We wanted to determine whether shear wave elastography (SWE) could be used to evaluate the aging degree of the corpus cavernosum (CC) and to identify the histological basis of changes in SWE measurements during the aging process. We performed a cross-sectional study enrolling healthy participants of different ages. We measured the Young's modulus (YM) of the penile CCs by SWE and assessed erectile function using the International Index of Erectile Function-5 (IIEF-5). Histological investigation was performed in surgically resected penile specimens from a separate group of patients to examine the smooth muscle and collagen content of the CCs. Furthermore, we measured the YM, erectile function, smooth muscle, and collagen content of the CCs in different age groups of rats. Finally, we enrolled 210 male volunteers in this study. The YM of the CC (CCYM) was positively correlated with age (r = 0.949, P < 0.01) and negatively correlated with erectile function (r = -0.843, P < 0.01). Histological examinations showed that CCs had increased collagen content but decreased smooth muscle content with increased age. The same positive correlation between CCYM and age was also observed in the animal study. In addition, the animal study showed that older rats, with increased CCYM and decreased erectile function, had lower smooth muscle content and higher collagen content. SWE can noninvasively and quantitatively evaluate the aging degree of the CC. Increased collagen content and decreased smooth muscle content might be the histological basis for the effect of aging on the CC and the increase in its YM.
Humans ; Male ; Rats ; Animals ; Erectile Dysfunction ; Elasticity Imaging Techniques ; Cross-Sectional Studies ; Penis/pathology* ; Penile Erection/physiology* ; Aging ; Collagen

Structural alterations in fibroelastic components of the penile corpus cavernousum (CC) may impair its compliance, resulting in venous leakage and erectile dysfunction (ED). Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography (2-D SWE) in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED. A total of 12 New Zealand white rabbits were randomly divided into two groups. Six were fed a high-cholesterol diet containing 2% cholesterol and 8.5% lard for 10 weeks and the other six were fed normal diet as controls. We measured the shear-wave elastic quantitative (SWQ) value of penile CC by 2-D SWE. Erectile function was investigated by intracavernous injection of papaverine, and immunohistochemical (IHC) staining and the western blot analysis to determine the penile CC lesions. After 10 weeks, the SWQ values obtained from penile CC were remarkably higher in the high-cholesterol-fed compared with the control group, and the ΔICP (ICP plateau minus ICP baseline)/MAP (ICP: intracavernous pressure, MAP: mean arterial pressure) was markedly decreased. The IHC staining and western blot revealed extracellular matrix (ECM) accumulation in penile cavernous tissues, and the smooth muscle cell (SMC) phenotypic transition was affected, as indicated by reduced alpha-smooth muscle actin and calponin-1 expression and increased phospho-myosin light chain₂₀ (p-MLC₂₀)/MLC₂₀ and osteopontin expression. Hyperlipidemia resulted in ECM accumulation accompanied with SMC phenotypic transition in penile CC and impaired the erectile function eventually. These might, in turn, lead to variations in the SWQ values. It suggests that 2-D SWE may be a novel, noninvasive and effective approach that distinguishes penile CC lesions secondary to hyperlipidemia from normal.
Animals ; Disease Models, Animal ; Elasticity Imaging Techniques/methods* ; Erectile Dysfunction/etiology* ; Hyperlipidemias/diagnostic imaging* ; Male ; Penile Erection/physiology* ; Penis/diagnostic imaging* ; Rabbits

ObjectiveTo make a preliminary investigation on the safety and efficacy of focused low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED).

METHODSWe treated 32 ED patients by focused LI-ESWT with the device of Medispec's ED1000. Before and at 4 and 12 weeks after treatment, we evaluated the erectile function of the patients using the International Index of Erectile Function-erectile function domain (IIEF-EF), Erection Hardness Score (EHS), Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), and Global Assessment Questionnaire questions 1 and 2 (GAQ1 and GAQ2), and recorded the incidence rate of adverse events.

RESULTSThe patients averaged 30.69 years of age. Compared with the baseline, the mean IIEF-EF score of the patients was significantly increased at 4 and 12 weeks after LI-ESWT (14.94 vs 20.97 and 21.47, P <0.01), and so were the EHS (1.75 vs 2.66 and 2.56, P <0.01) and the "Yes" answers to SEP2 (21.88% vs 68.75% and 71.88%), SEP3 (0 vs 43.75% and 56.25%), GAQ1 (NA vs 81.25% and 71.88%) and GAQ2 (NA vs 65.63% and 68.75%). The total effectiveness rates at 4 weeks and 12 weeks were 75% and 71.88% respectively. One of the patients felt penile shaft pain with mild ecchymosis after LI-ESWT but was recovered without special treatment a week later.

CONCLUSIONSLI-ESWT can significantly improve the erectile function of ED patients with no obvious adverse effects within 12 weeks after treatment.

Adult ; Double-Blind Method ; Ecchymosis ; etiology ; Erectile Dysfunction ; therapy ; Extracorporeal Shockwave Therapy ; adverse effects ; methods ; Humans ; Male ; Pain, Procedural ; Penile Erection ; physiology ; Surveys and Questionnaires ; Treatment Outcome

ObjectiveTo study the clinical application value of the penile erectile strength measurement (PESM) band in the differentiation of psychogenic from organic erectile dysfunction (ED).

METHODSEighty ED patients unable to achieve or maintain adequate penile erection to complete sexual intercourse were included in the experimental group and another 40 healthy subjects with normal erectile function enrolled as controls. The ED cases were classified into mild, moderate and severe ED according to the IIEF-5 scores and divided into psychogenic and organic ED based on the results of the nocturnal penile tumescence (NPT) test. Then all the subjects underwent a three-night continuous monitoring with the PESM band and, according to the band fracture rate, the ED cases were also classified into psychogenic and organic ED. The rates of missed diagnosis, misdiagnosis and diagnostic coincidence of PESM were calculated with the results of NPT as the standard for differentiating psychogenic from organic ED.

RESULTSThe results of NPT tests revealed 51 cases of psychogenic and 29 cases of organic ED in the experimental group. The band fracture rate in PESM was 95.0% in the mild, 80.9% in the moderate and 52.8% in the severe ED patients. Of the 51 cases of psychogenic ED detected by NPT test, 43 were diagnosed as psychogenic and the other 8 as organic ED with the PESM band, with a coincidence rate of 84.3%. Of the 29 cases of organic ED revealed by NPT test, 5 were diagnosed as psychogenic and the other 24 as organic ED by PESM, with a coincidence rate of 82.8%. Normal erectile function with three-level fracture of the band was observed in the PESM of the normal controls, which showed a coincidence rate of 100% with the results of NPT tests. Based on the standard of the NPT test, the rates of missed diagnosis, misdiagnosis and diagnostic coincidence of the PESM band in differentiating psychogenic from organic ED were 15.7%, 17.2%, and 83.8%, respectively, with a Kappa value of 0.656 (P <0.05).

CONCLUSIONSThe penile erectile strength measurement band can be used as a screening tool for initial differentiation of psychogenic from organic ED.

Case-Control Studies ; Coitus ; Diagnostic Errors ; statistics & numerical data ; Erectile Dysfunction ; classification ; diagnosis ; physiopathology ; psychology ; Humans ; Male ; Penile Erection ; physiology

ObjectiveTo investigate the protective effect of human urine-derived stem cells (USCs) on erectile function and cavernous structure in rats with cavernous nerve injury (CNI).

METHODSSixty adult male SD rats with normal sexual function were randomly divided into four groups of equal number: sham operation, bilateral CNI (BCNI) model control, phosphate buffered saline (PBS), and USC. The BCNI model was established in the latter three groups of rats by clamping the bilateral cavernous nerves. After modeling, the rats in the PBS and USC groups were treated by intracavernous injection of PBS at 200 μl and USCs at 1×106/200 μl PBS respectively for 28 days. Then, the maximum intracavernous pressure (mICP) and the ratio of mICP to mean arterial pressure (mICP/MAP) of the rats were calculated by electrical stimulation of the major pelvic ganglions, the proportion of nNOS- or NF200-positive nerve fibers in the total area of penile dorsal nerves determined by immunohistochemical staining, the levels of endothelial cell marker eNOS, smooth muscle marker α-SMA and collagen I detected by Western blot, and the smooth muscle to collagen ratio and the cell apoptosis rate in the corpus cavernosum measured by Masson staining and TUNEL, respectively.

RESULTSAfter 28 days of treatment, the rats in the USC group, as compared with those in the PBS and BCNI model control groups, showed significant increases in the mICP (［81 ± 9.9］ vs ［31 ± 8.3］ and ［33 ± 4.2］ mmHg, P <0.05), mICP/MAP ratio (0.72 ± 0.05 vs 0.36 ± 0.03 and 0.35 ± 0.04, P <0.05), the proportions of nNOS-positive nerve fibers (［11.31 ± 4.22］% vs ［6.86 ± 3.08］% and ［7.29 ± 4.84］% , P <0.05) and NF200-positive nerve fibers in the total area of penile dorsal nerves (［27.31 ± 3.12］% vs ［17.38 ± 2.87］% and ［19.49 ± 4.92］%, P <0.05), the eNOS/GAPDH ratio (0.52 ± 0.08 vs 0.31 ± 0.06 and 0.33 ± 0.07, P <0.05), and the α-SMA/GAPDH ratio (1.01 ± 0.09 vs 0.36 ± 0.05 and 0.38 ± 0.04, P <0.05), but a remarkable decrease in the collagen I/GAPDH ratio (0.28 ± 0.06 vs 0.68 ± 0.04 and 0.70 ± 0.10, P <0.05). The ratio of smooth muscle to collagen in the corpus cavernosum was significantly higher in the USC than in the PBS and BCNI model control groups (17.91 ± 2.86 vs 7.70 ± 3.12 and 8.21 ± 3.83, P <0.05) while the rate of cell apoptosis markedly lower in the former than in the latter two (3.31 ± 0.83 vs 9.82 ± 0.76, P <0.01; 3.31 ± 0.83 vs 9.75 ± 0.91, P <0.05).

CONCLUSIONSIntracavernous injection of USCs can protect the erectile function of the rat with cavernous nerve injury by protecting the nerves, improving the endothelial function, alleviating fibrosis and inhibiting cell apoptosis in the cavernous tissue.

Actins ; analysis ; Animals ; Arterial Pressure ; Collagen ; analysis ; Disease Models, Animal ; Erectile Dysfunction ; prevention & control ; Male ; Nitric Oxide Synthase Type I ; analysis ; Nitric Oxide Synthase Type III ; analysis ; Penile Erection ; physiology ; Penis ; innervation ; Pudendal Nerve ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; administration & dosage ; Stem Cell Transplantation ; methods ; Stem Cells ; Urine ; cytology

OBJECTIVETo investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

METHODSThe ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

RESULTSPreconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

CONCLUSIONBAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.

Animals ; Area Under Curve ; Berberis ; chemistry ; Blood Pressure ; drug effects ; Cyclic GMP ; metabolism ; Epoprostenol ; pharmacology ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Models, Biological ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Penile Erection ; drug effects ; Phenylephrine ; pharmacology ; Plant Extracts ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Pressure ; Rabbits

Penile erectile dysfunction (ED) is ascribed to the contraction-relaxation imbalance of smooth muscle cells (SMC), the weakening of their diastolic function and the strengthening of their systolic function. The contraction-related signaling pathways, cell membrane ion channels and SMC phenotypes all participate in the regulation of their contraction and its malfunction may cause a variety of SMC-related diseases. The signaling pathways RhoA/Rock and Raf/MEK/ERK1/2 interact with each other, suppressing the expression of the RhoA protein or reducing the level of Rock2 phosphorylation, which may contribute to the treatment of ED. The poor performance of VDCC or TRPC is reckoned to be an important cause of hypertension- or diabetes-related ED. The expressions of CaV1.2, TRPC1 and TRPC4 can be upregulated by many pathological factors, which may enhance the contraction of SMCs. The pathogenesis of ED may be associated with the differentiation of the phenotypes corpus cavernosal SMCs. This review focuses on the recent progress in the studies of the relationship between SMC contraction and ED.
Animals ; Diabetes Complications ; etiology ; physiopathology ; Erectile Dysfunction ; etiology ; physiopathology ; Humans ; Hypertension ; complications ; Ion Channels ; metabolism ; Male ; Mitogen-Activated Protein Kinase 3 ; Muscle Contraction ; physiology ; Myocytes, Smooth Muscle ; physiology ; Penile Erection ; physiology ; Phosphorylation ; Signal Transduction ; physiology

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Ang1 notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice. In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED.
Angiopoietin-1/genetics* ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Endothelium, Vascular/metabolism* ; Erectile Dysfunction/therapy* ; Genetic Therapy/methods* ; Intercellular Junctions/metabolism* ; Male ; Mesenchymal Stem Cell Transplantation ; Mice ; Penile Erection/physiology* ; Permeability

Erectile dysfunction (ED) associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase (PK) has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate (cGMP) levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.
Animals ; Cyclic GMP/metabolism* ; Diabetes Mellitus, Experimental/physiopathology* ; Erectile Dysfunction/physiopathology* ; Kallikreins/therapeutic use* ; Male ; Muscle, Smooth, Vascular/physiopathology* ; Nitric Oxide Synthase Type I/metabolism* ; Nitric Oxide Synthase Type III/metabolism* ; Penile Erection/physiology* ; Penis/metabolism* ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate/therapeutic use* ; Treatment Outcome ; Urological Agents/therapeutic use*

Objective: To evaluate the effects of three different medications with tadalafil on erectile dysfunction (ED) in young men with primary sexual failure. METHODS: This study included 76 male ED patients aged 21－35 years who had primary sexual failure but normal nocturnal penile tumescence and rigidity and failed to respond to psychotherapy. We randomly assigned them to receive oral tadalafil once daily, on demand, or once-daily + on-demand. After 2－3 months of treatment, we evaluated the effects based on the scores of the patients in the five domains of the International Index of Erectile Function (IIEF-5). RESULTS: After medication, all the patients showed significantly increased scores in the four domains of IIEF-5, namely, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction. The on-demand group achieved even higher scores in erectile and orgasmic functions but a lower score in sexual desire than the once-daily group. However, the patients in the once-daily + on-demand group exhibited more significant improvement than those in the other two in all the five domains. CONCLUSIONS Once-daily + on-demand medication with tadalafil can significantly enhance the therapeutic effect on psychogenic ED in young men with primary sexual failure.
Adult ; Coitus ; Double-Blind Method ; Drug Administration Schedule ; Erectile Dysfunction ; drug therapy ; psychology ; Humans ; Male ; Orgasm ; Patient Satisfaction ; Penile Erection ; physiology ; Tadalafil ; administration & dosage ; Treatment Outcome ; Urological Agents ; administration & dosage ; Vasodilator Agents ; administration & dosage ; Young Adult