Corpus Cavernosum Research Articles

Inhibition of YAP1 Rescues Erectile Dysfunction by Inhibiting Phenotypic Modulation through Myocardin in Diabetic Rats

Background. Phenotypic modulation was shown to be related to the pathological mechanism of diabetes mellitus erectile dysfunction (DMED), and excessive expression of YAP1 was measured in the cavernous tissues of rats with DMED. Objectives. This investigation was performed to explore the efficiency and mechanism of gene therapy through the knockdown of YAP1 in the field of ED treatment. Materials and Methods. Corpus cavernosum smooth muscle cells were obtained and cultivated in vitro employing the explant technique. EdU, CCK-8, and collagen gel lattice contraction assays were subsequently performed to assess cell proliferation and contractility, which indicate smooth muscle phenotypes. Results. Initially, overexpression of YAP1 enhanced the proliferation and expression of YAP1 and osteopontin (OPN) while reducing cell contractility and the expression of myocardin, α-SMA, and calpontin, which is consistent with phenotypic modulation. Moreover, knocking down YAP1 resulted in the opposite effects, and the blockade of myocardin attenuated the reversal of phenotypic transformation. Then, 45 screened DMED rats were randomly divided into three equal groups, named streptozotocin (STZ)-induced DMED with intracavernosal injection of Ad-myocardin (DMED + myocardin), DMED with lenti-shYAP1 (DMED + shYAP1) and DMED with PBS (DMED + PBS), and 10 rats were in the negative control group. Staining with H&E and Masson’s trichrome, immunochemistry, and determination of the ratio of the intracavernosal pressure/mean arterial pressure were performed to evaluate penile erection and histological changes. Western blotting was conducted to determine the molecular protein expression levels. In vivo, similar to myocardin overexpression, YAP1 inhibition rescued erectile function, repaired morphology, and maintained the contractile phenotype of smooth muscle tissues 14 days after treatment. Discussion and Conclusion. In conclusion, our study demonstrated the validity of gene therapy by downregulating excessive YAP1 expression to ameliorate ED in diabetic rats, and the ability of YAP1 inhibition to reverse phenotypic modulation was mediated through interaction with myocardin.

(019) Malignant Priapism: Case Report and Update on Management Protocols

Abstract Introduction Malignant priapism is a rare condition characterized by persistent erection resulting from the invasion or metastasis of a primary neoplasm. Penile metastases arise from the genitourinary tract 64% of the time (bladder: 28.6%, prostate: 27.9%, kidney: 6.9%, ureter: 0.5%) with colorectal adenocarcinoma, lung cancer, melanoma, and hematologic diseases comprising the remainder. Malignant priapism is reported to occur in 20-53% of patients with penile metastasis. The mechanism of malignant priapism remains unknown. The most accepted theory is an invasion of the corpus cavernosum as well as associated venous systems with malignant cells. This can occur from either hematogenous or lymphatic spread from the source tumor. Resulting derangement of arterial or veno-occlusive mechanism causes priapism. Both ischemic and non-ischemic priapism can occur. Objective While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. This study aims to present three cases of malignant priapism resulting from advanced genitourinary cancers and evaluate the efficacy of palliative penectomy as a treatment modality for relieving symptoms associated with malignant priapism. Methods We conducted a retrospective analysis of three cases of malignant priapism associated with advanced genitourinary cancers. Data were collected from medical records, including patient demographics, primary tumor characteristics, clinical presentation, treatment modalities, complications, and outcomes. The main treatment approach utilized in all cases was palliative penectomy. Symptom relief and complications were assessed as primary outcomes. Results All three patients presented with progressive penile pain, and imaging studies confirmed the presence of metastatic disease involving the penile structures. Palliative penectomy was performed in all cases, resulting in sustained relief of symptoms. No major complications were reported during the surgical procedures. Follow-up assessments showed improved quality of life in terms of pain relief, but all patients died within a short period following penectomy owing to the advanced predisposing malignancy. (figure 1) Conclusions Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes, and emphasis should be put on palliative care. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts. (figure 2) Disclosure No.

(404) National Trends of Penile Fracture Encounters 2016-2019

Abstract Introduction Penile Fracture (PF) is an acute urological emergency resulting from the rupture of the tunica albuginea and one or both of the corpus cavernosa. Immediate surgical intervention is crucial in avoiding long-term complications, however the epidemiology and treatment patterns remain understudied, especially with the introduction of the 10th Revision of the International Classification of Diseases (ICD-10). Objective To evaluate national trends of PF encounters as well as predictive factors of inpatient admission from the emergency department (ED). Methods All patients admitted to the ED for PF between 2016-2019 were extracted from the NEDS using the ICD-10 Diagnosis Code S39.840 and its modifiers. Multivariable logistic regression was performed to identify predictors of this inpatient admission. Results Between 2016-2019, there were an estimated 7,091 weighted encounters related to PF in the US with an overall 13% increase in cases (Figure 1). About 20.8% (1,477) of these encounters led to inpatient admission. The average age of a patient presenting with PF was 41 years old. The majority of encounters took place in the South (44.12%) at non-trauma center rural hospitals (63.99%) and involved private insurance holders (44.42%). For those admitted to inpatient service, the average length of stay was 1.44 days, with a maximum of 26 days. The average total charge for patients discharged from the ED was $11,224 USD and those admitted were faced with charges averaging $33,474 USD. Predictors of inpatient admission included an Elixhauser Comorbidity Score > 1, encounters in the Northeast, Midwest, and Western states, and being covered by Medicaid (p < .05). Conclusions Penile fractures have seen a small increase in incidence from 2016-2019. Although inpatient admissions are less common, they carry significantly higher costs. Further studies of treatments and regional analysis may be warranted to decrease the amount of inpatient admissions. Disclosure No.

The usefulness of shear wave elastography in evaluating erectile dysfunction severity before and after prostaglandin E1 test.

Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator's subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were "1" in 2 cases, "2" in 2 cases, and "3" in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was -26.7% and was significantly different between the poor (responses 1 and 2: -16.1%) and good erection (response 3: -30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.

Prolonged ischemic priapism in an adolescent with sickle cell anemia: Challenges of management

Introduction: Persistent penile erection lasting more than 4 hours and unrelated to sexual interest or stimulation is called priapism. Priapism is uncommon in children. Of the three widely accepted types: ischemic, non-ischemic, and stuttering priapism; ischemic priapism is the predominant type seen in children. A common cause of ischemic priapism in children is sickle cell disease. Ischemic priapism of prolonged duration is associated with a higher risk of complications especially irreversible loss of erectile function. It is a difficult clinical condition to manage and there are no established guidelines for its management in children. Adequate surgical treatment does not guarantee against the risk of devastating longterm sequelae. Case Report: We report a case of a 12-year-old boy with sickle cell anemia who presented after 48 hours of sustained painful penile erection. He required multiple surgical shunting procedures including distal corporoglanular shunt with tunneling of both corpora cavernosa with Hegar’s dilator to achieve detumescence. The management challenges encountered are highlighted. Conclusion: A potential role for anticoagulation and the use of low-dose hydroxyurea in the prevention of recurrent ischemic priapism in children with sickle cell anemia are advocated.

3-Hydroxy-3-methylglutaryl-CoA synthase 2 facilitates erectile dysfunction via inhibiting autophagy by enhancing the mammalian target of rapamycin pathway in type 1 diabetic mellitus rats.

The relationship between erectile dysfunction (ED) and type 1 diabetes mellitus (T1DM) is currently a hot topic of medical research. It has been reported that autophagy plays a crucial role in causing erectile dysfunction in T1DM. Recent research has shown that mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) is strongly linked to the development of T1DM. However, the specific mechanism by which it regulates the erectile function is not yet fully understood. To investigate whether HMGCS2 affects erectile function in type 1 diabetic rats by regulating autophagy in corpus cavernosum endothelial cells (CCECs). First, the rat model of T1DM was established. Then, the ratio of maximum penile intracavernous pressure (ICPmax) and mean arterial pressure (MAP) was detected to assess the erectile function in various groups, and the protein expression of HMGCS2, mTOR and p-mTOR was evaluated by western blot (WB) and immunohistochemistry (IHC). To explore the relationship between HMGCS2 and the mTOR signaling pathway in T1DM ED rats, we silenced the expression of HMGCS2 and activated the mTOR signaling pathway with MHY1485 in CCECs and then assessed the expression of beclin1, P62, LC3, autophagosome, endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS (p-eNOS), and nitric oxide (NO) to evaluate autophagy and the erectile function by reverse transcription quantitative polymerase chain reaction and western blot. The study conducted on T1DM ED rats showed that the expression of HMGCS2 was significantly increased, while the autophagy was suppressed. Additionally, the mTOR signaling pathway was highly activated. In contrast, when HMGCS2 was silenced in vitro, p-mTOR/mTOR was reduced, and autophagy was improved. These effects were accompanied by the enhanced activity of eNOS. Furthermore, when HMGCS2 was silenced and the mTOR signaling pathway was simultaneously activated, the results revealed a decrease in autophagy as well as a reduction in activity of eNOS in comparison to just silencing HMGCS2 alone. HMGCS2 upregulation in T1DM rats inhibited autophagy and eNOS activity by activating the mTOR pathway and led to a decrease in the erectile function.

Nitric Oxide Resistance in Priapism Associated with Sickle Cell Disease: Mechanisms, Therapeutic Challenges, and Future Directions.

Patients with sickle cell disease (SCD) display priapism, a prolonged penile erection in the absence of sexual arousal. The current pharmacological treatments for SCD-associated priapism are limited and focused on acute interventions rather than prevention. Thus, there is an urgent need for new drug targets and preventive pharmacological therapies for this condition. This review focuses on the molecular mechanisms linked to the dysfunction of the NO-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) pathway implicated in SCD-associated priapism. In murine models of SCD, reduced nitric oxide (NO)-cGMP bioavailability in the corpus cavernosum is associated with elevated plasma hemoglobin levels, increased reactive oxygen species levels that inactive NO, and testosterone deficiency that leads to endothelial nitric oxide synthase downregulation. We discuss the consequences of the reduced cGMP-dependent PDE5 activity in response to these molecular changes, highlighting it as the primary pathophysiological mechanism leading to excessive corpus cavernosum relaxation, culminating in priapism. We also further discuss the impact of intravascular hemolysis on therapeutic approaches, present current pharmacological strategies targeting the NO-cGMP-PDE5 pathway in the penis, and identify potential pharmacological targets for future priapism therapies. In men with SCD and priapism, PDE5 inhibitor therapy and testosterone replacement have shown promising results. Recent preclinical research reported the beneficial effect of treatment with haptoglobin and NO donors. SIGNIFICANCE STATEMENT: This review discusses the molecular changes that reduce NO-cGMP bioavailability in the penis in SCD and highlights pharmacological targets and therapeutic strategies for the treatment of priapism, including PDE5 inhibitors, hormonal modulators, NO donors, hydroxyurea, soluble guanylate cyclase stimulators, haptoglobin, hemopexin, and antioxidants.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Heme-induced corpus cavernosum relaxation and its implications for priapism in sickle cell disease: a mechanistic insight.

Patients with sickle cell disease (SCD) experience intravascular hemolysis, leading to elevated plasma heme levels. This phenomenon has been associated with increased priapism in men with SCD. The heme group can be metabolized by heme oxygenase (HO), generating carbon monoxide (CO), which is known to promote smooth muscle relaxation via soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP). However, the effects of heme on the relaxation responses of corpus cavernosum (CC) have not been investigated. To evaluate the functional and biochemical effects of the heme group on mouse CC smooth muscle in vitro. Male C57BL/6 mice were used. CC tissues were mounted in organ baths. Measurement of cGMP in mice CC was evaluated. The cumulative addition of heme concentrations promoted the relaxation of CC. HO inhibitor (1J, 100μM) or sGC inhibitor (ODQ, 10μM) blocked the relaxing effect of the heme group. Pre-incubation of CC with heme (100μM) enhanced relaxation induced by acetylcholine, sodium nitroprusside, and nitrergic relaxation (electrical field stimulation), which was abolished by 1J or ODQ. The heme group increased the cGMP production in CC, which was abolished by 1J or ODQ. cGMP levels were significantly higher in CC treated with heme, and pre-incubation with compound 1J or ODQ abolished the effect of heme in raising cGMP levels. The HO-CO-sGC-cGMP pathway appears to play a crucial role in promoting CC relaxation. Our study provides novel insight into the role of group heme in CC relaxation and its potential contribution to priapism in SCD. Heme may serve as a pharmacological target for new therapies to prevent priapism.

MiRNA-100 ameliorates diabetes mellitus-induced erectile dysfunction by modulating autophagy, anti-inflammatory, and antifibrotic effects.

Diabetes mellitus-induced erectile dysfunction (DMED) has become a common disease in adult men that can seriously reduce the quality of life of patients, and new therapies are urgently needed. miRNA-100 has many targets and can induce autophagy and reduce fibrosis by inhibiting the mTOR pathway and the TGF-β pathway. However, no research has been conducted with miR-100 in the field of DMED, and the specific mechanism of action is still unclear. To ascertain the effects of miR-100 on corpus cavernosum tissue of DMED rats and vascular endothelial cells in a high glucose environment and to elucidate the relevant mechanisms in autophagy, fibrosis and inflammation to find a new approach for the DMED therapy. Thirty rats were divided into three groups: the control group, the DMED group, and the DMED + miR-100 group. Using intraperitoneal injections of streptozotocin, all rats except the control group were modeled with diabetes mellitus, which was verified using the apomorphine (APO) test. For rats in the DMED + miR-100 group, rno-miR-100-5p agomir (50nmol/kg, every 2 days, 6 times in total) was injected via the tail vein. After 13weeks, the erectile function of each rat was assessed using cavernous manometry, and the corpus cavernosum tissue was harvested for subsequent experiments. For cellular experiments, human coronary microartery endothelial cells (HCMEC) were divided into four groups: the control group, the high-glucose (HG, 40mM) group, the HG + mimic group, and the HG + inhibitor group. The cells were cultured for 6 days and collected for subsequent experiments 2 days after transfection. Diabetic modeling impaired the erectile function in rats, and miR-100 reversed this effect. By measuring autophagy-related proteins such as mTOR/Raptor/Beclin1/p62/LC3B, we found that miR-100 could suppress the expression of mTOR and induce autophagy. The analysis of the eNOS/NO/cGMP axis function indicated that impaired endothelial function was improved by miR-100. By evaluating the TGF-β1/CTGF/Smad2/3 and NF-κB/TNF-α pathways, we found that miR-100 could lower the level of inflammation and fibrosis, which contributed to the improvement of the erectile function. Cellular experiments can be used as supporting evidence for these findings. MiR-100 can improve the erectile function by inhibiting mTOR and thus inducing autophagy, improving the endothelial function through the eNOS/NO/cGMP axis, and exerting antifibrotic and anti-inflammatory effects, which may provide new ideas and directions for the treatment of DMED.

Knockdown of programmed cell death factor 4 restores erectile function by attenuating apoptosis in rats with bilateral cavernous nerve crush injury.

Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear. This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush. The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate-buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate-buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting. The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway. Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18-month-old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level.

MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4.

The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Novel erectile analyses revealed augmentable penile Lyve-1, the lymphatic marker, expression.

The pathophysiology of penis extends to erectile dysfunction (ED) to conditions including sexually transmitted diseases (STDs) and cancer. To date, there has been little research evaluating vascular drainage from the penis. We aimed to evaluate penile blood flow invivo and analyze its possible relationship with the lymphatic maker. We established an invivo system designed to assess the dynamic blood outflow from the corpus cavernosum (CC) by dye injection. To analyze lymphatic characteristics in the CC, the expression of Lyve-1, the key lymphatic endothelium marker, was examined by the invitro system and lipopolysaccharide (LPS) injection to mimic the inflammatory conditions. A novel cavernography methods enable high-resolution morphological and functional blood drainage analysis. The expression of Lyve-1 was detected along the sinusoids. Furthermore, its prominent expression was also observed after penile LPS injection and in the erectile condition. The current invivo system will potentially contribute to the assessment of penile pathology from a novel viewpoint. In addition, current analyses revealed inducible Lyve-1 expression for LPS injection and the erection state, which requires further analyses on penile lymphatic system.

A novel modified penile disassembly procedure for isolated male epispadias repair: preliminary outcomes.

This study aimed to evaluate the preliminary outcome of a novel modification of a penile disassembly procedure. We retrospectively reviewed the data of 15 patients with isolated male epispadias (IME) who underwent a modified penile disassembly procedure. This modification involved leaving the glans connected while dissecting the urethral plate from the corpus cavernosum. This approach reserves the bundles of the anastomosis at the glans, which can prevent ischemic changes. One of the first two patients experienced glans ischemic changes on the first day after the operation, which ultimately resulted in the loss of half of the hemiglans. Urethral plate shortening was observed in two patients and was addressed with a transverse preputial island flap. Two patients developed a penopubic urethral fistula, which was repaired 6 months postoperatively. Of the 15 patients, 10 (66%) were continent or social continent, while 4 were incontinent and needed bladder neck reconstruction. One patient had not yet reached the age for continence evaluation. Additionally, Two patients had a residual dorsal curvature of approximately 10-15° and were advised to undergo continuous follow-up. The modified penile disassembly procedure is a simple, effective, and safe method for IME repair with an acceptable penile appearance and complication rate.

Tipik muayene bulguları olmadan üretral yaralanmanın eşlik ettiği penil fraktür: Nadir bir olgu sunumu

Penile fractures typically present unilaterally, although bilateral occurrences account for 2–10% of cases. Urethral injury concomitant with penile fracture is exceedingly rare and constitutes a urologic emergency. Emergency surgery is widely accepted as the standard approach. In the presented case, a 25-year-old male patient presented to the emergency department approximately two hours after experiencing blunt trauma to the penis during sexual intercourse, accompanied by a sudden crackling sound. Physical examination did not reveal classic signs of penile fracture such as eggplant deformity, butterfly sign, or penile deviation; however, urethrorrhagia was evident. Ultrasonography revealed a defect in the tunica albuginea at the distal portion of both cavernous bodies. Retrograde urethrography demonstrated filling of the corpus cavernosum from the urethra with an opaque substance. Surgical exploration identified rupture along two fracture lines on the dorsal aspect of the urethra. Primary anastomosis of the urethra was performed over a Foley catheter, and defects in both corpus cavernosum were sutured. This case underscores the variability in presentation of penile fractures and emphasizes the necessity of considering urethral injury in cases of penile fracture with associated symptoms. Keywords: penile erection, urethra, trauma

Immunohistochemical analysis of E-cadherin and Caspase-3 expression in equine penile squamous cell carcinoma

Neoplasms are an important cause of morbidity and mortality in horses, with squamous cell carcinoma (SCC), also called squamous cell carcinoma, being the most common genital malignant tumor in the species and the most common neoplasm in horses in the State of São Paulo. Neoplasms frequently infiltrate the corpus cavernosum and can cause metastases in regional lymph nodes, generally having a guarded to poor prognosis due to local invasion and recurrence. Given the importance of the disease, the objective was to verify whether there is a difference in the expression pattern of immunomarkers of apoptosis and cell adhesion, according to the degree of cellular differentiation of the neoplasms. Twenty equine penile SCC samples from the Animal Pathology Service of the Veterinary Hospital of the Faculty of Veterinary Medicine and Animal Science of the University of São Paulo were histologically analyzed and classified according to their degree of differentiation. In addition, they were also subjected to the immunohistochemistry technique, with the immunomarkers Caspase-3 and E-cadherin. Data were analyzed using Kendall’s correlation and the Mann-Whitney test. It was found that there is a positive correlation between the expression of immunomarkers and that there is no statistically significant difference in the expression of immunomarkers according to the degree of differentiation.

Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.

To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus.

Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM. Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650. The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups. NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.

Priapism in a Young Adult With Sickle Cell Disease.

This article presents a case study focusing on priapism in a patient with sickle cell disease, with repeated emergency department (ED) visits and hospitalizations. The patient was successfully identified and treated by the ED nurse practitioner (NP) with aspiration of the corpus cavernosum. Priapism is a persistent penile erection that continues for an extended time. There is some argument about what that length of time is, but generally, the consensus is more than 4 hr beyond sexual stimulation or unrelated to sexual stimulation or sexual interest (Bivalacqua et al., 2022). Priapism is a fairly common but underrecognized complication of sickle cell disease. It represents a urological emergency in which timely diagnosis and appropriate treatment are vital to preserving penile tissue and sexual function. The diagnosis is made clinically with a comprehensive history, physical examination, and appropriate laboratory test values. Initial management can be conservative with hydration and analgesics or, if necessary, more invasive with needle aspiration to promote detumescence. Permanent tissue damage or erectile dysfunction can result if priapism is unrecognized, untreated, or not treated immediately. The NP plays an integral role in treating and preventing permanent damage. Patient education should focus on instructions for preventing priapism and managing episodes at home.

Inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway ameliorates diabetes mellitus-induced erectile dysfunction by reducing cell death, fibrosis, and inflammation.

Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication in patients with diabetes mellitus. Necroptosis is regarded as a form of cell death that is intimately associated with the inflammatory response, which is not only initiated by inflammatory factors such as TNF-α, but also triggers the inflammatory cascade through the rupture of the dying cell. There is no definitive study on the role of necroptosis in the pathological process of DMED. In light of the pathological features of high inflammation levels in DMED patients, we assessed whether the necroptosis plays an important role in the course of DMED. Our study revealed that penile tissues of DMED rats showed high levels of key necroptosis factors such as receptor-interacting protein kinase 3 (RIP3), mixed-lineage kinase domain-like protein (MLKL), and transient receptor potential melatonin 7 (TRPM7). Furthermore, the inhibition of necroptosis with a receptor-interacting protein kinase 3 (RIP3) inhibitor or Yimusake (a common herbal remedy for ED) effectively rescued damage to corpus cavernosum smooth muscle cells (CCSMC) under high glucose conditions. Our findings suggest that inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway could effectively ameliorate CCSMCs fibrosis and death induced by high glucose and inhibited the inflammatory response.