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Phosphodiesterase Inhibitor

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181. Efficacy of phosphodiesterase-4 inhibitors in juvenile Batten disease (CLN3). Full Text available with Trip Pro

Efficacy of phosphodiesterase-4 inhibitors in juvenile Batten disease (CLN3). Juvenile neuronal ceroid lipofuscinosis (JNCL), or juvenile Batten disease, is a pediatric lysosomal storage disease caused by autosomal recessive mutations in CLN3, typified by blindness, seizures, progressive cognitive and motor decline, and premature death. Currently, there is no treatment for JNCL that slows disease progression, which highlights the need to explore novel strategies to extend the survival (...) and quality of life of afflicted children. Cyclic adenosine monophosphate (cAMP) is a second messenger with pleiotropic effects, including regulating neuroinflammation and neuronal survival. Here we investigated whether 3 phosphodiesterase-4 (PDE4) inhibitors (rolipram, roflumilast, and PF-06266047) could mitigate behavioral deficits and cell-specific pathology in the Cln3Δex7/8 mouse model of JNCL.In a randomized, blinded study, wild-type (WT) and Cln3Δex7/8 mice received PDE4 inhibitors daily beginning

2016 Annals of Neurology

182. Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink. Full Text available with Trip Pro

Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink. Laboratory evidence suggests that reduced phosphodiesterase type 5 (PDE5) expression increases the invasiveness of melanoma cells; hence, pharmacological inhibition of PDE5 could affect melanoma risk. Two major epidemiological studies have investigated this and come to differing conclusions. We therefore aimed to investigate whether (...) PDE5 inhibitor use is associated with an increased risk of malignant melanoma, and whether any increase in risk is likely to represent a causal relationship.We conducted a matched cohort study using primary care data from the UK Clinical Practice Research Datalink. All men initiating a PDE5 inhibitor and with no prior cancer diagnosis were identified and matched on age, diabetes status, and general practice to up to four unexposed controls. Ever use of a PDE5 inhibitor and time-updated cumulative

2016 PLoS medicine

183. Psychotherapy and phosphodiesterase-5 inhibitor in early rehabilitation after radical prostatectomy: a prospective randomised controlled trial. (Abstract)

Psychotherapy and phosphodiesterase-5 inhibitor in early rehabilitation after radical prostatectomy: a prospective randomised controlled trial. The aim of this study was to evaluate the impact of group psychotherapy and the use of a phosphodiesterase-5 inhibitor (PDE-5i) in the early rehabilitation stage of patients with prostate cancer undergoing radical prostatectomy (RP). Fifty-six patients undergoing RP for prostate cancer were randomised into four groups, and 53 completed the protocol

2016 Andrologia Controlled trial quality: uncertain

184. The Association Between Phosphodiesterase Type-5 Inhibitors and Prostate Cancer: Results from the REDUCE Study. Full Text available with Trip Pro

The Association Between Phosphodiesterase Type-5 Inhibitors and Prostate Cancer: Results from the REDUCE Study. Despite routine use of phosphodiesterase type 5 inhibitor to treat erectile dysfunction the role in prostate cancer chemoprevention remains unclear. Only a few studies have explored the link between phosphodiesterase type 5 inhibitor use and prostate cancer. We tested the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in the REDUCE (Reduction (...) by Dutasteride of Prostate Cancer Events) trial.REDUCE was a 4-year multicenter study testing the effect of daily dutasteride on prostate cancer risk in men with prostate specific antigen 2.5 to 10.0 ng/ml and negative biopsy who underwent study mandated biopsies at 2 and 4 years. The association of phosphodiesterase type 5 inhibitor with overall prostate cancer risk and disease grade (Gleason 2-6 and 7-10) was examined using adjusted logistic and multinomial regression analysis. Secondary analysis

2016 Journal of Urology Controlled trial quality: uncertain

185. Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical Full Text available with Trip Pro

Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life.We evaluated the efficacy and safety of apremilast in palmoplantar psoriasis.A post hoc analysis of data pooled from phase IIb (PSOR-005

2016 Journal of the American Academy of Dermatology

186. A Phase I Randomized Trial to Assess the Effect on skin infiltrate thickness and Tolerability of Topical Phosphodiesterase Inhibitors in the Treatment of Psoriasis Vulgaris Using a Modified Psoriasis Plaque Test. (Abstract)

A Phase I Randomized Trial to Assess the Effect on skin infiltrate thickness and Tolerability of Topical Phosphodiesterase Inhibitors in the Treatment of Psoriasis Vulgaris Using a Modified Psoriasis Plaque Test. Oral phosphodiesterase (PDE)4 inhibitors have shown efficacy in chronic obstructive pulmonary disease and psoriasis.To assess the effectiveness, local safety and tolerability, and systemic pharmacokinetics of two topical PDE4 inhibitors, roflumilast and TAK-084, in plaque psoriasis.An (...) on psoriasis plaques for 3 weeks.The primary end point of (mean) change from baseline in skin infiltrate thickness after 3 weeks of treatment showed statistically significant improvements for all treatments: betamethasone valerate cream (-286·9 μm), the selective PDE4 inhibitors roflumilast 0·5% (-237·1 μm) and TAK-084 (0·5% cream, -153·6 μm; 5% cream, -216·7 μm) and calcipotriol 0·005% (-187·7 μm) when compared with vehicle cream control (all P < 0·001). Both the TAK-084 5% and roflumilast 0·5

2016 The British journal of dermatology Controlled trial quality: uncertain

187. Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study. (Abstract)

Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study. Phosphodiesterase type 4 (PDE4) inhibition is a well-known anti-inflammatory mechanism. However, the clinical use of PDE4 inhibitors has been compromised by the occurrence of mechanism-associated adverse reactions, which often limit the maximum tolerated dose. To minimize systemic exposure, a topically active PDE4 inhibitor with low transdermal (...) bioavailability could be clinically useful. The purpose of this study was to evaluate the efficacy of a novel topical PDE4 inhibitor, E6005, in patients with atopic dermatitis.This randomized, investigator-blinded, vehicle-controlled, multiple ascending dose study included 40 adult male patients with atopic dermatitis, who were randomly assigned to 10 days of treatment with either E6005 ointment (0.01, 0.03, 0.1 or 0.2%) or vehicle ointment.Of 81 patients screened, 40 who had typical lesions

2016 The Journal of dermatological treatment Controlled trial quality: uncertain

188. Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders. (Abstract)

Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders. Phosphodiesterase-4 (PDE4) hydrolyses cyclic adenosine monophosphate (cAMP), a crucial secondary messenger for cellular adaptation to diverse external stimuli. The activity of PDE4 is tightly controlled by post-translational regulation, structure-based auto-regulation and locus specific 'compartmentalization' of PDE4 with its interactive proteins (signalsomes). Through these mechanisms, PDE4 regulates cAMP levels (...) are currently undergoing clinical evaluation for treating disorders such as type 2 diabetes and non-alcoholic steatohepatitis. The discovery of novel PDE4 allosteric inhibitors and signalsome-based strategies targeting individual PDE4 variants may allow PDE4 isoform selective inhibition, which may offer safer strategies for chronic treatment of metabolic disorders.© 2016 World Obesity.

2016 Obesity Reviews

189. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. Full Text available with Trip Pro

Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks.We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792).Two identically designed, vehicle

2016 Journal of American Academy of Dermatology Controlled trial quality: predicted high

190. Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor. Full Text available with Trip Pro

Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor. The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination of in vivo and ex vivo models together (...) either two doses of BLM (n = 7) or saline (n = 3) I.T., two days apart. The rats were euthanized fourteen days after the last dose. PCLS were made and cultured for 48 h in: medium, medium + 100 μM IBMX (PDE inhibitor), or medium + 10 μM GM6001 (MMP inhibitor). Turnover of type I collagen (P1NP, C1M), type III collagen (iP3NP, C3M) and elastin degradation (ELM7) was measured in the supernatant of the cultured PCLS.P1NP, C1M, iP3NP, C3M and ELM7 were significantly increased in supernatants from BLM

2016 Respiratory research

191. Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: Results of two phase III randomized, controlled trials. Full Text available with Trip Pro

Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: Results of two phase III randomized, controlled trials. Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis.To evaluate the impact of apremilast on health-related quality of life (HRQOL), general functioning and mental health using patient-reported outcome

2016 Journal of the European Academy of Dermatology and Venereology Controlled trial quality: uncertain

192. Therapeutic synergy and complementarity for ischemia/reperfusion injury: β<sub>1</sub>-adrenergic blockade and phosphodiesterase-3 inhibition. (Abstract)

Therapeutic synergy and complementarity for ischemia/reperfusion injury: β1-adrenergic blockade and phosphodiesterase-3 inhibition. The β1-blocker when administered before reperfusion activates myocyte prosurvival signaling via β2-adrenergic receptor (β2-AR) and protein kinase A (PKA)-dependent mechanism during ischemia/reperfusion (I/R). The heart is endowed with powerful self-protective ability executed by endogenous β2-adrenopeptide receptor activation. I/R triggers cardiac (...) mechanisms involved in I/R injury protection. While β2-adrenopeptide-mediated cardioprotection is important, age-related β2-adrenopeptide receptor decoupling can result in their ineffectiveness in response to the receptor-specific therapies. Accordingly, direct activation of receptor-coupled upstream PKA-dependent signaling may serve as a therapeutic alternative to achieve cardioprotection bypassing adrenopeptidergic receptor decoupling accompanied with aging. Phosphodiesterase-3 (PDE3) inhibitor reduces

2016 International journal of cardiology

193. Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy. Full Text available with Trip Pro

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy. Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition (...) of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects

2016 Journal of the American Society of Nephrology Controlled trial quality: predicted high

194. A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition. Full Text available with Trip Pro

A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition. The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter CD36 level are common in African Americans (AAs), a population at high risk of endothelial dysfunction.To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences endothelial function, insulin

2016 Journal of Clinical Endocrinology and Metabolism Controlled trial quality: predicted high

195. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. Full Text available with Trip Pro

OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity (...) for phosphodiesterase-4-B.We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD.This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks.The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4

2016 Journal of the American Academy of Dermatology Controlled trial quality: predicted high

196. Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells. Full Text available with Trip Pro

Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells. CD8 lymphocytes play an important role in the pathogenesis of COPD. Corticosteroids and phosphodiesterase 4 (PDE4) inhibitors are anti-inflammatory drugs used for COPD treatment. Little is known of the combined effect of these drugs on COPD CD8 cells. We studied the effect of corticosteroid combined with PDE4 inhibitors on cytokine release form circulating and pulmonary CD8 cells (...) , and on glucocorticoid (GR) nuclear translocation.The effect of dexamethasone alone and in combination with the PDE4 inhibitors roflumilast and GSK256066 on cytokine release from circulating and pulmonary CD8 cells was measured. The effect of the compounds on nuclear translocation of GR and cyclic AMP-responsive element-binding protein (CREB) was studied using immunofluorescence.Dexamethasone inhibited cytokine release from COPD CD8 cells in a concentration dependent manner. PDE4 inhibitors enhanced this anti

2016 Respiratory research

197. 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

198. 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

199. Dual Strategy With Oral Phosphodiesterase Type 5 Inhibition and Intracavernosal Implantation of Mesenchymal Stem Cells Is Superior to Individual Approaches in the Recovery of Erectile and Cavernosal Functions After Cavernous Nerve Injury in Rats. (Abstract)

Dual Strategy With Oral Phosphodiesterase Type 5 Inhibition and Intracavernosal Implantation of Mesenchymal Stem Cells Is Superior to Individual Approaches in the Recovery of Erectile and Cavernosal Functions After Cavernous Nerve Injury in Rats. Novel effective therapeutic strategies are necessary for treating erectile dysfunction secondary to cavernous nerve injury (CNI).To functionally evaluate the benefits of long-term oral treatment with a phosphodiesterase type 5 inhibitor (...) on the potential capacity of intracavernosal cell therapy to recover erectile function after CNI.Bilateral crush CNI (BCNI) was produced in anesthetized male rats. After BCNI, rats were treated with the phosphodiesterase type 5 inhibitor tadalafil (TAD; 5 mg/kg/d orally; BCNI + TAD), a single intracavernosal injection of bone marrow-derived mesenchymal stem cells (BMSCs; BCNI + BMSC), or dual therapy (BCNI + BMSC + TAD). Ex vivo function of the corpus cavernosum (CC) and in vivo intracavernosal pressure

2016 Journal Of Sexual Medicine

200. Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial. (Abstract)

Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial. The therapeutic potential of phosphodiesterase-5 inhibitor PF-03049423 was evaluated in a phase 2, multicenter, randomized, double-blind, placebo-controlled study of subjects with acute ischemic stroke (http://www.clinicaltrials.gov, unique identifier: NCT01208233; http://www.clinicaltrialsregister.eu, EudraCT number: 2010-021414-32).Subjects (N = 70) received PF

2016 Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Controlled trial quality: predicted high

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