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Phosphodiesterase

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https://www.readbyqxmd.com/read/29351585/core-differences-in-synaptic-signaling-between-primary-visual-and-dorsolateral-prefrontal-cortex
#1
Sheng-Tao Yang, Min Wang, Constantinos D Paspalas, Johanna L Crimins, Marcus T Altman, James A Mazer, Amy F T Arnsten
Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons...
January 17, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29350133/borrelia-miyamotoi-infections-in-humans-and-ticks-northeastern-china
#2
Bao-Gui Jiang, Na Jia, Jia-Fu Jiang, Yuan-Chun Zheng, Yan-Li Chu, Rui-Ruo Jiang, Ya-Wei Wang, Hong-Bo Liu, Ran Wei, Wen-Hui Zhang, Yan Li, Xiao-Wei Xu, Jin-Ling Ye, Nan-Nan Yao, Xiao-Jing Liu, Qiu-Bo Huo, Yi Sun, Ju-Liang Song, Wei Liu, Wu-Chun Cao
We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3...
February 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29346172/apremilast-use-in-a-case-of-cicatricial-ectropion-secondary-to-severe-lamellar-ichthyosis
#3
Jean-Paul J Abboud, Alexander Whittington, Masih Ahmed, Jesse T Himebaugh, Lee A Wiley, Ahmad Haffar, John Nguyen
Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry thickened skin surface scales. Ocular manifestations of ichthyosis include cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely corneal perforation. Topical emollients, anti-inflammatory ointments, and systemic retinoids have been used to control the disease process, while surgical correction with donor graft has been reserved for severe cases involving corneal exposure. The authors report a case of a Caucasian male with lamellar ichthyosis with severe bilateral upper and lower eyelid cicatricial ectropion and corneal ulceration requiring surgical correction...
January 17, 2018: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/29342993/-analysis-of-prognosis-and-associated-risk-factors-in-pediatric-idiopathic-pulmonary-arterial-hypertension
#4
Q Liu, C Zhang, Q Q Li, Y Zhu, D Zhang, W G Zhao, H Gu
Objective: To analyze the prognosis and associated risk factors of pediatric idiopathic pulmonary arterial hypertension. Methods: A total of 119 patients under 18 years of age diagnosed as idiopathic pulmonary arterial hypertension in the Pulmonary Arterial Hypertension Center in Beijing Anzhen Hospital between June 2007 and May 2017 were enrolled in this retrospective study. The clinical informations and follow-up data were collected. The endpoints of follow-up were defined as death or undergoing lung transplantation...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#5
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341896/luteinizing-hormone-signaling-phosphorylates-and-activates-the-cyclic-gmp-phosphodiesterase-pde5-in-mouse-ovarian-follicles-contributing-an-additional-component-to-the-hormonally-induced-decrease-in-cyclic-gmp-that-reinitiates-meiosis
#6
Jeremy R Egbert, Siu-Pok Yee, Laurinda A Jaffe
Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown...
January 13, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29341047/german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#7
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
January 16, 2018: Pneumologie
https://www.readbyqxmd.com/read/29341044/antenatal-medical-therapies-to-improve-lung-development-in-congenital-diaphragmatic-hernia
#8
Aidan Kashyap, Philip DeKoninck, Kelly Crossley, Marta Thio, Graeme Polglase, Francesca Maria Russo, Jan Deprest, Stuart Hooper, Ryan Hodges
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by failed closure of the diaphragm, allowing abdominal viscera to herniate into the thoracic cavity and subsequently impair pulmonary and vascular development. Despite improving standardized postnatal management, there remains a population of severe CDH for whom postnatal care falls short. In these severe cases, antenatal surgical intervention (fetoscopic endoluminal tracheal occlusion [FETO]) may improve survival; however, FETO increases the risk of preterm delivery, is not widely offered, and still fails in half of cases...
January 16, 2018: American Journal of Perinatology
https://www.readbyqxmd.com/read/29340522/penile-microvascular-endothelial-function-in-hypertensive-patients-effects-of-acute-type-5-phosphodiesterase-inhibition
#9
V Verri, A A Brandão, E Tibirica
The primary aim of this study was to evaluate penile endothelial microvascular function in patients with primary arterial hypertension and age-matched normotensive subjects using laser speckle contrast imaging (LSCI). Additionally, we analyzed the acute penile microvascular effects induced by oral phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration. Endothelium-dependent microvascular reactivity was evaluated in the penises and forearms of hypertensive patients (aged 58.8±6.6 years, n=34) and age-matched healthy volunteers (n=33) at rest and 60 min following oral SIL (100 mg) administration...
January 11, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29338351/a-new-lindenane-type-sesquiterpenoid-lactone-from-chloranthus-japonicus
#10
Cheng-Shi Jiang, Yan-Qiong Guo, Sheng Yin, Hua Zhang, Gui-Hua Tang
Chromatographic fractionation of the EtOH extracts of the Traditional Chinese Medicine (TCM) Chloranthus japonicus, has led to the isolation of a new lindenane-type sesquiterpenoid lactone derivative (1). Rosmarylchloranthalactone E (1), which consists of lindenane sesquiterpenoid lactone and rosmarinic acid moieties linked via an ester bridge, was structurally elucidated by 1D and 2D NMR and HRMS data. Compound 1 was a potent phosphodiesterase-4 (PDE4) inhibitor with an IC50 value of 0.96 ± 0.04 μM.
January 17, 2018: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/29337269/inhibitors-of-phosphodiesterases-in-the-treatment-of-cough
#11
REVIEW
Juraj Mokry, Anna Urbanova, Martin Kertys, Daniela Mokra
A group of 11 enzyme families of metalophosphohydrolases called phosphodiesterases (PDEs) is responsible for a hydrolysis of intracellular cAMP and cGMP. Xanthine derivatives (methylxanthines) inhibit PDEs without selective action on their single isoforms and lead to many pharmacological effects, e.g. bronchodilation, anti-inflammatory and immunomodulating effects, and thus they can modulate the cough reflex. Contrary, selective PDE inhibitors have been developed to inhibit PDE isoforms with different pharmacological effects based on their tissue expression...
January 11, 2018: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/29334287/efficacy-and-safety-of-alpha-blockers-in-medical-expulsive-therapy-for-ureteral-stones-a-mixed-treatment-network-meta-analysis-and-trial-sequential-analysis-of-randomized-controlled-clinical-trials
#12
Kannan Sridharan, Gowri Sivaramakrishnan
Alpha blockers (AB) are the main group of drugs used for medical expulsive therapy (MET) in patients with ureteral stones. However, there is no consensus on the relative efficacy and safety of individual AB in MET. Areas covered: The present work is a network meta-analysis of randomized controlled trials comparing AB with either placebo or standard of care in patients with ureteral stones. Electronic databases of Medline, Cochrane CENTRAL and Google Scholar were searched for eligible clinical studies. Inverse variance heterogeneity model was used for mixed treatment comparisons...
January 15, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29331766/roflumilast-type-4-phosphodiesterase-inhibitor-attenuates-inflammation-in-rats-with-ulcerative-colitis-via-down-regulation-of-inos-and-elevation-of-camp
#13
Nahla E El-Ashmawy, Naglaa F Khedr, Hoda A El-Bahrawy, Samar A El-Adawy
BACKGROUND: Roflumilast (Rof), a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be an effective agent in inflammatory diseases and marketed for chronic obstructive pulmonary disease. OBJECTIVE: This study was conducted to examine the potential anti-inflammatory effects of Rof in dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in rats and to investigate the molecular mechanisms underlying these effects. METHODS: Forty male Wistar rats were divided into four groups: normal control, colitis group (rats received 5% DSS in their drinking water continuously for 7 days), Rof group, and sulfasalazine (SLZ) group...
January 10, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29331003/oral-sildenafil-use-in-neonates-with-persistent-pulmonary-hypertension-of-newborn
#14
Ali Shabbir Hussain, Rehan Ali, Shakeel Ahmed, Farah Naz, Anila Haroon
BACKGROUND: The prevalence of PPHN has been estimated at 1.9 per 1000 live births. After the discovery of iNO's, its efficacy and benefit in PPHN is well established. Even in the best of centers equipped with iNo and ECMO the mortality is around 20%. Also, iNO is expensive and difficult to administer and monitor which makes it difficult choice in our part of the world. Furthermore About 40% of patients do not respond or have rebound pulmonary hypertension after discontinuation. Owing to these reasons, other treatment modalities like phosphodiesterase inhibitors such as Sildenafil need to be evaluated...
October 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/29330381/paper-based-inkjet-bioprinting-to-detect-fluorescence-resonance-energy-transfer-for-the-assessment-of-anti-inflammatory-activity
#15
Annie Agnes Suganya Samson, Jungmi Lee, Joon Myong Song
For the first time, a paper-based fluorescence resonance energy transfer (FRET) determination with cyclic AMP (cAMP)-specific phosphodiesterase 4B (PDE4B) inhibitory assay using an inkjet-printing technique is proposed. Non-fabricated parchment paper is found to constitute a unique substrate to measure fluorescent energy transfer, due to its insignificant self-absorption, and enables efficient sample interaction. Here, we report the responsive FRET signals generated on paper, upon sequentially printing reaction components on parchment paper using a conventional inkjet printer equipped with four cartridges...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329785/a-relapsing-fever-group-borrelia-sp-is-widely-distributed-among-wild-deer-in-japan
#16
Yumi Kumagai, Kozue Sato, Kyle R Taylor, Aya Zamoto-Niikura, Koichi Imaoka, Shigeru Morikawa, Makoto Ohnishi, Hiroki Kawabata
A relapsing fever group Borrelia sp. was detected from the blood of wild deer (Cervus nippon) in Japan. The Borrelia sp. was distributed nationwide among deer with an overall prevalence of 26% in blood samples. The prevalence of infection was significantly higher in fawns (48.4%) compared to adult deer (23.6%). Sequencing analysis reveals that this Borrelia sp. belongs to the hard tick-borne relapsing fever borreliae, and that it forms a single lineage based on sequences of the flagellin and glycerophosphodiester phosphodiesterase genes...
December 28, 2017: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29329614/bioassay-guided-isolation-of-novel-and-selective-urease-inhibitors-from-diospyros-lotus
#17
Abdur Rauf, Ghias Uddin, Bina S Siddiqui, Ajmal Khan, Umar Farooq, Farhan A Khan, Syed Majid Bukhari, Sher Bahadar Khan
Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were isolated from the chloroform fraction of extract of Diospyros lotus roots. Their structures were elucidated by advanced spectroscopic analyses, including HSQC, HMBC, NOESY, and J-resolved NMR experiments...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29325746/first-report-of-the-characterization-of-a-snake-venom-apyrase-ruviapyrase-from-indian-russell-s-viper-daboia-russelii-venom
#18
Bhargab Kalita, Aparup Patra, Shagufta Jahan, Ashis K Mukherjee
A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase). It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A. The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily. Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < ...
January 8, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29325221/naphthalene-derivatives-and-quinones-from-ventilago-denticulata-and-their-nitric-oxide-radical-scavenging-antioxidant-cytotoxic-antibacterial-and-phosphodiesterase-inhibitory-activities
#19
Wannapha Molee, Anuchit Phanumartwiwath, Chatchai Kesornpun, Sanya Sureram, Nattaya Ngamrojanavanich, Kornkanok Ingkaninan, Chulabhorn Mahidol, Somsak Ruchirawat, Prasat Kittakoop
New naphthalene derivatives (1 and 2) and a new isomer (3) of ventilagolin, together with known anthraquinones, chrysophanol (4), physcion or emodin 3-methyl ether (5), and emodin (6), were isolated from vines of Ventilago denticulata. The isolated compounds exhibited cytotoxic activity with IC50 values of 1.15-40.54 μg/mL. Compounds 1-3 selectively exhibited weak antibacterial activity (MIC values of 200.0-400.0 μg/mL), while emodin (6) displayed moderate antibacterial activity with MIC values of 25.0 μg/mL...
January 11, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29318783/tak-063-a-novel-pde10a-inhibitor-with-balanced-activation-of-direct-and-indirect-pathways-provides-a-unique-opportunity-for-the-treatment-of-schizophrenia
#20
REVIEW
Kazunori Suzuki, Haruhide Kimura
The basal ganglia regulates motor, cognitive, and emotional behaviors. Dysfunction of dopamine system in this area is implicated in the pathophysiology of schizophrenia characterized by positive symptoms, negative symptoms, and cognitive deficits. Medium spiny neurons (MSNs) are principal output neurons of striatum in the basal ganglia. Similar to current antipsychotics with dopamine D2 receptor antagonism or partial agonism, phosphodiesterase 10A (PDE10A) inhibitors activate indirect pathway MSNs, leading to the expectation of therapeutic potential for the treatment of psychosis...
January 9, 2018: CNS Neuroscience & Therapeutics
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