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Phosphodiesterase 5 inhibitors

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https://www.readbyqxmd.com/read/28105791/the-future-of-pleiotropic-therapy-in-heart-failure-lessons-from-the-benefits-of-exercise-training-on-endothelial-function
#1
REVIEW
Gilles W De Keulenaer, Vincent F M Segers, Faiez Zannad, Dirk L Brutsaert
A novel generation of drugs is introduced in the treatment of heart failure (HF). These drugs, including phosphodiesterase-5 inhibitors, guanylate cyclase stimulators and activators, share the feature that their action is either endothelial-mediated or substitutes for endothelial pathways, in particular the nitric oxide-cyclic guanosine monophosphate pathway, thereby influencing homeostatic balances in virtually each organ system in a pleiotropic fashion. Unfortunately, recent clinical trials with some of these drugs have shown disappointing results, at least in the setting of HF with a preserved ejection fraction...
January 19, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#2
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28097089/selective-inhibition-of-phosphodiesterases-4-5-and-9-induces-hsp20-phosphorylation-and-attenuates-amyloid-beta-1-42-mediated-cytotoxicity
#3
Ryan T Cameron, Ellanor Whiteley, Jon P Day, Anna I Parachikova, George S Baillie
Phosphodiesterase (PDE) inhibitors are currently under evaluation as agents that may facilitate the improvement of cognitive impairment associated with Alzheimer's disease. Our aim was to determine whether inhibitors of PDEs 4, 5 and 9 could alleviate the cytotoxic effects of amyloid beta 1-42 (Aβ1-42) via a mechanism involving the small heatshock protein HSP20. We show that inhibition of PDEs 4, 5 and 9 but not 3 induces the phosphorylation of HSP20 which, in turn, increases the colocalisation between the chaperone and Aβ1-42 to significantly decrease the toxic effect of the peptide...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28090289/an-international-physician-survey-of-chronic-thromboembolic-pulmonary-hypertension-management
#4
Henning Gall, Ioana R Preston, Barbara Hinzmann, Sabina Heinz, David Jenkins, Nick H Kim, Irene Lang
We conducted an international study to evaluate practices in the diagnosis and management of patients with chronic thromboembolic pulmonary hypertension (CTEPH) globally across different regions. Between August and October 2012, CTEPH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 2-5 most recent patients with CTEPH. Overall, 496 physicians (Europe: 260; United States: 152; Argentina: 52; Japan: 32) completed the questionnaire and provided patient record data for 1,748 patients...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28087362/clinical-phenotypes-and-outcomes-of-heritable-and-sporadic-pulmonary-veno-occlusive-disease-a-population-based-study
#5
David Montani, Barbara Girerd, Xavier Jaïs, Marilyne Levy, David Amar, Laurent Savale, Peter Dorfmüller, Andrei Seferian, Edmund M Lau, Mélanie Eyries, Jérôme Le Pavec, Florence Parent, Damien Bonnet, Florent Soubrier, Elie Fadel, Olivier Sitbon, Gérald Simonneau, Marc Humbert
BACKGROUND: Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH. METHODS: We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases)...
January 10, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28065587/ffpm-a-pde4-inhibitor-reverses-learning-and-memory-deficits-in-app-ps1-transgenic-mice-via-camp-pka-creb-signaling-and-anti-inflammatory-effects
#6
Haibiao Guo, Yufang Cheng, Canmao Wang, Jingang Wu, Zhengqiang Zou, Bo Niu, Hui Yu, Haitao Wang, Jiangping Xu
Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing...
January 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28065359/role-of-nanotechnology-in-erectile-dysfunction-treatment
#7
REVIEW
Alice Y Wang, Carol A Podlasek
INTRODUCTION: The biological importance of nanotechnology-based delivery vehicles for in vivo tissue regeneration is gaining acceptance by the medical community; however, its relevance and incorporation into the treatment of sexual dysfunction are evolving and have not been well evaluated. AIM: To provide scientific evidence examining the use of state-of-the-art nanotechnology-based delivery methodology in the treatment of erectile dysfunction (ED) in animal models and in patients...
January 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28062305/involvement-of-second-messengers-in-the-signaling-pathway-of-vitellogenesis-inhibiting-hormone-and-their-effects-on-vitellogenin-mrna-expression-in-the-whiteleg-shrimp-litopenaeus-vannamei
#8
Sun-Hye Bae, Tomoyuki Okutsu, Naoaki Tsutsui, Bong Jung Kang, Hsiang-Yin Chen, Marcy N Wilder
We incubated fragments of Litopenaeus vannamei ovary to investigate second messengers involved in the regulation of vitellogenin (vg) mRNA levels. The use of 100 nM recombinant vitellogenesis-inhibiting hormone (VIH) (corresponding to recombinant L. vannamei sinus gland peptide-G: rLiv-SGP-G) significantly reduced vg mRNA expression in sub-adults after 8 h incubation to less than 20% of the control. The concentration of intracellular cyclic guanosine monophosphate (cGMP) increased 3.2-fold relative to the control after 2 h incubation with rLiv-SGP-G...
January 3, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28053948/recreational-use-of-phosphodiesterase-5-inhibitors-and-its-associated-factors-among-undergraduate-male-students-in-an-ethiopian-university-a-cross-sectional-study
#9
Eyob Alemayehu Gebreyohannes, Akshaya Srikanth Bhagavathula, Begashaw Melaku Gebresillassie, Yonas Getaye Tefera, Sewunet Admasu Belachew, Daniel Asfaw Erku
PURPOSE: To assess the prevalence of phosphodiesterase 5 (PDE5) inhibitor use and associated factors among University of Gondar undergraduate students. MATERIALS AND METHODS: An institution-based, cross-sectional study, using a survey questionnaire, was conducted from October to December 2015 to assess PDE5 inhibitor use and associated factors among male students at the University of Gondar. A Self-Esteem and Relationship questionnaire (14 items), an International Index of Erectile Function questionnaire (15 items) and a questionnaire on PDE5 inhibitor use (14 items) were included in the survey...
December 2016: World Journal of Men's Health
https://www.readbyqxmd.com/read/28053897/effects-of-a-supplement-combining-pycnogenol-%C3%A2-and-l-arginine-aspartate-on-lower-urinary-dysfunction-compared-with-saw-palmetto-extract
#10
Hiroshi Yagi, Ryo Sato, Kojiro Nishio, Gaku Arai, Shigehiro Soh, Hiroshi Okada
OBJECTIVES: Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys by increasing nitric oxide levels. French maritime pine bark extract Pycnogenol(®), which is a potent nitric oxide donor, is reported to be effective for SDys...
January 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28053559/systemic-lupus-erythematosus-and-pulmonary-arterial-hypertension-links-risks-and-management-strategies
#11
REVIEW
Konstantinos Tselios, Dafna D Gladman, Murray B Urowitz
Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28042309/the-link-between-vascular-dysfunction-bladder-ischemia-and-aging-bladder-dysfunction
#12
REVIEW
Karl-Erik Andersson, Donna B Boedtkjer, Axel Forman
The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome. Chronic ischemia-related bladder dysfunction may progress to bladder underactivity and it would be desirable to treat not only lower urinary tract symptoms (LUTS) induced by chronic ischemia, but also the progression of the morphological bladder changes...
January 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28032424/relationship-between-age-and-erectile-dysfunction-diagnosis-or-treatment-using-real-world-observational-data-in-the-usa
#13
John P Mulhall, Xuemei Luo, Kelly H Zou, Vera Stecher, Aaron Galaznik
AIMS: With self-reporting of erectile dysfunction (ED) in population-based surveys, men with ED may not represent men who are bothered sufficiently to seek an ED diagnosis and treatment. We used real-world observational data to assess: 1) the prevalence of ED diagnosis or treatment by age subgroups; and 2) the relationship of age with ED diagnosis or treatment after controlling for ED-related comorbidities in the USA. METHODS: This cross-sectional study used de-identified claims data (MarketScan(®) databases; primary analysis)...
December 2016: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28018840/hand-impairment-in-systemic-sclerosis-various-manifestations-and-currently-available-treatment
#14
Amber Young, Rajaie Namas, Carole Dodge, Dinesh Khanna
Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life...
September 2016: Current Treatment Options in Rheumatology
https://www.readbyqxmd.com/read/28013386/potentiation-of-the-no-cgmp-pathway-and-blood-flow-responses-during-dynamic-exercise-in-healthy-humans
#15
Jacqueline K Limberg, Katherine R Malterer, J Mikhail Kellawan, William G Schrage, Brad W Wilkins, Wayne T Nicholson, John H Eisenach, Michael J Joyner, Timothy B Curry
PURPOSE: Previous work has shown nitric oxide (NO) contributes to ~15% of the hyperemic response to dynamic exercise in healthy humans. This NO-mediated vasodilation occurs, in part, via increases in intracellular cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase. We sought to examine the effect of phosphodiesterase-5 (PDE-5) inhibition on forearm blood flow (FBF) responses to dynamic handgrip exercise in healthy humans and the role of NO. We hypothesized exercise hyperemia would be augmented by sildenafil citrate (SDF, PDE-5 inhibitor)...
December 24, 2016: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28013355/effect-of-sildenafil-on-the-activity-of-some-antidepressant-drugs-and-electroconvulsive-shock-treatment-in-the-forced-swim-test-in-mice
#16
Katarzyna Socała, Dorota Nieoczym, Elżbieta Wyska, Piotr Wlaź
Sildenafil, a potent and selective inhibitor of phosphodiesterase type 5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. It is often taken by patients suffering from depression and receiving antidepressant drug treatment. However, its influence on the efficacy of antidepressant treatment was not sufficiently studied. Therefore, the aim of the present study was to investigate the influence of sildenafil on the anti-immobility action of several antidepressant drugs (i.e...
December 24, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27999095/a-case-report-of-fatal-desmethyl-carbodenafil-toxicity
#17
Erica L Bakota, Anna T Kelly, Jeffrey P Walterscheid, Darshan R Phatak
We present the case report of a 34-year-old Hispanic male who was found unresponsive in the carport of his residence. Surveillance video footage from a security camera showed that he collapsed as he was walking to his vehicle. The decedent had no medical history and no history of illicit drug use. Initial toxicology testing revealed no alcohol or illicit drugs. Autopsy findings indicated a need for additional toxicological analysis due to a lack of trauma and the paucity of pathophysiologically significant natural disease...
December 19, 2016: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/27998725/cgmp-signaling-increases-antioxidant-gene-expression-by-activating-forkhead-box-o-3a-in-the-colon-epithelium
#18
Rui Wang, Bianca Islam, Allison Bridges, Sarah Sharman, Muhan Hu, Yali Hou, Payaningal R Somanath, Laine Venable, Nagendra Singh, Sangmi Kim, Subbaramiah Sridhar, Franz Hofmann, Darren D Browning
Signaling through cGMP has therapeutic potential in the colon, where it has been implicated in the suppression of colitis and colon cancer. In this study, we tested the ability of cGMP and type 2 cGMP-dependent protein kinase (PKG2) to activate forkhead box O (FoxO) in colon cancer cells and in the colon epithelium of mice. We show that activation of PKG2 in colon cancer cells inhibited cell proliferation, inhibited AKT, and activated FoxO. Treatment of colon explants with 8Br-cGMP also activated FoxO target gene expression at both RNA and protein levels, and reduced epithelial reduction-oxidation (redox) stress...
December 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27998297/difficulties-in-diagnosis-and-treatment-of-severe-secondary-raynaud-s-phenomenon-in-a-cameroonian-woman-a-case-report
#19
Valirie Ndip Agbor, Tsi Njim, Leopold Ndemnge Aminde
BACKGROUND: Raynaud's phenomenon is a microvascular disorder that results in exaggerated vasoconstriction over vasodilatation secondary to an alteration in autonomic control. Though benign, it can result in severe ulceration and ultimately gangrene associated with disfiguration and permanent deformity. We present a case of severe secondary Raynaud's phenomenon in a black-African patient from a resource-limited setting, with focus on the difficulties encountered in the diagnosis and treatment...
December 20, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27997987/long-term-outcome-in-liver-transplantation-candidates-with-portopulmonary-hypertension
#20
Laurent Savale, Caroline Sattler, Audrey Coilly, Filoména Conti, Sébastien Renard, Claire Francoz, Hélène Bouvaist, Cyrille Feray, Patrick Borentain, Xavier Jaïs, David Montani, Florence Parent, Caroline O'Connell, Philippe Hervé, Marc Humbert, Gérald Simonneau, Didier Samuel, Yvon Calmus, Christophe Duvoux, François Durand, Jean Charles Duclos-Vallée, Olivier Sitbon
BACKGROUND: Portopulmonary hypertension (PoPH) is diagnosed in 2-6% of liver transplantation (LT) candidates. OBJECTIVE AND METHODS: To study outcomes of candidates for LT suffering from PoPH. Data were collected retrospectively from a prospective registry. Pulmonary hemodynamic variables were collected at the time of PoPH diagnosis, at last evaluation before LT, within 6 months and beyond 6 months after LT. RESULTS: Forty-nine patients (35 males, 48±8 years) were analysed (median MELD score 20)...
December 20, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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