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Phosphodiesterase 4

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https://www.readbyqxmd.com/read/28330503/caffeine-modulates-glucocorticoid-induced-expression-of-ctgf-in-lung-epithelial-cells-and-fibroblasts
#1
Markus Fehrholz, Kirsten Glaser, Christian P Speer, Silvia Seidenspinner, Barbara Ottensmeier, Steffen Kunzmann
BACKGROUND: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants...
March 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28302718/a-unique-choanoflagellate-enzyme-rhodopsin-with-cyclic-nucleotide-phosphodiesterase-activity
#2
Kazuho Yoshida, Satoshi P Tsunoda, Leonid S Brown, Hideki Kandori
Photoactivated adenylyl cyclase (PAC) and guanylyl cyclase rhodopsin (Rh-GC) increase the concentrations of intracellular cyclic nucleotides upon illumination, serving as promising second-generation tools in optogenetics. To broaden arsenal of such tools, it is desirable to have light-activatable enzymes which can decrease cyclic nucleotide concentrations in cells. Here, we report on an unusual microbial rhodopsin which may be able to meet the demand. It is found in the choanoflagellate Salpingoeca rosetta and contains a C-terminal cyclic nucleotide phosphodiesterase (PDE) domain...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28300440/review-of-atopic-dermatitis-and-topical-therapies
#3
Julia N Mayba, Melinda J Gooderham
Atopic dermatitis is one of the most common skin disorders in the developed world, affecting up to 20% of children and 1% to 3% of adults. This review concisely explains the pathophysiology and epidemiology of atopic dermatitis, as well as potential challenges facing its successful treatment. Furthermore, mainstay topical treatment modalities are evaluated, such as emollients, topical corticosteroids, and topical calcineurin inhibitors. The use of topical corticosteroids and topical calcineurin inhibitors in combination is discussed, as studies have indicated encouraging results...
December 1, 2016: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28299329/angiotensin-1-7-downregulates-diabetes-induced-cgmp-phosphodiesterase-activation-in-rat-corpus-cavernosum
#4
Gursev S Dhaunsi, Mariam Yousif, Batoul Makki, Saghir Akhtar, Ibrahim F Benter
Molecular mechanisms of the beneficial effects of angiotensin-(1-7), Ang-(1-7), in diabetes-related complications, including erectile dysfunction, remain unclear. We examined the effect of diabetes and/or Ang-(1-7) treatment on vascular reactivity and cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) in corpus cavernosum. Male Wistar rats were grouped as (1) control, (2) diabetic (streptozotocin, STZ, treated), (3) control + Ang-(1-7), and (4) diabetic + Ang-(1-7). Following 3 weeks of Ang-(1-7) treatment subsequent to induction of diabetes, rats were sacrificed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28298895/two-phase-modulation-of-formula-see-text-entry-and-cl-formula-see-text-exchanger-in-submandibular-glands-cells-by-dexmedetomidine
#5
Minjeong Ji, Chul-Kyu Park, Jin Woo Lee, Kook Yang Park, Kuk Hui Son, Jeong Hee Hong
Dexmedetomidine (Dex), a highly selective α2-adrenoceptor agonist, attenuates inflammatory responses induced by lipopolysaccharide (LPS) and induces sedative and analgesic effects. Administration of Dex also reduces salivary secretion in human subjects and inhibits osmotic water permeability in rat cortical collecting ducts. However, little is known about the mechanisms underlying the effects of Dex on salivary glands fluid secretion. We demonstrated the α2-adrenoceptor expression in the basolateral membrane of mouse submandibular glands (SMG)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28290219/2-crisaborole-topical-ointment-for-the-treatment-of-mild-to-moderate-atopic-dermatitis
#6
Alice C Cheape, Dedee F Murrell
Crisaborole 2% topical ointment is an anti-inflammatory, non-steroidal phosphodiesterase 4 inhibitor which is currently under investigation for its potential role in the treatment of atopic dermatitis and psoriasis. Areas covered: So far, 7 trials have been completed in atopic dermatitis. The 2% strength appeared to be the superior dosing regimen. Pruritus improved significantly within one week. The improvements in objective efficacy assessments in crisaborole-treated patients were also statistically significant compared to the vehicle...
March 14, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28289563/persistent-erectile-dysfunction-in-men-exposed-to-the-5%C3%AE-reductase-inhibitors-finasteride-or-dutasteride
#7
Tina Kiguradze, William H Temps, Paul R Yarnold, John Cashy, Robert E Brannigan, Beatrice Nardone, Giuseppe Micali, Dennis Paul West, Steven M Belknap
IMPORTANCE: Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-RIs). Clinical trial reports and the manufacturers' full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure. OBJECTIVE: Our chief objective was to assess whether longer duration of 5α-RI exposure increases risk of PED, independent of age and other known risk factors...
2017: PeerJ
https://www.readbyqxmd.com/read/28286190/outcome-of-adults-with-eisenmenger-syndrome-treated-with-drugs-specific-to-pulmonary-arterial-hypertension-a-french-multicentre-study
#8
Sebastien Hascoet, Emmanuelle Fournier, Xavier Jaïs, Lauriane Le Gloan, Claire Dauphin, Ali Houeijeh, Francois Godart, Xavier Iriart, Adelaïde Richard, Jelena Radojevic, Pascal Amedro, Gilles Bosser, Nathalie Souletie, Yvette Bernard, Pamela Moceri, Hélène Bouvaist, Pierre Mauran, Elise Barre, Adeline Basquin, Clement Karsenty, Damien Bonnet, Laurence Iserin, Olivier Sitbon, Jérôme Petit, Elie Fadel, Marc Humbert, Magalie Ladouceur
BACKGROUND: The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. AIMS: To investigate outcomes in patients with ES, and their relationship with PAH-SDT. METHODS: Retrospective, observational, nationwide, multicentre cohort study. RESULTS: We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22...
March 9, 2017: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/28281360/bioactive-triterpenoids-from-the-leaves-of-eriobotrya-japonica-as-the-natural-pde4-inhibitors
#9
Bing-Xin Tan, Lu Yang, Yi-You Huang, Yun-Yun Chen, Guang-Tian Peng, Si Yu, Yi-Nuo Wu, Hai-Bin Luo, Xi-Xin He
The ethanolic extract of the leaves of Eriobotrya japonica exhibited inhibitory activity against phosphodiesterase-4D (PDE4D), which is a therapeutic target of inflammatory disease. Subsequent bioassay-guided fractionation led to the isolation of a new triterpene (1), together with seven known triterpenoids, methyl corosolate (2), ursolic acid (3), oleanolic acid (4), methyl maslinate (5), α-amyin (6), 3β,19α,23-trihydroxy-urs-12-ene (7) and uvaol (8). The structure of compound 1 was established as 3β-hydroxyl-21β-acetoxyl-urs-12-en-28-carboxylate on the basis of interpretation of its 1D and 2D NMR and HR-ESI-MS spectroscopic data...
March 10, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28276777/apremilast-for-the-management-of-moderate-to-severe-plaque-psoriasis
#10
Ramya Vangipuram, Ali Alikhan
Psoriasis is a chronic inflammatory skin disease characterized by erythematous plaques on extensor surfaces, scalp, and back. Current therapies for psoriasis are limited by route of administration, side effects, and cost. Apremilast is the first oral phosphodiesterase inhibitor approved for moderate-to-severe plaque psoriasis. It is a small molecule inhibitor of phosphodiesterase-4, and decreases the inflammatory activity associated with psoriasis. Areas covered: This review will discuss the pharmacology of apremilast, mechanism of action, results from key clinical trials, and its use in managing psoriasis...
February 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28268167/low-intensity-extracorporeal-shockwave-therapy-in-sexual-medicine-a%C3%A2-questionnaire-based-assessment-of-knowledge-clinical-practice-patterns-and-attitudes-in-sexual-medicine-practitioners
#11
Mikkel Fode, Lior Lowenstein, Yacov Reisman
INTRODUCTION: Low-intensity extracorporeal shockwave therapy (LI-ESWT) has emerged as a treatment option for male sexual dysfunction. However, results have been contradictory. AIM: To investigate the knowledge, practice patterns, and attitudes regarding LI-ESWT among experts in sexual medicine. METHODS: A study-specific questionnaire was handed out at the 18th Congress for the European Society for Sexual Medicine. Participants were queried on their knowledge about LI-ESWT and about their use of the equipment...
March 4, 2017: Sexual Medicine
https://www.readbyqxmd.com/read/28263828/6-hydroxy-5-7-dimethoxy-flavone-suppresses-the-neutrophil-respiratory-burst-via-selective-pde4-inhibition-to-ameliorate-acute-lung-injury
#12
Yung-Fong Tsai, Tzu-Chi Chu, Wen-Yi Chang, Yang-Chang Wu, Fang-Rong Chang, Shun-Chin Yang, Tung-Ying Wu, Yu-Ming Hsu, Chun-Yu Chen, Shih-Hsin Chang, Tsong-Long Hwang
Over-activated neutrophils produce enormous oxidative stress and play a key role in the development of acute and chronic inflammatory diseases. 6-Hydroxy-5,7-dimethoxy-flavone (UFM24), a flavone isolated from the Annonaceae Uvaria flexuosa, showed inhibitory effects on human neutrophil activation and salutary effects on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. UFM24 potently inhibited superoxide anion (O2(•-)) generation, reactive oxidants, and CD11b expression, but not elastase release, in N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils...
March 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28263187/aggregation-of-scaffolding-protein-disc1-dysregulates-phosphodiesterase-4-in-huntington-s-disease
#13
Motomasa Tanaka, Koko Ishizuka, Yoko Nekooki-Machida, Ryo Endo, Noriko Takashima, Hideyuki Sasaki, Yusuke Komi, Amy Gathercole, Elaine Huston, Kazuhiro Ishii, Kelvin Kai-Wan Hui, Masaru Kurosawa, Sun-Hong Kim, Nobuyuki Nukina, Eiki Takimoto, Miles D Houslay, Akira Sawa
Huntington's disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DISC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice)...
March 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28261676/efficacy-of-phosphodiesterase-type-5-inhibitors-for-the-treatment-of-distal-ureteral-calculi-a-systematic-review-and-meta-analysis
#14
Carlos Eduardo Montes Cardona, Herney Andrés García-Perdomo
PURPOSE: To determine the efficacy of phosphodiesterase type 5 inhibitors (PDE5i) as medical expulsive therapy (MET) for the treatment of distal ureteral calculi. MATERIALS AND METHODS: A search strategy was conducted in the MEDLINE, CENTRAL, and Embase databases. Searches were also conducted in other databases and unpublished literature. Clinical trials were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool...
March 2017: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/28260869/efficacy-and-safety-of-short-and-long-term-regular-and-on-demand-regimens-of-phosphodiesterase-type-5-inhibitors-in-treating-erectile-dysfunction-after-nerve-sparing-radical-prostatectomy-a-systematic-review-and-meta-analysis
#15
Daxue Tian, Xiao-Yan Wang, Huan-Tao Zong, Yong Zhang
BACKGROUND: We performed a meta-analysis to evaluate the efficacy and safety of short-term (≤6 months) and long-term (>6 months), regular (OaD) and on-demand (PRN) regimens of phosphodiesterase type 5 inhibitors (PDE5-Is) in treating erectile dysfunction (ED) after nerve-sparing radical prostatectomy (NSRP). METHODS: We conducted a literature search in August 2016. Sources included PubMed, EMBASE, and MEDLINE databases. The main outcome was International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, and the secondary outcome was treatment-emergent adverse events (TEAEs)...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28258955/inhibition-of-cyclic-gmp-export-by-multidrug-resistance-protein-4-a-new-strategy-to-treat-erectile-dysfunction
#16
Charlotte Boydens, Bart Pauwels, Laura Vanden Daele, Johan Van de Voorde
BACKGROUND: Intracellular cyclic guanosine monophosphate (cGMP) concentrations are regulated by degradation enzymes (phosphodiesterases) and by active transport across the plasma membrane by multidrug resistance proteins (MRPs) 4 and 5. AIM: To evaluate the functional effect of MRP-4 inhibition and the role of MRP-4-mediated cGMP export in mouse corpora cavernosa. METHODS: Isometric tension of mouse corpora cavernosa was measured after cumulative addition of MK-571, an inhibitor of MRP-4, or sildenafil, a phosphodiesterase type 5 inhibitor...
February 28, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28258674/ibudilast-a-non%C3%A2-selective-phosphodiesterase-inhibitor-in-brain-disorders
#17
Joanna Schwenkgrub, Małgorzata Zaremba, Dagmara Mirowska-Guzel, Iwona Kurkowska-Jastrzębska
Ibudilast (IBD) is a non‑selective (3, 4, 10, 11) phosphodiesterase (PDE) inhibitor, used mainly as a bronchodilator for the treatment of bronchial asthma. PDE play a central role in cellular function (e.g. differentiation, synaptic plasticity and inflammatory response) by metabolizing cyclic nucleotides. The results from preclinical and clinical studies indicate that IBD has a broader range of action through suppression of pro‑inflammatory cytokines (IL‑6, IL‑1β, TNF‑α), toll‑like receptor 4 blockade (TLR‑4), inhibition of a macrophage migration inhibitory factor (MIF), up‑regulation the anti‑inflammatory cytokine (IL‑10), and promotion of neurotrophic factors (GDNF, NGF, NT‑4)...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28255962/bringing-stability-to-the-chronic-obstructive-pulmonary-disease-patient-clinical-and-pharmacological-considerations-for-frequent-exacerbators
#18
REVIEW
Swati Gulati, J Michael Wells
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with an accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A 'frequent exacerbator' is a sub-phenotype of chronic obstructive pulmonary disease (COPD) and is defined as an individual who experiences two or more moderate-to-severe exacerbations per year...
March 3, 2017: Drugs
https://www.readbyqxmd.com/read/28255338/apremilast-in-the-treatment-of-psoriatic-arthritis-a-perspective-review
#19
REVIEW
Michael Reed, David Crosbie
Apremilast is an orally-active small molecule which inhibits phosphodiesterase-4 (PDE4). Clinical trials have demonstrated its efficacy and safety in psoriatic arthritis (PsA) and psoriasis. Established therapeutic options have variable effectiveness across the different domains of psoriatic disease. Whilst biologic therapies have proven to be of significant benefit to many patients, not all patients respond, and others are not eligible or do not tolerate biologic therapy. We review the mechanism of action, pharmacokinetics and clinical trial data with regards to both efficacy and safety for apremilast and consider where this new treatment may be positioned in the treatment of PsA...
February 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28248021/-new-data-on-the-effectiveness-of-tadalafil-alone-and-in-combination-with-neyrodoz-in-treating-erectile-dysfunction-associated-with-secondary-premature-ejaculation
#20
N D Akhvlediani, I P Matyukhov
AIM: To compare the effectiveness of the phosphodiesterase type 5 inhibitor (PDE-5i) tadalafil alone and in combination with a biologically active dietary supplement (BADS) NeyroDoz, containing the precursors of serotonin in patients with erectile dysfunction (ED) associated with secondary premature ejaculation (SPE). MATERIAL AND METHODS: 105 patients (mean age 36.2+/-9.1 years) with concomitant ED and SPE were included in a prospective study and divided into 2 groups...
November 2016: Urologii︠a︡
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