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Phosphodiesterase Inhibitor

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241. Journal Club: Phosphodiesterase-4 Inhibitors Full Text available with Trip Pro

Journal Club: Phosphodiesterase-4 Inhibitors 28848894 2018 11 13 2372-952X 3 3 2016 Jul 14 Chronic obstructive pulmonary diseases (Miami, Fla.) Chronic Obstr Pulm Dis Journal Club: Phosphodiesterase-4 Inhibitors. 693-697 10.15326/jcopdf.3.3.2016.0157 Balkissoon Ron R Denver, Colorado. eng Journal Article 2016 07 14 United States Chronic Obstr Pulm Dis 101635411 2372-952X chronic obstructive pulmonary disease copd phosphodiesterase-4 inhibitors 2017 8 30 6 0 2017 8 30 6 0 2017 8 30 6 1 epublish

2016 Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation

242. Twelve-Month Efficacy and Safety of Low-Intensity Shockwave Therapy for Erectile Dysfunction in Patients Who Do Not Respond to Phosphodiesterase Type 5 Inhibitors Full Text available with Trip Pro

Twelve-Month Efficacy and Safety of Low-Intensity Shockwave Therapy for Erectile Dysfunction in Patients Who Do Not Respond to Phosphodiesterase Type 5 Inhibitors Low-intensity shockwave therapy (LISWT) has recently emerged as a promising method in the treatment of erectile dysfunction (ED).To assess the long-term results of the effectiveness and safety of LISWT in patients with ED who are non-responders to phosphodiesterase type 5 inhibitor (PDE5i) treatment.This open-label, longitudinal

2016 Sexual Medicine

243. Chemotherapeutic Efficacy of Phosphodiesterase Inhibitors in Chagasic Cardiomyopathy Full Text available with Trip Pro

Chemotherapeutic Efficacy of Phosphodiesterase Inhibitors in Chagasic Cardiomyopathy Chagasic cardiomyopathy (CCM) caused by Trypanosoma cruzi (Tc) infection is prevalent in Latin America and recognized as an emerging infectious heart disease in the US. The NO-cGMP-PKG1α pathway maintains cardiac homeostasis and inotropy and may be disturbed due to phosphodiesterase (PDE5) mediated cGMP catabolism in CCM.C57BL/6 mice were infected with Tc, and at the end of acute parasitemia (i.e. 45 days post (...) in chagasic mice. Sildenafil treatment resulted in normal levels of PDE5 and cGMP/PKG activity and preserved the LV function in chagasic mice. The cardioprotective effects of SIL were provided through inhibition of cardiac collagenosis and chronic inflammation that otherwise were pronounced in CCM. Further, mtDNA-encoded gene expression and ADP-coupled mitochondrial respiration were decreased and mitochondrial oxidative stress and cellular oxidative damage (lipid hydroperoxides and protein carbonyls) were

2016 JACC: Basic to Translational Science

244. Pharmacological characterization of a novel potent, selective, and orally active phosphodiesterase 10A inhibitor, PDM‐042 [(E)‐4‐(2‐(2‐(5,8‐dimethyl‐[1,2,4]triazolo[1,5‐a]pyrazin‐2‐yl)vinyl)‐6‐(pyrrolidin‐1‐yl)pyrimidin‐4‐y Full Text available with Trip Pro

Pharmacological characterization of a novel potent, selective, and orally active phosphodiesterase 10A inhibitor, PDM‐042 [(E)‐4‐(2‐(2‐(5,8‐dimethyl‐[1,2,4]triazolo[1,5‐a]pyrazin‐2‐yl)vinyl)‐6‐(pyrrolidin‐1‐yl)pyrimidin‐4‐y Recently, we identified a novel phosphodiesterase 10A (PDE10A) inhibitor, PDM-042 ((E)-4-(2-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)vinyl)-6-(pyrrolidin-1-yl)pyrimidin-4-yl)morpholine). PDM-042 showed potent inhibitory activities (...) for human and rat PDE10A with IC 50 values of less than 1 nmol/L and more than 1000-fold selectivity against other phosphodiesterases. Tritiated PDM-042, [3H]PDM-042, had high affinity for membranes prepared from rat striatum with a Kd value of 8.5 nmol/L. The specific binding of [3H]PDM-042 was displaced in a concentration-dependent manner by PDM-042 and another structurally unrelated PDE10A inhibitor, MP-10. In rat studies, PDM-042 showed excellent brain penetration (striatum/plasma ratio = 6.3

2016 Pharmacology research & perspectives

245. Novel role of phosphodiesterase inhibitors in the management of end-stage heart failure Full Text available with Trip Pro

Novel role of phosphodiesterase inhibitors in the management of end-stage heart failure In advanced heart failure (HF), chronic inotropic therapy with intravenous milrinone, a phosphodiesterase III inhibitor, is used as a bridge to advanced management that includes transplantation, ventricular assist device implantation, or palliation. This is especially true when repeated attempts to wean off inotropic support result in symptomatic hypotension, worsened symptoms, and/or progressive organ

2016 World journal of cardiology

246. Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice Full Text available with Trip Pro

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice Mice lacking the endogenous β2-adrenoceptor (β2AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chronic administration of β2AR agonists to PNMT-KO mice restores the phenotype. Based (...) assays suggest antiinflammatory effects of Gαs-cAMP signaling. This study was designed to test whether the in vitro antiinflammatory effects of phosphodiesterase 4 inhibitors, known to increase intracellular cAMP in multiple airway cell types, attenuate the asthma-like phenotype produced by the β2AR agonists formoterol and salmeterol in vivo in PNMT-KO mice, based on the hypothesis that skewing β2AR signaling toward Gαs-cAMP pathway is beneficial. Airway inflammatory cells, epithelial mucus

2016 American journal of respiratory cell and molecular biology

247. The Efficacy of Medical Treatment of Peyronie's Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor Full Text available with Trip Pro

The Efficacy of Medical Treatment of Peyronie's Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor This study was designed to evaluate the efficacy of medical treatment of Peyronie's disease.A total of 109 patients with Peyronie's disease who had been treated from January 2011 to December 2014 were retrospectively reviewed in this study. Forty-four patients (Group 1) were treated with 12 mg of potassium (...) para-aminobenzoate daily. Sixty-five patients (Group 2) were treated with combination therapy: tamoxifen (20 mg) and acetyl-L-carnitine (300 mg) twice daily in addition to a phosphodiesterase type 5 inhibitor. Ability to perform sexual intercourse, pain during erection, size of plaque, and penile curvature angle were assessed.In Group 1, 30 of 44 patients (68.2%) discontinued treatment within 12 weeks, while 5 patients (7.7%) in Group 2 discontinued treatment. Pain during erection and plaque size

2016 The world journal of men's health

248. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain Full Text available with Trip Pro

Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain Perinatal ischemic stroke is the most frequent form of cerebral infarction in neonates; however, evidence-based treatments are currently lacking. We have previously demonstrated a beneficial effect of sildenafil citrate, a PDE-5 inhibitor, on stroke lesion size in neonatal rat pups. The present study investigated the effects of sildenafil in a neonatal mouse

2016 Journal of neuroinflammation

249. Effects of a novel phosphodiesterase 10A inhibitor in non-human primates: a therapeutic approach for schizophrenia with improved side effect profile Full Text available with Trip Pro

Effects of a novel phosphodiesterase 10A inhibitor in non-human primates: a therapeutic approach for schizophrenia with improved side effect profile Schizophrenia symptoms are associated with alterations in basal ganglia-cortical networks that include the cyclic nucleotides (cAMP/cGMP) signaling pathways. Phosphodiesterase 10A (PDE10A) inhibitors have been considered as therapeutic agents for schizophrenia because the regulation of cAMP and cGMP in the striatum by PDE10A plays an important role (...) in the signaling mechanisms of the striatal-cortical network, and thereby in cognitive function. In the present study we assessed in non-human primates (NHPs) the effects of a novel PDE10A inhibitor (FRM-6308) that has demonstrated high potency and selectivity for human recombinant PDE10A in vitro. The behavioral effects of FRM-6308 in a dose range were determined in rhesus monkeys using a standardized motor disability scale for primates, motor tasks, and the "drug effects on the nervous system" (DENS) scale

2016 Neuropharmacology

250. Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle Full Text available with Trip Pro

Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is the most common muscular dystrophy. Characterized by rounds of muscle degeneration and regeneration, DMD features progressive muscle wasting and is fatal. One approach for treatment is transplantation of muscle progenitor cells to repair (...) and restore dystrophin expression to damaged muscle. However, the success of this approach has been limited by difficulties in isolating large numbers of myogenic progenitors with strong regenerative potential, poor engraftment, poor survival of donor cells, and limited migration in the diseased muscle. We demonstrate that induction of the transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) using the cyclic adenosine monophosphate phosphodiesterase inhibitor isobutylmethylxanthine (IBMX

2016 Stem cells translational medicine

251. Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction Full Text available with Trip Pro

Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction The aim of this review was to summarize the ocular action of the most common phosphodiesterase (PDE) inhibitors used for the treatment of erectile dysfunction and the subsequent visual disorders.This is a literature review of several important articles focusing on the pathophysiology of visual disorders induced by PDE inhibitors.PDE inhibitors have been associated with ocular (...) of sildenafil and tadalafil on retinal perfusion.So far, PDE inhibitors do not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors. However, physicians should write down any visual symptom observed during PDE treatment and refer the patients to ophthalmologists.

2016 Drug design, development and therapy

252. Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase-5A inhibitor vardenafil in rats with type 2 diabetes. Full Text available with Trip Pro

Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase-5A inhibitor vardenafil in rats with type 2 diabetes. Heart failure with preserved ejection fraction (HFpEF) has a great epidemiological burden. The pathophysiological role of cyclic guanosine monophosphate (cGMP) signalling has been intensively investigated in HFpEF. Elevated levels of cGMP have been shown to exert cardioprotective effects in various cardiovascular diseases, including (...) diabetic cardiomyopathy. We investigated the effect of long-term preventive application of the phosphodiesterase-5A (PDE5A) inhibitor vardenafil in diabetic cardiomyopathy-associated HFpEF.Zucker diabetic fatty (ZDF) rats were used as a model of HFpEF and ZDF lean rats served as controls. Animals received vehicle or 10 mg/kg body weight vardenafil per os from weeks 7 to 32 of age. Cardiac function, morphology was assessed by left ventricular (LV) pressure-volume analysis and echocardiography at week 32

2016 European Journal of Heart Failure

253. Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality. Full Text available with Trip Pro

Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality. Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study.Between January 2007 and May 2015, 5956 men aged 40-89 years diagnosed with type 2 diabetes

2016 Heart

254. Phosphodiesterase-5 Inhibitor Use: An Under-reported Cause of Profuse Nasal Bleeding. (Abstract)

Phosphodiesterase-5 Inhibitor Use: An Under-reported Cause of Profuse Nasal Bleeding. Phosphodiesterase-5 (PDE-5) inhibitors enhance penile erection and have gained popularity not only for erectile dysfunction, but also in recreational settings. Nevertheless, adverse effects have been associated with their use, with nasal bleeding among them. PDE-5 inhibitor action is materialized through the inhibition of the cyclic guanosine monophosphate (cGMP) enzyme. cGMP is present at several sites (...) of the human body in addition to the corpus cavernosum, leading to the adverse effects associated with its nonselective inhibition.Two male patients with severe epistaxis who were taking PDE-5 inhibitors for erectile dysfunction or recreational purposes are discussed. Surgical intervention was required in both patients to control the nasal hemorrhage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Nasal bleeding in patients who are taking PDE-5 inhibitors might represent an under-reported cause

2016 Journal of Emergency Medicine

255. A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients. Full Text available with Trip Pro

A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients. CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety of CHF6001 were investigated in a double blind, placebo controlled, 3-way cross-over study using the allergen challenge model. Thirty-six atopic asthmatics who were not taking inhaled corticosteroids and who demonstrated a late (...) reductions of 19.7% (p = 0.015) and 28.2% (p < 0.001) respectively of the weighted FEV1 AUC4-10h compared with placebo. The difference between the CHF6001 doses was not statistically significant (p = 0.223). Compared with placebo, CHF6001 caused greater reduction in sputum eosinophil counts, although these changes were not statistically significant. CHF6001 was well tolerated, with similar numbers of adverse events in each treatment period. This inhaled PDE4 inhibitor has the potential to provide

2016 Pulmonary Pharmacology & Therapeutics Controlled trial quality: predicted high

256. Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. Full Text available with Trip Pro

Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF).To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity (...) (94.2) (P = .85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, -26.0 to 45.0]) or sildenafil (5.0 m [IQR, -37.0 to 55.0]; P = .92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%).Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks

2013 JAMA Controlled trial quality: predicted high

257. Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis. (Abstract)

Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis. The purpose of the present studies was to assess the safety, tolerability and pharmacokinetics of topical application of a novel phosphodiesterase inhibitor, E6005, in healthy volunteers and in patients with atopic dermatitis (AD).In two randomized, investigator-blind, vehicle-controlled studies, we evaluated the topical application

2015 Journal of Dermatological Treatment Controlled trial quality: uncertain

258. Phosphodiesterase-5 inhibition improves macrocirculation and microcirculation during cardiopulmonary resuscitation. (Abstract)

Phosphodiesterase-5 inhibition improves macrocirculation and microcirculation during cardiopulmonary resuscitation. This study is to clarify whether sildenafil, which is a selective inhibitor of the isoform 5 of the enzyme phosphodiesterase, improves macrocirculation or/and microcirculation during ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR) so as to improve outcomes of resuscitation.Sixteen female pigs were used. After anesthesia, the abdominal cavity was opened

2015 American Journal of Emergency Medicine

259. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2). Full Text available with Trip Pro

Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2). In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in moderate to severe psoriasis.We sought to evaluate efficacy of apremilast in nail/scalp psoriasis in ESTEEM

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

260. Clinical and preclinical treatment of urologic diseases with phosphodiesterase isoenzymes 5 inhibitors: an update Full Text available with Trip Pro

Clinical and preclinical treatment of urologic diseases with phosphodiesterase isoenzymes 5 inhibitors: an update Phosphodiesterase isoenzymes 5 inhibitors (PDE5-Is) are the first-line therapy for erectile dysfunction (ED). The constant discoveries of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cell-signaling pathway for smooth muscle (SM) control in other urogenital tracts (UGTs) make PDE5-Is promising pharmacologic agents against other benign urological diseases. This article (...) reviews the literature and contains some previously unpublished data about characterizations and activities of PDE5 and its inhibitors in treating urological disorders. Scientific discoveries have improved our understanding of cell-signaling pathway in NO/cGMP-mediated SM relaxation in UGTs. Moreover, the clinical applications of PDE5-Is have been widely recognized. On-demand PDE5-Is are efficacious for most cases of ED, while daily-dosing and combination with testosterone are recommended

2015 Asian journal of andrology

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