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PDE or phosphodiesterase

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https://www.readbyqxmd.com/read/28548283/novel-selective-phosphodiesterase-type-1-inhibitors-cause-vasodilatation-and-lower-blood-pressure-in-rats
#1
Morten Laursen, Lilliana Beck, Jan Kehler, Claus Tornby Christoffersen, Christoffer Bundgaard, Susie Mogensen, Tomas Mow, Estefano Pinilla, Jakob Schöllhammer Knudsen, Elise Røge Hedegaard, Morten Grunnet, Ulf Simonsen
BACKGROUND AND PURPOSE: Phosphodiesterase enzymes (PDE1-11) break down cyclic nucleotides and are important in the regulation of the cardiovascular system. The purpose of the present study was to investigate the effect on the cardiovascular system of two novel selective PDE1 inhibitors, Lu AF41228 and Lu AF58027. EXPERIMENTAL APPROACH: We used rat mesenteric small arteries (internal diameters of 200-300 µm), RT-PCR and measurement of isometric wall tension. The effect of Lu AF41228 and Lu AF58027 on heart rate and blood pressure was assessed in both anesthetized and conscious male rats...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28546870/reply-to-efficacy-and-safety-of-phosphodiesterase-5-inhibitors-for-treatment-of-erectile-dysfunction-secondary-to-spinal-cord-injury-a-systemic-review-and-meta-analysis
#2
https://www.readbyqxmd.com/read/28546515/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#3
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28544981/synthesis-and-in%C3%A2-vitro-evaluation-of-new-fluorinated-quinoline-derivatives-with-high-affinity-for-pde5-towards-the-development-of-new-pet-neuroimaging-probes
#4
Jianrong Liu, Aurélie Maisonial-Besset, Barbara Wenzel, Damien Canitrot, Ariane Baufond, Jean-Michel Chezal, Peter Brust, Emmanuel Moreau
The increasing incidence of Alzheimer's disease (AD) worldwide is a major public health problem. Current treatments provide only palliative solutions with significant side effects. Therefore, new efficient treatment options and novel early diagnosis tools are urgently needed. Recently, strong pre-clinical evidences suggested that phosphodiesterase 5 (PDE5) may be clinically relevant both as biomarker and drug-target in AD. In this study, we intended to develop a new radiofluorinated tracer for the visualisation of PDE5 in brain using PET imaging...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28544208/ultra-high-field-magnetic-resonance-spectroscopy-in-non-alcoholic-fatty-liver-disease-novel-mechanistic-and-diagnostic-insights-of-energy-metabolism-in-non-alcoholic-steatohepatitis-and-advanced-fibrosis
#5
Stefan Traussnigg, Christian Kienbacher, Martin Gajdošík, Ladislav Valkovič, Emina Halilbasic, Judith Stift, Christian Rechling, Harald Hofer, Petra Steindl-Munda, Peter Ferenci, Fritz Wrba, Siegfried Trattnig, Martin Krššák, Michael Trauner
BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD. METHODS: MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22)...
April 24, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28544201/influence-of-highly-porous-electrospun-plga-pcl-nha-fibrous-scaffolds-on-the-differentiation-of-tooth-bud-cells-in-vitro
#6
Xinjie Cai, Sofie Ten Hoopen, Weibo Zhang, Charles Yi, Wanxun Yang, Fang Yang, John A Jansen, X Frank Walboomers, Pamela C Yelick
In this study, we investigated the use of three-dimensional electrospun poly(lactic-co-glycolic acid)/poly(ε-caprolactone) (PLGA/PCL) scaffolds seeded and cultured with postnatal dental cells, for improved dental tissue regeneration. Wet-electrospinning combined with ultrasonic treatment was studied as a method to enhance scaffold porosity and to promote cell-cell interactions. We also investigated whether nano-hydroxyapatite (nHA) incorporation could enhance dental cell differentiation. All scaffolds were seeded with human tooth pulp-derived dental mesenchymal (hDM) cells, or a combination of hDM and pig dental epithelial (pDE) cells, cultured for up to 28 days...
May 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28542295/therapeutic-benefits-of-phosphodiesterase-4b-inhibition-after-traumatic-brain-injury
#7
Nicole M Wilson, Mark E Gurney, W Dalton Dietrich, Coleen M Atkins
Traumatic brain injury (TBI) initiates a deleterious inflammatory response that exacerbates pathology and worsens outcome. This inflammatory response is partially mediated by a reduction in cAMP and a concomitant upregulation of cAMP-hydrolyzing phosphodiesterases (PDEs) acutely after TBI. The PDE4B subfamily, specifically PDE4B2, has been found to regulate cAMP in inflammatory cells, such as neutrophils, macrophages and microglia. To determine if PDE4B regulates inflammation and subsequent pathology after TBI, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury (2 ± 0...
2017: PloS One
https://www.readbyqxmd.com/read/28540724/pde%C3%AE-binding-to-ras-isoforms-provides-a-route-to-proper-membrane-localization
#8
Serena Muratcioglu, Hyunbum Jang, Attila Gursoy, Ozlem Keskin, Ruth Nussinov
To signal, Ras isoforms must be enriched at the plasma membrane (PM). It was suggested that phosphodiesterase-δ (PDEδ) can bind and shuttle some farnesylated Ras isoforms to the PM - but not all. Among these, interest focused on K-Ras4B, the most abundant oncogenic Ras isoform. To study PDEδ/Ras interactions, we modeled and simulated the PDEδ/K-Ras4B complex. We obtained structures which were similar to two subsequently determined crystal structures. We next modeled and simulated complexes of PDEδ with the farnesylated hypervariable regions (HVRs) of K-Ras4A and N-Ras...
May 25, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28540239/the-impact-and-management-of-sexual-dysfunction-secondary-to-pharmacological-therapy-of-benign-prostatic-hyperplasia
#9
REVIEW
Jason Gandhi, Steven J Weissbart, Noel L Smith, Steven A Kaplan, Gautam Dagur, Anna Zumbo, Gargi Joshi, Sardar Ali Khan
Benign prostatic hyperplasia (BPH) is one of the most common genitourinary complications in men over 50 years of age and typically presents with lower urinary tract symptoms (LUTS). Classes of medications include α1-adrenoceptor blockers, 5α-reductase inhibitors, and phosphodiesterase 5 inhibitors. Today, α1-adrenoceptor blockers and 5α-reductase inhibitors are often combined to give a synergistic effect. A review of the current literature identified several adverse sexual side effects, including erectile dysfunction (ED), decreased libido, orgasmic disorders, and ejaculatory disorders...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28540228/research-in-pharmacotherapy-for-erectile-dysfunction
#10
REVIEW
Ji-Kan Ryu, Jun-Kyu Suh, Arthur L Burnett
Although oral phosphodiesterase-5 (PDE5) inhibitors are generally accepted as an effective therapy for erectile dysfunction (ED), men with ED from diabetes or radical prostatectomy respond poorly to these drugs. Many researchers have tried to develop novel therapeutics that target alternative molecular pathways. A group of therapeutics belongs to centrally acting agents that target dopamine and melanocortin receptors. The other one is the peripherally acting agents that target soluble guanylate cyclase, Rho-kinase pathway, and Maxi-K channel, etc...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28539286/-expression-purification-and-activity-analysis-of-ggdef-and-eal-domain-containing-proteins-from-lactobacillus-acidophilus
#11
Jia-Hui He, Jie-Li Sun, Wen-Juan Yan, Fang Wang
OBJECTIVE: To identify the functions of the proteins containing the GGDEF or EAL domain in Lactobacillus acidophilus for investigation of the regulatory mechanism of c-di-GMP in this strain. METHODS: The DNA fragments of NH13_07045-GGDEF, NH13_07050 and NH13_07055 from Lactobacillus acidophilus ATCC4356 were amplified by PCR and cloned into the expression vector pMAL-His-c2. After sequencing, the recombinant plasmids were transformed into competent Escherichia coli cells, which were induced by IPTG to express the recombinant proteins fused with maltose binding protein (MBP)...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28537861/use-of-an-oral-phosphodiesterase-4-inhibitor-apremilast-for-the-treatment-of-chronic-severe-atopic-dermatitis-a-case-report
#12
Benjamin Farahnik, Kourosh Beroukhim, Mio Nakamura, Michael Abrouk, Tian Hao Zhu, Rasnik Singh, Kristina Lee, Tina Bhutani, John Koo, Wilson Liao
Atopic dermatitis (AD) is a common inflammatory dermatosis characterized by pruritus, erythema, induration, and lichenification. Current treatment options for generalized atopic dermatitis are limited and have potentially serious adverse effects, especially in patients with severe, chronic AD who frequently require systemic anti-inflammatory agents. Apremilast, an oral phosphodiesterase-4 inhibitor, was FDA approved in September 2014 for the treatment of moderate-to-severe plaque psoriasis. However, its upstream anti-inflammatory effects, ease of use as an oral agent, and mild side-effect profile make it an interesting treatment option for AD as well...
May 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28536559/new-functions-and-subcellular-localization-patterns-of-c-di-gmp-components-ggdef-domain-proteins-in-b-subtilis
#13
Patricia Bedrunka, Peter L Graumann
The universal and pleiotropic cyclic dinucleotide second messenger c-di-GMP is most prominently known to inversely regulate planktonic and sessile lifestyles of Gram-negative species. In the Gram-positive model organism Bacillus subtilis, intracellular c-di-GMP levels are modulated by a concise set of three diguanylate cylases (DgcK, DgcP, DgcW) and one phosphodiesterase (PdeH). Two recent studies have reported the negative influence of the c-di-GMP receptor DgrA (PilZ domain protein) on swarming motility indicating a conserved role of this second messenger across the bacterial domain...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28535123/topical-otic-drugs-in-a-multi-purpose-manufacturing-facility-a-guide-on-determination-and-application-of-permitted-daily-exposure-pde
#14
Lisa Wiesner, Maarten Prause, Ester Lovsin Barle
Due to newly introduced EU GMP guideline for Medicinal Products for Human and Veterinary use (PIC/S, 2015), product specific PDE for toxicological evaluation in multi-purpose facilities are required within a documented process for risk assessment. EMA (2014) guidance on setting PDE limits so far focused on systemic administration routes such as IV, oral or inhalation. This manuscript wants to give guidance on setting PDE values for risk management purposes in multi-purpose facilities for Active Pharmaceutical Ingredients (APIs) applied as topical otic drugs to the outer ear canal...
May 23, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28533405/spatial-evolutionary-games-with-weak-selection
#15
Mridu Nanda, Richard Durrett
Recently, a rigorous mathematical theory has been developed for spatial games with weak selection, i.e., when the payoff differences between strategies are small. The key to the analysis is that when space and time are suitably rescaled, the spatial model converges to the solution of a partial differential equation (PDE). This approach can be used to analyze all [Formula: see text] games, but there are a number of [Formula: see text] games for which the behavior of the limiting PDE is not known. In this paper, we give rules for determining the behavior of a large class of [Formula: see text] games and check their validity using simulation...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533285/phosphodiesterase-inhibitors-such-as-viagra-do-not-increase-melanoma-risk-review-finds
#16
Susan Mayor
No abstract text is available yet for this article.
May 21, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28533270/classical-activation-of-macrophages-and-vardenafil
#17
Richmond Muimo
Inhibitors of phosphodiesterase 5 (PDE5) - sildenafil citrate (Viagra; Pfizer) and vardenafil hydrochloride (Levitra; Bayer/GlaxoSmithKline) - approved for the treatment of erectile dysfunction and pulmonary arterial hypertension also rescue the loss of cystic fibrosis (CF) chloride channel function and the mislocalization of F508del-CFTR in affected tissues in CF. Can PDE5 inhibitors provide a therapeutic strategy which combines ability to correct the basic ion transport defect and to control de-regulated lung inflammation in CF?...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28532471/perfusion-by-arterial-spin-labelling-following-single-dose-tadalafil-in-small-vessel-disease-pastis-study-protocol-for-a-randomised-controlled-trial
#18
Mathilde M H Pauls, Natasha Clarke, Sarah Trippier, Shai Betteridge, Franklyn A Howe, Usman Khan, Christina Kruuse, Jeremy B Madigan, Barry Moynihan, Anthony C Pereira, Debbie Rolfe, Egill Rostrup, Caroline E Haig, Thomas R Barrick, Jeremy D Isaacs, Atticus H Hainsworth
BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial...
May 22, 2017: Trials
https://www.readbyqxmd.com/read/28532389/the-use-of-macitentan-in-fontan-circulation-a-case-report
#19
Polyvios Demetriades, Amir Aziz, Robin Condliffe, Sarah E Bowater, Paul F Clift
BACKGROUND: The Fontan circulation, a result of a palliative procedure in patients with single systemic ventricles, is defined by chronically elevated pulmonary vascular resistance. When traditional heart failure therapies fail, pharmacological agents that reduce pulmonary artery pressures may be used. These include endothelial-receptor antagonists, prostanoids and phosphodiesterase type 5 inhibitors. We report the first use of macitentan, an endothelin-receptor antagonist, in a patient with a Fontan circulation...
May 22, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28531338/placental-exosomes-as-early-biomarker-of-preeclampsia-potential-role-of-exosomal-micrornas-across-gestation
#20
Carlos Salomon, Dominic Guanzon, Katherin Scholz-Romero, Sherri Longo, Paula Correa, Sebastian E Illanes, Gregory E Rice
Context: There is a need to develop strategies for early prediction of patients who will develop preeclampsia (PE), in order to establish preventive strategies to reduce the prevalence and severity of the disease and their associated complications. Objective: The objective of this study was to investigate whether exosomes and their microRNA cargo present in maternal circulation can be used as early biomarker for PE. Design, Setting, Patients, and Interventions: A retrospective stratified study design was used to quantify total exosomes (EXO) and placenta-derived exosomes (PdE) present in maternal plasma of normal (n=32 per time point) and PE (n=15 per time point) pregnancies...
May 22, 2017: Journal of Clinical Endocrinology and Metabolism
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