Restoration of erectile function by a combination of antiapoptosis by JNK inhibitor and preservation of smooth muscle or endothelium by hepatocyte growth factor in a rat model of cavernous nerve injury.

BACKGROUND: Because of structural alterations in the corpus cavernosum after radical prostatectomy (RP), post-RP erectile dysfunction remains a very difficult condition to treat. We aimed to determine if the combined administration of a Jun-amino terminal kinase (JNK) inhibitor and hepatocyte growth factor (HGF) in the immediate post-injury period would restore erectile function by antiapoptotic and pro-regenerative effects through the rectification of molecular pathways related to the structural integrity of the penis in a rat model of bilateral cavernosal nerve crush injury (CNCI). METHODS: A total of 70 rats were divided into five groups: Sham surgery (S), CNCI (I), and once-daily intraperitoneal administration of 10.0 mg/kg JNK inhibitor + twice-weekly intracavernosal administration of low-dose (2.1 µg), medium-dose (4.2 µg), or high-dose (8.4 µg) HGF (I + J + LH or I + J + MH or I + J + HH, respectively) in the immediate post-injury period. Erectile responses to electrostimulation (1.0, 3.0, and 5.0 V), histological staining, caspase-3 activity, and Western blotting were evaluated 9 days after surgery. RESULTS: Group I showed lower intracavernosal pressure (ICP)/mean arterial pressure (MAP) after stimulation at each voltage, lower area under the curve (AUC)/MAP after stimulation at each voltage, less smooth muscle (SM) content, a lower SM/collagen ratio, higher caspase-3 activity, increased cJun phosphorylation, decreased protein expression of PECAM-1, decreased cMet phosphorylation, and decreased endothelial nitric oxide synthase (eNOS) phosphorylation compared to Group S. The SM content, SM/collagen ratio, protein expression of ICP/MAP, or AUC/MAP after stimulation at each voltage in Group I + J + LH were partially restored, despite the normalization of cJun phosphorylation and caspase-3 activity. The ICP/MAP, AUC/MAP, caspase-3 activity, SM content, protein expression of PECAM-1, cJun phosphorylation, cMet phosphorylation, and eNOS phosphorylation in both Groups I + J + MH and I + J + HH were restored to the levels observed in Group S, while the SM/collagen ratio was significantly improved but not completely normalized. CONCLUSIONS: Our data indicated that the combined administration of a JNK inhibitor and medium or high-dose HGF to nerve-injured rats in the immediate post-injury period after CNCI may restore erectile function to a level comparable to the normal level by suppressing cavernosal apoptosis and preserving the integrity of SM or endothelium via rectification of the cJun and cMet/eNOS pathways.

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules.

ETHNOPHARMACOLOGICAL RELEVANCE: Leeches (pinyin name Shui Zhi; Latin scientific name Hirudo; Hirudinea; Hirudinidae) and centipedes (pinyin name Wu Gong; Latin scientific name Scolopendridae; Chilopoda; Scolopendridae) are traditional Chinese medicines, and they belong to the family entomology. A combination of leech and centipede is used as an effective medicine to promote blood circulation and remove blood stasis in traditional Chinese medicine, and "leech-centipede" medicine has been used in many prescriptions to treat diabetic vascular disease, including diabetic erectile dysfunction (DIED). However, its specific mechanism remains unclear and requires in-depth study. AIM OF THE STUDY: This study aimed to investigate the mechanism of "leech-centipede" medicine to improve erectile dysfunction-associated diabetes by detecting PKC pathway-related molecules. MATERIALS AND METHODS: The active ingredients of "leech-centipede" medicine were identified using high performance liquid chromatography (HPLC). Fifty male SPF rats were injected with streptozotocin to induce the DM model. Eight weeks later, the DMED model was validated with apomorphine. The DIED rats were divided into five groups-T,P,DD,DZ, and DG-and were separately treated with tadalafil, pathway inhibitor LY333531 and low-, medium-, and high-dose "leech-centipede" medicine for 8 weeks. After treatment, the blood glucose level was measured, erectile function with apomorphine was assessed, the LOX-1, sE-selectin, sICAM-1, SOD, and MDA in serum was evaluated by enzyme-linked immunosorbent assay, and flow cytometry was performed. After the collection of penile tissue, the related protein and mRNA expression was assessed by Western blotting and PCR, and the tissue and ultrastructure were analysed by HE staining, immunohistochemistry and scanning electron microscopy. RESULTS: After treatment, the erectile function of rats was significantly improved in the T,P,DD,DZ, and DG groups compared with that in the model group. Thus, "leech-centipede" medicine can significantly reduce the levels of LOX-1, sE-selectin, sICAM-1, EMPs and CD62P to protect vascular endothelial function and anti-platelet activation, improving DIED rat erectile function. Additionally, "leech-centipede" medicine can increase SOD expression and decrease MDA expression, reducing the possibility of oxidative stress injury in DIED rats and improving the antioxidant capacity. Moreover, "leech-centipede" therapy can dramatically reduce the protein and mRNA expression of DAG, PKCß, NF-κB, and ICAM-1, improve vascular endothelial injury in DIED rats and inhibit abnormal platelet activation. CONCLUSION: "leech-centipede" medicine can improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protects endothelial function and anti-platelet activation.

Effects of Chaga Medicinal Mushroom Inonotus obliquus (Agaricomycetes) Extracts on NOS-cGMP-PDE5 Pathway in Rat Penile Smooth Muscle Cells.

Some medicinal mushrooms have effects on sexual dysfunctions. Nitric oxide synthase (NOS)-cyclic gua-nosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway is one of the pathophysiological basis of erectile dysfunction (ED). The normal erectile function involves the synthesis of nitric oxide (NO), and the subsequent accumulation of cGMP, whereas cGMP degradation is specifically controlled by PDE5, which promotes corporal smooth muscle cell (SMC) tone and terminates erection. The antioxidant activities of Inonotus obliquus (chaga) water extracts (IO1) and water extraction and alcohol precipitation extracts (IO2) were compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and oxygen radical absorbance capacity (ORAC) method. Three subtypes of NOS (nNOS, iNOS, and eNOS) and PDE5 protein expressions were tested by Western blotting, and cGMP was determined by ELISA on a rat corporal primary SMC. The results revealed that IO2, which had a significantly higher polysaccharide content than IO1, showed a significantly higher ORAC value and a significantly lower half inhibitory concentration for DPPH scavenging activity than IO1. We observed that both IO1 and IO2 increased the expression of eNOS and iNOS significantly compared with the control. Furthermore, when compared with the control, IO1 increased PDE5 expression significantly, while IO2 showed no effect. The different impacts on PDE5 might be the reason that IO2, not IO1, showed significant inducible effect on cGMP compared with the control. This is to our knowledge, the first study exploring the effect of I. obliquus on NOS-cGMP-PDE5 pathway on SMC. The results provide a possible selection of I. obliquus for the treatment of ED.

Fluted pumpkin (Telfairia occidentalis) seed modulates some markers of erectile function in isolated rat's corpus cavernosum: Influence of polyphenol and amino acid constituents.

Pumpkin seeds are often used in traditional medicine in the management of erectile dysfunction. However, there is insufficient information about the possible biochemical rationale behind this practice. Hence, this study investigated the influence of fluted pumpkin seed on critical enzymes involved in erectile function in isolated rats' corpus cavernosum in vitro. The phenolics and amino acid contents of fluted pumpkin seed were determined using HPLC-DAD and GC-PFPD analyses respectively. The aqueous extract of the fluted pumpkin seed significantly (p < .05) scavenged free radicals and inhibited PDE-5, arginase, AChE, and ACE in rats' corpus cavernosum in a concentration-dependent pattern. Quercitrin and luteolin were the most dominant phenolics, while arginine, aspartate, and cysteine were the most aboundant amino acid constituents. The positive modulatory effect of the fluted pumpkin seed on these critical markers of erectile function could be attributed to its polyphenolics and amino acid constituents. PRACTICAL APPLICATIONS: This study brought to limelight the medicinal importance of fluted pumpkin seed in erectile functions. Therefore, this seed could be used as a functional food ingredient in the management of erectile dysfunctions and also in improving erectile functions in men. In addition, the dominant phenolics and amino acid constituents of this seed might be an effective nutraceutical in enhancing erections in men.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum.

Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Activity-Based Training Alters Penile Reflex Responses in a Rat Model of Spinal Cord Injury.

INTRODUCTION: Multisystem functional gains have been reported in males with spinal cord injury (SCI) after undergoing activity-based training (ABT), including increases in scoring of sexual function and reports of improved erectile function. AIM: This study aims to examine the effect of daily 60-minute locomotor training and exercise in general on sexual function in a rat SCI contusion model. METHODS: Male Wistar rats received a T9 contusion SCI. Animals were randomized into 4 groups: a quadrupedal stepping group (SCI + QT), a forelimb-only exercise group (SCI + FT), a non-trained harnessed group (SCI + NT), and a home cage non-trained group (SCI + HC). The 2 non-trained groups were combined (SCI) post hoc. Daily training sessions were 60 minutes in duration for 8 weeks. Urine samples were collected during bi-weekly 24-hour metabolic cage behavioral testing. Latency, numbers of penile dorsiflexion, and glans cupping were recorded during bi-weekly penile dorsiflexion reflex (PDFR) testing. Terminal electromyography (EMG) recordings of the bulbospongiosus muscle (BSM) were recorded in response to stimulation of the dorsal nerve of the penis (DNP). OUTCOMES: ABT after SCI had a significant effect on PDFR, as well as BSM EMG latency and burst duration. RESULTS: SCI causes a significant decrease in the latency to onset of PDFR. After 8 weeks of ABT, SCI + QT animals had a significantly increased latency relative to the post-SCI baseline. BSM EMG response to DNP stimulation had a significantly decreased latency and increase in average and maximum amplitude in SCI + QT animals. SCI animals had a significantly longer burst duration than trained animals. Time between PDFR events, penile dorsiflexion, glans cupping, and urine testosterone were not affected by ABT. CLINICAL IMPLICATIONS: ABT has a positive influence on sexual function and provides a potential therapy to enhance the efficacy of current sexual dysfunction therapies in the male SCI population. STRENGTHS AND LIMITATIONS: Several significant small improvements in sexual function were found in a clinically relevant rat model of SCI using a readily available rehabilitative therapy. The limited findings could reflect insensitivity of the PDFR as a measure of erectile function. CONCLUSIONS: These results indicate that task-specific stepping and/or loading provide sensory input to the spinal cord impacting the neural circuitry responsible for sexual function. Steadman CJ, Hoey RF, Montgomery LR, et al. Activity-Based Training Alters Penile Reflex Responses in a Rat Model of Spinal Cord Injury. J Sex Med 2019; 16:1143-1154.

Effects of combined extracts of Lepidium meyenii and Allium tuberosum Rottl. on erectile dysfunction.

BACKGROUND: Sexual problems are widespread and adversely affect the interpersonal relationships and the quality of life. Currently, synthetic drugs improving sexual function are available, but expenditures for such agents are extremely high. To discover relatively inexpensive, widely available and effective natural drugs, we identified a combined extracts from Lepidium meyenii (maca) root and Allium tuberosum Rottl. (Chinese chive) seed, assessed the effects of this combined extracts on erectile dysfunction, and explored its potential mechanisms. METHODS: The extracts were obtained via supercritical fluid extraction. Male BALB/c mice received doses of extract from single plant or the combined extracts (200 mg/kg) by gastric gavage for 14 d, and Viagra was used as the positive control drug. Sexual behaviour was observed, and concentrations of serum testosterone, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) in serum as well as in penis were measured. In addition, weights of genital organs were also measured. RESULTS: The combined extracts of maca root and Chinese chive seed (1:1, w/w) had a 45-fold increase in macamide content compared with maca extract. It also led to significantly higher ejaculation frequency (P < 0.05) than single extract from maca root or Chinese chive seed, with no corresponding effect on genital indices. In addition, the NO level in serum (P < 0.01) and penis (P < 0.05) increased notably, as well as the level of cGMP in penis (P < 0.05). CONCLUSIONS: The results indicated that the combined extracts produced better synergistic effects on male sexual function than maca extract or Chinese chive extract alone. These positive effects may involve the upregulation of NO and cGMP concentrations in penis.

Novel Concept Enabling an Old Idea: A Flexible Electrode Array to Treat Neurogenic Erectile Dysfunction.

INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement. AIM: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively. METHODS: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system. MAIN OUTCOME MEASURE: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array. RESULTS: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01). CLINICAL IMPLICATIONS: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury. STRENGTH & LIMITATIONS: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice. CONCLUSION: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569.

Endothelial colony forming cells from human umbilical cord blood improved severe erectile dysfunction in obese type II diabetic rats.

AIM: To investigate the effect of intracavernous injection of human umbilical cord blood derived endothelial colony forming cells (HUCB ECFCs) on erectile dysfunction (ED) in Zucker Diabetic Fatty (ZDF) rat model. METHODS: Erectile function was assessed by cavernous nerve electrostimulation in ZDF rats aged 20-28 weeks. Following confirmation of severe ED at the age of 28 weeks, 21 ZDF rats were randomly assigned to three experimental groups: 1 million ECFCs, 2 million ECFCs, and phosphate buffered saline (PBS). Four weeks after intracavernous injection, the efficacy of ECFCs was quantified by intracavernous pressure (ICP) measurement, Masson's trichrome staining, immunohistologic and immunoblot analyses and TUNEL assay. KEY FINDINGS: Intracavernous ECFC administration improved ICP in a dose-dependent manner in comparison to the age-matched PBS group. Functional improvement in ICP was accompanied by a significant restoration of the cavernosal endothelial and smooth muscle cell content and cavernosal nerve function. The percentage eNOS and nNOS positive cavernosal cells, and their respective protein expression levels and nNOS positive cells in the dorsal penile nerve in 2 million ECFCs treated groups were significantly higher than the PBS group. TUNEL stain quantification showed a significant decrease in cavernosal apoptosis following ECFC treatment. SIGNIFICANCE: The results are expected to provide a scientific basis to further study the clinical application of HUCB ECFCs in ameliorating ED in human. CONCLUSIONS: HUCB ECFCs significantly improved severe ED in ZDF rats through improvement of the nerve and endothelium function and restoration of smooth muscle in the cavernosum by overcoming the cavernosal apoptosis.

Dietary supplementation of tiger nut alters biochemical parameters relevant to erectile function in l-NAME treated rats.

Tiger nut tubers have been reportedly used for the treatment of erectile dysfunction (ED) in folk medicine without scientific basis. Hence, this study evaluated the effect of tiger nut on erectile dysfunction by assessing biochemical parameters relevant to ED in male rats by nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) treatment. Rats were divided into five groups (n = 10) each: Control group; l-NAME plus basal diet; l-NAME plus Sildenafil citrate; diet supplemented processed tiger nut (20%) plus l-NAME;diet supplemented raw tiger nut (20%) plus l-NAME. l-NAME pre-treatment (40 mg/kg/day) lasted for 14 days. Arginase, acetycholinesterase (AChE) and adenosine deaminase (ADA) activities as well as nitric oxide levels (NO) in serum, brain and penile tissue were measured. l-NAME increased the activity of arginase, AChE and ADA and reduced NO levels. However, dietary supplementation with tiger nut caused a reduction on the activities of the above enzymes and up regulated nitric oxide levels when compared to the control group. The effect of tiger nut supplemented diet may be said to prevent alterations of the activities of the enzymes relevant in erectile function. Quercetin was revealed to be the most active component of tiger nut tuber by HPLC finger printing.

Effects of aqueous leaf extract of Tridax procumbens on contractile activity of corpus cavernosum in N-nitro-l-arginine methyl ester-induced hypertensive male rats.

OBJECTIVE: This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on contractile activity of corpus cavernosum in N-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive male rats. METHODS: Twenty normal, adult male rats (130-150 g) were divided into four groups of five rats each. Group I (control) was given normal saline (0.6 mL/kg) and group II was given l-NAME (40 mg/kg) for 6 weeks. Groups III and IV also received l-NAME (40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP) (10-9-10-5mol/L) after contraction with phenylephrine (10-7 mol/L) to test for a dose-response effect. Response to potassium and calcium was also measured after cumulatively adding potassium and calcium (10-50 mmol/L) to potassium- and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system. RESULTS: Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and l-NAME-only groups (P < 0.05). Cavernosa strips from ALETP co-treated rats exhibited significant inhibition of contraction in response to phenylephrine, potassium chloride, and calcium chloride (P < 0.05). Relaxation in response to Ach and SNP was also significantly impaired in cavernosa strips from the l-NAME-only treated group (P < 0.05), while ALETP co-treated groups showed enhanced percentage relaxation. CONCLUSION: ALETP treatment of l-NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension.

Acute Ischemia of the Glans Penis after Circumcision Treated with Hyperbaric Therapy and Pentoxifylline: Case Report and Revision of the Literature.

Acute severe ischemia of glans penis after circumcision is a very rare event and, if not treated, can lead to irreversible necrosis with severe consequences such as loss of part of the penis. The possible causes for this condition could be blood-vessel binding or cauterization, dorsal penile nerve block (DPNB), local anesthesia with vasoconstricting agents and wound dressing compression. The aim of the treatment is to provide good blood supply and thus, oxygen delivery to the ischemic penis. The therapeutic options include hyperbaric therapy (HBOT), pentoxifylline (PTX), enoxaparina, iloprost, antiplatelet, corticosteroids and peridural anesthesia. We report the case of a 24-year-old male who developed an acute severe glans penis ischemia after circumcision done under DPNB. The patient was successfully treated with HBOT in combination with PTX.

Penile transplantation as an appropriate response to botched traditional circumcisions in South Africa: an argument against.

Traditional male circumcision is a deeply entrenched cultural practice in South Africa. In recent times, there have been increasing numbers of botched circumcisions by untrained and unscrupulous practitioners, leading to genital mutilation and often, the need for penile amputation. Hailed as a world's first, a team of surgeons conducted the first successful penile transplant in Cape Town, South Africa in 2015. Despite the euphoria of this surgical victory, concerns about the use of this costly intervention in a context of severe resource constraints have been raised. In this paper, we explore some of the ethical implications of penile transplants as a clinical and public health response to the adverse consequences of traditional male circumcision. Given the current fiscal deficits in healthcare and public health sectors, how can one justify costly, high-technology interventions for conditions affecting a small section of the population? Since botched traditional male circumcisions are preventable, is a focus on penile transplantation as a form of treatment reasonable? Finally, do such interventions create undue expectations and false hope among a highly vulnerable and stigmatised group of young men? In this paper, we argue that given limited healthcare resources in South Africa and competing healthcare needs, prevention is a more appropriate response to botched traditional circumcisions than penile transplants.

Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats.

BACKGROUND: Testosterone is believed to mediate the penile erectile response by producing adequate nitric oxide; therefore, testosterone deficiency results in erectile dysfunction through decreased nitric oxide bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone deficiency remain unclear. AIM: To investigate the mechanism of endothelial dysfunction in a rat model of testosterone deficiency. METHODS: Rats were distributed into 3 groups: castrated (Cast), castrated and supplemented with testosterone (Cast + T), and sham (Sham). In the Cast + T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats received only the vehicle. OUTCOMES: Erectile function using intracavernosal pressure and mean arterial pressure measurements after electrical stimulation of the cavernous nerve, endothelial function using isometric tension, asymmetric dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and tandem mass spectrometry, and inflammatory biomarker expression were performed 4 weeks after the operation. RESULTS: In the Cast group, the ratio of intracavernosal pressure to mean arterial pressure significantly decreased, acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and inflammation biomarker levels were significantly increased (P < .01). Testosterone injection significantly improved each of these parameters (P < .01). CLINICAL TRANSLATION: The present results provide scientific evidence of the effect of testosterone deficiency on erectile function and the effect of testosterone replacement therapy. STRENGTHS AND LIMITATIONS: This study provides evidence of the influence of testosterone deficiency on endothelial function by investigating ADMA and oxidative stress. A major limitation of this study is the lack of a direct link of increased ADMA by oxidative stress to inflammation. CONCLUSION: Testosterone deficiency increased not only ADMA levels but also oxidative stress and inflammation in castrated rats, which can cause damage to the corpus cavernosum, resulting in erectile dysfunction. Kataoka T, Hotta Y, Maeda Y, Kimura K. Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats. J Sex Med 2017;14:1540-1548.

Does Transfer Capacitive Resistive Energy Has a Therapeutic Effect on Peyronie's Disease? Randomized, Single-Blind, Sham-Controlled Study on 96 Patients: Fast Pain Relief.

Background/Aims/Objectives: We have investigated the clinical and physiological effects of Transfer Capacitive Resistive Energy (TCARE) therapy on men with Peyronie's disease (PD). METHODS: Ninety-six men with PD have been randomized in a 2:1 ratio to receive 3 sessions of TCARE therapy or sham therapy. Pain, penile curvature and erectile function have been assessed before the first treatment and up to 9 months after the end of treatment, using the Visual Analogue Scale for the pain, a goniometer to measure the degree of curvature using at-home photography and an International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: A significant pain reduction at the end of the treatment in 51 (79.6%) patients (p < 0.01) of the treated group was observed. No significant improvements in the sham group (p = 0.23) have been observed. No statistical differences in the degree of curvature have been observed in both groups. No statistical improvements have been observed in the IIEF-5 questionnaire. Adverse events have not been reported. CONCLUSION: This is, to our knowledge, the first randomized, single-blind, sham-controlled study that shows that TCARE has a positive short-term clinical effect on pain in patients with PD. The feasibility and tolerability of this treatment produce an attractive new therapeutic option for men with PD.

Effect of Testosterone on the Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in a Castrated Rat Model.

OBJECTIVE: To investigate the effect of testosterone (T) on the phenotypic modulation of corpus cavernosum smooth muscle (CCSM) cells in a castrated rat model. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: control, castration, and castration with T supplementation (castration + T). Erectile function, histologic change, and biochemical markers were assessed for phenotypic modulation of CCSM cells in corporal tissue. Moreover, the primary rat CCSM cells were isolated and examined by Western blot analysis. RESULTS: Our data showed that serum T level, mean weight of the body, erectile function, and smooth muscle-to-collagen ratio were significantly decreased in the castration group compared with those in the control and castration + T groups. The expressions of CCSM cells' phenotypic markers, such as α-smooth muscle actin, calponin, and smooth muscle myosin heavy chain 11, were markedly lower, whereas osteopontin protein expression was significantly higher in castrated rats than in control and castrated + T rats. In addition, the immunofluorescence staining of α-smooth muscle actin and calponin markedly decreased in the primary CCSM cells of the castrated rats compared with the intensity of the control and the castration + T rats. CONCLUSION: CCSM cells undergo phenotype modulation in castrated rats, whereas T reversed the alterations. T may play a key role in the phenotype modulation of CCSM cells.

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP/CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1ß, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function.

Hyperuricemia Is an Independent Risk Factor for Erectile Dysfunction.

INTRODUCTION: Hyperuricemia may be related to the development of endothelial dysfunction and cardiovascular diseases. However, the association between hyperuricemia and erectile dysfunction (ED) is not currently clear. AIM: The goal of this study is to investigate the effect of hyperuricemia on erectile function and possible mechanisms. METHODS: Twenty-four 8-week-old male SD rats were randomly divided into 4 groups. Group A (control): Rats received normal saline and served as controls. Group B (hyperuricemia): rats were given oxonic acid 250 mg/kg bw/day through gastric gavage for 4 weeks. Group C (febuxostat): normal rats were treated with 5 mg/kg febuxostat through gastric gavage for 4 weeks. Group D (hyperuricemia + Febuxostat): normal rats were treated with 250 mg/kg bw/day oxonic acid and 5 mg/kg bw/day febuxostat with 1 hour interval for 4 weeks. MEASUREMENTS: The level of serum uric acid, the maximum intracavernosal pressure (ICPmax), mean arterial pressure (MAP), and the expression of endothelial nitric oxide synthase (eNOS), phospho-eNOS, neuronal NOS, Rho-associated protein kinaise (ROCK)1 and ROCK2 and the level of nitric oxide (NO) and reactive oxygen species (ROS) in cavernous tissue were determined. RESULTS: The level of serum uric acid and ROS in hyperuricemic rats was significantly higher than that in the other 3 groups (P < .05). After electrostimulation with 3 and 5 voltage, the ratio of ICPmax/MAP in hyperuricemic rats was significantly less than that in other 3 groups (P < .05), respectively. eNOS, p-eNOS, and nNOS expression in hyperuricemic rats were significantly decreased compared to the other 3 groups (P < .05), respectively. CONCLUSION: Erectile function is impaired by hyperuricemia. The decrease of eNOS, p-eNOS, and nNOS protein expression and increase of ROS in cavernous tissue may be one of the key mechanisms of ED caused by hyperuricemia.