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Phosphodiesterase Inhibitor

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201. The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the effects of lipopolysaccharide in human cells and rodent models of peripheral and CNS inflammation. (Abstract)

The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the effects of lipopolysaccharide in human cells and rodent models of peripheral and CNS inflammation. Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain (...) penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent (EC50∼14nM) inhibitor of lipopolysaccharide (LPS) induced TNF-α release from mouse microglia and human PBMCs. ABI-4 (0.32mg/kg) blocked LPS-induced release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in blood and brain of mice. In a rat model of endotoxin induced uveitis, ABI-4 (0.03-0.3mg/kg) demonstrated steroid-like efficacy in preventing leucocyte infiltration of the aqueous humor when administered 4h after LPS. LPS (0.32mg/kg

2017 Brain, behavior, and immunity

202. Effect of phosphodiesterase-5 inhibition with Tadalafil on SystEmic Right VEntricular size and function - A multi-center, double-blind, randomized, placebo-controlled clinical trial - SERVE trial - Rational and design. Full Text available with Trip Pro

Effect of phosphodiesterase-5 inhibition with Tadalafil on SystEmic Right VEntricular size and function - A multi-center, double-blind, randomized, placebo-controlled clinical trial - SERVE trial - Rational and design. Patients with a systemic right ventricle (RV) have a compromised late outcome caused by ventricular dysfunction. Standard medical heart failure therapy has not been shown to improve RV function and survival in these patients. Phosphodiesterase (PDE)-5 inhibition increases (...) contractility in experimental models of RV hypertrophy, but not in the normal RV. In clinical practice, the effects of PDE-5 inhibition on systemic RV function and exercise capacity in adults with a systemic RV have not been tested.The SERVE protocol is a double-blind, randomized placebo-controlled multicenter superiority trial to study the effect of PDE-5 inhibition with Tadalafil on RV volumes and function in patients with either D-transposition of the great arteries repaired with an atrial switch

2017 International journal of cardiology Controlled trial quality: predicted high

203. 2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase 4 inhibitor for atopic dermatitis. Full Text available with Trip Pro

2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase 4 inhibitor for atopic dermatitis. Crisaborole is a novel, topical nonsteroidal, anti-inflammatory, phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild to moderate atopic dermatitis.As part of a nonclinical safety testing program, these 2-year studies tested the carcinogenic potential of crisaborole.Crisaborole ointment, 2%, 5%, or 7%, was applied once daily topically to mice, and crisaborole

2017 Journal of dermatological science

204. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Full Text available with Trip Pro

RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO

2017 European Respiratory Journal

205. Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials. Full Text available with Trip Pro

Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials. Previous studies suggested that phosphodiesterase 5 inhibitors (PDE5i) have a beneficial effect in patients with heart failure (HF), although the results were inconsistent. We performed a meta-analysis to evaluate the effect of PDE5i in HF patients, and investigated the relationship between PDE5i effects and pulmonary hemodynamics.We searched PubMed, EMBASE

2017 BMC Cardiovascular Disorders

206. Effect of phosphodiesterase-5 inhibitors on cerebral blood flow in human beings: a systematic review Full Text available with Trip Pro

Effect of phosphodiesterase-5 inhibitors on cerebral blood flow in human beings: a systematic review Redirecting

2017 The Lancet

208. Phosphodiesterase 5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review

Phosphodiesterase 5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review Untitled Document The CRD Databases will not be available from 08:00 BST on Friday 4th October until 08:00 BST on Monday 7th October for essential maintenance. We apologise for any inconvenience.

2011 DARE.

209. Phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis

Phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis Untitled Document The CRD Databases will not be available from 08:00 BST on Friday 4th October until 08:00 BST on Monday 7th October for essential maintenance. We apologise for any inconvenience.

2011 DARE.

210. Work Productivity Improvement Associated With Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis Results Of A Phase 3, Randomized, Controlled Trial. Full Text available with Trip Pro

Work Productivity Improvement Associated With Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis Results Of A Phase 3, Randomized, Controlled Trial. 27200801 2016 06 10 2016 05 21 1524-4733 17 7 2014 Nov Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Value Health Work Productivity Improvement Associated With Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis Results

2016 Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Controlled trial quality: uncertain

211. Present and future treatment strategies for pulmonary arterial hypertension : focus on phosphodiesterase-5 inhibitors. (Abstract)

Present and future treatment strategies for pulmonary arterial hypertension : focus on phosphodiesterase-5 inhibitors. Idiopathic pulmonary arterial hypertension (IPAH) is a rare progressive disorder historically associated with mortality in <3 years post-diagnosis. The etiology of PAH is complex, multifactorial, and likely involves the interplay between genetic and environmental factors. These are reviewed with emphasis on the nitric oxide pathway. Use of treatment modalities including (...) with PAH, each of them has limitations. The phosphodiesterase-5 (PDE-5) inhibitors are a relatively new form of treatment for PAH. They are designed to potentiate the effects of cyclic guanosine monophosphate, thereby mimicking endogenous nitric oxide within the vasculature. PDE-5 inhibitors are selective pulmonary vasodilators effective in animal models of pulmonary hypertension. The published clinical studies evaluating their use have been small in size to date but appear to demonstrate benefit

2016 Treatments in Respiratory Medicine Controlled trial quality: uncertain

212. Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle Full Text available with Trip Pro

Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is the most common muscular dystrophy. Characterized by rounds of muscle degeneration and regeneration, DMD features progressive muscle wasting and is fatal. One approach for treatment is transplantation of muscle progenitor cells to repair (...) and restore dystrophin expression to damaged muscle. However, the success of this approach has been limited by difficulties in isolating large numbers of myogenic progenitors with strong regenerative potential, poor engraftment, poor survival of donor cells, and limited migration in the diseased muscle. We demonstrate that induction of the transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) using the cyclic adenosine monophosphate phosphodiesterase inhibitor isobutylmethylxanthine (IBMX

2016 Stem cells translational medicine

213. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling Full Text available with Trip Pro

The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance (...) and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral

2016 Oncotarget

214. Usage and perceptions of phosphodiesterase type 5 inhibitors among the male partners of infertile couples Full Text available with Trip Pro

Usage and perceptions of phosphodiesterase type 5 inhibitors among the male partners of infertile couples We aimed to investigate the prevalence of erectile dysfunction (ED) and the usage of phosphodiesterase type 5 (PDE5) inhibitors for ED treatment in infertile couples.A total of 260 male partners in couples reporting infertility lasting at least 1 year were included in this study. In addition to an evaluation of infertility, all participants completed the International Index of Erectile (...) Function (IIEF)-5 questionnaire to evaluate their sexual function. The participants were asked about their use of PDE5 inhibitors while trying to conceive during their partner's ovulatory period and about their concerns regarding the risks of PDE5 inhibitor use to any eventual pregnancy and/or the fetus.Based on the IIEF-5 questionnaire, 41.5% of the participants (108/260) were classified as having mild ED (an IIEF-5 score of 17-21), while 10.4% of the participants (27/260) had greater than mild ED

2016 Clinical and experimental reproductive medicine

215. The devil is in the details: an analysis of the subtleties between phosphodiesterase inhibitors for erectile dysfunction Full Text available with Trip Pro

The devil is in the details: an analysis of the subtleties between phosphodiesterase inhibitors for erectile dysfunction Erectile dysfunction (ED) is a common sexual disorder with numerous etiologies involving multiple organ systems that leads to significant distress and decreased quality of life for the affected men. Fortunately, there are several modalities and interventions for treating ED. Oral medications, intra-urethral compounds, intracorporeal injections, vacuum-assist devices (...) and surgically implanted prostheses are all part of the treatment algorithm. One of the first-lines and certainly the most widely used options for treating ED is the family of oral phosphodiesterase type 5 inhibitors (PDE5I). The introduction of these medications in the late 1990s revolutionized the field of sexual medicine. Currently there are no guidelines and minimal literature to help providers choose among drugs in this class. This review will address differences in efficacy and side effects between

2016 Translational andrology and urology

216. Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications Full Text available with Trip Pro

Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications The fronto-striatal circuits are the common neurobiological basis for neuropsychiatric disorders, including schizophrenia, Parkinson's disease, Huntington's disease, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's syndrome. Fronto-striatal circuits consist of motor circuits, associative circuits, and limbic circuits. All circuits share 2 (...) for pharmacological intervention in neuropsychiatric disorders related to dopaminergic regulation of fronto-striatal circuits.Clinical studies of the effects of different phosphodiesterase inhibitors on cognition, affect, and motor function in relation to the fronto-striatal circuits are reviewed.Several selective phosphodiesterase inhibitors have positive effects on cognition, affect, and motor function in relation to the fronto-striatal circuits.Increased understanding of the subcellular localization

2016 International Journal of Neuropsychopharmacology

217. Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line Full Text available with Trip Pro

, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study. (...) Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression

2016 PloS one

218. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain Full Text available with Trip Pro

Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain Perinatal ischemic stroke is the most frequent form of cerebral infarction in neonates; however, evidence-based treatments are currently lacking. We have previously demonstrated a beneficial effect of sildenafil citrate, a PDE-5 inhibitor, on stroke lesion size in neonatal rat pups. The present study investigated the effects of sildenafil in a neonatal mouse

2016 Journal of neuroinflammation

219. The Efficacy of Medical Treatment of Peyronie's Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor Full Text available with Trip Pro

The Efficacy of Medical Treatment of Peyronie's Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor This study was designed to evaluate the efficacy of medical treatment of Peyronie's disease.A total of 109 patients with Peyronie's disease who had been treated from January 2011 to December 2014 were retrospectively reviewed in this study. Forty-four patients (Group 1) were treated with 12 mg of potassium (...) para-aminobenzoate daily. Sixty-five patients (Group 2) were treated with combination therapy: tamoxifen (20 mg) and acetyl-L-carnitine (300 mg) twice daily in addition to a phosphodiesterase type 5 inhibitor. Ability to perform sexual intercourse, pain during erection, size of plaque, and penile curvature angle were assessed.In Group 1, 30 of 44 patients (68.2%) discontinued treatment within 12 weeks, while 5 patients (7.7%) in Group 2 discontinued treatment. Pain during erection and plaque size

2016 The world journal of men's health

220. Phosphodiesterase type 5 inhibitors: Irrational use in Saudi Arabia Full Text available with Trip Pro

Phosphodiesterase type 5 inhibitors: Irrational use in Saudi Arabia To identify the criteria of phosphodiesterase type 5 inhibitor (PDE5i) users and to analyse the knowledge, attitude, and practices of PDE5i use amongst Saudi men.A web-based, cross-sectional survey was conducted in Saudi Arabia between January and April 2015. Sexually active adult men were interviewed using a website questionnaire designed by the authors. Descriptive statistics were used to analyse the data.In all, 1008 men

2016 Arab journal of urology

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