Calpain activation contributes to hyperglycemia-induced endothelial dysfunction and apoptosis. This study was designed to investigate the role of calpain inhibition in improving diabetic erectile dysfunction (ED) in mice. Thirty-eight-week-old male C57BL/6J mice were divided into three groups: (1) nondiabetic control group, (2) diabetic mice + vehicle group, and (3) diabetic mice + MDL28170 (an inhibitor of calpain) group. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin at 60 mg kg^-1 body weight for 5 consecutive days. Thirteen weeks later, diabetic mice were treated with MDL28170 or vehicle for 4 weeks. The erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were collected for measurement of calpain activity and the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining was used to evaluate apoptosis. Caspase-3 expression and activity were also measured to determine apoptosis. Our results showed that erectile function was enhanced by MDL28170 treatment in diabetic mice compared with the vehicle diabetic group. No differences in calpain-1 and calpain-2 expressions were observed among the three groups. However, calpain activity was increased in the diabetic group and reduced by MDL28170. The eNOS-NO-cGMP pathway was upregulated by MDL28170 treatment in diabetic mice. Additionally, MDL28170 could attenuate apoptosis and increase the endothelium and smooth muscle levels in corpus cavernosum. Inhibition of calpain could improve erectile function, probably by upregulating the eNOS-NO-cGMP pathway and reducing apoptosis.
Animals ; Apoptosis/drug effects* ; Calpain/antagonists & inhibitors* ; Cyclic GMP/biosynthesis* ; Diabetes Complications/drug therapy* ; Diabetes Mellitus, Experimental/complications* ; Dipeptides/therapeutic use* ; Endothelium/metabolism* ; Enzyme Inhibitors/therapeutic use* ; Erectile Dysfunction/etiology* ; In Situ Nick-End Labeling ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth/metabolism* ; Nitric Oxide Synthase Type III/biosynthesis* ; Penis/enzymology* ; Up-Regulation

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*

Objective: To evaluate the safety, efficacy and tolerability of China-made sildenafil citrate (Jinge) in the treatment of ED. METHODS: We conducted a multi-center, randomized, double-blind and placebo-controlled clinical trial among 222 ED patients in five urological or andrological clinics of China. The patients were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n = 111) for 8 weeks. We obtained and analyzed the demographic and clinical characteristics of the patients, the scores of International Index of Erectile Function (IIEF), the success rate of sexual intercourse, and the incidence of adverse events. RESULTS: No statistically significant differences were found between the patients of the SC and those of the placebo group in the mean age (［47.2±11.32］ yr vs ［46.67±13.08］ yr, P>0.05), psychological etiology (27.93% vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of smoking, drinking or allergy. Compared with the placebo controls, the SC-treated patients showed significant increases in the excellence rate of effectiveness (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%, P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The effectiveness rates on organic, psychogenic and mixed types ED were remarkably higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were observed in 32 cases in the SC group as compared with 13 in the placebo control. CONCLUSIONS China-made sildenafil citrate is an effective, safe and well-tolerated drug for ED of different etiologies in the Chinese population.
Aged ; China ; Coitus ; Double-Blind Method ; Drug Compounding ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Smoking ; Treatment Outcome

Objective: To prove the clinical efficacy of umbilicus application of Huobi Powder for the treatment of erectile dysfunction (ED) with the traditional Chinese medicine (TCM) syndrome of kidney deficiency dampness by related clinical indexes. METHODS: This randomized controlled double-blind clinical study included 72 ED patients with the TCM syndrome of kidney deficiency dampness treated by 12-hour application of Huobi Powder (the trial group, n = 36) or placebo (the control group, n = 36) to the umbilicus qd for 28 consecutive days. We recorded the IIEF-5 and Erection Quality Scale (EQS) scores, TCM syndrome indexes, radial rigidity of the erectile penis, and the angle of penile erection before and after treatment. We established a database with the collected data and performed statistical analysis with the SPSS21.0 software. RESULTS: Statistically significant differences were observed after treatment between the trial and control groups in the TCM syndrome-based efficacy (69.44% vs 36.11%, P <0.01) and Western medicine-based clinical effectiveness (77.78% vs 36.11%, P <0.01). The trial group, as compared with the control, showed remarkably decreased TCM syndrome indexes (18.19 ± 9.12 vs 12.97 ± 11.92, P <0.05), increased IIEF-5 score (13.83 ± 4.91 vs 18.67 ± 3.09, P <0.01), radial rigidity of the erectile penis (［53.43 ± 11.05］% vs ［71.96 ± 12.92］%, P <0.01) and the angle of penile erection (［42.15 ± 11.77］% vs ［66.96 ± 12.34］%, P <0.01), but no significant difference in the EQS score (37.11 ± 16.70 vs 35.33 ± 14.11, P >0.05). CONCLUSIONS Umbilicus application of Huobi Powder has a definite clinical effect on ED with the TCM syndrome of kidney deficiency dampness.
Double-Blind Method ; Drugs, Chinese Herbal ; administration & dosage ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Kidney Diseases ; complications ; drug therapy ; Male ; Medicine, Chinese Traditional ; Penile Erection ; Powders ; administration & dosage ; Treatment Outcome ; Umbilicus

Objective: To make a real-world study on the efficacy and safety of traditional Chinese medicine (TCM) combined with sildenafil in the treatment of erectile dysfunction (ED) that failed to respond to TCM medication. METHODS: This study included 1 038 ED patients with the International Index of Erectile Function-5 (IIEF-5) scores ≤21 and improvement <30% after 4 weeks of TCM medication, differentially diagnosed with kidney-yang or kidney-yin deficiency syndrome. We administered TCM combined with sildenafil (Viagra, Pfizer Pharmaceutical Co., Ltd) at 100 mg 1 hour before sexual intercourse. After 2 and 4 weeks of medication, we recorded the scores in IIEF-5, erection hardness, Sexual Encounter Profile question 2 (SEP-2: whether vaginal penetration is successful), SEP-3 (whether sexual intercourse is successful), and TCM Syndromes Scale as well as the indexes of routine blood, urine, liver function, and renal function of the patients, and compared them with those obtained before treatment. RESULTS: No serious adverse reactions were observed in any of the patients. Compared with the baseline, the patients achieved significantly increased IIEF-5 scores after 2 and 4 weeks of medication (15.01 ± 2.25 vs 16.96 ± 2.55 and 19.41 ± 2.82, P <0.05), penileelectionhardness remarkably improved at 4 weeks (3.36% vs 44.58%, P<0.05), and the positive answers to SEP-2 and SEP-3 both markedly increased at 2 (38.11% vs 90.49%, P<0.05; 22.01% vs 63.77% , P<0.05) and 4 weeks (38.11% vs 96.95% , P<0.05; 22.01% vs 89.73%, P<0.05). CONCLUSIONS TCM combined with sildenafil is safe and effective in the treatment of ED in Chinese men, which can significantly improve the IIEF-5 score and erection hardness of the patients.
Aged ; Asian Continental Ancestry Group ; Coitus ; Drug Therapy, Combination ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Male ; Medicine, Chinese Traditional ; Penile Erection ; drug effects ; physiology ; Sildenafil Citrate ; therapeutic use ; Treatment Outcome ; Yang Deficiency ; complications ; Yin Deficiency ; complications

Objective: To investigate the safety and efficacy of pancreatic kininogenase combined with sildenafil in the treatment of erectile dysfunction(ED) in type 2 diabetes mellitus (DM) patients in the high-altitude area. METHODS: This study included 93 ED patients with type 2 DM, all residents of the Xining area 1500 meters above sea level. We randomly divided them into an experimental group (n = 48) and a control group (n = 45), the former treated with pancreatic kininogenase(120 u, tid) and sildenafil (25 mg, qd at bedtime), while the latter with sildenafil only (25 mg, qd at bedtime).After 4 and 8 weeks of medication, we obtained the penile hemodynamic parameters,IIEF-5 scores, and sexual intercourse satisfaction(SIS) scores and compared them between the two groups of patients. RESULTS: There were no statistically significant differences in age or DM course between the two groups of patients (P >0.05).Compared with the baseline, both the experimental and control groups showed remarkably improvement inthe IIEF-5 score (8.81 ± 2.06 vs 11.54 ± 7.72 and 8.29 ± 1.91 vs 9.37± 1.65, P <0.05), SIS score (3.35 ± 2.43vs6.83± 2.61and 3.41 ± 2.38 vs 4.92± 2.49, P <0.05), and penile hemodynamic parameters obtained by color duplex Doppler ultrasonography(P <0.05), with significant differences between the two groups in the IIEF-5 score (11.54 ± 7.72 vs 9.37± 1.65, P <0.05) and SIS score (6.83± 2.61 vs 4.92± 2.49, P <0.05) but not in the penile hemodynamic parameters (P >0.05). Even more remarkable improvement was observed at 8 weeks in the experimental and control groups in the IIEF-5 score (19.29± 1.85 and 15.43± 1.74)(P <0.05), SIS score (11.73 ± 2.57 and 6.55± 2.71) (P <0.05), and penile hemodynamic parameters(P <0.05), all with significant differences between the two groups (P <0.05). CONCLUSIONS Pancreatic kininogenase combined with sildenafil has a better clinical effect than sildenafil alone on ED in type 2 DM patientsin the high-altitude area.
Aged ; Altitude ; Coitus ; Diabetes Mellitus, Type 2 ; complications ; Drug Therapy, Combination ; Erectile Dysfunction ; etiology ; therapy ; Humans ; Kallikreins ; therapeutic use ; Male ; Pancreas ; enzymology ; Penile Erection ; drug effects ; physiology ; Penis ; physiology ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Treatment Outcome

The treatment of Peyronie's disease has been a challenge to urologists, as most of the current oral medications are considered hardly valid and the rest of the therapies require strict control of indications, some of which remain controversial, while the final surgical option may be associated with complications such as penile shortening or erectile dysfunction. Collagenase clostridium histolyticum has been proved to be effective in dissolving the penile cavernosal plaque and approved by the Food and Drug Administration of the USA as the first drug to be used for the treatment of Peyronie's disease. This article presents an introduction to the characteristics, safety, efficacy, and procedures of this new treatment, which may benefit urologists and the patients with Peyronie's disease.
Erectile Dysfunction ; etiology ; Humans ; Injections, Intralesional ; Male ; Microbial Collagenase ; therapeutic use ; Penile Induration ; drug therapy ; surgery ; Penis ; Postoperative Complications ; etiology ; Treatment Outcome

The vacuum erectile device (VED) uses negative pressure to increase blood inflow into the corpora cavernosum, with a ring at the base of the penis to maintain erection for intercourse or without a ring for penile rehabilitation. Owing to the limitation of phosphodiesterase 5 inhibitors (PDE5I) shown in the treatment of refractory erectile dysfunction (ED), the use of VED has resurged and is becoming the first line therapy in the treatment of ED following radical prostatectomy (RP). Currently, the combination therapy of VED with PDE5I and that of VED with intracavernous injection are advocated for post-RP ED. Hereby, we review the role of VED in penile rehabilitation, its underlying mechanisms, and the combination therapies for it.
Coitus ; Combined Modality Therapy ; methods ; Erectile Dysfunction ; drug therapy ; etiology ; rehabilitation ; Humans ; Male ; Penile Prosthesis ; Penis ; blood supply ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Prostatectomy ; adverse effects ; Regional Blood Flow ; Vacuum

PURPOSE: This study was performed to examine the treatment of erectile dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI). MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately after the cavernous nerve injury in group 3, SPION-MSCs were injected into the cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs revealed abundant uptake of SPION in the cytoplasm. After injection of 1x10(6) SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense signal induced by the injection. The presence of SPION in the corpora cavernosa was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous nerve injury had significantly lower erectile function than did rats without cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed higher erectile function than did the group without SPION-MSCs (p<0.05). The presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION-MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats. Erectile dysfunction recovered and could be monitored by MRI.
Animals ; Contrast Media/pharmacology ; Dextrans/*pharmacology ; Disease Models, Animal ; Drug Delivery Systems/methods ; *Erectile Dysfunction/diagnosis/etiology/therapy ; Magnetic Resonance Imaging/methods ; *Magnetite Nanoparticles ; Male ; Mesenchymal Stem Cell Transplantation/*methods ; Monitoring, Physiologic/methods ; Penis/*innervation ; *Peripheral Nerve Injuries/complications/diagnosis/physiopathology/therapy ; Rats ; Suspensions ; Treatment Outcome

PURPOSE: To evaluate how much the improvement of lower urinary tract symptoms (LUTS) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function. MATERIALS AND METHODS: A total of 187 patients were enrolled in this study. Patients were randomly assigned to receive either tamsulosin 0.2 mg (group A) or tamsulosin 0.2 mg and solifenacin 5 mg (group B). At 4 weeks and 12 weeks, the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 (IIEF5), International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS) questionnaire, uroflowmetry, and bladder scan. RESULTS: Both groups A and B showed statistically significant improvements in IPSS, OABSS, and quality of life (QoL). Group A showed improved maximum flow rate, mean flow rate, and residual urine volume by time. Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time. The IIEF5 score was not improved in either group. In group A, the IIEF5 score dropped from 13.66+/-4.97 to 11.93+/-6.14 after 12 weeks (p=0.072). Group B showed a decline in the IIEF5 score from 13.19+/-5.91 to 12.45+/-6.38 (p=0.299). Although group B showed a relatively smaller decrease in the IIEF5 score, the difference between the two groups was not significant (p=0.696). CONCLUSIONS: Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL. The improvement in storage symptoms did not affect erectile function.
Aged ; Drug Therapy, Combination/methods ; Erectile Dysfunction/*drug therapy/etiology ; Humans ; Lower Urinary Tract Symptoms/complications/*drug therapy ; Male ; Middle Aged ; Quality of Life ; Questionnaires ; Quinuclidines/*administration & dosage ; Rheology ; Sulfonamides/*administration & dosage ; Tetrahydroisoquinolines/*administration & dosage ; Treatment Outcome ; Urological Agents/*administration & dosage