Maintenance Of Erection Research Articles

Fiber counts and architecture of the human dorsal penile nerve

The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human penis differs from the penes of other hominids. The lack of a baculum makes the human penis dependent on erectile tissue, which is under control of neural signals activated by tactile stimulation. Accordingly, the penile sensory innervation is crucial for human sexual behavior. To clarify penile innervation, we analyzed the architecture of the dorsal penile nerve of five male subjects who donated their body. We stained the sensory fibers in the penile dorsal nerve with anti-neurofilament H antibody, and identified myelinated axons with Luxol fast blue staining. Furthermore, we visualized nerve bundles as they travel along the shaft of the penis by performing microfocus computed tomography scans after counterstaining penes with iodine. Our results show that the dorsal penile nerve is organized in 25–45 loosely packed nerve bundles, running mediodorsally in the shaft of the penis. This organization corresponds to that in penes of other mammalian species, but differs from the organization of the other peripheral sensory nerves. Around half of the dorsal penile nerve fibers were myelinated and a human hemipenis contained a total of 8290 ± 2553 (mean ± SD) axons. Thus, the number of sensory axons in the human dorsal penile nerve is higher than in other species described so far. The large fraction of unmyelinated nerve fibers suggests that the conduction speed is not a crucial aspect of penile sensory transmission.

Indicators of questionnaires of the International index of erectile function-5 (MIEF-5) of men injured as a result of hostilities

The modern scientific understanding of erectile dysfunction indicates the predominant secondary nature of sexual disorders in relation to the diseases that cause them. This largely applies to male victims of hostilities. The basis of the work was the results of a survey of 298 men injured as a result of combat operations (shrapnel and bullet wounds) using the International Index of Erectile Function-5 (MIEF-5) questionnaires. The research group was divided into two: men aged 20–39 years (group 1) and men aged 40–53 years (group 2). The control group consisted of 48 practically healthy men without complaints of sexual dysfunction or cardiac, neurological or endocrinological pathology. Among the men of the control group were 30 men aged 20–39 years (group 3) and 18 men aged 40–60 years (group 4). It is shown that 196 men of the 1st group aged 20–39 years have a mild form of erectile dysfunction (ED) where a total score was 19.57 ± 0.44. 102 men of the 2nd group aged 40–53 years also had a mild form of ED, but the total score was much lower as well as 17.94 ± 0.41. The indicators of individual 5 components of male sexual function and the erection hardness scale were also lower in patients of the 2nd group. The ED-MIEF-5 domain decreases most significantly with the severity of ED. All domains of the MIEF are significantly reduced in ED compared to a healthy group of respondents, but there is no differentiation according to the severity of ED. That is, with ED of any severity, all other sexual functions simultaneously suffer as well as sexual desire, confidence in erection, firmness and maintenance of erection, pleasure from sexual intercourse and sexual life.

Ethno- Medicinal Properties of Glycyrrhiza Glabra L. (Licorice): A Mini Review

Plants have long been valued for their medicinal properties. The secret to efficient treatment is finding the right herb. The purpose of this review is to provide an updated overview of Glycyrrhiza glabra L., “the guardian of herbs” regarding its traditional uses, phytochemistry, and emphasizing the relevance of a few key characteristics of this plant. This review covers a combination of all aspects from an aphrodisiac point of view that were missed by previous articles. This article is presented to include all of the most recent information on its phytochemical and pharmacological effects, which were investigated using a variety of approaches. The plant can be a suitable candidate to manage the long fought erectile dysfunction in men. The extract and the constituents have been found effective in inducing NO signaling pathway that has beneficial effects in initiation and maintenance of erection. It is an age-old plant that belongs to the family Fabaceae. G. glabra (Licorice) has been used in folk medicine all over the world for its ethnomedicinal characteristics, and has historically been recognized as a preventative treatment for stomach ulcers, according to pharmacological research. It comprises a wide range of biological actions, including antibacterial, anti-inflammatory, antiviral, antioxidant, as well as others, for which it has been used to treat a variety of disorders ranging from simple cough to hepatitis, as well as more serious conditions like SARS and cancers. This study presents a critical, and thorough assessment of the current understanding of G. glabra composition and therapeutic potential. This article concludes that G. glabra is actually a potent herb that can cure almost all illnesses. ., , ,

A novel approach to treating erectile dysfunction with a light-controlled nitric oxide donor

It has long been known that nitric oxide (NO) is involved in the initiation and maintenance of erection. For this reason, NO supplementation has been considered a useful target for the treatment of erectile dysfunction (ED), and many studies have been conducted. However, to date, no compounds have been launched for a variety of reasons. One of the reasons is the systemic adverse reactions. In order to solve this problem, we focused on light-controlled NO donors and investigate their potential application in ED treatment. Light-controlled NO donors have three main characteristics: first, they release NO only at the site of light irradiation, second, they release NO only during the time of light irradiation, and third, the amount of NO released can be controlled according to the light intensity. These features suggest that light-responsive NO donors may be useful for ED therapy. Our group has been working on the development of light-controlled NO donors, and has so far developed the blue light-controlled NO donor "NOBL-1", the yellowish-green light-controlled NO donor "NO-Rosa", and the red light-controlled NO donor "NORD-1". Our recent studies have shown that NORD-1 and red light can enhance the erectile response in rats at the in vivo level. Next, we examined the effects of NORD-1 and red light using a neurogenic ED model, which is believed to be less effective than existing ED drugs. The results showed that red light irradiation after NORD-1 administration enhanced the erectile response and improved ED in the neurogenic ED model. These results suggest that NORD-1, a light-controlled NO donor, and red light can enhance the erectile response in rats and may have potential as an ED drug. Although optimization of the compound is essential, it is expected that a new therapeutic approach called photobiotherapy for ED will be developed in the future.

Assessment of Female Sexual Dysfunction and Erectile Dysfunction and Its Association with Lower Urinary Tract Symptoms in Women and Men Over 18 Years Old: Results From the COBaLT Study

BackgroundFemale sexual dysfunction and erectile dysfunction (FSD/ED) have been linked with lower urinary tract symptoms (LUTS), from both epidemiological data and basic research studies, but few studies have been conducted in Latin America addressing these issues and most of them do not include the young population. AimTo determine the prevalence of FSD/ED and its association with LUTS in Colombia. MethodsSub-analysis of a cross-sectional, population-based study conducted in subjects ≥18 years old to evaluate LUTS/OAB. The estimated sample size was 1,054. ED was defined as ≤21 points in the SHIM and FSD as ≤19 in the FSFI-6. For LUTS/OAB, we used the 2002 ICS and 2010 IUGA/ICS definitions and validated questionnaires. Descriptive and inferential statistics were employed. OutcomesPrevalence of FSD/ED and association of FSD/ED and LUTS. ResultsWe included 1,060 participants; the median age was 40 (IQR 27–54) years. Fifty-seven (11.4%) men and 182 (32.7%) women were sexually inactive. The prevalence of FSD/ED in sexually active participants was 47% (men 52.9%, women 38.9%). The most common FSD/ED symptoms were diminished/absent lubrication in women (42%) and diminished erection maintenance after penetration in men (13%). Individuals with FSD/ED had higher rates of various LUTS. The multivariable logistic regression model found that the city of residence (OR = 0.4, 95% CI 0.2–0.9), diabetes mellitus (DM) (OR = 8.4, 95% CI 1.4–48.7), menopause (OR=3.5, 95% CI 1.9–6.2), urge urinary incontinence (UUI) (OR=1.9, 95% CI 1.1–3.3) and nocturia ≥2 (OR = 2.2, 95% CI 1.2–4.2) were associated with FSD. In men, age 40–59 (OR = 2.3, 95% CI 1.4–3.7) and ≥60 (OR = 5.5, 95% CI 2.4–12.5), the city of residence (OR = 0.2, 95% CI 0.1–0.3), less than a high-school diploma vs higher education (OR = 2.0, 95% CI 1.2–3.2), depression (OR = 4.6, 95% CI 1.8–11.5), UUI (OR = 3.2, 95% CI 1.1–10.2) and feeling of incomplete bladder emptying (OR = 2.1, 95% CI 1.3–3.5) were associated with ED. Clinical ImplicationsThis study underlines the importance of assessing LUTS in women and men of all affected age groups who present with symptoms of FSD/ED and vice versa, which could help achieve a better approach for these patients. Strengths & LimitationsThis is the first study in Colombia and one of the few in Latin America that addresses both FSD/ED and LUTS in men and women aged 18 years and older. Limitations include being a sub-analysis of a study aiming to determine the prevalence of LUTS/OAB and not FSD/ED. ConclusionsRegardless of age, LUTS were observed more frequently in patients with FSD/ED. Various LUTS were associated with FSD/ED.Bravo-Balado A, Trujillo CG, Caicedo JI, et al. Assessment of Female Sexual Dysfunction and Erectile Dysfunction and Its Association with Lower Urinary Tract Symptoms in Women and Men Over 18 Years Old: Results From the COBaLT Study. J Sex Med 2021;18:1065–1074.

Epidemiology of erectile dysfunction: A cross-sectional web-based survey conducted in an Indonesian national referral hospital

Background: Many epidemiological studies have demonstrated a high prevalence of erectile dysfunction (ED) in different parts of the world. The objective of the present study was to establish the prevalence of ED in a healthy population from Indonesia and risk factors associated with ED. Methods: We performed a cross-sectional study to estimate the prevalence of erectile dysfunction in relatively healthy males in Jakarta that aged 20 to 80 years old. This cross-sectional study utilizes a web-based survey containing a translated version of The International Index of Erectile Function (IIEF-5) in Indonesian. Sexual domain functions in the IIEF-5 include 4 domains of erectile function starting from erection confidence, erection firmness, erection maintenance and sexual satisfaction. Results: The mean age of respondents is 38.7±12.6 years old. Most of the respondents were married (77.2%), had completed or undertaking tertiary education (66.3%) and worked in privately established companies (35.7%). The prevalence of ED was 35.6% (22.3% mild, 13.7% mild to moderate, 3.1% moderate and 0.8% severe). The prevalence of ED ranges from 6.5% in the 20-29 year old group, to as high as 88.0% in respondents aged 60 years old and above. Age, hypertension, stroke, history of heart disease, diabetes, kidney disease, history of prostate operations and interpersonal stress are significantly associated with ED (p-value = <0.001, <0.001, 0.015 0.000, 0.01, 0.002, <0.001 and 0.022 respectively). Conclusion: The prevalence of ED in Indonesia is about 35.6%. The prevalence of ED in this study ranges from 6.5% to as high as 88.0%. Age, hypertension, stroke, history of heart disease, diabetes, kidney disease, history of prostate operation and interpersonal stress are significantly associated with ED.

1115 - Prevalence of sexual dysfunction and its association with lower urinary tract symptoms in men and women over 18 years old: Results from the Colombian Overactive Bladder and Lower urinary Tract symptoms (COBaLT) study

Introduction & Objectives: There is an age-independent association between sexual dysfunction (SD) and LUTS. Few studies have been conducted in Latin America addressing these issues. We aim to determine the prevalence of SD and its association with LUTS in Colombia. Materials & Methods: This is a sub-analysis of a cross-sectional, population-based study conducted in subjects ≥18 years old to evaluate LUTS and overactive bladder (OAB). A sample size of 1,054 subjects was estimated (prevalence of LUTS/OAB 15%, CI 95%, statistical power 80%, precision 3%). We used a multi-stage probabilistic sampling technique to randomly select individuals in the community. SD was defined as ≤21 points in the SHIM and ≤19 in the FSFI-6. For LUTS, we used the 2002 ICS definitions and validated questionnaires. Descriptive and inferential statistics were employed. Results: We included 1,060 participants. Sixty-three (12%) men and 175 (33%) women were sexually inactive. The prevalence of SD was 47% (men 53%, women 39%). The most common SD symptoms were diminished erection maintenance after penetration in men (13%) and poor lubrication in women (43%). Individuals with SD had higher rates of LUTS (Figure 1). Patients with moderate-to-severe LUTS had lower sexual satisfaction rates (men 89% vs 95%, women 72% vs 88%). The multivariate logistic regression model found that diabetes (DM), menopause, urge urinary incontinence (UUI) and nocturia>2 were associated with SD in women. In men, age, depression, high-school education or less and LUTS were associated with SD (Table 1).

Importance of Kegel Exercises for Male and Female Sexuality and Prevention of Vaginismus

The superficial perineal muscles have an important function on female and male sexual response cycle. Understand the importance of Kegel exercises in male and female sexuality. Review of the literature. The erection of male and female erectile organs consists of three phases: a) Latent b) Turgid c) Rigid o muscular Perineal muscles are innervated by branches of the pudendal nerve which originate from Onuf’s nucleus located in the sacral spinal cord. The tonic contraction of ischiocavernosum muscles during erection is necessary for the rigidity of penis. This is necessary not only for that, but also for the maintenance of erection. Ejaculation includes two phases: ... Ejecting of the semen in jets is caused by the rhythmic contraction of the bulbocavernosus muscle. In elderly men, ejaculation takes place with less strength or without squirting. Immediately after the expulsion phase male enters in a post-ejaculatory refractory period. Age affects the recovery time: as a man grows older, the refractory period increases. Vaginismus is characterized by a reflex contraction of the sphincter of vulvo-vaginal orifice. The bulbocavernosus muscles are implicated in inferior vaginismus, while the pubovaginalis muscle is responsible for superior vaginismus. Kegel exercises allow the contraction of pubovaginalis and puborectalis muscles, and, as well as perineal muscles especially superficial ones.

In adult men with diabetes and erectile dysfunction, does a PDE-5 inhibitor improve sexual function?

EVIDENCE-BASED ANSWER Yes. PDE-5 inhibitors significantly improve frequency of vaginal penetration, maintenance of erection to completion of intercourse, and percentage of successful intercourse attempts in diabetic men with erectile dysfunction when compared with placebo (SOR: A, systematic review and meta-analysis of RCTs, single high-quality RCT).

Efficacy and Safety of Sildenafil by Age in Men With Erectile Dysfunction.

Sildenafil, an oral phosphodiesterase type 5 inhibitor, has been extensively investigated for the treatment of erectile dysfunction in randomized controlled trials. To assess the efficacy and safety of sildenafil vs placebo according to age subgroups (<65, 65-74, and ≥75years) in 11,364 men with erectile dysfunction using pooled data from 48 randomized, double-blinded, placebo-controlled, parallel-group, flexible-dose trials. Most trials had a 12-week treatment duration. The starting sildenafil dose was 50 mg, taken 1 hour before sexual activity, with subsequent adjustment to 100 or 25 mg based on efficacy and safety. Men taking nitrate therapy or nitric oxide donors and men with severe cardiac failure, unstable angina, or recent stroke or myocardial infarction were excluded. Efficacy analyses included all subjects with baseline and at least one postrandomization evaluation. Safety analyses included subjects who received study medication. The International Index of Erectile Function and a global assessment question ("Did the treatment improve your erections?"). Mean International Index of Erectile Function scores for question 3 (frequency of penetration), question 4 (maintenance of erections after penetration), and the erectile function domain were statistically significantly improved with sildenafil vs placebo for each age subgroup; orgasmic function, intercourse satisfaction, sexual desire, and overall satisfaction domain scores also were statistically significantly improved with sildenafil vs placebo. The percentage of men reporting improved erections on the global assessment question was statistically significantly higher with sildenafil vs placebo for all age subgroups; the percentage with sildenafil tended to decrease with increasing age (<65 years, 80%; 65-74 years, 69%; ≥75 years, 59%). The most common adverse events with sildenafil were headache and flushing in each age subgroup. Sildenafil is an effective and well-tolerated treatment for erectile dysfunction regardless of patient age, including men at least 75 years old.

Male Sexual Dysfunction

Normal male sexual function requires complex interactions among psychological, neurologic, hormonal, and vascular systems. Under the influence of proper stimulation, the acquisition and maintenance of a penile erection occur. Male sexual dysfunction includes erectile dysfunction (ED), impaired libido, and abnormal ejaculation, which occur due to aberrations in normal male sexual response. Estimates suggest a prevalence of approximately 10 to 20% in the adult male population. Thus, sexual dysfunction is a common problem in this country. This chapter focuses on several key, common components of male sexual dysfunction: namely, ED, premature ejaculation (PE), and Peyronie disease (PD). Figures include management algorithms, a graph depicting distribution of intravaginal ejaculation latency time values in a random cohort of men, and a Sexual Health Inventory for Men (SHIM). Tables list medications associated with ED, oral therapies for the treatment of PD, intralesional therapies for PD, indications for surgical correction of PD, recommended questions to establish the diagnosis of PE, treatment options for PE, and causes of delayed ejaculation, anejaculation, and anorgasmia.This chapter contains 5 highly rendered figures, 8 tables, 116 references, 1 teaching slide set, and 5 MCQs.

Vardenafil demonstrates first-dose success and reliability of penetration and maintenance of erection in men with erectile dysfunction — RELY-II

Vardenafil has been shown to be efficacious in patients with erectile dysfunction (ED). We evaluated first-dose and repeat-dose response to vardenafil 20 mg. This randomized, placebo-controlled study consisted of a 4-week, treatment-free run-in phase; a 1-week, open-label challenge phase; and a 12-week, double-blind treatment phase. Primary efficacy was assessed in terms of reliability of insertion based on dose as measured by the Sexual Encounter Profile question 2 (SEP2). We assessed safety by evaluating adverse events (AEs). Baseline patient characteristics in the 2 treatment groups were similar. The most common comorbidities were hypertension (41%), dyslipidemia (28%) and diabetes mellitus (24%). Of the 573 patients receiving the 20-mg vardenafil challenge dose, 464 (81%) achieved first-time successful penetration (SEP2), and 401 (70%) reported successful erection maintenance (SEP3). Patients receiving vardenafil 20 mg had statistically (p < 0.001) and clinically superior SEP2 rates (85%) through weeks 0-12, compared with patients receiving placebo (45%). The increase in reliability of insertion was seen within the first 4 weeks of treatment. Vardenafil therapy was statistically (p < 0.001) and clinically superior to placebo for all secondary efficacy end points as well. Most AEs associated with vardenafil were mild to moderate, with headache, flushing and nasal congestion most frequently reported. Vardenafil 20 mg had a high first-dose success rate for both SEP2 (81%) and SEP3 (70%); this was maintained through to the study end point (85% for SEP2 and 78% for SEP3). These findings were achieved in men with frequently associated comorbidities including hypertension, dyslipidemia and diabetes.

Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection

Nitric oxide (NO) generated by neuronal NO synthase (nNOS) initiates penile erection, but has not been thought to participate in the sustained erection required for normal sexual performance. We now show that cAMP-dependent phosphorylation of nNOS mediates erectile physiology, including sustained erection. nNOS is phosphorylated by cAMP-dependent protein kinase (PKA) at serine(S)1412. Electrical stimulation of the penile innervation increases S1412 phosphorylation that is blocked by PKA inhibitors but not by PI3-kinase/Akt inhibitors. Stimulation of cAMP formation by forskolin also activates nNOS phosphorylation. Sustained penile erection elicited by either intracavernous forskolin injection, or augmented by forskolin during cavernous nerve electrical stimulation, is prevented by the NOS inhibitor L-NAME or in nNOS-deleted mice. Thus, nNOS mediates both initiation and maintenance of penile erection, implying unique approaches for treating erectile dysfunction.

Adenosine Signaling

The erectile status of penile tissue is governed largely by the tone of cavernosal smooth muscle cells, which is determined by the balance of vascular relaxants and constrictors. Vascular relaxants play a key role in regulating the tone of cavernosal smooth muscle and thus the initiation and maintenance of penile erection. Early studies drew attention to the potential role of adenosine signaling in this process. However, the serendipitous discovery of the effect of sildenafil on erectile physiology drew more attention toward nitric oxide (NO) as a vasodilator in the process of penile erection, and a recently discovered, unexpected erectile phenotype of adenosine deaminase-deficient mice reemphasizes the importance of adenosine as a key regulatory of erectile status. Adenosine, like NO, is a potent and short-lived vasorelaxant that functions via cyclic nucleotide second messenger signaling to promote smooth muscle relaxation. Recent studies reviewed here show that adenosine functions to relax the corpus cavernosum and promote penile erection. Excess adenosine in penile tissue contributes to the disorder called priapism, and impaired adenosine signaling is associated with erectile dysfunction. More recent research summarized in this review reveals that adenosine functions as a key endogenous vasodilator in the initiation and maintenance of normal penile erection. This new insight highlights adenosine signaling pathways operating in penile tissue as significant therapeutic targets for the treatment of erectile disorders.

1143 A REAL-TIME MOTION ANALYSIS OF PENILE ERECTION WITH TURBO-FLASH MR IMAGING SYSTEM

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Evaluation I1 Apr 20121143 A REAL-TIME MOTION ANALYSIS OF PENILE ERECTION WITH TURBO-FLASH MR IMAGING SYSTEM Jintetsu Soh, Noriyuki Kanemitsu, Atsushi Ochiai, Yasuyuki Naitoh, Yoshio Naya, kazumi Kamoi, Akihiro Kawauchi, and Tsuneharu Miki Jintetsu SohJintetsu Soh Kyoto, Japan More articles by this author , Noriyuki KanemitsuNoriyuki Kanemitsu Kyoto, Japan More articles by this author , Atsushi OchiaiAtsushi Ochiai Kyoto, Japan More articles by this author , Yasuyuki NaitohYasuyuki Naitoh Kyoto, Japan More articles by this author , Yoshio NayaYoshio Naya Kyoto, Japan More articles by this author , kazumi Kamoikazumi Kamoi Kyoto, Japan More articles by this author , Akihiro KawauchiAkihiro Kawauchi Kyoto, Japan More articles by this author , and Tsuneharu MikiTsuneharu Miki Kyoto, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1253AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There have been no reports of real-time image analysis in the corpus cavernosum from the initiation to the end of erection without artificial induction. Using Turbo-FLASH MRI, we were able to obtain a series of high resolution images through tumescence, maintenance and detumescence phases of erection. The aim of this study was to analyze the dynamic morphological changes in the penis during a normal erection. METHODS The participants in this study included 5 healthy volunteers without experience of erectile dysfunction. Ages ranged from 22 to 47 (median 33) years. IIEF-5 score ranged from 22 to 25 (median 23) points. Audio-visual sexual stimulation was used to induce erection. MRI was conducted using Siemens MAGNETOM Sonata 1.5T with body array and spine coils. True-FISP sequence was used with conditions of TR: 4.38 ms, TE: 2.19 ms, and scan time: 0.85 sec/slice. Using dynamic images, the volume of the corpus cavernosum within the tunica albuginea were consecutively calculated by measuring length, width, and thickness in sagittal and coronal section during all phases of a normal erection (Figure 1). Morphological changes were evaluated with indices including the maximum changes in the volume between latent and full erection phases of the corpus cavernosum as well as the consecutive volume increase rate per second. RESULTS From initiation to completion of erection, range of time required from 110 to 120 (median 115) seconds, changes in volume of corpus cavernosum ranged from 28 to 35 (median 32) ml. Maximum volume increase rate ranged from0.5 to 0.8 (median 0.66) ml/sec (Figure 2). CONCLUSIONS By using Turbo-FLASH MRI, dynamic phases of a normal erection can be analyzed calculating the maximum changes in volume of corpus cavernosum as well as volume increase rate per second. Further study is warranted to prove these novel parameters as a measurement of vascular function. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e463-e464 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jintetsu Soh Kyoto, Japan More articles by this author Noriyuki Kanemitsu Kyoto, Japan More articles by this author Atsushi Ochiai Kyoto, Japan More articles by this author Yasuyuki Naitoh Kyoto, Japan More articles by this author Yoshio Naya Kyoto, Japan More articles by this author kazumi Kamoi Kyoto, Japan More articles by this author Akihiro Kawauchi Kyoto, Japan More articles by this author Tsuneharu Miki Kyoto, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The relaxant effect of methanolic extract of yohimbe bark (&amp;lt;i&amp;gt;Pausinystalia yohimbe&amp;lt;/i&amp;gt;) on rabbit corpus cavernosum smooth muscles

Background: Development and maintenance of penile erection requires the relaxation of corpus cavernosum smooth muscle (CCSM) cells and it is essentially mediated by nitric oxide (NO). Pausinystalia yohimbe bark is traditionally used for the treatment of erectile dysfunction (ED). Objectives and Methods: This study aimed to evaluate the effects of the methanolic extract of P. yohimbe bark (10 mg/ml) on isolated rabbit corpus cavernosum smooth muscle (CCSM). Results: Methanolic extract of P. yohimbe bark blocked contractions in CCSM induced by adrenergic agonists, through facilitating NO release from the endothelial cells. Conclusion: The obtained results revealed that, methanolic extract of P. yohimbe bark caused relaxation of CCSM that validates its traditional aphrodisiac property, thus it could be used to initiate and maintain erection in cases of erectile dysfunction.

Focal cryotherapy for localized prostate cancer: a report from the national Cryo On‐Line Database (COLD) Registry

Study Type – Therapy (cohort)Level of Evidence 2bWhat's known on the subject? and What does the study add?Selective destruction of targeted prostate tissue is now technically feasible. Much has been theorized but little is known about the proper patient selection or treatment outcomes to determine if this organ preserving approach to prostate cancer has merit for further study and diffusion into wider practice.Herein we present the largest retrospective registry report of men treated with sub‐total prostate cryotherapy in order to begin to understand how this treatment is being applied despite the paucity of data.OBJECTIVES To identify recent trends in focal cryotherapy from a prospectively maintained treatment registry. To describe treatment outcomes after uncontrolled application of focally ablative techniques within community practice. MATERIALS AND METHODS We conducted an analysis of the COLD Registry to identify patients treated with partial gland prostate cryoablation between 1997 and 2007. Preoperative characteristics and postoperative cancer‐specific and functional outcomes were assembled for analysis. RESULTS The COLD Registry contained information for 5853 patients and focal cryotherapy was the codified procedure in 1160 patients (19.8%). A dramatic increase in focal treatments was observed, from 46 in 1999 to 567 in 2005 (P &lt; 0.01). The biochemical recurrence‐free rate (ASTRO definition) at 36 months was 75.7%. Prostate biopsy, performed in 164/1160 of patients (14.1%), was positive in 43 (26.3%) of those suspected of cancer recurrence, but in only 3.7% (43/1160) of treated patients. Urinary continence (defined as use of 0 pads) was 98.4%. Maintenance of spontaneous erections was 58.1%. Prolonged urinary retention (&gt;30 days) occurred in six (1.1%) patients. Rectourethral fistula was observed in one (0.1%) patient. CONCLUSIONS Focal cryoablation is increasingly used for selected patients with prostate cancer. Oncological efficacy in the present series appears similar to that of whole‐gland cryoablation. The impact of focal cryoablation on urinary, sexual and bowel function appears to be less than that of radical therapies, although preservation of sexual function is not as high as might be expected.

Improvement in Sexual Quality of Life of the Female Partner Following Vardenafil Treatment of Men with Erectile Dysfunction: A Randomized, Double‐Blind, Placebo‐Controlled Study

Erectile dysfunction (ED) impacts on both members of the couple. Female partners of men with ED are more likely to report reduced sexual quality of life than women whose partners do not have ED. To assess vardenafil efficacy in men with ED and determine the effects of treatment on their female partner's sexual quality of life. Study participants comprised men aged 18-64 years with ED and their female partners. Eligible men had ED of ≥6 months' duration and a female partner who was motivated to support their ED treatment. Eligible women had a total Female Sexual Function Index score >23.55, indicating absence of significant sexual dysfunction. Following a 4-week screening period, men were randomized to treatment with vardenafil 10 mg or placebo, which could be titrated to 20 or 5 mg after 4 weeks. Primary efficacy variables were question 3 of the Sexual Encounter Profile questionnaire (SEP3) and the quality-of-life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL). The intent-to-treat population included 343 couples, with 168 and 175 men receiving vardenafil or placebo, respectively. Vardenafil treatment significantly improved both erection maintenance and the female partners' sexual quality of life. Least squares (LS) mean SEP3 overall success rates after 12 weeks of treatment were 9.5 (baseline) vs. 67.2 (week 12) and 12.4 (baseline) vs. 24.2 (week 12) in the vardenafil and placebo groups, respectively (P < 0.0001). In female partners, LS mean mSLQQ-QOL scores were 28.8 (baseline) vs. 68.2 (last observation carried forward [LOCF]) in the vardenafil group and 24.6 (baseline) vs. 40.5 (LOCF) in the placebo group (P < 0.0001). Vardenafil treatment of men with ED improved both their erectile function and the sexual quality of life of their female partners.

Impaired Erectile Function in CD73‐deficient Mice with Reduced Endogenous Penile Adenosine Production

Adenosine has been implicated in normal and abnormal penile erection. However, a direct role of endogenous adenosine in erectile physiology and pathology has not been established. To determine the functional role of endogenous adenosine production in erectile function. CD73-deficient mice (CD73(-/-)) and age-matched wild-type (WT) mice were used. Some WT mice were treated with alpha, beta-methylene adenosine diphosphate (ADP) (APCP), a CD73-specific inhibitor. High-performance liquid chromatography was used to measure adenosine levels in mouse penile tissues. In vivo assessment of intracorporal pressure (ICP) normalized to mean arterial pressure (MAP) in response to electrical stimulation (ES) of the cavernous nerve was used. The main outcome measures of this study were the in vivo assessment of initiation and maintenance of penile erection in WT mice and mice with deficiency in CD73 (ecto-5'-nucleotidase), a key cell-surface enzyme to produce extracellular adenosine. Endogenous adenosine levels were elevated in the erected state induced by ES of cavernous nerve compared to the flaccid state in WT mice but not in CD73(-/-) mice. At cellular levels, we identified that CD73 was highly expressed in the neuronal, endothelial cells, and vascular smooth muscle cells in mouse penis. Functionally, we found that the ratio of ES-induced ICP to MAP in CD73(-/-) mice was reduced from 0.48 ± 0.03 to 0.33 ± 0.05 and ES-induced slope was reduced from 0.30 ± 0.13 mm Hg/s to 0.15 ± 0.05 mm Hg/s (both P < 0.05). The ratio of ES-induced ICP to MAP in APCP-treated WT mice was reduced from 0.49 ± 0.03 to 0.38 ± 0.06 and ES-induced slope was reduced from 0.29 ± 0.11 mm Hg/s to 0.19 ± 0.04 mm Hg/s (both P < 0.05). Overall, our findings demonstrate that CD73-dependent production of endogenous adenosine plays a direct role in initiation and maintenance of penile erection.

1129 PROTEIN KINASE-A DEPENDENT PHOSPHORYLATION OF NEURONAL NITRIC OXIDE SYNTHASE: NOVEL MECHANISM FOR REGULATION OF NEURONAL NITRIC OXIDE SYNTHASE ACTIVATED PENILE ERECTION

INTRODUCTION AND OBJECTIVES: Penile erection is mediated by nitric oxide (NO) that is formed by both neuronal NO synthase (nNOS) and endothelial NOS (eNOS) in the penis. We have previously shown that eNOS is phosphorylated by protein kinase (PK)B/Akt in response to increased blood flow in the penis, leading to activation of eNOS and maintenance of erection. This study investigates the regulation and mechanism of nNOS activation by phosphorylation using rodent models of penile erection. METHODS: Male Sprague-Dawley rats (300–375g) or 8–10 weeks old C57BL6/J (wild type, wt) and nNOS knockout (ko) mice were used. Penile erection was monitored as intracavernous pressure (ICP) via a needle inserted to right corpus cavernosum. For electricallyinduced penile erection studies, cavernous nerve (CN) or major pelvic ganglion (MPG) was stimulated at various stimulation parameters and durations. Inhibition of nNOS phosphorylation was tested after perigangliar injection of Akt inhibitors [LY294002 (LY, 50 uM) and wortmannin (WT, 1uM)] and PKA inhibitors [H-89 (30 uM) and PKA inhibitor peptide (PKA-I, 60uM)]. For pharmacologically-induced erections, papaverine (1.5mg), forskolin (FSK, 0.25-5ug) or deoxy-FSK (dFSK, 0.25-5ug) were injected intracavernosally (ic) or directly beneath the MPG. Some mice were pretreated with L-NAME (100mg/kg, ip) 30 min prior to FSK injection. MPG and penis from various experiments were collected and processed for phospho(P)-protein analysis with western blot or for immunohistochemistry. RESULTS: P-specific antibody to nNOS-S1412 (homologous to S1177 in eNOS) revealed a 5–10 fold increase in P-nNOS-S1412 after CN electrical stimulation (ES) in rat MPG (p 0.05). nNOS-S1412 phosphorylation was voltageand time-dependent and sustained for 3–5 min after ES. Papaverine, a direct vasorelaxant, injected ic stimulated P-eNOS-S1177 in the rat penis, but did not increase P-nNOSS1412. Perigangliar injection of FSK, an activator of PKA, increased P-nNOS-S1412, while Akt inhibitors, WT and LY, had no effect. Furthermore, ic injection of FSK dose-dependently increased ICP in wt mice (p 0.05) while d-FSK, an inactive analog of FSK, had no effect. Pretreatment with L-NAME (100mg/kg, ip) abolished the effect of FSK in wt. In nNOS-ko mice, the ICP increase after FSK injection was 30–50% of the wt response. CONCLUSIONS: Our data suggests a novel mechanism of nNOS activation which involves PKA-dependent phosphorylation and reveals differentially regulated pools of NOS activity mediating penile erection.