , Yong Sun ChoiYong Sun Choi More articles by this author , Bae WoongjinBae Woongjin More articles by this author , Samuel SorkhiSamuel Sorkhi More articles by this author , Jae Hak JeongJae Hak Jeong More articles by this author , Tung-Chin HsiehTung-Chin Hsieh More articles by this author , and M. Raj RajasekaranM. Raj Rajasekaran More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Physiological aging is associated with the impairment of microvascular function in several organs, including the penis. Low-intensity extracorporeal shock-wave therapy (Li-ESWT) is a non-invasive intervention for the restoration of the pathological alterations of penile tissue. However, the effect of ESWT on penile microvascular function is still unclear. In addition, most previous studies have employed focused ESWT, which is known to target deeper organs, while radial ESWT is more superficial. Thus, our objective is to evaluate the effect of radial type Li-ESWT (targeting superficial penile tissue) on microvascular perfusion (MVP) in an aging rat model and elucidate a possible mechanism of action. METHODS: We anesthetized male rats (n=5; age 15-18 months) and subjected them to radial type Li-ESWT (Fig A-C) while monitoring penile hemodynamics via Laser Speckle Contrast imaging techniques immediately before and after Li-ESWT. The penile shaft was positioned beneath the ESWT applicator (HNT MEDICAL Co., Ltd, Seoul, Korea; Fig B). A level 1 intensity (L1i) (0.12 mJ/mm2) ESWT session for 500 counts at 120 HZ (Fig C) was chosen to increase blood penile microvascular perfusion (PMP). Baseline and peak PMP was assessed by the PeriCam PSI system (Perimed AB, Järfälla, Sweden). This technique quantifies PMP in arbitrary perfusion units (AU) and displays a real-time perfusion image. To assess the involvement of the nitric oxide (NO) pathway, an intracavernosal injection of L-NAME (NO synthase inhibitor) was given [200 µg/kg], and the response to ESWT was recorded again after 15 minutes. RESULTS: ESWT produced a 2-fold increase in PMP (mean±SEM) from baseline (68.456±9.021 AU) to max (163.742±11.787 AU). In addition, the L-NAME injection (n=4) resulted in a ∼40-50% decrease (from 185.293±20.604 AU to 101.008±13.077 AU) in ESWT-induced MVP response. CONCLUSIONS: Our results suggest ESWT is a novel, non-invasive intervention to improve penile circulation and treat erectile and sexual dysfunction following cancer treatment, possibly by improving penile hemodynamics and preventing penile hypoxia and fibrosis. Our findings suggest that the Li-ESWT-induced increase in MVP is mediated by the NO pathway, and future studies are warranted to confirm its efficacy in human subjects. Source of Funding: UCSD Academic Senate © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e365 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Saager Chawla More articles by this author Yong Sun Choi More articles by this author Bae Woongjin More articles by this author Samuel Sorkhi More articles by this author Jae Hak Jeong More articles by this author Tung-Chin Hsieh More articles by this author M. Raj Rajasekaran More articles by this author Expand All Advertisement PDF downloadLoading ...

Cellular nitric oxide synthesis is affected by disorders in the interdependent [Formula: see text] and [Formula: see text] dynamics during cystic fibrosis disease.

Calcium ([Formula: see text]), inositol trisphosphate ([Formula: see text]), and nitric oxide (NO) signaling are essential to maintain the structural integrity and physiological activity of fibroblast cells. The accumulation of excess quantity of NO for longer periods can lead to a variety of fibrotic disorders, including heart disease, penile fibrosis in Peyronie's disease (PD), and cystic fibrosis. The dynamics of these three signaling processes and their interdependence in fibroblast cells are not clearly known to date. A systems biology model is proposed using reaction-diffusion equations for calcium, [Formula: see text], and calcium-dependent NO synthesis in fibroblast cells. The finite element method (FEM) is used to examine [Formula: see text], [Formula: see text], and NO regulation and dysregulation in cells. The results throw light on the conditions that disturb the coupled [Formula: see text] and [Formula: see text] dynamics and the influence of these factors on the levels of NO concentration in the fibroblast cell. The findings suggest that changes in source inflow, buffers, and diffusion coefficient might induce an increase or reduction in nitric oxide and [Formula: see text] synthesis, resulting in fibroblast cell diseases. Furthermore, the findings provide new information regarding the size and intensity of diseases in response to changes in several factors of their dynamics, which has been linked to the development of cystic fibrosis and cancer. This knowledge could be valuable for developing novel approaches to the diagnosis of diseases and therapies for various disorders of fibroblast cells.

Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats

Introduction: Male sexual potency and vigor are a complex neuroendocrine process and an important component of well-being. Psychological stress is one of the leading causes of male impotence worldwide. Therefore, to better understand the effects of psychological stress on male sexual potency, vigor, and the physiology of erection, we used the rat restraint stress (RS) model, which can most aptly simulate psychological stress. Methods: Adult male SD rats were exposed to RS for 1.5 or 3 h/day for 30 days. Neuromodulators and hormones of sexual potency and penile erection were quantified using ELISA kit. The histoarchitecture of the penis was examined using Masson trichrome staining. Immunoblotting and immunofluorescence were used to assess the expression and immunolocalization patterns of penile erection markers. To assess sexual potency and vigor, a noncontact erection and a copulatory test were performed. Results: RS exposure decreased the circulatory levels of gonadotropins and testosterone while increasing the serum corticosterone level. RS exposure altered the histomorphology of the penis by decreasing the smooth muscle/collagen ratio and increasing oxidative stress in penile tissue. Furthermore, RS adversely affected NO availability for penile erection by decreasing the neurotransmitter acetylcholine and other erection facilitatory markers such as p-Akt, nNOS, eNOS, and cGMP, while increasing the inhibitory marker PDE5α in the penis. RS exposure significantly reduced the frequencies of mount, intromission, and ejaculation, whereas it prolonged sexual exhaustion by increasing latencies of postejaculatory mount, intromission, and ejaculation. Conclusion: The current findings suggest that psychological stressors, such as RS, cause erectile dysfunction in adult male rats by modulating the hypothalamic-pituitary-testicular axis, oxidative balance, penile fibrosis, and the NO/cGMP/PDE5α pathway of penile erection.

Preliminary Application of a Novel Autologous Scrotal Dartos Flap Method for Enlargement of Penile Girth in Men with Small Penis Syndrome.

Augmentative phalloplasty is a controversial issue. A safe, stable, and efficient surgical method for penile girth enlargement has not been available. This article introduces a novel autologous scrotal flap-turning procedure, the scrotal dartos flap method, for men with small penis syndrome and addresses its efficacy and safety. A single-center, prospective study was conducted at the Zhongnan Hospital of Wuhan University, where 29 patients were treated with the scrotal dartos flap method. The key procedure for this technique is fully turning the scrotal dartos flap to the loose plane just between the superficial penile fascia and the Buck fascia to increase the circumference of the penis. Penile girth improvement and adverse events were recorded. Complete follow-up data were collected for 27 of 29 patients (93.1 percent). It yielded a girth improvement of 3.59 ± 0.80 cm (50.8 percent). This enlargement surpassed that of most previous published surgical procedures. In addition, there were no serious adverse events (e.g., penile fibrosis, flap infection, sclerosis, or removal) during the 6-month follow-up. Wound infection ( n = 1), hematoma ( n = 2), and folding ( n = 1) were all slight. This novel autologous flap-turning procedure performed better than the majority of previously published penile girth enlargement methods and was accompanied by only slight and acceptable adverse events. The scrotal dartos flap method appears to be a viable method for the penile girth enlargement treatment of small penis syndrome. Therapeutic, IV.

Intratunical injection of rat-derived bone marrow mesenchymal stem cells prevents fibrosis and is associated with increased Smad7 expression in a rat model of Peyronie’s disease

ObjectivePeyronie’s disease (PD) is a fibrotic disorder of the penis, but effective treatments are lacking. Here, we observed the effects of rat-derived bone marrow mesenchymal stem cells (BMSCs) injection in the active phase and chronic phase in a rat model of PD, and the possible mechanism was analysed with fibroblasts derived from rat penile tunica albuginea (TA).MethodsThirty-two male Sprague-Dawley rats were divided into four groups. In sham group, the rats were injected with 50 µL of vehicle. In the PD group, the rats were injected with 50 µg TGF-β1. In the PD + BMSCs early treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 1 day. In the PD + BMSCs late treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 28 days. Twenty-seven days after the last injection, the erectile function of the rats was measured, and then, penile fibrosis was analysed by histology and western blot. In vitro, fibroblasts derived from rat penile TA were used to identify a possible antifibrotic mechanism of BMSCs, and a Smad7 expression vector was used as a positive control. Fibroblasts were pretreated with the Smad7 expression vector or BMSCs for 48 h and then activated with 10 ng/mL TGF-β1 for 24 h. Cells viability was assessed, and Smad7, collagen 3, elastase-2B and osteopontin expression levels were analysed by immunofluorescence and western blot. Furthermore, fibroblasts were transfected with Smad7 siRNA or scramble control to observe whether the effects of BMSCs could be offset.ResultsErectile function obviously improved, and fibrosis of penile TA was prevented after BMSCs treatment compared with that in the rats with PD. Furthermore, the effects of BMSCs treatment in the active phase were better than those in the chronic phase. After cocultured with BMSCs, cell viability was not affected, Smad7 expression was upregulated, and collagen 3, elastase-2B and osteopontin levels were decreased in the TGF-β1-treated fibroblasts. After transfection with Smad7 siRNA, the antifibrotic effects of BMSCs were offset.ConclusionsThe antifibrotic effects of BMSCs treatment in the active phase of the PD rat model were better than those in the chronic phase. A possible mechanism of BMSCs treatment was related to increased Smad7 expression, suggesting a possible effective and safe procedure for the treatment of PD.