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Phosphodiesterase Inhibitor

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141. 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

143. Rolipram, a Selective Phosphodiesterase 4 Inhibitor, Ameliorates Mechanical Hyperalgesia in a Rat Model of Chemotherapy-Induced Neuropathic Pain through Inhibition of Inflammatory Cytokines in the Dorsal Root Ganglion Full Text available with Trip Pro

Rolipram, a Selective Phosphodiesterase 4 Inhibitor, Ameliorates Mechanical Hyperalgesia in a Rat Model of Chemotherapy-Induced Neuropathic Pain through Inhibition of Inflammatory Cytokines in the Dorsal Root Ganglion Chemotherapy-induced neuropathic pain is a significant side effect of chemotherapeutic agents and is the most common reason for stopping chemotherapy. The aim of the present study was to find the major site and mechanisms of action by which rolipram, a selective phosphodiesterase (...) -4 inhibitor, alleviates paclitaxel-induced neuropathic pain. Chemotherapy-induced neuropathic pain was induced in adult male Sprague-Dawley rats by intraperitoneal injection of paclitaxel on four alternate days. Rolipram was administered systemically or locally into the lumbar spinal cord, L5 dorsal root ganglion, sciatic nerve, or skin nerve terminal. The mechanical threshold, the protein level of several inflammatory cytokines, and the cellular locations of phosphodiesterase-4 and interleukin

2017 Frontiers in pharmacology

144. The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17 responses induced by 6-sulfo LacNAc (slan) dendritic cells. Full Text available with Trip Pro

The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17 responses induced by 6-sulfo LacNAc (slan) dendritic cells. The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory (...) cytokines and to program Th17/Th1 T cell responses.The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs.In vitro studies were performed analyzing the effects of apremilast on the proinflammatory function of slanDCs and their capacity to induce Th1/Th17-biased T cell responses.Increasing cAMP levels in slanDCs by PDE4 inhibition strongly reduced production of IL-12 and TNF-α. In line with these findings, co-culture experiments

2017 Journal of dermatological science

145. 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

146. Combination therapy of phosphodiesterase 4 inhibitors for management in stable COPD patients: a meta-analysis

Combination therapy of phosphodiesterase 4 inhibitors for management in stable COPD patients: a 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") for correspondence: Organisation

2018 PROSPERO

147. The hemodynamic interactions of combination therapy with a-blockers and phosphodiesterase-5 inhibitors compared with monotherapy with a-blockers

The hemodynamic interactions of combination therapy with a-blockers and phosphodiesterase-5 inhibitors compared with monotherapy with a-blockers 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

2018 PROSPERO

148. Systematic review and meta-analysis of topical application of phosphodiesterase 4 (PDE4) inhibitors in atopic dermatitis

Systematic review and meta-analysis of topical application of phosphodiesterase 4 (PDE4) inhibitors in atopic dermatitis 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

2018 PROSPERO

149. Effect of combination therapy of endothelin receptor antagonist and phosphodiesterase 5 inhibitor on pulmonary haemodynamics and exercise capacity in patients with pulmonary arterial hypertension: a meta-analysis

Effect of combination therapy of endothelin receptor antagonist and phosphodiesterase 5 inhibitor on pulmonary haemodynamics and exercise capacity in patients with pulmonary arterial hypertension: a 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

2018 PROSPERO

150. Phosphodiesterase Inhibitor

providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See for financial assistance information. Ontology: Phosphodiesterase Inhibitors (C0031638) Definition (NCI) Any substance that inhibits phosphodiesterase, an enzyme that catalyzes the breaking of a phosphodiester bond. Usually, this refers to cyclic nucleotide phosphodiesterase, an enzyme that breaks the phosphodiester bond (...) ) Compounds that specifically inhibit PHOSPHODIESTERASE 5. Concepts Pharmacologic Substance ( T121 ) MSH SnomedCT 407313002 , 407316005 English Phosphodiesterase 5 inhibitor , PDE-V Inhibitor , Phosphodiesterase V Inhibitor , PDE5 Inhibitor , Inhibitors, PDE5 , Phosphodiesterase Type 5 Inhibitors , Phosphodiesterase 5 Inhibitors , Inhibitors, PDE-5 , PDE 5 Inhibitors , PDE-5 Inhibitors , Inhibitors, Phosphodiesterase 5 , PDE5 Inhibitors , pde 5 inhibitor , 5 inhibitors phosphodiesterase

2018 FP Notebook

151. Phosphodiesterase-4 Inhibitor

Phosphodiesterase-4 Inhibitor Phosphodiesterase-4 Inhibitor Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Phosphodiesterase-4 (...) Inhibitor Phosphodiesterase-4 Inhibitor Aka: Phosphodiesterase-4 Inhibitor , Roflumilast , Daliresp From Related Chapters II. Mechanism Phosphodiesterase-4 Inhibitor increases lung, intracellular cAMP III. Indications Severe, refractory with frequent exacerbations IV. Dosing Roflumilast 500 mcg orally daily ($250/month) V. Adverse Effects Gastrointestinal (common, intolerable in 5%) Weight loss (may be >10%) Other common symptoms Psychiatric (3%) Depression Anxiety VI. Drug Interactions Cytochrome P450

2018 FP Notebook

152. The efficacy of the combination of alpha-blocker and Phosphodiesterase-5 inhibitor in improving the quality of life in comparison to monotherapy in patients with lower urinary tract symptoms with or without erectile dysfunction

The efficacy of the combination of alpha-blocker and Phosphodiesterase-5 inhibitor in improving the quality of life in comparison to monotherapy in patients with lower urinary tract symptoms with or without erectile dysfunction 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

2018 PROSPERO

153. Phosphodiesterase Type 5 Inhibitor Use and Disease Recurrence After Prostate Cancer Treatment Full Text available with Trip Pro

Phosphodiesterase Type 5 Inhibitor Use and Disease Recurrence After Prostate Cancer Treatment Phosphodiesterase type 5 inhibitor (PDE5i) use is common for management of erectile dysfunction. Single-institution studies have reported conflicting data on the relationship between PDE5i use and biochemical recurrence of prostate cancer (BCR) after radical prostatectomy.To evaluate the association between PDE5i use and BCR after radical prostatectomy and radiation therapy in a nationwide population

2015 EvidenceUpdates

154. 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

155. 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

156. 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

157. 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

158. First-in-human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males. Full Text available with Trip Pro

First-in-human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males. The aim of the present study was to investigate the safety, tolerability, dose proportionality and relative bioavailability of tablet and oral solution formulations of BI 409306 in healthy male subjects, and to compare the safety and pharmacokinetics in subjects who were extensive metabolizers (EMs) or poor metabolizers (PMs) of cytochrome P450

2017 British journal of clinical pharmacology Controlled trial quality: uncertain

159. Effects of chronic administration of the phosphodiesterase inhibitor vardenafil on serum levels of adrenal and testicular steroids in men with type 2 diabetes mellitus. Full Text available with Trip Pro

Effects of chronic administration of the phosphodiesterase inhibitor vardenafil on serum levels of adrenal and testicular steroids in men with type 2 diabetes mellitus. To investigate whether long-term, chronic treatment with the phosphodiesterase-5 inhibitor vardenafil affects adrenal and testicular steroidogenesis in diabetic men, using liquid chromatography-tandem mass spectrometry. A longitudinal, prospective, investigator-started, randomized, placebo-controlled, double-blind, clinical

2017 Endocrine Controlled trial quality: uncertain

160. Inhibition of phosphodiesterase 4 (PDE4) reduces dermal fibrosis by interfering with the release of interleukin-6 from M2 macrophages. (Abstract)

Inhibition of phosphodiesterase 4 (PDE4) reduces dermal fibrosis by interfering with the release of interleukin-6 from M2 macrophages. To investigate the disease-modifying effects of phosphodiesterase 4 (PDE4) inhibition in preclinical models of systemic sclerosis (SSc).We studied the effects of PDE4 inhibition in a prevention and a treatment model of bleomycin-induced skin fibrosis, in the topoisomerase mouse model as well as in a model of sclerodermatous chronic graft-versus-host disease (...) . To better understand the mode of action of PDE4 blockade in preclinical models of SSc, we investigated fibrosis-relevant mediators in fibroblasts and macrophages from healthy individuals and patients suffering from diffuse-cutaneous SSc on blockade of PDE4.Specific inhibition of PDE4 by rolipram and apremilast had potent antifibrotic effects in bleomycin-induced skin fibrosis models, in the topoisomerase I mouse model and in murine sclerodermatous chronic graft-versus-host disease. Fibroblasts were

2017 Annals of the rheumatic diseases

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