Treatment Of Erectile Dysfunction Research Articles

Inflammatory cytokine profiles in erectile dysfunction: a bidirectional Mendelian randomization

ObjectivesInflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach.MethodsSingle nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion.ResultsFrom a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis.ConclusionsChanges in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.

Evaluating the efficacy and safety of platelet-rich plasma injection for erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

Platelet-rich plasma (PRP) is rich in factors that play a role in stem cell recruitment, inflammation modulation, and angiogenesis. With numerous preclinical and clinical studies exploring PRP as a potential treatment for erectile dysfunction (ED), this study focused on assessing the effectiveness of intracorporeal PRP injection for ED patients based on randomized controlled trials (RCTs). The study sought to evaluate the efficacy and safety of intracorporeal injection of PRP in treating ED through a systematic review and meta-analysis of RCTs. This study adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was conducted on online databases (PubMed, Scopus, and ScienceDirect) to identify RCTs comparing PRP with a placebo for ED treatment. The primary outcomes assessed were the proportion of patients achieving the minimal clinically important difference in the International Index of Erectile Function (IIEF) domain and the change in the IIEF domain from baseline. The results were combined as a standardized mean difference between the PRP and placebo groups. Three RCTs comprising 230 patients were included. The overall effect favored PRP over placebo: total patients attaining minimal clinically important difference in the IIEF domain (odds ratio [OR], 5.64; 95% confidence interval [CI], 2.05 to 15.55; P = .0008), IIEF change from baseline (mean difference [MD], 2.99; 95% CI, 1.74 to 4.24; P = .00001), PSV (MD, 9.34; 95% CI, 0.84 to 17.84; P = .03), end-diastolic volume (standardized MD, 0.50; 95% CI, 0.17 to 0.83; P = .003), Sexual Encounter Profile question 3 (standardized MD, 0.78; 95% CI, 0.45 to 1.12; P = .00001), and visual analog scale score (MD, -0.30; 95% CI, -0.53 to -0.08; P = .008). PRP appears to be a safe and effective treatment for mild-to-moderate ED. However, further support from high-quality RCTs is needed to strengthen these findings.

A Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening

Background: PDE5 inhibitors have had a surge in popularity over the last decade owing to their efficacy in the treatment of erectile dysfunction, coronary vasculopathy, and pulmonary arterial hypertension. These inhibitors exhibit competitive binding with phosphodiesterase type 5 and inhibit the hydrolysis of cyclic guanosine monophosphate, hence elevating the levels of cGMP in smooth muscle cells and prolonging the duration of an erection. However, due to production costs and side effects, further research is needed to discover new PDE5 inhibitors. background: The field of PDE5 inhibitors has risen in popularity in the past decade because of the success of PDE5 inhibitors in treating erectile dysfunction. Due to the structural identity with cGMP; PDE5 inhibitors competitively bind with PDE5 and limit cGMP hydrolysis, which raises the cGMP level in smooth muscle cells and lengthens the duration of an erection. PDE5 inhibitors were also found to be beneficial for coronary vasculopathy, pulmonary arterial hypertension, and benign prostatic hyperplasia. But, due to the expensive cost of production and unwanted side effects, it is necessary to explore the possibility of the discovery of new PDE5 inhibitors. Objective: The study aimed to identify potent PDE5 inhibitors by employing the extensive application of computer-aided drug design. objective: To identify potent PDE5 inhibitors by employing the extensive application of computer-aided drug design. Method: Three different databases, named Million Molecules Database, Natural Product Database, and NCI Database, have been screened, which has been followed by filtering based on various druglikeness rules, docking, ADME, toxicity, consensus molecular docking, and 100 ns molecular dynamics simulation. method: Three different databases named Million Molecules Database, Natural Product Database, and NCI Database has been screened followed by filtering based on various drug-likeness such as Lipinski rule of five, Ghose rule, Veber rule, and Muegge rule, docking, ADME, toxicity, consensus molecular docking, and 100 ns Molecular dynamics simulation Results: Three compounds (ZINC05351336, ZINC12030898, and ZINC17949426) have exhibited stable-binding characteristics at the active site of PDE5, demonstrating a robust binding affinity. These molecules have been found to possess drug-like capabilities, effective ADME features, low toxicity, and high stability. Conclusion: The study has delved into the realm of PDE5 inhibitors, which have been found to be effective in treating erectile dysfunction, but high production costs and side effects necessitate new ones. Through computer-aided drug design and screening, three compounds have been identified with promising binding characteristics, drug-appropriate properties, effective ADME profiles, minimal toxicity, and stability, making them potential candidates for future PDE5 inhibitors

Responses of Five Different Artificial Intelligence Chatbots to the Top Searched Queries About Erectile Dysfunction: A Comparative Analysis

The aim of the study is to evaluate and compare the quality and readability of responses generated by five different artificial intelligence (AI) chatbots—ChatGPT, Bard, Bing, Ernie, and Copilot—to the top searched queries of erectile dysfunction (ED). Google Trends was used to identify ED-related relevant phrases. Each AI chatbot received a specific sequence of 25 frequently searched terms as input. Responses were evaluated using DISCERN, Ensuring Quality Information for Patients (EQIP), and Flesch-Kincaid Grade Level (FKGL) and Reading Ease (FKRE) metrics. The top three most frequently searched phrases were “erectile dysfunction cause”, “how to erectile dysfunction,” and “erectile dysfunction treatment.” Zimbabwe, Zambia, and Ghana exhibited the highest level of interest in ED. None of the AI chatbots achieved the necessary degree of readability. However, Bard exhibited significantly higher FKRE and FKGL ratings (p = 0.001), and Copilot achieved better EQIP and DISCERN ratings than the other chatbots (p = 0.001). Bard exhibited the simplest linguistic framework and posed the least challenge in terms of readability and comprehension, and Copilot’s text quality on ED was superior to the other chatbots. As new chatbots are introduced, their understandability and text quality increase, providing better guidance to patients.

Androgenic Properties and Subchronic Toxicity of the Aqueous Extract of Pycnanthus angolensis (Welw.) Warb. Wood (Myristicaceae)

Aims: Pycnanthus angolensis (Welw.) Warb. also known as “Etengué” in the Baka language, is a medicinal plant used by the Baka Pygmies of Cameroon to treat erectile dysfunction. This study aimed to evaluate the androgenic activity and subchronic toxicity of the aqueous extract of Pycnanthus angolensis wood.
 Study Design:  Experimental design.
 Place and Duration of Study: Laboratory of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, between November 2022 and October 2023.
 Methodology: Twenty-five male Wistar strain rats were divided into 5 groups of 5 rats each including a positive control group that received testosterone enanthate (5 mg/kg) intramuscularly once a week; a normal control group that received distilled water (10 ml/kg) and three test groups which received 134 and 267 and 533 mg/kg of the aqueous extract of Pycnanthus angolensis daily per os. On the 29th day, the animals were killed, and several biochemical parameters were assessed for androgenic properties.
 Results: At a dose of 134 mg/kg, the extract significantly increased (p<0.05) the levels of testicular cholesterol, testosterone and serum prostatic acid phosphatase activity compared to those of the normal control. A toxicity study showed that at doses of 134 and 267 mg/kg, the extract did not induce any significant variation (p>0.05) in the creatinine level, but a significant reduction (p<0.05) in of aspartate and alanine aminotransferase activities was recorded. Histopathology revealed destruction of testicular spermatozoa at a dose of 533 mg/kg compared to that of the controls.
 Conclusion: These results showed that at a dose of 134 mg/kg, the aqueous extract of Pycnanthus angolensis (Welw.) Warb. wood is capable of stimulating the production of androgens and is tolerated by the rat's body. Our results justified the traditional use of this plant for the treatment of male infertility and erectile dysfunction.

Comparative Assessment of Online Written Health Information on Treatment of Erectile Dysfunction in English and Hindi Language Webpages

Objectives: To assess and compare the overall quality of online written information on the treatment of erectile dysfunction (ED) in English and Hindi language webpages. Also, correlates of the quality of online health information were explored. Methods: First 50 links obtained on Google search in both English and Hindi language were screened, and a total of 86 (45 English, 41 Hindi) webpages providing patient-oriented information on the treatment of ED were analysed. Content quality and reliability were assessed using the DISCERN scale and the JAMA benchmark criteria respectively. Additionally, aesthetics, interactivity, and readability were evaluated. Results: The DISCERN score indicative of content quality was significantly higher for English webpages compared to Hindi webpages. English webpages were more likely to meet disclosure and attribution JAMA criteria for the reliability of medical information. English webpages with HONcode certification were more likely to have better content quality than those without it. However, none of the Hindi web pages analyzed were HONcode certified. Conclusion: English language webpages provided better overall quality of information on treatment of ED as compared to Hindi language. HONcode label might be used as a proxy indicator of better content quality for online resources informing on ED treatment by laypersons. There is a need to develop and popularize the usage of HONcode or other similar online health information quality accreditation systems for webpages in non-English languages like Hindi.

Which PDE5 inhibitor is the most effective in the treatment of erectile dysfunction in men with spinal cord injury? A systematic review and network meta-analysis.

Phosphodiesterase 5 inhibitors (PDE5i) are the first-line drugs for erectile dysfunction (ED) but differences among available molecules should drive therapy personalization. Choosing one PDE5i over another is a challenge in men with spinal cord injury (SCI), as the evidence of efficacy for each molecule is derived from few studies and comparative "head-to-head" trials are lacking. To assess the efficacy of the different PDE5i for SCI-related ED with a network meta-analysis (NMA) approach. Databases from PubMed, Web of Science, Scopus, and Cochrane Library were checked for randomized controlled trials (RCTs) comparing any PDE5i to each other or placebo in men with traumatic SCI lasting ≥6 months. Data were incorporated in a random-effect NMA, where treatments' efficacy was ranked using the surface under the cumulative ranking curve (SUCRA). The 10 RCTs included provided information about 1,492 men with ED due to traumatic SCI. Intervention arms included sildenafil, tadalafil, and/or vardenafil. Overall, at the pairwise meta-analysis, PDE5i were four times more effective than placebo in improving erectile function (risk ratio: 4.13, 95% CI: 2.76, 6.19). The comparative analysis from NMA revealed that tadalafil was associated with the highest SUCRA value (81%), followed by vardenafil (68%) and sildenafil (49%). Within the grading of comparison network, tadalafil appeared to be the best PDE5i in the treatment of SCI-related ED. Further focused studies are warranted to confirm these findings and define optimal doses and duration of therapy.

Age-related pharmacokinetics differences were observed between young and elderly populations of a novel PDE5 inhibitor, youkenafil, and its metabolite M459

PurposeYoukenafil is a novel oral selective PDE5 inhibitor for treating Erectile Dysfunction. This investigation assessed pharmacokinetics (PK), safety, and tolerability of youkenafil and its main metabolite (M459) after taking 100 mg youkenafil hydrochloride tablets in elderly and young subjects. MethodsThis Phase I, single-center, open-label, parallel-group, single-dose study was conducted on 24 individuals (12 elders and 12 youngsters). Each subject received a single oral 100 mg youkenafil hydrochloride tablets. Blood samples were collected before medication and up to 48 h after medication for PK analysis. Safety and tolerability were also assessed, including treatment-emergent adverse events (TEAEs), laboratory tests, 12-lead ECG, vital sign inspections, color vision examinations, and physical examinations. ResultsPlasma concentrations of youkenafil and M459 were quantified. PK parameters were determined by non-compartmental analysis. Median Tmax of elderly and young groups were both 0.733 h. However, Cmax, AUC0-t, and AUC0-∞ of youkenafil were separately 16.8 %, 37.2 %, and 37.5 % higher in elders and t1/2 of youkenafil was 2.1 h longer in elders. More great differences were observed for M459. T1/2 values were 4.05 h longer in elders, with Cmax, AUC0-t and AUC0-∞ 73.7 %, 81.1 %, and 81.4 % higher in elders. Two (8.3 %) elderly subjects reported TEAEs (all grade Ⅰ in severity) and both recovered without any treatment. No serious adverse reactions (SAEs) or serious unexpected suspected adverse reactions (SUSARs) occurred in this study. ConclusionsThis was the first PK research of youkenafil and M459 in elderly men. PK parameters differences between youkenafil and M459 were comparable between elderly and young groups. Moreover, safety and tolerability of youkenafil were favorable in both groups.

(O-01) PREDICTORS OF INTRACAVERNOSAL INJECTION THERAPY IN MEN WITH ERECTILE DYSFUNCTION

Abstract Introduction & Objective Oral phosphodiesterase type 5 inhibitors (PDE5i) and intracavernosal injections (ICI) are effective treatments for erectile dysfunction (ED). However, the risk factors associated with the transition from oral therapy to ICI use remain less established. We aimed to identify predictive factors contributing to the progression from oral PDE5i to ICI therapy. Methods Retrospective chart review was conducted on patients presenting with erectile dysfunction at our clinic. Patients initiating therapy before clinical documentation or without follow-up were excluded. Statistical analysis utilized chi-square test, two-tailed student's t-test, and multivariable logistic regression performed in R. Results Among 259 men treated for ED, 61% (158) reported subjective improvement with oral PDE5i therapy alone, while 18% (46) initiated ICI therapy. Table 1 summarizes demographic information and cardiovascular risk factors. Men progressing to ICI had higher rates of hypertension (54.3% vs. 28.4%, p=0.0015), type 2 diabetes mellitus (32.6% vs. 11.4%, p=0.0013), and a history of radical prostatectomy (26.1% vs. 3.8%, p<0.001) compared to those satisfied with oral therapy. Significant predictors for ICI progression on multivariate analysis were history of radical prostatectomy (OR 19.4, [95% CI, 1.42-678.88]) and diabetes mellitus (OR 8.6, [95% CI, 1.36-76.49]). Two patients (4.3%) experienced priapism as a complication of ICI use. Among the patients using ICI, 54% (25/46) reported satisfaction with their erections. Conclusions Cardiovascular risk factors and a history of radical prostatectomy were more prevalent among patients progressing from oral therapy to ICI in our cohort. These findings may guide early counseling on ED treatment progression for patients with these predictive factors. Financing No conflict.

(O-26) INITIAL EXPERIENCE IN IMPLEMENTING AN INTRACAVERNOSAL INJECTABLE THERAPY PROGRAM FOR THE TREATMENT OF ERECTILE DYSFUNCTION IN PATIENTS AT A PUBLIC HOSPITAL

Abstract Introduction Intracavernous injectable therapy (IIT) has been considered a second-line therapy for the treatment of erectile dysfunction (ED) since the emergence of phosphodiesterase type 5 inhibitors (IPDE-5) for oral use in the late 1990s. The ease of access to IPDE-5, with increasingly accessible costs, in addition to the safety and efficacy with the use of these medications, caused IIT to fall into disuse for a good period. In turn, about 30% of men with ED do not respond satisfactorily to the oral use of IPDE-5, needing to resort to some other form of treatment. Materials and Method Patients with ED unresponsive to oral IPDE-5 were referred for IIT. Subsequently, they were submitted to a questionnaire to evaluate the results. Results Eight men answered the applied questionnaire. The mean age of patients was 61 years (44-75 years). All patients reported that their partner was aware of the treatment used, and 75% of patients reported the presence of some comorbidity. The response to the test was considered satisfactory in 75% of the patients, with full erection (EHS 4) in 37.5%, and partial erection with penetration (EHS 3) in 37.5%. Only one patient (12.5%) reported not having adapted to the proposed treatment, despite having a satisfactory erection. After a 12-month follow-up, only one patient (12.5%) continues to use IIT, 3 (37.5%) opted for penile prosthesis implantation, while the others chose not to adhere to any subsequent treatment. In 62.5% of patients there was no report of any side effect. Conclusion Despite high rates of efficacy and satisfaction reported in the literature, our initial experience showed a low rate of adherence to IIT. The team's lack of experience and difficulty in following up patients probably contributed to these results, revealing a need for better team training and patient guidance. Financing No conflict.

Bioavailability enhancement of sildenafil citrate via hydrogel-forming microneedle strategy in combination with cyclodextrin complexation

Sildenafil citrate (SIL) as a first-line treatment for erectile dysfunction is currently reported to have poor solubility and bioavailability. Moreover, SIL undergoes first-pass metabolism when taken orally and its injection can lead to discomfort. In this study, we introduce a novel transdermal delivery system that integrates hydrogel-forming microneedles with the inclusion complex tablet reservoir. The hydrogel-forming microneedle was prepared from a mixture of polymers and crosslinkers through a crosslinking process. Importantly, the formulations showed high swelling capacity (>400 %) and exhibited adequate mechanical and penetration properties (needle height reduction < 10 %), penetrating up to five layers of Parafilm® M (assessed to reach the dermis layer). Furthermore, to improve the solubility of SIL in the reservoir, the SIL was pre-complexed with β-cyclodextrin. Molecular docking analysis showed that SIL was successfully encapsulated into the β-cyclodextrin cavity and was the most suitable conformation compared to other CD derivatives. Moreover, to maximize SIL delivery, sodium starch glycolate was also added to the reservoir formulation. As a proof of concept, in vivo studies demonstrated the effectiveness of this concept, resulting in a significant increase in AUC (area under the curve) compared to that obtained after administration of pure SIL oral suspension, inclusion complex, and Viagra® with relative bioavailability > 100 %. Therefore, the approach developed in this study could potentially increase the efficacy of SIL in treating erectile dysfunction by being non-invasive, safe, avoiding first-pass metabolism, and increasing drug bioavailability.

(O-20) COMPARISON OF THREE SHOCKWAVE THERAPY PROTOCOLS FOR THE TREATMENT OF ERECTILE DYSFUNCTION

Abstract Introduction Multiple treatment modalities have been used to treat erectile dysfunction (ED), including focal shock waves. This therapy has demonstrated a short-term positive effect in patients who respond or not to PDE-5i, with variability in therapeutic protocols. Aim To evaluate the effectiveness of 3 shock wave protocols for the treatment of ED. Methods Randomized, multicenter clinical trial. 277 men with non-psychological ED, over 18 years of age, without cancer or major surgeries in the pelvic area or any neurological disease that affected their erectile function, were randomized to one of three groups: weekly (6 wave sessions (WS), 1 x wk), monthly (6 WS 1 x month) or reinforcement (6 WS, 1 x week + 5 sessions, 1 x month). The wave parameters were the same in all groups, no patient received medication. The primary outcome was the change in IIEF-EF score at 6 months of follow-up. The change in the IIEF at the end of therapy and at 3 months of follow-up, erection hardness with the EHS, self-esteem with the SEAR questionnaire, and side effects were also evaluated. Results 222 patients completed the study. In the 6-month evaluation, the average change in the IIEF-EF in the monthly schedule was 4.3 (+/-6.7), 1.9 (+/-6.5) in the weekly schedule, and 5.0 (+/-6.1) in the reinforcement schedule ( p=0.0086). At the end of therapy and at 3 months the change in the IIEF-EF was 3.2 (+/-5.8) and 2.9 (+/-5.5) in the monthly group, 2.7 (+/-4.5) and 3.0 (+/-5.3) in the weekly one, and 4.2 (+/-6.4) and 4.4 (+/-6.5) in the reinforcement one. No differences were found between the groups in the proportion of patients who increased at least one point in erection hardness, nor in the average in the SEAR questionnaire in the evaluations carried out. No patient reported adverse effects to the therapy. Conclusions The results suggest that monthly and reinforcement wave schemes present good results for the treatment of ED. Financing Boston Medical Group.

Evaluation of tadalafil supplementation on the neutrophil/lymphocyte and the platelet/lymphocyte ratios in patients with erectile dysfunction: A prospective study.

We aimed to evaluate the effect of daily 5 mg tadalafil on the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) in patients with erectile dysfunction (ED). 30 subjects with ED were given tadalafil as well as 30 subjects with ED who were not receiving tadalafil were recruited. 30 healthy individuals served as controls. Receiver operating characteristic curve (ROC) showed that the best cut off point of pre-treatment and post treatment NLR in the ED treatment group was found <1.51, <1.51, sensitivity of 68.3%, 58.3%, specificity of 53.3%, 53.3%, lower bound of 0.558, 0.517, upper bound of 0.789, 0.757, total accuracy of 67.4%, 63.7% and p 0.003, 0.0025, respectively. Additionally, the best cut off point of pre-treatment and post treatment PLR in the ED treatment group was found <5.89, <5.99, sensitivity of 65%, 63.3%, specificity of 63.3%, 53.3%, lower bound of 0.515, 0.435, upper bound of 0.755, 0.687, total accuracy of 63.5%, 56.1% and p 0.027, 0.341, respectively. Daily 5 mg Tadalafil supplementation significantly improves erectile function through decreasing these markers as well as depression and anxiety.

Recovery of the hibernating cavernosum by penile revascularization

ABSTRACT Objective Chronic ischemia-related cavernous dysfunction is considered irreversible. However, in certain patients, cavernous function appears to recover with penile revascularization. In this study, we investigated a potential cavernous dysfunction reversibility from a clinical perspective. Patients and Methods We involved 93 young patients in the study with arterial erectile dysfunction (ED) (median age: 30 years). Erectile function tests were performed according to the standard operating procedures of the International Society of Sexual Medicine. Among the participants, 63 and 30 displayed pure arteriogenic and mixed vasculogenic (due to both arterial insufficiency and cavernous dysfunction) ED, respectively. Penile revascularization was performed by anastomosing the inferior epigastric artery to the dorsal artery. The ED treatment success was considered from a score of at least 24 on the International Index of Erectile Function-6. Results Our results proved that penile revascularization cured 92.1% and 73.8% of the patients with pure arteriogenic and mixed vasculogenic ED, respectively (Kaplan-Meier method, log-rank test: no significant difference). The required time for curing 50% of the patients was 10.5 and 10.0 months for pure arteriogenic and mixed vasculogenic ED, respectively, indicating no recovery delay in patients with mixed vascular ED. Furthermore, the cavernous dysfunction degree did not influence cavernous function recovery. Conclusion Penile revascularization cured ED in 73.8% of the patients with mixed vasculogenic ED. Cavernous dysfunction appears to be reversible in certain cases. Furthermore, we observed no delay in functional recovery compared to participants with healthy cavernous function. These two discoveries suggest that cavernous function recovery after penile revascularization is similar to the concept of hibernating myocardium in ischemic myocardium. Although cavernous dysfunction is considered irreversible, it could be reversed in multiple cases with blood flow restoration to the cavernous tissue.

Research Advances in Stem Cell Therapy for Erectile Dysfunction.

Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie's disease, smoking, and psychological disorders. Current treatments for ED are limited to symptom relief and do not address the root cause. Stem cells, with their powerful ability to proliferate and differentiate, are a promising approach for the treatment of male ED and are gradually gaining widespread attention. Current uses for treating ED have been studied primarily in experimental animals, with most studies observing improvements in erectile quality as well as improvements in erectile tissue. However, research on stem cell therapy for human ED is still limited. This article summarizes the recent literature on basic stem cell research on ED, including cavernous nerve injury, aging, diabetes, and sclerosing penile disease, and describes mechanisms of action and therapeutic effects of various stem cell therapies in experimental animals. Stem cells are also believed to interact with host tissue in a paracrine manner, and improved function can be supported through both implantation and paracrine factors. To date, stem cells have shown some preliminary promising results in animal and human models of ED.

A primer on the restorative therapies for erectile dysfunction: a narrative review.

Erectile dysfunction (ED) is a common condition that affects millions worldwide. Patients and urologists alike are seeking alternative therapies that can provide long-lasting results in the treatment of ED. This review provides a comprehensive overview of restorative treatments available for ED, such as platelet-rich plasma, stem cell therapy, and shockwave therapy. The aim of this narrative review is to provide a primer for urologists and general practitioners on the basics of implementing ED restorative therapies in their practice. The PubMed, MEDLINE, and Google Scholar databases were searched for articles in the English language through August 31, 2023, that included key terms such as "erectile dysfunction," "restorative therapy," "shockwave therapy," "platelet-rich plasma," "stem cell therapy," and "stromal vascular fraction." Reference lists of selected studies were manually reviewed to find articles not identified by the initial database search. Shockwave therapy has demonstrated effectiveness in treating ED, with devices like the Medispec ED1000 and Storz Duolith showing statistically significant improvements in patient scores for International Index of Erectile Function (IIEF)-Erectile Function scores in clinical trials. In reported studies of platelet-rich plasma injections, a substantial percentage of patients reached a minimal clinically important difference in the IIEF-Erectile Function scale after treatment. Studies of ED treatment with stem cell therapy, while limited and with small sample sizes, have demonstrated encouraging improvements in patient scores for the abridged 5-item version of the IIEF after treatment. Shockwave, platelet-rich plasma, and stem cell therapies are important, novel, noninvasive restorative treatments for ED that can provide relief for patients wishing to avoid a more invasive approach. While these therapies have shown promising results in clinical trials, more research is required to establish them as standardized and efficacious options in the management of ED.

Intracerebral Haemorrhage after Illicit Use of Sildenafil: A Case Report

Sildenafil(viagra) has become one of the top selling over the counter product for the treatment of male erectile dysfunction.(1) We report a case of 34year male patient admitted in our ICU with history of severe headache followed by sudden loss of consciousness after ingestion of two tablets of sildenafil(50mg) land up intracerebral bleed and died. There are many cases in the literature reporting intracerebral or subarachnoid haemorrhage associated with use of sildenafil while sexual contact.

PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration

AbstractPhosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti‐cancer agents for cancer management to enhance the anti‐tumor immune response by mediating various immune cells, which included the myeloid‐derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI‐based approach for future drug repurposing exploration.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

(014) Safety and Efficacy of Platelet-Rich Plasma Injection for the Treatment of Erectile Dysfunction; A Randomized Prospective Study

Abstract Introduction Platelet-rich plasma (PRP) intracorporeal injection is one of the popular regenerative therapies that has been gaining much interest in recent years as an adjunct or alternative treatment for erectile dysfunction (ED). Nevertheless, scientific evidence to support its clinical efficacy remains controversial. Objective The aim of this study was to evaluate the safety and efficacy of PRP injections for the treatment of ED. Methods A prospective, randomized, double-blinded, placebo-controlled, interventional clinical study was conducted on 52 subjects at the Department of Urology, Faculty of Medicine, Beni-Suef University. Patients were randomized into two groups: the PRP group (n=26) and the placebo (saline) group (n=26). Each participant received three sessions (at two-week intervals) of PRP or saline injections according to his assigned group. International index of erectile function-5 (IIEF-5) scores and safety-related observations were collected at the 1st, 3rd, and 6th months of follow-up. Results The median age and ED duration were statistically comparable for both groups, 52.2 versus 52.5 years and 12.87 versus 11.8, respectively (P = 0.285). With regards to the efficacy of PRP, there were no statistically significant differences between both groups after 1, 3, and 6 months of treatment. After 1 month of treatment, the mean IIEF-5 score for the PRP group was 16.12 ± 1.25 versus 15.99 ± 1.21 for the placebo group (P = 0.683). After 3 months, the IIEF-5 score for the PRP group was 16.44 ± 1.17 compared to 16.31 ± 1.06 for the placebo group (P = 0.653). Also after 6 months, the IIEF-5 score for the PRP group was 16.35 ± 1.45 close to 16.23 ± 1.19 for the placebo group (P = 0.727). No transient hemorrhagic adverse events (hematuria, local petechial bleeding, or ecchymosis) or other side effects were reported during the injection and follow-up period for both groups. Conclusions The results of this trial suggest that although the treatment of ED with 3 injections of intracavernosal PRP separated by two-week intervals may be safe, it is not more effective than a placebo injection. Disclosure No.