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Phosphodiesterase Inhibitor

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181. Low-Intensity Extracorporeal Shockwave Therapy Can Improve Erectile Function in Patients Who Failed to Respond to Phosphodiesterase Type 5 Inhibitors Full Text available with Trip Pro

Low-Intensity Extracorporeal Shockwave Therapy Can Improve Erectile Function in Patients Who Failed to Respond to Phosphodiesterase Type 5 Inhibitors Managing patients with erectile dysfunction (ED) who failed to respond to phosphodiesterase type 5 inhibitors (PDE5is) is a challenging task. Recently, low-intensity extracorporeal shockwave therapy (LI-ESWT) was reported to improve ED by enhancing perfusion of the penis. The current study was performed to evaluate whether combined treatment

2017 American journal of men's health

182. Liposomal-delivery of phosphodiesterase 5 inhibitors augments UT-15C-stimulated ATP release from human erythrocytes Full Text available with Trip Pro

Liposomal-delivery of phosphodiesterase 5 inhibitors augments UT-15C-stimulated ATP release from human erythrocytes The use of liposomes to affect targeted delivery of pharmaceutical agents to specific sites may result in the reduction of side effects and an increase in drug efficacy. Since liposomes are delivered intravascularly, erythrocytes, which constitute almost half of the volume of blood, are ideal targets for liposomal drug delivery. In vivo, erythrocytes serve not only in the role (...) to pulmonary hypertension in these individuals. In contrast to deformation, both healthy human and PAH erythrocytes do release ATP in response to incubation with prostacyclin analogs via a well-characterized signaling pathway. Importantly, inhibitors of phosphodiesterase 5 (PDE5) have been shown to significantly increase prostacyclin analog-induced ATP release from human erythrocytes. Here we investigate the hypothesis that targeted delivery of PDE5 inhibitors to human erythrocytes, using a liposomal

2017 Biochemistry and Biophysics Reports

183. Protective efficacy of phosphodiesterase-1 inhibition against alpha-synuclein toxicity revealed by compound screening in LUHMES cells Full Text available with Trip Pro

Protective efficacy of phosphodiesterase-1 inhibition against alpha-synuclein toxicity revealed by compound screening in LUHMES cells α-synuclein-induced neurotoxicity is a core pathogenic event in neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. There is currently no disease-modifying therapy available for these diseases. We screened 1,600 FDA-approved drugs for their efficacy to protect LUHMES cells from degeneration (...) induced by wild-type α-synuclein and identified dipyridamole, a non-selective phosphodiesterase inhibitor, as top hit. Systematic analysis of other phosphodiesterase inhibitors identified a specific phosphodiesterase 1 inhibitor as most potent to rescue from α-synuclein toxicity. Protection was mediated by an increase of cGMP and associated with the reduction of a specific α-synuclein oligomeric species. RNA interference experiments confirmed PDE1A and to a smaller extent PDE1C as molecular targets

2017 Scientific reports

184. Phosphodiesterase type 5 inhibitors and risk of melanoma: A meta-analysis. Full Text available with Trip Pro

Phosphodiesterase type 5 inhibitors and risk of melanoma: A meta-analysis. The association between phosphodiesterase type 5 (PDE5) inhibitors and melanoma risk is controversial.We quantify the association between use of PDE5 inhibitors and melanoma.We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for studies that were conducted up to July 13, 2016, and evaluated the association between PDE5 inhibitors and skin (...) cancer. Random effects meta-analyses were used to calculate the adjusted odds ratio (OR) with the 95% confidence interval (CI).Five observational studies were included. Compared with PDE5 inhibitor nonuse, PDE5 inhibitor use was slightly but significantly associated with an increased risk for development of melanoma (OR, 1.12; 95% CI, 1.03-1.21) and basal cell carcinoma (OR, 1.14; 95% CI, 1.09-1.19) but not squamous cell carcinoma. For melanoma risk, none of the prespecified factors (dose of PDE5

2017 Journal of American Academy of Dermatology

185. Rapid Screening of Potential Phosphodiesterase Inhibitors from the Roots of <i>Ilex pubescens</i> Hook. et Arn. Using a Combination of Ultrafiltration and LC-MS. Full Text available with Trip Pro

Rapid Screening of Potential Phosphodiesterase Inhibitors from the Roots of Ilex pubescens Hook. et Arn. Using a Combination of Ultrafiltration and LC-MS. The cyclic nucleotide phosphodiesterase (PDE) plays an important role in regulating the levels of second messenger molecules cAMP and cGMP. Various PDE inhibitors have been successfully developed into drugs for targeted diseases. In addition, PDE inhibitors can also be found in different foods and natural medicines. In this study (...) , ultrafiltration liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry (ultrafiltration LC-DAD-ESI-IT-TOF-MS) was applied to screen PDE inhibitors from the roots of Ilex pubescens Hook. et Arn. As a result, 11 major compounds were identified in I. pubescens roots, with nine compounds as potential PDE inhibitors, among which five were further confirmed to be active against PDEI and PDE5A dose-dependently in vitro, with ilexsaponin A1 and ilexsaponin B2

2017 Evidence-based Complementary and Alternative Medicine (eCAM)

186. Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast Full Text available with Trip Pro

debated. Our group previously reported that in vitro primary blast exposure reduced long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) and that primary blast affects key proteins governing LTP. Recent studies have investigated phosphodiesterase-4 (PDE4) inhibition as a therapeutic strategy for reducing LTP deficits following inertia-driven TBI. We investigated the therapeutic potential of PDE4 inhibitors (...) Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast Due to recent military conflicts and terrorist attacks, blast-induced traumatic brain injury (bTBI) presents a health concern for military and civilian personnel alike. Although secondary blast (penetrating injury) and tertiary blast (inertia-driven brain deformation) are known to be injurious, the effects of primary blast caused by the supersonic shock wave interacting with the skull and brain remain

2017 Experimental neurology

187. Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases Full Text available with Trip Pro

Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases. Both diseases have incompletely distinct pathophysiology, clinical manifestation, and treatment responsiveness. Pulmonary and systemic inflammations are the hallmarks of COPD. Most asthma responds to inhaled corticosteroid (ICS) treatment. In contrast, COPD is a corticosteroid-resistant disease. Bronchodilators (...) are a preferred treatment method of COPD, with the aim of improving symptoms and preventing exacerbation. In addition, corticosteroid insensitivity is an underlying mechanism in severe asthma. An overlap of features between asthma and COPD, which was described as asthma-COPD overlap syndrome (ACOS) is not uncommon in practice. Novel nonsteroidal therapies focusing on inflammation in asthma and COPD have been developed. Selective phosphodiesterase 4 (PDE4) inhibitor is a promising class of drugs that has been

2017 Journal of thoracic disease

188. Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes Full Text available with Trip Pro

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men.We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I

2017 World journal of diabetes

189. Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7 Full Text available with Trip Pro

Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7 Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular

2017 Scientific reports

190. Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair Full Text available with Trip Pro

Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit (...) in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies. The only known negative regulators of cyclic nucleotides are a family of enzymes called phosphodiesterases (PDEs) that hydrolyze cyclic nucleotides into adenosine monophosphate (AMP

2017 International journal of molecular sciences

191. Psiguajadials A–K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava Full Text available with Trip Pro

Psiguajadials A–K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A-K (1-11), along with 17 known ones (12-28). Their structures and absolute configurations were elucidated by spectroscopic methods and comparison of experimental and calculated ECD. Compounds 1 and 2 represent two (...) unprecedented skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3 is the first example of Psidium meroterpenoids coupling via an oxepane ring. Putative biosynthetic pathways towards 1 and 2 are proposed. Compounds 1-13 and 16-26 exhibited moderate inhibitory activities against phosphodiesterase-4 (PDE4), a drug target for asthma and chronic obstructive pulmonary disease, with IC50 values in the range of 1.34-7.26 μM.

2017 Scientific reports

192. The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities Full Text available with Trip Pro

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the strength of excitatory neural circuits and/or decrease inhibitory synaptic plasticity. Abnormally, synchronized synaptic transmission in the brain leads to seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently attracted

2017 Frontiers in molecular neuroscience

193. Phosphodiesterase type 5 inhibitor to riociguat transition is associated with hemodynamic and symptomatic improvement in pulmonary hypertension Full Text available with Trip Pro

Phosphodiesterase type 5 inhibitor to riociguat transition is associated with hemodynamic and symptomatic improvement in pulmonary hypertension Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. We studied the clinical and hemodynamics effects of transitioning 12 pulmonary hypertension patients from Phosphodiesterase type 5 inhibitor (PDE5i) to riociguat, and demonstrated

2017 Pulmonary circulation

194. Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC Full Text available with Trip Pro

Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC Phosphodiesterase 5 (PDE-5) is a major isoform of cGMP phosphodiesterase in diverse tissues and plays a critical role in regulating intracellular cGMP concentrations. However, the distribution and expression of PDE-5 in colitis-related colon cancer was still unclear, not even the function and mechanism. Western blotting and ELISA were performed to detect colonic PDE-5 (...) expression and the prevention role of PDE-5 inhibition in AOM/DSS-induced tumorigenesis model. More importantly, PDE-5 inhibitor Sildenafil inhibited colonic tumorigenesis dependent on inflammation and suppressed DSS-induced colitis. Molecular mechanism investigation indicated that Sildenafil regulated inflammation microenvironment via directly inhibiting MDSC infiltration in colonic tissue. The study provides solid evidence for the use of PDE-5 inhibitor in preventing and treating colonic inflammation

2017 American journal of cancer research

195. Phosphodiesterase Inhibitors Sildenafil and Vardenafil Reduce Zebrafish Rod Photoreceptor Outer Segment Shedding. Full Text available with Trip Pro

Phosphodiesterase Inhibitors Sildenafil and Vardenafil Reduce Zebrafish Rod Photoreceptor Outer Segment Shedding. The vertebrate rod photoreceptor undergoes daily growth and shedding to renew the rod outer segment (ROS), a modified cilium that contains the phototransduction machinery. It has been demonstrated that ROS shedding is regulated by the light-dark cycle; however, we do not yet have a satisfactory understanding of the molecular mechanisms that underlie this regulation. Given (...) that phototransduction relies on the hydrolysis of cGMP via phosphodiesterase 6 (PDE6), we examined ROS growth and shedding in zebrafish treated with cGMP-specific PDE inhibitors.We used transgenic zebrafish that express an inducible, transmembrane-bound mCherry protein, which forms a stripe in the ROS following a heat shock pulse and serves as a marker of ROS renewal. Zebrafish were reared in constant darkness or treated with PDE inhibitors following heat shock. Measurements of growth and shedding were analyzed

2017 Investigative Ophthalmology & Visual Science

196. Phosphodiesterase 4 (PDE4) Inhibitors. (Abstract)

Phosphodiesterase 4 (PDE4) Inhibitors. Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating (...) AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US

2017 Journal of American Academy of Dermatology

197. Off-Label Use of Phosphodiesterase Type 5 Inhibitor Erectile Dysfunction Medication to Enhance Sex Among Gay and Bisexual Men in Australia: Results From the FLUX Study. Full Text available with Trip Pro

Off-Label Use of Phosphodiesterase Type 5 Inhibitor Erectile Dysfunction Medication to Enhance Sex Among Gay and Bisexual Men in Australia: Results From the FLUX Study. Gay and bisexual men (GBM) use oral erectile dysfunction medications (EDMs) often with little evidence of medical indication necessitating their use.To investigate the prevalence, contexts, and motivations for oral EDM use and its relation to sexual risk behavior.A total of 2,250 Australian GBM completed an online survey (...) risky sexual behavior). Hammoud MA, Jin F, Lea T, et al. Off-Label Use of Phosphodiesterase Type 5 Inhibitor Erectile Dysfunction Medication to Enhance Sex Among Gay and Bisexual Men in Australia: Results From the FLUX Study. J Sex Med 2017;14:774-784.Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

2017 Journal Of Sexual Medicine

198. Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. Full Text available with Trip Pro

Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate

2017 The Journal of dermatology Controlled trial quality: uncertain

199. Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats. (Abstract)

Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats. Phosphodiesterase inhibitors possess anti-inflammatory properties. In addition, some studies report that phosphodiesterase 2A (PDE2A) are highly expressed in the dorsal horn of the spinal cord. The present study aimed to investigate whether intrathecal administration of Bay 60-7550, a specific PDE2A inhibitor, could alleviate mechanical allodynia (...) factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) expressions were measured by ELISA. Furthermore, PDE2A mRNA and protein expressions in spinal cord were measured by Real-Time PCR and Western blot.Intrathecal administration of the PDE2A inhibitor Bay 60-7550, significantly attenuated mechanical allodynia, down-regulated spinal TNF-α, IL-1β and IL-6 over-expressions, increased the expression of spinal cAMP

2017 European Spine Journal

200. Prospective Case-Crossover Study Investigating the Possible Association Between Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) and Phosphodiesterase Type 5 Inhibitor (PDE5i) Exposure. (Abstract)

Prospective Case-Crossover Study Investigating the Possible Association Between Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) and Phosphodiesterase Type 5 Inhibitor (PDE5i) Exposure. To evaluate the association between intermittent phosphodiesterase type 5 inhibitor (PDE5i) exposure and risk of acute nonarteritic anterior ischemic optic neuropathy (NAION) using a case-crossover design.Male adults with suspected NAION were enrolled at 41 US ophthalmology sites from 2010 to 2015

2017 Urology

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