Hyperbaric oxygen preconditioning normalizes scrotal temperature, sperm quality, testicular structure, and erectile function in adult male rats subjected to exertional heat injury.

Testicular hyperthermia has been noted in men who work in high ambient temperatures. Scrotal temperatures above the normal range caused germ cell loss in the testes and resulted in male subfertility. In adult male rats, exercising at a higher environmental temperature (36 °C with relative humidity of 50%, 52 min) caused exertional heat stroke (EHS) characterized by scrotal hyperthermia, impaired sperm quality, dysmorphology in testes, prostates and bladders, and erectile dysfunction. Here, we aim to ascertain whether hyperbaric oxygen preconditioning (HBOP: 100% O2 at 2.0 atm absolute [ATA] for 2 h daily for 14 days consequently before the onset of EHS) is able to prevent the problem of EHS-induced sterility, testes, prostates, and bladders dysmorphology and erectile dysfunction. At the end of exertional heat stress compared to normobaric air (NBA or non-HBOP) rats, the HBOP rats exhibited lower body core temperature (40 °C vs. 43 °C), lower scrotal temperature (34 °C vs. 36 °C), lower neurological severity scores (2.8 vs. 5.8), higher erectile ability, (5984 mmHg-sec vs. 3788 mmHg-sec), higher plasma testosterone (6.8 ng/mL vs. 3.5 ng/mL), lower plasma follicle stimulating hormone (196.3 mIU/mL vs. 513.8 mIU/mL), lower plasma luteinizing hormone (131 IU/L vs. 189 IU/L), lower plasma adrenocorticotropic hormone (5136 pg/mL vs. 6129 pg/mL), lower plasma corticosterone (0.56 ng/mL vs. 1.18 ng/mL), lower sperm loss and lower values of histopathological scores for epididymis, testis, seminal vesicle, prostate, and bladder. Our data suggest that HBOP reduces body core and scrotal hyperthermia and improves sperm loss, testis/prostate/bladder dysmorphology, and erectile dysfunction after EHS in rats.

HCG supplement did not accelerate tunica albuginea remodeling to facilitate penile growth.

Penile size is closely concerned and short penis contributes serious sexual dysfunction and tremendous psychological problems to couples. Androgen is essential for penile development and testosterone replacement is recommended to patients with micropenis. We previously proved that inhibiting activity of lysyl oxidase (Anti-lysyl oxidase, Anti-LOX) combined with vacuum erectile device (VED) lengthened penis by remodeling tunica albuginea. We thus explored whether HCG supplement could accelerate tunica albuginea remodeling (induced by Anti-LOX + VED) to promote penile growth. Forty-two SD male rats (4 weeks old) were purchased and divided into 7 groups: control, Anti-LOX, HCG, VED (with a negative aspirated pressure of - 300 mmHg), Anti-LOX + VED, HCG + VED, and Anti-LOX + HCG + VED. After an intervention for 4 weeks, all rats' penile length, exposed penile length, and erectile function were measured. Serum samples were collected to detect hormone levels and penile corpus cavernosum were harvested for histo-pathological analysis. All intervention groups showed significantly longer penis than controlled rats. Anti-LOX sharply increased penile length and exposed length by 15% and 9% respectively, this lengthening effect was more obvious in Anti-LOX + VED group (26% and 19%, respectively). Although HCG promoted penile length by 8%, this effect was slight for exposed length (3%). Moreover, Anti-LOX + HCG + VED dramatically increased penile length and exposed length by 22% and 18%, respectively, which was similar with that in Anti-LOX + VED (26% and 19%, respectively). HCG dramatically stimulated testosterone and dihydrotestosterone secretions than control group, whether with or without Anti-LOX and VED; while it induced more AR expression than other groups. Finally, all procedures did not improve or deteriorate normal erectile function. Although we verified that Anti-LOX + VED lengthened penis by inducing tunica albuginea remodeling, however, HCG supplement did not synergize with Anti-LOX + VED to accelerate albuginea remodeling to facilitate penile growth.

Comparison of preoperative penile elastographic ultrasound findings and pathological tissue results of patients implemented with penile prosthesis.

OBJECTIVE: Histopathological analysis of the relationship between penile elastography and erectile dysfunction. MATERIAL AND METHOD: 12 patients who applied to our clinic for erectile dysfunction in the last 1 year and accepted this study were included. Preoperative two-dimensional shear wave elastography imaging was performed in 12 patients and recorded in the Pascal (kPa) unit. Approximately 0.5 × 0.5 × 0.5 cm tissue samples were taken from the right and left cavernous tissue during penile prosthesis implantation operation. Tissue samples were sent to the pathology department. The percentage of the area covered by muscle fibers and elastic fibers in the corpus cavernosum was noted semi-quantitatively (ratio of muscle fibers and cavernous body elastic fiber score). All data obtained were compared with each other. RESULTS: Cavernous body elastic fiber score data(Grouped Score 1, 2 and 3) and percentage of cavernous body muscle fibers data (Grouped %10, %20, %30… %100) were compared with Shear wave elastography data (kPa). The results were not statistically significant according to the Kruskal Wallis Test. Cavernous body elastic fiber score and the percentage of cavernous body muscle fibers were also compared, it was not statistically significant according to the Kruskal Wallis test and Spearman's correlation test. CONCLUSIONS: Penile shear wave elastography can be used clinically to quantitatively assess the amount of smooth muscle cells and elastic fibers in the penis, but it deserves to be studied with a larger number of patients and a more specific interpretation of the pathology preparation.

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction.

Purpose: To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level. Methods: Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB. Results: Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED. Conclusions: Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats.

Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1ß, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.

Lithium and Erectile Dysfunction: An Overview.

Lithium has been a mainstay of therapy for patients with bipolar disorders for several decades. However, it may exert a variety of adverse effects that can affect patients' compliance. Sexual and erectile dysfunction has been reported in several studies by patients who take lithium as monotherapy or combined with other psychotherapeutic agents. The exact mechanisms underlying such side effects of lithium are not completely understood. It seems that both central and peripheral mechanisms are involved in the lithium-related sexual dysfunction. Here, we had an overview of the epidemiology of lithium-related sexual and erectile dysfunction in previous clinical studies as well as possible pathologic pathways that could be involved in this adverse effect of lithium based on the previous preclinical studies. Understanding such mechanisms could potentially open a new avenue for therapies that can overcome lithium-related sexual dysfunction and improve patients' adherence to the medication intake.

Restoring erectile function by combined treatment with JNK inhibitor and HDAC inhibitor in a rat model of cavernous nerve injury.

BACKGROUND: The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury. OBJECTIVES: In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide-hydroxamic-7 acid (SAHA), for 2 weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways. MATERIALS AND METHODS: Seventy 12-week-old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10 mg/kg JNKi, CNCI treated with daily oral administration of 25.0 mg/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase-3 activity assay, and western blot analysis. RESULTS: CNCI alone resulted in significantly reduced intracavernosal pressure/mean arterial pressure (MAP) and area under the curve/MAP, decreased smooth muscle (SM)/collagen ratio and SM content, higher caspase-3 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)-ß, fibronectin, and c-Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile-responses and SM/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM/collagen ratio compared to the single agent treatment. SM content, caspase-3 activity, and c-Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF-ß. DISCUSSION AND CONCLUSIONS: The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC/TGF-ß and JNK pathways.

Comprehensive analysis of complications after transperineal prostate biopsy without antibiotic prophylaxis: results of a multicenter trial with 30 days' follow-up.

BACKGROUND: To investigate infectious and non-infectious complications after transperineal prostate biopsy (TPB) without antibiotic prophylaxis in a multicenter cohort. Secondly, to identify whether increasing the number of cores was predictive for the occurrence of complications. Thirdly, to examine the relation between TPB and erectile dysfunction. METHODS: We analyzed a retrospective multicenter cohort of 550 patients from three different urological centers undergoing TPB without antibiotic prophylaxis. The median number of cores was 26. Demographic and clinical data were extracted by reviewing patients' electronic medical records and follow-up data such as postoperative complications obtained by structured phone interviews. To investigate the influence of the number of cores taken on the occurrence of complications, we performed univariate and multivariate mixed effects logistic regression models. RESULTS: There was no case of sepsis reported. Overall, 6.0% of patients (33/550) presented with any complication besides mild macrohematuria. In all, 46/47 (98%) complications were ≤Grade 2 according to Clavien-Dindo. In multivariate regression analyses, an increased number of cores was associated with overall complications (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.02-1.14, P = 0.01) and specifically bleeding complications (OR 1.28, 95% CI 1.11-1.50, P = 0.01) but not with infectious complications (OR 1.03, 95% CI 0.97-1.10, P = 0.67). A total of 14.4% of patients referred impairment of erectile function after TPB. Of note, 98% of these men were diagnosed with prostate cancer. CONCLUSIONS: This is the first multicenter trial to investigate complications after TPB without antibiotic prophylaxis. In our study, we found no case of sepsis. This underlines the safety advantage of TPB even without antibiotic prophylaxis and supports the ongoing initiative to abandon TRB of the prostate. A higher number of cores were associated with an increase in overall complications specifically bleeding complications, but not with infectious complications. Post-biopsy erectile dysfunction was mainly present in patients diagnosed with PCa.

Spray-dried co-amorphous Tadalafil ternary mixtures: a promising platform towards the enhancement of solubility and bioavailability

Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad.

Combination Therapy with a JNK Inhibitor and Hepatocyte Growth Factor for Restoration of Erectile Function in a Rat Model of Cavernosal Nerve Injury: Comparison with a JNK Inhibitor Alone or Hepatocyte Growth Factor Alone.

We determined if combined administration of JNK-inhibitors and HGF (hepatocyte-growth-factor) would restore erectile-function through both antiapoptotic and regenerative effects in a rat model of cavernous-nerve-crush-injury (CNCI), and compared the results with administration of JNK-inhibitor alone or HGF alone. We randomized 70 rats into 5 groups: sham-surgery-group (S), CNCI (I) group, a group treated with once-daily intraperitoneal-administration of 10.0-mg/kg of JNK-inhibitors (J), a twice-weekly intracavernosal-administration of 4.2-µg HGF group (H), and a combined-treatment with 10.0-mg/kg JNK-inhibitors and 4.2-µg HGF group (J+H). We investigated erectile-responses to electrostimulation, histological-staining, caspase-3-activity-assay, and immunoblotting at two-weeks postoperatively. The three treatment groups showed improvements in erectile-responses (ICP/MAP and AUC/MAP ratios) compared to Group-I. The erectile-responses in Group-J+H were greater than those in Group-J or Group-H. The erectile-responses in Group-J+H were generally normalized. Caspase-3-activity and cJun-phosphorylation in Group-J and Group-J+H improved compared to Group-I, whereas caspase-3-activity in Group-H partially improved. Protein-expression of PECAM-1, eNOS-phosphorylation, and smooth-muscle content in Group-J+H were normalized, although those in Group-J or Group-H were partially restored. Combination therapy with JNK-inhibitors and HGF can generally normalize erectile-function through anti-apoptosis and preservation of endothelium or SM in rat CNCI model. The combined treatment appears to be superior to the respective agent alone in terms of therapeutic effects.

Androgen regulated protein and pyruvate dehydrogenase kinase 4 in severe erectile dysfunction: A gene expression analysis, and computational study of protein structure.

Erectile dysfunction (ED) is one of the most common sexual disorders in men. During the past 30 years, there has been no new drug development for ED. Thus, exploring the genetic basis of ED deserves further study, in hope of developing new pharmacological treatments for ED. In this study, Real-Time PCR analysis was used to assess the expression of androgen regulatory protein (Andpro) and pyruvate dehydrogenase kinase 4 (Pdk4) genes in ED. For this purpose, the experiment was performed on 20 men with severe ED and 20 potent men. IIEF-15 was used to determine the ED severity. The study was conducted in the Department of Sexual Medicine of the Kermanshah University of Medical Sciences, Kermanshah, Iran. The EDTA-Na vacuum blood tube was taken from ED patients and controls. Informed consent was obtained from all participants. After blood sampling, RNA was extracted from whole blood. Then cDNA was synthesized. The gene expression was analyzed through the qPCR method. The ß-actin was used as a reference gene. To further study these two proteins, their three-dimensional structures were predicted through I-TASSER. Compared with controls, in ED patients, the expression of the Andpro gene decreased, while the expression of the Pdk4 gene increased (p<0.01). Predicting the structure of the protein showed that Pyruvate Dehydrogenase Kinase 4 had a double subunit and androgen-regulated protein had a single subunit.

Enhancement of the RhoA/Rho kinase pathway is associated with stress-related erectile dysfunction in a restraint water immersion stress model.

Stress is a risk factor for erectile dysfunction (ED); however, the pathology of stress-induced ED remains unclear. Accordingly, in this study, we investigated the mechanisms of stress-induced ED using a rat model. Ten-week-old male Wistar/ST rats were maintained in a cage filled with water to a height of 2 cm (stress group) or a normal cage (control group). We found that water immersion stress significantly enhanced the contractile response to noradrenaline in the corpus cavernosum (CC) (p < 0.05). Moreover, stress significantly decreased erectile function, as assessed by changes in intracavernous pressure (p < 0.01). In addition, Rho kinase-1 (ROCK-1) protein expression was significantly upregulated under stress conditions (p < 0.05), and phosphorylated myosin light chain (phospho-MLC) levels, contribute to smooth muscle contraction, were also upregulated (p < 0.01). Treatment with fasudil hydrochloride, a Rho kinase inhibitor, for 5 days significantly improved erectile function (p < 0.01) and normalized ROCK-1 and phospho-MLC levels (p < 0.01). Thus, the RhoA/Rho kinase pathway may be associated with stress-induced ED via contraction of CC. Stress also decreased the smooth muscle/collagen ratio of CC (p < 0.01), and fasudil treatment did not alleviate these effects (p = 0.50). These findings suggested that penile fibrosis gradually progressed under stress conditions and that fibrosis may be independent of the RhoA/Rho kinase pathway, implying that longer exposure to stress may promote ED. We conclude that stress-induced ED was caused by contraction of CC mediated by the RhoA/Rho kinase pathway.

Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction.

Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response. We examine two important aspects required for clinical application of the biomaterials: if SHH PA suppresses intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms.

Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial.

BACKGROUND: Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes. METHODS: The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. REWIND was done at 371 sites in 24 countries. Men and women aged older than 50 years with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors, were randomly assigned (1:1) to receive either dulaglutide or placebo. Participating men were offered the opportunity to complete the standardised International Index of Erectile Function (IIEF) questionnaire at baseline, 2 years, 5 years, and study end. We did an exploratory analysis, in which we included participants who completed a baseline and at least 1 follow-up IIEF questionnaire. The primary outcome for these analyses was the first occurrence of moderate or severe erectile dysfunction following randomisation, assessed by the erectile function subscores on IIEF. This analysis was part of the REWIND trial, which is registered with ClinicalTrials.gov, NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 3725 (70·1%) of 5312 male participants with a mean age of 65·5 years (SD 6·4 years) were analysed, of whom 1487 (39·9%) had a history of cardiovascular disease, and 2104 (56·5%) had moderate or severe erectile dysfunction at baseline. The incidence of erectile dysfunction following randomisation was 21·3 per 100 person-years in the dulaglutide group and 22·0 per 100 person-years in the placebo group (HR 0·92, 95% CI 0·85-0·99, p=0·021). Men in the dulaglutide group also had a lesser fall in erectile function subscore compared with the placebo group, with a least square mean difference of 0·61 (95% CI 0·18-1·05, p=0·006). INTERPRETATION: Long-term use of dulaglutide might reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes. FUNDING: Eli Lilly and Company.

Influencing Factors for Erectile Dysfunction of Young Adults with No Response to PDE5i.

Erectile dysfunction (ED) is a common male disorder. Although orally-administered phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are now recognized as the primary pharmacological treatment method for ED, 20%-30% of the patients treated with PDE5 inhibitors exhibit no significant effects. This study aims to investigate the influencing factors of ED in young adults with no response to PDE5 inhibitors. ED patients who would take PDE5 inhibitors were included and investigated with a questionnaire. Patients with no response to PDE5 inhibitors (tadalafil and sildenafil) served as study group, and those with response to PDE5 inhibitors as control group. Then Chi square test and logistic regression analysis were applied to find the potential influencing factors. In total, 378 ED patients were included. Ninety-three (24.6%) cases were non-responsive to PDE5 inhibitors, and the remaining 285 (75.4%) responded to PDE5 inhibitors. In multiple logistic regression analysis, we found that history of drinking (OR=3.152; 95%CI 1.672-6.975), spousal noncooperation (OR=2.994; 95%CI 1.589-5.638), number of fixed sex partners (OR=0.358; 95%CI 0.132-0.651), duration of ED (OR=3.356; 95%CI 1.352-8.333), and depression (OR=3.689; 95%CI 1.579-8.979) could be the influencing factors for ED patients' non-response to PDE5 inhibitors. In conclusion, history of drinking, spousal noncooperation, number of fixed sex partner, long duration of ED, and depression could be the influencing factors for ED patients' non-response to PDE5 inhibitors. Patients and doctors should pay attention to these factors.

Prevalence of erectile dysfunction among Egyptian male patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: The relation between type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED) has been identified in multiple studies. The aim of this cross-sectional study was to estimate the prevalence and to determine some associated factors of ED among a sample of adult Egyptian male patients with T2DM. METHODS: This cross-sectional study included 150 adult male patients with T2DM (aged 40-60 years) who attended the outpatient clinic of Diabetes in Alexandria Main University hospital. They were evaluated for the presence of ED which was assessed by the validated Arabic-translated five-item version of the International Index of Erectile Function-5 (IIEF-5) questionnaire. Fasting blood glucose (FBG), HbA1c, total serum cholesterol, HDL-C, total serum testosterone (TT) and urinary albumin creatinine ratio (uACR) were measured for all study subjects. RESULTS: The prevalence of ED was 80% among the studied sample. Significant negative correlation was found between IIEF-5 score and age, duration of diabetes, FBG and urinary ACR; while there was a significant positive correlation between IIEF-5 score and serum total testosterone. On performing multiple linear regression analysis for the parameters affecting IIEF-5 questionnaire score, TT, urinary ACR, age and FBG were the independent predictors of ED. CONCLUSION: ED was a common finding in our sample of Egyptian men with T2DM. Poor glycemic control and albuminuria may be considered as independent risk factors for ED.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

Erectile dysfunction and its associated factors among the male population in Adigrat Town, Tigrai Region, Ethiopia: A cross-sectional study.

BACKGROUND: Erectile dysfunction is one of the common sexual dysfunctions, but it is generally misunderstood as it is not a condition that threatens life. It affects an individual's physical as well as psychosocial health and has a significant impact on sufferers and their families' quality of life. No data are suggesting the prevalence of erectile dysfunction at the population level in Ethiopia. This research aimed to assess the prevalence and associated factors of erectile dysfunction among the male population. METHODS: We employed a community based cross-sectional study among 802 study participants. A two-stage random sampling method was used for enrolling study participants. Including the International Index of Erectile Function Questionnaire-5 (IIEF-5) for erectile dysfunction, data were collected using pretested and a structured questionnaire administered by an interviewer. Binary logistic regression was performed to identify factors associated with erectile dysfunction. RESULT: Out of the total of 802 individuals, 25.4%(95% CI:(22.4, 28.3%)) (n = 204) reported erectile dysfunction. The mean age of the participants was 34.3 ± 9.6 years. Age of 40years and above [AOR = 10.74, 95% CI: (7.07, 16.35)], physical inactivity [AOR = 3.62, 95% CI: (2.40, 5.45)], depression [AOR = 4.01, 95% CI: (2.22, 7.21)], poor quality of life [AOR = 1.59, 95% CI: (1.07, 2.36)] were significantly associated with erectile dysfunction. CONCLUSIONS: In this study, the prevalence of erectile dysfunction was high. Therefore, it is recommended that erectile dysfunction treatment be integrated into the health care system that focuses on educating and inspiring people on healthy eating, physical activity, and behavior enhancing wellbeing.

Structural Determination, Biological Function, and Molecular Modelling Studies of Sulfoaildenafil Adulterated in Herbal Dietary Supplement.

Unapproved ingredients included in herbal medicines and dietary supplements have been detected as adulterated synthetic drugs used for erectile dysfunction. Extraction from a dietary supplement was performed to isolate the compounds by HPLC analysis. The structural characterization was confirmed using mass spectrometry (ESI-TOF/MS and LC-MS/MS), 1H NMR, and 13C NMR spectroscopy techniques. Results identified the thus-obtained compound to be sulfoaildenafil, a thioketone analogue of sildenafil. The biological activities of this active compound have been focused for the first time by the experimental point of view performance in vitro. The results revealed that sulfoaildenafil can affect the therapeutic level of nitric oxide through the upregulation of nitric oxide synthase and phosphodiesterase type 5 (PDE5) gene expressions. This bulk material, which displays structural similarity to sildenafil, was analyzed for the presence of a PDE5 inhibitor using a theoretical calculation. These unique features of the potential activity of PDE5 protein and its inhibitors, sildenafil and sulfoaildenafil, may play a key consideration for understanding the mode of actions and predicting the biological activities of PDE5 inhibitors.

Low androgen status inhibits erectile function by increasing pyroptosis in rat corpus cavernosum.

BACKGROUND: The mechanism of erectile dysfunction (ED) caused by low androgen status is not fully understood. OBJECTIVES: To investigate whether low androgen status inhibits erectile function of rats by inducing pyroptosis in the corpus cavernosum (CC). MATERIALS AND METHODS: Thirty-six eight-weeks-old healthy male Sprague-Dawley rats were equally divided into six groups: sham-operated group (4w sham, 8w sham), castration group (4w cast, 8w cast), and castration + testosterone (T) group (4w cast + T, 8w cast + T). The rats in castration + T groups were injected with testosterone propionate subcutaneously every other day. After 4 and 8 weeks, the ratio of maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP), the level of serum T, the concentration of nitric oxide (NO) and interleukin-1ß (IL-1ß), the expression of NOD-like receptor pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), Caspase-1 p20, gasdermin D-N (GSDMD-N), transforming growth factor ß1 (TGF-ß1), collagen-I, and collagen-III, the ratio of smooth muscle/collagen (SM/C), and the proportion of pyroptotic cells in the CC were analyzed. RESULTS: The ratio of ICPmax/MAP (3/5 V) and SM/C, the level of NO and serum T was significantly decreased in castration groups when compared to other groups (p < 0.01). NLRP3, ASC, Caspase-1, and GSDMD were mainly expressed in the cytoplasm of smooth muscle cells (SMCs) and endothelial cells (ECs) in the CC. The expression of NLRP3, ASC, Caspase-1p20, GSDMD-N, IL-1ß, TGF-ß1, collagen-I, and collagen-III was significantly increased in castration groups when compared with other groups (p < 0.01). The proportion of pyroptotic cells in the CC was increased significantly in castration groups when compared with other groups (p < 0.05). DISCUSSION AND CONCLUSION: Low androgen status inhibits erectile function of rats by promoting CC fibrosis and reducing NO synthesis through pyroptosis of SMCs and ECs in the CC.