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Phosphodiesterase Inhibitor

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81. Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function. Full Text available with Trip Pro

Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function. Background and Purpose- Acetylsalicylic acid and clopidogrel are the 2 main antithrombotic drugs for secondary prevention in patients with ischemic stroke (IS) without indication for anticoagulation. Because of their limited efficacy and potential side effects, novel antiplatelet agents are urgently needed. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor (...) cerebral ischemia. Reduced blood-brain barrier damage, attenuated brain tissue inflammation, and decreased local cell death could be identified as potential mechanisms. PDE-3 inhibitor treatment did neither increase the number of intracerebral hemorrhages nor affect platelet function. Conclusions- The novel PDE-3 inhibitor substance V protected mice from IS independent from platelet function. Pharmaceutical inactivation of PDE-3 might become a promising therapeutic approach to combat IS via inhibition

2018 Stroke

82. Effect of phosphodiesterase 5 inhibitors on blood pressure [Cochrane protocol]

Effect of phosphodiesterase 5 inhibitors on blood pressure [Cochrane protocol] 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. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email

2020 PROSPERO

83. Effect of phosphodiesterase 5 inhibitors on blood pressure [Cochrane protocol]

Effect of phosphodiesterase 5 inhibitors on blood pressure [Cochrane protocol] 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. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email

2020 PROSPERO

84. Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II alveolar epithelial cell injury Full Text available with Trip Pro

Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II alveolar epithelial cell injury Fibrosis of the lung constitutes a major clinical challenge and novel therapies are required to alleviate the associated morbidity and mortality. Investigating the antifibrotic efficacy of drugs that are already in clinical practice offers an efficient strategy to identify new therapies. The phosphodiesterase 4 (PDE4) inhibitors, approved for the treatment of chronic obstructive (...) pulmonary disease, harbor therapeutic potential for pulmonary fibrosis by augmenting the activity of endogenous antifibrotic mediators that signal through cyclic AMP. In this study, we tested the efficacy of several PDE4 inhibitors including a novel compound (Compound 1) in a murine model of lung fibrosis that results from a targeted type II alveolar epithelial cell injury. We also compared the antifibrotic activity of PDE4 inhibition to the two therapies that are FDA-approved for idiopathic pulmonary

2018 Physiological reports

85. Phosphodiesterase-5 inhibitors for colon cancer chemoprevention Full Text available with Trip Pro

Phosphodiesterase-5 inhibitors for colon cancer chemoprevention 30187889 2018 11 14 1945-4589 10 9 2018 Sep 05 Aging Aging (Albany NY) Phosphodiesterase-5 inhibitors for colon cancer chemoprevention. 2216-2217 10.18632/aging.101545 Islam Bianca N BN Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. Browning Darren D DD Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta (...) , GA 30912, USA. eng Journal Article United States Aging (Albany NY) 101508617 1945-4589 cGMP cancer colon phosphodiesterase prevention 2018 07 04 2018 09 04 2018 9 7 6 0 2018 9 7 6 0 2018 9 7 6 0 ppublish 30187889 101545 10.18632/aging.101545 PMC6188491 Cancer Prev Res (Phila). 2018 Feb;11(2):81-92 29301746 Pharmacol Ther. 2004 Nov;104(2):137-62 15518884 Gut. 2006 Mar;55(3):367-73 16150858 Am J Gastroenterol. 2018 Mar;113(3):329-338 29380823 PLoS One. 2017 Apr 27;12(4):e0176673 28448580 Cancer

2018 Aging (Albany NY)

86. Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide nucleosides as drug prototypes for anti-cancer therapy Full Text available with Trip Pro

Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide nucleosides as drug prototypes for anti-cancer therapy A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors based on disaccharide nucleosides was identified. TDP1 plays an essential role in the resistance of cancer cells to currently used antitumour drugs based on Top1 inhibitors such as topotecan and irinotecan. The most effective inhibitors investigated in this study have IC50 values (half-maximal (...) inhibitory concentration) in 0.4-18.5 µM range and demonstrate relatively low own cytotoxicity along with significant synergistic effect in combination with anti-cancer drug topotecan. Moreover, kinetic parameters of the enzymatic reaction and fluorescence anisotropy were measured using different types of DNA-biosensors to give a sufficient insight into the mechanism of inhibitor's action.

2018 Journal of enzyme inhibition and medicinal chemistry

87. Therapeutic benefits of phosphodiesterase 4B inhibition after traumatic brain injury. Full Text available with Trip Pro

Therapeutic benefits of phosphodiesterase 4B inhibition after traumatic brain injury. Traumatic brain injury (TBI) initiates a deleterious inflammatory response that exacerbates pathology and worsens outcome. This inflammatory response is partially mediated by a reduction in cAMP and a concomitant upregulation of cAMP-hydrolyzing phosphodiesterases (PDEs) acutely after TBI. The PDE4B subfamily, specifically PDE4B2, has been found to regulate cAMP in inflammatory cells, such as neutrophils (...) , macrophages and microglia. To determine if PDE4B regulates inflammation and subsequent pathology after TBI, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury (2 ± 0.2 atm) and were then treated with a PDE4B - selective inhibitor, A33, or vehicle for up to 3 days post-surgery. Treatment with A33 reduced markers of microglial activation and neutrophil infiltration at 3 and 24 hrs after TBI, respectively. A33 treatment also reduced cortical contusion

2017 PLoS ONE

88. Phosphodiesterase-5 inhibitors for the treatment of premature ejaculation

Phosphodiesterase-5 inhibitors for the treatment of premature ejaculation 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. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email

2020 PROSPERO

89. The antineoplastic potential of phosphodiesterase type 5 inhibitors in different types of cancer: a systematic review

The antineoplastic potential of phosphodiesterase type 5 inhibitors in different types of cancer: a systematic review 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. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated

2020 PROSPERO

90. The efficacy of transitioning from phosphodiesterase type 5 inhibitors (PDE5i) to riociguat: a systematic and single-centre retrospective chart-review

The efficacy of transitioning from phosphodiesterase type 5 inhibitors (PDE5i) to riociguat: a systematic and single-centre retrospective chart-review 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. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content

2020 PROSPERO

91. 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

92. 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

94. 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

95. The mechanism of attenuation of epithelial‐mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression Full Text available with Trip Pro

The mechanism of attenuation of epithelial‐mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression Phosphodiesterase-5 (PDE-5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the downregulation (...) of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE-5 inhibitor could preserve epithelial-mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression. Ten-week-old SD rats (N = 24, 200 g, male) were divided (N = 6) into four groups, which received: A LSD, L-NAME 1 mg/mL in drinking water, Udenafil 5 mg/kg subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil gelatinase

2017 Clinical and experimental pharmacology & physiology

96. EDEUS, a Real-Life Study on the Users of Phosphodiesterase Type 5 Inhibitors: Prevalence, Perceptions, and Health Care-Seeking Behavior Among European Men With a Focus on 2nd-Generation Avanafil Full Text available with Trip Pro

EDEUS, a Real-Life Study on the Users of Phosphodiesterase Type 5 Inhibitors: Prevalence, Perceptions, and Health Care-Seeking Behavior Among European Men With a Focus on 2nd-Generation Avanafil Erectile dysfunction (ED) is a multidimensional disorder with an estimated prevalence of 1% to 10% in men younger than 40 years and up to 100% in men in their 70s and 80s.To evaluate the real-life characteristics and unmet needs of men with ED, its impact on well-being, and treatment rates across (...) ) using on-demand phosphodiesterase type 5 inhibitors (PDE5is) were designated "performers" (60%) without a formal ED diagnosis or "patients" with a medical diagnosis. Patients were older than performers, with more self-reported comorbidities; patients used a higher PDE5i dosage and purchased it from official pharmacies more often than performers did. Of avanafil users (n = 39), no differences in total IIEF or subdomain scores were observed after adjusting for confounders. However, avanafil users less

2017 Sexual Medicine

97. Potent Phosphodiesterase Inhibition and Nitric Oxide Release Stimulation of Anti-Impotence Thai Medicinal Plants from Full Text available with Trip Pro

Potent Phosphodiesterase Inhibition and Nitric Oxide Release Stimulation of Anti-Impotence Thai Medicinal Plants from Seven plants in the top rank were selected from the "MANOSROI III" database using the two Thai keywords which meant impotence and sexual tonic. Boesenbergia rotunda (L.) Mansf. extract [EDP1-001(1)] gave the highest PDE inhibition activity of 4.36-fold sildenafil, a standard anti-impotence drug. Plumbago indica Linn. extract [EDP2-001(1)] exhibited the highest NO release

2017 Evidence-based Complementary and Alternative Medicine (eCAM)

98. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Full Text available with Trip Pro

RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO

2017 European Respiratory Journal

99. Phosphodiesterase 4 (PDE4) Inhibitors. (Abstract)

Phosphodiesterase 4 (PDE4) Inhibitors. Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating (...) AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US

2017 Journal of American Academy of Dermatology

100. Phosphodiesterase Inhibitors Sildenafil and Vardenafil Reduce Zebrafish Rod Photoreceptor Outer Segment Shedding. Full Text available with Trip Pro

Phosphodiesterase Inhibitors Sildenafil and Vardenafil Reduce Zebrafish Rod Photoreceptor Outer Segment Shedding. The vertebrate rod photoreceptor undergoes daily growth and shedding to renew the rod outer segment (ROS), a modified cilium that contains the phototransduction machinery. It has been demonstrated that ROS shedding is regulated by the light-dark cycle; however, we do not yet have a satisfactory understanding of the molecular mechanisms that underlie this regulation. Given (...) that phototransduction relies on the hydrolysis of cGMP via phosphodiesterase 6 (PDE6), we examined ROS growth and shedding in zebrafish treated with cGMP-specific PDE inhibitors.We used transgenic zebrafish that express an inducible, transmembrane-bound mCherry protein, which forms a stripe in the ROS following a heat shock pulse and serves as a marker of ROS renewal. Zebrafish were reared in constant darkness or treated with PDE inhibitors following heat shock. Measurements of growth and shedding were analyzed

2017 Investigative Ophthalmology & Visual Science

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