Efficacy of tadalafil on improvement of men with erectile dysfunction caused by COVID-19:A randomized placebo-controlled trial

Objective: According to the high prevalence of COVID-19 and the subsequent risk of men's sexual health, we decided to investigate the efficacy of tadalafil on improvement of men with erectile dysfunction caused by COVID-19.Methods: In this study, 70 outpatients who were recovered from COVID-19 without acute respiratory distress syndrome with negative polymerase chain reaction test and a complaint of erectile dysfunction were divided into two groups: 35 patients who received tadalafil 5 mg daily and 35 who received placebo. For each patient, basic assessment of sexual function was performed using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Then, treatment was started from 2 months after complete recovery of COVID-19 with negative polymerase chain reaction test for 3 months. At the end of the treatments, the patients were re-evaluated for sexual function using the complete version of IIEF questionnaire. Finally, the results before and after treatment in the intervention group were compared with those of the control group.Results: Treatment with both tadalafil and placebo improved the patients' sexual function criteria compared to the baseline. However, this improvement was significantly higher in the intervention group with tadalafil than the control group with placebo (p<0.05).Conclusion: Daily administration of tadalafil 5 mg seems to be effective and safe for improvement of erectile dysfunction caused by COVID-19.

Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.

The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.

Mesenchymal stem cell secretome: A promising therapeutic strategy for erectile dysfunction?

Objective:The secretome,comprising bioactive chemicals released by mesenchymal stem cells(MSCs),holds therapeutic promise in regenerative medicine.This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology,particularly for treating erectile dysfunction(ED),and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales,mechanisms,preclinical investigations,and therapeutic potential of the MSC secretome in this context.Methods:The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED.Subsequently,it delved into the existing knowledge regarding the MSC secretome,exploring its therapeutic potential.The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome.

Enhancing Erectile Function and Alleviating Andropause Symptoms: Clinical Efficacy of a Human Stem Cell Conditioned Medium Cream

Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, along with endothelial dysfunction of the corpora cavernosa and impaired blood flow to the penis considered underlying factors. However, the current treatments are limited to Phosphodiesterase-5 (PDE5) inhibitors. ED is the primary symptom of andropathy. This study reports the clinical efficacy of human stem cell-conditioned medium cream for ED treatment. Ten men without underlying diseases suspected of andropause with ED (mean age 43.2 ± 4.4 y, Hb 15.2 ± 0.6 gm/dL, AST/ALT 30.2/37.9 ± 12.4/14.0, eGFR 82.7 ± 12.4 mL/min/1.73 m2) were targeted. The cream was applied twice daily to the genital and scrotal areas. The erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Male Symptoms (AMS) scale were used to evaluate the participants before and 30 days after use, and the results were compared using paired t-tests. The post-use qualitative opinions were collected through interviews. Significant improvements were observed compared to baseline in the IIEF-5 (11.8 ± 4.6→17.2 ± 5.1, P < 0.001), and AMS (46.3 ± 6.7→37.6 ± 5.3, P < 0.001) scores post cream use. EHS did not show a statistically significant difference, but a trend towards improvement was observed. Qualitative feedback included increased morning erection, improved maintenance of erection during intercourse, and reduced post work fatigue. Human stem cell-conditioned medium contains endothelial growth factors that potentially contribute to the improvement of ED and andropause by enhancing corporal endothelial function. Future studies should include control groups to further investigate the efficacy of these treatments.

Frequency and Associated Factors of Erectile Dysfunction among Patients with Liver Cirrhosis in Parakou, Republic of Benin in 2022

Introduction: Erectile dysfunction is a pathology less expressed by patients, but it affects their quality of life. The objective of this work is to study erectile dysfunction among patients with cirrhosis in Parakou in 2022. Patients and Methods: This was a descriptive and analytical cross-sectional study with prospective data collection, conducted from February 1 to June 30, 2022 at the Teaching Hospital of Borgou/Alibori and the Military Teaching Hospital of Parakou. Men with liver cirrhosis who gave their informed verbal consent were included. Erectile dysfunction was diagnosed using IIEF-5 score. The prognosis of cirrhosis was assessed using Child-Pugh score. The data were analyzed by Epi Data analysis 2.3 software. Results: A total of 64 patients were included. Their mean age was 43.53 ± 13.13 years. Cirrhosis was secondary to chronic hepatitis B virus infection in 55 patients (85.94%). In this study, 42 patients (65.63%) had at least one decompensation of cirrhosis. Among the 64 patients included, 27 (42.18%) had erectile dysfunction. This erectile dysfunction was moderate in 12 patients (44.44%). The other sexual disorders found in these patients were decreased libido and ejaculation disorders. After multivariate analysis, the factors statistically associated with erectile dysfunction were: age (p Conclusion: Erectile dysfunction is common in patients with liver cirrhosis. It is more frequent when the cirrhosis is complicated and the patients are elderly. Nevertheless, it should be systematically sought in any patient with liver cirrhosis.

Mechanism of the Xuefu Zhuyu decoction in treating diabetes mellitus erectile dysfunction based on the CaSR/Gq-PLC-PKC pathway

Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin and randomly assigned into model,low-dose herbal,and high-dose herbal groups.All rats were administered normal saline or the corresponding drugs by oral gavage for 4 weeks.The related indices were detected using enzyme-linked immunosorbent assays,immunohistochemistry,western blotting,and transmission electron microscopy.Results:The levels of lectin-like oxidized low-density protein receptor-1,endothelin-1,NADH oxidase,vascular cell adhesion molecule-1,and intercellular adhesion molecule-1 in the model group were significantly higher than they were in the mock group but lower than they were in the herbal treatment group.The level of nitric oxide was lower in the model group than was in the mock group but higher than the level in the herbal treatment group.The calcium-sensitive receptor,phospho-protein kinase Cδ/protein kinase Cδ,phosphorylated c-Jun amino-terminal kinase/c-Jun amino-terminal kinase,and phospho-P38 mitogen-activated protein kinase/P38 mitogen-activated protein kinase expression levels in the model group were higher than were in the mock group but lower than were in the herbal treatment group.The structures of the Corpus cavernosum penis endothelial cells were significantly improved in the herbal treatment group than they did in the model group.Conclusion:Xuefu Zhuyu decoction can decrease injury to the endothelium,improve vascular endothelial diastolic and contractive function,and inhibit vascular fibrosis in rats with diabetes mellitus erectile dysfunction.This mechanism may be related to the CaSR/Gq-PLC-PKC pathway.

Headaches and Erectile Dysfunction Medications at UTH-Kara (Togo)

Introduction: Headaches are a common symptom affecting individuals worldwide, including in the tropical zone, and have been extensively studied in Togo. Phosphodiesterase-5 inhibitors, commonly prescribed for erectile dysfunction, are known to induce headaches, yet there is a lack of research on this topic in sub-Saharan Africa and Togo. Methods: A cross-sectional study conducted from February 1st to June 30th, 2023, including adult patients seeking erectile dysfunction treatment and prescribed PDE-5 inhibitors. Results: A total of 28 patients were included in the study, with an average age of 34.46 ± 7.5 years. The age group of 30 - 39 years was the most represented (53.57%). Among the participants, 67.86% had a history of chronic headaches. During the intake of PDE-5 inhibitors, 71.43% reported the onset of headaches. Among the 19 patients with chronic headaches, 68.42% developed headaches following PDE-5 inhibitor use (RR = 0.88, 95% CI: 0.55 - 1.40, p = 0.484). The characteristics of the induced headaches were similar to the patients’ pre-existing headaches in 78.95% of cases. Additional symptoms included nasal congestion (36.84%) and an urge to have a bowel movement (26.32%). Sildenafil (75.00%) and Tadalafil (25.00%) were the primarily prescribed PDE-5 inhibitors. The incidence of headaches did not significantly differ between the two groups (RR = 1.33, 95% CI: 0.67 - 2.64, p = 0.306). Treatment for the induced headaches involved self-medication with paracetamol (65.00%) and nonsteroidal anti-inflammatory drugs (NSAIDs) (35.00%). Conclusion: Headaches induced by PDE-5 inhibitors are a well-established reality, emphasizing the need for caution and warning in patients with pre-existing headache conditions, while individualized approaches are necessary to address the potential interplay between migraine medications and erectile dysfunction treatments.

Prevalence and Factors Associated with Erectile Dysfunction in Diabetic Patients at the National University Hospital Center Hubert Koutoukou Maga in Cotonou

Erectile dysfunction was one of the most common complications in diabetic patients. According to several studies, its prevalence was two to three times higher in diabetics than in the general population. But it has often been overlooked despite the fact that it seriously affects the quality of life. The aim of this study was to determine the prevalence of erectile dysfunction and its associated factors in diabetics’ patients. This was a cross-sectional analysis study of 76 male diabetic patients who consulted by the Department of Endocrinology from June 22, 2019 to September 25, 2019. Erectile dysfunction was diagnosed by calculating the IIEF score. Statistical comparisons were made between patients without and with Erectile dysfunction chi-square test with a significance level p Conclusion: This study showed a high prevalence of erectile dysfunction in diabetics. Significant concomitant factors were hypertension, diabetes imbalance and the duration of diabetes. It was, therefore, important to include systematic screening for erectile dysfunction at least annually, as well as other complications of diabetes.

Prevalence and risk factors of erectile dysfunction in three cities of China: a community-based study

Aim: To determine the age-adjusted prevalence of erectile dysfunction (ED) in 3 big cities of China and to explore its potential sociodemographic, medical and lifestyle correlates. Methods: A cross-sectional, population-based survey was conducted in three cities of China. Structured questionnaires were administered to 2 226 men, aged 20 - 86 years, by trained interviewers. Results: The age-adjusted prevalence of ED was 28.34 % (mild 15.99 %, moderate 7.14 %, severe 5.21 %). In the men above 40, the prevalence was 40.2%. Age was positively correlated with ED (P<0.01). Education was negatively correlated with ED (P<0.01). Spouse companionship, living condition were positively correlated with ED (P<0.01). Histories of cardiovascular disease, diabetes, and hyperlipidemia were positively correlated with ED (P<0.01). Cigarette smoking was not correlated with ED (P>0.05), while the cigarette consumption and duration were positively correlated with ED (P<0.01). Alcohol drinking is negatively correlated with ED (P<0.01). The duration of drinking was positively correlated with ED (P<0.01). Weekly alcohol consumption was not correlated with ED (P>0.05). Conclusion: The prevalence of ED increased with age. Cardiovascular disease, diabetes and hyperlipidemia were positively correlated with the increased prevalence. Sociodemographic and lifestyle factors, such as education, spouse companionship, living condition, cigarette and alcohol consumption or duration also have association with the prevalence of ED.

Improved spontaneous erectile function in men with mild-tomoderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year： a randomized trial

Aim： To test the hypothesis that sildenafil （50 mg nightly for one year） can improve spontaneous erectile function （EF） in men with mild-to-moderate arteriogenic erectile dysfunction （ED） responsive to erectogenic treatment. Methods： In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function （IIEF EF） and the peak systolic velocity （PSV） of penile cavernous arteries were used to measure the efficacy. Results： After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 （60.4%, 95% confidence interval [CI]： 45.3-74.2%） of the nightly group vs. 4 of 49 （8.2%, 95% CI： 2.3-19.6%） of the as-needed group. PSV improved by 11.2 cm/s （95% CI： 4.7-21.4; P = 0.012） in the nightly group but only by 3.4 cm/s （-5.1- 14.7; P = 0.435） in the as-needed group. IIEF EF normalized in 1 of 18 （5.6%, 95% CI： 0.1-27.3%） non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most （28/29, 97%） nightly group men who had initially normalized. Conclusion： Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

Our aim was to assess the impact of the association between elevated oestradiol （E2） and low testosterone （T） levels on erectile dysfunction （ED） severity. A total of 614 male patients with ED and a normal or low T level in association with normal or elevated E2 levels were enrolled. Patients underwent routine laboratory investigations in addition to measurements of total T, total E2, follicle-stimulating hormone （FSH）, luteinizing hormone （LH） and prolactin. We compared the responses to the erectile function domain, Q3 （achieving erection） and Q4 （maintaining erection） of the International Index for Erectile Function （IIEF） score in patients with the following： normal T and E2 levels; low T level; low T level and elevated E2 level; and elevated E2 level. Of the patients included, 449 （73.1%） had normal T and E2 levels, 110 （17.9%） had a low T level, 36 （5.9%） had a low T level and an elevated E2 level, and 19 （3.1%） had an elevated E2 level. Increased ED severity was significantly associated with low T levels, elevated E2 levels, and both a low T level and an elevated E2 level. Additionally, the mean values of the EF-domain, Q3 and Q4 were significantly lower in patients with both a low T level and an elevated E2 level compared to patients with any condition alone. In conclusion, a low T level had the primary effect on erectile function; however, a concomitantly elevated E2 level had an additive impairment effect.

Endothelium-specific gene and stem cell-based therapy for erectile dysfunction

Erectile dysfunction （ED） commonly results from endothelial dysfunction of the systemic vasculature. Although phosphodiesterase type 5 （PDE-5） inhibitors are effective at treating most cases of ED, they must be taken routinely and are ineffectual for a meaningful number of men. In recent years gene and stem cell-based therapies targeted at the penile endothelium have been gaining momentum in preclinical studies. These early studies reveal that gene and stem cell-based therapies may be both enduring and efficacious, and may eventually lead to a cure for ED. The following review will highlight our current understanding of endothelial-specific gene and stem cell-based therapies performed to date in a number of experimental animal models.

Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction:a randomized double-blind,parallel,placebo-controlled clinical study

Aim： To assess the efficacy and safety of tadalafil in comparison to a placebo, when taken on demand for 12 weeks by East/Southeast Asian men with erectile dysfunction （ED）, Methods： This multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August 2002 and February 2003. Men more than 18 years of age with mild to severe ED of various etiologies were randomized to receive a placebo or 20 mg of tadalafil taken as needed （maximum once daily）. Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile diary and Global Assessment Questions. Results： Tadalafil significantly improved erectile function as compared to the placebo （P 〈 0.001）. At the endpoint, the patients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts （Sexual Encounter Profile question 3： 70.9% compared to 33.5% in the placebo） and a greater proportion of improved erections （Global Assessment Question： 86.2% compared to 30.1%）. Most （≥3%） treatment emergent adverse events were mild or moderate. The most common treatment emergent adverse events were headache, back pain, dizziness and dyspepsia. Conclusion： Tadalafil was an effective and well-tolerated treatment for ED in East and Southeast Asian men.

Application of pudendal evoked potentials in diagnosis of erectile dysfunction

Aim: Extensive neurophysiological investigations were carried out in 100 healthy subjects and 84 patients with penileerectile dysfunction. Methods: Following examinations were performed, spinal and scalp somatosensory evoked poten-tials (SEPs) to stimulation of the dorsal nerve of penis, motor evoked potentials (MEPs) from bulbocavernosus (BC) inresponse to scalp and spinal root stimulation, and measurement of sacral reflex latency (SRL) from anal sphincter (AS).Results: In the healthy subjects, the mean sensory total conduction time (sensory TCT), as measured at the peak of thescalp P1 (P40) wave was 39.73 ms. The mean sensory central conduction time (sensory CCT = spinal-to-scalp conductiontime) was 28.98 ms. The mean peripheral conduction time (PCP) was 9.40 ins. Transcranial brain stimulation was per-formed by using a magnetic stimulator during voluntary contraction of the examined muscle. Spinal root stimulation wasperformed at rest. Motor total conduction time (motor TCT) to BC muscles was 20.48 ms. Motor central conductiontime (motor CCT) to sacral cord segments controlling BC muscles was 14.42 ms at rest. The mean SRL was 35.13 ms.Conclusion: Combined or isolated abnormalities of SEPs, MEPs, and SRL were found in patients with erectile dysfunc-tion. (Asian J Androl 1999 Sep; 1 : 145 - 150)

Mobilisation of endothelial progenitor cells： one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats

Diabetes-induced oxidative stress plays a critical role in the mobilisation of endothelial progenitor cells （EPCs） from the bone marrow to the circulation. This study was designed to explore the effects of chronic melatonin administration on the promotion of the mobilisation of EPCs and on the preservation of erectile function in type I diabetic rats. Melatonin was administered to streptozotocin-induced type I diabetic rats. EPCs levels were determined using flow cytometry. Oxidative stress in the bone marrow was indicated by the levels of superoxide dismutase and malondialdehyde. Erectile function was evaluated by measuring the intracavernous pressure during an electrostimulation of the cavernous nerve. The density of the endothelium and the proportions of smooth muscle and collagen in the corpus cavernosum were determined by immunohistochemistry. The administration of melatonin increased the superoxide dismutase level and decreased the malondialdehyde level in the bone marrow. This effect was accompanied by an increased level of circulating EPCs in the diabetic rats. The intracavernous pressure to mean arterial pressure ratio of the rats in the treatment group was significantly greater, compared with diabetic control rats. The histological analysis demonstrated an increase in the endothelial density of the corpus cavernosum after the administration of melatonin. However, melatonin treatment did not change the proportions of smooth muscle and collagen in the corpus cavernosum of diabetic rats. Chronic administration of melatonin has a beneficial effect on preventing erectile dysfunction （ED） in type I diabetic rats. Promoting the mobilisation of EPCs is one of the possible mechanisms involved in the improvement of ED.

Help-seeking behavior for erectile dysfunction： clinic-based survey in China

The behavior of Chinese patients seeking help for erectile dysfunction （ED） has not been described in detail. This was an observational study conducted using an outpatient clinic-based questionnaire survey of ED patients. From 2008 to 2009, physicians in 10 medical centers in China enrolled 2693 men （aged 25-70years） diagnosed with ED. The diagnosis was based on the International Index of Erectile Function 5 （IIEF-5） Questionnaire. The men completed a survey that asked questions about demographics, marital status, education level and household income as well as help-seeking behavior and awareness of medical therapy. The mean age of the 2693 men was 43.4 5.3years; 73% were 〈50-years-old and 49% had a high household income. The mean time between noticing ED and taking the first treatment was 4.3 2.1months. Of the 2577 respondents, physicians （54%） and the internet （52%） were most frequently consulted sources for information about ED. Young ED patients preferred using the internet and older patients preferred consulting with physicians. Western medicine （19%） and traditional Chinese medicine （16%） were most frequently used for treatment. Young ED patients preferred to first search the internet for information, whereas older patients first asked physicians for help. Side effects of treatment were the greatest concern, especially for older patients. Physicians and the internet are frequently consulted for ED information and therapy. On the basis of these survey results, we believe that physicians in China should enhance health education about ED, especially via the internet.

Adipose-derived stem cells modified by BDNF gene rescue erectile dysfunction after cavernous nerve injury

Cavernous nerve injury is the main cause of erectile dysfunction following radical prostatectomy.The recovery of erectile function following radical prostatectomy remains challenging.Our previous studies found that injecting adipose-derived stem cells(ADSCs)into the cavernosa could repair the damaged cavernous nerves,but the erectile function of the treated rats could not be restored to a normal level.We evaluated the efficacy of ADSCs infected with a lentiviral vector encoding rat brain-derived neurotrophic factor(lenti-rBDNF)in a rat model of cavernous nerve injury.The rats were equally and randomly divided into four groups.In the control group,bilateral cavernous nerves were isolated but not injured.In the bilateral cavernous nerve injury group,bilateral cavernous nerves were isolated and injured with a hemostat clamp for 2 minutes.In the ADSCGFP and ADSCrBDNF groups,after injury with a hemostat clamp for 2 minutes,rats were injected with ADSCs infected with lenti-GFP(1×106 in 20μL)and lenti-rBDNF(1×106 in 20μL),respectively.Erectile function was assessed 4 weeks after injury by measuring intracavernosal pressures.Then,penile tissues were collected for histological detection and western blot assay.Results demonstrated that compared with the bilateral cavernous nerve injury group,erectile function was significantly recovered in the ADSCGFP and ADSCrBDNF groups,and to a greater degree in the ADSCrBDNF group.Neuronal nitric oxide synthase content in the dorsal nerves and the ratio of smooth muscle/collagen were significantly higher in the ADSCrBDNF and ADSCGFP groups than in the bilateral cavernous nerve injury group.Neuronal nitric oxide synthase expression was obviously higher in the ADSCrBDNF group than in the ADSCGFP group.These findings confirm that intracavernous injection with ADSCs infected with lenti-rBDNF can effectively improve erectile dysfunction caused by cavernous nerve injury.This study was approved by the Medical Animal Care and Welfare Committee of Wuhan University,China(approval No.2017-1638)on June 20,2017.

The effects of long-term administration of tadalafil on STZ-induced diabetic rats with erectile dysfunction via a local antioxidative mechanism

Type 5 phosphodiesterase inhibitors （PDE51s） are well known being effective via the nitric oxide and cyclic guanosine monophosphate （NO-cGMP） pathway and are widely used in the treatment of diabetic erectile dysfunction （ED）. However, it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE51s. The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE51s. Three groups of Sprague-Dawley rats were utilized： Group N, the normal control; Group D, streptozotocin （STZ）-induced diabetic rats as a control; and Group D＋T, STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks. Erectile function was assessed by intracavernous pressure （ICP） and mean arterial pressure （MAP） during electrical stimulation of the cavernous nerve before euthanasia. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD） and mitochondrial membrane potential （MMP） of cavernous tissue were assessed by biochemical analysis. The morphology of mitochondria was observed by electron microscopy. The ICP/MAP ratio was higher in Group D＋T than in Group D （P〈O.05）. The levels of MDA decreased and the activities of SOD increased in Group D＋T in comparison with Group D （P〈O.05）. The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks. The morphology changes of mitochondria were also remarkably ameliorated in Group D＋T. Collectively, the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis via a local antioxidative stress pathway. Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.

Emerging neuromodulatory molecules for the treatment of neurogenic erectile dysfunction caused by cavernous nerve injury

Advances in the neurobiology of growth factors, neural development, and prevention of cell death have resulted in a heightened clinical interest for the development of protective and regenerative neuromodulatory strategies for the cavernous nerves （CNs）, as therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function. Nitric oxide released from the axonal end plates of these nerves within the corpora cavernosa causes relaxation of smooth muscle, initiating the haemodynamic changes of penile erection as well as contributing to maintained tumescence; the loss of CN function is primarily responsible for the development of erectile dysfunction （ED） after pelvic surgery and serves as the primary target for potential neuroprotective or regenerative strategies. Evidence from pre-clinical studies for select neuromodulatory approaches is reviewed, including neurotrophins, glial cell line-derived neurotrophic factors （GDNF）, bone morphogenic proteins, immunophilin ligands, erythropoetin （EPO）, and stem cells.