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Phosphodiesterase Inhibitor

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221. Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1–42‐mediated cytotoxicity Full Text available with Trip Pro

Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1–42‐mediated cytotoxicity Phosphodiesterase (PDE) inhibitors are currently under evaluation as agents that may facilitate the improvement of cognitive impairment associated with Alzheimer's disease. Our aim was to determine whether inhibitors of PDEs 4, 5 and 9 could alleviate the cytotoxic effects of amyloid beta 1-42 (Aβ1-42) via a mechanism involving the small heatshock (...) protein HSP20. We show that inhibition of PDEs 4, 5 and 9 but not 3 induces the phosphorylation of HSP20 which, in turn, increases the colocalisation between the chaperone and Aβ1-42 to significantly decrease the toxic effect of the peptide. We conclude that inhibition of PDE9 is most effective to combat Aβ1-42 cytotoxicity in our cell model.

2016 FEBS open bio

222. Early-onset fetal growth restriction treated with the long-acting phosphodiesterase-5 inhibitor tadalafil: a case report Full Text available with Trip Pro

Early-onset fetal growth restriction treated with the long-acting phosphodiesterase-5 inhibitor tadalafil: a case report Severe early-onset fetal growth restriction occurs in 0.4 % of all pregnancies, and the prognoses of these patients are dismal. Severely growth-restricted fetuses (far below 500 g) are thought to be nonviable. Since there have not been effective treatments for such fetal patients, obstetricians have simply tried to identify the optimal timing for their delivery (...) . There are a few reports suggesting that the phosphodiesterase type 5 inhibitor sildenafil has some limited beneficial effects on fetal growth, but there are no such reports on tadalafil, another derivative phosphodiesterase type 5 inhibitor which has a much longer half-life than sildenafil. Here we present a case in which the administration of tadalafil to the mother revived the arrested growth and severe oligohydramnios of the very prematurely growth-restricted fetus.We describe a case of early-onset fetal

2016 Journal of medical case reports

223. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model Full Text available with Trip Pro

Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs

2016 EBioMedicine

224. cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats Full Text available with Trip Pro

cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats GEBR-7b, a potential phosphodiesterase 4D inhibitor, has been shown to have memory-enhancing effects in rodents. However, it is still unknown whether GEBR-7b also has the antidepressant-like effects in rats. Herein, we examined the potential of GEBR-7b to attenuate depression-like behaviors in the rat model of depression induced by chronic unpredictable stress (CUS). Next

2016 Neuropsychiatric disease and treatment

225. Anti‐inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus‐inducible cytokines Full Text available with Trip Pro

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

226. The devil is in the details: an analysis of the subtleties between phosphodiesterase inhibitors for erectile dysfunction Full Text available with Trip Pro

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

227. Usage and perceptions of phosphodiesterase type 5 inhibitors among the male partners of infertile couples Full Text available with Trip Pro

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

228. Phosphodiesterase inhibitors as adjunctive therapies for tuberculosis Full Text available with Trip Pro

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

229. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling Full Text available with Trip Pro

The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance (...) and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral

2016 Oncotarget

230. Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications Full Text available with Trip Pro

Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications The fronto-striatal circuits are the common neurobiological basis for neuropsychiatric disorders, including schizophrenia, Parkinson's disease, Huntington's disease, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's syndrome. Fronto-striatal circuits consist of motor circuits, associative circuits, and limbic circuits. All circuits share 2 (...) for pharmacological intervention in neuropsychiatric disorders related to dopaminergic regulation of fronto-striatal circuits.Clinical studies of the effects of different phosphodiesterase inhibitors on cognition, affect, and motor function in relation to the fronto-striatal circuits are reviewed.Several selective phosphodiesterase inhibitors have positive effects on cognition, affect, and motor function in relation to the fronto-striatal circuits.Increased understanding of the subcellular localization

2016 International Journal of Neuropsychopharmacology

231. Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line Full Text available with Trip Pro

, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study. (...) Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression

2016 PloS one

232. Inhibition of P. aeruginosa c-di-GMP phosphodiesterase RocR and swarming motility by a benzoisothiazolinone derivative †Electronic supplementary information (ESI) available: All experimental, spectroscopic details and supplemental figures. See DOI: 10.1 Full Text available with Trip Pro

are terminated by EAL or HD-GYP domain phosphodiesterases (PDEs), which hydrolyze c-di-GMP to linear pGpG or GMP. Thus far the majority of efforts have been dedicated to the development of inhibitors of DGCs but not PDEs. This is probably because the old view was that inhibiting any c-di-GMP PDE would lead to biofilm formation, an undesirable phenotype. Recent data however suggest that some PDEs only change the localized (not global) concentration of c-di-GMP to increase bacterial virulence and do not affect (...) Inhibition of P. aeruginosa c-di-GMP phosphodiesterase RocR and swarming motility by a benzoisothiazolinone derivative †Electronic supplementary information (ESI) available: All experimental, spectroscopic details and supplemental figures. See DOI: 10.1 Various important cellular processes in bacteria are controlled by c-di-GMP, such as motility, biofilm formation and virulence factors production. C-di-GMP is synthesized from two molecules of GTP by diguanylate cyclases (DGCs) and its actions

2016 Chemical Science

233. Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis Full Text available with Trip Pro

Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome (...) and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics

2016 Frontiers in immunology

234. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice Full Text available with Trip Pro

Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen (...) species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression

2016 Scientific reports

235. Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A Full Text available with Trip Pro

Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate (...) therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice.

2016 Translational psychiatry

236. Lipoxin A4 as a possible mediator of the beneficial actions of phosphodiesterase-5 enzyme inhibitors Full Text available with Trip Pro

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

237. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: A novel treatment option for nurse practitioners treating patients with psoriatic disease Full Text available with Trip Pro

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: A novel treatment option for nurse practitioners treating patients with psoriatic disease Apremilast is an oral nonbiologic medication approved for the treatment of adult patients with active psoriatic arthritis and for patients with moderate to severe plaque psoriasis. This article summarizes the efficacy and safety of apremilast and provides characterization of the novel medication with clinical perspectives to successfully incorporate

2016 Journal of the American Association of Nurse Practitioners

238. Potential Treatment of Cognitive Impairment in Schizophrenia by Phosphodiesterase 2 (PDE2) Inhibitors Full Text available with Trip Pro

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

239. Recreational Use of Phosphodiesterase 5 Inhibitors and Its Associated Factors among Undergraduate Male Students in an Ethiopian University: A Cross-Sectional Study Full Text available with Trip Pro

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

240. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation Full Text available with Trip Pro

previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins) or platelet inhibitors that impede post-receptor thrombin signaling [phosphodiesterase (PDE) antagonists] would inhibit EHV-1-induced (...) Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have

2016 Frontiers in veterinary science

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