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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
#1
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/29135645/phosphodiesterase-type-5-inhibitors-sport-and-doping
#2
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/29134978/testicular-and-epididymal-histology-of-rats-chronically-administered-high-doses-of-phosphodiesterase-5-inhibitors-and-tramadol
#3
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/29132113/fluorometric-detection-of-protein-ligand-engagement-the-case-of-phosphodiesterase5
#4
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/29094398/early-improvement-of-storage-or-voiding-symptoms-by-tadalafil-predicts-treatment-outcomes-in-patients-with-lower-urinary-tract-symptoms-from-benign-prostatic-hyperplasia
#5
Osamu Yokoyama, Akichika Ozeki, Nahoko Suzuki, Masahiro Murakami
OBJECTIVES: To determine whether early changes in International Prostate Symptom Score predict final improvement in the quality of life and treatment satisfaction of patients with lower urinary tract symptoms from benign prostatic hyperplasia receiving tadalafil. METHODS: This post-hoc analysis of three randomized-controlled trials of tadalafil for lower urinary tract symptoms from benign prostatic hyperplasia used subpopulations based on treatment status (tadalafil, placebo) and region (Japan, Asia)...
November 1, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29094165/phosphodiesterase-inhibitors-sildenafil-and-vardenafil-reduce-zebrafish-rod-photoreceptor-outer-segment-shedding
#6
Leah J Campbell, Abbie M Jensen
Purpose: The vertebrate rod photoreceptor undergoes daily growth and shedding to renew the rod outer segment (ROS), a modified cilium that contains the phototransduction machinery. It has been demonstrated that ROS shedding is regulated by the light-dark cycle; however, we do not yet have a satisfactory understanding of the molecular mechanisms that underlie this regulation. Given that phototransduction relies on the hydrolysis of cGMP via phosphodiesterase 6 (PDE6), we examined ROS growth and shedding in zebrafish treated with cGMP-specific PDE inhibitors...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29089445/novel-imaging-of-the-prostate-reveals-spontaneous-gland-contraction-and-excretory-duct-quiescence-together-with-different-drug-effects
#7
Robert Kügler, Andrea Mietens, Mathias Seidensticker, Sabine Tasch, Florian M Wagenlehner, Andre Kaschtanow, Yudy Tjahjono, Claudia U Tomczyk, Daniela Beyer, Gail P Risbridger, Betty Exintaris, Stuart J Ellem, Ralf Middendorff
Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect...
October 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29080533/pt-nanoparticles-supported-on-nitrogen-doped-porous-graphene-for-sensitive-detection-of-tadalafil
#8
Abdulwahab Salah, Mehboob Hassan, Jian Liu, Minghui Li, Xiangjie Bo, Jean Chrysostome Ndamanisha, Liping Guo
Graphene (GR) is one of the most promising candidates for utilization in the electroanalytical field because of its superior electrocatalytic activity, excellent electronic conductivity, and high chemical stability. However, the GR sheets usually tend to stack together with π-π interaction. The spontaneous stacking leads to the aggregation of the GR sheets and imposes a negative feedback in the surface area of the GR, which obviously limits its electrochemical application. In this study, nitrogen-doped porous GR (NPGR) with different pore sizes is prepared by using silica (SiO2) as a template...
October 7, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29073911/successful-transition-from-treprostinil-to-selexipag-in-patient-with-severe-pulmonary-arterial-hypertension
#9
Asuka Furukawa, Yuichi Tamura, Hiroya Iwahori, Masato Goto, Narutaka Ohashi, Teruo Okabe, Akio Kawamura
BACKGROUND: In this report, we describe the first successful case of transition from subcutaneous administration of treprostinil to selexipag in a patient with severe pulmonary arterial hypertension (PAH), by evaluating hemodynamic changes and exercise tolerance. CASE PRESENTATION: A 38-year-old female with idiopathic PAH (IPAH) had received initial triple combination therapy (macitentan PO, tadalafil PO, and treprostinil SC) and achieved excellent improvement in hemodynamics...
October 26, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29068218/design-synthesis-and-biological-evaluation-of-orally-available-first-generation-dual-target-selective-inhibitors-of-acetylcholinesterase-ache-and-phosphodiesterase-5-pde5-for-the-treatment-of-alzheimer-s-disease
#10
Fei Mao, Huan Wang, Wei Ni, Xinyu Zheng, Manjiong Wang, Keting Bao, Dazheng Ling, Xiaokang Li, Yixiang Xu, Haiyan Zhang, Jian Li
Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for AD. Among these derivatives, 1p and 1w exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, 1w·Cit (citrate of 1w) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity...
October 25, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29064468/neuromuscular-disease-tadalafil-fails-to-halt-the-progression-of-duchenne-muscular-dystrophy
#11
Heather Wood
No abstract text is available yet for this article.
October 23, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29038811/model-averaging-of-ab-initio-spectra-for-the-absolute-configuration-assignment-via-vibrational-circular-dichroism
#12
Guglielmo Monaco, Francesco Aquino, Riccardo Zanasi, Wouter Herrebout, Patrick Bultinck, Antonio Massa
Vibrational absorption and vibrational circular dichroism spectra (VA and VCD) have been recorded for two hybrid isoindolinone-phtalide stereoisomers dissolved in CDCl3. Density-functional calculations have been performed to determine their absolute configuration. A comparison of calculated and measured values has been made using several goodness-of-fit indicators, and also introducing a model-averaging technique, taking into account the variation of calculated spectra with the details of the computational method...
October 25, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28994364/comparison-of-the-therapeutic-effects-and-side-effects-of-tadalafil-and-sildenafil-after-surgery-in-young-infants-with-pulmonary-arterial-hypertension-due-to-systemic-to-pulmonary-shunts
#13
Mohammad Reza Sabri, Hamid Bigdelian, Mohsen Hosseinzadeh, Alireza Ahmadi, Mehdi Ghaderian, Mohammad Shoja
Young children with CHD and large systemic-to-pulmonary shunts eventually develop pulmonary hypertension. At present, phosphodiesterase type-5 inhibitors such as sildenafil have been used to control pulmonary pressure before and after cardiac surgery. Recently, tadalafil has been utilised in older children with similar efficacy, but it has been used to a lesser extent in young infants. From April, 2015 to June, 2016, 42 patients aged 3-24 months with a large septal defect and pulmonary arterial hypertension were randomly divided into two equal groups: one group received oral sildenafil (1-3 mg/kg/day every 8 hours), whereas the other group received oral tadalafil (1 mg/kg once a day) from 7-10 days before surgery to 3-4 weeks after surgery...
November 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/28992178/tadalafil-improves-l-ng-nitroarginine-methyl-ester-induced-preeclampsia-with-fetal-growth-restriction-like-symptoms-in-pregnant-mice
#14
Kento Yoshikawa, Takashi Umekawa, Shintaro Maki, Michiko Kubo, Masafumi Nii, Kayo Tanaka, Hiroaki Tanaka, Kazuhiro Osato, Yuki Kamimoto, Eiji Kondo, Kenji Ikemura, Masahiro Okuda, Kan Katayama, Takekazu Miyoshi, Hiroshi Hosoda, Ning Ma, Toshimichi Yoshida, Tomoaki Ikeda
BACKGROUND: We investigated the efficacy and mechanisms of tadalafil, a selective phosphodiesterase 5 inhibitor, in treating preeclampsia (PE) with fetal growth restriction (FGR) using L-NG-nitroarginine methyl ester (L-NAME)-induced PE with FGR in pregnant mice as our experimental model. METHODS: C57BL/6 mice were divided into 2 groups 11 days postcoitum (d.p.c.). A control group of dams (C dam) received 0.5% carboxymethylcellulose (CMC). A L-NAME-treated group received 1 mg/ml L-NAME dissolved in CMC...
August 3, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28987539/statistical-investigation-of-the-full-concentration-range-of-fasted-and-fed-simulated-intestinal-fluid-on-the-equilibrium-solubility-of-oral-drugs
#15
Jeremy Perrier, Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G Wilson, Gavin Halbert
Upon oral administration the solubility of a drug in intestinal fluid is a key property influencing bioavailability. It is also recognised that simple aqueous solubility does not reflect intestinal solubility and to optimise in vitro investigations simulated intestinal media systems have been developed. Simulated intestinal media which can mimic either the fasted or fed state consists of multiple components each of which either singly or in combination may influence drug solubility, a property that can be investigated by a statistical design of experiment technique...
October 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28977204/tadalafil-protective-action-against-the-development-of-multiple-organ-failure-syndrome
#16
Granville G de Oliveira, Samer A H de Oliveira, Paulo Henrique H Botelho, Marcos Aurelio Barboza de Oliveira, Ka Bian, Ferid Murad
INTRODUCTION: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation...
July 2017: Brazilian Journal of Cardiovascular Surgery
https://www.readbyqxmd.com/read/28977106/daily-use-of-phosphodiesterase-type-5-inhibitors-as-prevention-for-recurrent-priapism
#17
Archimedes Nardozza, Marcelo Rodrigues Cabrini
OBJECTIVE: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. METHOD: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24...
August 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28972192/a-phase-3-randomized-placebo-controlled-trial-of-tadalafil-for-duchenne-muscular-dystrophy
#18
RANDOMIZED CONTROLLED TRIAL
Ronald G Victor, H Lee Sweeney, Richard Finkel, Craig M McDonald, Barry Byrne, Michelle Eagle, Nathalie Goemans, Krista Vandenborne, Alberto L Dubrovsky, Haluk Topaloglu, M Carrie Miceli, Pat Furlong, John Landry, Robert Elashoff, David Cox
OBJECTIVE: To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD). METHODS: Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg(-1)·d(-1), tadalafil 0.6 mg·kg(-1)·d(-1), or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks...
October 24, 2017: Neurology
https://www.readbyqxmd.com/read/28964803/cyclic-guanosine-monophosphate-modulates-accumulation-of-phosphodiesterase-5-inhibitors-in-human-platelets
#19
Gzona Bajraktari, Jürgen Burhenne, Peter Bugert, Walter Emil Haefeli, Johanna Weiss
Sildenafil and tadalafil are widely-used phosphodiesterase 5 (PDE5) inhibitors for which no clear dose-response relationship could be established. Using isolated and/or recombinant PDE5, it has been demonstrated that cGMP can increase the affinity of this enzyme for sildenafil and tadalafil. We thus hypothesized that in cells expressing the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate - PDE5 (NO-sGC-cGMP-PDE5) pathway such as platelets, the presence of NO increases the intracellular cGMP content and thus promotes the intracellular accumulation of sildenafil or tadalafil...
September 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28948321/contralateral-pulmonary-hypertension-following-resuscitation-of-unilateral-ductal-origin-of-a-pulmonary-artery-a-multi-institutional-review
#20
Hitesh Agrawal, Christopher J Petit, Joaquim Miro, Carlos D Miranda, Damien Kenny, Henri Justino
In isolated unilateral ductal origin of a pulmonary artery (DOPA), intervention to establish reperfusion of the affected lung without direct re-anastomosis may lead to pulmonary hypertension (PH) in the contralateral lung. Multicenter retrospective review of patients with unilateral DOPA, who underwent palliation with a ductal stent (DS) or Blalock-Taussig (BT) shunt with subsequent development of PH in the contralateral lung, was conducted. Ten patients (4 females; median weight 3.2 kg, range 2.1-5.2) who underwent DS or BT shunt and developed contralateral PH were identified...
September 25, 2017: Pediatric Cardiology
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