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PDE or phosphodiesterase

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https://www.readbyqxmd.com/read/28101622/-use-of-vasopressors-and-inotropics-in-cardiogenic-shock
#1
H Lemm, S Dietz, M Janusch, M Buerke
Vasoactive drugs and inotropic agents are important for the hemodynamic management of cardiogenic shock. In this article the use of different vasoactive and ionotropic drugs in cardiogenic shock is presented. Hemodynamic management during cardiogenic shock occurs after initial moderate volume delivery by dobutamine to increase inotropism. If adequate perfusion pressures are not achieved norepinephrine is administered. If a sufficient increase in cardiac performance can still not be achieved by the treatment, administration of levosimendan or phosphodiesterase (PDE) inhibitors may be necessary...
January 18, 2017: Herz
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#2
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28097089/selective-inhibition-of-phosphodiesterases-4-5-and-9-induces-hsp20-phosphorylation-and-attenuates-amyloid-beta-1-42-mediated-cytotoxicity
#3
Ryan T Cameron, Ellanor Whiteley, Jon P Day, Anna I Parachikova, George S Baillie
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...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28096287/prediction-models-for-exacerbations-in-patients-with-copd
#4
REVIEW
Beniamino Guerra, Violeta Gaveikaite, Camilla Bianchi, Milo A Puhan
Personalised medicine aims to tailor medical decisions to the individual patient. A possible approach is to stratify patients according to the risk of adverse outcomes such as exacerbations in chronic obstructive pulmonary disease (COPD). Risk-stratified approaches are particularly attractive for drugs like inhaled corticosteroids or phosphodiesterase-4 inhibitors that reduce exacerbations but are associated with harms. However, it is currently not clear which models are best to predict exacerbations in patients with COPD...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28094963/four-step-total-synthesis-of-selaginpulvilin-d
#5
Madison J Sowden, Michael S Sherburn
An extremely concise total synthesis of a potent phosphodiesterase-4 inhibitory natural product, selaginpulvilin D, is reported. The synthesis features a one-pot, 3-fold electrophilic aromatic substitution sequence to assemble a 9,9-diarylfluorene core. The approach allows access to useful quantities of a selaginpulvilin natural product for the first time.
January 17, 2017: Organic Letters
https://www.readbyqxmd.com/read/28093982/pde7-selective-and-dual-inhibitors-advances-in-chemical-and-biological-research
#6
Agnieszka Jankowska, Artur Świerczek, Grażyna Chłoń-Rzepa, Maciej Pawłowski, Elżbieta Wyska
A Phosphodiesterase 7 (PDE7) is an intracellular enzyme that specifically hydrolyses the second messenger, cyclic-3',5'-adenosine monophosphate (cAMP), into inactive non-cyclic nucleotide, 5'-AMP. To date, many structurally diverse compounds with PDE7 inhibitory properties have been described, including selective PDE7 inhibitors, dual PDE4/PDE7, PDE7/PDE8, and PDE7/GSK-3 inhibitors, and non-selective PDE inhibitors with high affinity for PDE7. Inhibitors of PDE7 provided beneficial effects in animal models of inflammatory and neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and many others...
January 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28092955/flow-optimization-in-vascular-networks
#7
Radu C Cascaval, Ciro D'Apice, Maria Pia D'Arienzo, Rosanna Manzo
The development of mathematical models for studying phenomena observed in vascular networks is very useful for its potential applications in medicine and physiology. Detailed 3D studies of flow in the arterial system based on the Navier-Stokes equations require high computational power, hence reduced models are often used, both for the constitutive laws and the spatial domain. In order to capture the major features of the phenomena under study, such as variations in arterial pressure and flow velocity, the resulting PDE models on networks require appropriate junction and boundary conditions...
June 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28092946/carcinogenesis-of-the-oral-cavity-environmental-causes-and-potential-prevention-by-black-raspberry
#8
Karam El-Bayoumy, Kun-Ming Chen, Shang-Min Zhang, Yuan-Wan Sun, Shantu Amin, Gary Stoner, Joseph B Guttenplan
Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092671/pde4d-promotes-fak-mediated-cell-invasion-in-braf-mutated-melanoma
#9
J Delyon, A Servy, F Laugier, J André, N Ortonne, M Battistella, S Mourah, A Bensussan, C Lebbé, N Dumaz
The cyclic AMP (cAMP) signaling pathway is critical in melanocyte biology for regulating differentiation. It is downregulated by phosphodiesterase (PDE) enzymes, which degrade cAMP itself. In melanoma evidence suggests that inhibition of the cAMP pathway by PDE type 4 (PDE4) favors tumor progression. For example, in melanomas harboring RAS mutations, the overexpression of PDE4 is crucial for MAPK pathway activation and proliferation induced by oncogenic RAS. Here we showed that PDE4D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cAMP pathway activation...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28091532/development-of-the-neuroimmune-modulator-ibudilast-for-the-treatment-of-alcoholism-a-randomized-placebo-controlled-human-laboratory-trial
#10
Lara A Ray, Spencer Bujarski, Steve Shoptaw, Daniel Jo Roche, Keith Heinzerling, Karen Miotto
Current directions in medication development for alcohol use disorder (AUD) emphasize the need to identify novel molecular targets and efficiently screen new compounds aimed at those targets. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterases -4 and -10 and macrophage migration inhibitory factor and was recently found to reduce alcohol intake in rats by approximately 50%. To advance medications development for AUD, the present study consists of a randomized, crossover, double-blind, placebo-controlled laboratory study of IBUD in non-treatment seeking individuals with current (ie, past month) mild-to-severe AUD...
January 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28090289/an-international-physician-survey-of-chronic-thromboembolic-pulmonary-hypertension-management
#11
Henning Gall, Ioana R Preston, Barbara Hinzmann, Sabina Heinz, David Jenkins, Nick H Kim, Irene Lang
We conducted an international study to evaluate practices in the diagnosis and management of patients with chronic thromboembolic pulmonary hypertension (CTEPH) globally across different regions. Between August and October 2012, CTEPH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 2-5 most recent patients with CTEPH. Overall, 496 physicians (Europe: 260; United States: 152; Argentina: 52; Japan: 32) completed the questionnaire and provided patient record data for 1,748 patients...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089463/anti-inflammatory-effects-of-the-selective-phosphodiesterase-3-inhibitor-cilostazol-and-antioxidants-enzymatically-modified-isoquercitrin-and-%C3%AE-lipoic-acid-reduce-dextran-sulphate-sodium-induced-colorectal-mucosal-injury-in-mice
#12
Yumi Kangawa, Toshinori Yoshida, Hajime Abe, Yoshiki Seto, Taishi Miyashita, Michi Nakamura, Tohru Kihara, Shim-Mo Hayashi, Makoto Shibutani
Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0...
January 12, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28088261/parquetina-nigrescens-leaves-chemical-profile-and-influence-on-the-physical-and-biochemical-indices-of-sexual-activity-of-male-wistar-rats
#13
Omowumi Titilola Kayode, Musa Toyin Yakubu
OBJECTIVE: The leaves of Parquetina nigrescens have been claimed in folk medicine to be useful for managing sexual dysfunction, but there is inadequate scientific evidence for this claim. This investigation was conducted to assess the effects of aqueous leaf extract of Parquetina nigrescens (AEPN) in rats induced with sexual dysfunction. METHODS: Male rats were allocated into various groups after being induced into sexual dysfunction with paroxetine hydrochloride...
January 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28087462/impact-of-disease-linked-mutations-targeting-the-oligomerization-interfaces-of-aldehyde-dehydrogenase-7a1
#14
David A Korasick, John J Tanner, Michael T Henzl
Aldehyde dehydrogenase 7A1 (ALDH7A1) is involved in lysine catabolism, catalyzing the oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Certain mutations in the ALDH7A1 gene, which are presumed to reduce catalytic activity, cause an autosomal recessive seizure disorder known as pyridoxine-dependent epilepsy (PDE). Although the genetic association between ALDH7A1 and PDE is well established, little is known about the impact of PDE-mutations on the structure and catalytic function of the enzyme. Herein we report the first study of the molecular consequences of PDE mutations using purified ALDH7A1 variants...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28087362/clinical-phenotypes-and-outcomes-of-heritable-and-sporadic-pulmonary-veno-occlusive-disease-a-population-based-study
#15
David Montani, Barbara Girerd, Xavier Jaïs, Marilyne Levy, David Amar, Laurent Savale, Peter Dorfmüller, Andrei Seferian, Edmund M Lau, Mélanie Eyries, Jérôme Le Pavec, Florence Parent, Damien Bonnet, Florent Soubrier, Elie Fadel, Olivier Sitbon, Gérald Simonneau, Marc Humbert
BACKGROUND: Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH. METHODS: We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases)...
January 10, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28080219/adipose-tissue-insulin-resistance-in-gestational-diabetes
#16
Batbayar Tumurbaatar, Aaron T Poole, Gayle Olson, Michel Makhlouf, Hanaa S Sallam, Shwetha Thukuntla, Sucharitha Kankanala, Obos Ekhaese, Guillermo Gomez, Manisha Chandalia, Nicola Abate
BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1...
January 12, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28076795/hangover-links-nuclear-rna-signaling-to-camp-regulation-via-the-phosphodiesterase-4d-ortholog-dunce
#17
Manuela Ruppert, Mirjam Franz, Anastasios Saratsis, Laura Velo Escarcena, Oliver Hendrich, Li Ming Gooi, Isabell Schwenkert, Ansgar Klebes, Henrike Scholz
The hangover gene defines a cellular stress pathway that is required for rapid ethanol tolerance in Drosophila melanogaster. To understand how cellular stress changes neuronal function, we analyzed Hangover function on a cellular and neuronal level. We provide evidence that Hangover acts as a nuclear RNA binding protein and we identified the phosphodiesterase 4d ortholog dunce as a target RNA. We generated a transcript-specific dunce mutant that is impaired not only in ethanol tolerance but also in the cellular stress response...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076777/antagonistic-functions-of-mbp-and-cnp-establish-cytosolic-channels-in-cns-myelin
#18
Nicolas Snaidero, Caroline Velte, Matti Myllykoski, Arne Raasakka, Alexander Ignatev, Hauke B Werner, Michelle S Erwig, Wiebke Möbius, Petri Kursula, Klaus-Armin Nave, Mikael Simons
The myelin sheath is a multilamellar plasma membrane extension of highly specialized glial cells laid down in regularly spaced segments along axons. Recent studies indicate that myelin is metabolically active and capable of communicating with the underlying axon. To be functionally connected to the neuron, oligodendrocytes maintain non-compacted myelin as cytoplasmic nanochannels. Here, we used high-pressure freezing for electron microscopy to study these cytoplasmic regions within myelin close to their native state...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076654/estimating-varying-coefficients-for-partial-differential-equation-models
#19
Xinyu Zhang, Jiguo Cao, Raymond J Carroll
Partial differential equations (PDEs) are used to model complex dynamical systems in multiple dimensions, and their parameters often have important scientific interpretations. In some applications, PDE parameters are not constant but can change depending on the values of covariates, a feature that we call varying coefficients. We propose a parameter cascading method to estimate varying coefficients in PDE models from noisy data. Our estimates of the varying coefficients are shown to be consistent and asymptotically normally distributed...
January 11, 2017: Biometrics
https://www.readbyqxmd.com/read/28074710/canine-spinal-cord-glioma
#20
Daniel R Rissi, Renee Barber, Annabelle Burnum, Andrew D Miller
Spinal cord glioma is uncommonly reported in dogs. We describe the clinicopathologic and diagnostic features of 7 cases of canine spinal cord glioma and briefly review the veterinary literature on this topic. The median age at presentation was 7.2 y. Six females and 1 male were affected and 4 dogs were brachycephalic. The clinical course lasted from 3 d to 12 wk, and clinical signs were progressive and associated with multiple suspected neuroanatomic locations in the spinal cord. Magnetic resonance imaging of 6 cases revealed T2-weighted hyperintense lesions with variable contrast enhancement in the spinal cord...
January 2017: Journal of Veterinary Diagnostic Investigation
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