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Phosphodiesterase Inhibitor

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261. Phosphodiesterase-5 Inhibitors: Action on the Signaling Pathways of Neuroinflammation, Neurodegeneration, and Cognition Full Text available with Trip Pro

Phosphodiesterase-5 Inhibitors: Action on the Signaling Pathways of Neuroinflammation, Neurodegeneration, and Cognition Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and memory loss diseases. Mechanistically, PDE5-Is produce an anti-inflammatory and neuroprotection effect by increasing expression of nitric oxide synthases and accumulation of cGMP and activating protein kinase G (PKG

2015 Mediators of inflammation

262. Phosphodiesterase Type 5 Inhibitor Use Following Radical Prostatectomy is not Associated with an Increased Risk of Biochemical Recurrence. (Abstract)

Phosphodiesterase Type 5 Inhibitor Use Following Radical Prostatectomy is not Associated with an Increased Risk of Biochemical Recurrence. Recently, conflicting findings have been reported on the effect of phosphodiesterase type 5 inhibitor (PDE5I) use on biochemical outcome following radical prostatectomy (RP). Thus, we investigated the impact of PDE5I treatment following RP, including therapeutic strategy, timing, duration, and drug type, on oncologic outcomes.We analyzed records of 1082

2015 Annals of Surgical Oncology

263. Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: Results from a randomized, vehicle-controlled exploratory trial. (Abstract)

Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: Results from a randomized, vehicle-controlled exploratory trial. This exploratory study was designed to evaluate the safety and efficacy profile of the topical phosphodiesterase 4 inhibitor E6005 in Japanese children with mild-to-moderate atopic dermatitis. The present randomized, multicenter study included 62 patients who were treated with 0.05% E6005, 0.2% E6005 or vehicle ointment twice daily

2015 The Journal of dermatology Controlled trial quality: uncertain

264. Roflumilast, a type 4 phosphodiesterase inhibitor, shows promising adjunctive, host-directed therapeutic activity in a mouse model of tuberculosis. Full Text available with Trip Pro

Roflumilast, a type 4 phosphodiesterase inhibitor, shows promising adjunctive, host-directed therapeutic activity in a mouse model of tuberculosis. With phosphodiesterase inhibitors (PDE-Is) showing significant promise in shortening tuberculosis treatment, we assessed the effect of roflumilast, an FDA-approved type 4 PDE-I, in both acute and chronic murine models of tuberculosis. Alone, roflumilast had no effect on lung bacillary burden and mortality. However, when roflumilast was used

2015 Antimicrobial Agents and Chemotherapy

265. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2). Full Text available with Trip Pro

Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2). Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis.ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis.This phase III, double-blind, placebo-controlled trial randomized adults

2015 The British journal of dermatology Controlled trial quality: predicted high

266. Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition. Full Text available with Trip Pro

Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition. Cognitive dysfunction is a core feature of dementia and a prominent feature in psychiatric disease. As non-redundant regulators of intracellular cAMP gradients, phosphodiesterases (PDE) mediate fundamental aspects of brain function relevant to learning, memory, and higher cognitive functions. Phosphodiesterase-4B (PDE4B) is an important phosphodiesterase in the hippocampal formation, is a major (...) days in PDE4B(Y358C) mice, an effect replicated pharmacologically with a non-selective PDE4 inhibitor, implicating cAMP signaling by PDE4B in a very late phase of consolidation. No effect of the PDE4B(Y358C) mutation was observed in the prepulse inhibition and forced swim tests. Our data establish specific inhibition of PDE4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory.

2015 Neuropsychopharmacology

267. Phosphodiesterase Type 5 Inhibition to Improve Endothelial Function and Vascular Remodeling in Chronic Kidney Disease and End Stage Renal Disease Patients Requiring New Arteriovenous Fistula

Phosphodiesterase Type 5 Inhibition to Improve Endothelial Function and Vascular Remodeling in Chronic Kidney Disease and End Stage Renal Disease Patients Requiring New Arteriovenous Fistula Phosphodiesterase Type 5 Inhibition to Improve Endothelial Function and Vascular Remodeling in Chronic Kidney Disease and End Stage Renal Disease Patients Requiring New Arteriovenous Fistula - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting (...) registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Phosphodiesterase Type 5 Inhibition to Improve Endothelial Function and Vascular Remodeling in Chronic Kidney Disease and End Stage Renal Disease Patients Requiring New Arteriovenous Fistula The safety and scientific validity of this study is the responsibility of the study

2015 Clinical Trials

268. Treatment Satisfaction of Men and Partners Following Switch from On-Demand Phosphodiesterase Type 5 Inhibitor Therapy to Tadalafil 5 mg Once Daily. (Abstract)

Treatment Satisfaction of Men and Partners Following Switch from On-Demand Phosphodiesterase Type 5 Inhibitor Therapy to Tadalafil 5 mg Once Daily. Treatment satisfaction of men receiving phosphodiesterase 5 inhibitors (PDE5) for erectile dysfunction (ED) and their partners is essential to successful long-term therapy.This study aims to assess treatment satisfaction, in men with a partial response to on-demand (PRN) PDE5 and their female partners, following tadalafil 5 mg once daily

2015 The journal of sexual medicine Controlled trial quality: predicted high

269. Phosphodiesterase 5a Inhibition with Adenoviral Short Hairpin RNA Benefits Infarcted Heart Partially through Activation of Akt Signaling Pathway and Reduction of Inflammatory Cytokines Full Text available with Trip Pro

Phosphodiesterase 5a Inhibition with Adenoviral Short Hairpin RNA Benefits Infarcted Heart Partially through Activation of Akt Signaling Pathway and Reduction of Inflammatory Cytokines Treatment with short hairpin RNA (shRNA) interference therapy targeting phosphodiesterase 5a after myocardial infarction (MI) has been shown to mitigate post-MI heart failure. We investigated the mechanisms that underpin the beneficial effects of PDE5a inhibition through shRNA on post-MI heart failure.An (...) adenoviral vector with an shRNA sequence inserted was adopted for the inhibition of phosphodiesterase 5a (Ad-shPDE5a) in vivo and in vitro. Myocardial infarction (MI) was induced in male C57BL/6J mice by left coronary artery ligation, and immediately after that, the Ad-shPDE5a was injected intramyocardially around the MI region and border areas.Four weeks post-MI, the Ad-shPDE5a-treated mice showed significant mitigation of the left ventricular (LV) dilatation and dysfunction compared to control mice

2015 PloS one

270. Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2. Full Text available with Trip Pro

Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2. Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli (...) with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signaling microdomains.How individual cAMP microdomains affect cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth.Using pharmacological and genetic manipulation of PDE activity, we

2015 Circulation Research

271. Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) as Medical Expulsive Therapy in Distal Ureteral Stones

Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) as Medical Expulsive Therapy in Distal Ureteral Stones Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) as Medical Expulsive Therapy in Distal Ureteral Stones - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100 (...) ). Please remove one or more studies before adding more. Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) as Medical Expulsive Therapy in Distal Ureteral Stones The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our for details. ClinicalTrials.gov Identifier: NCT02519153 Recruitment Status : Active, not recruiting First Posted : August 10, 2015 Last

2015 Clinical Trials

272. Evolution of Phosphodiesterase-5 Inhibitors Full Text available with Trip Pro

Evolution of Phosphodiesterase-5 Inhibitors 26770931 2016 01 15 2018 11 13 2287-4208 33 3 2015 Dec The world journal of men's health World J Mens Health Evolution of Phosphodiesterase-5 Inhibitors. 123-4 10.5534/wjmh.2015.33.3.123 Moon Du Geon du G Department of Urology, Korea University Guro Hospital, Seoul, Korea. eng Journal Article 2015 12 23 Korea (South) World J Mens Health 101596899 2287-4208 2016 1 16 6 0 2016 1 16 6 0 2016 1 16 6 1 ppublish 26770931 10.5534/wjmh.2015.33.3.123

2015 The world journal of men's health

273. Phosphodiesterase 3 (PDE3) inhibition with Cilostazol does not block in vivo oocyte maturation in rhesus macaques (Macaca mulatta). Full Text available with Trip Pro

Phosphodiesterase 3 (PDE3) inhibition with Cilostazol does not block in vivo oocyte maturation in rhesus macaques (Macaca mulatta). Studies in mice suggest that cilostazol, an FDA-approved phosphodiesterase 3 (PDE3) inhibitor, might have a contraceptive effect within the approved dose range. We sought to evaluate the potential contraceptive effects of cilostazol in a nonhuman primate model.Adult female rhesus macaques were stimulated to develop multiple preovulatory follicles by administering (...) human recombinant gonadotropins, and oocytes were collected by follicle aspiration 36 h after an ovulatory stimulus (human chorionic gonadotropin). Monkeys received no further treatment (controls) or the PDE3 inhibitor cilostazol at the maximum approved human dose of 100mg twice daily starting 6 days prior to follicle aspiration. Recovered oocytes were scored for meiotic stage [germinal vesicle (GV) intact, GV breakdown], and metaphase II stage oocytes were fertilized in vitro and observed

2015 Contraception

274. The Role of Phosphodiesterase Inhibitors in Incretin Secretion

The Role of Phosphodiesterase Inhibitors in Incretin Secretion The Role of Phosphodiesterase Inhibitors in Incretin Secretion - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. The Role of Phosphodiesterase (...) are involved in the regulation of glucagon-like peptide-1 (GLP-1) secretion from L cells in humans. We hypothesize that: (1) phosphodiesterase-4D (PDE4D) inhibitor (roflumilast) enhance GLP-1 secretion from L cells; (2) PDE4D inhibitor (roflumilast) and DPP4 inhibitor (sitagliptin) have synergistic effect on increasing the amount of circulating active GLP-1. Experimental Design and Methods: Twenty healthy adults, age 21-55, will be recruited for this study. This is a randomized, double-blind, placebo

2015 Clinical Trials

275. A Detailed Analysis of the Association Between Postoperative Phosphodiesterase Type 5 Inhibitor Use and the Risk of Biochemical Recurrence After Radical Prostatectomy. (Abstract)

A Detailed Analysis of the Association Between Postoperative Phosphodiesterase Type 5 Inhibitor Use and the Risk of Biochemical Recurrence After Radical Prostatectomy. A recent study reported a detrimental effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa). We tested the association between PDE5-I use, PDE5-I therapy scheme, number of PDE5-I pills taken, and BCR in 2579 patients treated (...) of administration schedule, and number of PDE5-I pills were not significantly associated with higher risk of BCR (all p ≥ 0.2) after accounting for multiple confounders including time from RP to PDE5-I use. While awaiting further studies, patients should not be denied PDE5-I treatment after RP.Among patients treated with radical prostatectomy, phosphodiesterase type 5 inhibitor use was not associated with an increased risk of biochemical recurrence, regardless of the therapeutic regimen used.Copyright © 2015

2015 European Urology

276. Inhibition of type 5 phosphodiesterase counteracts β2-adrenergic signalling in beating cardiomyocytes. Full Text available with Trip Pro

production and hydrolysis modulate downstream signals resulting in different biological responses. The interplay between beta receptors (βARs) signalling and phosphodiesterase 5 (PDE5) activity remains to be addressed.Using combined strategies with pharmacological inhibitors and genetic deletion of PDEs and βAR isoforms, we revealed a specific pool of cAMP that is under dual regulation by PDE2 and, indirectly, PDE5 activity. Inhibition of PDE5 with sildenafil produces a cGMP-dependent activation of PDE2 (...) Inhibition of type 5 phosphodiesterase counteracts β2-adrenergic signalling in beating cardiomyocytes. Compartmentalization of cAMP and PKA activity in cardiac muscle cells plays a key role in maintaining basal and enhanced contractility stimulated by sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor increases cAMP production, which is countered by the hydrolytic activity of selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP

2015 Cardiovascular Research

277. Risk-benefit assessment of oral phosphodiesterase type 5 inhibitors for treatment of erectile dysfunction: a multiple criteria decision analysis. (Abstract)

Risk-benefit assessment of oral phosphodiesterase type 5 inhibitors for treatment of erectile dysfunction: a multiple criteria decision analysis. Erectile dysfunction (ED) is a common male sexual disorder worldwide. Three oral phosphodiesterase type 5 inhibitors (PDE5Is) - sildenafil, tadalafil and vardenafil - are available for treatment of ED. This study quantitatively evaluated the therapeutic efficacy and safety of these medications to assist treatment decision making.We used multiple

2015 International journal of clinical practice

278. Pharmacological characterization of the interaction between the dual phosphodiesterase (PDE) 3/4 inhibitor RPL554 and glycopyrronium on human isolated bronchi and small airways. (Abstract)

Pharmacological characterization of the interaction between the dual phosphodiesterase (PDE) 3/4 inhibitor RPL554 and glycopyrronium on human isolated bronchi and small airways. The dual PDE3/4 inhibitor RPL 554 causes bronchodilation in patients with asthma or COPD and synergistically interacts with muscarinic receptor antagonists in relaxing human isolated bronchi in acute experimental settings. In the present study we investigated the long-lasting interaction between RPL554

2015 Pulmonary Pharmacology & Therapeutics

279. Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure). Full Text available with Trip Pro

or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53).In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function (...) Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure). This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains.Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased

2015 JACC. Heart failure Controlled trial quality: uncertain

280. A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model. (Abstract)

A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model. In Alzheimer's disease (AD), activated microglia invade and surround β-amyloid plaques, possibly contributing to the aggregation of amyloid β (Aβ), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD (...) . In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6 mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze

2015 Mechanisms of Ageing and Development

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