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Phosphodiesterase Inhibitor

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41. Study on the clinical efficacy of specific phosphodiesterase inhibitor in patients with pulmonary hypertension due to left heart disease Full Text available with Trip Pro

Study on the clinical efficacy of specific phosphodiesterase inhibitor in patients with pulmonary hypertension due to left heart disease Pulmonary hypertension due to left heart disease (PH-LHD) is caused by left ventricular (LV) systolic and/or diastolic dysfunction and left heart valve disease. LV diseases lead to left ventricular filling pressure increases, pulmonary venous obstruction and pulmonary venous pressure increases, and thus to secondary PH. Exercise tolerance is lower and fatality

2018 Experimental and therapeutic medicine

42. Inhibition of phosphodiesterase 4 by FCPR16 protects SH-SY5Y cells against MPP+-induced decline of mitochondrial membrane potential and oxidative stress Full Text available with Trip Pro

Inhibition of phosphodiesterase 4 by FCPR16 protects SH-SY5Y cells against MPP+-induced decline of mitochondrial membrane potential and oxidative stress Phosphodiesterase 4 (PDE4) is a promising target for the treatment of Parkinson's disease (PD). However, the underlying mechanism has not yet been well elucidated. Additionally, most of current PDE4 inhibitors produce severe nausea and vomiting response in patients, which limit their clinical application. FCPR16 is a novel PDE4 inhibitor (...) ) and protein kinase B (Akt) down-regulated by MPP+ in SH-SY5Y cells. Moreover, the inhibitory effects of FCPR16 on the production of ROS and Δψm loss could be blocked by PKA inhibitor H-89 and Akt inhibitor KRX-0401. Collectively, these results suggest that FCPR16 attenuates MPP+-induced dopaminergic degeneration via lowering ROS and preventing the loss of Δψm in SH-SY5Y cells. Mechanistically, cAMP/PKA/CREB and Epac/Akt signaling pathways are involved in these processes. Our findings indicate that FCPR16

2018 Redox biology

43. Penile microvascular endothelial function in hypertensive patients: effects of acute type 5 phosphodiesterase inhibition Full Text available with Trip Pro

Penile microvascular endothelial function in hypertensive patients: effects of acute type 5 phosphodiesterase inhibition The primary aim of this study was to evaluate penile endothelial microvascular function in patients with primary arterial hypertension and age-matched normotensive subjects using laser speckle contrast imaging (LSCI). Additionally, we analyzed the acute penile microvascular effects induced by oral phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration (...) anti-hypertensive treatment. LSCI may be a valuable non-invasive tool for the evaluation of penile vascular responses to phosphodiesterase type 5 inhibitor.

2018 Brazilian Journal of Medical and Biological Research

44. Late-Stage Microsomal Oxidation Reduces Drug–Drug Interaction and Identifies Phosphodiesterase 2A Inhibitor PF-06815189 Full Text available with Trip Pro

Late-Stage Microsomal Oxidation Reduces Drug–Drug Interaction and Identifies Phosphodiesterase 2A Inhibitor PF-06815189 Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2 inhibitor 1 to reduce its clearance by cytochrome P450 enzymes, introduce renal clearance, and minimize the risk for victim drug-drug interactions. This approach yielded PF-06815189 (2) with improved physicochemical properties and a mixed metabolic profile. This example highlights the importance

2018 ACS medicinal chemistry letters

45. East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease Full Text available with Trip Pro

East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric (...) eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation

2018 Frontiers in pharmacology

46. Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission Full Text available with Trip Pro

Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission Nitric oxide (NO) and hydrogen sulfide (H2S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous (...) inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H2S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover

2018 Scientific reports

47. The Human Tyrosyl-DNA Phosphodiesterase 1 (hTdp1) Inhibitor NSC120686 as an Exploratory Tool to Investigate Plant Tdp1 Genes Full Text available with Trip Pro

The Human Tyrosyl-DNA Phosphodiesterase 1 (hTdp1) Inhibitor NSC120686 as an Exploratory Tool to Investigate Plant Tdp1 Genes The hTdp1 (human tyrosyl-DNA phosphodiesterase 1) inhibitor NSC120686 has been used, along with topoisomerase inhibitors, as a pharmacophoric model to restrain the Tdp1 activity as part of a synergistic treatment for cancer. While this compound has an end-point application in medical research, in plants, its application has not been considered so far. The originality (...) of our study consists in the use of hTdp1 inhibitor in Medicago truncatula cells, which, unlike human cells, contain two Tdp1 genes. Hence, the purpose of this study was to test the hTdp1 inhibitor NSC120686 as an exploratory tool to investigate the plant Tdp1 genes, since their characterization is still in incipient phases. To do so, M. truncatula calli were exposed to increasing (75, 150, 300 μM) concentrations of NSC120686. The levels of cell mortality and DNA damage, measured via diffusion assay

2018 Genes

48. Phosphodiesterase-5 Inhibition Alleviates Pulmonary Hypertension and Basal Lamina Thickening in Rats Challenged by Chronic Hypoxia Full Text available with Trip Pro

Phosphodiesterase-5 Inhibition Alleviates Pulmonary Hypertension and Basal Lamina Thickening in Rats Challenged by Chronic Hypoxia Background: Hypoxia represents both an outcome of cardiopulmonary diseases and a trigger for severe pulmonary complications as pulmonary hypertension. Because nitric oxide (NO) is a critical mediator in the development of pulmonary hypertension, the modulators of its downstream function may become target of pharmacological interventions aimed at alleviating (...) the impact of this condition. Here, we investigate the effects of an early administration of phosphodiesterase-5 inhibitor in rats where pulmonary artery hypertension was induced by chronic exposure to hypoxia. Methods: Rats were divided into three groups: normoxic control, hypoxic with no treatments (2 weeks breathing an atmosphere containing 10% oxygen), and hypoxic treated with sildenafil (1.4 mg/Kg per day in 0.3 mL i.p.). After sacrifice, hearts and lungs were removed and harvested for analyses

2018 Frontiers in physiology

49. Use of phosphodiesterase inhibitors and prevalence of self-reported glaucoma in the United States. Full Text available with Trip Pro

Use of phosphodiesterase inhibitors and prevalence of self-reported glaucoma in the United States. While decreased ocular blood flow is thought to be a possible contributor to glaucoma pathogenesis, it is unclear what role systemic phosphodiesterase inhibitors (PDEi) play. We performed a cross-sectional study of a nationally representative sample of the U.S. population to investigate the relationship between the most commonly used PDEi, sildenafil and theophylline, and self-reported glaucoma.We

2017 PLoS ONE

50. Docking and quantitative structure-activity relationship of bi-cyclic heteroaromatic pyridazinone and pyrazolone derivatives as phosphodiesterase 3A (PDE3A) inhibitors. Full Text available with Trip Pro

Docking and quantitative structure-activity relationship of bi-cyclic heteroaromatic pyridazinone and pyrazolone derivatives as phosphodiesterase 3A (PDE3A) inhibitors. PDE3s belong to the phosphodiesterases family, where the PDE3A isoform is the major subtype in platelets involved in the cAMP regulation pathway of platelet aggregation. PDE3A inhibitors have been designed as potential antiplatelet agents. In this work, a homology model of PDE3A was developed and used to obtain the binding modes (...) of bicyclic heteroaromatic pyridazinones and pyrazolones. Most of the studied compounds adopted similar orientations within the PDE3A active site, establishing hydrogen bonds with catalytic amino acids. Besides, the structure-activity relationship of the studied inhibitors was described by using a field-based 3D-QSAR method. Different structure alignment strategies were employed, including template-based and docking-based alignments. Adequate correlation models were obtained according to internal

2017 PLoS ONE

51. The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson's disease. Full Text available with Trip Pro

The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson's disease. Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson's disease (PD) is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to the abundant

2017 PLoS ONE

52. Beneficial effects of rolipram, a phosphodiesterase 4 specific inhibitor, on testicular torsion-detorsion injury in rats. (Abstract)

Beneficial effects of rolipram, a phosphodiesterase 4 specific inhibitor, on testicular torsion-detorsion injury in rats. The aim of the study is to investigate the effect of Rolipram, a selective phosphodiesterase 4 inhibitor, on testicular torsion - detorsion injury.Sixty young male rats were divided into five groups. In each group, the right testes of six rats were removed four hours after detorsion for biochemical analysis, and the right testes of the remaining six rats were removed 24 h

2018 Journal of Pediatric Surgery

53. Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition: A Translational Study in the Dog and Rabbit. Full Text available with Trip Pro

Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition: A Translational Study in the Dog and Rabbit. Phosphodiesterase type-1 (PDE1) hydrolyzes cAMP and cGMP and is constitutively expressed in the heart, although cardiac effects from its acute inhibition in vivo are largely unknown. Existing data are limited to rodents expressing mostly the cGMP-favoring PDE1A isoform. Human heart predominantly expresses PDE1C with balanced selectivity for cAMP and cGMP. Here, we (...) determined the acute effects of PDE1 inhibition in PDE1C-expressing mammals, dogs, and rabbits, in normal and failing hearts, and explored its regulatory pathways.Conscious dogs chronically instrumented for pressure-volume relations were studied before and after tachypacing-induced heart failure (HF). A selective PDE1 inhibitor (ITI-214) was administered orally or intravenously±dobutamine. Pressure-volume analysis in anesthetized rabbits tested the role of β-adrenergic and adenosine receptor signaling

2018 Circulation

54. Chronic pelvic pain and prostate inflammation in rat experimental autoimmune prostatitis: Effect of a single treatment with phosphodiesterase 5 inhibitors on chronic pelvic pain. (Abstract)

Chronic pelvic pain and prostate inflammation in rat experimental autoimmune prostatitis: Effect of a single treatment with phosphodiesterase 5 inhibitors on chronic pelvic pain. Experimental autoimmune prostatitis (EAP) is most often used as a nonbacterial model of chronic prostatitis/chronic pelvic pain. We investigated the development of chronic pelvic pain and inflammatory changes in rat EAP and examined the effect of a single treatment with phosphodiesterase 5 (PDE5) inhibitors (...) drugs, celecoxib and pregabalin, which are clinically used for the treatment of prostatitis-related pain. Subsequently, we examined the effects of single treatments with three phosphodiesterase 5 inhibitors, including tadalafil, on pelvic pain in this model.On day 42, after antigen injection, the mRNA levels of 44 of 84 kinds of cytokines/chemokines and their receptors increased significantly in EAP rats, as did the protein levels of seven of 23 kinds of cytokines/chemokines. Histological analysis

2018 Prostate

55. Longitudinal recovery patterns of penile length and the underexplored benefit of long-term phosphodiesterase-5 inhibitor use after radical prostatectomy. Full Text available with Trip Pro

Longitudinal recovery patterns of penile length and the underexplored benefit of long-term phosphodiesterase-5 inhibitor use after radical prostatectomy. Penile length (PL) shortening is an underreported phenomenon following radical prostatectomy (RP) and risk factors are not fully explored. We aimed to describe longitudinal patterns of PL recovery and evaluate factors predicting complete return to baseline PL.PL measurement was performed during a preoperative and postoperative follow-up visits (...) at 7 days and 3, 6, 9, and 12 months. Patients who completely recovered (CR: N = 397) their preoperative stretched PL measured during at least one of their follow-up visits were compared to those with incomplete recovery (IR: N = 131). Recovery patterns were analyzed for both groups and were also compared in regards to demographics, nerve-sparing techniques, prostate size, cardiovascular risk profiles, and phosphodiesterase-5 inhibitor (PDE5i) uses. Logistic regression analyses were performed using

2018 BMC Urology

56. Evaluation of the Efficacy, Safety, and Tolerability of BI 409306, a Novel Phosphodiesterase 9 Inhibitor, in Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial. Full Text available with Trip Pro

Evaluation of the Efficacy, Safety, and Tolerability of BI 409306, a Novel Phosphodiesterase 9 Inhibitor, in Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial. Patients with cognitive impairment associated with schizophrenia may benefit from treatments targeting dysfunctional glutamatergic neurotransmission. BI 409306, a potent and selective phosphodiesterase 9 inhibitor, was assessed in patients with schizophrenia using a learn-and-confirm

2018 Schizophrenia bulletin Controlled trial quality: predicted high

57. Sexual habits of men with ED who take phosphodiesterase 5 inhibitors: a survey conducted in 7 countries. Full Text available with Trip Pro

Sexual habits of men with ED who take phosphodiesterase 5 inhibitors: a survey conducted in 7 countries. Western cultural perceptions that favour spontaneous sex may create unrealistic expectations for erectile dysfunction (ED) treatment. Little is known about how users of phosphodiesterase type 5 inhibitors (PDE5Is) plan sexual activity and timing of their preactivity PDE5I ingestion. Because various PDE5Is vary in their duration of action and dosage regimen, this may be an important

2018 International journal of clinical practice

58. Non-invasive Management Options for Erectile Dysfunction When a Phosphodiesterase Type 5 Inhibitor Fails. (Abstract)

Non-invasive Management Options for Erectile Dysfunction When a Phosphodiesterase Type 5 Inhibitor Fails. Phosphodiesterase type 5 inhibitors (PDE5Is) are the drug of choice for medical management of erectile dysfunction (ED). On-demand PDE5Is have an overall efficacy of 60-70% for ED; 30-35% of patients fail to respond to a PDE5I, and 30-50% of non-responders can be salvaged with detailed counseling on proper use and physician follow-up to ensure that the patient has been prescribed

2018 Drugs & Aging

59. [<sup>11</sup>C]( R)-Rolipram positron emission tomography detects DISC1 inhibition of phosphodiesterase type 4 in live Disc1 locus-impaired mice. (Abstract)

[11C]( R)-Rolipram positron emission tomography detects DISC1 inhibition of phosphodiesterase type 4 in live Disc1 locus-impaired mice. Although still a matter of controversy, disrupted in schizophrenia protein 1 (DISC1) was suggested as a potential inhibitor of phosphodiesterase 4 (PDE4). We used Disc1 locus impairment (LI) mice to investigate the interaction between PDE4 and DISC 1 in vivo and in vitro. [11C]( R)-Rolipram binding was measured by PET in LI ( n = 11) and C57BL/6 wild

2018 Journal of Cerebral Blood Flow and Metabolism

60. Sexual Rehabilitation After Nerve-Sparing Radical Prostatectomy: Free-of-Charge Phosphodiesterase Type 5 Inhibitor Administration Improves Compliance to Treatment. (Abstract)

Sexual Rehabilitation After Nerve-Sparing Radical Prostatectomy: Free-of-Charge Phosphodiesterase Type 5 Inhibitor Administration Improves Compliance to Treatment. In December 2006, the region of Tuscany (Italy) authorized the free-of-charge provision of phosphodiesterase type 5 inhibitors (PDE5I) for all patients with Tuscan citizenship who undergo nerve-sparing radical prostatectomy (NSRP).To compare sexual rehabilitation outcomes in patients with low risk of erectile dysfunction and minimal (...) , Mari A, Canale A, et al. Sexual Rehabilitation After Nerve-Sparing Radical Prostatectomy: Free-of-Charge Phosphodiesterase Type 5 Inhibitor Administration Improves Compliance to Treatment. J Sex Med 2018;15:120-123.Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

2018 Journal Of Sexual Medicine

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