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PDE or phosphodiesterase

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https://www.readbyqxmd.com/read/28448580/sildenafil-normalizes-bowel-transit-in-preclinical-models-of-constipation
#1
Sarah K Sharman, Bianca N Islam, Yali Hou, Margaux Usry, Allison Bridges, Nagendra Singh, Subbaramiah Sridhar, Satish Rao, Darren D Browning
Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation...
2017: PloS One
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/28442892/bioequivalence-study-of-a-new-sildenafil-100-mg-orodispersible-film-compared-to-the-conventional-film-coated-100-mg-tablet-administered-to-healthy-male-volunteers
#3
Milko Radicioni, Chiara Castiglioni, Andrea Giori, Irma Cupone, Valeria Frangione, Stefano Rovati
A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra(®)) after single-dose administration to 53 healthy male volunteers (aged 18-51 years) in a randomized, open, two-way crossover bioequivalence study...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28439226/the-phosphodiesterase-10a-inhibitor-pf-2545920-enhances-hippocampal-excitability-and-seizure-activity-involving-the-upregulation-of-glua1-and-nr2a-in-post-synaptic-densities
#4
Yanke Zhang, Baobing Gao, Fangshuo Zheng, Shanshan Lu, Yun Li, Yan Xiong, Qin Yang, Yong Yang, Pengfei Fu, Fei Xiao, Xuefeng Wang
Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the strength of excitatory neural circuits and/or decrease inhibitory synaptic plasticity. Abnormally, synchronized synaptic transmission in the brain leads to seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently attracted attention as a potential therapy for neurological and psychiatric disorders. We hypothesized that PF-2545920 plays an important role in status epilepticus (SE) and investigated the underlying mechanisms...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28438565/improvements-in-oocyte-competence-in-superovulated-mice-following-treatment-with-cilostazol-ovulation-of-immature-oocytes-with-high-developmental-rates
#5
Ahmed M Taiyeb, Saeeda A Muhsen-Alanssari, William L Dees, Jill Hiney, Michael E Kjelland, Duane C Kraemer, Mundhir T Ridha-Albarzanchi
Exogenous administration of superovulatory hormones negatively affects oocyte competence in mammals. Phosphodiesterase 3A inhibitors were found to improve competence of oocytes matured in vitro in several species, including humans. This study was therefore designed to define oocyte maturation synchronization and competence in superovulated mice treated with cilostazol, a selective phosphodiesterase 3A inhibitor. Swiss Webster mice were superovulated and treated orally with 7.5mg cilostazol once or twice to result in ovulation of immature oocytes at the metaphase I (MI) or germinal vesicle (GV) stage, respectively...
April 21, 2017: Biochemical Pharmacology
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
#6
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/28437655/peripheral-artery-disease-redox-signaling-oxidative-stress-basic-and-clinical-aspects
#7
REVIEW
Sebastian Steven, Andreas Daiber, Jörn F Dopheide, Thomas Münzel, Christine Espinola-Klein
Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage)...
April 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28436911/sampled-data-fuzzy-control-for-nonlinear-coupled-parabolic-pde-ode-systems
#8
Zi-Peng Wang, Huai-Ning Wu, Han-Xiong Li
In this paper, a sampled-data fuzzy control problem is addressed for a class of nonlinear coupled systems, which are described by a parabolic partial differential equation (PDE) and an ordinary differential equation (ODE). Initially, the nonlinear coupled system is accurately represented by the Takagi-Sugeno (T-S) fuzzy coupled parabolic PDE-ODE model. Then, based on the T-S fuzzy model, a novel time-dependent Lyapunov functional is used to design a sampled-data fuzzy controller such that the closed-loop coupled system is exponentially stable, where the sampled-data fuzzy controller consists of the ODE state feedback and the PDE static output feedback under spatially averaged measurements...
April 17, 2017: IEEE Transactions on Cybernetics
https://www.readbyqxmd.com/read/28436147/rapid-detection-of-six-phosphodiesterase-type-5-enzyme-inhibitors-in-health-care-products-using-thin-layer-chromatography-and-surface-enhanced-raman-spectroscopy-combined-with-bp-neural-network
#9
Xiaopeng Hu, Guozhen Fang, Ailing Han, Yunpeng Fu, Rui Tong, Shuo Wang
A novel facile method for the detection of the phosphodiesterase type 5 enzyme inhibitors added illegally into health products was established using thin-layer chromatography and surface enhanced Raman spectroscopy combined with BP neural network. When the detecting conditions were optimized in detail, a repetitive adding procedure of silver colloids with the total amount keeping constant was used to improve the enhancement effect of surface enhanced Raman spectroscopy. According to the main Raman peaks and the retention factor of analyte, the data predictive model was established...
April 24, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28434676/meta-analysis-of-results-of-testosterone-therapy-on-sexual-function-based-on-international-index-of-erectile-function-scores
#10
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
#11
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
#12
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
#13
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/28428823/combining-manipulation-of-transcription-factors-and-overexpression-of-the-target-genes-to-enhance-lignocellulolytic-enzyme-production-in-penicillium-oxalicum
#14
Liwei Gao, Zhonghai Li, Chengqiang Xia, Yinbo Qu, Meng Liu, Piao Yang, Lele Yu, Xin Song
BACKGROUND: Lignocellulolytic enzymes are the main enzymes to saccharify lignocellulose from renewable plant biomass in the bio-based economy. The production of these enzymes is transcriptionally regulated by multiple transcription factors. We previously engineered Penicillium oxalicum for improved cellulase production via manipulation of three genes in the cellulase expression regulatory network. However, the potential of combinational engineering of multiple regulators and their targets at protein abundance and activity levels has not been fully explored...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28427395/protein-antigen-of-bird-related-hypersensitivity-pneumonitis-in-pigeon-serum-and-dropping
#15
Tsuyoshi Shirai, Haruhiko Furusawa, Asuka Furukawa, Yuki Ishige, Keisuke Uchida, Yasunari Miyazaki, Yoshinobu Eishi, Naohiko Inase
BACKGROUND: Avian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated. METHOD: Pigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers...
April 20, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28427099/role-of-phosphodiesterases-on-the-function-of-aryl-hydrocarbon-receptor-interacting-protein-aip-in-the-pituitary-gland-and-on-the-evaluation-of-aip-gene-variants
#16
Laura C Hernández-Ramírez, Giampaolo Trivellin, Constantine A Stratakis
Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by loss-of-function germline mutations in the AIP gene. Patients harboring AIP mutations usually present with somatotropinomas resulting either in gigantism or young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor suppressor properties in somatotroph cells. Among other mechanisms proposed to explain this function, a regulatory effect over the 3',5'-cyclic adenosine monophosphate (cAMP) signaling pathway seems to play a prominent role...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28427096/pde-2015-camp-signaling-protein-kinase-a-pka-and-phosphodiesterases-pdes-how-genetics-changed-the-way-we-look-at-one-of-the-most-studied-signaling-pathways
#17
Constantine A Stratakis, Fahrettin Kelestimur, Jérôme Bertherat
No abstract text is available yet for this article.
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28427004/enzymatic-activity-of-the-cam-pde1-system-upon-addition-of-actinyl-ions
#18
Florian Brulfert, Samir Safi, Aurélie Jeanson, Harald Foerstendorf, Stephan Weiss, Catherine Berthomieu, Sandrine Sauge-Merle, Éric Simoni
The threat of a dirty bomb which could cause internal contamination has been of major concern for the past decades. Because of their high chemical toxicity and their presence in the nuclear fuel cycle, uranium and neptunium are two actinides of high interest. Calmodulin (CaM) which is a ubiquitous protein present in all eukaryotic cells and is involved in calcium-dependent signaling pathways has a known affinity for uranyl and neptunyl ions. The impact of the complexation of these actinides on the physiological response of the protein remains, however, largely unknown...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28426333/existence-and-uniqueness-for-a-coupled-pde-model-for-motor-induced-microtubule-organization
#19
Thomas Hillen, Diana White, Gerda de Vries, Adriana Dawes
Microtubules (MTs) are protein filaments that provide structure to the cytoskeleton of cells and a platform for the movement of intracellular substances. The spatial organization of MTs is crucial for a cell's form and function. MTs interact with a class of proteins called motor proteins that can transport and position individual filaments, thus contributing to overall organization. In this paper, we study the mathematical properties of a coupled partial differential equation (PDE) model, introduced by White et al...
April 20, 2017: Journal of Biological Dynamics
https://www.readbyqxmd.com/read/28425346/ambrisentan-a-review-of-its-use-in-pulmonary-arterial-hypertension
#20
Belinda N Rivera-Lebron, Michael G Risbano
Pulmonary arterial hypertension (PAH) is a progressive disease defined by an elevation in pulmonary arterial pressure that can lead to right heart failure and death. Ambrisentan is a selective endothelin receptor antagonist approved for the treatment of idiopathic, heritable PAH and connective tissue disease-associated PAH. Ambrisentan has been shown to improve exercise capacity and hemodynamics with an acceptable side-effect profile. It has also proven to be safely used in combination with other PAH-specific medications, especially with phosphodiesterase-5 inhibitors...
April 1, 2017: Therapeutic Advances in Respiratory Disease
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