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Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and epithelial-mesenchymal transition of alveolar epithelial cells in lung fibrosis model rats caused by paraquat (PQ). Methods Lung fibrosis model was constructed by a single intraperitoneal injection of PQ (30 mg·kg
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Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl
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Aim To investigate the effect of CPD1 , a novel phosphodiesterase 5 inhibitor, on contractile ten- sion of pulmonary artery and aorta in rats with pulmonary arterial hypertension ( PAH ) .Methods MCT- induced PAH was generated by a single intraperitoneal injection of MCT(50 mg • kg"1) in rats.Seven days after MCT injection, the rats were treated with CPD1 ( 10 mg • kg-1 • d"1) for 14 days.The tension of vascular rings was examined in MCT-induced PAH rats.Results MCT treated rats exhibited profound PAH when examined 3 weeks after injection.In contrast, gavage administration of CPD1 led to significant decrease in the right ventricle systolic pressure ( RVSP) and right ventricular mass index (RVMI), as well as MCT-induced pulmonary arterial wall thinning and enlarged lumen, indicating that CPD1 inhibited the de- velopment of PAH.Cavage administration of CPD1 also reduced phenylephrine and endothelin-1-induced pulmonary artery contraction and aorta contraction in MCT-treated rats.Conclusions Treatment with CPD1 attenuates vascular reactivity, lessens vascular smooth muscle cell proliferation and remodeling, and inhibits PAH via inhibition of non-voltage dependent Ca2∗ channels in normal and PAH rats.
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Erectile dysfunction (ED) is considered a condition with a broad range of etiologies. Obstructive sleep apnea (OSA) syndrome is one of the lesser studied risk factors for ED. We intend to summarize the current evidence on the relationship between OSA and sexual impairment, focusing on the results in terms of erectile function of the different therapies offered to OSA patients. A systematic review was conducted, selecting articles related to the physiology of OSA and ED, and to the treatments of OSA syndrome and their reported outcomes in erectile and sexual function. Higher prevalences of ED in the OSA groups have been published. However, whether this effect on the erectile function occurs in the entire range of OSA severities remains unclear. Several hypotheses were proposed to explain the physiology of this association. Continuous Positive Airway Pressure as a treatment for OSA patients with ED has achieved a significative improvement in the sexual parameters in most of the studies. Phosphodiesterase type 5 inhibitors (iPDE5) on demand are useful as a treatment for ED in this subgroup of patients, with high satisfaction rates. The surgical treatment for the OSA evidenced benefits over the erectile function, and the effect on the sexual satisfaction of the therapy using Mandibular Advancement Devices is still undefined.
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The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin (10−7, 10−6, 10−5 and 10−4 M). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.
Subject(s)
Humans , Male , Erectile Dysfunction , Guanylate Cyclase , Muscle, Smooth , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase , Nucleotides, Cyclic , Phenylephrine , Phosphodiesterase 5 Inhibitors , Quercetin , Radioimmunoassay , Relaxation , Sildenafil CitrateABSTRACT
The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaborations tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% (95% CI: -9.120% to -2.017%) reduction in RR for GAQ-1, and -0.229 (95% CI: -0.425 to -0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.
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Sintomas do trato urinário inferior (STUI) representam uma das queixas mais comuns em homens. Diferentes distúrbios da micção podem resultar em STUI. Hipogonadismo é umadoença comum e subdiagnosticada no idoso, podendo estar associado a STUI. O objetivodeste estudo foi avaliar os efeitos da administração crônica da Tadalafila em camundongos hipogonádicos com deficiência crônica de óxido nítrico através de estudo cistométrico in vivo. Para tanto, foi comparado a resposta da Tadalafila em animais castrados(hipogonádicos) e após reposição de testosterona (normogonádicos). Um total de quarenta edois camundongos foram randomizados em seis grupos. Grupo 1(L-NAME): L-NAME(60mg/kg), que é um inibidor da síntese da óxido-nítrico sintase, foi administrado em água debeber. Grupo 2 (DTAD): L-NAME (60mg/kg) + diluente da Tadalafila (goma xantana emanitol). Grupo 3 (TAD): L-NAME (60mg/kg) + Tadalafila diário (4mg/kg). Grupo 4(ORQ): L-NAME (60mg/kg) + orquiectomia...
Lower Urinary Tract Symptoms (LUTS) represents one of the most commonly complaints in male. Several voiding disorders can be involved in the pathogenesis of LUTS. Hipogonadism is a common and underdiagnoseddisease in the aging male, usually presenting simultaneously with LUTS. The objective of thisstudy wasto evaluate the cystometric effects of chronic tadalafil administration in castrated micewith nitric oxide cronic deficiency.The results of tadalafiladministration were compared in castrated mice (hypogonadics) and after testosterone replacement (eugonadics). A total of 42 mice were randomized to six groups. Group 1 (L-NAME): L-name (60mg/kg), which is an oxide-nitric sintethase inhibitor, was administrated in drinking water. Group 2 (DTAD): L-name (60mg/kg) + diluent of tadalafil (mannitol and xantane gum). Group 3 (TAD): L-name + daily tadalafil (4mg/kg). Group 4 (ORQ): L-name + orchiectomy...
Subject(s)
Humans , Prostatic Hyperplasia , Androgens , Phosphodiesterase InhibitorsABSTRACT
BACKGROUND: Phosphodiesterase Type 5 Inhibitors (PDE5Is), which are prescription drug in South Korea, have been concerned about misuse, overuse and illegal provision of the drugs. This study was performed to investigate utilization and safety of illegal Phosphodiesterase Type 5 Inhibitors (PDE5Is), and related factors among South Korean men. METHODS: A questionnaire survey was conducted from May to July in 2013 among 1,500 nationally representative general males using computer-assisted telephone interview (CATI). The questionnaire included the characteristics of population, the characteristics of PDE5Is use, the experience with the use of illegally obtained PDE5Is, and adverse events after PDE5Is use. RESULTS: Among study population, the 1,015 (67.7%) men answered that they have used the illegally obtained PDE5Is. Younger age, single, lower frequency of PDE5Is use in a lifetime was associated with an increased use of illegally obtained PDE5Is. The men experienced adverse events after PDE5Is use is 528 (35.2%). The most common adverse event was mild to moderate hot flashes. CONCLUSION: We need to enhance awareness about the risk of illegally obtained PDE5Is use, especially in younger men and single. Proactive educations and public relations on safe use of PDE5Is for proper patients are needed.
Subject(s)
Humans , Male , Hot Flashes , Interviews as Topic , Korea , Phosphodiesterase 5 Inhibitors , Prescriptions , Public RelationsABSTRACT
Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. Originally considered to be a disorder of vasoconstriction and vasodilatation, it has become clear that the predominant characteristic of PAH is abnormal cellular proliferation leading to progressive obliteration of the pulmonary vasculature. Current PAH-specific therapies target one of three major pathways involved in development and progression of PAH: 1) The endothelin pathway targeted by the endothelin receptor antagonists (ERAs); 2) the prostacyclin pathway, targeted by prostacyclin analogs and 3) the nitric oxide (NO) pathway, targeted by the phosphodiesterase type 5 (PDE-5) inhibitors.
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PURPOSE: This post hoc integrated analysis assessed the efficacy and safety of tadalafil 5 mg once daily in a large Korean population with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS). MATERIALS AND METHODS: Individual Korean participant data were integrated from three 12-week, randomized, double-blind, placebo-controlled studies in Asian men with BPH-LUTS, wherein 177 Korean men received placebo and 177 received tadalafil 5 mg once daily. The primary objective was to compare the change from baseline to week 12 in total International Prostate Symptom Score (IPSS) after treatment with tadalafil versus placebo. RESULTS: A significantly greater improvement (p<0.001) in total IPSS from baseline to week 12 was observed for tadalafil compared to placebo (least squares mean: tadalafil=-5.97; placebo=-3.94 ). Total IPSS at weeks 4 and 12, IPSS voiding and storage subscores at weeks 4, 8, and 12, and IPSS quality of life index at weeks 8 and 12 were also significantly improved (p<0.05) for tadalafil compared to placebo. There was significant improvement (p<0.001) in the patient global Impression of improvement responses and numerical improvement in the clinician global impression of improvement responses with tadalafil compared to placebo. There were no significant treatment differences for peak urine flow rate or postvoid residual volume . Few participants had treatment-emergent adverse events and there were no unexpected safety findings. CONCLUSIONS: This integrated analysis of three randomized, placebo-controlled Asian studies confirmed tadalafil 5 mg once daily as an efficacious and well-tolerated treatment for Korean men with BPH-LUTS.
Subject(s)
Humans , Male , Asian People , Lower Urinary Tract Symptoms , Phosphodiesterase 5 Inhibitors , Prostate , Prostatic Hyperplasia , Quality of Life , Residual Volume , TadalafilABSTRACT
The introduction of oral phosphodiesterase type 5 inhibitor therapy in 1998 revolutionized the treatment of erectile dysfunction. Erectile dysfunction is the most common sexual problem in men. It often has a profound effect on intimate relationships and quality of life. The analysis of pharmaceuticals is an important part of the drug development process as well as for routine analysis and quality control of commercial formulations. Whereas the determination of sildenafil citrate, vardenafil and tadalafil are well documented by a variety of methods, there are few publications about the determination of udenafil, lodenafil carbonate, mirodenafil and avanafil. The paper presents a brief review of the action mechanism, adverse effects, pharmacokinetics and the most recent analytical methods that can determine drug concentration in biological matrices and pharmaceutical formulations of these four drugs.
A introdução da terapia oral com inibidores da fosfodiesterase tipo 5, em 1998, revolucionou o tratamento da disfunção erétil. A disfunção erétil é o problema sexual mais comum em homens. Muitas vezes tem um efeito profundo nas relações íntimas e na qualidade de vida. A análise de produtos farmacêuticos é uma parte importante do processo de desenvolvimento de fármacos, bem como para a análise de rotina e controle de qualidade das formulações comerciais. Enquanto a determinação do citrato de sildenafila, vardenafila e tadalafila está bem documentada por uma variedade de métodos, existem poucas publicações sobre a determinação de udenafila, carbonato de lodenafila, mirodenafila e avanafila. O artigo apresenta uma breve revisão do mecanismo de ação, efeitos adversos, farmacocinética e os mais recentes métodos analíticos, que podem determinar a concentração do fármaco em matrizes biológicas e formulações farmacêuticas destes quatro fármacos.
Subject(s)
Biological Specimen Banks , Phosphodiesterase 5 Inhibitors/analysis , Wind Scale , Erectile Dysfunction/classificationABSTRACT
In February 2011, the Korean Society for Sexual Medicine and Andrology (KSSMA) realized the necessity of developing a guideline on erectile dysfunction (ED) appropriate for the local context, and established a committee for the development of a guideline on ED. As many international guidelines based on objective evidence are available, the committee decided to adapt these guidelines for local needs instead of developing a new guideline. Considering the extensive research activities on ED in Korea, data with a high level of evidence among those reported by Korean researchers have been collected and included in the guideline development process. The latest KSSMA guideline on ED has been developed for urologists. The KSSMA hopes that this guideline will help urologists in clinical practice.
Subject(s)
Male , Andrology , Erectile Dysfunction , Korea , Phosphodiesterase 5 InhibitorsABSTRACT
Currently, phosphodiesterase type 5 (PDE5) inhibitors are the initial treatment option for erectile dysfunction. The reported efficacy of PDE5 inhibitors is about 70%, although it is significantly lower in difficult-to-treat subpopulations. Treatment failures might be due to the severity of the underlying pathophysiology, improper use of medication, unrealistic patient expectations, difficult relationship dynamics, severe performance anxiety, and other psychological problems. Physicians must address these issues to identify true treatment failures attributable to the drugs. This article discusses factors that might affect the response to PDE5 inhibitors and develops a strategy to maximize the overall efficacy of PDE5 inhibitors in initial non-responders to PDE5 inhibitors.
Subject(s)
Humans , Male , Carbolines , Erectile Dysfunction , Imidazoles , Performance Anxiety , Phosphodiesterase 5 Inhibitors , Piperazines , Purines , Sulfones , Treatment Failure , Triazines , Sildenafil Citrate , Tadalafil , Vardenafil DihydrochlorideABSTRACT
OBJECTIVES: To investigate the acute effect of phosphodiesterase type 5 (PDE5) inhibitor on erectile dysfunction by evaluating serum oxidative status and prolidase activity. METHODS: Serum samples of 36 patients with erectile dysfunction and 30 control cases were analyzed for total antioxidant status, total oxidant status, and prolidase activity, before and after the administration of tadalafil citrate. RESULTS: Before and after tadalafil citrate administration, serum total antioxidant status, total oxidant status, and prolidase were 1.1+0.0 vs. 1.6 + 0.0 umol H2O2 Eq/L, 10.3+1.1 vs. 6.9 + 1.2 umol H2O2 Eq/L, and 236.4+19.5 vs. 228.2 + 19.2 U/L, respectively (p<0.0001 for all). CONCLUSIONS: Evaluation of serum oxidative status and prolidase activity confirmed the beneficial acute effects of PDE5 inhibitor in patients with erectile dysfunction.