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Phosphodiesterase Inhibitor

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161. cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants. Full Text available with Trip Pro

cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants. Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP) has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose (...) of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE) with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2) for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation) mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities

2016 PLoS ONE

162. Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors. Full Text available with Trip Pro

Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors. Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity (...) of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral), 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated

2016 PLoS ONE

163. Apremilast: A Phosphodiesterase 4 Inhibitor for the Treatment of Psoriatic Arthritis. Full Text available with Trip Pro

Apremilast: A Phosphodiesterase 4 Inhibitor for the Treatment of Psoriatic Arthritis. Psoriatic arthritis (PsA) is a spondyloarthritis that occurs in up to 30% of psoriasis patients. Patients with PsA are at risk for decreased quality of life due to both joint and skin symptoms, impaired physical function and disease progression. Treatments include non-steroidal anti-inflammatory drugs, conventional systemic disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate, and biologic (...) agents, including tumor necrosis factor-α inhibitors. The most recently introduced treatment option is apremilast, an oral phosphodiesterase 4 inhibitor.This review provides an in-depth discussion of apremilast's mechanism of action, and evidence of its clinical efficacy and safety from the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) phase III pivotal clinical trials (PALACE 1, 2, and 3).These trials demonstrate that apremilast is effective for the treatment of active PsA

2014 Rheumatology and therapy Controlled trial quality: uncertain

164. Additive effects of the Rho Kinase Inhibitor Y-27632 and vardenafil on relaxation of corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure. Full Text available with Trip Pro

Additive effects of the Rho Kinase Inhibitor Y-27632 and vardenafil on relaxation of corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure. To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue (...) of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is).Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR]). Potent control subjects (n = 5) underwent penile needle biopsy. qPCR was performed for the expression of RhoA and ROCK subtypes 1 and 2. Immunohistochemistry staining against ROCK and α smooth muscle actin (αSMA) was performed

2016 BJU international

165. Inhibition of adrenergic and non-adrenergic smooth muscle contraction in the human prostate by the phosphodiesterase 10-selective inhibitor TC-E 5005. (Abstract)

Inhibition of adrenergic and non-adrenergic smooth muscle contraction in the human prostate by the phosphodiesterase 10-selective inhibitor TC-E 5005. The phosphodiesterase (PDE) 5 inhibitor tadalafil is available for treatment of male lower urinary tract symptoms (LUTS), while the role of other PDE isoforms for prostate smooth muscle tone is still unknown. Here, we examined effects of the PDE10-selective inhibitor TC-E 5005 on smooth muscle contraction in human prostate tissue.Prostate samples (...) contractions by tadalafil (10 μM). The prostacyclin analog treprostinil and the nitric oxide donor DEA NONOate induced relaxations of precontracted prostate strips, which were significantly amplified by TCE 5005.The PDE10-selective inhibitor TC-E 5005 inhibits adrenergic and neurogenic smooth muscle contractions in the human prostate. TC-E 5005 inhibits neurogenic contractions with similar efficacy than tadalafil, so that urodynamic effects in vivo appear possible. Prostate 76:1364-1374, 2016. © 2016 Wiley

2016 Prostate

166. Calmodulin kinase II inhibition limits the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors. Full Text available with Trip Pro

Calmodulin kinase II inhibition limits the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors. A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under β-adrenergic receptor (β-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via (...) with cilostamide induced an SR Ca(2+) leak, which was also blocked by CaMKII inhibition.Our results show that PDE inhibitors exert inotropic effects via PKA but lead to SCWs via both PKA and CaMKII activation partly via Epac2, suggesting the potential use of CaMKII inhibitors as adjuncts to PDE inhibition to limit their pro-arrhythmic effects.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

2016 Cardiovascular Research

167. Icariside II, a novel phosphodiesterase 5 inhibitor, protects against H2O2‐induced PC12 cells death by inhibiting mitochondria‐mediated autophagy Full Text available with Trip Pro

Icariside II, a novel phosphodiesterase 5 inhibitor, protects against H2O2‐induced PC12 cells death by inhibiting mitochondria‐mediated autophagy Oxidative stress is a major cause of cellular injury in a variety of human diseases including neurodegenerative disorders. Thus, removal of excessive reactive oxygen species (ROS) or suppression of ROS generation may be effective in preventing oxidative stress-induced cell death. This study was designed to investigate the effect of icariside II (...) (ICS II), a novel phosphodiesterase 5 inhibitor, on hydrogen peroxide (H2 O2 )-induced death of highly differentiated rat neuronal PC12 cells, and to further examine the underlying mechanisms. We found that ICS II pre-treatment significantly abrogated H2 O2 -induced PC12 cell death as demonstrated by the increase of the number of metabolically active cells and decrease of intracellular lactate dehydrogenase (LDH) release. Furthermore, ICS II inhibited H2 O2 -induced cell death through attenuating

2016 Journal of cellular and molecular medicine

168. The effect of phosphodiesterase 5 inhibitors on cerebral blood flow in humans: a systematic review

The effect of phosphodiesterase 5 inhibitors on cerebral blood flow in humans: a systematic review Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence: Organisation web

2017 PROSPERO

169. Comparison of efficacy and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a systematic review and network meta-analysis

Comparison of efficacy and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a systematic review and network meta-analysis Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g

2017 PROSPERO

170. Phosphodiesterase 5 inhibitors for pulmonary hypertension [Cochrane protocol]

Phosphodiesterase 5 inhibitors for pulmonary hypertension [Cochrane protocol] Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence: Organisation web address: Timing and effect

2017 PROSPERO

171. Phosphodiesterase 4 inhibitors for psoriatic arthritis [Cochrane protocol]

Phosphodiesterase 4 inhibitors for psoriatic arthritis [Cochrane protocol] Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence: Organisation web address: Timing and effect

2017 PROSPERO

172. Phosphodiesterase 4 inhibitors for psoriatic arthritis [Cochrane Protocol]

Phosphodiesterase 4 inhibitors for psoriatic arthritis [Cochrane Protocol] Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence: Organisation web address: Timing and effect

2017 PROSPERO

173. The association between phosphodiesterase type 5 inhibitors use and risk of nonarteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis

The association between phosphodiesterase type 5 inhibitors use and risk of nonarteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr

2017 PROSPERO

174. Systematic review and meta-analysis of the efficacy of phosphodiesterase-5 inhibitors in secondary Raynaud's phenomenon

Systematic review and meta-analysis of the efficacy of phosphodiesterase-5 inhibitors in secondary Raynaud's phenomenon Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence

2017 PROSPERO

175. Efficacy and safety of Phosphodiesterase 5 Inhibitors for erectile dysfunction of any cause: a systematic review and network meta-analyses

Efficacy and safety of Phosphodiesterase 5 Inhibitors for erectile dysfunction of any cause: a systematic review and network meta-analyses Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne

2017 PROSPERO

176. Phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of fetal growth restriction: individual patient data meta-analysis

Phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of fetal growth restriction: individual patient data meta-analysis Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne

2017 PROSPERO

177. Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase-5 inhibitors in the treatment of premature ejaculation. (Abstract)

Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase-5 inhibitors in the treatment of premature ejaculation. We aimed to evaluate the effectiveness of paroxetine and tadalafil combination in the treatment of premature ejaculation (PE). A total of 150 primary (lifelong)PE patients were randomly distributed into three groups of 50 patients each. Group 1 received 20 mg paroxetine every day for 1 month, Group 2 received 20 mg tadalafil on demand 2 h before (...) significant changes were detected (60.6 ± 30.2-117.3 ± 67.3, 68.5 ± 21.4-110.2 ± 37.3, 71.56 ± 40.23-175.2 ± 60.2)(P < 0.01). IELT scores after discontinuation of treatment were found to be close to the baseline IELT scores (P > 0.05). IIEF scores were evaluated both prior to and after the treatment, and no statistically significant difference was detected (P > 0.05). It is concluded that utilisation of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase-5 inhibitors (PDE5i) combination

2015 Andrologia Controlled trial quality: uncertain

178. New atopic dermatitis drug approved - Crisaborole (Eucrisa) phosphodiesterase-4 inhibitor, applied topically twice daily

New atopic dermatitis drug approved - Crisaborole (Eucrisa) phosphodiesterase-4 inhibitor, applied topically twice daily Allergy Notes: New atopic dermatitis drug approved - Crisaborole (Eucrisa) phosphodiesterase-4 inhibitor, applied topically twice daily Allergy, Asthma and Immunology News Updated Daily by Board-certified Allergist at Cleveland Clinic Florida Pages New atopic dermatitis drug approved - Crisaborole (Eucrisa) phosphodiesterase-4 inhibitor, applied topically twice daily The FDA (...) approved crisaborole (Eucrisa) as a treatment for eczema (atopic dermatitis) in patients aged 2 years and older in December 2016. The drug is a phosphodiesterase-4 inhibitor, applied topically twice daily. What is crisaborole? Crisaborole is a boron-based, small-molecule, topical phosphodiesterase-4 inhibitor . Chemically, crisaborole is a phenoxybenoxaborole. It contains a boron atom that helps penetrate the skin and is essential for its binding activity. How effective is crisaborole? Two trials

2017 Allergy Notes blog

179. Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat in patients with pulmonary arterial hypertension who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors. Full Text available with Trip Pro

Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat in patients with pulmonary arterial hypertension who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors. Patients with pulmonary arterial hypertension (PAH) who do not have an adequate response to therapy with phosphodiesterase-5 inhibitors (PDE-5i) may have insufficient synthesis of cyclic guanosine monophosphate (cGMP). These patients may respond to a direct soluble guanylate

2016 Respiratory medicine

180. Phosphodiesterase 4 inhibitors have wide-ranging activity in B cell malignancies. Full Text available with Trip Pro

Phosphodiesterase 4 inhibitors have wide-ranging activity in B cell malignancies. Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3',5'-cyclic adenosine monophosphate in lymphocytes. In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases spleen tyrosine kinase and phosphatidylinositol 3-kinase and inhibits vascular endothelial growth factor A secretion by tumor cells, inducing cancer cell apoptosis and blocking (...) angiogenesis in the microenvironment. We describe the successful clinical repurposing of PDE4 inhibitors in B-cell malignancies, and propose that given their anti-inflammatory/immunomodulatory activity, these agents will suppress BCR signals without the toxicity associated with other targeted biological doublets.

2016 Blood

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