Vardenafil increases intracellular accumulation of the most prevalent mutant cystic fibrosis transmembrane conductance regulator (CTFR) in human bronchial epithelial cells.

Cystic fibrosis (CF) is a genetic disease characterized by progressive lung and chronic digestive manifestations. We have shown that therapeutic doses of vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, corrects CF Transmembrane conductance Regulator (CFTR)-dependent chloride transport in respiratory and intestinal tissues of F508del homozygous mice. Here, we studied the effect of vardenafil on CFTR in 16HBE14o and CFBE41o cell lines.

A novel device for the endoscopic management of buried bumper syndrome.

Background: Buried bumper syndrome (BBS) is a complication of percutaneous endoscopic gastrostomy (PEG) in which the internal bumper is overgrown by the gastric mucosa. Apart from loss of patency of the PEG tube, the buried bumper may evoke symptoms such as abdominal pain or peritubular leakage. While the management of an incompletely buried bumper is fairly straightforward, this is not the case for a completely buried bumper.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

Background: Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD).

Objective: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life.

Methods: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015).

Vardenafil reduces macrophage pro-inflammatory overresponses in cystic fibrosis through PDE5- and CFTR-dependent mechanisms.

Chronic inflammation that progressively disrupts the lung tissue is a hallmark of cystic fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF.

Azithromycin Attenuates -Induced Lung Inflammation by Targeting Bacterial Proteins Secreted in the Cultured Medium.

Background: airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Azithromycin improves the related clinical outcomes, but its mechanisms of action remain poorly understood. We tested the hypothesis that azithromycin downregulates -induced pro-inflammatory responses by modifying release of bacterial proteins.

Strategies in early clinical development for the treatment of basic defects of cystic fibrosis.

Introduction: Twenty-six years after the identification of the gene responsible for cystic fibrosis (CF), controversies still surround the pathogenesis of the disease that continues to burden and shorten lives. Therefore, finding effective therapeutic strategies that target the basic defect of CF is crucially needed.

Areas Covered: This review offers a comprehensive survey of fundamental therapies in early stages of development for the treatment of CF.

Resveratrol increases F508del-CFTR dependent salivary secretion in cystic fibrosis mice.

Cystic fibrosis (CF) is a fatal genetic disease associated with widespread exocrine gland dysfunction. Studies have suggested activating effects of resveratrol, a naturally-occurring polyphenol compound with antioxidant and anti-inflammatory properties, on CF transmembrane conductance regulator (CFTR) protein function. We assayed, in F508del-CFTR homozygous (CF) and in wild-type mice, the effect of resveratrol on salivary secretion in basal conditions, in response to inhibition by atropine (basal β-adrenergic-dependent component) and to stimulation by isoprenaline (CFTR-dependent component).

Lung inflammation in cystic fibrosis: pathogenesis and novel therapies.

Despite remarkable progress following the identification of the causing gene, the final outcome of cystic fibrosis (CF) remains determined mainly by the progressive reduction of lung function. Inflammation of the airways is one of the key elements of the pathogenesis of the disease: it is responsible for the destruction of lung architecture, resulting in progressive loss of respiratory function. Bronchial infection induces an intense inflammatory reaction characterized by a massive invasion of neutrophils, the properties of which seems altered in CF.

Correction of chloride transport and mislocalization of CFTR protein by vardenafil in the gastrointestinal tract of cystic fibrosis mice.

Although lung disease is the major cause of mortality in cystic fibrosis (CF), gastrointestinal (GI) manifestations are the first hallmarks in 15-20% of affected newborns presenting with meconium ileus, and remain major causes of morbidity throughout life. We have previously shown that cGMP-dependent phosphodiesterase type 5 (PDE5) inhibitors rescue defective CF Transmembrane conductance Regulator (CFTR)-dependent chloride transport across the mouse CF nasal mucosa. Using F508del-CF mice, we examined the transrectal potential difference 1 hour after intraperitoneal injection of the PDE5 inhibitor vardenafil or saline to assess the amiloride-sensitive sodium transport and the chloride gradient and forskolin-dependent chloride transport across the GI tract.

Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

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.

PDE5 Inhibitors as Potential Tools in the Treatment of Cystic Fibrosis.

Despite great advances in the understanding of the genetics and pathophysiology of cystic fibrosis (CF), there is still no cure for the disease. Using phosphodiesterase type 5 (PDE5) inhibitors, we and others have provided evidence of rescued F508del-CFTR trafficking and corrected deficient chloride transport activity. Studies using PDE5 inhibitors in mice homozygous for the clinically relevant F508del mutation have been conducted with the aim of restoring F508del-CFTR protein function.

Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy.

Cystic fibrosis is the most common life-threatening recessively inherited disease in Caucasians. Due to early provision of care in specialized reference centers and more comprehensive care, survival has improved over time. Despite great advances in supportive care and in our understanding of its pathophysiology, there is still no cure for the disease.

Immunomodulatory activity of vardenafil on induced lung inflammation in cystic fibrosis mice.

Background: We tested the hypothesis that vardenafil, a common drug used for improving erectile dysfunction and able to partially normalize transepithelial chloride transport in cystic fibrosis (CF), modulates CF lung inflammation.

Methods: Inflammatory markers in lungs of F508del-CF and wild-type mice were monitored in response to lipopolysaccharide from Pseudomonas aeruginosa (LPS). The effect of pretreatment with vardenafil (0.