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Phosphodiesterase Inhibitor

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281. A double-blind placebo-controlled study of the effects of olprinone, a specific phosphodiesterase-III inhibitor, for preventing postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. (Abstract)

A double-blind placebo-controlled study of the effects of olprinone, a specific phosphodiesterase-III inhibitor, for preventing postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. We previously reported that patients with elevated preoperative B-type natriuretic peptide (BNP) levels have an increased risk for postoperative atrial fibrillation following lung cancer surgery. The present study evaluated whether the specific phosphodiesterase III inhibitor

2015 Chest Controlled trial quality: predicted high

282. The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats. (Abstract)

The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats. Chemotherapy-induced neuropathic pain is a significant side effect of chemotherapeutic agents. Currently, there are no effective analgesics for chemotherapy-induced neuropathic pain. Rolipram is a selective phosphodiesterase 4 inhibitor, which increases intracellular cyclic AMP in nerve and immune cells. The aim of our study was to determine the analgesic effects of rolipram (...) of developing pain behavior did not prevent the development of mechanical allodynia induced by PAC.These results suggest that rolipram alleviated mechanical allodynia induced by PAC in rats. Thus, phosphodiesterase 4 inhibitors may prove useful in the treatment of chemotherapy-induced neuropathic pain. However, further studies are needed to clarify their effects in clinical settings.

2015 Anesthesia and Analgesia

283. The effects of phosphodiesterase-5 inhibitor sildenafil against post-resuscitation myocardial and intestinal microcirculatory dysfunction by attenuating apoptosis and regulating microRNAs expression: essential role of nitric oxide syntheses signaling Full Text available with Trip Pro

The effects of phosphodiesterase-5 inhibitor sildenafil against post-resuscitation myocardial and intestinal microcirculatory dysfunction by attenuating apoptosis and regulating microRNAs expression: essential role of nitric oxide syntheses signaling Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. Sildenafil has been shown to attenuate postresuscitation myocardial dysfunction in piget models of ventricular (...) -positive cells, increased anti-apoptotic Bcl-2/Bax ratio and inhibited caspase-3 activity in myocardium. Additionally, sildenafil treatment inhibited the increases in the microRNA-1 levels and alleviated the decreases in the microRNA-133a levels which negatively regulates pro-apoptotic genes. At 6 h after ROSC, post-resuscitation perfused vessel density and microcirculatory flow index were significantly lower in the saline group than in the sildenafil group.The major findings of this study

2015 Journal of translational medicine

284. Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice Full Text available with Trip Pro

and pulmonary hypertension (PH) in mice. We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects. Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both.C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both. Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar (...) Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available. Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease. Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema

2015 PloS one

285. Interaction between leucine and phosphodiesterase 5 inhibition in modulating insulin sensitivity and lipid metabolism Full Text available with Trip Pro

Interaction between leucine and phosphodiesterase 5 inhibition in modulating insulin sensitivity and lipid metabolism Leucine activates SIRT1/AMP-activated protein kinase (AMPK) signaling and markedly potentiates the effects of other sirtuin and AMPK activators on insulin signaling and lipid metabolism. Phosphodiesterase 5 inhibition increases nitric oxide-cGMP signaling, which in turn exhibits a positive feedback loop with both SIRT1 and AMPK, thus amplifying peroxisome proliferator-activated (...) . The combination also inhibited hepatic lipogenesis, stimulated hepatic and muscle fatty acid oxidation, suppressed hepatic inflammation, and reversed high-fat diet-induced steatosis.These robust improvements in insulin sensitivity, glycemic control, and lipid metabolism indicate therapeutic potential for leucine-PDE5 inhibitor combinations.

2015 Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

286. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). Full Text available with Trip Pro

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). Apremilast works intracellularly to regulate inflammatory mediators.ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis.This phase III, multicenter, double-blind, placebo-controlled

2015 Journal of the American Academy of Dermatology Controlled trial quality: predicted high

287. The Pharmacodynamic Impact of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, on Circulating Levels of Inflammatory Biomarkers in Patients with Psoriatic Arthritis: Substudy Results from a Phase III, Randomized, Placebo-Controlled Trial (PALACE 1). Full Text available with Trip Pro

The Pharmacodynamic Impact of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, on Circulating Levels of Inflammatory Biomarkers in Patients with Psoriatic Arthritis: Substudy Results from a Phase III, Randomized, Placebo-Controlled Trial (PALACE 1). Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial

2015 Journal of immunology research Controlled trial quality: uncertain

288. Dual phosphodiesterase type 5 inhibitor therapy for refractory pulmonary arterial hypertension: a pilot study. Full Text available with Trip Pro

Dual phosphodiesterase type 5 inhibitor therapy for refractory pulmonary arterial hypertension: a pilot study. Recent vasodilating drugs have improved prognosis of Pulmonary arterial hypertension (PAH). Some reports describe the merits of combination therapies for PAH, and this study evaluated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5i) combination therapy, using sildenafil and tadalafil, for multi-drug-resistant PAH.We retrospectively analyzed 7 consecutive

2015 BMC pulmonary medicine

289. Metabolic effects of newly synthesized phosphodiesterase-3 inhibitor 6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one on rat adipocytes Full Text available with Trip Pro

Metabolic effects of newly synthesized phosphodiesterase-3 inhibitor 6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one on rat adipocytes Clinical use of selective PDE3 inhibitors as cardiotonic agents is limited because of their chronotropic and lipolytic side effects. In our previous work, we synthesized a new PDE3 inhibitor named MC2 (6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one) which produced a high positive inotropic action with a negative (...) data indicate that selective PDE3 inhibitors produce differential effects on adipogenesis and lipolysis. MC2 has proapoptotic and antilipolytic effects on adipocytes and does not stimulate adipogenesis. Therefore, in comparison with the clinically available selective PDE3 inhibitors, MC2 has lowest metabolic side effects and might be a good candidate for treatment of congestive heart failure.

2015 DARU Journal of Pharmaceutical Sciences

290. Targeted protection of donor graft vasculature using a phosphodiesterase inhibitor increases survival and predictability of autologous fat grafts. (Abstract)

Targeted protection of donor graft vasculature using a phosphodiesterase inhibitor increases survival and predictability of autologous fat grafts. Fat grafting is limited by unpredictable long-term graft retention. The authors postulate that injury to the donor-derived microvasculature during harvest and subsequent ischemia may account for this clinical variability. They examined the use of the U.S. Food and Drug Administration-approved phosphodiesterase-5 inhibitor sildenafil citrate

2015 Plastic and reconstructive surgery

291. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial (Abstract)

Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH (...) with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor.A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-min walk distance (6MWD) at week 16. Secondary end points included time to clinical worsening, change

2012 EvidenceUpdates Controlled trial quality: predicted high

292. Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload. (Abstract)

Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload. Phosphodiesterase type 3 (PDE3) inhibitors block the cAMP hydrolyzing activity of both PDE3 isoforms, PDE3A and PDE3B, which have distinct roles in the heart. Although PDE3 inhibitors improve cardiac function in heart disease patients, they also increase mortality. Nevertheless, PDE3 inhibitors can provide benefit to non-ischemic heart disease patients (...) and are used extensively to treat heart failure in dogs. Since the isoform-dependence of the complex cardiac actions of PDE3 inhibition in diseased hearts remains unknown, we assessed the effects of PDE3 inhibitors as well as gene ablation of PDE3A or PDEB in mice following the induction of non-ischemic heart disease by pressure-overload with transverse-aortic constriction (TAC). As expected, after 6 weeks of TAC, mice exhibited left ventricular contractile dysfunction, dilation, hypertrophy

2019 Journal of Molecular and Cellular Cardiology

293. Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin-; the role of phosphodiesterase 3A. Full Text available with Trip Pro

Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin-; the role of phosphodiesterase 3A. Prostacyclin (PGI2) controls platelet activation and thrombosis through a cyclic adenosine monophosphate (cAMP) signalling cascade. However, in patients with cardiovascular diseases this protective mechanism fails for reasons that are unclear. Using both pharmacological and genetic approaches we describe a mechanism by which oxidised low density (...) lipoproteins (oxLDL) associated with dyslipidaemia promote platelet activation through impaired PGI2 sensitivity and diminished cAMP signalling. In functional assays using human platelets, oxLDL modulated the inhibitory effects of PGI2, but not a PDE-insensitive cAMP analogue, on platelet aggregation, granule secretion and in vitro thrombosis. Examination of the mechanism revealed that oxLDL promoted the hydrolysis of cAMP through the phosphorylation and activation of phosphodiesterase 3A (PDE3A), leading

2019 Haematologica

294. Phosphodiesterase 10A IgG: A novel biomarker of paraneoplastic neurologic autoimmunity. Full Text available with Trip Pro

Phosphodiesterase 10A IgG: A novel biomarker of paraneoplastic neurologic autoimmunity. To describe a novel antibody biomarker of neurologic paraneoplastic autoimmunity specific for phosphodiesterase 10A (PDE10A), a striatum-enriched phosphodiesterase, and to characterize the clinical phenotype of patients with PDE10A immunoglobulin G (IgG).We describe 7 patients with autoantibodies specific for PDE10A identified in the Mayo Clinic Neuroimmunology Laboratory. Patient specimens (sera, 7; CSF, 4 (...) ] and parkinsonism in 1). All patients but one had cancer (lung [adenocarcinoma 1, squamous cell carcinoma 1, poorly differentiated mesenchymal carcinoma 1], renal adenocarcinoma 2, and pancreatic adenocarcinoma 1). Two of the 7 patients developed hyperkinetic movement disorders during treatment with immune checkpoint inhibitors (nivolumab and pembrolizumab), though none of 26 cancer control patients treated with immune checkpoint inhibitors harbored PDE10A IgG in their serum. MRIs from those 2 patients

2019 Neurology

295. Phosphodiesterase 5 inhibitors: a review of the clinical effectiveness and cost-effectiveness

Phosphodiesterase 5 inhibitors: a review of the clinical effectiveness and cost-effectiveness Phosphodiesterase 5 inhibitors: a review of the clinical effectiveness and cost-effectiveness Phosphodiesterase 5 inhibitors: a review of the clinical effectiveness and cost-effectiveness Canadian Agency for Drugs and Technologies in Health Record Status This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment (...) has been made for the HTA database. Citation Canadian Agency for Drugs and Technologies in Health. Phosphodiesterase 5 inhibitors: a review of the clinical effectiveness and cost-effectiveness. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH). 2010 Authors' conclusions The majority of the information identified addressed the question about comparative clinical effectiveness of the PDE=5 inhibitors for the treatment of erectile dysfunction. Two meta-analyses demonstrated

2010 Health Technology Assessment (HTA) Database.

296. Targeting the Paracrine Hormone-Dependent Guanylate cyclase/cGMP/Phosphodiesterases Signaling Pathway for Colorectal Cancer Prevention. (Abstract)

and silencing of GUCY2C-signaling in colon epithelial cells, leading to tumorigenesis. Thus, GUCY2C agonists, such as linaclotide, exhibit considerable role in preventing CRC tumorigenesis. However, phosphodiesterases (PDEs) are elevated in intestinal epithelial cells during CRC tumorigenesis and block GUCY2C-mediated signaling by degrading cyclic GMP to 5`-GMP. PDE5-specific inhibitors, such as sildenafil, show considerable anti-tumorigenic potential against CRC by amplifying the GUCY2C/cGMP signaling (...) Targeting the Paracrine Hormone-Dependent Guanylate cyclase/cGMP/Phosphodiesterases Signaling Pathway for Colorectal Cancer Prevention. Colorectal cancer (CRC) is one of the leading causes of cancer related-deaths. The risk of development of CRC is complex and multifactorial, and includes disruption of homeostasis of the intestinal epithelial layer mediated though dysregulations of tumor suppressing/promoting signaling pathways. Guanylate cyclase 2C (GUCY2C), a membrane-bound guanylate cyclase

2018 Seminars in cancer biology

297. Altered expression of microRNA-23a in psoriatic arthritis modulates synovial fibroblast pro-inflammatory mechanisms via phosphodiesterase 4B. Full Text available with Trip Pro

. For regulation experiments, PsA synovial fibroblasts (SFC) were cultured with Toll-like receptor (TLR) ligands and pro-inflammatory cytokines. PsA SFC were transfected with a miR-23a inhibitor to assess the functional effect on migration, invasion and expression of pro-inflammatory meditators. The direct interaction between miR-23a and predicted target mRNA, phosphodiesterase 4B (PDE4B), was examined by luciferase reporter gene assay, with the expression and regulation confirmed by RT-PCR and western blot (...) Altered expression of microRNA-23a in psoriatic arthritis modulates synovial fibroblast pro-inflammatory mechanisms via phosphodiesterase 4B. To investigate the functional role of miR-23a in synovial fibroblasts (SFC) activation in psoriatic arthritis (PsA).Differential expression of the miR-23a-27a-24-2 cluster was identified by real-time quantitative PCR in PsA synovial tissue and peripheral blood mononuclear cells (PBMC) compared to osteoarthritis (OA) and correlated with disease activity

2018 Journal of Autoimmunity

298. Dunce Phosphodiesterase Acts as a Checkpoint for Drosophila Long-Term Memory in a Pair of Serotonergic Neurons Full Text available with Trip Pro

Dunce Phosphodiesterase Acts as a Checkpoint for Drosophila Long-Term Memory in a Pair of Serotonergic Neurons A key function of the brain is to filter essential information and store it in the form of stable, long-term memory (LTM). We demonstrate here that the Dunce (Dnc) phosphodiesterase, an important enzyme that degrades cAMP, acts as a molecular switch that controls LTM formation in Drosophila. We show that, during LTM formation, Dnc is inhibited in the SPN, a pair of newly characterized (...) serotonergic neurons, which stimulates the cAMP/PKA pathway. As a consequence, the SPN activates downstream dopaminergic neurons, opening the gate for LTM formation in the olfactory memory center, the mushroom body. Strikingly, transient inhibition of Dnc in the SPN by RNAi was sufficient to induce LTM formation with a training protocol that normally generates only short-lived memory. Thus, Dnc activity in the SPN acts as a memory checkpoint to guarantee that only the most relevant learned experiences

2018 Neuron

299. Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice Full Text available with Trip Pro

Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Design and Methods: Male CD1 mice were

2018 International journal of medical sciences

300. Glucocorticoid-induced CREB activation and myostatin expression in C2C12 myotubes involves phosphodiesterase-3/4 signaling Full Text available with Trip Pro

Akt-PDE3/4 signaling paradigm, we hypothesized that reduced Akt signaling contributes to CREB activation and myostatin expression. C2C12 myotubes were incubated with dexamethasone (Dex), an atrophy-inducing synthetic glucocorticoid. Akt/CREB signaling and myostatin expression were evaluated by immunoblot and qPCR analyses. Inhibitors of Akt, phosphodiesterase (PDE)-3/4, and protein kinase A (PKA) signaling were used to test our hypothesis. Incubating myotubes with Dex for 3-24 h inhibited Akt (...) phosphorylation and enhanced CREB phosphorylation as well as myostatin mRNA and protein. Inhibition of PI3K/Akt signaling with LY294002 similarly increased CREB phosphorylation. Isobutyl-methylxanthine (IBMX, a pan PDE inhibitor), milrinone (PDE3 inhibitor) and rolipram (PDE4 inhibitor) augmented CREB phosphorylation and myostatin expression. Inhibition of protein kinase A by PKI reverted Dex- or IBMX-induced CREB phosphorylation and myostatin expression. Our study provides evidence supporting a newly

2018 Biochemical and biophysical research communications

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