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https://www.readbyqxmd.com/read/29141319/-homozygous-ectonucleotide-pyrophosphatase-phosphodiesterase-1-variants-in-a-girl-with-hypophosphatemic-rickets-and-literature-review
#1
Z Q Liu, X B Chen, F Y Song, K Gao, M F Qiu, Y Qian, M Du
Objective: To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants. Method: The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" ...
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29140789/mechanism-and-dynamics-of-inpp5e-transport-into-and-inside-the-ciliary-compartment
#2
Stefanie Kristine Kösling, Eyad Kalawy Fansa, Stefano Maffini, Alfred Wittinghofer
The inositol polyphosphate 5´-phosphatase E (INPP5E) localizes to cilia. We showed that the carrier protein phosphodiesterase 6 delta subunit (PDE6δ) mediates the sorting of farnesylated INPP5E into cilia due to high affinity binding and release by Arl3 GTP. However, the dynamics of INPP5E transport into and inside the ciliary compartment are not fully understood. Here we first investigate the movement of INPP5E using live cell fluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29138698/soluble-epoxide-hydrolase-inhibitor-and-14-15-epoxyeicosatrienoic-acid-facilitated-long-term-potentiation-through-camp-and-camkii-in-the-hippocampus
#3
Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, Hui-Ching Lin
Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29138357/tadalafil-a-long-acting-phosphodiesterase-inhibitor-promotes-bone-marrow-stem-cell-survival-and-their-homing-into-ischemic-myocardium-for-cardiac-repair
#4
Ibrahim Elmadbouh, Muhammad Ashraf
The aim was to evaluate the tadalafil-mediated effects at molecular level on bone marrow-derived mesenchymal stem cells (MSCs) survival and their homing into the infarcted hearts to promote cardiac repair and improve function. MSCs were pretreated in vitro with inhibitors of PKG, MAPK, FasL, nitric oxide synthase (NOS) (L-NAME), CXCR4 (AMD3100), or miR-21 inhibitors (+/-luciferase construction +/-Fas) prior to tadalafil treatment for 2 h. These MSCs were then subjected to H2O2 stress to assess their injury...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29137892/role-of-pyrophosphate-in-vascular-calcification-in-chronic-kidney-disease
#5
Daniel Azpiazu, Sergio Gonzalo, Emilio González-Parra, Jesús Egido, Ricardo Villa-Bellosta
Vascular calcification is a pathology characterized by the deposition of calcium-phosphate in cardiovascular structures, mainly in the form of hydroxyapatite crystals, resulting in ectopic calcification. It is correlated with increased risk of cardiovascular disease and myocardial infarction in diabetic patients and in those with chronic kidney disease (CKD). Vascular smooth muscle cells are sensitive to changes in inorganic phosphate (Pi) levels. They are able to adapt and modify some of their functions and promote changes which trigger calcification...
November 11, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29135645/phosphodiesterase-type-5-inhibitors-sport-and-doping
#6
Luigi Di Luigi, Massimiliano Sansone, Andrea Sansone, Roberta Ceci, Guglielmo Duranti, Paolo Borrione, Clara Crescioli, Paolo Sgrò, Stefania Sabatini
Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition...
November 2017: Current Sports Medicine Reports
https://www.readbyqxmd.com/read/29135158/-the-role-of-pharmacological-preconditioning-in-renal-ischemic-and-reperfusion-injury
#7
D A Kostina, T G Pokrovskaya, Yu V Olefir, A N Yavorskii, V V Elagin
Renal ischemic and reperfusion injury resulting in acute renal failure is a multidisciplinary problem at the junction of pathophysiology, transplantology, urology, nephrology, cardiac surgery and pharmacology. One of renal protection strategies is using the phenomenon of preconditioning. Preconditioning is one of the ways to adopt a tissue to repeated short-term effects of damaging factors to induce an enhanced tolerance to the long period of hypoxia and/or ischemia. There are multiple cellular and molecular mechanisms of the renal protective effects of preconditioning stimuli, but the key effectors and signaling molecules are ATP-dependent potassium channels, nitric oxide synthase, nitric oxide, and mitochondrial pore...
October 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/29134978/testicular-and-epididymal-histology-of-rats-chronically-administered-high-doses-of-phosphodiesterase-5-inhibitors-and-tramadol
#8
Victor U Nna, Augustine L Udefa, Emmanuel O Ofutet, Eme O Osim
Testicular oxidative stress, endocrine disruption and abnormal spermatogenesis in rats exposed to high doses ofphosphodiesterase-5 inhibitors (PDE5i) and opioids, with poor reversibility following withdrawal of treatment had beenreported. In this study, we examined the histopathological effects of high doses of sildenafil, tadalafil, tramadol andsildenafil+tramadol on the testes and epididymis of rats. Seventy male rats (180 - 200 g b.w) were assigned to one of fivegroups (n = 14), namely; A: control (0.2 mL normal saline), B: sildenafil (1 mg/100g b...
June 30, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
https://www.readbyqxmd.com/read/29132351/therapeutic-efficacy-of-pentoxifylline-on-proteinuria-and-renal-progression-an-update
#9
REVIEW
Yung-Ming Chen, Wen-Chih Chiang, Shuei-Liong Lin, Tun-Jun Tsai
Blood pressure control with renin-angiotensin system (RAS) blockade has remained the gold standard for treating patients with proteinuric chronic kidney disease (CKD) up to date. Nevertheless, RAS blockade slows but does not halt the progression of kidney disease, thus highlighting the need to search for additional therapeutic approaches. The nonselective phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) is an old drug that exhibits prominent anti-inflammatory, anti-proliferative and anti-fibrotic activities both in vitro and in vivo...
November 13, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29132113/fluorometric-detection-of-protein-ligand-engagement-the-case-of-phosphodiesterase5
#10
Giulia Di Rocco, Ilaria Martinelli, Salvatore Pacifico, Remo Guerrini, Elena Cichero, Paola Fossa, Silvia Franchini, Silvia Cardarelli, Mauro Giorgi, Marco Sola, Glauco Ponterini
Phosphodiesterases (PDEs) regulate the intracellular levels of cAMP and cGMP. The great clinical success of the PDE5 inhibitors, Sildenafil (Viagra), Vardenafil (Levitra) and Tadalafil (Cialis) has led to an increasing interest for this class of enzymes. Recent studies have shown a correlation between tumor growth and PDE5 overexpression, making PDE5-selective inhibitors promising candidates for cancer treatment. The search for such inhibitors rests today on radioactive assays. In this work, we exploit the conserved catalytic domain of the enzyme and propose a faster and safer method for detecting the binding of ligands and evaluate their affinities...
November 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29130985/heptamethoxyflavone-reduces-phosphodiesterase-activity-and-t-cell-growth-in-vitro
#11
Yui Hamada, Mitsunari Nakajima, Kazuna Tsuzuki, Yoshiaki Amakura, Morio Yoshimura, Satoshi Okuyama, Yoshiko Furukawa
In a previous study, we reported that interleukin-4 production was reduced in spleen cells of mice administered 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), which is a polymethoxyflavone found at high concentrations in the peel of various citrus fruits. In this study, we investigated the function of HMF on the growth of T cells cultured from the spleens of mice. HMF decreased the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by anti-CD3/CD28 antibody-stimulated mouse spleen cells...
November 8, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29130591/familial-choreoathetosis-due-to-novel-heterozygous-mutation-in-pde10a
#12
Dhanya L Narayanan, Dipti Deshpande, Aneek Das Bhowmik, Dandu R Varma, Ashwin Dalal
PDE10A encodes a dual cAMP-cGMP phosphodiesterase that is enriched in the medium spiny neurons of the corpus striatum in the brain and plays an important role in basal ganglia circuitry. Three unrelated patients with childhood onset chorea and striatal abnormalities on MRI brain with heterozygous de novo variants in PDE10A have been described previously. Two families with eight affected individuals with biallelic mutations in PDE10A have also been described previously. We report a family with multiple affected individuals with childhood onset chorea, striatal abnormalities, and a novel heterozygous mutation, c...
November 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29129027/factors-affecting-the-efficacy-and-safety-of-phosphodiesterase-5-inhibitor-and-placebo-in-treatment-for-lower-urinary-tract-symptoms-meta-analysis-and-meta-regression
#13
Hwa Yeon Sun, Bora Lee, Jae Heon Kim
PURPOSE: We aimed to investigate the real benefit and safety of phosphodiesterase 5 inhibitor (PDE 5I) for benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) by determining the affecting factors and to overcome the previous meta-analysis studies. METHODS: We conducted a systematic review of improvements in LUTS using International Prostate Symptom Score (IPSS), voiding subscore of IPSS (voiding IPSS), storage subscore of IPSS (storage IPSS), quality of life (QoL), maximal urinary flow rate (Qmax), and post-voided residual volume (PVR), and also investigated adverse events and relevant withdrawal rate...
November 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29128622/efficacy-and-tolerability-of-pharmacological-interventions-for-pulmonary-arterial-hypertension-a-network-meta-analysis
#14
Hongjing Lin, Mupeng Wang, Ying Yu, Zeyu Qin, Xin Zhong, Jiahui Ma, Fangbo Zhao, Xueli Zhang
PURPOSE: This network meta-analysis (NMA) is designed to compare the efficacy and tolerability of various therapies and combinations for pulmonary arterial hypertension (PAH). METHOD: We conducted a systematic search in databases PubMed, Embase, and Cochrane Library. Treatment efficacy and tolerability were compared by synthesizing direct and indirect evidence. The surface under the curve ranking area was utilized to rank multiple interventions. RESULT: A total of 43 randomized clinical trials were included in our NMA...
November 8, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29124927/integrated-continuous-emulsion-creamer
#15
Wesley Cochrane, Amber L Hackler, Valerie J Cavett, Alexander K Price, Brian M Paegel
Reaction incubation is ubiquitous in high-throughput screening workflows, including those at the microfluidic droplet scale. Fully integrated microfluidic processors that generate, incubate, and sort droplets for continuous droplet screening must passively handle a flowing emulsion such that droplet-droplet incubation time variation is minimized. Here, we disclose an integrated microfluidic emulsion creamer that close packs assay droplets by draining away excess oil through microfabricated drain channels. The drained oil co-flows with creamed emulsion and then reintroduces the oil to disperse the droplets at the circuit terminus for analysis...
November 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29123207/atropine-augments-cardiac-contractility-by-inhibiting-camp-specific-phosphodiesterase-type-4
#16
Ruwan K Perera, Thomas H Fischer, Michael Wagner, Matthias Dewenter, Christiane Vettel, Nadja I Bork, Lars S Maier, Marco Conti, Juergen Wess, Ali El-Armouche, Gerd Hasenfuß, Viacheslav O Nikolaev
Atropine is a clinically relevant anticholinergic drug, which blocks inhibitory effects of the parasympathetic neurotransmitter acetylcholine on heart rate leading to tachycardia. However, many cardiac effects of atropine cannot be adequately explained solely by its antagonism at muscarinic receptors. In isolated mouse ventricular cardiomyocytes expressing a Förster resonance energy transfer (FRET)-based cAMP biosensor, we confirmed that atropine inhibited acetylcholine-induced decreases in cAMP. Unexpectedly, even in the absence of acetylcholine, after G-protein inactivation with pertussis toxin or in myocytes from M2- or M1/3-muscarinic receptor knockout mice, atropine increased cAMP levels that were pre-elevated with the β-adrenergic agonist isoproterenol...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122629/long-term-cilostazol-administration-prevents-age-related-decline-of-hippocampus-dependent-memory-in-mice
#17
Shuichi Yanai, Hideki Ito, Shogo Endo
Phosphodiesterases (PDEs) are enzymes that hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and/or 3', 5'-cyclic guanosine monophosphate (cGMP). The regulation of intracellular signaling pathways mediated by cyclic nucleotides is imperative to synaptic plasticity and memory in animals. Because PDEs play an important role in this regulation, PDE inhibitors are considered as candidate compounds for treating cognitive and memory disorders. In the present study, we tested whether cilostazol, a selective PDE3 inhibitor, prevents the cognitive deterioration that occurs during the course of normal aging in mice...
November 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29122494/penile-rehabilitation-therapy-following-radical-prostatectomy-a-meta-analysis
#18
REVIEW
Chunhui Liu, David S Lopez, Ming Chen, Run Wang
BACKGROUND: Penile rehabilitation, defined as the use of any drug or device at or after radical prostatectomy to maximize erectile function recovery, is commonly used for post-prostatectomy erectile dysfunction; however, conflicting results based on each study make it difficult to give a recommendation for clinical practice. AIM: To clarify the effect of oral phosphodiesterase type 5 inhibitors (PDE5is), vacuum erection devices, intracorporeal injection therapy, and the combination of these treatments on penile rehabilitation...
November 6, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29120675/utility-of-adenosine-monophosphate-detection-system-for-monitoring-the-activities-of-diverse-enzyme-reactions
#19
Subhanjan Mondal, Kevin Hsiao, Said A Goueli
Adenosine monophosphate (AMP) is a key cellular metabolite regulating energy homeostasis and signal transduction. AMP is also a product of various enzymatic reactions, many of which are dysregulated during disease conditions. Thus, monitoring the activities of these enzymes is a primary goal for developing modulators for these enzymes. In this study, we demonstrate the versatility of an enzyme-coupled assay that quantifies the amount of AMP produced by any enzymatic reaction regardless of its substrates. We successfully implemented it to enzyme reactions that use adenosine triphosphate (ATP) as a substrate (aminoacyl tRNA synthetase and DNA ligase) by an elaborate strategy of removing residual ATP and converting AMP produced into ATP; so it can be detected using luciferase/luciferin and generating light...
October 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29119630/mycobacterium-tuberculosis-rv3651-is-a-triple-sensor-domain-protein
#20
Jan Abendroth, Andrew Frando, Isabelle Q Phan, Bart L Staker, Peter J Myler, Thomas E Edwards, Christoph Grundner
The genome of the human pathogen Mycobacterium tuberculosis (Mtb) encodes ∼4,400 proteins, but one third of them have unknown functions. We solved the crystal structure of Rv3651, a hypothetical protein with no discernible similarity to proteins with known function. Rv3651 has a three-domain architecture that combines one cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA (GAF) domain and two Per-ARNT-Sim (PAS) domains. GAF and PAS domains are typically sensor domains that are linked to signaling effector molecules...
November 9, 2017: Protein Science: a Publication of the Protein Society
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