Improved Peyronie's Disease Curvature Outcomes Using a Novel Collagenase Administration Protocol.

OBJECTIVE: To report outcomes of a novel collagenase clostridium histolyticum (CCH) injection protocol. METHODS: A prospective, sequential database was maintained of all Peyronie's men undergoing CCH injections since 2015. Our protocol has evolved to include changes with injection technique, timing, aggressive modeling/traction, and wrapping. Results of the "traditional" and "novel" techniques were compared using two definitions: "most recent" assessment and final assessments among men who "completed eight (injections) or were satisfied." RESULTS: A total of 509 men underwent greater than or equal to 1 CCH series (traditional, n = 280; novel n = 229). Baseline demographic/clinicopathologic characteristics were similar between groups. Results demonstrated significantly greater curve improvements with the novel technique ("most recent" median 30° vs 20° or 46% vs 28%; "completed eight or satisfied" 34° vs 20° or 58% vs 30%). Using the "completed eight or satisfied" definition, 94% vs 66% of men achieved greater than or equal to 20% improvement (odds ratio 7.6), and 60% vs 24% achieved greater than or equal to 50% improvements (odds ratio 5.0) in the novel cohort (all P < .0001). Importantly, the International Index of Erectile Function Erectile Function Domain score was unchanged, and subjective erectile function (50% vs 5%, P < .0001) and sensation improved (17% vs 8% improved, P = .01) with the new protocol. The novel cohort also reported higher rates of surgery prevention (53% vs 18%), restored/facilitated penetration (57% vs 21%), and hematomas (56% vs 26%), necessitating changes to wrapping procedures (all P < .0001). CONCLUSIONS: Use of the novel CCH protocol results in significant improvements with curvature without negatively impacting erectile function or sensation. Given its specialized nature, it is not recommended for low-volume CCH injectors.

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.

Expression of mRNA vascular endothelial growth factor in hypospadias patients.

BACKGROUND: Hypospadias is a relatively common genital anomaly in humans, usually followed by inelastic dartos that causes penile chordee. Vascular endothelial growth factor (VEGF) is strongly linked to the viscoelasticity of tissues and their elastic phase. This study aimed to evaluate VEGF expressions in (1) fascia dartos between hypospadias and controls and (2) chordee severity. METHODS: This prospective cohort study involved 65 specimens from patients with hypospadias and ten specimens from controls. The samples were analyzed by quantitative real-time polymerase chain reaction (qPCR) for VEGF expression. RESULTS: The expressions of VEGF were not different between proximal and distal hypospadias patients and controls (fold change: distal - 0.25; fold change: proximal - 0.2; p = 0.664). The scaled expressions related to chordee severity were mild - 0.1; moderate 0.1; severe - 0.25 (p = 0.660). CONCLUSIONS: VEGF expressions might not affect the severity of hypospadias and chordee, implying the pathogenesis is complex involving many growth factors. Further study with a larger sample size is necessary to clarify and confirm our findings.

Ageing-induced hypercontractility is related to functional enhancement of STIM/Orai and upregulation of Orai 3 in rat and human penile tissue.

The role of STIM/Orai calcium entry system on vascular ageing has not been elucidated. We aimed to evaluate the influence of ageing on STIM/Orai signalling and its role on ageing-induced alterations of contractile function in rat corpus cavernosum (RCC) and human penile resistance arteries (HPRA) and corpus cavernosum (HCC). RCC was obtained from 3 months-old and 20 months-old animals. HPRA and HCC were obtained from organ donors of varied ages without history of erectile dysfunction. Aging was associated with enhanced norepinephrine (NE)- and thromboxane analogue (U46619)-induced contractions in RCC which were significantly inhibited by the STIM/Orai inhibitor, YM-58483 (20 µM). Other STIM/Orai inhibitor, 2-aminoethyldiphenylborate also reduced NE-induced contractions in RCC from aged rats. YM-58483 significantly reduced neurogenic contractions and potentiated neurogenic relaxations in RCC from aged rats. In HCC and HPRA, NE-induced contractions were significantly enhanced in older subjects (>65 years-old) but YM-58483 completely reversed ageing-related hypercontractility. Ageing did not modify STIM-1 and Orai1 protein expressions but Orai3 was significantly overexpressed in cavernosal tissue from old rats and older subjects. Contribution of STIM/Orai to cavernosal contraction increases with ageing together with increased expression of Orai3. Orai inhibition could be a potential therapeutic strategy to reduce ageing-related impact on vascular/erectile function.

Acute Ischemic Priapism: An AUA/SMSNA Guideline.

PURPOSE: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction. MATERIALS AND METHODS: A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report. RESULTS: This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement. CONCLUSIONS: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

GYY4137 attenuates functional impairment of corpus cavernosum and reduces fibrosis in rats with STZ-induced diabetes by inhibiting the TGF-ß1/Smad/CTGF pathway.

Erectile dysfunction (ED) is a common diabetic complication. Recent evidence has illuminated the role of hydrogen sulfide (H2S) as a dynamic mediator of the erection process. H2S is a potent endogenous relaxant gas. It has been shown to relax human and animal penile tissue in vitro and induce erection in animals in vivo. The reported penile expression of H2S-synthesizing enzymes also supports the potential role of the endogenous L-cysteine/H2S pathway in penile homeostasis. Several pathological changes take place in the diabetic penile tissue, including inflammation, oxidative stress, neuropathy and fibrosis of the corpus cavernosum (CC), the major erectile structure of the penis. The present study is experimental and has been performed in the diabetic rat model. The study will investigate the role of H2S as a potential protective mediator against diabetes-induced structural and functional alterations in the CC by examining if it: (1) reduces corporal contraction and/or enhances corporal relaxation following pharmacological stimulation, (2) attenuates fibromuscular changes in diabetic CC, and (3) whether there is a link with H2S plasma/urine level and CC tissue generation, as well as studying the expression of some proteins in the transforming growth factor (TGF)-ß1-associated pathway. The major findings of the study reveal that- compared to the nondiabetic controls - the diabetic animals CC showed: (1) augmented contraction and attenuated relaxation in response to phenylephrine and carbachol, respectively, (2) marked fibromuscular degeneration with a significantly lower smooth muscle/collagen ratio and upregulation of TGF-ß-1/Smad/CTGF fibrosis signaling pathway, (3) reduced H2S plasma and urinary levels and cavernosal tissue generation. Chronic GYY4137 treatment prevented most of these pathological changes in diabetic CC, thus may be considered a potential new strategy for the prevention and/or treatment of diabetes-induced ED.

Modified partial penile disassembly repair for improved functional and cosmetic outcome in isolated male epispadias.

INTRODUCTION AND OBJECTIVE: The objective of the study was to evaluate the functional and cosmetic outcome of single-stage modified partial penile disassembly repair in isolated male epispadias. MATERIALS AND METHODS: A retrospective analysis of 15 cases of primary epispadias repair, from June 2015 to December 2018, was performed. Patients were classified by the type of epispadias, urinary incontinence, chordee, and rotation. SURGICAL TECHNIQUE: Penile degloving with the mobilization of the urethral plate from the ventral to the dorsal aspect with the preservation of blood supply at both ends, distally up to the level of mid-glans and proximally up to the pubic symphysis is done. Tubularization of urethral plate followed by spongioplasty, corporoplasty with medial rotation of corporeal bodies, and glanuloplasty with meatoplasty was done to bring the meatus ventrally. The skin cover is done by the rotation of the ventral flaps and the z-plasty whenever required. RESULTS: Age of the patients varied from 4 months to 21 years with a mean of 11 years. Thirteen patients had excellent cosmetic outcome while two patients had minimal residual chordee but did not require any surgery in a follow-up. Five patients with partial incontinence in the study group achieved continence after surgery. None of the patients developed complications such as fistula or stricture. All five male patients in the post-pubertal group reported normal erections and successful ejaculations after the surgery. Follow-up ranged from 3 months to 18 months. CONCLUSIONS: Modified partial penile disassembly incorporates all the benefits of Cantwell Ransley repair and needs less extensive dissection than total penile disassembly. Both functional and cosmetic results are good with a low complication rate.

Spongiosum-combined glanuloplasty reduces glans complications after proximal hypospadias repair.

We aim to design a new glanuloplasty procedure combined with spongiosum to reduce the incidence of glans dehiscence and coronal fistula after proximal hypospadias repair. Patients who underwent urethroplasty by dorsal preputial island flap for proximal hypospadias between January 2014 and December 2016 were reviewed in this retrospective cohort study. Those who underwent spongiosum-combined glanuloplasty comprised the new-maneuver group, whereas those who underwent conventional glanuloplasty comprised the control group. The incidence of complications was then compared. In the new-maneuver group, dysplastic corpus spongiosum alongside lateral Buck's fascia (0.3-0.4 cm wide) on both sides of the urethral plate was separated from the proximal normal spongy tissue, joining into the glans wings to increase tissue volume and covering the neourethra in the glans penis. In the control group, the neourethra was covered with superficial fascia under the coronal sulcus. As a result, the new-maneuver and control groups comprised 47 and 28 patients, respectively. In the new-maneuver group, no glans dehiscence was detected; however, two (4.3%) patients had coronal fistula, two (4.3%) had urethral stricture, and four (8.5%) had diverticulum. In the control group, two (7.1%) patients had glans dehiscence, eight (28.6%) had coronal fistula, four (14.3%) had urethral stricture, one (3.6%) had diverticulum, and one (3.6%) had penile curvature recurrence. The new-maneuver group had less incidences of coronal fistula (P < 0.001), glans dehiscence (P = 0.033), and urethral stricture (P = 0.008) but had a higher incidence of diverticulum than the control group (P = 0.040). It clearly demonstrates that spongiosum-combined glanuloplasty can significantly reduce the incidences of coronal fistula and glans dehisce.

The impact of extracorporeal shock wave therapy for the treatment of young patients with vasculogenic mild erectile dysfunction: A prospective randomized single-blind, sham controlled study.

BACKGROUND: Low-intensity extracorporeal shock wave therapy (ESWT) for the treatment of vasculogenic erectile dysfunction (ED) has emerged as a promising method directly targeting the underlying pathophysiology of the disease. OBJECTIVES: To compare outcomes in ED patients after ESWT and placebo treatment. MATERIALS AND METHODS: Prospective randomized placebo-controlled single-blinded trial on 66 patients with mild ED. The study comprised a 4-week washout phase, a 4-week treatment phase, and a 48-week follow-up. Inclusion criteria included age between 18 and 75 years and diagnosis of mild ED (IIEF-EF score = 17-25) being made at least six months prior to study inclusion and being confirmed by Penile Doppler ultrasonography (US) at baseline examination. Efficacy endpoints were changes from baseline in patient-reported outcomes of erectile function (International Index of Erectile Function domain scores [IIEF-EF]), as well as erection hardness and duration (Sexual Encounter Profile diary [SEP] and Global Assessment Questions [GAQ]). Safety was assessed throughout the study. RESULTS: A total of 66 enrolled patients were allocated to ESWT (n = 44) or placebo (n = 22). Mean age of ESWT and placebo group was 42.32 ± 9.88 and 39.86 ± 11.64 (p = 0.374), respectively. Mean baseline IIEF-EF scores of ESWT group and placebo were 20.32 ± 2.32 and 19.68 ± 1.55 respectively (p = 0.34). At 3-months follow-up, mean IIEF-EF scores were significantly higher in ESWT patients than in placebo patients (23.10 ± 2.82 vs. 20.95 ± 2.19, p = 0.003), and IIEF-EF scores of ESWT patients remained high during the 6 months (22.67 ± 3.35 vs. 19.82 ± 1.56) follow-up. The percentage of patients reporting both successful penetration (SEP2) and intercourse (SEP3) in more than 50% of attempts was significantly higher in ESWT-treated patients than in placebo patients (p = 0.001). A minimal clinically important difference between the IIEF = EF baseline and 3-months follow-up was found in 74% of ESWT and 36% of placebo. No serious adverse events were reported. DISCUSSION AND CONCLUSION: ESWT significantly improved the erectile function of relatively young patients with vasculogenic mild ED when compared to placebo and the beneficial effect of this treatment up to 6 months. These findings suggest that ESWT could be a useful treatment option in vasculogenic ED.

Early surgical repair or conservative treatment? Comparing patients with penile fracture concerning long-term sexual functions.

BACKGROUND: To compare the patients who underwent early surgical repair of penile fracture, which is one of the urological emergencies, and patients who recovered with conservative treatment concerning long-term sexual functions. METHODS: The data of 42 patients who applied to our clinic with penile fracture between January 2010 and January 2020 were retrospectively analyzed. The patients were categorized into two groups as early operated and followed-up conservatively. The preoperative and postoperative findings of the patients were compared with the International Erectile Function Scale (IIEF-6) scores in the long-term follow-up. RESULTS: The median age of the patients was 35 (20-65) years and the median follow-up period was 52 (8-120) months. The postoperative mean IIEF-6 score of the patients was 22.98±6.52. There was no significant difference between the surgical and the conservative groups concerning postoperative complications (p=0.460). In the follow-up period, the presence of palpable plaque on the rupture area was significantly higher in the conservative group (p=0.041). However, there was no significant difference between the groups concerning IIEF-6 scores (p=0.085). CONCLUSION: Although there is no significant difference in long-term IIEF-6 scores between the two groups, the rate of palpable plaque formation is higher in patients followed-up conservatively. Therefore, early surgical repair should be considered in the foreground, especially in patients with a large rupture area.

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.

Aberrant default mode network and auditory network underlying the sympathetic skin response of the penis (PSSR) of patients with premature ejaculation: A resting-state fMRI study.

INTRODUCTION: Hyperactivity of the sympathetic nervous system is considered as an important component involved in the pathological mechanisms of premature ejaculation (PE). However, the neural mechanisms of PE with high sympathetic activity are still not well understood. METHODS: The activity of the sympathetic innervations in the penis was evaluated by the sympathetic skin response of the penis (PSSR) with an electromyograph and evoked potential equipment. Resting-state functional magnetic resonance imaging (fMRI) data were acquired from 18 PE patients with high sympathetic activity (sPE), 17 PE patients with normal sympathetic activity (nsPE), and 24 healthy controls (HC). We investigated the neural basis of sPE based on the measure of regional homogeneity (ReHo). Moreover, the correlations between brain regions with altered ReHo and PEDT scores and PSSR latencies in the patient group were explored. RESULTS: Altered ReHo values among three groups were found in the temporal, cingulated, and parietal cortex in the default mode network (DMN), as well as the temporal cortex in the auditory network (AUD). Compared with HC, Patients with sPE had increased ReHo values of brain regions in DMN, AUD, and decreased ReHo values of brain regions in DMN. In addition, increased ReHo values were found in DMN of patients with nsPE, while decreased ReHo values were found in DMN and the attention network (AN). Moreover, sPE patients had increased ReHo values in AUD and decreased ReHo values in DMN when compared with nsPE patients. Finally, altered ReHo values of brain regions in DMN and AUD were associated with PEDT scores and PSSR latencies in the patient group. CONCLUSION: Our results suggested that PE patients had abnormal ReHo values in DMN, AUD, and AN. Patients with sPE were characterized by increased neuronal activity in AUD and decreased activity in DMN. This highlighted the significances of DMN, AUD, and AN in the pathophysiology of PE and also provided potential neuroimaging biomarkers for distinguishing sPE from nsPE and HC.

Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation.

Timely activation of the luteinizing hormone receptor (LHCGR) is critical for fertility. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP) due to premature synthesis of testosterone. A mouse model of FMPP (KiLHRD582G), expressing a constitutively activating mutation in LHCGR, was previously developed in our laboratory. KiLHRD582G mice became progressively infertile due to sexual dysfunction and exhibited smooth muscle loss and chondrocyte accumulation in the penis. In this study, we tested the hypothesis that KiLHRD582G mice had erectile dysfunction due to impaired smooth muscle function. Apomorphine-induced erection studies determined that KiLHRD582G mice had erectile dysfunction. Penile smooth muscle and endothelial function were assessed using penile cavernosal strips. Penile endothelial cell content was not changed in KiLHRD582G mice. The maximal relaxation response to acetylcholine and the nitric oxide donor, sodium nitroprusside, was significantly reduced in KiLHRD582G mice indicating an impairment in the nitric oxide (NO)-mediated signaling. Cyclic GMP (cGMP) levels were significantly reduced in KiLHRD582G mice in response to acetylcholine, sodium nitroprusside and the soluble guanylate cyclase stimulator, BAY 41-2272. Expression of NOS1, NOS3 and PKRG1 were unchanged. The Rho-kinase signaling pathway for smooth muscle contraction was not altered. Together, these data indicate that KiLHRD582G mice have erectile dysfunction due to impaired NO-mediated activation of soluble guanylate cyclase resulting in decreased levels of cGMP and penile smooth muscle relaxation. These studies in the KiLHRD582G mice demonstrate that activating mutations in the mouse LHCGR cause erectile dysfunction due to impairment of the NO-mediated signaling pathway in the penile smooth muscle.

Kinematic analysis of penile reflexes in a rat model of spinal cord injury.

The ex-copula penile dorsiflexion reflex (PDFR) is an established measure of sexual dysfunction in male rat models of spinal cord injury. Although the PDFR after complete spinal transection is well described, information regarding the more clinically relevant incomplete spinal contusion injury model is limited. This study examined, using two-dimensional (2D) kinematic analysis, the relationship between the PDFR and degree of white matter sparing (WMS). Male Wistar rats received a T9 contusion with varying degrees of impactor forces. Weekly kinematic recordings of the PDFR were made 3-8 weeks postinjury. Sexual reflex components examined included maximum angle of penile dorsiflexion, total penile event duration, and penile ascent speed. Post hoc comparison between animals grouped based upon injury severity (moderate-severe: 13.33%-17.15% WMS vs moderate: 20.85%-33.50% WMS) indicated PDFR effects. Specifically, the numbers of animals with more moderate contusions having data points above the median in both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe injuries. Total penile event duration was also affected but only at more chronic time points (6-8 weeks). Thus, 2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.

Risk factors for penile fracture compared with a surgical control cohort in the United States: the role of substance abuse.

Penile fracture (PF) is a surgical emergency. Given its rarity, we queried a national cohort over an 11-year period to study the temporal and demographic variations in presentation, evaluation, and management of patients with PF compared with a cohort of control patients. The National Inpatient Sample was queried between the years 2005 and 2016 for patients with a diagnosis of PF. Appendectomy patients were selected as a control cohort, given the non-discriminatory nature of this disease. Clinical and demographic data of the patients were compared with that of controls. Presenting symptoms, rates of surgical repair, and rates of associated surgical procedures were evaluated in the PF cohort. During the study period, 5802 patients were hospitalized for PF. The annual incidence of PF remained unchanged at 1.0-1.8 cases per 100 000 hospitalizations over the study period. Compared with the control cohort, PF patients were more likely to be younger (38.7 years vs 41.2 years, P ≤ 0.001), have lower rates of comorbidities except erectile dysfunction (1.4% vs 0.1%, P ≤ 0.001), and were more likely of Black race (25.4% vs 6.2%, P ≤ 0.001). Notably, PF patients had significantly higher rates of substance abuse (26.4% vs 18.1%, P ≤ 0.001), despite no difference in the diagnosed psychiatric disorders. PF rarely presented with hematuria (3.5%); however, urethral evaluation was performed in 23.1%, most commonly with cystoscopy (19.2%). PF occurs more commonly in a younger, healthier male population, and among minorities. Importantly, rates of substance abuse appear to be higher in the PF cohort compared with those of controls.

Robinow syndrome: Genital analysis, genetic heterogeneity, and associated psychological impact.

Robinow syndrome (RS) is a rare, pleiotropic genetic disorder. While it has been reported that males with Robinow syndrome may have genitourinary atypicalities, these have not been systematically studied. We hypothesized that the underlying gene involved plays a role in the clinical variability of associated genital findings and that the phenotypic appearance of the genitalia in RS may have a psychological impact. Urologic-specific examination consisted of detailed examination and a questionnaire to investigate the psychological impact of the genital phenotype. Nine males agreed to a full evaluation. Average age was 19.9 years, penile length was 32.5 mm, stretched length 53 mm, and width 24.4 mm. Penile transposition occurred in all 9 male who allowed full examination. Undescended testicles were noted in 4/10, testicular atrophy in 5/9, buried penis in 7/9, hypospadias in 5/8, and a large penopubic gap (space between dorsum of penis base and pubic bone) in 5/6. In this cohort, 78% answered our semi-quantitative pilot questionnaire that identified diminished sexuality, sexual function, and self-perception. In conclusion, RS has unique, hallmark genital findings including penile transposition, buried penis, undescended testes, and large penopubic gaps. Genital phenotype in males was not shown to correlate with the specific gene involved for each patient. Surgical approaches and other interventions should be studied to address the findings of decreased sexuality and self-perception. It is the authors' opinion that intervention to provide the appearance of penile lengthening be postponed until puberty to allow for maximal natural phallic growth.

Effect of Asthma on Erectile Dysfunction in Rats as Determined by Biological Network Analysis.

BACKGROUND We explored the effect of asthma on erectile dysfunction (ED) and the effects of the expression of related proteins. MATERIAL AND METHODS We used a bioinformatics database to predict the targets and pathways associated with asthma and ED. The rat model of asthma was caused by an ovalbumin solution. The number of erections in 30 min was observed by injecting apomorphine into the neck at a dose of 100 µg/kg. Rats with no erection were regarded as the model group (group B), and the previous random 6 normal rats were regarded as the control group (group A). We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression levels of insulin (INS), interleukin 6 (IL6), albumin (ALB), tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGFA) at both the protein and messenger ribonucleic acid (mRNA) levels. RESULTS HE staining results show that compared with group A, the blood sinus distribution of the cavernous body in group B was disordered, and the density of endothelial cells and smooth muscle cells decreased significantly. Western blotting and RT-qPCR showed that the levels of IL6, TNF, and VEGFA protein and mRNA in group B were significantly higher (P<0.05) than those in group A. The levels of INS and ALB were not significantly different between the 2 groups. CONCLUSIONS On the basis of the results, we found that asthma caused pathological changes in the penises of rats and led to reduced erectile function via changes in the expression of IL6, TNF, and VEGFA proteins.

Expression of AIF, PARP, and miRNAs MIR-145, MIR-210, and MIR-486 associated with apoptosis in the corpus cavernosum of rats subjected to chronic alcoholism model / Expresión de AIF, PARP y miRNAs MIR-145, MIR-210 y MIR-486 asociados con apoptosis en el cuerpo cavernoso de ratas sometidas a modelo de alcoholismo crónico

SUMMARY: Previous studies from our group described the consequences of using ethanol on penile erection. Nevertheless, the molecular mechanisms surrounding microRNAs, apoptosis process and their relationship with erectile dysfunction associated with alcohol consumption are still poorly understood. The objective of this analysis was to evaluate the mechanism of apoptosis by the expression of AIF and PARP, as well as their regulatory microRNAs: miR-145, miR-210 and miR-486, in the corpus cavernosum of rats submitted to a semivoluntary alcoholism model. For this study 24 Wistar rats were divided into two groups: control (C) and treated with 20 % ethanol (A) for seven weeks. The corpus cavernosum samples were prepared for immunohistochemical analysis of AIF and PARP protein expression, and microRNAs miR-145, miR-210, miR-486 gene expression in cavernous tissue was performed by real time PCR. The immunohistochemical analysis showed little nuclear positive labeling for the protein PARP and AIF in the corpus cavernosum of control and ethanol treated animals. After analysis of miR-145, -210 and -486 microRNA expression in the 12 animals studied, no results were found with significant statistical difference between the control and alcoholized groups. The expression of AIF and PARP and their regulatory microRNAs involved in apoptotic process (miR-145, miR-210 and miR-486) were not altered in the corpus cavernosum of rats submitted to semivoluntary alcoholism.

RESUMEN: Estudios previos de nuestro grupo describieron las consecuencias del uso de etanol en la erección del pene. Sin embargo, los mecanismos moleculares que rodean a los microARN, el proceso de apoptosis y su relación con la disfunción eréctil asociada con el consumo de alcohol aún no se conocen bien. El objetivo de este análisis fue evaluar el mecanismo de apoptosis mediante la expresión de AIF y PARP, así como sus microARN reguladores: miR-145, miR-210 y miR-486, en el cuerpo cavernoso de ratas sometidas a un modelo de alcoholismo semivoluntario. Se dividieron 24 ratas Wistar en dos grupos: control (C) grupo de ratas tratadas con etanol al 20 % (A) durante siete semanas. Las muestras del cuerpo cavernoso se prepararon para el análisis inmunohistoquímico de la expresión de la proteína AIF y PARP, y la expresión del gen microRNAs miR-145, miR-210, miR-486 en tejido cavernoso se realizó por PCR en tiempo real. El análisis inmunohistoquímico mostró escaso etiquetado nuclear positivo para la proteína PARP y AIF en el cuerpo cavernoso de los animales de control y tratados con etanol. Después del análisis de la expresión de microARN miR-145, -210 y -486 no se encontraron resultados con diferencias estadísticas significativas entre los grupos control y alcoholizados. La expresión de AIF y PARP y sus microARN reguladores involucrados en el proceso apoptótico (miR-145, miR-210 y miR-486) no se alteraron en el cuerpo cavernoso de las ratas sometidas a alcoholismo semivoluntario.

Mesenchymal stem cells-derived exosomal microRNA-21-5p downregulates PDCD4 and ameliorates erectile dysfunction in a rat model of diabetes mellitus.

Erectile dysfunction (ED) is a common comorbidity in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells (CCSMCs). Gene Expression Omnibus repository-based analysis identified the differentially expressed PDCD4 in DM rats. PDCD4 has also been determined as a putative gene under the regulatory control of microRNA-21-5p (miR-21-5p). This study aimed to further determine the functional role of miR-21-5p in CCSMCs in a rat model of diabetes mellitus-induced erectile dysfunction (DMED). CCSMCs were isolated from penile cavernous tissue and cultured in high glucose (HG) medium. The expression of miR-21-5p and/or PDCD4 was altered in CCSMCs, as directly or indirectly measured by CCK-8 assay, flow cytometry, and TUNEL assays. Furthermore, exosomes were isolated from mesenchymal stem cells (MSCs) transfected with miR-21-5p mimic or miR-21-5p inhibitor and co-cultured with CCSMCs. DMED rats were injected with lentivirus carrying PDCD4/siRNA-PDCD4 plasmids, or exosomes from MSCs containing miR-21-5p-agomir to explore their roles in vivo. The experimental data validated that PDCD4 was upregulated in cavernous tissue of DMED rats. miR-21-5p targeted and inhibited PDCD4. miR-21-5p was enriched in MSC-exosomes. Moreover, PDCD4 downregulation, miR-21-5p elevation or MSC-derived exosomal miR-21-5p reduced apoptosis and enhanced proliferation of CCSMCs cultured in HG medium. PDCD4 silencing or miR-21-5p-containing MSC-exosomes improved erectile function and smooth muscle density in DMED rats. Collectively, our findings suggested that MSC-derived exosomal miR-21-5p suppressed PDCD4 expression and ED in rats with DM.