-
Sexual Medicine Jun 2024The endothelial glycocalyx is an important barrier that protects the structure and function of endothelial cells. Androgen deficiency is a common factor that causes...
BACKGROUND
The endothelial glycocalyx is an important barrier that protects the structure and function of endothelial cells. Androgen deficiency is a common factor that causes structural and functional impairment of endothelial cells.
AIM
To investigate changes in the endothelial glycocalyx in the penile corpus cavernosum of the rat with low androgen status and its relationship with erection function.
METHODS
Eighteen 10-week-old Sprague-Dawley male rats were randomly divided into 3 groups (n = 6 each): sham operation, castration, and castration + testosterone replacement. The maximum intracavernosal pressure/mean arterial pressure of the penis was measured after modeling for 4 weeks. The expression levels of endothelial nitric oxide synthase (eNOS), phospho-eNOS, syndecan 1, heparanase, and nitric oxide in penile cavernous tissue and the serum levels of heparan sulfate, hyaluronic acid, tumor necrosis factor α, and interleukin 6 were determined. Transmission electron microscopy was used to observe the ultrastructure of the endothelial glycocalyx in penile tissue.
OUTCOMES
The thickness of the endothelial glycocalyx in the penile corpus cavernosum of castrated rats was significantly lower than that of the control group.
RESULTS
In the castrated rats, the endothelial glycocalyx thickness, syndecan 1 level, ratio of phospho-eNOS to eNOS, nitric oxide level, and maximum intracavernosal pressure/mean arterial pressure (3 V, 5 V) were significantly lower than those in the sham group ( < .05). The expression of heparanase and the serum levels of tumor necrosis factor α and interleukin 6 were significantly higher in the castrated group than in the sham group ( < .05).
CLINICAL TRANSLATION
Upregulating the expression of the endothelial glycocalyx in the penile corpus cavernosum may be a new method for treating erectile dysfunction caused by low androgen levels.
STRENGTHS AND LIMITATIONS
This study confirms that low androgen status promotes the breakdown of the endothelial glycocalyx. However, further research is needed to determine whether androgens are related to the synthesis of the endothelial glycocalyx.
CONCLUSION
Low androgen status may suppress the level of nitric oxide in the cavernous tissue of the penis via impairment of the endothelial glycocalyx, resulting in inhibited erection function in rats.
PubMed: 38883807
DOI: 10.1093/sexmed/qfae039 -
Frontiers in Endocrinology 2024As an important gas signaling molecule, hydrogen sulfide (HS) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary,... (Review)
Review
As an important gas signaling molecule, hydrogen sulfide (HS) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, HS not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between HS and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of HS in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of HS in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on HS. Therefore, understanding the role of HS in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.
Topics: Hydrogen Sulfide; Humans; Male; Genitalia, Male; Animals; Erectile Dysfunction; Signal Transduction
PubMed: 38883604
DOI: 10.3389/fendo.2024.1377090 -
Advanced Science (Weinheim,... Jun 2024The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus...
The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus cavernosum, adenosine deaminase (ADA) and adenosine receptors knock-out mice (ADA, A1, A2a, A2b, and A3), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine-induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age-related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus-induced ED. In single-cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock-out abolishes adenosine-induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF-1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60-6583 improves erectile function and down-regulates HIF-1α and TGF-β. Administering Dipyridamole (40 mg Kg) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine-induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.
PubMed: 38874549
DOI: 10.1002/advs.202306514 -
Irish Journal of Medical Science Jun 2024The purpose of this study is to identify the clinical outcomes of patients during acute phase of Peyronie's disease (PD) treated with daily Tadalafil 5 mg associated...
AIM
The purpose of this study is to identify the clinical outcomes of patients during acute phase of Peyronie's disease (PD) treated with daily Tadalafil 5 mg associated with non-surgical treatments such as intra-plaque verapamil injections (IVI), vacuum erection devices (VED) or extra corporeal shockwave therapy (ESWT).
METHODS
445 patients with PD in acute stage were treated as it follows: Group 1(G1) 117 men with only Tadalafil 5 mg once a day for 3 months; Group 2(G2) 106 men with IVI plus Tadalafil 5 mg for a period of 12 weeks; Group 3(G3) 124 men that received ESWT for 6 weeks plus Tadalafil with the same protocol of G1; Group 4(G4) 98 men with VED plus Tadalafil 5 mg for 3 months. There were assessed at baseline and follow-up: Erectile dysfunction (ED), presence and severity of painful erections, penile plaque size and penile curvature degree. The results were evaluated at baseline and 3,6,12 months.
RESULTS
Not statistically significant differences emerged between the two groups at baseline, except for higher presence of patients with ED in in G3(7.4%) vs other groups(p < 0.001). Three months after the treatment in G3 men had a significant reduction of penile curvature degrees after 1 year by treatments, whereas pain in an erection or during intercourse was resolved completely in 75% of the patients.
CONCLUSIONS
Our study highlights that multimodal therapy has beneficial long-term effects not only in the decrease of ED symptoms, but also in the relief of the penile curvature and the quality of life.
PubMed: 38861101
DOI: 10.1007/s11845-024-03734-1 -
ELife Jun 2024Erectile dysfunction (ED) affects a significant proportion of men aged 40-70 and is caused by cavernous tissue dysfunction. Presently, the most common treatment for ED...
Erectile dysfunction (ED) affects a significant proportion of men aged 40-70 and is caused by cavernous tissue dysfunction. Presently, the most common treatment for ED is phosphodiesterase 5 inhibitors; however, this is less effective in patients with severe vascular disease such as diabetic ED. Therefore, there is a need for development of new treatment, which requires a better understanding of the cavernous microenvironment and cell-cell communications under diabetic condition. Pericytes are vital in penile erection; however, their dysfunction due to diabetes remains unclear. In this study, we performed single-cell RNA sequencing to understand the cellular landscape of cavernous tissues and cell type-specific transcriptional changes in diabetic ED. We found a decreased expression of genes associated with collagen or extracellular matrix organization and angiogenesis in diabetic fibroblasts, chondrocytes, myofibroblasts, valve-related lymphatic endothelial cells, and pericytes. Moreover, the newly identified pericyte-specific marker, Limb Bud-Heart (Lbh) in mouse and human cavernous tissues, clearly distinguishing pericytes from smooth muscle cells. Cell-cell interaction analysis revealed that pericytes are involved in angiogenesis, adhesion, and migration by communicating with other cell types in the corpus cavernosum; however, these interactions were highly reduced under diabetic conditions. Lbh expression is low in diabetic pericytes, and overexpression of LBH prevents erectile function by regulating neurovascular regeneration. Furthermore, the LBH-interacting proteins (Crystallin Alpha B and Vimentin) were identified in mouse cavernous pericytes through LC-MS/MS analysis, indicating that their interactions were critical for maintaining pericyte function. Thus, our study reveals novel targets and insights into the pathogenesis of ED in patients with diabetes.
Topics: Male; Pericytes; Erectile Dysfunction; Single-Cell Analysis; Animals; Mice; Humans; Penis; Gene Expression Profiling; Transcriptome; Mice, Inbred C57BL; Single-Cell Gene Expression Analysis
PubMed: 38856719
DOI: 10.7554/eLife.88942 -
Eplasty 2024First described by Michal et al in 1972, penile revascularization for vasculogenic impotence and its outcomes has been scarcely reported in plastic surgery literature....
BACKGROUND
First described by Michal et al in 1972, penile revascularization for vasculogenic impotence and its outcomes has been scarcely reported in plastic surgery literature. Such injuries are often secondary to atherosclerosis of the distal internal pudendal, common penile or proximal cavernosal artery, or locoregional trauma. Various techniques have been described to restore blood flow to the cavernosal body.
METHODS
In this report, we review 2 cases of penile revascularization for arteriogenic erectile dysfunction at our level 1 trauma center in 2021-2022 completed by the senior author in conjunction with urology.
RESULTS
Both patients sustained pelvic crush injuries with resultant arteriogenic impotence minimally responsive to medical management with phosphodiesterase inhibitors and/or injection therapy. After thorough urologic and vascular workup, they underwent microsurgical revascularization of the penis utilizing the deep inferior epigastric arteries with anastomosis to the deep dorsal penile veins. Both patients demonstrated improvement in erectile dysfunction and were able to achieve sustained erection with adequate glans tumescence on minimal pharmacotherapy postoperatively. One patient noted ability to achieve penetration. Patient 1 experienced postoperative retention requiring Foley placement, and both patients experienced glans edema requiring additional urologic procedures (patient 1: dorsal slit, patient 2: completion circumcision).
CONCLUSIONS
Overall, we have demonstrated improvement of sexual function with the most common complication being prolonged penile edema requiring release of constriction by our urology colleagues. Additional research in the plastic surgery field is warranted to further refine the technique and improve outcomes.
PubMed: 38846509
DOI: No ID Found -
The Journal of Sexual Medicine May 2024
Topics: Humans; Male; Erectile Dysfunction; Fibroblasts; Penile Erection; Penis
PubMed: 38825574
DOI: 10.1093/jsxmed/qdae047 -
Radiographics : a Review Publication of... Jun 2024High-frequency US, with a linear transducer and gray-scale, color, and spectral Doppler US techniques, is the primary imaging modality for evaluation of the penis. It... (Review)
Review
High-frequency US, with a linear transducer and gray-scale, color, and spectral Doppler US techniques, is the primary imaging modality for evaluation of the penis. It can allow delineation of anatomy and assessment of dynamic blood flow; it is easily available and noninvasive or minimally invasive; it is cost effective; and it is well tolerated by patients. US assessment after pharmacologic induction of erection is an additional tool in assessing patients with suspected vasculogenic impotence, and also in selected patients with penile trauma and suspected Peyronie disease. Penile injuries, life-threatening infections, and vascular conditions such as priapism warrant rapid diagnosis to prevent long-term morbidities due to clinical misdiagnosis or delayed treatment. US can facilitate a timely diagnosis in these emergency conditions, even at the point of care such as the emergency department, which can facilitate timely treatment. In addition, color and spectral Doppler US are valuable applications in the follow-up of patients treated with endovascular revascularization procedures for vasculogenic erectile dysfunction. Image optimization and attention to meticulous techniques including Doppler US is vital to improve diagnostic accuracy. Radiologists should be familiar with the detailed US anatomy, pathophysiologic characteristics, scanning techniques, potential pitfalls, and US manifestations of a wide spectrum of vascular and nonvascular penile conditions to suggest an accurate diagnosis and direct further management. The authors review a range of common and uncommon abnormalities of the penis, highlight their key US features, discuss differential diagnosis considerations, and briefly review management. RSNA, 2024 Supplemental material is available for this article.
Topics: Humans; Male; Penis; Penile Diseases; Erectile Dysfunction; Ultrasonography; Diagnosis, Differential
PubMed: 38814798
DOI: 10.1148/rg.230157 -
BMC Psychiatry May 2024This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with...
OBJECTIVE
This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database.
METHODS
This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs.
RESULTS
The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound).
CONCLUSION
Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.
Topics: Humans; Vilazodone Hydrochloride; Male; Female; Adverse Drug Reaction Reporting Systems; Middle Aged; United States; Adult; Aged; Databases, Factual; United States Food and Drug Administration; Young Adult; Adolescent; Bayes Theorem
PubMed: 38755677
DOI: 10.1186/s12888-024-05813-0 -
Sexual Medicine Reviews Jun 2024Erectile dysfunction (ED) and kidney dysfunction share common risk factors linked to conditions involving endothelial impairment, such as coronary artery disease,... (Review)
Review
INTRODUCTION
Erectile dysfunction (ED) and kidney dysfunction share common risk factors linked to conditions involving endothelial impairment, such as coronary artery disease, dyslipidemia, diabetes mellitus, hypertension, smoking, and obesity. Men with chronic kidney disease experience a high incidence and prevalence of ED. While a functional renal graft can alleviate the issue for some patients, a significant portion of recipients still experience ED (20%-50%).
OBJECTIVES
This narrative review describes the variety of current treatments modalities on ED in kidney transplant recipients (KTRs) and their clinical outcomes.
METHODS
MEDLINE, Web of Science, PubMed, and Google Scholar were used to find eligible articles pertaining to the treatment options of ED in KTRs. A total of 64 articles were evaluated.
RESULTS
In KTRs, ED stems from a multifaceted etiology: anxiety, drug side effects, interference with penile vascularity, or the response of cavernosal muscle to neurotransmitters, along with changes in the endocrine milieu. A diverse range of treatments to restore erectile function has proven to be safe and effective for KTRs. Options include drug therapy, surgical interventions, intracavernosal injection therapies, vacuum erection devices, and extracorporeal shockwave therapy.
CONCLUSION
The initial treatment approach may involve the use of a phosphodiesterase type 5 inhibitors at a low dosage, especially if testosterone-circulating levels align with the diagnosis of hypogonadism. The consideration of a combination therapy involving testosterone and phosphodiesterase type 5 inhibitors should be contemplated due to the associated beneficial effects. Extracorporeal shockwave therapy has shown positive short-term clinical and physiological effects on erectile function in patients who did not respond to first-line treatments, resulting in spontaneous erections sufficient for sexual penetration in 50% of cases. Penile implants should be considered as third-line options based on specific patient needs and compliance with clinical conditions.
Topics: Humans; Male; Erectile Dysfunction; Kidney Transplantation; Phosphodiesterase 5 Inhibitors; Transplant Recipients
PubMed: 38724235
DOI: 10.1093/sxmrev/qeae028