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PDE or phosphodiesterase

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https://www.readbyqxmd.com/read/28937238/effects-of-roflumilast-a-phosphodiesterase-4-inhibitor-on-the-lung-functions-in-a-saline-lavage-induced-model-of-acute-lung-injury
#1
P Kosutova, P Mikolka, M Kolomaznik, S Rezakova, A Calkovska, D Mokra
Acute lung injury (ALI) is associated with deterioration of alveolar-capillary lining and transmigration and activation of inflammatory cells. Whereas a selective phosphodiesterase-4 (PDE4) inhibitor roflumilast has exerted potent anti-inflammatory properties, this study evaluated if its intravenous delivery can influence inflammation, edema formation, and respiratory parameters in rabbits with a lavage-induced model of ALI. ALI was induced by repetitive saline lung lavage (30 ml/kg). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with roflumilast i...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28935920/inhibition-of-pde2-reverses-beta-amyloid-induced-memory-impairment-through-regulation-of-pka-pkg-dependent-neuro-inflammatory-and-apoptotic-pathways
#2
Li Wang, Yilixiati Xiaokaiti, Gang Wang, Xiaoxiao Xu, Ling Chen, Xianfeng Huang, Li Liu, Jianchun Pan, Shuqun Hu, Zhuoyou Chen, Ying Xu
Beta amyloid peptides (Aβ) are known risk factors involved in cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Phosphodiesterase 2 (PDE2) inhibitors increase the intracellular cAMP and/or cGMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE2 mediated neuroapoptotic and neuroinflammatory events, as well as cognitive performance in AD are related to cAMP/cGMP-dependent pathways. The present study investigated how the selective PDE2 inhibitor BAY60-7550 (BAY) affected Aβ-induced learning and memory impairment in two classic rodent models...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935242/supplementation-of-cilostazol-during-in-vitro-maturation-enhances-the-meiosis-and-developmental-competence-of-yak-oocytes-by-influencing-camp-content-and-mrna-expression
#3
Xian-Rong Xiong, Dao-Liang Lan, Jian Li, Ya-Qiu Lin, Ming-Yang Li
The efficiency of in vitro embryo production remains low compared with that observed in vivo. Recent studies have independently shown that cyclic adenosine monophosphate (cAMP) modulation prior to in vitro maturation (IVM) supplementation improves oocyte developmental competence. In this context, special cAMP modulators have been applied during IVM as promising alternatives to improve this biotechnology. Accordingly, this study was conducted to evaluate the effects of treatment with cilostazol, a PDE3 inhibitor, during pre-IVM culture on oocyte meiotic maturation in yak...
August 24, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28935183/identification-of-novel-pde%C3%AE-interacting-proteins
#4
Philipp Küchler, Gunther Zimmermann, Michael Winzker, Petra Janning, Herbert Waldmann, Slava Ziegler
Prenylation is a post-translational modification that increases the affinity of proteins for membranes and mediates protein-protein interactions. The retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDEδ) is a prenyl binding protein that is essential for the shuttling of small GTPases between different membrane compartments and, thus, for their proper functioning. Although the prenylome comprises up to 2% of the mammalian proteome, only few prenylated proteins are known to interact with PDEδ...
August 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28932631/tadalafil-has-biologic-activity-in-human-melanoma-results-of-a-pilot-trial-with-tadalafil-in-patients-with-metastatic-melanoma-tame
#5
Jessica C Hassel, Huanhuan Jiang, Carolin Bender, Julia Winkler, Alexandra Sevko, Ivan Shevchenko, Niels Halama, Antonia Dimitrakopoulou-Strauss, Walter E Haefeli, Dirk Jäger, Alexander Enk, Jochen Utikal, Viktor Umansky
Myeloid-derived suppressor cells (MDSCs) are known to play a critical role in the suppression of T cell antitumor responses. Our preclinical data showed that the phosphodiesterase (PDE)-5 inhibitor sildenafil impaired MDSC functions, enhanced intratumoral T cell activity and prolonged survival of melanoma-bearing mice. In this study, we evaluated biologic effects, safety and efficacy of palliative treatment with the PDE-5 inhibitor tadalafil in metastatic melanoma patients. We conducted an open-label, dose de-escalation trial with tadalafil in pretreated metastatic melanoma patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928205/bola-is-required-for-the-accurate-regulation-of-c-di-gmp-a-central-player-in-biofilm-formation
#6
Ricardo N Moreira, Clémentine Dressaire, Susana Barahona, Lisete Galego, Volkhard Kaever, Urs Jenal, Cecília M Arraiano
The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28926093/pulmonary-hypertension-molecular-aspects-of-current-therapeutic-intervention-and-future-direction
#7
Taruna Katyal Arora, Amit KumarArora, Monika Katyal Sachdeva, Satyendra Kumar Rajput, Arun Kumar Sharma
Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics and long acting prostacyclin analogue, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925560/apremilast-in-psoriasis-a-prospective-real-world-study
#8
I Vujic, R Herman, M Sanlorenzo, C Posch, B Monshi, K Rappersberger, L Richter
BACKGROUND: Apremilast is a novel oral phosphodiesterase-4 inhibitor approved for psoriasis treatment. Randomized trials have documented its efficacy and safety, but data on real-world patients are scarce. OBJECTIVES: We aim to characterize psoriasis patients treated with apremilast in a real-world setting and calculate drug survival as an important measure of efficacy and compliance. METHODS: All psoriasis patients that received apremilast between April 1(st) 2015 and January 19(th) 2017 were evaluated every 4 weeks and we documented: age, weight, height, smoking status, family history of psoriasis, joint involvement, previous treatments, psoriasis area severity index (PASI) scores, and the onset and duration of adverse events (AE)...
September 19, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28924693/phosphodiesterase-4-inhibition-affects-both-the-direct-and-indirect-pathway-an-electrophysiological-study-examining-the-tri-phasic-response-in-the-substantia-nigra-pars-reticulata
#9
P R A Heckman, J V Schweimer, T Sharp, J Prickaerts, A Blokland
Fronto-striatal circuits constitute the neurobiological basis of many neuropsychiatric disorders. Part of the intracellular signaling within these circuits, including its dopaminergic modulation, is regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling cascade. Based on the overall expression in human fronto-striatal circuitry, we tested the effects of a cAMP selective phosphodiesterase 4 (PDE4) inhibitor on the tri-phasic response in the dorsomedial substantia nigra pars reticulata (SNr) upon stimulation of the infralimbic cortex in rats...
September 18, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28923561/update-on-the-safety-of-phosphodiesterase-type-5-inhibitors-for-the-treatment-of-erectile-dysfunction
#10
REVIEW
Faysal A Yafi, Ira D Sharlip, Edgardo F Becher
INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5Is) have demonstrated efficacy in the treatment of erectile dysfunction (ED). Although historically found to have limited drug-related adverse events, emerging data have suggested that PDE5Is might be associated with melanoma or recurrence of prostate cancer after radical prostatectomy. AIM: To summarize the literature on the safety of PDE5Is. METHODS: A literature review was performed through PubMed from 1990 through 2016 regarding ED...
September 8, 2017: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/28923309/altered-penile-caveolin-expression-in-diabetes-potential-role-in-erectile-dysfunction
#11
Jay Parikh, Alice Zemljic-Harpf, Johnny Fu, Dimosthenis Giamouridis, Tung-Chin Hsieh, Adam Kassan, Karnam S Murthy, Valmik Bhargava, Hemal H Patel, M Raj Rajasekaran
BACKGROUND: The pathophysiology of increased severity of erectile dysfunction in men with diabetes and their poor response to oral pharmacotherapy are unclear. Defective vascular endothelium and consequent impairment in the formation and action of nitric oxide (NO) are implicated as potential mechanisms. Endothelial NO synthase, critical for NO generation, is localized to caveolae, plasma membrane lipid rafts enriched in structural proteins, and caveolins. Type 2 diabetes mellitus (T2DM)-induced changes in caveolin expression are recognized to play a role in cardiovascular dysfunction...
September 8, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28923049/roflumilast-reverses-cftr-mediated-ion-transport-dysfunction-in-cigarette-smoke-exposed-mice
#12
S Vamsee Raju, Lawrence Rasmussen, Peter A Sloane, Li Ping Tang, Emily Falk Libby, Steven M Rowe
BACKGROUND: Dysfunction in cystic fibrosis transmembrane conductance regulator (CFTR) can be elicited by cigarette smoke and is observed in patients with chronic bronchitis. We have previously demonstrated in human airway epithelial cell monolayers that roflumilast, a clinically approved phosphodiesterase 4 inhibitor that reduces the risk of exacerbations in chronic obstructive pulmonary disease patients with chronic bronchitis and a history of exacerbations, activates CFTR-dependent chloride secretion via a cAMP-mediated pathway, partially restores the detrimental effects of cigarette smoke on CFTR-mediated ion transport, and increases CFTR-dependent gastrointestinal fluid secretion in isolated murine intestine segments...
September 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28922692/phosphodiesterase-4-inhibitors-for-chronic-obstructive-pulmonary-disease
#13
REVIEW
Jimmy Chong, Bonnie Leung, Phillippa Poole
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013...
September 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28919201/macitentan-for-the-treatment-of-inoperable-chronic-thromboembolic-pulmonary-hypertension-merit-1-results-from-the-multicentre-phase-2-randomised-double-blind-placebo-controlled-study
#14
Hossein-Ardeschir Ghofrani, Gérald Simonneau, Andrea M D'Armini, Peter Fedullo, Luke S Howard, Xavier Jaïs, David P Jenkins, Zhi-Cheng Jing, Michael M Madani, Nicolas Martin, Eckhard Mayer, Kelly Papadakis, Dominik Richard, Nick H Kim
BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm(5) and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo...
September 8, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28915270/the-single-cyclic-nucleotide-specific-phosphodiesterase-of-the-intestinal-parasite-giardia-lamblia-represents-a-potential-drug-target
#15
Stefan Kunz, Vreni Balmer, Geert Jan Sterk, Michael P Pollastri, Rob Leurs, Norbert Müller, Andrew Hemphill, Cornelia Spycher
BACKGROUND: Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, and treatment options are limited. According to the Center for Disease Control and Prevention, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the adult population in the developed world. This study describes the single cyclic nucleotide-specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new generation of anti-giardial drugs...
September 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28913868/alterations-of-c-di-gmp-turnover-proteins-modulate-semi-constitutive-rdar-biofilm-formation-in-commensal-and-uropathogenic-escherichia-coli
#16
Annika Cimdins, Roger Simm, Fengyang Li, Petra Lüthje, Kaisa Thorell, Åsa Sjöling, Annelie Brauner, Ute Römling
Agar plate-based biofilm of enterobacteria like Escherichia coli is characterized by expression of the extracellular matrix components amyloid curli and cellulose exopolysaccharide, which can be visually enhanced upon addition of the dye Congo Red, resulting in a red, dry, and rough (rdar) colony morphology. Expression of the rdar morphotype depends on the transcriptional regulator CsgD and occurs predominantly at ambient temperature in model strains. In contrast, commensal and pathogenic isolates frequently express the csgD-dependent rdar morphotype semi-constitutively, also at human host body temperature...
September 15, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28913588/efficacy-of-pde5is-and-ssris-in-men-with-premature-ejaculation-a-new-systematic-review-and-five-meta-analyses
#17
Yi Sun, Lu Yang, Yige Bao, Zhenhua Liu, Liangren Liu, Qiang Wei
PURPOSE: To clarify the efficacy of phosphodiesterase-5 inhibitors (PDE5Is) and selective serotonin reuptake inhibitors (SSRIs) in men with premature ejaculation (PE). METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify all randomized, controlled trials (RCTs) and compared the results, including intravaginal ejaculation latency time, satisfaction, intercourse per-week and side effects after treatment with PDE5I or SSRIs versus placebo, combined use of PDE5I with SSRIs versus PDE5I or SSRIs alone, and PDE5I versus SSRIs for treating PE...
September 14, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28912134/zatt-znf451-mediated-resolution-of-topoisomerase-2-dna-protein-cross-links
#18
Matthew J Schellenberg, Jenna Ariel Lieberman, Andrés Herrero-Ruiz, Logan R Butler, Jason G Williams, Ana M Muñoz-Cabello, Geoffrey A Mueller, Robert E London, Felipe Cortés-Ledesma, R Scott Williams
Topoisomerase 2 (TOP2) DNA transactions are essential for life, and proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28910498/phosphodiesterase-1a-inhibition-elicits-cgmp-dependent-relaxation-of-rat-mesenteric-arteries
#19
Makhala Michell Khammy, Thomas Dalsgaard, Peter Hjørringgaard Larsen, Claus Tornby Christoffersen, Dorte Clausen, Lars Kyhn Rasmussen, Lasse Folkersen, Morten Grunnet, Jan Kehler, Christian Aalkjaer, Jacob Nielsen
BACKGROUND AND PURPOSE: Phosphodiesterase 1 (PDE1), a subfamily of cyclic nucleotide phosphodiesterases consisting of three isoforms, PDE1A, PDE1B, and PDE1C, has been implicated in regulation of vascular tone. The PDE1 isoform(s) responsible for tone regulation is unknown. This study used isoform-preferring PDE1 inhibitors, Lu AF58027, Lu AF64196, Lu AF66896, and Lu AF67897, to investigate the relative contribution of PDE1 isoforms to regulation of vascular tone. EXPERIMENTAL APPROACH: In rat mesenteric arteries, expression and localisation of Pde1 isoforms were determined by qPCR and in situ hybridisation, and physiological impact of PDE1 inhibition were evaluated by isometric tension recordings...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28910378/neuroinflammation-myelin-and-behavior-temporal-patterns-following-mild-traumatic-brain-injury-in-mice
#20
Toufik Taib, Claire Leconte, Juliette Van Steenwinckel, Angelo H Cho, Bruno Palmier, Egle Torsello, Rene Lai Kuen, Somfieme Onyeomah, Karine Ecomard, Chiara Benedetto, Bérard Coqueran, Anne-Catherine Novak, Edwige Deou, Michel Plotkine, Pierre Gressens, Catherine Marchand-Leroux, Valérie C Besson
Traumatic brain injury (TBI) results in white matter injury (WMI) that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i) neuroinflammation, (ii) WMI and (iii) behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact...
2017: PloS One
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