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PDE or phosphodiesterase

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https://www.readbyqxmd.com/read/28214792/suppression-of-tumorigenicity-2-in-heart-failure-with-preserved-ejection-fraction
#1
Omar F AbouEzzeddine, Paul M McKie, Shannon M Dunlay, Susanna R Stevens, G Michael Felker, Barry A Borlaug, Horng H Chen, Russell P Tracy, Eugene Braunwald, Margaret M Redfield
BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) receptor is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity-driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF...
February 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#2
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213862/apremilast-a-review-in-psoriasis-and-psoriatic-arthritis
#3
Gillian M Keating
Apremilast (Otezla(®)) is an orally administered, small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast 30 mg twice daily reduced the severity of moderate to severe plaque psoriasis in the phase 3 ESTEEM trials, as well as improving difficult-to-treat nail, scalp and palmoplantar psoriasis. Most patient-reported outcomes, including pruritus and the total Dermatology Life Quality Index, also improved to a significantly greater extent with apremilast than with placebo, with significant improvements in pruritus and skin discomfort/pain visual analogue scale scores seen as early as week 2 with apremilast...
February 18, 2017: Drugs
https://www.readbyqxmd.com/read/28213324/qing-hua-granule-induces-glp-1-secretion-via-bitter-taste-receptor-in-db-db-mice
#4
Junyan Li, Jie Xu, Ruifang Hou, Xin Jin, Jingyi Wang, Na Yang, Li Yang, Li Liu, Feng Tao, Hao Lu
Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks...
February 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28212851/the-high-affinity-phosphodiesterase-pdeh-regulates-development-and-aflatoxin-biosynthesis-in-aspergillus-flavus
#5
Kunlong Yang, Yinghang Liu, Linlin Liang, Zhenguo Li, Qiuping Qin, Xinyi Nie, Shihua Wang
Cyclic AMP signaling controls a range of physiological processes in response to extracellular stimuli in organisms. Among the signaling cascades, cAMP, as a second messenger, is orchestrated by adenylate cyclase(biosynthesis) and cAMP phosphodiesterases (PDEs)(hydrolysis). In this study, we investigated the function of the high-affinity (PdeH) and low-affinity (PdeL) cAMP phosphodiesterase from the carcinogenic aflatoxin producing fungus Aspergillus flavus, and found that instead of PdeL, inactivation of PdeH exhibited a reduction in conidiation and sclerotia formation...
February 14, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28211580/inhibition-of-pde5a1-guanosine-cyclic-monophosphate-cgmp-hydrolysing-activity-by-sildenafil-analogues-that-inhibit-cellular-cgmp-efflux
#6
Anna Subbotina, Aina W Ravna, Roy A Lysaa, Ruben Abagyan, Ryszard Bugno, Georg Sager
OBJECTIVES: To determine the ability of 11 sildenafil analogues to discriminate between cyclic nucleotide phosphodiesterases (cnPDEs) and to characterise their inhibitory potencies (Ki values) of PDE5A1-dependent guanosine cyclic monophosphate (cGMP) hydrolysis. METHODS: Sildenafil analogues were identified by virtual ligand screening (VLS) and screened for their ability to inhibit adenosine cyclic monophosphate (cAMP) hydrolysis by PDE1A1, PDE1B1, PDE2A1, PDE3A, PDE10A1 and PDE10A2, and cGMP hydrolysis by PDE5A, PDE6C, PDE9A2 for a low (1 nm) and high concentration (10 μm)...
February 17, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28210757/sildenafil-a-phosphodiesterase-type-5-inhibitor-downregulates-osteopontin-in-human-peripheral-blood-mononuclear-cells
#7
Beata Kaleta, Agnieszka Boguska
The aim of this study was to investigate the ability of sildenafil to regulate osteopontin (OPN) gene and protein in peripheral blood mononuclear cells (PBMCs) from healthy blood donors. OPN is expressed by a wide variety of cell types, including immune cells. OPN functions are linked to various physiological and pathological conditions. Sildenafil is a selective inhibitor of type 5 phosphodiesterase. Sildenafil has recently been found to have immunomodulatory effects in animal models and in studies performed in humans...
February 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28209630/inhibition-of-phosphodiesterase-4-pde4-reduces-dermal-fibrosis-by-interfering-with-the-release-of-interleukin-6-from-m2-macrophages
#8
Christiane Maier, Andreas Ramming, Christina Bergmann, Rita Weinkam, Nicolai Kittan, Georg Schett, Jörg H W Distler, Christian Beyer
OBJECTIVES: To investigate the disease-modifying effects of phosphodiesterase 4 (PDE4) inhibition in preclinical models of systemic sclerosis (SSc). METHODS: We studied the effects of PDE4 inhibition in a prevention and a treatment model of bleomycin-induced skin fibrosis, in the topoisomerase mouse model as well as in a model of sclerodermatous chronic graft-versus-host disease. To better understand the mode of action of PDE4 blockade in preclinical models of SSc, we investigated fibrosis-relevant mediators in fibroblasts and macrophages from healthy individuals and patients suffering from diffuse-cutaneous SSc on blockade of PDE4...
February 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28205223/abdominal-adiposity-is-not-a-mediator-of-the-protective-effect-of-mediterranean-diet-on-colorectal-cancer
#9
Francesca Fasanelli, Daniela Zugna, Maria Teresa Giraudo, Vittorio Krogh, Sara Grioni, Salvatore Panico, Amalia Mattiello, Giovanna Masala, Saverio Caini, Rosario Tumino, Graziella Frasca, Veronica Sciannameo, Fulvio Ricceri, Carlotta Sacerdote
Adherence to the Mediterranean diet (MD) has a preventive effect on colorectal cancer (CRC). Several biological mechanisms have been hypothesized to explain this effect, but the involvement of clinical mediators has not been experimentally proven. We examined the role of abdominal adiposity (i.e. waist-to-hip ratio, WHR) as a potential mediator of the relationship between the MD and CRC in the Italian centres of the European Prospective Investigation into Cancer and Nutrition. We evaluated the effect of the Italian Mediterranean Index (IMI) on WHR and of WHR on CRC risk...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28204955/inactivation-of-non-canonical-cyclic-nucleotides-hydrolysis-and-transport
#10
Erich H Schneider, Roland Seifert
This chapter addresses cNMP hydrolysis by phosphodiesterases (PDEs) and export by multidrug resistance associated proteins (MRPs). Both mechanisms are well-established for the canonical cNMPs, cAMP, and cGMP. Increasing evidence shows that non-canonical cNMPs (specifically cCMP, cUMP) are also PDE and MRP substrates. Hydrolysis of cUMP is achieved by PDE 3A, 3B, and 9A, which possibly explains the cUMP-degrading activities previously reported for heart, adipose tissue, and brain. Regarding cCMP, the only known "conventional" (class I) PDE that hydrolyzes cCMP is PDE7A...
February 16, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28202289/rolipram-potentiates-bevacizumab-induced-cell-death-in-human-glioblastoma-stem-like-cells
#11
Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Mahmoudreza Hadjighasem, Parisa Hayat, Naser Amini, Mohammad Taghi Joghataei
AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system...
February 12, 2017: Life Sciences
https://www.readbyqxmd.com/read/28201975/selective-inhibition-of-phosphodiesterases-4a-b-c-and-d-isoforms-in-chronic-respiratory-diseases-current-and-future-evidences
#12
Sonia Contreras, Javier Milara, Esteban Morcillo, Julio Cortijo
Chronic respiratory diseases affect millions of people every day. According to World Health Organization estimates, ~235 million people suffer from asthma, ~64 million suffer from chronic obstructive pulmonary disease (COPD), and millions more suffer from allergic rhinitis around the world. In recent last years, the first phosphodiesterase 4 (PDE4) inhibitor, roflumilast, was approved as a treatment to reduce the risk of exacerbations in stable and severe COPD associated with chronic bronchitis and a history of exacerbations...
February 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28196856/vardenafil-reduces-macrophage-pro-inflammatory-overresponses-in-cystic-fibrosis-through-pde5-and-cftr-dependent-mechanisms
#13
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type littermates...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28194663/cilostazol-use-is-associated-with-reduced-risk-of-dementia-a-nationwide-cohort-study
#14
Shu-Yu Tai, Chen-Yu Chien, Yu-Han Chang, Yuan-Han Yang
Whether antiplatelet agents have a preventive effect on cognitive function remains unknown. We examined the potential association between the use of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, and the risk of dementia in an Asian population. Patients initiating cilostazol therapy between 1 January 2004 and 31 December 2009 without a prior history of dementia were identified from Taiwan's National Health Insurance database. Participants were stratified by age, sex, comorbidities, and comedication...
February 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28194402/corrigendum-unfractionated-and-low-molecular-weight-heparin-and-the-phosphodiesterase-inhibitors-ibmx-and-cilostazol-block-ex-vivo-equid-herpesvirus-type-1-induced-platelet-activation
#15
Tracy Stokol, Priscila B S Serpa, Muhammad N Zahid, Marjory B Brooks
[This corrects the article on p. 99 in vol. 3, PMID: 27909693.].
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28194132/molecular-imaging-markers-to-track-huntington-s-disease-pathology
#16
REVIEW
Heather Wilson, Rosa De Micco, Flavia Niccolini, Marios Politis
Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28191858/impact-of-the-pde4d-gene-polymorphism-and-additional-snp-snp-and-gene-smoking-interaction-on-ischemic-stroke-risk-in-chinese-han-population
#17
Xianxiang Wang, Zhongwu Sun, Yiquan Zhang, Xuefeng Tian, Qingxin Li, Jing Luo
AIMS: To investigate the association between phosphodiesterase 4D gene (PDE4D) gene single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) risk, and impact of additional SNP- SNP and gene- smoking interaction on IS risk in Chinese population. METHODS: A total of 1228 subjects (666 males, 562 females) were selected, including 610 IS patients and 618 control subjects. Logistic regression model was used to examine the association between SNPs in PDE4D gene and IS risk...
February 13, 2017: Neurological Research
https://www.readbyqxmd.com/read/28190786/survival-in-portopulmonary-hypertension-outcomes-of-the-united-kingdom-national-pulmonary-arterial-hypertension-registry
#18
Sasiharan Sithamparanathan, Arun Nair, Logan Thirugnanasothy, J Gerry Coghlan, Robin Condliffe, Konstantinos Dimopoulos, Charlie A Elliot, Andrew J Fisher, Sean Gaine, J Simon R Gibbs, Michael A Gatzoulis, Clive E Handler, Luke S Howard, Martin Johnson, David G Kiely, James L Lordan, Andrew J Peacock, Joanna Pepke-Zaba, Benjamin E Schreiber, Karen K K Sheares, Stephen J Wort, Paul A Corris
BACKGROUND: Portopulmonary hypertension (PoPH) is a rare condition associated with poor survival, and the effect of modern therapies that target pulmonary arterial hypertension (PAH) on long-term outcome is unknown. This study investigated the baseline characteristics and survival in the cohort of patients diagnosed with PoPH in the United Kingdom National Pulmonary Hypertension Service. METHODS: A retrospective review was conducted of all incident treatment-naïve patients with PoPH within the United Kingdom national registry diagnosed between January 2001 and December 2010...
December 31, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28188872/pre-transplantation-31-p-magnetic-resonance-spectroscopy-for-quality-assessment-of-human-pancreatic-grafts-a-feasibility-study
#19
Lina Carlbom, Jan Weis, Lars Johansson, Olle Korsgren, Håkan Ahlström
OBJECTIVE: To investigate the feasibility of using (31)P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation. MATERIALS AND METHODS: Pancreata from 5 human donors, 3 males and 2 females, aged 49-78years, with body mass index (BMI) 22-31kg/m(2), were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4°C) for 21-44h...
February 8, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28188618/paroxysmal-hemicrania-like-headache-secondary-to-phosphodiesterase-inhibitors-administration-a-case-report
#20
Arens Taga, Marco Russo, Antonio Genovese, Gian Camillo Manzoni, Paola Torelli
No abstract text is available yet for this article.
February 11, 2017: Headache
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