ABSTRACT
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ABSTRACT
Epalrestat, an aldose reductase inhibitor (ARI), was adopted to improve the function of peripheral nerves in diabetic patients. The aim of this study was to investigate whether epalrestat could restore the erectile function of diabetic erectile dysfunction using a rat model. From June 2016, 24 rats were given streptozocin (STZ) to induce the diabetic rat model, and epalrestat was administered to ten diabetic erectile dysfunction (DED) rats. Intracavernous pressure (ICP) and mean systemic arterial pressure (MAP), levels of aldose reductase (AR), nerve growth factor (NGF), neuronal nitric oxide synthase (nNOS), α-smooth muscle antigen (α-SMA), and von Willebrand factor (vWF) in the corpus cavernosum were analyzed. We discovered that epalrestat acted on cavernous tissue and partly restored erectile function. NGF and nNOS levels in the corpora were increased after treatment with epalrestat. We also found that the content of α-SMA-positive smooth muscle cells and vWF-positive endothelial cells in the corpora cavernosum were declined. Accordingly, epalrestat might improve erectile function by increasing the upregulation of NGF and nNOS to restore the function of the dorsal nerve of the penis.
Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Diabetes Mellitus, Experimental/physiopathology , Erectile Dysfunction/drug therapy , Rhodanine/analogs & derivatives , Thiazolidines/pharmacology , Animals , Diabetes Mellitus, Experimental/chemically induced , Male , Muscle, Smooth/metabolism , Myocytes, Smooth Muscle/metabolism , Nerve Growth Factor/metabolism , Nitric Oxide Synthase Type I/metabolism , Penile Erection/drug effects , Penis/physiopathology , Rats , Rats, Sprague-Dawley , Rhodanine/pharmacology , StreptozocinABSTRACT
OBJECTIVE: To investigate the clinical effects of circumcision by surgical plane positioning with a disposable circumcision suture device in the treatment of phimosis and redundant prepuce. METHODS: From September 2016 to June 2017, we treated 250 patients with phimosis or redundant prepuce, 127 by conventional circumcision (the control group) and the other 123 by surgical plane positioning with a disposable circumcision suture device (the observation group). We compared the operation time, intra-operative bleeding, preputial frenulum alignment, postoperative ecchymosis, and postoperative penile appearance between the two groups of patients. RESULTS: Compared with the controls, the patients in the observation group showed significantly longer operation time (ï¼»4.48 ± 1.18ï¼½ vs ï¼»7.17 ± 1.42ï¼½ min, P<0.05), lower rates of intra-operative frenulum bleeding (15.0% ï¼»19/127ï¼½ vs 4.1% ï¼»5/123ï¼½, P<0.05) and frenulum misalignment (26.8% ï¼»34/127ï¼½ vs 0.8% ï¼»1/123ï¼½, P<0.05), higher incidence of postoperative ecchymosis (41.7% ï¼»53/127ï¼½ vs 21.1% ï¼»26/123ï¼½, P<0.05), and higher satisfaction of the patients with the postoperative penile appearance (92.9% ï¼»18/127ï¼½ vs 98.4% ï¼»121/123ï¼½, P<0.05). However, no statistically significant difference was found between the control and observation groups in intra-operative non-frenulum bleeding (4.7% ï¼»6/127ï¼½ vs 1.6% ï¼»2/123ï¼½, P = 0.164). CONCLUSIONS: Circumcision by surgical plane positioning with a disposable circumcision suture device can effectively avoid preputial frenulum misalignment, reduce intra-operative bleeding, and improve postoperative penile appearance.
Subject(s)
Circumcision, Male/instrumentation , Penis/abnormalities , Penis/surgery , Phimosis/surgery , Suture Techniques/instrumentation , Disposable Equipment , Ecchymosis/etiology , Foreskin , Humans , Incidence , Male , Operative Time , Personal Satisfaction , Postoperative Complications/etiology , Postoperative PeriodABSTRACT
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.
Subject(s)
Diabetes Mellitus, Experimental/complications , Erectile Dysfunction/drug therapy , Kallikreins/therapeutic use , Penile Erection/drug effects , Penis/drug effects , Urological Agents/therapeutic use , Animals , Cyclic GMP/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Erectile Dysfunction/etiology , Erectile Dysfunction/metabolism , Erectile Dysfunction/physiopathology , Kallikreins/pharmacology , Male , Muscle, Smooth, Vascular/metabolism , 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/pharmacology , Sildenafil Citrate/therapeutic use , Treatment Outcome , Urological Agents/pharmacologyABSTRACT
Erectile dysfunction (ED) is a major complication of diabetes, and many diabetic men with ED are refractory to common ED therapies. Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in diabetic animal models. However, inadequate cell homing to damaged sites has limited their efficacy. Therefore, we explored the effect of ADSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) on improving the erectile function of streptozotocin-induced diabetic rats with an external magnetic field. We found that SPIONs effectively incorporated into ADSCs and did not exert any negative effects on stem cell properties. Magnetic targeting of ADSCs contributed to long-term cell retention in the corpus cavernosum and improved the erectile function of diabetic rats compared with ADSC injection alone. In addition, the paracrine effect of ADSCs appeared to play the major role in functional and structural recovery. Accordingly, magnetic field-guided ADSC therapy is an effective approach for diabetes-associated ED therapy.
Subject(s)
Adipocytes , Diabetes Complications/drug therapy , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Magnetite Nanoparticles , Stem Cell Transplantation/methods , Stem Cells , Adipocytes/metabolism , Animals , Cell Survival , Diabetes Mellitus, Experimental/complications , Drug Delivery Systems , Magnetic Fields , Male , Penile Erection , Penis/cytology , Penis/drug effects , Penis/metabolism , Rats , Rats, Sprague-Dawley , Stem Cells/metabolism , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
Methylation modification is an important cellular mechanism of gene expression regulation. Dimethylarginine dimethylaminohydrolase-2 (DDAH-2) protein is a pivotal molecular for endothelium function. To explore the effects of 5-aza-deoxycytidine (5-aza), a demethylation agent, in hyperhomocysteinemia (hhcy)-related erectile dysfunction (ED) rats, 5-aza (1 mg kg-1 ) was administrated to Sprague-Dawley hhcy-rats induced by supplemented methionine chow diet. Erectile function, nitric oxide-cyclic guanosine monophosphate (NO-cGMP) levels, expression of DDAH-2 protein and promoter methylation status of DDAH-2 were studied in the corpora cavernosa. We found that supplemented methionine diet induced a high homocysteine level after 6 weeks of treatment. DDAH-2 protein was down-regulated in the corpora cavernosa while the administration of 5-aza up-regulated DDAH-2 expression and restored erectile function. The methionine-fed rats showed high methylation levels of DDAH-2 promoter region while the group treated with 5-aza demonstrated lower-methylation levels when compared to the methionine-fed group. Besides, the administration of 5-aza improved NO and cGMP levels in methionine-fed rats. Therefore, the methylation mechanism involves in ED pathogenesis, and demethylation offers a potential new strategy for ED treatment.
Subject(s)
Azacitidine/therapeutic use , Erectile Dysfunction/drug therapy , Homocysteine/blood , Hyperhomocysteinemia/drug therapy , Penis/metabolism , Amidohydrolases/metabolism , Animals , Cyclic GMP/blood , Disease Models, Animal , Down-Regulation , Erectile Dysfunction/etiology , Hyperhomocysteinemia/complications , Male , Nitric Oxide/blood , Promoter Regions, Genetic , Rats , Rats, Sprague-DawleyABSTRACT
The transformation of tunica albuginea-derived fibroblasts (TAFs) into myofibroblasts plays an important role in the pathological progress of Peyronie's disease (PD). However, no treatment which addresses this transformation is currently available. Estrogen has been shown to inhibit the progression of fibrosis in a number of fibrotic diseases. The aim of this study was to determine whether estrogen [17ßestradiol (E2)] suppresses the diffentiation of primary rat TAFs into myofibroblasts in vitro. TAFs obtained from male SpragueDawley rats were stimulated with either transforming growth factorß1 (TGFß1) or E2. Western blot analysis and immunofluorescence staining were used to assess changes in the expression levels of αsmooth muscle actin (αSMA). The expression levels of additional proteins (GAPDH, pSmad2, Smad2, Smad4, RhoA, Rac1, ROCK1 and ROCK2) were also measured by western blot analysis. We used collagen gel assays to assess cell contractility. Additionally, the concentration of hydroxyproline in the TAF cell culture medium was detected using commercially available kits. We found that E2 reduced αSMA expression which was induced by TGFß1. E2 also suppressed the TGFß1induced increase in the concentration of hydroxyproline (a marker of collagen) in addition to suppressing the contraction of TAFs. The key processes affected by TGFß1 treatment included the phosphorylation of Smad2, ras homolog gene family, member A (RhoA) and Rhoassociated, coiled-coil containing protein kinase 2 (ROCK2); this increase in phosphorylation was inhibited by treatment with E2. Collectively, these results demonstrate that by modulating the activation of the TGFß1Smad and RhoAROCK2 signaling pathways, E2 inhibited the transformation of TAFs into myofibroblasts, decreased the expression of collagen and suppressed the contraction of myofibroblasts in response to TGF-ß1 stimulation.