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Journal of Proteome Research Mar 2018Priapism is a disorder in which prolonged penile erection persists uncontrollably, potentially leading to tissue damage. Priapism commonly afflicts patient populations...
Priapism is a disorder in which prolonged penile erection persists uncontrollably, potentially leading to tissue damage. Priapism commonly afflicts patient populations with severely low nitric oxide (NO) bioavailability. Because NO is a primary mediator of erection, the molecular mechanisms involved in priapism pathophysiology associated with low NO bioavailability are not well-understood. The objective of this study was to identify dysregulated molecular targets and signaling pathways in penile tissue of a mouse model of low NO bioavailability that have potential relevance to priapism. Neuronal plus endothelial NO synthase double knockout mice (NOS1/3) were used as a model of low NO bioavailability. Priapic-like activity was demonstrated in the NOS1/3 mice relative to wild-type (WT) mice by the measurement of prolonged erections following cessation of electrical stimulation of the cavernous nerve. Penile tissue was processed and analyzed by reverse-phase liquid chromatography tandem mass spectrometry. As a result, 1279 total proteins were identified and quantified by spectral counting, 46 of which were down-regulated and 110 of which were up-regulated in NOS1/3 versus WT (P < 0.05). Ingenuity Pathway Analysis of differentially expressed proteins revealed increased protein kinase A and G-protein coupled receptor signaling in NOS1/3 penises, which represent potential mechanisms contributing to priapism for secondary to low NO bioavailability.
Topics: Animals; Chromatography, Reverse-Phase; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Electric Stimulation; Endothelial Cells; Gene Expression Regulation; Gene Ontology; Humans; Male; Mice; Mice, Knockout; Molecular Sequence Annotation; Neurons; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Penile Erection; Penis; Priapism; Proteome; Receptors, G-Protein-Coupled; Signal Transduction; Splanchnic Nerves; Tandem Mass Spectrometry
PubMed: 29394072
DOI: 10.1021/acs.jproteome.7b00657 -
The Journal of Sexual Medicine Aug 2020Penile duplex Doppler ultrasound (PDDU) is a minimally invasive tool to evaluate erectile hemodynamics in patients with erectile dysfunction (ED). Despite decades of... (Review)
Review
A Critical Analysis of Methodology Pitfalls in Duplex Doppler Ultrasound in the Evaluation of Patients With Erectile Dysfunction: Technical and Interpretation Deficiencies.
BACKGROUND
Penile duplex Doppler ultrasound (PDDU) is a minimally invasive tool to evaluate erectile hemodynamics in patients with erectile dysfunction (ED). Despite decades of use, there is still a large variability in PDDU protocols, and a high rate of false diagnosis is reported.
AIM
Review of PDDU methodology in the published literature addressing protocol heterogeneity, technical and interpretation challenges.
METHODS
A PubMed literature search was performed using the search terms "penile doppler ultrasound", "penile duplex ultrasound" or "penile ultrasound", and "Erectile dysfunction". Studies were analyzed for the presence of the following elements in reporting of the PDDU protocol: (i) intracavernosal vasoactive agents used, (ii) use of a redosing protocol, (iii) means of rigidity assessment, (iv) report of at-home best-quality erection, (v) normative criteria for peak systolic velocity (PSV) and end-diastolic velocity (EDV), and (vi) use of time-based hemodynamics assessment. Inclusion criteria were studies available in English, from 2005 onwards, and with full text. Exclusion criteria were review, descriptive or short communication articles, animal studies, and studies in populations other than those with ED.
OUTCOMES
A critical review of the heterogeneity in published literature was performed to guide a structured discussion of methodological challenges and to create a list of recommendations.
RESULTS
Significant heterogeneity was seen in key methodological aspects. Fifty percent of studies reported the use of prostaglandin E1 only, and 12% of studies did not mention the agent used. Redosing as part of the PDDU protocol was mentioned in only 26% of studies. The majority (56%) did not mention any form of rigidity assessment. The most frequently used grading system was the Erection Hardness Score (14%). Overall, most studies (59%) used a timed-base protocol for hemodynamic assessment. No clear consensus was defined for normative criteria for PSV and EDV, 39% defining a normal PSV as ≥30 cm/s, and 57% using EDV values ≤5 cm/sec as normal.
CLINICAL IMPLICATIONS
The absence of standardization has led to inadequate reporting of key factors which has rendered data interpretation and comparison between studies challenging.
STRENGTHS AND LIMITATIONS
Our strengths include an extensive review of literature, with a structured analysis of the impact of each methodological pitfall. Our main limitation is the fact that protocol reporting, and not its application, was assessed.
CONCLUSION
Despite its widespread use, analysis of the literature on PDDU use in the ED population shows marked protocol heterogeneity, rendering data interpretation a problem. Nascimento B, Miranda EP, Terrier JE, et al. A Critical Analysis of Methodology Pitfalls in Duplex Doppler Ultrasound in the Evaluation of Patients With Erectile Dysfunction: Technical and Interpretation Deficiencies. J Sex Med 2020;17:1416-1422.
Topics: Erectile Dysfunction; Humans; Male; Penile Erection; Penis; Ultrasonography, Doppler; Ultrasonography, Doppler, Duplex
PubMed: 32631763
DOI: 10.1016/j.jsxm.2020.05.023 -
Journal of Radiation Research May 2021Since sexual function and testosterone levels after image-guided proton therapy (IGPT) have not yet been examined in detail, we prospectively evaluated changes before...
Since sexual function and testosterone levels after image-guided proton therapy (IGPT) have not yet been examined in detail, we prospectively evaluated changes before and after IGPT. Among patients treated with IGPT with or without combined androgen blockade (CAB) therapy between February 2013 and September 2014, patients who agreed to participate in the study and were followed up for >3 years after IGPT were evaluated. Serum testosterone levels were regularly measured together with prostate-specific antigen (PSA) levels before and after IGPT. The Erection Hardness Score (EHS) and the sexual domain summary, function subscale and bother subscale of the sexual domain in the Expanded Prostate Cancer Index Composite (EPIC) were assessed. There were 38 low-risk, 46 intermediate-risk and 43 high- or very-high-risk patients (NCCN classification). Although serum testosterone levels in low-risk patients did not decrease after IGPT, reductions were observed in the average EHS and the sexual domain summary score of the EPIC. In intermediate-, high- and very-high-risk patients, testosterone and PSA levels both increased following the termination of CAB after IGPT, and the average EHS increased. The sexual domain summary score gradually increased, but not above minimally important differences. In intermediate-risk patients, the function subscale increased from 4.4 to 14.8 (P < 0.05) 12 months after IGPT and reached a plateau after 60 months. The results of the present study would suggest the potential of IGPT, and further prospective studies to directly compare IGPT with other modalities are warranted.
Topics: Aged; Aged, 80 and over; Humans; Male; Middle Aged; Penile Erection; Prostate-Specific Antigen; Prostatic Neoplasms; Proton Therapy; Radiotherapy, Image-Guided; Risk Factors; Testosterone
PubMed: 33675355
DOI: 10.1093/jrr/rrab002 -
The Journal of Sexual Medicine Oct 2017The pathophysiology of increased severity of erectile dysfunction in men with diabetes and their poor response to oral pharmacotherapy are unclear. Defective vascular...
BACKGROUND
The pathophysiology of increased severity of erectile dysfunction in men with diabetes and their poor response to oral pharmacotherapy are unclear. Defective vascular endothelium and consequent impairment in the formation and action of nitric oxide (NO) are implicated as potential mechanisms. Endothelial NO synthase, critical for NO generation, is localized to caveolae, plasma membrane lipid rafts enriched in structural proteins, and caveolins. Type 2 diabetes mellitus (T2DM)-induced changes in caveolin expression are recognized to play a role in cardiovascular dysfunction.
AIMS
To evaluate DM-related changes to male erectile tissue in a mouse model that closely resembles human T2DM and study the specific role of caveolins in penile blood flow and microvascular perfusion using mice lacking caveolin (Cav)-1 or Cav-3.
METHODS
We used wild-type C57BL6 (control) and Cav-1 and Cav-3 knockout (KO) male mice. T2DM was induced by streptozotocin followed by a high-fat diet for 4 months. Penile expressions of Cav-1, Cav-3, and endothelial NO synthase were determined by western blot, and phosphodiesterase type 5 activity was measured using [H] cyclic guanosine monophosphate as a substrate. For hemodynamic studies, Cav-1 and Cav-3 KO mice were anesthetized, and penile blood flow (peak systolic velocity and end-diastolic velocity; millimeters per second) was determined using a high-frequency and high-resolution digital imaging color Doppler system. Penile tissue microcirculatory blood perfusion (arbitrary perfusion units) was measured using a novel PeriCam PSI system.
OUTCOMES
Penile erectile tissues were harvested for histologic studies to assess Cav-1, Cav-3, and endothelial NO synthase expression, phosphodiesterase type 5 activity, and blood flow, and perfusion measurements were assessed for hemodynamic studies before and after an intracavernosal injection of prostaglandin E (50 ng).
RESULTS
In T2DM mice, decreased Cav-1 and Cav-3 penile protein expression and increased phosphodiesterase type 5 activity were observed. Decreased response to prostaglandin E in peak systolic velocity (33 ± 4 mm/s in Cav-1 KO mice vs 62 ± 5 mm/s in control mice) and perfusion (146 ± 12 AU in Cav-1 KO mice vs 256 ± 12 AU in control mice) was observed. Hemodynamic changes in Cav-3 KO mice were insignificant.
CLINICAL TRANSLATION
Our findings provide novel mechanistic insights into erectile dysfunction severity and poor pharmacotherapy that could have potential application to patients with T2DM.
STRENGTHS AND LIMITATIONS
Use of KO mice and novel hemodynamic techniques are the strengths. A limitation is the lack of direct evaluation of penile hemodynamics in T2DM mice.
CONCLUSION
Altered penile Cav-1 expression in T2DM mice and impaired penile hemodynamics in Cav-1 KO mice suggests a regulatory role for Cav-1 in DM-related erectile dysfunction. Parikh J, Zemljic-Harpf A, Fu J, et al. Altered Penile Caveolin Expression in Diabetes: Potential Role in Erectile Dysfunction. J Sex Med 2017;14:1177-1186.
Topics: Animals; Caveolin 1; Cyclic GMP; Diabetes Mellitus, Type 2; Endothelium, Vascular; Erectile Dysfunction; Male; Mice; Mice, Knockout; Microcirculation; Nitric Oxide Synthase Type III; Penile Erection; Penis
PubMed: 28923309
DOI: 10.1016/j.jsxm.2017.08.006 -
Drug Design, Development and Therapy 2016The aim of this review was to summarize the ocular action of the most common phosphodiesterase (PDE) inhibitors used for the treatment of erectile dysfunction and the... (Review)
Review
AIM
The aim of this review was to summarize the ocular action of the most common phosphodiesterase (PDE) inhibitors used for the treatment of erectile dysfunction and the subsequent visual disorders.
METHOD
This is a literature review of several important articles focusing on the pathophysiology of visual disorders induced by PDE inhibitors.
RESULTS
PDE inhibitors have been associated with ocular side effects, including changes in color vision and light perception, blurred vision, transient alterations in electroretinogram (ERG), conjunctival hyperemia, ocular pain, and photophobia. Sildenafil and tadalafil may induce reversible increase in intraocular pressure and be involved in the development of non-arteritic ischemic optic neuropathy. Reversible idiopathic serous macular detachment, central serous chorioretinopathy, and ERG disturbances have been related to the significant impact of sildenafil and tadalafil on retinal perfusion.
DISCUSSION
So far, PDE inhibitors do not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors. However, physicians should write down any visual symptom observed during PDE treatment and refer the patients to ophthalmologists.
Topics: Animals; Choroid; Erectile Dysfunction; Humans; Male; Penile Erection; Phosphodiesterase Inhibitors; Photoreceptor Cells, Vertebrate; Retina; Risk Factors; Treatment Outcome; Vision Disorders; Vision, Ocular
PubMed: 27799745
DOI: 10.2147/DDDT.S118015 -
International Braz J Urol : Official... 2019
Topics: Age Factors; Body Mass Index; Erectile Dysfunction; Humans; Male; Penile Erection; Prostatectomy; Recovery of Function; Robotic Surgical Procedures; Urinary Incontinence; Urination
PubMed: 31397985
DOI: 10.1590/S1677-5538.IBJU.2019.04.01 -
International Braz J Urol : Official... 2018Obesity is a worldwide challenging health problem. Weight loss through medical management of obesity has not always been successful, thus, giving rise to the need for... (Review)
Review
Obesity is a worldwide challenging health problem. Weight loss through medical management of obesity has not always been successful, thus, giving rise to the need for surgical intervention. Bariatric surgery has been shown to be helpful for morbidly obese patients. However, studies have also shown the effect of surgery on stone formation, fertility and erectile function. This review summarizes the main findings of several studies that analyze stone formation and fertility in men as well as erectile function post bariatric surgery. The underlying pathophysiologic alterations post bariatric surgery include increased absorption of oxalate leading to hyperoxaluria, hypocitraturia and increased urinary calcium oxalate supersaturation. Contradicting data exist on the effect of bariatric surgery on fertility and erectile function. Further studies are needed to analyze the mechanisms.
Topics: Bariatric Surgery; Calcium Oxalate; Erectile Dysfunction; Gastric Bypass; Humans; Infertility, Male; Kidney Calculi; Male; Obesity; Penile Erection; Postoperative Complications; Risk Factors
PubMed: 29412550
DOI: 10.1590/S1677-5538.IBJU.2017.0416 -
PloS One 2021Erectile dysfunction (ED) is defined as the inability to achieve and/or maintain penile erection sufficient for satisfactory sexual relations, and aging is one of the...
Erectile dysfunction (ED) is defined as the inability to achieve and/or maintain penile erection sufficient for satisfactory sexual relations, and aging is one of the main risk factors involved. The D-(+)-Galactose aging model is a consolidated methodology for studies of cardiovascular aging; however, its potential for use with ED remain unexplored. The present study proposed to characterize a new experimental model for ED, using the D-(+)-Galactose aging model. For the experiments, the animals were randomly divided into three groups receiving: vehicle (CTL), D-galactose 150 mg/kg (DGAL), and D-(+)-galactose 150 mg/Kg + sildenafil 1.5 mg/Kg (DGAL+SD1.5) being administered daily for a period of eight weeks. All of the experimental protocols were previously approved by the Ethics Committee on the Use of Animals at the Federal University of Paraíba n° 9706070319. During the treatment, we analyzed physical, molecular, and physiological aspects related to the aging process and implicated in the development of ED. Our findings demonstrate for the first time that D-(+)-Galactose-induced aging represents a suitable experimental model for ED assessment. This was evidenced by an observed hyper-contractility in corpora cavernosa, significant endothelial dysfunction, increased ROS levels, an increase in cavernous tissue senescence, and the loss of essential penile erectile components.
Topics: Aging; Animals; Disease Models, Animal; Electric Stimulation; Erectile Dysfunction; Galactose; Male; Penile Erection; Penis; Rats; Rats, Wistar; Reactive Oxygen Species; Sildenafil Citrate
PubMed: 33857158
DOI: 10.1371/journal.pone.0249487 -
European Urology Focus Jan 2023Current noninvasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Although these therapies... (Review)
Review
Current noninvasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Although these therapies work well for many, some patients experience side effects or are unsatisfied with these therapeutic modalities. Restorative therapies are the newest frontier for ED treatments and are focused on regenerating injured tissue and delivering a possible "cure". Stem cell therapy is a regenerative treatment aimed at restoring normal erectile physiology and curing ED. It is promising in cell-based and animal studies and has now been studied in humans. Although the clinical results are not robust, future research may shed more light on the efficacy of this treatment for ED. PATIENT SUMMARY: Stem cell therapy is a promising regenerative treatment for erectile dysfunction, but the clinical results are not robust. It is currently considered an experimental treatment and should not be used outside a clinical trial setting.
Topics: Male; Animals; Humans; Erectile Dysfunction; Penile Erection; Cell- and Tissue-Based Therapy
PubMed: 36396562
DOI: 10.1016/j.euf.2022.11.009 -
Korean Journal of Urology Oct 2014Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive... (Review)
Review
PURPOSE
Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive agents can carry a serious risk of priapism. Risk factors include young age, good baseline erectile function, and no coronary artery disease. In addition, patients with Peyronie's disease undergoing PDDU in an outpatient setting are at increased risk given the inability to predict optimal dosing. The present study was conducted to provide support for a standard protocol of early administration of phenylephrine in patients with a sustained erection after diagnostic intracavernosal injection of vasoactive agents to prevent the deleterious effects of iatrogenic priapism.
MATERIALS AND METHODS
This was a retrospective review of Peyronie's disease patients who received phenylephrine reversal after intracavernosal alprostadil (prostaglandin E1) administration to look at the priapism rate. Safety was determined on the basis of adverse events reported by subjects and efficacy was determined on the basis of the rate of priapism following intervention.
RESULTS
Patients with Peyronie's disease only had better hemodynamic values on PDDU than did patients with Peyronie's disease and erectile dysfunction. All of the patients receiving prophylactic phenylephrine had complete detumescence of erections without adverse events, including no priapism cases.
CONCLUSIONS
The reversal of erections with phenylephrine after intracavernosal injections of alprostadil to prevent iatrogenic priapism can be effective without increased adverse effects.
Topics: Alprostadil; Drug Evaluation; Humans; Male; Middle Aged; Penile Erection; Penile Induration; Phenylephrine; Pilot Projects; Priapism; Retrospective Studies; Ultrasonography, Doppler, Duplex; Vasoconstrictor Agents; Vasodilator Agents
PubMed: 25324950
DOI: 10.4111/kju.2014.55.10.665