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Phosphodiesterase 5 inhibitors

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https://www.readbyqxmd.com/read/28225505/nonrevascularizable-buttock-claudication-improved-with-sildenafil-a-case-report
#1
Loukman Omarjee, Audrey Camarzana, Samir Henni, Pierre Abraham
RATIONALE: Sildenafil, a phosphodiesterase-5-inhibitor (PDE5i), could represent a new treatment in addition to the medical treatment and advice to walk in peripheral arterial disease (PAD). PATIENT CONCERNS AND DIAGNOSES: We report a case of a 62-year-old heavy smoker man who developed a buttock claudication and a severe walking limitation following an aorto-bi-femoral bypass in 1992. Since 2003, each year, he has been referred for investigation of bilateral buttock claudication on treadmill using transcutaneous oxygen pressure (tcpO2) measurement during exercise to argue for the vascular origin of the walking impairment...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28217454/erectile-dysfunction-treatment-and-traditional-medicine-can-east-and-west-medicine-coexist
#2
REVIEW
Joe K C Lee, Ronny B W Tan, Eric Chung
Erectile dysfunction (ED) is a common sexual problem affecting many men irrespective of cultures, beliefs and nationalities. While medical therapy for ED has been revolutionized by the advent of oral phosphodiesterase type 5 inhibitors and intracavernosal injection of vasoactive agents, recent technological advances such stem cell therapy, low intensity shock wave and newer generation of penile prosthesis implant offer hope to men who do not respond to conventional medical therapy. In contrast, traditional and complementary medicine (TCM) focuses on the restoration and better overall bodily regulation with the use of various herbal and animal products as well as exercises to invigorate qi (energy) in vital organs...
February 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28217449/penile-prosthesis-implant-scientific-advances-and-technological-innovations-over-the-last-four-decades
#3
REVIEW
Eric Chung
Despite introduction of oral phosphodiesterase type 5 inhibitors and intracavernosal vasoactive agents, penile prosthesis implant remains a relevant and desired option with sales of penile prostheses continue to stay high, as many men became refractory to medical therapy and/or seeking a more effective and permanent therapy. There are two types of penile prosthesis implants: inflatable and non-inflatable types, and the inflatable penile implants can be subdivided into single-, two- and three-piece devices. Non-inflatable penile prosthesis (non-IPP) may be referred to as semi-rigid rod or malleable prosthesis...
February 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28217446/the-dangers-of-sexual-enhancement-supplements-and-counterfeit-drugs-to-treat-erectile-dysfunction
#4
REVIEW
Jason Chiang, Faysal A Yafi, Philip J Dorsey, Wayne J G Hellstrom
Counterfeit phosphodiesterase-5 inhibitors (PDE-5i) are an increasing problem. Already in widespread use, the market for PDE-5i is steadily growing as the population ages. Counterfeiters are taking advantage of this growing market by developing illicit and counterfeit PDE-5i products. Many factors are contributing to the rapid growth of the illicit market, such as the low risk of prosecution, potentially high financial reward, and ease of distribution via Internet pharmacies. Consumers of illicit PDE-5i often do not realize they are using counterfeit products and placing themselves at an unnecessary health risk...
February 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28215172/the-phosphodiesterase-5-inhibitors-pde-5i-for-erectile-dysfunction-ed-a-therapeutic-challenge-for-psychiatrists
#5
Chong Siew Koon, Hatta Sidi, Jaya Kumar, Srijit Das, Ong Wan Xi, Muhammad Hizri Hatta, Cesar Alfonso
Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually leads to orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in the context of treating ED constitutes a therapeutic challenge...
February 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#6
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28210757/sildenafil-a-phosphodiesterase-type-5-inhibitor-downregulates-osteopontin-in-human-peripheral-blood-mononuclear-cells
#7
Beata Kaleta, Agnieszka Boguska
The aim of this study was to investigate the ability of sildenafil to regulate osteopontin (OPN) gene and protein in peripheral blood mononuclear cells (PBMCs) from healthy blood donors. OPN is expressed by a wide variety of cell types, including immune cells. OPN functions are linked to various physiological and pathological conditions. Sildenafil is a selective inhibitor of type 5 phosphodiesterase. Sildenafil has recently been found to have immunomodulatory effects in animal models and in studies performed in humans...
February 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28204955/inactivation-of-non-canonical-cyclic-nucleotides-hydrolysis-and-transport
#8
Erich H Schneider, Roland Seifert
This chapter addresses cNMP hydrolysis by phosphodiesterases (PDEs) and export by multidrug resistance associated proteins (MRPs). Both mechanisms are well-established for the canonical cNMPs, cAMP, and cGMP. Increasing evidence shows that non-canonical cNMPs (specifically cCMP, cUMP) are also PDE and MRP substrates. Hydrolysis of cUMP is achieved by PDE 3A, 3B, and 9A, which possibly explains the cUMP-degrading activities previously reported for heart, adipose tissue, and brain. Regarding cCMP, the only known "conventional" (class I) PDE that hydrolyzes cCMP is PDE7A...
February 16, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28196856/vardenafil-reduces-macrophage-pro-inflammatory-overresponses-in-cystic-fibrosis-through-pde5-and-cftr-dependent-mechanisms
#9
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type littermates...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28190786/survival-in-portopulmonary-hypertension-outcomes-of-the-united-kingdom-national-pulmonary-arterial-hypertension-registry
#10
Sasiharan Sithamparanathan, Arun Nair, Logan Thirugnanasothy, J Gerry Coghlan, Robin Condliffe, Konstantinos Dimopoulos, Charlie A Elliot, Andrew J Fisher, Sean Gaine, J Simon R Gibbs, Michael A Gatzoulis, Clive E Handler, Luke S Howard, Martin Johnson, David G Kiely, James L Lordan, Andrew J Peacock, Joanna Pepke-Zaba, Benjamin E Schreiber, Karen K K Sheares, Stephen J Wort, Paul A Corris
BACKGROUND: Portopulmonary hypertension (PoPH) is a rare condition associated with poor survival, and the effect of modern therapies that target pulmonary arterial hypertension (PAH) on long-term outcome is unknown. This study investigated the baseline characteristics and survival in the cohort of patients diagnosed with PoPH in the United Kingdom National Pulmonary Hypertension Service. METHODS: A retrospective review was conducted of all incident treatment-naïve patients with PoPH within the United Kingdom national registry diagnosed between January 2001 and December 2010...
December 31, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28165743/design-and-synthesis-of-novel-and-selective-phosphodiesterase-2-pde2-inhibitors-for-the-treatment-of-memory-disorders
#11
Laurent Gomez, Mark Eben Massari, Troy Vickers, Graeme Freestone, William F Vernier, Kiev Ly, Rui Xu, Margaret McCarrick, Tami Marrone, Markus Metz, Yingzhou G Yan, Zachary W Yoder, Robert Lemus, Nicola J Broadbent, Richard Barido, Noelle Warren, Kara Schmelzer, David Neul, Dong Lee, Carsten B Andersen, Kristen Sebring, Kathleen Aertgeerts, Xianbo Zhou, Ali Tabatabaei, Marco Peters, J Guy Breitenbucher
A series of potent and selective [1,2,4]triazolo[1,5-a]pyrimidine PDE2 inhibitors is reported. The design and improvement of the binding properties of this series was achieved using X-ray crystal structures in conjunction with careful analysis of electronic and structural requirements for the PDE2a enzyme. One of the lead compounds, compound 27 (DNS-8254), was identified as a potent and highly selective PDE2a enzyme inhibitor with favorable rat pharmacokinetic properties. Interestingly, increased potency of compound 27 was facilitated by the formation of a halogen bond with the oxygen of Tyr827 present in the PDE2 active site...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28162947/fty720-supplementation-partially-improves-erectile-dysfunction-in-rats-with-streptozotocin-induced-type-1-diabetes-through-inhibition-of-endothelial-dysfunction-and-corporal-fibrosis
#12
Kai Cui, Yajun Ruan, Tao Wang, Ke Rao, Zhong Chen, Shaogang Wang, Jihong Liu
INTRODUCTION: Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis. AIM: To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED)...
February 2, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28155571/the-augmentation-of-bk-channel-activity-by-nitric-oxide-signaling-in-rat-cerebral-arteries-involves-co-localized-regulatory-elements
#13
Barry D Kyle, Ramesh C Mishra, Andrew P Braun
Large conductance, Ca(2+)-activated K(+) (BK) channels control cerebrovascular tone; however, the regulatory processes influencing these channels remain poorly understood. Here, we investigate the cellular mechanisms underlying the enhancement of BK current in rat cerebral arteries by nitric oxide (NO) signaling. In isolated cerebral myocytes, BK current magnitude was reversibly increased by sodium nitroprusside (SNP, 100 μM) and sensitive to the BK channel inhibitor, penitrem-A (100 nM). Fostriecin (30 nM), a protein phosphatase type 2A (PP2A) inhibitor, significantly prolonged the SNP-induced augmentation of BK current and a similar effect was produced by sildenafil (30 nM), a phosphodiesterase 5 (PDE5) inhibitor...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28144281/lipoxin-a4-as-a-possible-mediator-of-the-beneficial-actions-of-phosphodiesterase-5-enzyme-inhibitors
#14
Undurti N Das
No abstract text is available yet for this article.
February 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28139291/phosphodiesterase-type-5-inhibitors-for-the-treatment-of-erectile-dysfunction-pharmacology-and-clinical-impact-of-the-sildenafil-citrate-orodispersible-tablet-formulation
#15
REVIEW
Francesco Scaglione, Shaantanu Donde, Tarek A Hassan, Emmanuele A Jannini
PURPOSE: The purpose of this review is to provide an overview of the pharmacology, tolerability, and efficacy of the different phosphodiesterase type 5 (PDE5) inhibitors available for the treatment of erectile dysfunction (ED), with a special focus on the sildenafil orodispersible tablet (ODT) formulation. METHODS: A literature search was performed in PubMed, EMBASE, and Cochrane Reviews using the terms erectile dysfunction, patient preference, sildenafil, and PDE5 inhibitors to identify articles published in English between May 1, 2006, and November 18, 2016...
January 27, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28133708/tadalafil-improves-lean-mass-and-endothelial-function-in-nonobese-men-with-mild-ed-luts-in-vivo-and-in-vitro-characterization
#16
Antonio Aversa, Simona Fittipaldi, Davide Francomano, Viviana M Bimonte, Emanuela A Greco, Clara Crescioli, Luigi Di Luigi, Andrea Lenzi, Silvia Migliaccio
PURPOSE: Phosphodiesterase type-5 inhibitor administration in diabetic men with erectile dysfunction (ED) is associated with reduced waist circumference. We evaluated potential effects of daily tadalafil administration on body composition and investigated its possible mechanism(s) of action in C2C12 skeletal muscle cells in vitro. METHODS: Forty-three men on stable caloric intake (mean age 48.5 ± 7; BMI 25.5 ± 0.9 kg/m(2)) complaining mild ED and/or low urinary tract symptoms (LUTS) were randomly assigned to receive tadalafil (TAD) 5 mg/daily (once-a-day=OAD-TAD; n = 23) or 20 mg on-demand (on-demand=OD-TAD; n = 20) for 2 months...
January 30, 2017: Endocrine
https://www.readbyqxmd.com/read/28132591/exploring-pyrazolo-3-4-d-pyrimidine-phosphodiesterase-1-pde1-inhibitors-a-predictive-approach-combining-comparative-validated-multiple-molecular-modeling-techniques
#17
Sk Abdul Amin, Sonam Bhargava, Nilanjan Adhikari, Shovanlal Gayen, Tarun Jha
Phosphodiesterase 1 (PDE1) is a potential target for a number of neurodegenerative disorders such as Schizophrenia, Parkinson's and Alzheimer's diseases. A number of pyrazolo[3,4-d]pyrimidine PDE1 inhibitors were subjected to different molecular modeling techniques [such as regression-based quantitative structure-activity relationship (QSAR): multiple linear regression (MLR), support vector machine (SVM) and artificial neural network (ANN); classification-based QSAR: Bayesian modeling and Recursive partitioning; Monte Carlo based QSAR; Open3DQSAR; pharmacophore mapping and molecular docking analyses] to get a detailed knowledge about the physicochemical and structural requirements for higher inhibitory activity...
January 29, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28132040/erectile-dysfunction-as-a-predictor-of-cardiovascular-disease
#18
Sh Janjgava, T Doliashvili
Endothelial dysfunction precedes the clinical stage of atherosclerotic disease and is recognized as an additional risk factor when detecting symptomatic patients. Endothelial function is largely mediated by nitric oxide, and this vasodilatory mechanism is also responsible for the venous and arterial dilatation required to obtain and maintain an erection. The physiological effects and clinical aspects of sexual function have been extensively studied and reported in patients who have angina or who have experienced a myocardial infarction and in those who have undergone coronary artery bypass graft surgery or heart transplant...
December 2016: Georgian Medical News
https://www.readbyqxmd.com/read/28129714/time-of-onset-of-vardenafil-orodispersible-tablet-in-a-real-life-setting-looking-beyond-randomized-clinical-trials
#19
Paolo Capogrosso, Eugenio Ventimiglia, Luca Boeri, Alessandro Serino, Andrea Russo, Giovanni La Croce, Umberto Capitanio, Federico Dehò, Francesco Montorsi, Andrea Salonia
BACKGROUND: A rapid onset of action for phosphodiesterase type 5 inhibitors (PDE5is) emerged to be of clinical importance in men treated for erectile dysfunction (ED). Data from randomized clinical trials (RCTs) showed a rapid onset of action for vardenafil 10 mg orodispersible tablet (ODT). However, the effectiveness of vardenafil ODT has never been tested in a real-life setting. We assessed the efficacy and time to onset of action of vardenafil ODT in men seeking medical help for ED in the everyday real-life clinical practice...
March 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28129699/advances-in-the-pharmacotherapy-of-chronic-heart-failure-with-preserved-ejection-fraction-an-ideal-opportunity-for-precision-medicine
#20
Vincenzo B Polsinelli, Sanjiv J Shah
Heart failure with preserved ejection fraction (HFpEF), which comprises approximately 50% of all heart failure patients, is a challenging and complex clinical syndrome that is often thought to lack effective treatments. Areas covered: Despite the common mantra that HFpEF has no effective treatments, closer inspection of HFpEF clinical trials reveals that several of the drugs tested are associated with benefits in exercise capacity and quality of life, and reduction in heart failure hospitalization. Here we review major randomized controlled trials in HFpEF, focusing on renin-angiotensin-aldosterone system antagonists, organic nitrates, digoxin, beta-blockers, and phosphodiesterase-5 inhibitors...
January 27, 2017: Expert Opinion on Pharmacotherapy
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