Lymphangioma is a rare developmental anomaly of the lymphatic system, commonly arising at birth, in infancy, or early childhood. Treatment is rarely curative. We report a case of macrocystic lymphangioma treated with sildenafil in a 16-year-old Filipino child diagnosed clinically, radiologically and histologically. The patient presented with grouped papulovesicles on the left lower extremity, associated with limb length discrepancy, unilateral leg pain and difficulty in ambulation. Given the recurrent course of this condition, even with surgical management, the use of a non-invasive approach such as sildenafil as a potential treatment option for lymphangioma is an important emerging area of study.

Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

OBJECTIVE: To explore the effects of Qiwei No.3 combined with sildenafil on Rho kinase activity and AKT/eNOS pathways in the penile cavernous tissue of male rats with diabetic erectile dysfunction (DED). METHODS: We constructed a model of DED in 24 SD male rats by intraperitoneal injection of streptozotocin solution and injecting apomorphine into the neck after 8 weeks of feeding, equally randomized the model rats into a model control (MC), a sildenafil (S), a low-dose Qiwei No.3 combined with sildenafil (LQ+S) and a high-dose Qiwei No.3 combined with sildenafil (HQ+S) group, and took another 6 normal male rats as blank controls (BC). We treated intragastrically the animals in the BC and MC groups with normal saline, and those in the S, LQ+S and HQ+S groups with sildenafil (5 mg/kg/d), Qiwei No.3 (10 g/kg/d) + sildenafil (5mg/kg/d), and Qiwei No.3 (20g/kg/d) + sildenafil (5mg/kg/d), respectively. After 6 weeks of treatment, we recorded the number of penile erections of all the rats by injecting apomorphine into the neck, and measured the activity of Rho kinase and expressions of p-AKT and eNOS proteins in the corpus cavernosum by Western blot. RESULTS: Compared with the blank controls, all the DED model rats showed evidently elevated blood glucose and reduced body weight. The number of penile erections was significantly increased in the S, LQ+S and HQ+S groups in comparison with that in the model controls (P< 0.05), even higher in the HQ+S than in the S group (P< 0.05). The activity of Rho kinase in the penile cavernosum was significantly higher in the MC than in the BC group (P<0.05), but lower in the HQ+S than in the S group (P< 0.05). No statistically significant difference was observed in the expression level of the p-AKT protein in the penile cavernosum among the five groups of rats (P > 0.05). The expression of eNOS was remarkably up-regulated in the BC and HQ+S groups (P< 0.05) compared with that in the MC group, even more significantly in the HQ+S than in the LQ+S and S groups (P< 0.05). CONCLUSION The combination of high-dose "Qiwei No. 3" and sildenafil can improve erectile function in DED rats, which may be attributed to its effect of releasing more nitric oxide (NO) by inhibiting the activity of Rho kinase and up-regulating the expression of the e-NOS protein.
Animals ; Male ; Sildenafil Citrate ; Rats ; rho-Associated Kinases/antagonists & inhibitors* ; Rats, Sprague-Dawley ; Penis/drug effects* ; Erectile Dysfunction/etiology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Nitric Oxide Synthase Type III/metabolism* ; Diabetes Mellitus, Experimental/complications* ; Drugs, Chinese Herbal/therapeutic use*

PURPOSE: To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival. MATERIALS AND METHODS: A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas. RESULTS: Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma. CONCLUSIONS: There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.
Gene Expression ; Genome ; Guanosine Monophosphate ; Humans ; Melanoma ; Phosphodiesterase 5 Inhibitors ; Sequence Analysis, RNA ; Sildenafil Citrate ; Statistics as Topic ; Tadalafil ; Vardenafil Dihydrochloride

Obesity is a major public health issue worldwide and is frequently associated with erectile dysfunction (ED). Both conditions may share an internal pathologic environment, also known as common soil. Their main pathophysiologic processes are oxidative stress, inflammation, and resultant insulin and leptin resistance. Moreover, the severity of ED is correlated with comorbid medical conditions, including obesity. Therefore, amelioration of these comorbidities may increase the efficacy of ED treatment with phosphodiesterase 5 inhibitors, the first-line medication for patients with ED. Although metformin was originally developed as an insulin sensitizer six decades ago, it has also been shown to improve leptin resistance. In addition, metformin has been reported to reduce oxidative stress, inflammatory response, and body weight, as well as improve ED, in animal and human studies. Moreover, administration of a combination of metformin and phosphodiesterase 5 inhibitors improves erectile function in patients with ED who have a poor response to sildenafil and are insulin resistant. Thus, concomitant treatment of metabolic derangements associated with obesity in patients with ED who are obese would improve the efficacy and reduce the refractory response to penile vasodilators. In this review, we discuss the connecting factors between obesity and ED and the possible combined treatment modalities.
Animals ; Body Weight ; Comorbidity ; Erectile Dysfunction ; Humans ; Inflammation ; Insulin ; Leptin ; Male ; Metformin ; Obesity ; Oxidative Stress ; Phosphodiesterase 5 Inhibitors ; Public Health ; Sildenafil Citrate ; Soil ; Vasodilator Agents

OBJECTIVES: To report our experiences in pregnant patients with pulmonary arterial hypertension (PAH) who were treated with targeted therapy. METHODS: From 2011 to 2017, women who decided to maintain pregnancies in our PAH clinic were included. Clinical data, management, and outcomes of the mothers and fetuses were reviewed. RESULTS: Nine women with PAH and 10 deliveries were reviewed. The median maternal age was 28 (26–32) years old. The functional status of each patient was New York Heart Association functional class II or III at first visit. Sildenafil was prescribed in advance in 9 cases of delivery. Multidiscipline team approach management and intensive care were performed during the peripartum period. There was no maternal or fetal mortality. Severe cardiac events occurred in 2 patients with Eisenmenger syndrome: cardiac arrest and uncontrolled arrhythmia. Non-cardiac events occurred in 3 cases: postpartum bleeding, urinary tract infection, and pneumonia. The median gestational period at delivery was about 34 (32–38) weeks. Three cases were emergent delivery because of unexpected preterm labor. Intrauterine growth restriction developed in 4 fetuses. CONCLUSIONS: Pregnancy could be maintained by the introduction of targeted therapy rather more safely than the previous era in the case of maintenance of pregnancy. Intensive care and a multidisciplinary team approach can possibly improve the outcomes of the pregnant women with PAH and their babies. However, pregnancy in patients with PAH is still strongly prohibited and it can be tried in expert center where there has sufficient multidisciplinary team approach in case of inevitability.
Arrhythmias, Cardiac ; Critical Care ; Eisenmenger Complex ; Female ; Fetal Mortality ; Fetus ; Heart ; Heart Arrest ; Hemorrhage ; Humans ; Hypertension ; Hypertension, Pulmonary ; Maternal Age ; Mothers ; Obstetric Labor, Premature ; Peripartum Period ; Pneumonia ; Postpartum Period ; Pregnancy ; Pregnant Women ; Sildenafil Citrate ; Urinary Tract Infections

Fixed drug eruption is a commonly reported mucocutaneous drug eruption. A 61-year-old male presented to our clinic with a complaint of an itchy round erythematous patch on the left hand dorsum with myalgia. On taking medical history, the patient correlated the episode with the intake of an oral sexual enhancer that he had obtained over the counter. We found the medicine contained tadalafil and sildenafil in combination with herbal ingredients. A short course of oral corticosteroid therapy resulted in the complete resolution of the lesion leaving residual hyperpigmentation of the skin involved. Various sexual enhancers with fancy names and attractive packaging are available without requiring a doctor's prescription. Most contain phosphodiesterase-5 inhibitors in various concentrations, often with herbal additions. These drugs are used erratically by the lay public, and often produce side effects. Herein, we report a case of fixed drug rash related to a sexual enhancer, which we believe to be the first report in Korea.
Cyclic Nucleotide Phosphodiesterases, Type 5 ; Drug Eruptions* ; Exanthema ; Hand ; Humans ; Hyperpigmentation ; Korea ; Male ; Middle Aged ; Myalgia ; Phosphodiesterase 5 Inhibitors ; Prescriptions ; Product Packaging ; Sildenafil Citrate ; Skin ; Tadalafil

PURPOSE: A case of a transient visual field defect and a change in spectral-domain optical coherence tomography (SD-OCT) after an overdose of sildenafil citrate is described. CASE SUMMARY: A 67-year-old male with no previous medical history presented with a bluish tinge and visual field defect in both eyes. He had consumed eight tablets of sildenafil citrate (800 mg) 3 days before the visit. His best-corrected visual acuity was 14/20 in the right eye and 20/20 in the left eye. No specific finding was noted on slit-lamp examination. Fundus examination and fundus photography revealed focal foveal hypopigmentation in both eyes. He underwent SD-OCT imaging with the Cirrus HD-OCT (Carl Zeiss Meditec, Oberkochen, Germany), and thickening of the ellipsoid zone and choroid was revealed by SD-OCT scans. He was advised not to take any more sildenafil citrate and was followed for 1 week after the first visit. Central scotomas of both eyes were revealed by a visual field test, and thickening of the ellipsoid zone and choroid remained. His eyes were re-evaluated 1 and 3 months after the first visit, and although the symptoms nearly disappeared, abnormalities in the visual field test and on SD-OCT remained, albeit with some degree of improvement. He revisited us 4 months after the first visit, at which time the visual field test and SD-OCT scans showed results within normal ranges. CONCLUSIONS: Sildenafil citrate overdose can result in a color anomaly (bluish tinge), visual field defects, and thickening of the ellipsoid zone and choroid on SD-OCT scans.
Aged ; Choroid ; Humans ; Hypopigmentation ; Male ; Photography ; Reference Values ; Scotoma ; Sildenafil Citrate ; Tablets ; Tolnaftate ; Tomography, Optical Coherence ; Visual Acuity ; Visual Field Tests ; Visual Fields

BACKGROUND AND OBJECTIVES: Macitentan (MAC) reduces morbidity and mortality among advanced-stage pulmonary arterial hypertension (PAH) patients. However, data regarding the histopathologic and hemodynamic benefits of MAC treatment at an early stage of PAH is lacking. METHODS: One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=16), MAC combined with sildenafil (SIL) (MAC+SIL, n=16), or normal saline (MCT, n=16). Twelve sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 7 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis. RESULTS: RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. RV-FAC was less deteriorated in the MAC, compared to that in the MCT (44±3% vs. 25±7%, p < 0.05), and the co-administration of SIL showed no additional benefit (45±8%, p > 0.05 vs. the MAC). On invasive hemodynamic analyses, RV end-systolic (196±78 µL) and end-diastolic volumes (310±86 µL), pulmonary artery systolic pressure (89±7.2 mmHg), and end-systolic pressure-volume relationship (−254±25.1) were significantly worse in the MCT vs. in the MAC (101±45 µL, 235±55 µL, 40±10.5 mmHg, and −145±42.1, respectively) and MAC+SIL (109±47 µL, 242±46 µL, 38±9.2 mmHg, and −151±39.2, respectively) (all p < 0.05). However, the MAC and MAC+SIL did not differ (all p > 0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC and MAC+SIL vs. in the MCT (all p < 0.05); the 2 treatment groups did not differ. CONCLUSIONS: MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.
Animals ; Atrial Pressure ; Blood Pressure ; Catheters ; Echocardiography ; Fibrosis ; Hemodynamics ; Humans ; Hypertension ; Hypertension, Pulmonary ; Lung ; Models, Animal ; Monocrotaline ; Mortality ; Pathology ; Pulmonary Artery ; Rats ; Sildenafil Citrate

PURPOSE: The 5-alpha reductase inhibitors (5ARI) are one of the most commonly used medications for the treatment of benign prostatic hyperplasia (BPH). Phosphodiesterase type-5 inhibitors are also used to treat BPH. 5ARI is a drug with adverse effects of sexual dysfunction. In this study, we investigated the safety and efficacy of coadministration of finasteride and sildenafil on sexual function and lower urinary symptoms in patients with BPH. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who were receiving finasteride and sildenafil daily regimens for treatment of BPH in 2 university hospitals. Patients with adverse effects, vital sign, physical exam, laboratory test, 5-item version of the international index of erectile function (IIEF-5), International Prostate Symptom Score (IPSS), quality of life (QoL) were analyzed. RESULTS: The number of patients analyzed in this study was 218. The mean age of the patients was 62.63±8.37 years and the mean duration of medication was 18.23±10.97 weeks. Significant changes were not observed in the vital signs measured before and after the drug administration. Compared with before treatment, improvement of lower urinary tract symptom (IPSS: 17.56±4.21 vs. 11.64±5.33, p < 0.001) was observed and improvement of sexual function (IIEF-5: 9.44±5.21 vs. 12.73±6.81, p < 0.001) was also confirmed. CONCLUSIONS: Daily coadministration of finasteride and sildenafil for the treatment of BPH could be used safely, and improvement of lower urinary tract symptom as well as improvement of sexual function could be expected.
5-alpha Reductase Inhibitors ; Erectile Dysfunction ; Finasteride ; Hospitals, University ; Humans ; Lower Urinary Tract Symptoms ; Male ; Medical Records ; Prostate ; Prostatic Hyperplasia ; Quality of Life ; Retrospective Studies ; Sildenafil Citrate ; Urinary Tract ; Vital Signs