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Morbi-mortality in cystic fibrosis (CF) is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.
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Vardenafil significantly improved treatment satisfaction in men with ED, and in their partners. The results provide further evidence of the validity of the TSS.
Primary efficacy variable was the between-group difference in change in International Index of Erectile Function-Erectile Function domain (IIEF-EF) score from baseline to end of washout. Secondary variables included change from baseline in proportion of positive respondents to Sexual Encounter Profile questions and in satisfaction with treatment as assessed with the Treatment Satisfaction Scale (TSS).
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This study demonstrated that vardenafil had no adverse effects on sperm concentration, compared with sildenafil and placebo, when administered daily at the maximum recommended dose for 6 months. Specifically, use of vardenafil for 6 months does not impair sperm concentration, total sperm count per ejaculate, or sperm morphology and motility. Levels of reproductive hormones were also unaffected.
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Phosphodiesterase type 5 inhibitors are the first choice therapy in the treatment of erectile dysfunction. Many men in their reproductive years are now using phosphodiesterase type 5 inhibitors. The purpose of this study was to determine the effects of 6 months of treatment with 20 mg vardenafil, compared with 100 mg sildenafil and placebo, on semen characteristics and reproductive hormones in men with and without erectile dysfunction.
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To investigate the effects of phosphodiesterase type 5 (PDE5) inhibitors on erectile variables during a period with no sexual stimulation in a laboratory setting double-blind study.
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To evaluate the effects of Huafenqinutang combined with vardenafil for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with erectile dysfunction.
The aim of this study was to evaluate the safety and efficacy of vardenafil in outpatients with chronic schizophrenia and erectile dysfunction and to investigate any effect on quality of life in this population.
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In this placebo-controlled, double-blind, multicentre parallel-group study, men with mild-to-moderate ED were randomised to 24 wk of treatment, followed by a 4-wk washout.
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Phosphodiesterase 5 inhibitors are preferred by most men for the oral treatment of erectile dysfunction. In many guidelines, this therapy is recommended as first-line therapy because of convenience, high efficacy, and low rates of side-effects. Sildenafil was the first drug for the treatment of erectile dysfunction, introduced in 1998. There are now two new phosphodiesterase 5 inhibitors, vardenafil and tadalafil, for which approval was recently given in the European Union and is expected this year in the United States.
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More than one-third of men may experience erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy. A recent study has shown that vardenafil, a phosphodiesterase 5 inhibitor, could significantly improve the key indices of erectile function in men after unilateral or bilateral nerve-sparing radical retropubic prostatectomy. Few adverse events were observed in the study.
The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil.
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The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD).
Owing to their vasodilatory effects, the phosphodiesterase-5 inhibitors have become widely used for the treatment of erectile dysfunction. Among the reported adverse events of these agents are epistaxis, variceal bleeding, intracranial hemorrhage, and hemorrhoidal bleeding. We report a case of vocal fold hemorrhage that occurred after vardenafil use in a 31-year-old man who was a professional singer.
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The phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, tadalafil and vardenafil, are a class of medications that are safe and effective in treating erectile dysfunction (ED). Yet, resuming sexual activity following a period of abstinence in response to ED may be anxiety-provoking for the man, his partner and their relationship, causing the sexual encounter to become a stressful event. The differences between PDE5 inhibitors in terms of duration of action can be successfully utilized by healthcare professionals to mitigate some of the psychosocial barriers that interfere with treating ED. PDE5 inhibitors with a longer duration of responsiveness provide some men with ED and their partners, a treatment option that may offer greater flexibility and potentially less anxiety surrounding the resumption of sexual activity. Shorter-acting PDE5s may be preferred by men/couples with predictable sexual scripts, excellent communication strategies and concerns regarding the duration of side effects.
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Vardenafil was effective, reliable and well tolerated in patients with ED treated under real-life conditions.
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In women suffering from low sexual desire-associated with low attention for sexual cues-the combination of testosterone and vardenafil may be a promising new treatment.
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In this retrospective analysis, the percentage of patients "returning to normal" erectile function at week 12 (as defined by scores > or =26 on erectile function domain of International Index of Erectile Function [IIEF-EF]) was determined, with further stratification by baseline ED severity, etiology, age, and duration of ED.
PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension.
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Heme oxygenase (HO) enzyme catalyzes oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO shares many properties with nitric oxide (NO) including the activation of soluble guanyl cyclase.
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Erectile dysfunction and depression are highly associated. Previous studies have shown benefits of phosphodiesterase-5 inhibitor treatment for erectile dysfunction associated with antidepressant therapy or subsyndromal depression. The present study assessed the safety and efficacy of vardenafil in men with erectile dysfunction and untreated mild depression.
Vascular smooth muscle cells express endothelial nitric oxide synthase (eNOS) and produce nitric oxide (NO). Recently, increased NO production has been reported to induce the synthesis and secretion of vascular endothelial growth factor (VEGF) via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Expression of eNOS in corpus cavernosal smooth muscle has also been reported. However, it is unclear whether CCSMCs can generate NO.
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In patients on the doxazosin gastrointestinal therapeutic system for benign prostatic hyperplasia a single 10 mg dose of vardenafil had no symptomatic hemodynamic effects.
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Ion mobility spectrometry was used as a rapid screening tool for the detection of acetildenafils, sildenafils and avanafil within adulterated herbal supplement matrices. Acetildenafils show a tendency for partial fragmentation during the desorption/ionization process affording two peaks in the ion mobility spectrum in addition to the intact compound. The fragmentation appears to occur α to the carbonyl group along the CN bond attaching the piperazine moiety, producing a common fragment (K₀=1.0280 cm²V⁻¹s⁻¹) along with the respective piperazine fragment. The sildenafils and avanafil afford one molecular ion peak per compound.
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CCSMCs express eNOS and synthesize NO. NO synthesis leads to enhancement of VEGF synthesis via the NO/cGMP pathway. Combined L-arg and vardenafil treatment, which can enhance VEGF production, may provide a novel therapeutic strategy for the treatment of erectile dysfunction as well as endothelial dysfunction in general.
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TSS domain scores increased from baseline to last observation carried forward (LOCF) in the vardenafil-treated men and untreated women partners, but exhibited little change for the placebo group (P < 0.0001 vs. placebo). For both patients and partners in the vardenafil group, correlations between TSS domains, the IIEF-EF and the mSLQQ-QoL scores at LOCF were moderate to strong.
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The objective of the present study was to determine the efficacy and safety of a fixed dose of vardenafil in the treatment of patients with erectile dysfunction (ED).
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Under doctor's office conditions vardenafil was reliable and highly effective, already at the 10 mg dose, when the patients utilized its effect within a time window ranging from < 0.5 to 12 hours (tablet ingestion to SI). In addition, vardenafil was very well tolerated. Patient satisfaction with the treatment was reportedly very high.
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The aim of this study was to compare the effect of the first intake of tadalafil and vardenafil in men with DN and DED.