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Metabolic syndrome (MetS) can contribute to a chronic ischemia-relative overactive bladder (OAB). Using fructose-fed rats (FFRs), a rat model of MetS, we investigated the effects of tadalafil (a phosphodiesterase-5 inhibitor) on MetS-associated chronic bladder ischemia and bladder overactivity. Phenotypes of the OAB, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with reduced bladder blood perfusion (in empty bladders) via laser color Doppler imaging and elevated serum nitrite levels, suggesting chronic ischemia-related bladder dysfunction. Treatment with tadalafil (2 mg/kg) promoted pelvic angiogenesis, as shown by magnetic resonance imaging, and increased VEGF and p-eNOS overexpression in the bladder. This treatment restored bladder perfusion and alleviated bladder overactivity without significantly altering most MetS parameters. At the molecular level, FFRs exhibited increased ischemia markers (NGF, HIF-2α, and AMPK-α2) and decreased p-AMPK-α2, along with elevated proinflammatory mediators (ICAM-1, nuclear NF-κB, COX-2, IL-1β, IL-6, and TNF-α), enhanced mitochondria biogenesis (PGC-1α, TFAM, and mitochondria DNA copy number), oxidative stress (decreased nuclear NRF2, increase MnSOD and 8-OHdG staining), and tissue fibrosis (increased TGF-β1, collagen I, and fibronectin). Tadalafil treatment improved these effects. Together, these findings suggest that tadalafil may promote VEGF-associated angiogenesis, enhance p-eNOS staining in the bladder vasculature, normalize bladder perfusion in microcirculation, and reduce serum nitrite levels. Consequently, tadalafil mitigates the adverse effects of chronic ischemia/hypoxia, improving bladder overactivity. We elucidated the mechanisms underlying the tadalafil-mediated amelioration of MetS-associated OAB symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Adulteration of herbal products can have a negative impact on the health of populations, as adulterants can lead to developmental defects, chronic diseases or death. Recently, in the literature, it has been reported that these products are used as adulterants in several traditional medicines. Therefore, it is strongly recommended to monitor synthetic adulterants in marketed liquid herbal products, which are most commonly used as strength and energy stimulants in Mali, for the safety of populations. Methods: In this study, we investigated the presence of sildenafil and tadalafil in the most popular marketed herbal products in Mali by HPLC for regulatory measurements. Results: A total of 16 samples were collected and analyzed, of which 14 revealed the presence of adulteration corresponding to 87%. Among these samples, 8 revealed the presence of Sildenafil and 6, the presence of Tadalafil at varying concentrations. These samples consist mostly of liquid, powder or paste preparations and are used as traditional medicines and food supplements for the treatment of physical and sexual weakness. Conclusion: These results clearly raise the issue of adulteration of traditional medicines and food supplements used for the treatment of physical and sexual weakness in Mali by chemicals and the need to strengthen regulatory controls to prevent the falsification of these products. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and safety of on-demand 20 mg tadalafil alone or combined with lidocaine spray for treating patients with comorbid erectile dysfunction (ED) and premature ejaculation (PE). Methods: This randomized controlled trial included 98 patients with comorbid ED and PE, randomly assigned to the experimental group (n = 50, tadalafil alone) or the active control group (n = 48, tadalafil combined with lidocaine spray). Patients took tadalafil 30 min before sexual intercourse, while the combination therapy group also used lidocaine spray 5 min before intercourse. After 12 weeks of treatment, changes in the International Index of Erectile Function (IIEF-5), Chinese Index of Premature Ejaculation (CIPE-5), Intravaginal Ejaculatory Latency Time (IELT), and Sexual Satisfaction Score (SSS) were evaluated. Results: Both groups showed significant improvement in IIEF-5 scores, but the difference between groups was not significant (F = 0.89, p = 0.45). The active control group showed significant improvement in CIPE-5 scores (p < 0.001), while the experimental group showed no significant change (p > 0.05). IELT in the active control group increased significantly from 25.7 s to 198.6 s (Z = 6.03, p < 0.001), while the experimental group showed no significant change (Z = 0.74, p = 0.46). SSS improved significantly in the active control group (p < 0.001) but not in the experimental group (p > 0.05). The incidence of adverse events was similar in both groups (14% vs 20.8%, p = 0.575). Conclusion: Tadalafil combined with lidocaine spray is superior to tadalafil alone in improving symptoms, prolonging IELT, and enhancing sexual satisfaction in patients with comorbid ED and PE, with comparable safety. This combination therapy provides a new approach for improving treatment strategies for patients with comorbid ED and PE. Large-scale, multi-center randomized controlled trials are needed to further validate these findings. [ABSTRACT FROM AUTHOR]

As the demand for "quick-fixes" and instant gratification intensifies among consumers of the US health care delivery system, health care providers remain essential to ensuring patients receive safe, evidenced-based care. Erectile dysfunction is a common health condition affecting as many as 42% of US men. As such, it is unsurprising that American health care consumers affected by erectile dysfunction (ED) may be tempted by "quick fixes" to ameliorate their symptoms—particularly if such fixes are perceived to be less embarrassing, more accessible, and/or more affordable. Although multiple therapies for the treatment of ED are approved by the US Food and Drug Administration, unregulated and/or counterfeit treatments are abundantly available to health care consumers on the Internet and US retail settings. These unregulated treatments may take the form of over-the-counter supplements or tainted prescription medications from illegal Internet pharmacies. This clinical brief is a call to action for health care professionals to advocate for patient safety, educate patients, and champion evidence-based therapies approved for the treatment of erectile dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To determine the optimum combination therapy of Silodosin–Tadalafil versus Silodosin–Vardenafil in terms of both tolerability and efficacy for the management of distal ureteric stones. Methods: This prospective, double blinded, randomized clinical trial included 140 patients with distal ureteric stones, randomized into two groups: Group I (n = 67) received Silodosin 8 mg once daily combined with Tadalafil 5 mg once daily, and Group II (n = 68) received Silodosin 8 mg once daily combined with Vardenafil 10 mg once daily. The primary outcome was the tolerability of the combination therapies, assessed through the incidence of adverse events. Secondary outcomes included stone expulsion rate, expulsion time, and the need for analgesics. Results: Both combination therapies demonstrated similar efficacy, with no significant differences in stone expulsion rate (70.1% vs. 67.6%, P = 0.754), expulsion time (19 ± 3 days for both groups, P = 0.793), and analgesic requirements (P > 0.05). However, the Silodosin–Tadalafil combination showed a significantly lower occurrence of adverse events, with notable differences in headache (23.9% vs. 57.4%, P < 0.001), dizziness (32.8% vs. 60.3%, P = 0.001), and gastrointestinal upset (9% vs. 66.2%, P < 0.001), and other adverse effects. The overall occurrence of any adverse event was significantly lower in the Silodosin–Tadalafil group (88.1% vs. 98.5%, P = 0.017). Conclusions: Both Silodosin–Tadalafil and Silodosin–Vardenafil therapies are effective in managing distal ureteric stones. However, the Silodosin–Tadalafil combination is associated with a significantly lower incidence of adverse events, making it a more tolerable option for patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies had shown that the neutrophils/lymphocytes (NLR) and platelets/lymphocytes (PLR) ratios could be used as markers of inflammatory load as well as prognostic factors in several medical conditions. The current study aimed to compare the effect of using daily tadalafil 5 mg/day versus daily sildenafil 25 mg/day in improving erectile function as well as their ability to reduce NLR and PLR. Methods: One hundred and four participants were recruited. Seventy-four randomized patients with erectile dysfunction were equally divided into 2 groups. Patients in group A used daily tadalafil 5 mg for 2 months while patients in group B used daily sildenafil 25 mg for 2 months. Patients were collected from June 2022 to June 2023. Thirty healthy individuals served as controls. All patients and controls were evaluated using the validated Arabic version of the international index of erectile function (ArIIEF-5) at baseline and after 2 months of medical treatment. Five cc of venous blood sample was obtained before and after 2 months of medical treatment to compare the effect of phosphodiesterase type 5 inhibitors (PDE-5Is) intake for erectile dysfunction on PLR and NLR before and after treatment. Results: The current study showed that there were no statistically significant differences between the cases and the controls apart from the ArIIEF-5 scores. Moreover, there was no significant difference between patients in group A and those in group B regarding PLR and NLR post administration of PDE-5Is. Interestingly, patients in group A demonstrated a highly significant difference between the ArIIEF-5 scores as well as the PLR and the NLR before and 2 months after administration of daily tadalafil 5 mg. On the other hand, patients in group B who were administrated daily sildenafil 25 mg for 2 months demonstrated only a highly significant difference between the ArIIEF-5 scores before and after administration. Meanwhile, patients in group B did not reveal any statistically significant difference in the PLR and the NLR before and 2 months after administration of sildenafil 25 mg. Further regression analysis after adjustment of different variables of the study showed a significant correlation between ArIIEF-5 and PLR in patients who received daily tadalafil 5 mg (r=0.430, p=0.004). Conclusions: Tadalafil and sildenafil have similar clinical efficacy in treating erectile dysfunction. However, tadalafil is more effective in lowering PLR and NLR compared to sildenafil. [ABSTRACT FROM AUTHOR]

Yi Liu,1,2 Changqing He,1 Quanhai Zhong,3 Xianbao Shi,4 Hongyan Li,1 Gaoge Fu,1 Lixuan Guo,1 Churong Zhao,1 Lei Tian,1 Xin Li,1 Xue Jiao,1 Lina Shan1 1Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 2Department of Critical Care Medicine, Panzhihua Central Hospital, Panzhihua, 61700, People’s Republic of China; 3Clinical Drug Laboratory, People’s Hospital of Yichun City, Yichun, Jiangxi, 336000, People’s Republic of China; 4Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Lina Shan, Email shanlina321@163.comIntroduction: Pulmonary hypertension (PH) is a progressive and life-threatening condition. Recent research has demonstrated that exosomes derived from mesenchymal stem cells (MSC) exhibit significant therapeutic potential in the treatment of PH. The composition of these exosomes is often substantially influenced by the characteristics of their parental cells. This study aimed to identify an intervention strategy to enhance the efficacy of mesenchymal stem cell exosomes in treating PH.Methods: Exosomes were isolated from control MSC and tadalafil-pretreated MSCs. In vitro and in vivo studies were conducted.Results: MSCTAD-Exo attenuated macrophage inflammation and improved endothelial cell (EC) apoptosis while also reducing pulmonary arterial pressure in a hypoxia-induced rat model. Furthermore, MSC exosomes can mitigate hypoxia-induced proliferation and migration of smooth muscle cells (SMC) by influencing the secretion of endothelial exosomes. MiR-29a-3p has been identified as a crucial mediator in this process, with its expression regulated by cAMP responsive element binding protein 1 (CREB1). MiR-29a-3p exerts anti-inflammatory effects by modulating the expression of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Notably, the anti-inflammatory and anti-vascular remodeling activities of exosomes were diminished following the depletion of MiR-29a-3p.Discussion: MSC treated with tadalafil can secrete better exosomes. MSCTAD-Exo may enhance anti-inflammatory and anti-vascular remodeling properties by upregulating mir-29a-3p expression, providing a novel idea for PH therapy. Future studies could explore the clinical application of this finding. Keywords: exosome, tadalafil, hypoxia pulmonary hypertension, mesenchymal stem cell, miR-29a-3p

Introduction: Adverse events, such as erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), are significant concerns in prostate cancer (PCa) patients treated with Iodine 125 (I-125) low-dose rate (LDR) prostate brachytherapy (PB). Alpha antagonists and phosphodiesterase-5 inhibitors are used to manage these events. The present study compared the efficacy of low-dose tadalafil with that of tamsulosin for concomitant ED and LUTS in PCa patients treated with I-125 LDR PB. Materials and methods: One hundred and seventeen patients who received PB for low- or intermediate-risk localized PCa were analyzed. They were randomized into two groups, one receiving tamsulosin (N = 58) and the other receiving low-dose tadalafil (N = 59) immediately after PB. Sexual and urinary functions were assessed at various time points post-PB using questionnaires and objective measurements. The primary endpoint was sexual function measured by the International Index of Erectile Function-15 (IIEF-15) EF domain scores 6 months after PB. Secondary endpoints were sexual function measured by total IIEF-15 scores and Erection Hardness Scores 6 months after PB. The exploratory endpoint was the LUTS status 6 months after PB. Results: No significant differences were observed in baseline characteristics between the two groups. Tadalafil exerted stronger effects on sexual function, particularly erection hardness, than tamsulosin. No significant differences were observed in the management of LUTS between both treatments. Conclusion: Low-dose tadalafil and tamsulosin may manage LUTS equally after PB. Low-dose tadalafil may contribute to the maintenance of erectile function, particularly erection hardness, after PB; therefore, it is a viable option for patients with baseline erectile function.

ObjectiveTo perform a cost analysis of generic and brand-name Phosphodiesterase Type 5 (PDE5) inhibitors at different dosages and pharmacies across the US.MethodsUsing an all-payer retail pharmacy-claims database, we analyzed prescription drug data for three generic and six brand-name oral PDE5 inhibitors at different dosages across US chain and independent pharmacies in 2019.ResultsWe obtained cash price data from 60,186 pharmacies (35,976 chain and 24,210 independent). The nationwide mean cash price per unit (PPU) ranged from $8.6 ± 5.2 (sildenafil 20 mg at chain pharmacies) to $107.1 ± 71 (Adcirca 20 mg at independent pharmacies) equal to 1145.3% difference. Chain pharmacies provided significantly lower average prices for one brand-name and six generic PDE5 inhibitors. Tadalafil PPU was cheaper at higher quantities, however, PPU increased with quantity prescribed for sildenafil. Looking at the top 10 metropolitan statistical areas, the highest PPUs were observed for tadalafil (Cialis) 10 mg and sildenafil (Viagra) 50 mg in Atlanta ($67.4 ± 8.7) and Los Angeles ($50.3 ± 24.0), while New York ($9.7 ± 2.6) and Miami ($27.9 ± 16.4) had the lowest PPUs for tadalafil (Cialis) 5 mg and sildenafil (Viagra) 100 mg, respectively.ConclusionA substantial variability in PDE5 inhibitor cash prices exists across manufacturer, dosage, quantity, pharmacy type, and location. In addition, the pricing does not necessarily correlate with the regional socioeconomic factors. This highlights the importance of provider awareness and patient counseling on drug price including potentially assisting patients in identifying opportunities for cost savings.

PurposeTo explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs).MethodsWe queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients.ResultsFrom a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively).ConclusionsPDE5i use shows disproportionate priapism signals which are higher in young patients.