keyword
MENU ▼
Read by QxMD icon Read
search

Phosphodiesterase 4

keyword
https://www.readbyqxmd.com/read/28454120/phosphodiesterase-3a-a-new-player-in-development-of-interstitial-cells-of-cajal-and-a-prospective-target-in-gastrointestinal-stromal-tumors-gist
#1
Pierre Vandenberghe, Perrine Hagué, Steven C Hockman, Vincent C Manganiello, Pieter Demetter, Christophe Erneux, Jean-Marie Vanderwinden
We previously identified phosphodiesterase 3A (PDE3A) as a marker for interstitial cells of Cajal (ICC) in adult mouse gut. However, PDE3A expression and function during gut development and in ICC-derived gastrointestinal stromal tumors (GIST) remained unknown. Here we found that PDE3A was expressed throughout ICC development and that ICC density was halved in PDE3A-deficient mice. In the human imatinib-sensitive GIST882 cell line, the PDE3 inhibitor cilostazol halved cell viability (IC50 0.35 μM) and this effect synergized with imatinib (Chou-Talalay's CI50 0...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443667/identification-of-a-phosphodiesterase-inhibiting-fraction-from-roasted-coffee-coffea-arabica-through-activity-guided-fractionation
#2
Teresa Röhrig, David Liesenfeld, Elke Richling
Recent reports that coffee can significantly inhibit cAMP phosphodiesterases (PDE) in vitro, as well as in vivo, have added another beneficial effect of coffee consumption. However, the PDE-inhibiting substances remain mostly unknown. We chose activity-guided fractionation and an in vitro test system to identify the coffee components responsible for PDE inhibition. This approach indicated that a fraction of melanoidins reveals strong PDE inhibiting potential (IC50 = 130 ± 42 µg/mL). These melanoidins were characterized as water soluble, low molecular weight melanoidins (< 3kDa) with a nitrogen content of 4...
April 26, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28438557/the-isozyme-selective-phosphodiesterase-4-inhibitor-abi-4-attenuates-the-effects-of-lipopolysaccharide-in-human-cells-and-rodent-models-of-peripheral-and-cns-inflammation
#3
Joseph R Hedde, Ashley N Hanks, Christopher J Schmidt, Zoë A Hughes
Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent (EC50 ∼14 nM) inhibitor of lipopolysaccharide (LPS) induced TNF-α release from mouse microglia and human PBMCs. ABI-4 (0.32 mg/kg) blocked LPS-induced release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in blood and brain of mice...
April 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28434676/meta-analysis-of-results-of-testosterone-therapy-on-sexual-function-based-on-international-index-of-erectile-function-scores
#4
Giovanni Corona, Giulia Rastrelli, Abraham Morgentaler, Alessandra Sforza, Edoardo Mannucci, Mario Maggi
CONTEXT: The interpretation of available clinical evidence related to the effect of testosterone (T) treatment (TTh) on sexual function has been inconsistent, in part due to the use of different and self-reported measures to assess outcomes. The International Index of Erectile Function (IIEF) is the most frequently used validated tool to assess male sexual function. OBJECTIVE: To perform a meta-analysis of available data evaluating the effect of TTh on male sexual function using IIEF as the primary outcome...
April 20, 2017: European Urology
https://www.readbyqxmd.com/read/28432317/psiguajadials-a-k-unusual-psidium-meroterpenoids-as-phosphodiesterase-4-inhibitors-from-the-leaves-of-psidium-guajava
#5
Gui-Hua Tang, Zhen Dong, Yan-Qiong Guo, Zhong-Bin Cheng, Chu-Jun Zhou, Sheng Yin
Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A-K (1-11), along with 17 known ones (12-28). Their structures and absolute configurations were elucidated by spectroscopic methods and comparison of experimental and calculated ECD. Compounds 1 and 2 represent two unprecedented skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3 is the first example of Psidium meroterpenoids coupling via an oxepane ring...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431996/comparison-of-silodosin-monotherapy-versus-silodosin-with-tadalafil-add-on-therapy-in-patients-with-benign-prostatic-hyperplasia
#6
Takashi Yoshida, Hidefumi Kinoshita, Seiji Shimada, Makoto Taguchi, Tadashi Matsuda
OBJECTIVE: To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil for patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) treated with the α1-adrenoceptor blocker silodosin. METHODS: We analyzed 103 patients with LUTS/BPH with an International Prostate Symptom Score (IPSS) of >8 after ≥4 weeks of silodosin treatment from April 2016 through December 2016 at Kori Hospital...
April 18, 2017: Urology
https://www.readbyqxmd.com/read/28429038/-phosphodiesterase-4-inhibition-for-treatment-of-endothelial-barrier-and-microcirculation-disorders-in-sepsis
#7
REVIEW
J Wollborn, N Schlegel, M A Schick
Sepsis is commonly associated with loss of microvascular endothelial barrier function (capillary leak) and dysfunctional microcirculation, which both promote organ failure. The development of a distinct therapy of impaired endothelial barrier function and disturbed microcirculation is highly relevant because both of these phenomena constitute crucial processes which critically influence the prognosis of patients. Numerous in vivo and in vitro trials over the past years have fostered a better understanding of the pathophysiology of capillary leak...
April 20, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28421639/cilostazol-adjunctive-therapy-in-treatment-of-negative-symptoms-in-chronic-schizophrenia-randomized-double-blind-placebo-controlled-study
#8
Farzin Rezaei, Bita Mesgarpour, Alireza Jeddian, Atefeh Zeionoddini, Payam Mohammadinejad, Elaheh Salardini, Mona Shahriari, Arefeh Zeinoddini, Shahin Akhondzadeh
OBJECTIVE: To evaluate the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase III, as an adjunctive to risperidone in alleviating the negative symptoms of schizophrenia. METHODS: Eighty-four in-patients with diagnosis of chronic schizophrenia participated in a randomized, placebo-controlled trial and underwent 8 weeks of treatment with either cilostazol (50 mg twice a day) or placebo as an adjuvant to risperidone. Participants were assessed using the positive and negative syndrome scale (PANSS) at baseline and at weeks 2, 4, 6, and 8...
April 18, 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28420826/efficacy-and-safety-of-an-orally-administered-selective-prostacyclin-receptor-agonist-selexipag-in-japanese-patients-with-pulmonary-arterial-hypertension
#9
Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika Takeishi, Mitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama
BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28419462/modeling-and-simulation-of-pivotal-clinical-trials-using-linked-models-for-multiple-endpoints-in-chronic-obstructive-pulmonary-disease-with-roflumilast
#10
Axel Facius, Andreas Krause, Laurent Claret, Rene Bruno, Gezim Lahu
Roflumilast is a selective phosphodiesterase 4 inhibitor (PDE4i) for the treatment of severe chronic obstructive pulmonary disease (COPD). In 2 large phase 3 trials in a broader population of COPD patients (BY217/M2-111, ClinicalTrials.gov: NCT00076089 and BY217/M2-112, ClinicalTrials.gov: NCT00430729), treatment with roflumilast reduced the rate of exacerbations; however, the reduction did not reach statistical significance. Two linked dose-response models for the primary (annualized COPD exacerbation counts) and secondary (change from baseline in forced expiratory volume in 1 second [FEV1 ]) end points were therefore developed to characterize and quantify effect sizes and the patient characteristics influencing them...
April 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28416366/2-year-animal-carcinogenicity-results-for-crisaborole-a-novel-phosphodiesterase-4-inhibitor-for-atopic-dermatitis
#11
Vic Ciaravino, Dina Coronado, Cheryl Lanphear, Sanjay Chanda
BACKGROUND: Crisaborole is a novel, topical nonsteroidal, anti-inflammatory, phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild to moderate atopic dermatitis. OBJECTIVE: As part of a nonclinical safety testing program, these 2-year studies tested the carcinogenic potential of crisaborole. METHODS: Crisaborole ointment, 2%, 5%, or 7%, was applied once daily topically to mice, and crisaborole was administered orally to rats at doses of 30, 100, or 300mg/kg/day for up to 104 weeks...
March 30, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28414142/doxofylline-does-not-increase-formoterol-induced-camp-nor-mkp-1-expression-in-asm-cells-resulting-in-lack-of-anti-inflammatory-effect
#12
Brijeshkumar S Patel, Michael J Kugel, Gina Baehring, Alaina J Ammit
The xanthine doxofylline has been examined in clinical trials and shown to have efficacy and greater tolerability than theophylline in asthma and chronic obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental models of respiratory disease. However, there are limited studies in vitro. We address this herein and examine whether doxofylline has anti-inflammatory impact on primary cultures of airway smooth muscle (ASM) cells...
April 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28414103/apoptosis-induction-of-poly-s-nitrosated-human-serum-albumin-in-resistant-solid-tumor-under-hypoxia-can-be-restored-by-phosphodiesterase-5-inhibition
#13
Mayumi Ikeda, Yu Ishima, Victor T G Chuang, Tsuyoshi Ikeda, Ryo Kinoshita, Hiroshi Watanabe, Tatsuhiro Ishida, Masaki Otagiri, Toru Maruyama
Poly-S-nitrosated human serum albumin (Poly-SNO-HSA) delivered and accumulated nitric oxide (NO) in tumors and induces apoptosis. Tumor hypoxia is strongly associated with malignant progression and tumor resistance to therapy. In this study, we examined the cytotoxic effect of Poly-SNO-HSA under hypoxia on the murine colon 26 adenocarcinoma (C26) cells in vitro and in vivo. Under hypoxia, at about 4 times LD50 dose of Poly-SNO-HSA in vitro, the reactive oxygen species production was hindered but apoptotic cells were induced via cGMP pathway as the effect was suppressed by a soluble guanylate cyclase inhibitor, NS2028...
April 13, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28406621/discovery-of-selective-phosphodiesterase-1-inhibitors-with-memory-enhancing-properties
#14
Brian Dyck, Bryan Branstetter, Tawfik Gharbaoui, Andrew R Hudson, J Guy Breitenbucher, Laurent Gomez, Iriny Botrous, Tami Marrone, Richard Barido, Charles K Allerston, E Peder Cedervall, Rui Xu, Vandana Sridhar, Ryan Barker, Kathleen Aertgeerts, Kara Schmelzer, David Neul, Dong Lee, Mark Eben Massari, Carsten B Andersen, Kristen Sebring, Xianbo Zhou, Robert Petroski, James Limberis, Martin Augustin, Lawrence E Chun, Thomas E Edwards, Marco Peters, Ali Tabatabaei
A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures of example compounds from this series in complex with the catalytic domain of PDE1B and PDE10A were determined, allowing optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led to greater than a 3000-fold selectivity for PDE1B over hERG. 6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one was identified as an orally bioavailable and brain penetrating PDE1B enzyme inhibitor with potent memory-enhancing effects in a rat model of object recognition memory...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28405029/protein-kinase-enzymes-in-the-human-vagina-relation-to-key-mediators-of-the-cyclic-amp-and-cyclic-gmp-pathways
#15
S Ückert, J Sonnenberg, J E Sonnenberg, W Kauffels, K Albrecht, M A Kuczyk, P Hedlund
Aside from phosphodiesterase (PDE) isoenzymes, protein kinases (cAK=cyclic AMP-binding protein kinase, cGK=cyclic GMP-binding protein kinase) have also been identified as important receptors for cyclic nucleotides. A significance of protein kinases in the control of the function of the male and female reproductive tract has been suggested; however, up until today, only a few approaches have addressed these enzymes in female genital tissues. The present study aimed to investigate by means of biochemical and immunohistochemical methods the expression of cAK and cGK...
April 13, 2017: International Journal of Impotence Research
https://www.readbyqxmd.com/read/28402318/memory-enhancing-effects-of-gebr-32a-a-new-pde4d-inhibitor-holding-promise-for-the-treatment-of-alzheimer-s-disease
#16
Roberta Ricciarelli, Chiara Brullo, Jos Prickaerts, Ottavio Arancio, Carla Villa, Claudia Rebosio, Elisa Calcagno, Matilde Balbi, Britt T J van Hagen, Elentina K Argyrousi, Hong Zhang, Maria Adelaide Pronzato, Olga Bruno, Ernesto Fedele
Memory loss characterizes several neurodegenerative disorders, including Alzheimer's disease (AD). Inhibition of type 4 phosphodiesterase (PDE4) and elevation of cyclic adenosine monophosphate (cAMP) has emerged as a promising therapeutic approach to treat cognitive deficits. However, PDE4 exists in several isoforms and pan inhibitors cannot be used in humans due to severe emesis. Here, we present GEBR-32a, a new PDE4D full inhibitor that has been characterized both in vitro and in vivo using biochemical, electrophysiological and behavioural analyses...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28398017/differential-effects-of-phosphodiesterase-5-inhibition-in-chronic-cardiac-decompensation-depending-on-the-type-whether-hfref-or-hfpef-of-heart-failure-a-meta-analysis
#17
Renato DE Vecchis, Arturo Cesaro, Carmelina Ariano
INTRODUCTION: According to 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension(PH), no specific drug is currently indicated for PH related to left heart disease( PH-LDH), i.e., the one secondary to left chronic heart failure (CHF), which coincides with the group 2 of the PH classification endorsed by the above-mentioned guidelines. In fact, adoption of therapies that specifically apply for so-called pulmonary arterial hypertension (group 1 of the PH classification) has been regarded as substantially contraindicated in patients with PH- LHD, according to current ESC/ERS guidelines...
April 10, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/28391657/apremilast-an-oral-phosphodiesterase-4-inhibitor-in-the-treatment-of-japanese-patients-with-moderate-to-severe-plaque-psoriasis-efficacy-safety-and-tolerability-results-from-a-phase-2b-randomized-controlled-trial
#18
Mamitaro Ohtsuki, Yukari Okubo, Mayumi Komine, Shinichi Imafuku, Robert M Day, Peng Chen, Rosemary Petric, Allan Maroli, Osamu Nemoto
Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68...
April 9, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28390814/meeting-report-of-the-pathogenesis-of-pemphigus-and-pemphigoid-meeting-in-munich-september-2016
#19
Enno Schmidt, Volker Spindler, Rüdiger Eming, Masayuki Amagai, Frank Antonicelli, John F Baines, Meriem Belheouane, Philippe Bernard, Luca Borradori, Marzia Caproni, Giovanni Di Zenzo, Sergei Grando, Karen Harman, Marcel F Jonkman, Hiroshi Koga, Ralf J Ludwig, Andrew P Kowalczyk, Eliane J Müller, Wataru Nishie, Hendri Pas, Aimee S Payne, Christian D Sadik, Allan Seppänen, Jane Setterfield, Hiroshi Shimizu, Animesh A Sinha, Eli Sprecher, Michael Sticherling, Hideyuki Ujiie, Detlef Zillikens, Michael Hertl, Jens Waschke
Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lübeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases...
April 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28389413/influence-of-cell-confluence-on-the-camp-signalling-pathway-in-vascular-smooth-muscle-cells
#20
M Belacel-Ouari, L Zhang, F Hubert, R Assaly, R Gerbier, R Jockers, F Dauphin, P Lechêne, R Fischmeister, B Manoury, V Leblais
The influence of cell confluence on the β-adrenoceptor (β-AR)/cAMP/phosphodiesterase (PDE) pathway was investigated in cultured rat aortic smooth muscle cells (RASMCs). Cells were plated either at low density (LD: 3·10(3)cells/cm(2)) or high density (HD: 3·10(4)cells/cm(2)) corresponding to non-confluent or confluent cells, respectively, on the day of experiment. β-AR-stimulated cAMP was monitored in real-time using the fluorescence resonance energy transfer (FRET)-based cAMP sensor, Epac2-camps. A brief application (15s) of the β-AR agonist isoprenaline (Iso) induced a typical transient FRET signal, reflecting cAMP production followed by its rapid degradation...
April 4, 2017: Cellular Signalling
keyword
keyword
29573
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"