PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase.

Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCß2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.

What Is Priapism?

This JAMA Patient Page describes the diagnosis, prevention, and treatment of priapism.

Single-cell RNA sequencing reveals critical modulators of extracellular matrix of penile cavernous cells in erectile dysfunction.

Erectile dysfunction (ED) is a common and difficult to treat disease, and has a high incidence rate worldwide. As a marker of vascular disease, ED usually occurs in cardiovascular disease, 2-5 years prior to cardiovascular disease events. The extracellular matrix (ECM) network plays a crucial role in maintaining cardiac homeostasis, not only by providing structural support, but also by promoting force transmission, and by transducing key signals to intracardiac cells. However, the relationship between ECM and ED remains unclear. To help fill this gap, we profiled single-cell RNA-seq (scRNA-seq) to obtain transcriptome maps of 82,554 cavernous single cells from ED and non-ED samples. Cellular composition of cavernous tissues was explored by uniform manifold approximation and projection. Pseudo-time cell trajectory combined with gene enrichment analysis were performed to unveil the molecular pathways of cell fate determination. The relationship between cavernous cells and the ECM, and the changes in related genes were elucidated. The CellChat identified ligand-receptor pairs (e.g., PTN-SDC2, PTN-NCL, and MDK-SDC2) among the major cell types in the cavernous tissue microenvironment. Differential analysis revealed that the cell type-specific transcriptomic changes in ED are related to ECM and extracellular structure organization, external encapsulating structure organization, and regulation of vasculature development. Trajectory analysis predicted the underlying target genes to modulate ECM (e.g., COL3A1, MDK, MMP2, and POSTN). Together, this study highlights potential cell-cell interactions and the main regulatory factors of ECM, and reveals that genes may represent potential marker features of ED progression.

Corpora cavernosa fibroblasts mediate penile erection.

Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily down-regulating Notch signaling. Inhibition of Notch increases fibroblast numbers and consequently raises penile blood flow. Continuous Notch activation lowers fibroblast numbers and reduces penile blood perfusion. Recurrent erections stimulate fibroblast proliferation and limit vasoconstriction, whereas aging reduces the number of fibroblasts and lowers penile blood flow. Our findings reveal adaptive, erectile activity-dependent modulation of penile blood flow by fibroblasts.

Penile Color Doppler Ultrasonography in Patients with Type 2 Diabetes Mellitus Presenting with Erectile Dysfunction: A Single-Center Experience from Bangladesh.

Erectile dysfunction (ED) is common in type 2 diabetes mellitus (T2DM). ED is considered the earliest marker of widespread endothelial dysfunction. Color Doppler ultrasonography (CDUS) of the penis is a valuable tool in identifying vasculogenic ED and may predict coronary vascular disease. In Bangladesh, no study has evaluated CDUS of the penis in such patients. This study assessed the penile CDUS characteristics of adult patients with T2DM having ED. This cross-sectional study was conducted from January to December 2021 at a specialized diabetes hospital in Cumilla, Bangladesh. The baseline velocities of the right and the left cavernosal arteries were measured at the penile base. Arterial insufficiency was defined as a peak systolic velocity (PSV) value <25 cm/s and venous insufficiency was described as an end-diastolic velocity (EDV) >5 cm/s at the end of the examination. Eighty-seven subjects were evaluated; the mean age was 44.2±9.2 years, mean duration of DM was 7.9±2.8 years; of them, 31.0% were smokers, 75.9% obese, 92.0% central obese, 69.0% hypertensive, 96.6% dyslipidemic and 51.7% with low testosterone. The mean HbA1c was 9.3±1.9%; DM was uncontrolled in 89.7% of the study subjects. Penile vasculopathy was found in 21.8% (17.2% had arterial insufficiency, 2.3% had a venous leak, and 2.3% had arterial insufficiency with a venous leak). There were no statistical differences between the two groups, with and without penile vasculopathy, except for diastolic blood pressure, which was higher in the vasculopathy group. CDUS may be incorporated into the tools for evaluating diabetic ED to direct specific management.

Is marijuana a foe of male sexuality? Data from a large cohort of men with sexual dysfunction.

BACKGROUND: Although it has been assumed that chronic cannabis use may have an unfavorable impact on male sexual function and its metabolic correlates, evidence from clinical studies remains inconclusive. OBJECTIVE: To investigate the relationship between cannabis use and sexual behavior, anthropometrics and metabolic/vascular profiles in a large series of men evaluated for sexual dysfunction. METHODS: A total of 4800 men (mean age 50.8 years) attending an andrology outpatient clinic for sexual dysfunction were studied. Sexual symptoms, hormonal, metabolic, and instrumental (penile color Doppler ultrasound, PCDU) parameters were evaluated according to the reported habitual use of recreational substances (no use, 1-2 joints/week, >2 joints/week, and use of illicit drugs other than cannabis). RESULTS: When compared with non-users, cannabis users were younger and exhibited a lower prevalence of comorbidities as well as better PCDU parameters, despite reporting higher alcohol and tobacco consumption. After adjustment for confounders, cannabis use was associated with a greater instability in the couple's relationship and a higher frequency of masturbation. In addition, the group smoking >2 joints/week showed a significantly lower body mass index than both controls and users of substances other than cannabis. Men who reported using recreational drugs (either cannabis or other) exhibited significantly lower levels of both total and low-density lipoprotein cholesterol than non-users. At the PCDU, smoking 1-2 joints/week was associated with significantly higher dynamic peak systolic velocity than both non-drug use and use of >2 joints/week. Prolactin levels were significantly higher in individuals smoking 1-2 joints/week and in those who used substances other than cannabis when compared with controls, whereas no difference in total testosterone levels was observed. DISCUSSION: In men with sexual dysfunction, mild cannabis consumption may be associated with a more favorable anthropometric and lipid profile and with a better penile arterial vascular response to intracavernous prostaglandin injection.

Serum folic acid: an effective indicator for arteriogenic erectile dysfunction.

Background: The present study is the first to explore the correlation between serum folic acid (FA) level and penile arterial peak systolic velocity (PSV) as measured via penile color Doppler ultrasonography (PDU), which directly reflects endothelial function in the penile artery. Materials and methods: A total of 244 consecutive erectile dysfunction (ED) patients and 72 healthy controls, recruited from the Andrology department and the Healthy Physical Examination Center of our hospital, respectively, from June 2020 to April 2022, were included in the study. Serum FA was measured in ED patients and healthy controls, and PDU examinations were conducted for all eligible ED patients. The Pearson method was used to evaluate the correlation between FA levels and PDU parameters in ED patients. A receiver operating characteristic (ROC) curve analysis was also performed to calculate the sensitivity and specificity of these parameters for prediction of arteriogenic ED. Results: After the PDU test, the average serum FA level among patients diagnosed with arteriogenic ED was 8.08 ± 2.64 ng/ml, lower than the average of 10.78 ± 2.87 ng/ml among healthy controls. There were no statistically significant inter-group differences on any basic parameters, including age, body mass index, fasting blood glucose, total cholesterol, and triglyceride. For further analysis, we divided the arteriogenic ED group into three subgroups by PSV range to compare serum FA levels among these subgroups. The mean FA levels in each of these groups were 5.97 ± 1.51ng/ml, and 8.21 ± 2.37ng/ml, and 10.55 ± 2.56ng/ml, while the corresponding PSV values were 15.75 ± 2.39cm/s, 23.53 ± 2.19cm/s, and 32.72 ± 1.64cm/s. Overall, a positive correlation between PSV and FA level was found among patients with arteriogenic ED (r=0.605, P<0.001). Furthermore, when FA level was used, with a cut-off value of 10.045 ng/ml, as a criterion to distinguish patients with arteriogenic ED from healthy controls, the area under the curve (AUC) was 0.772 (95% confidential interval: [0.696, 0.848]), for a sensitivity of 0.611 and specificity of 0.824. Conclusion: Serum FA level is positively correlated with PSV in ED patients, and has the ability to distinguish patients with arteriogenic ED from healthy controls. Taking these findings together, FA deficiency should be regarded as an independent risk factor for arteriogenic ED.

[A Case of Penile Calciphylaxis in a Hemodialysis Patient].

In the present case of a 56-year-old male, hemodialysis was introduced from December 20XX-2 due to chronic renal failure caused by diabetic nephropathy. In February 20XX, a glans penis ulcer was observed. It gradually expanded. Angiography conducted in April revealed complete occlusion of the left internal pudendal artery and poor visualization of the bilateral penile arteries. Given the high risk of obstruction, endovascular treatment was not conducted. The glans penis ulcer continued to expand, and maintenance dialysis became difficult due to intractable pain. Opioids were introduced, but the pain could not be controlled. In May 20XX, the patient was referred to our department for surgical treatment, and partial penile resection was performed. The patient was diagnosed with penile calciphylaxis based on clinical findings and pathological diagnosis. After the surgery, the pain subsided considerably, and the patient is being followed on an out-patient basis.

[The relationship between penile hemodynamic parameters in cavernous rteries and penile rigidity].

INTRODUCTION: Blood flow parameters in cavernous arteries during full-erection phase on Doppler ultrasonography are associated with intracavernosal pressure and, consequently, with penile rigidity. AIM: To examine the relationship between blood flow parameters in cavernous arteries and the penile rigidity. MATERIALS AND METHODS: A total of 54 healthy men and patients with erectile dysfunction of various degrees of severity, with mean age of 43,0 +/- 2,2 years ranging from 18 to 74 years, were included in the study. Erectile function was examined and 81 Doppler ultrasonography were performed after intracavernosal injection of alprostadil (10 mcg). In full-erection phase, peak systolic velocity (PSV) and systolic acceleration (SA) were measured, as well as resistive index (RI). Mean values were calculated for both cavernous arteries. Penile rigidity was assessed in three ways: clinical evaluation according to I. Goldstein, measurement of surface rigidity and evaluation of longitudinal rigidity. RESULTS: During Doppler ultrasonography a strong correlation of penile rigidity with RI (0,71-0,85) and SA (0,63-0,69) was found. Indirect assessment of penile rigidity using PSV values was less precise. With RI values close to 1,0, SA is a more reliable method for indirect rigidity assessment. CONCLUSION: Penile blood flow parameters, RI and SA, allow to evaluate a degree of rigidity and to eliminate subjectivity of the specialist performing the examination, as well as to obtain a range of penile rigidity values.

Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury.

As a peripheral nerve injury disease, cavernous nerve injury (CNI) caused by prostate cancer surgery and other pelvic surgery causes organic damage to cavernous blood vessels and nerves, thereby significantly attenuating the response to phosphodiesterase-5 inhibitors. Here, we investigated the role of heme-binding protein 1 (Hebp1) in erectile function using a mouse model of bilateral CNI, which is known to promote angiogenesis and improve erection in diabetic mice. We found a potent neurovascular regenerative effect of Hebp1 in CNI mice, demonstrating that exogenously delivered Hebp1 improved erectile function by promoting the survival of cavernous endothelial-mural cells and neurons. We further found that endogenous Hebp1 delivered by mouse cavernous pericyte (MCP)-derived extracellular vesicles promoted neurovascular regeneration in CNI mice. Moreover, Hebp1 achieved these effects by reducing vascular permeability through regulation of claudin family proteins. Our findings provide new insights into Hebp1 as a neurovascular regeneration factor and demonstrate its potential therapeutic application to various peripheral nerve injuries.

Hydrogen sulfide regulates the redox state of soluble guanylate cyclase in CSE-/- mice corpus cavernosum microcirculation.

The corpus cavernosum (CC) is a highly vascularized tissue and represents an excellent example of microcirculation. Indeed, erectile dysfunction is considered an early index of cardiovascular disease. Hydrogen sulfide (H2S) at the vascular level is endogenously produced from L-cysteine mainly by the action of cystathionine-γ-lyase (CSE) and plays a role in CC vascular homeostasis. Here we have evaluated the involvement of the endogenous H2S in the regulation of the soluble guanylate cyclase (sCG) redox state. The lack of CSE-derived endogenous H2S, in CSE-/- mice, disrupted the eNOS/NO/sGC/PDE pathway. Indeed, the absence of CSE-derived endogenous H2S caused a significant reduction of the relaxant response to riociguat, an sGC redox-dependent stimulator. Conversely, the response to cinaciguat, an sGC redox-independent activator, was not modified. The relevance of the role played at the redox level of the endogenous H2S was confirmed by the findings that in CC harvested from CSE-/- mice there was a significant reduction of GCß1 expression coupled with a decrease in CYP5R3, a reductase involved in the regulation of the redox state of sGC. These molecular changes driven by the lack of endogenous H2S translate into a significant reduction in cGMP levels. The replenishment of the lack of H2S with an H2S donor rescued the relaxant response to riociguat in CC of CSE-/- mice. In conclusion, the endogenous CSE-derived H2S plays a physiological key role in the regulation of the redox state of sGC in CC microcirculation.

[Penile epithelioid hemangioma]. / A hímvesszo epithelioid haemangiomája.

Epithelioid hemangioma is a benign vascular tumor. Complete surgical excision is curative, there is no tendency to recurrence or metastasize. Its penile occurrence is extremely rare, only 33 cases have been reported in English literature. A patient with epithelioid hemangioma of the deep dorsal vein of the penis is reported. To our knowledge, this is the first report of penile epithelioid hemangioma in Hungarian literature. The 64-year-old patient presented to our department with painful erection caused by a palpable penile mass. Physical examination revealed a mobile subcutaneous nodule on the dorsum of the penis. Penile ultrasound showed a 10 mm homogeneous, well circumscribed lesion superficial to the tunica albuginea of the corpora cavernosa without intralesional blood flow. Local excision was performed through a dorsal longitudinal penile incision. The deep dorsal vein was dissected circumferentially, then the lesion was removed following ligation of the vein proximal and distal to the mass. Histopathological examination revealed epithelioid hemangioma. At three months after surgery, the patient reported complete resolution of pain, his International Index of Erectile Function Score was 21. At four years after the operation, there were no signs of recurrence or metastasis. Successful treatment of epithelioid hemangioma of the penis requires in-depth knowledge of processes resulting in penile subcutaneous masses, therefore the differential diagnosis is detailed in discussion. Orv Hetil. 2023; 164(21): 836-840.

The atherosclerotic cardiovascular disease risk score is a reliable tool to identify patients with arteriogenic erectile dysfunction.

BACKGROUND: The atherosclerotic cardiovascular disease risk score is a validated algorithm predicting an individual's 10-year risk of developing acute cardiovascular events (cardiovascular disease). Patients who suffer from arteriogenic erectile dysfunction are susceptible to developing cardiovascular disease in the future. OBJECTIVES: To apply the atherosclerotic cardiovascular disease score at a homogenous cohort of men with erectile dysfunction undergoing a dynamic penile colour Doppler duplex ultrasound and explore its predictive ability to identify patients with vasculogenic erectile dysfunction at colour Doppler duplex ultrasound. MATERIALS AND METHODS: Complete data of 219 patients undergoing colour Doppler duplex ultrasound were analysed. All patients completed the International Index of Erectile Function. The atherosclerotic cardiovascular disease score and Charlson comorbidity index were applied to the entire cohort. Patients were divided into those with normal vs. pathological parameters at colour Doppler duplex ultrasound. Descriptive statistics were used to explore differences between the two groups. Logistic regression models tested the potential role of atherosclerotic cardiovascular disease to predict arteriogenic and/or venogenic erectile dysfunction. Local polynomial smoothing models graphically displayed the probability of pathological colour Doppler duplex ultrasound parameters at different atherosclerotic cardiovascular disease scores. RESULTS: Overall, arteriogenic erectile dysfunction and venous leakage were diagnosed in 88 (40.2%) and 28 (12.8%) patients respectively. The median (interquartile range) atherosclerotic cardiovascular disease score was 7.7 (3.9-14). Patients with pathologic colour Doppler duplex ultrasound were older (59 vs. 54 years, p < 0.001), had higher Body Mass Index (26.5 vs. 25.6 kg/m2 , p = 0.04), more comorbidities (Charlson comorbidity index ≥ 1) (76.5% vs. 54.4%, p = 0.002) and higher median atherosclerotic cardiovascular disease scores (9.95 vs. 7, p = 0.005), respectively. At logistic regression analysis, a higher atherosclerotic cardiovascular disease risk score was independently associated with arteriogenic erectile dysfunction at colour Doppler duplex ultrasound (odds ratio: 1.03, 95% confidence interval: 1.01-1.08, p = 0.02) after adjusting for Body Mass Index, physical activity, alcohol consumption and severe erectile dysfunction. DISCUSSION: As vasculogenic erectile dysfunction may precede by some years the onset of acute cardiovascular diseases, the rigorous identification of patients with deficient cavernosal arterial blood flow, would definitely allow the implementation of earlier and more effective cardiovascular prevention strategies in men with erectile dysfunction. CONCLUSIONS: The atherosclerotic cardiovascular disease risk score represents a reliable tool to identify patients with arteriogenic erectile dysfunction in everyday clinical practice.

Value of transrectal color Doppler ultrasound of the common penile arteries in the diagnosis of arteriogenic erectile dysfunction: A pilot study.

BACKGROUND: Penile duplex Doppler ultrasound in combination with intra-cavernous injection of vasoactive agents (PDDU-ICI) is the most accepted tool for diagnosis of arteriogenic erectile dysfunction (AED), but is invasive, time consuming and at risk of side effects. OBJECTIVES: The purpose of this pilot study is to evaluate the potential of transrectal color Doppler ultrasound (TR-CDU) of the common penile arteries as a non-invasive method for the diagnosis of AED. MATERIALS AND METHODS: A consecutive series of 61 men consulting for erectile dysfunction (ED) and 20 controls underwent TR-CDU examination, aged from 40 to 80 years. Sonographic parameters were correlated with the International Index of Erectile Function, short form (IIEF-5). Sensitivity and specificity were calculated and the areas under the receiver operating characteristic curves (AUC) were compared to evaluate the diagnostic performance. RESULTS: Receiver operating characteristic curve analysis showed no significant results for IIEF-5 score ⩾21 in relation to the Doppler parameters. However, we found a good diagnostic performance for patients with ED grading from moderate to severe at IIEF-5. In this cohort, we found that mean peak systolic velocity >15.8 cm/s predicted IIEF-5 ⩾17 (AUC = 0.73, p = 0.002) with 61.5% sensitivity and 85.7% specificity. Mean end diastolic velocity >1.46 cm/s predicted IIEF-5 ⩾17 (AUC = 0.68, p = 0.02) with 80.7% sensitivity and 52.4% specificity. Mean resistance index ⩽0.72 predicted IIEF-5 ⩾17 (AUC = 0.71, p = 0.004) with 46.2% sensitivity and 95.2% specificity. Mean pulsatility index ⩽1.41 predicted IIEF-5 ⩾17 (AUC = 0.75, p = 0.0005) with 48.5% sensitivity and 95.14% specificity. CONCLUSIONS: TR-CDU proved to be a feasible and non-invasive procedure, easily repeatable and not time consuming, overcoming the limits of PDDU-ICI. Diagnostic accuracy seems to be promising in discriminating patients with normal erectile function or mild dysfunction from those with moderate to severe ED. However, these findings need to be verified in future controlled randomized clinical trials.

Venous Leak Embolization in Patients with Venogenic Erectile Dysfunction via Deep Dorsal Penile Vein Access: Safety and Early Efficacy.

PURPOSE: This all-comers registry aimed to assess safety and early efficacy of venous embolization in patients with venogenic erectile dysfunction due to venous leak in an unselected cohort. METHODS: Between October 2019 and September 2022, patients with venogenic erectile dysfunction resistant to phosphodiesterase-5-inhibitors were treated with venous embolization using ultrasound-guided anterograde access via a deep dorsal penile vein in a single center. A mix of ethiodized oil and modified cyanoacrylate-based glue n-butyl 2 cyanoacrylate (NBCA) monomer plus methacryloxy-sulpholane monomer (Glubran-2, GEM, Italy) was used as liquid embolic agent. Prior to embolization, venous leak had been verified based on penile duplex sonography and computed tomography cavernosography. Procedural success was defined as technically successful and complete target vein embolization. The primary safety outcome measure was any major adverse event 6 weeks after the procedure. The primary feasibility outcome measure was IIEF-15 (International Index of Erectile Function-15) score improvement ≥ 4 points in ≥ 50% of subjects on 6 weeks follow-up post intervention. RESULTS: Fifty consecutive patients (mean age 61.8 ± 10.0 years) with severe erectile dysfunction due to venous leak underwent venous embolization. Procedural success was achieved in 49/50 (98%) of patients with no major adverse events on follow-up. The primary feasibility outcome measure at 6 weeks was reached by 34/50 (68%) of patients. CONCLUSION: Venous leak embolization via deep dorsal penile vein access using a liquid embolic agent was safe for all and efficacious in the majority of patients with severe venogenic erectile dysfunction on 6 weeks follow-up.

Modified Surgical Model for Genitourinary Vascularized Composite Allotransplantations: An Anatomical Study.

SUMMARY: Total penile reconstruction represents a surgical challenge. Autologous reconstructions offer limited aesthetic results and variable urinary function recovery. To date, five genitourinary vascularized composite allotransplantations have been performed worldwide. However, in all cases, vascular complications have been reported. The objective of this study was to develop a modified surgical model for penile allotransplantation to limit the number of microsurgical anastomoses and ensure vascular reliability. The authors studied penile allotransplantation by performing dissections on 12 subjects. The study was carried out to ensure the vascularization of the entire penis shaft while limiting the number of anastomoses. The penis vasculature includes numerous angiosomes between its different subunits. The penile skin envelope is supplied by both external and internal pudendal vessels. The cavernous and spongy bodies are supplied by terminal branches of the internal pudendal vessels. The anterior pubic osteotomy approach allows access to the root of the cavernous bodies and to the Alcock ducts. This modified surgical model for penile allotransplantation could help future teams involved in genitourinary vascularized composite allotransplantations to improve urinary and sexual function. CLINICAL RELEVANCE STATEMENT: The authors introduce an improved surgical technique for penile transplantation that enhances vascularization and graft viability. This innovative procedure optimizes blood flow through meticulous microsurgical anastomosis, resulting in improved functional outcomes. Its potential to revolutionize penile transplantation warrants further exploration and validation within the surgical community.

Bilateral Cavernosal Artery Ligation to Treat Ischemic Priapism Following Inflatable Penile Prosthesis Implantation.

OBJECTIVE: To describe the first known case of recurrent acute priapism after penile prosthesis implantation. MATERIALS AND METHODS: A 60-year-old gentleman with a history of recurrent ischemic priapism without hemoglobinopathy presented with refractory erectile dysfunction and underwent uncomplicated penile prosthesis placement. His course was complicated by early acute ischemic priapism confirmed via ultrasound. Due to his pain, attempts to relieve the priapism using ultrasound-guided phenylephrine injections were attempted but were unsuccessful. RESULTS: He subsequently underwent exploration with confirmation of distal ischemic priapism followed by brisk bright red blood from the proximal corpora upon device externalization. A perineal exploration was performed and the bilateral cavernosal arteries were suture ligated with immediate relief. The device was reimplanted and the patient recovered uneventfully. CONCLUSION: We report the first known case of ischemic priapism following inflatable penile prosthesis implantation. The details of this case challenge the dogma that priapism is a binary event and instead supports an imbalance between unopposed cavernosal artery inflow possibly due to vascular calcifications and compromised venous outflow due to the presence of the device. Prosthetic urologists should be aware of this rare phenomenon and consider all available approaches on an individualized case-by-case basis.

Argonaute 2 Restores Erectile Function by Enhancing Angiogenesis and Reducing Reactive Oxygen Species Production in Streptozotocin (STZ)-Induced Type-1 Diabetic Mice.

Severe vascular and nerve damage from diabetes is a leading cause of erectile dysfunction (ED) and poor response to oral phosphodiesterase 5 inhibitors. Argonaute 2 (Ago2), a catalytic engine in mammalian RNA interference, is involved in neurovascular regeneration under inflammatory conditions. In the present study, we report that Ago2 administration can effectively improve penile erection by enhancing cavernous endothelial cell angiogenesis and survival under diabetic conditions. We found that although Ago2 is highly expressed around blood vessels and nerves, it is significantly reduced in the penis tissue of diabetic mice. Exogenous administration of the Ago2 protein restored erectile function in diabetic mice by reducing reactive oxygen species production-signaling pathways (inducing eNOS Ser1177/NF-κB Ser536 signaling) and improving cavernous endothelial angiogenesis, migration, and cell survival. Our study provides new evidence that Ago2 mediation may be a promising therapeutic strategy and a new approach for diabetic ED treatment.

Low-intensity shockwave treatment (LISWT) improves penile rigidity in eugonadal subjects with erectile dysfunction: a pilot study.

BACKGROUND: Since low-intensity shockwave treatment (LISWT) has putative effects on penile hemodynamics remodeling, the aim of this study was to evaluate any improvement of penile vascular flows after LISWT treatment in patients with erectile dysfunction (ED) and poor response to PDE5i. METHODS: Twenty-one eugonadal patients with different ED severity underwent 6 weekly LISWT sessions (1500-4000 pulses) after 2 weeks withdrawal from PDE5i assumption. Once daily Tadalafil (2.5 mg daily) was reintroduced 4 weeks apart from LISWT termination and patients were evaluated at 1, 2 and 6 months follow-up (T1, T2, T6) by the International Index of Erectile Function-15 items questionnaire (IIEF-15) erectile function (EF) domain, Erection Hardness Score (EHS) and Global Assessment Questionnaires (GAQ). Basal Penile Color-Doppler Ultrasound parameters in the flaccid state (B-PCDU) were evaluated before, during and after interventional protocol. RESULTS: Mean EHS score improved in 35% of patients at T1, and in up to 50% of patients at T2 and T6 follow-up visits (P<0.05). We found 25% improvement of EF scores at T1 session, 43.75% at T2 and 62.5% at T6, respectively (P<0.05). No statistically significant differences in flow parameters, EF-domain and testosterone levels were found when baseline and last observation carried forward (LOCF) parameters were compared. The GAQ questionnaire scored higher satisfaction rates either at the end of the treatment (100%), or at LOCF (92.5%). CONCLUSIONS: Despite the study limitations with respect to B-PCDU in this setting, our results confirm a trend toward improvement of erectile questionnaire scores after LISWT with higher overall satisfaction rates among patients with ED. We conclude that LISWT may be an effective option in some difficult-to-treat patients with ED by improving the erectile response to PDE5i.