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Phosphodiesterase Inhibitor

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181. Phosphodiesterase inhibitors as adjunctive therapies for tuberculosis (Full text)

Phosphodiesterase inhibitors as adjunctive therapies for tuberculosis 26981560 2016 08 24 2018 12 02 2352-3964 4 2016 Feb EBioMedicine EBioMedicine Phosphodiesterase inhibitors as adjunctive therapies for tuberculosis. 7-8 10.1016/j.ebiom.2016.02.016 Ahidjo Bintou Ahmadou BA Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Bishai William R WR Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA (...) ; Howard Hughes Medical Institute, Chevy Chase, MD, USA. eng Journal Article Comment 2016 02 09 Netherlands EBioMedicine 101647039 2352-3964 0 Antitubercular Agents 0 Phosphodiesterase 3 Inhibitors 0 Phosphodiesterase 4 Inhibitors 0 Phosphodiesterase 5 Inhibitors 0 Phosphodiesterase Inhibitors E0399OZS9N Cyclic AMP IM EBioMedicine. 2016 Feb;4:104-14 26981575 Antitubercular Agents therapeutic use Cyclic AMP Humans Mycobacterium tuberculosis Phosphodiesterase 3 Inhibitors Phosphodiesterase 4 Inhibitors

2016 EBioMedicine

182. Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle (Full text)

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

183. The devil is in the details: an analysis of the subtleties between phosphodiesterase inhibitors for erectile dysfunction (Full text)

The devil is in the details: an analysis of the subtleties between phosphodiesterase inhibitors for erectile dysfunction Erectile dysfunction (ED) is a common sexual disorder with numerous etiologies involving multiple organ systems that leads to significant distress and decreased quality of life for the affected men. Fortunately, there are several modalities and interventions for treating ED. Oral medications, intra-urethral compounds, intracorporeal injections, vacuum-assist devices (...) and surgically implanted prostheses are all part of the treatment algorithm. One of the first-lines and certainly the most widely used options for treating ED is the family of oral phosphodiesterase type 5 inhibitors (PDE5I). The introduction of these medications in the late 1990s revolutionized the field of sexual medicine. Currently there are no guidelines and minimal literature to help providers choose among drugs in this class. This review will address differences in efficacy and side effects between

2016 Translational andrology and urology

184. Usage and perceptions of phosphodiesterase type 5 inhibitors among the male partners of infertile couples (Full text)

Usage and perceptions of phosphodiesterase type 5 inhibitors among the male partners of infertile couples We aimed to investigate the prevalence of erectile dysfunction (ED) and the usage of phosphodiesterase type 5 (PDE5) inhibitors for ED treatment in infertile couples.A total of 260 male partners in couples reporting infertility lasting at least 1 year were included in this study. In addition to an evaluation of infertility, all participants completed the International Index of Erectile (...) Function (IIEF)-5 questionnaire to evaluate their sexual function. The participants were asked about their use of PDE5 inhibitors while trying to conceive during their partner's ovulatory period and about their concerns regarding the risks of PDE5 inhibitor use to any eventual pregnancy and/or the fetus.Based on the IIEF-5 questionnaire, 41.5% of the participants (108/260) were classified as having mild ED (an IIEF-5 score of 17-21), while 10.4% of the participants (27/260) had greater than mild ED

2016 Clinical and experimental reproductive medicine

185. Chemotherapeutic Efficacy of Phosphodiesterase Inhibitors in Chagasic Cardiomyopathy (Full text)

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

2016 JACC: Basic to Translational Science

186. 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)

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

187. 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)

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

188. Phosphodiesterase type 5 inhibitors: Irrational use in Saudi Arabia (Full text)

Phosphodiesterase type 5 inhibitors: Irrational use in Saudi Arabia To identify the criteria of phosphodiesterase type 5 inhibitor (PDE5i) users and to analyse the knowledge, attitude, and practices of PDE5i use amongst Saudi men.A web-based, cross-sectional survey was conducted in Saudi Arabia between January and April 2015. Sexually active adult men were interviewed using a website questionnaire designed by the authors. Descriptive statistics were used to analyse the data.In all, 1008 men

2016 Arab journal of urology

189. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain (Full text)

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

190. Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy (Full text)

Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 (...) phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomyopathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly decreased CXCL10 protein secretion (IC50 = 2.6 × 10(-7

2016 Inflammation

191. Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft (Full text)

Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally verified their selective inhibitory (...) activity. Three inhibitors exhibited low-micromolar IC50 values. Molecular dynamics simulations revealed a common binding mode for these inhibitors, involving association to the TDP2 DNA-binding cleft. MM-PBSA per-residue energy decomposition identified important interactions of the compounds with specific TDP2 residues. These interactions could provide new avenues for synthetic optimization of these scaffolds.Copyright © 2016 Elsevier Ltd. All rights reserved.

2016 Bioorganic & medicinal chemistry letters

192. Treatment satisfaction among men with concurrent benign prostatic hyperplasia and erectile dysfunction treated with tadalafil or other phosphodiesterase type-5 inhibitor combinations (Full text)

Treatment satisfaction among men with concurrent benign prostatic hyperplasia and erectile dysfunction treated with tadalafil or other phosphodiesterase type-5 inhibitor combinations Erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) frequently co-occur in men aged ≥40, along with lower urinary tract symptoms (LUTS) secondary to BPH. Given little real-world evidence on treatment use or satisfaction with treatment for concurrent BPH/LUTS and/or ED, this study examined medication (...) Prostate Symptom Score, sleep quality) were self-reported. Generalized linear models examined the association of regimen with treatment satisfaction and HRQoL, adjusting for covariates (eg, age and comorbidities).Final analyses included participants (N=507) using: tadalafil once-daily monotherapy (22%), tadalafil for ED with an alternate BPH therapy (36%), or another phosphodiesterase type-5 inhibitor (PDE5-I) combination (41%). These groups represented the major categories of treatment regimens found

2016 Patient preference and adherence

193. Journal Club: Phosphodiesterase-4 Inhibitors (Full text)

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

194. Anti‐inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus‐inducible cytokines (Full text)

Anti‐inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus‐inducible cytokines Respiratory virus infections precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations, with most exacerbations due to rhinovirus infection. Both asthma and COPD exacerbations are not well controlled by steroid therapies, and there is a much research interest in finding improved therapies or combinations of therapies for controlling exacerbations (...) . CHF6001 is a new, inhaled highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor. Using in vitro human bronchial epithelial cells (BEAS-2B), we investigated the potential anti-inflammatory effects of CHF6001 on rhinovirus (RV1B)-induced cytokines. Cytokine mRNA was measured by real-time PCR, while protein release was measured by ELISA. CHF6001 was used in a 7-point dose-response curve (1000-0.001 nmol/L) as a 1.5-h pretreatment prior to infection in comparison with roflumilast. Both

2016 Pharmacology research & perspectives

195. Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase–Knockout Mice (Full text)

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

196. Effects of a novel phosphodiesterase 10A inhibitor in non-human primates: a therapeutic approach for schizophrenia with improved side effect profile (Full text)

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

197. Recreational Use of Phosphodiesterase 5 Inhibitors and Its Associated Factors among Undergraduate Male Students in an Ethiopian University: A Cross-Sectional Study (Full text)

Recreational Use of Phosphodiesterase 5 Inhibitors and Its Associated Factors among Undergraduate Male Students in an Ethiopian University: A Cross-Sectional Study To assess the prevalence of phosphodiesterase 5 (PDE5) inhibitor use and associated factors among University of Gondar undergraduate students.An institution-based, cross-sectional study, using a survey questionnaire, was conducted from October to December 2015 to assess PDE5 inhibitor use and associated factors among male students (...) at the University of Gondar. A Self-Esteem and Relationship questionnaire (14 items), an International Index of Erectile Function questionnaire (15 items) and a questionnaire on PDE5 inhibitor use (14 items) were included in the survey.Across all respondents (age, 21.9±1.88 years), more than half (55.7%, n=233) had heard about PDE5 inhibitors, but only 23 men (5.5%) reported trying a PDE5 inhibitor drug at least once. Older students were more likely to use PDE5 inhibitors compared to younger students (adjusted

2016 The world journal of men's health

198. Lipoxin A4 as a possible mediator of the beneficial actions of phosphodiesterase-5 enzyme inhibitors (Full text)

Lipoxin A4 as a possible mediator of the beneficial actions of phosphodiesterase-5 enzyme inhibitors 28144281 2018 11 13 1734-1922 13 1 2017 Feb 01 Archives of medical science : AMS Arch Med Sci Lipoxin A4 as a possible mediator of the beneficial actions of phosphodiesterase-5 enzyme inhibitors. 263-266 10.5114/aoms.2017.64723 Das Undurti N UN UND Life Sciences, USA. eng Journal Article 2016 12 19 Poland Arch Med Sci 101258257 1734-1922 The author declares no conflict of interest. 2015 04 03

2016 Archives of medical science : AMS

199. Potential Treatment of Cognitive Impairment in Schizophrenia by Phosphodiesterase 2 (PDE2) Inhibitors (Full text)

Potential Treatment of Cognitive Impairment in Schizophrenia by Phosphodiesterase 2 (PDE2) Inhibitors 28105267 2018 11 13 1948-5875 8 1 2017 Jan 12 ACS medicinal chemistry letters ACS Med Chem Lett Potential Treatment of Cognitive Impairment in Schizophrenia by Phosphodiesterase 2 (PDE2) Inhibitors. 17-18 10.1021/acsmedchemlett.6b00514 Abdel-Magid Ahmed F AF Therachem Research Medilab (India) Pvt. Ltd. , Jaipur, India. eng Editorial 2016 12 29 United States ACS Med Chem Lett 101521073 1948-5875

2016 ACS medicinal chemistry letters

200. Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor (Full text)

Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates (...) phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague-Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task

2016 The Journal of Neuroscience

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