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PDE or phosphodiesterase

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https://www.readbyqxmd.com/read/29784642/identification-of-key-lipids-critical-for-platelet-activation-by-comprehensive-analysis-of-the-platelet-lipidome
#1
Bing Peng, Sascha Geue, Cristina Coman, Patrick Münzer, Dominik Kopczynski, Canan Has, Nils Hoffmann, Mailin-Christin Manke, Florian Lang, Albert Sickmann, Meinrad Gawaz, Oliver Borst, Robert Ahrends
Platelet integrity and function critically depend on lipid composition. However, the lipid inventory in platelets was hitherto not quantified. Here, we examined the lipidome of murine platelets using lipid-category tailored protocols on a quantitative lipidomics platform. We could show that the platelet lipidome comprises almost 400 lipid species and covers a concentration range of seven orders of magnitude. A systematic comparison of the lipidomics network in resting and activated murine platelets, validated in human platelets, revealed that less than 20% of the platelet lipidome is changed upon activation, involving mainly lipids containing arachidonic acid...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29783211/-the-association-between-enpp1-rs997509-polymorphism-and-type-2-diabetes-mellitus-development-in-ukrainian-population
#2
Irina V Marchenko, Yevhen I Dubovyk, Gennadii F Tkach, Olena S Maksymova, Olha I Matlai, Alexander V Ataman, Viktoriia Yu Harbuzova
OBJECTIVE: Introduction: Genome-Wide Association Studies have identified a large number of polymorphic loci associated with type 2 diabetes mellitus (T2DM). Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) gene is one of the candidate genes which have primary importance in T2DM development. Several studies revealed the association between ENPP1 polymorphisms, including rs997509, and T2DM, obesity, insulin resistance and metabolic syndrome in different populations. The aim: To test the association between ENPP1 rs997509 polymorphism and T2DM development in patients with different risk factors in the Ukrainian population...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29783161/candidate-gene-analysis-in-the-s%C3%A3-o-paulo-epidemiologic-sleep-study-episono-shows-an-association-of-variant-in-pde4d-and-sleepiness
#3
Victoria M Pak, Diego R Mazzotti, Brendan T Keenan, Camila Hirotsu, Philip Gehrman, Lia Bittencourt, Allan I Pack, Sergio Tufik
INTRODUCTION: Sleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D)...
January 12, 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29782174/expression-of-concentrative-nucleoside-transporters-slc28a-in-the-human-placenta-effects-of-gestation-age-and-prototype-differentiation-affecting-agents
#4
Lucie Jiraskova, Lukas Cerveny, Sara Karbanova, Zuzana Ptackova, Frantisek Staud
Equilibrative ( SLC29A) and concentrative ( SLC28A) nucleoside transporters contribute to proper placental development and mediate uptake of nucleosides/nucleoside-derived drugs. We analyzed placental expression of SLC28A mRNA during gestation. Moreover, we studied in choriocarcinoma-derived BeWo cells whether SLC29A and SLC28A mRNA levels can be modulated by activity of adenylyl cyclase, retinoic acid receptor activation, CpG islands methylation, or histone acetylation, using forskolin, all- trans-retinoic acid, and 5-azacytidine, and sodium butyrate/sodium valproate, respectively...
May 21, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29780645/sustained-regression-of-hydroxycarbamide-induced-actinic-keratoses-after-switching-to-anagrelide
#5
Georgios Gaitanis, Dora Gougopoulou, Eleni Kapsali, Ioannis D Bassukas
Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatment with HC can result in the development of confluent actinic keratoses (AK) followed by invasive keratinocytic carcinomas ("squamous dysplasia"), preferentially on sun-exposed skin. Discontinuation or dose reduction of HC may result in partial improvement. A 59-year-old farmer after 14 years on HC (2 gr/d) and acetylsalicylic acid (100 mg/d) for ET, was referred for numerous, hyperkeratotic AK on face, scalp, and hands that could not be controlled with repeated ( N = 15) cryosurgery sessions in the previous 3 years...
2018: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/29778746/betulinic-acid-a-natural-pde-inhibitor-restores-hippocampal-camp-cgmp-and-bdnf-improve-cerebral-blood-flow-and-recover-memory-deficits-in-permanent-bccao-induced-vascular-dementia-in-rats
#6
Madhu Kaundal, Saima Zameer, Abul Kalam Najmi, Suhel Parvez, Mohd Akhtar
Vascular dementia (VaD) is the second most common form of senile dementia, embraces memory deficits, neuroinflammation, executive function damage, mood and behavioral changes and abnormal cerebral blood flow. The purpose of the study was to explore the therapeutic potential of betulinic acid in bilateral common carotid artery occlusion (BCCAO) induced VaDin experimental rats.VaD was induced by BCCAO in rats and betulinic acid (10 and 15mg/kg/day po) was administered 1 week after surgery. The cerebral blood pressure of the animal was recorded before and after the treatment using Laser Doppler flow meter...
May 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29778625/the-mediating-role-of-phosphodiesterase-type-4-in-the-dopaminergic-modulation-of-motor-impulsivity
#7
P R A Heckman, A Blokland, N P Van Goethem, B T J Van Hagen, J Prickaerts
The current study investigated the mediating role of phosphodiesterase type 4 (PDE4) regulated cAMP in the dopaminergic modulation of premature responding (action restraint) in rats. Response inhibition, which includes action restraint, finds its neurobiological origin in cortico-striatal-thalamic circuitry and can be modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cAMP/PKA signaling cascade. Areas in the prefrontal cortex are very sensitive to their neurochemical environment, including catecholamine levels...
May 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29777732/antinociceptive-effect-of-tadalafil-in-various-pain-models-involvement-of-opioid-receptors-and-nitric-oxide-cyclic-gmp-pathways
#8
Mohammad M Mehanna, Souraya Domiati, Hania Nakkash Chmaisse, Ahmed El Mallah
Nitric oxide has been proven to play an important role in nociception, accordingly, its promoters, phosphodiesterase inhibitors have been investigated as pain response modulators. Aiming to evaluate the central effect of tadalafil, a phosphodiesterase 5 inhibitor, and to determine its EC50, tail flick and hot plate tests were utilized. On the other hand, its nociceptive peripheral analgesic effect was assessed through acetic-acid induced writhing model. Formalin test was used to appraise both non-inflammatory and inflammatory pain responses...
May 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29777610/phenolic-rich-extracts-of-eurycoma-longifolia-and-cylicodiscus-gabunensis-inhibit-enzymes-responsible-for-the-development-of-erectile-dysfunction-and-are-antioxidants
#9
Ganiyu Oboh, Adeniyi A Adebayo, Ayokunle O Ademosun
BACKGROUND: Herbs have been used from ages to manage male sexual dysfunction. Hence, this study sought to investigate the effects of Eurycoma longifolia (EL) and Cylicodiscus gabunensis (CG) stem bark extracts on some enzymes implicated in erectile dysfunction in vitro. METHODS: The extracts were prepared, and their effects on phosphodiesterase-5 (PDE-5), arginase, and angiotensin-1-converting enzyme (ACE) as well as pro-oxidant-induced lipid peroxidation were assessed...
May 19, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29776351/a-computational-study-of-hedgehog-signalling-involved-in-basal-cell-carcinoma-reveals-the-potential-and-limitation-of-combination-therapy
#10
Antoine Buetti-Dinh, Rebecca Jensen, Ran Friedman
BACKGROUND: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations. METHODS: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29776091/modeling-persistence-of-motion-in-a-crowded-environment-the-diffusive-limit-of-excluding-velocity-jump-processes
#11
Enrico Gavagnin, Christian A Yates
Persistence of motion is the tendency of an object to maintain motion in a direction for short time scales without necessarily being biased in any direction in the long term. One of the most appropriate mathematical tools to study this behavior is an agent-based velocity-jump process. In the absence of agent-agent interaction, the mean-field continuum limit of the agent-based model (ABM) gives rise to the well known hyperbolic telegraph equation. When agent-agent interaction is included in the ABM, a strictly advective system of partial differential equations (PDEs) can be derived at the population level...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775418/prolonged-activation-of-camp-signaling-leads-to-endothelial-barrier-disruption-via-transcriptional-repression-of-rras
#12
Carole Y Perrot, Junko Sawada, Masanobu Komatsu
The increase in cAMP levels in endothelial cells triggers cellular signaling to alter vascular permeability. It is generally considered that cAMP signaling stabilizes the endothelial barrier function and reduces permeability. However, previous studies have only examined the permeability shortly after cAMP elevation and thus have only investigated acute responses. Because cAMP is a key regulator of gene expression, elevated cAMP may have a delayed but profound impact on the endothelial permeability by altering the expression of the genes that are vital for the vessel wall stability...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29773995/hypoxia-reoxygenation-of-rat-renal-arteries-impairs-vasorelaxation-via-modulation-of-endothelium-independent-sgc-cgmp-pkg-signaling
#13
Diana Braun, Christa Zollbrecht, Stefanie Dietze, Rudolf Schubert, Stefan Golz, Holger Summer, Pontus B Persson, Mattias Carlström, Marion Ludwig, Andreas Patzak
Ischemia/reperfusion injury holds a key position in many pathological conditions such as acute kidney injury and in the transition to chronic stages of renal damage. We hypothesized that besides a reported disproportional activation of vasoconstrictor response, hypoxia/reoxygenation (H/R) adversely affects endothelial dilatory systems and impairs relaxation in renal arteries. Rat renal interlobar arteries were studied under isometric conditions. Hypoxia was induced by application of 95% N2 , 5% CO2 for 60 min to the bath solution, followed by a 10 min period of reoxygenation (95% O2 , 5% CO2 )...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29773452/beneficial-effects-of-rolipram-a-phosphodiesterase-4-specific-inhibitor-on-testicular-torsion-detorsion-injury-in-rats
#14
Deniz Abat, Yıldırım Bayazıt, Arbil Açıkalın, Kenan Dağlıoğlu, Ebru Dündar Yenilmez, Adem Altunkol, Şeyda Erdoğan, Abdullah Tuli
INTRODUCTION: The aim of the study is to investigate the effect of Rolipram, a selective phosphodiesterase 4 inhibitor, on testicular torsion - detorsion injury. METHODS: Sixty young male rats were divided into five groups. In each group, the right testes of six rats were removed four hours after detorsion for biochemical analysis, and the right testes of the remaining six rats were removed 24 h after detorsion for pathological analysis. In group 1 (sham-operated) right orchiectomy was performed without torsion, and right testes were sent to the laboratory for biochemical and pathologic analyses...
April 14, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29772649/pulmonary-arterial-hypertension-pathophysiology-and-treatment
#15
REVIEW
Norris S H Lan, Benjamin D Massam, Sandeep S Kulkarni, Chim C Lang
Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and subsequent pulmonary arterial pressure, causing right ventricular failure which leads to eventual death if untreated. The management of PAH has advanced rapidly in recent years due to improved understanding of the condition's pathophysiology, specifically the nitric oxide, prostacyclin-thromboxane and endothelin-1 pathways...
May 16, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29768196/loss-of-abhd15-impairs-the-anti-lipolytic-action-of-insulin-by-altering-pde3b-stability-and-contributes-to-insulin-resistance
#16
Wenmin Xia, Ariane R Pessentheiner, Dina C Hofer, Melina Amor, Renate Schreiber, Gabriele Schoiswohl, Thomas O Eichmann, Evelyn Walenta, Bianca Itariu, Gerhard Prager, Hubert Hackl, Thomas Stulnig, Dagmar Kratky, Thomas Rülicke, Juliane G Bogner-Strauss
Elevated circulating fatty acids (FAs) contribute to obesity-associated metabolic complications, but the mechanisms by which insulin suppresses lipolysis are poorly understood. We show that α/β-hydrolase domain-containing 15 (ABHD15) is required for the anti-lipolytic action of insulin in white adipose tissue (WAT). Neither insulin nor glucose treatments can suppress FA mobilization in global and conditional Abhd15-knockout (KO) mice. Accordingly, insulin signaling is impaired in Abhd15-KO adipocytes, as indicated by reduced AKT phosphorylation, glucose uptake, and de novo lipogenesis...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767441/hydrogen-sulfide-pathway-and-skeletal-muscle-an-introductory-review
#17
REVIEW
Valentina Vellecco, Chiara Armogida, Mariarosaria Bucci
The presence of H2 S pathway in skeletal muscle (SKM) has been recently established. SKM expresses the three constitutive H2 S generating enzymes in animals and humans and it actively produces H2 S. The main recognized molecular targets of H2 S, i.e. potassium channels and phosphodiesterases, have been evaluated in SKM physiology in order to hypothesize a role for H2 S signaling. SKM dysfunctions, including muscular dystrophy and malignant hyperthermia, have been also evaluated as conditions in which H2 S-pathway and the trans-sulfuration pathway have been suggested to be involved...
May 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29765373/compartmentalized-cyclic-amp-production-by-the-bordetella-pertussis-and-bacillus-anthracis-adenylate-cyclase-toxins-differentially-affects-the-immune-synapse-in-t-lymphocytes
#18
Vijay B Arumugham, Cristina Ulivieri, Anna Onnis, Francesca Finetti, Fiorella Tonello, Daniel Ladant, Cosima T Baldari
A central feature of the immune synapse (IS) is the tight compartmentalization of membrane receptors and signaling mediators that is functional for its ability to coordinate T cell activation. Second messengers centrally implicated in this process, such as Ca2+ and diacyl glycerol, also undergo compartmentalization at the IS. Current evidence suggests a more complex scenario for cyclic AMP (cAMP), which acts both as positive and as negative regulator of T-cell antigen receptor (TCR) signaling and which, as such, must be subjected to a tight spatiotemporal control to allow for signaling at the IS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29761313/genomewide-dna-methylation-responses-in-patients-with-%C3%AE-thalassemia-treated-with-yisui-shengxue-granules
#19
Yan-Ling Cheng, Xin-Hua Zhang, Yu-Wen Sun, Wen-Juan Wang, Jie Huang, Na-Li Chu, Su-Ping Fang, Zhi-Kui Wu
OBJECTIVE: To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. METHODS: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention...
May 3, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29757020/recent-advances-in-the-treatment-of-brugada-syndrome
#20
Mariana Argenziano, Charles Antzelevitch
Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome characterized by ST-segment elevation in right precordial ECG leads and associated with sudden cardiac death in young adults. The ECG manifestations of BrS are often concealed but can be unmasked by sodium channel blockers and fever. Areas covered: Implantation of a cardioverter defibrillator (ICD) is first-line therapy for BrS patients presenting with prior cardiac arrest or documented VT. A pharmacological approach to therapy is recommended in cases of electrical storm, as an adjunct to ICD and as preventative therapy...
May 14, 2018: Expert Review of Cardiovascular Therapy
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