Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

With the onset of a metabolic syndrome epidemic and the increasing life expectancy, erectile dysfunction (ED) has become a more common condition. As incidence and prevalence increase, the medical field is focused on providing more appropriate therapies. It is common knowledge that ED is a chronic condition that is also associated with a myriad of other disorders. Conditions such as aging, diabetes mellitus, hypertension, obesity, prostatic hypertrophy, and prostate cancer, among others, have a direct implication on the onset and progression of ED. Characterization and recognition of risk factors may help clinicians recognize and properly treat patients suffering from ED. One of the most reliable treatments for ED is penile prosthetic surgery. Since the introduction of the penile prosthesis (PP) in the early seventies, this surgical procedure has improved the lives of thousands of men, with reliable and satisfactory results. The aim of this review article is to characterize the epidemiology of men undergoing penile prosthetic surgery, with a discussion about the most common conditions involved in the development of ED, and that ultimately drive patients into electing to undergo PP placement.
Diabetes Complications/surgery* ; Diabetes Mellitus/epidemiology* ; Erectile Dysfunction/surgery* ; Humans ; Hypertension ; Impotence, Vasculogenic/surgery* ; Male ; Pelvic Bones/injuries* ; Penile Implantation/statistics & numerical data* ; Penile Induration/surgery* ; Penile Prosthesis ; Penis/injuries* ; Prostatectomy/adverse effects* ; Prostatic Neoplasms/surgery* ; Radiation Injuries/surgery* ; Radiotherapy/adverse effects* ; Reoperation ; Spinal Cord Injuries/epidemiology* ; Vascular Diseases/epidemiology* ; Wounds and Injuries/epidemiology*

We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg^-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg^-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg^-1 LIMK2i and 20.0 mg kg^-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.
Animals ; Apoptosis/drug effects* ; Arterial Pressure ; Electric Stimulation ; Erectile Dysfunction/pathology* ; Lim Kinases/antagonists & inhibitors* ; Male ; Nerve Crush ; Nitric Oxide Synthase Type III/metabolism* ; Penis/pathology* ; Peripheral Nerve Injuries/pathology* ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Phosphorylation ; Pyrimidines/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Sulfonamides/therapeutic use*

ObjectiveTo investigate the diagnosis and management of penile fracture.

METHODSFrom June 1993 to May 2017, 46 cases of penile fracture were treated in our hospital, averaging 33.5 (25－42) years of age and 3.45 (1－10) hours in duration, of which 41 occurred during sexual intercourse, 4 during masturbation and 1 during prone sleeping, 4 with hematuria, but none with dysuria or urethral bleeding. Hematoma was confined to the penis. Emergency surgical repair was performed for all the patients, 45 under spinal anesthesia and 1 under local anesthesia, 16 by coronal proximal circular incision and the other 30 by local longitudinal incision according to the rupture location on ultrasonogram. The tunica albuginea ruptures averaged 1.31 (0.5－2.5) cm in length, which were sutured in the "8" pattern for 6 cases and with the 3－0 absorbable thread for 18 cases. The skin graft or negative pressure drainage tube was routinely placed, catheters indwelt, and gauze used for early pressure dressing. In the recent few years, elastic bandages were employed for 3－5 days of pressure dressing and antibiotics administered to prevent infection. The stitches and catheter were removed at 7 days after surgery.

RESULTSShort-term postoperative foreskin edema occurred in 14 of the 16 cases of circular degloving incision, but no postoperative complications were observed in any of the cases of local incision. Twenty-eight of the patients completed a long-term follow-up of 49.4 (10－125) months, which revealed good erectile function, painless erection, and satisfactory sexual intercourse.

CONCLUSIONSFor most penile fractures, local longitudinal incision is sufficient for successful repair of the tunica albuginea, with mild injury, no influence on the blood supply or lymph reflux, and a low rate complications. It therefore is obviously advantageous over circular degloving incision except when the cavernous body of urethra is to be explored, which necessitates circular degloving incision below the coronal groove.

Adult ; Coitus ; Edema ; etiology ; Hematoma ; diagnosis ; etiology ; Humans ; Male ; Masturbation ; complications ; Penile Erection ; Penis ; injuries ; Postoperative Complications ; etiology ; Rupture ; diagnosis ; etiology ; surgery ; Surgical Wound ; Ultrasonography ; Urethra ; surgery

Penile disease is one of the male urological diseases. Although the penis is a small organ, once the problem occurs, it often brings great trouble to the patient. Therefore, the accurate diagnosis of penile disease is particularly important. High-frequency ultrasonography, with its advantages of noninvasiveness, safety, low cost, easy operation and reproducibility, can clearly show the structure and blood flow of the penis and has a significant value in the diagnosis and follow-up of penile diseases such as vascular erectile dysfunction, priapism, penile injury, penile neoplastic and non neoplastic nodules. Meanwhile, the development of new technologies such as shear wave elastography (SWE) and contrast enhanced ultrasound (CEUS) has made up for the shortcomings of traditional ultrasound imaging, expanded the application of ultrasound in penile diseases, and improved the efficiency of ultrasound diagnosis of the diseases. This article focuses on the application value of ultrasound in erectile dysfunction, priapism, penile cavernous injury and penile tubercle, as well as the latest progress in such new technologies as SWE and CEUS applied to penile diseases.
Contrast Media ; Elasticity Imaging Techniques ; Erectile Dysfunction ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Penile Diseases ; diagnostic imaging ; Penile Neoplasms ; diagnostic imaging ; Penis ; diagnostic imaging ; injuries ; Priapism ; diagnostic imaging ; Reproducibility of Results ; Ultrasonography ; methods

Objective: To explore the treatment of penile incarceration with a metal ring. METHODS: Based on our experience in the successful management of a case of penile incarceration with a metal ring by coiling and bloodletting from the corpus cavernosum, we reviewed the relevant literature and analyzed the indications, advantages and disadvantages of different methods for the treatment of penile incarceration with a circular foreign body. RESULTS: The clamping and cutting methods were non-invasive, fast, effective, and with few complications, which could be applied to the treatment of penile strangulation at all levels. However, clamping was not desirable enough for a hard metal ring and the cutting method took a longer time and might increase the risk of unnecessary damage to the penile skin, urethra and cavernous body. Prepuce edema decompression and the thin tube-coiling method, with the advantages of minimal invasiveness, simple operation and no need of special tools, were suitable for penile strangulation injury under level 3, but might cause penile skin injury and potential postoperative erectile dysfunction. Surgical resection, as an invasive procedure, could be applied to severe penile strangulation at level 4 or 5. CONCLUSIONS The principle for the treatment of penile incarceration with a circular foreign body is to remove the foreign object as soon as possible and not to add secondary damage.
Bloodletting ; methods ; Constriction, Pathologic ; therapy ; Erectile Dysfunction ; prevention & control ; Foreign Bodies ; complications ; therapy ; Humans ; Jewelry ; adverse effects ; Male ; Penis ; blood supply ; injuries ; pathology ; Postoperative Complications ; prevention & control ; Urethra

The present study aimed to identify which mitogen-activated protein kinase (p38 or Jun amino-terminal kinase [JNK]) was involved in cavernosal apoptosis during the acute phase after cavernosal nerve crush injury (CNCI) in rats to ameliorate apoptosis of cavernosal tissue, such as smooth muscle (SM). A total of twenty 10-week-old male Sprague-Dawley rats were divided equally into two groups: sham surgery (S) and CNCI (I). The I group approximated the clinical situation of men undergoing radical prostatectomy using two 60-second compressions of both CNs with a microsurgical vascular clamp. At 2-week postinjury, erectile response was assessed using electrostimulation. Penile tissues were harvested for immunohistochemistry analysis of alpha-SM actin (α-SMA), western blot analysis, and double immunofluorescence analysis of α-SMA and phosphorylated p38 or JNK, as well as double immunofluorescent of TUNEL and phosphorylated p38 or JNK. At 2-week postinjury, the I group had a significantly lower intracavernous pressure (ICP)/mean arterial pressure (MAP) and a lower area under the curve (AUC)/MAP than the S group. The I group also exhibited decreased immunohistochemical staining of α-SMA, an increase in the number of SM cells positive for phosphorylated JNK, an increased number of apoptotic cells positive for phosphorylated JNK, and increased JNK phosphorylation compared with the S group. However, there was no significant difference in p38 phosphorylation expression or the number of SM cells positive for phosphorylated p38 between the two groups. In conclusion, our data suggest that JNK, not p38, is involved in cavernosal apoptosis during the acute phase after partial CN damage.
Animals ; Apoptosis ; Disease Models, Animal ; Electric Stimulation ; MAP Kinase Kinase 4/metabolism* ; Male ; Penile Erection ; Penis/pathology* ; Peripheral Nerve Injuries/pathology* ; Phosphorylation ; Prostatectomy ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases/metabolism*

Adult ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Penis/injuries* ; Postoperative Complications/epidemiology* ; Retrospective Studies ; Treatment Outcome ; Urogenital Surgical Procedures/methods* ; Young Adult

We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg^-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg^-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.
Animals ; Cofilin 1/metabolism* ; Electric Stimulation ; Erectile Dysfunction/etiology* ; Fibroblasts/pathology* ; Fibrosis/drug therapy* ; Lim Kinases/antagonists & inhibitors* ; Male ; Penile Diseases/drug therapy* ; Penis/innervation* ; Peripheral Nerve Injuries/pathology* ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; rho-Associated Kinases/genetics*