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Phosphodiesterase 5 inhibitors

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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
#1
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
#2
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/28540239/the-impact-and-management-of-sexual-dysfunction-secondary-to-pharmacological-therapy-of-benign-prostatic-hyperplasia
#3
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
#4
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/28533270/classical-activation-of-macrophages-and-vardenafil
#5
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
#6
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
#7
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/28515693/rolipram-improves-outcome-in-a-rat-model-of-infant-sepsis-induced-cardiorenal-syndrome
#8
Clark R Sims, Sharda P Singh, Shengyu Mu, Neriman Gokden, Dala Zakaria, Trung C Nguyen, Philip R Mayeux
While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28515348/relation-of-phosphodiesterase-type-5-inhibitors-and-malignant-melanoma-a-meta-analysis-and-systematic-review
#9
Jie Wang, Yigen Shen, Jiaoni Wang, Yangjing Xue, Lianming Liao, Saroj Thapa, Kangting Ji
Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up to February 2017, and a random effects model was used to calculate the summary risk estimates. Five observational studies were included. Five studies reports encompassed a total of 15,979 melanoma cases occurring among 1, 188,414 participants. The pooled multivariable-adjusted RR of melanoma in patients with using PDE5 inhibitors was 1...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507431/targeted-drugs-for-pulmonary-arterial-hypertension-a-network-meta-analysis-of-32-randomized-clinical-trials
#10
Xiao-Fei Gao, Jun-Jie Zhang, Xiao-Min Jiang, Zhen Ge, Zhi-Mei Wang, Bing Li, Wen-Xing Mao, Shao-Liang Chen
BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28507310/molecular-and-functional-characterization-of-the-bmpr2-gene-in-pulmonary-arterial-hypertension
#11
Guillermo Pousada, Vincenzo Lupo, Sheila Cástro-Sánchez, María Álvarez-Satta, Ana Sánchez-Monteagudo, Adolfo Baloira, Carmen Espinós, Diana Valverde
Pulmonary arterial hypertension is a progressive disease that causes the obstruction of precapillary pulmonary arteries and a sustained increase in pulmonary vascular resistance. The aim was to analyze functionally the variants found in the BMPR2 gene and to establish a genotype-phenotype correlation. mRNA expression studies were performed using pSPL3 vector, studies of subcellular localization were performed using pEGFP-N1 vector and luciferase assays were performed using pGL3-Basic vector. We have identified 30 variants in the BMPR2 gene in 27 of 55 patients...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28503744/treatment-using-tadalafil-for-severe-pre-eclampsia-with-fetal-growth-restriction
#12
Hiroaki Tanaka, Michiko Kubo, Masafumi Nii, Sintarou Maki, Takashi Umekawa, Tomoaki Ikeda
For severe pre-eclampsia (PE) with fetal growth restriction (FGR), the only effective treatment is early delivery of the placenta. Clinicians are often forced to end the pregnancy because of maternal indications. We report a case of severe PE with FGR in which the PE was temporarily improved and pregnancy successfully prolonged with tadalafil, a phosphodiesterase 5 inhibitor. A 35-year-old primigravid woman presented at 27 3/7 weeks of gestation with severe PE and FGR. After commencing tadalafil administration, biochemical and angiogenic markers improved...
May 15, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28497446/the-role-of-water-jet-dissection-in-improving-erectile-function-and-urinary-continence-after-nerve-sparing-prostatectomy
#13
Peter V Glybochko, Leonid M Rapoport, Eugene A Bezrukov, Eugene S Sirota, Gurgen A Martirosyan
OBJECTIVES: The aim of this study was to assess erectile function (EF) and urinary continence (UC) recovery after nerve-sparing retropubic radical prostatectomy (NS-RRPE) and nerve-sparing laparoscopic radical prostatectomy (NS-LRPE) depending on the neurovascular bundle (NVB) dissection technique used. METHODS: Twenty-four hour pad test was used to assess the degree of postoperative UC 1, 6 and 12 months after the surgery. For the purpose of EF assessment, International Index of Erectile Function-5 (IIEF-5) questionnaire was used...
May 10, 2017: Urologia
https://www.readbyqxmd.com/read/28496549/phosphodiesterase-5-inhibitors-improve-clinical-outcomes-exercise-capacity-and-pulmonary-hemodynamics-in-patients-with-heart-failure-with-reduced-left-ventricular-ejection-fraction-a-meta-analysis
#14
Renato De Vecchis, Arturo Cesaro, Carmelina Ariano, Anna Giasi, Carmela Cioppa
BACKGROUND: Several studies have compared the use of phosphodiesterase-5 (PDE5) inhibitors sildenafil or udenafil with the placebo in patients suffering from pulmonary hypertension (PH) due to left chronic heart failure (CHF), corresponding to group 2 (PH due to left heart disease) of the PH classification (according to 2015 ESC/ERS guidelines for the diagnosis and treatment of PH). The results of the use of PDE5 inhibitors in the PH due to left heart disease were inconsistent and heterogeneous...
June 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28494463/plasma-drug-concentrations-in-patients-with-pulmonary-arterial-hypertension-on-combination-treatment
#15
Ekkehard Grünig, Johanna Ohnesorge, Nicola Benjamin, Jürgen Burhenne, Yeliz Enderle, Benjamin Egenlauf, Christine Fischer, Satenik Harutyunova, Andrea Huppertz, Hans Klose, Walter E Haefeli
BACKGROUND: Combination therapy with the phosphodiesterase type 5 inhibitors (PDE-5i) sildenafil or tadalafil and the endothelin receptor antagonists (ERA) bosentan, ambrisentan, or macitentan may cause mutual pharmacokinetic interactions in patients with pulmonary arterial hypertension (PAH). OBJECTIVE: The objective of this study was to analyze plasma drug concentrations in PAH patients receiving different combination treatments. METHODS: PAH patients receiving a stable combination treatment with ERA and PDE-5i with targeted dosage for at least 1 month were routinely assessed, including clinical parameters and plasma drug concentrations...
May 12, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28487391/functional-characterization-of-the-gucy1a3-coronary-artery-disease-risk-locus
#16
Thorsten Kessler, Jana Wobst, Bernhard Wolf, Juliane Eckhold, Baiba Vilne, Ronja Hollstein, Simon von Ameln, Tan An Dang, Hendrik B Sager, Philipp Moritz Rumpf, Redouane Aherrahrou, Adnan Kastrati, Johan L M Bjoerkegren, Jeanette Erdmann, Aldons J Lusis, Mete Civelek, Frank J Kaiser, Heribert Schunkert
Background -A chromosomal locus at 4q32.1 has been genome-wide significantly associated with coronary artery disease risk. The locus encompasses GUCY1A3, which encodes the α1-subunit of the soluble guanylyl cyclase (sGC), a key enzyme in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. The mechanism linking common variants in this region with coronary risk is not known. Methods -Gene and protein expression were analyzed using quantitative polymerase chain reaction (qPCR) and immunoblotting, respectively...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28486684/superior-vasodilation-of-human-pulmonary-vessels-by-vardenafil-compared-with-tadalafil-and-sildenafil-additive-effects-of-bosentan%C3%A2
#17
Michael Ried, Reiner Neu, Karla Lehle, Christian Großer, Tamas Szöke, Gunter Lang, Hans-Stefan Hofmann, Markus Hoenicka
OBJECTIVES: Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model. METHODS: Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens...
May 9, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28483456/protective-role-of-cgmp-in-early-sepsis
#18
Vanessa Kovalski, Ana P Prestes, Junior G Oliveira, Gustavo F Alves, Daiandra Fr Colarites, Jheniffer El Mattos, Regina Sordi, José Cr Vellosa, Daniel Fernandes
Septic shock, which is triggered by microbial products, is mainly characterised by inadequate tissue perfusion, which can lead to multiple organ dysfunction and death. An intense release of vasoconstrictors agents occurs in the early stages of shock, which can lead to ischemic injury. In this scenario, cGMP could play a key role in counterbalancing these agents and preventing tissue damage. Sildenafil, which is a phosphodiesterase-5 inhibitor, increases cGMP in smooth muscle cells and promotes vasodilation...
May 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28477089/the-phosphodiesterase-4-inhibitor-roflumilast-decreases-ethanol-consumption-in-c57bl-6j-mice
#19
Xin Liu, Pi-Da Hao, Ming-Feng Yang, Jing-Yi Sun, Lei-Lei Mao, Cun-Dong Fan, Zong-Yong Zhang, Da-Wei Li, Xiao-Yi Yang, Bao-Liang Sun, Han-Ting Zhang
RATIONALE: Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption...
May 6, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28468928/sildenafil-suppresses-inflammation-driven-colorectal-cancer-in-mice
#20
Bianca N Islam, Sarah K Sharman, Yali Hou, Allison E Bridges, Nagendra Singh, Sangmi Kim, Ravindra Kolhe, Jimena Trillo-Tinoco, Paulo C Rodriguez, Franklin G Berger, Subbaramiah Sridhar, Darren D Browning
Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against DSS-induced barrier dysfunction...
May 3, 2017: Cancer Prevention Research
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