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https://www.readbyqxmd.com/read/28922964/oral-treprostinil-in-the-treatment-of-pulmonary-arterial-hypertension
#1
Jeremy Feldman, Naomi Habib, John Radosevich, Mohan Dutt
Pulmonary arterial hypertension (PAH) is a rare disease resulting in progressive remodeling of the pulmonary vasculature and eventual right ventricular failure. Despite the development of 13 therapies for PAH since 2000, the use of continuously infused prostanoids retains a special role. Infused medications present unique challenges, and the search for an efficacious oral prostanoid culminated in the FDA approval of oral treprostinil - a first in class oral prostanoid medication approved to treat pulmonary arterial hypertension (PAH)...
September 19, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28888986/pde-5-inhibitor-improves-insulin-sensitivity-by-enhancing-mitochondrial-function-in-adipocytes
#2
Hea Min Yu, Hyo Kyun Chung, Koon Soon Kim, Jae Min Lee, Jun Hwa Hong, Kang Seo Park
Adipocytes are involved in many metabolic disorders. It was recently reported that phosphodiesterase type 5 (PDE5) is expressed in human adipose tissue. In addition, PDE5 inhibitors have been shown to improve insulin sensitivity in humans. However, the mechanism underlying the role of PDE5 inhibitors as an insulin sensitizer remains largely unknown. The present study was undertaken to investigate the role of the PDE5 inhibitor udenafil in insulin signaling in adipocytes and whether this is mediated through the regulation of mitochondrial function...
September 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28860509/age-related-differences-in-responsiveness-to-sildenafil-and-tamsulosin-are-due-to-myogenic-smooth-muscle-tone-in-the-human-prostate
#3
Sophie N Lee, Basu Chakrabarty, Brad Wittmer, Melissa Papargiris, Andrew Ryan, Mark Frydenberg, Nathan Lawrentschuk, Ralf Middendorff, Gail P Risbridger, Stuart J Ellem, Betty Exintaris
Lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) are highly prevalent in older men, having a profound impact on patient quality of life. Current therapeutics for BPH/LUTS target neurogenic smooth muscle tone, but response is unpredictable and many patients fail to respond. Spontaneous myogenic tone is another component of smooth muscle contractility that is uncharacterized in human prostate. To better understand and improve the predictability of patient response, we defined myogenic contractility using human prostate specimens and examined the effect of existing therapeutics...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830281/administration-of-daily-5%C3%A2-mg-tadalafil-improves-endothelial-function-in-patients-with-benign-prostatic-hyperplasia
#4
Toshiyasu Amano, Carolyn Earle, Tetsuya Imao, Yuki Matsumoto, Takahiro Kishikage
INTRODUCTION: Tadalafil is a promising phosphodiesterase (PDE) 5 inhibitor prescribed for erectile dysfunction (ED). Daily low dose (5 mg) of tadalafil has also been used for the treatment of male lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). PDE5 inhibitors induce relaxation of smooth muscle cells in the urethra, prostate, bladder neck, and blood vessels. The aim of this study was to investigate the efficacy of tadalafil on vessels endothelial function, in patients with male LUTS symptoms associated with BPH...
August 22, 2017: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/28798396/flavonoid-glycosides-isolated-from-epimedium-brevicornum-and-their-estrogen-biosynthesis-promoting-effects
#5
Fu Li, Bao-Wen Du, Dan-Feng Lu, Wen-Xuan Wu, Kanjana Wongkrajang, Lun Wang, Wen-Chen Pu, Chang-Lu Liu, Han-Wei Liu, Ming-Kui Wang, Fei Wang
Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1-4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798156/phosphodiesterase-4-inhibitor-and-phosphodiesterase-5-inhibitor-combination-therapy-has-antifibrotic-and-anti-inflammatory-effects-in-mdx-mice-with-duchenne-muscular-dystrophy
#6
Yasunori Nio, Masayuki Tanaka, Yoshihiko Hirozane, Yo Muraki, Mitsugi Okawara, Masatoshi Hazama, Takanori Matsuo
Duchenne muscular dystrophy (DMD) is the most common inherited muscular dystrophy. Patients experience DMD in their 20s from cardiac or respiratory failure related to progressive muscle wasting. Currently, the only treatments for the symptoms of DMD are available. Muscle fibrosis, a DMD feature, leads to reduced muscle function and muscle mass, and hampers pharmaceutical therapeutic efficacy. Although antifibrotic agents may be useful, none is currently approved. Phosphodiesterase (PDE)-4 inhibitors have exhibited antifibrotic effects in human and animal models...
August 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28792962/aberrant-cgmp-signaling-persists-during-recovery-in-mice-with-oxygen-induced-pulmonary-hypertension
#7
Marta Perez, Keng Jin Lee, Herminio J Cardona, Joann M Taylor, Mary E Robbins, Gregory B Waypa, Sara K Berkelhamer, Kathryn N Farrow
Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease...
2017: PloS One
https://www.readbyqxmd.com/read/28776160/-acute-monocular-loss-of-vision-differential-diagnostic-considerations-apart-from-the-internistic-etiological-clarification
#8
A Rickmann, M A Macek, P Szurman, K Boden
We report the case of acute painless monocular loss of vision in a 53-year-old man. An interdisciplinary etiological evaluation remained without pathological findings with respect to arterial branch occlusion. A reevaluation of the patient history led to a possible association with the administration of phosphodiesterase type 5 inhibitor (PDE5 inhibitor). A critical review of the literature on PDE5 inhibitor administration with ocular participation was performed.
August 3, 2017: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#9
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#10
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728871/phosphodiesterase-type-5-inhibitors-and-risk-of-melanoma-a-meta-analysis
#11
Huilin Tang, Wenting Wu, Shuangshuang Fu, Suodi Zhai, Yiqing Song, Jiali Han
BACKGROUND: The association between phosphodiesterase type 5 (PDE5) inhibitors and melanoma risk is controversial. OBJECTIVE: We quantify the association between use of PDE5 inhibitors and melanoma. METHODS: We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for studies that were conducted up to July 13, 2016, and evaluated the association between PDE5 inhibitors and skin cancer...
September 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28725593/buccal-mucosal-graft-urethroplasty-in-men-risk-factors-for-recurrence-and-complications-a-third-referral-centre-experience-in-anterior-urethroplasty-using-buccal-mucosal-graft
#12
Marco Spilotros, Neha Sihra, Sachin Malde, Mahreen H Pakzad, Rizwan Hamid, Jeremy L Ockrim, Tamsin J Greenwell
BACKGROUND: Urethral stricture disease is a challenging condition to treat and several approaches including direct visual internal urethrotomy (DVIU) and anastomotic or augmentation urethroplasties based on the use of flaps and graft have been reported. The aim of this study is to determine risk factors for stricture recurrence and complications in patients having buccal mucosal graft (BMG) urethroplasty for anterior urethral stricture under a single surgeon in a third referral centre in UK...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28720356/phosphodiesterase-type-5-inhibitors-for-premature-ejaculation-a-systematic-review-and-meta-analysis
#13
REVIEW
Marrissa Martyn-St James, Katy Cooper, Shijie Ren, Eva Kaltenthaler, Kath Dickinson, Anna Cantrell, Kevan Wylie, Leila Frodsham, Catherine Hood
CONTEXT: Phosphodiesterase type 5 inhibitors (PDE5-Is) are prescribed off-label for the treatment of premature ejaculation (PE). OBJECTIVE: To systematically review the evidence from randomised controlled trials (RCTs) for PDE5-Is in the management of PE. EVIDENCE ACQUISITION: Medline and other databases were searched through September 2015. Quality of RCTs was assessed. Intravaginal ejaculatory latency time (IELT) data were pooled in a meta-analysis...
February 2017: European Urology Focus
https://www.readbyqxmd.com/read/28719717/audiometry-results-and-teoae-and-dpoae-amplitudes-in-men-taking-a-phosphodiesterase-type-5-inhibitor-for-erectile-dysfunction
#14
Sertan Öntepeli, Nuray Bayar Muluk, Devrim Tuğlu, Timuçin Şipal
We conducted a prospective study of transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in men who were taking an oral phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction. Our study group was made up of 30 men (60 ears), aged 34 to 60 years (mean: 50.9). They were randomly divided into three groups; 10 men were given sildenafil (Viagra) at 50 mg twice a week, 10 were given tadalafil (Cialis) at 20 mg twice a week, and 10 were given vardenafil (Levitra) at 20 mg twice a week...
July 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28705807/augmentation-of-cgmp-pkg-pathway-and-colonic-motility-by-hydrogen-sulfide
#15
Ancy D Nalli, Sayak Bhattacharya, Hongxia Wang, Derek M Kendig, John R Grider, Karnam S Murthy
Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cGMP. The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse and human, L-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser(1756) (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor, s-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28686445/discovery-and-optimization-of-chromeno-2-3-c-pyrrol-9-2h-ones-as-novel-selective-and-orally-bioavailable-phosphodiesterase-5-inhibitors-for-the-treatment-of-pulmonary-arterial-hypertension
#16
Deyan Wu, Tianhua Zhang, Yiping Chen, Yadan Huang, Haiju Geng, Yanfa Yu, Chen Zhang, Zengwei Lai, Yinuo Wu, Xiaolei Guo, Jianwen Chen, Hai-Bin Luo
Phosphodiesterase 5 (PDE5) inhibitors have been used as clinical agents to treat erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, we detail the discovery of a novel series of chromeno[2,3-c]pyrrol-9(2H)-one derivatives as selective and orally bioavailable inhibitors against phosphodiesterase 5. Medicinal chemistry optimization resulted in 2, which exhibits a desirable inhibitory potency of 5.6 nM with remarkable selectivity as well as excellent pharmacokinetic properties and an oral bioavailability of 63...
August 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28677661/a-novel-therapeutic-approach-in-the-treatment-of-pulmonary-arterial-hypertension-allium-ursinum-liophylisate-alleviates-symptoms-comparably-to-sildenafil
#17
Mariann Bombicz, Daniel Priksz, Balazs Varga, Andrea Kurucz, Attila Kertész, Akos Takacs, Aniko Posa, Rita Kiss, Zoltan Szilvassy, Bela Juhasz
Right-sided heart failure-often caused by elevated pulmonary arterial pressure-is a chronic and progressive condition with particularly high mortality rates. Recent studies and our current findings suggest that components of Wild garlic (Allium ursinum, AU) may play a role in reducing blood pressure, inhibiting angiotensin-converting enzyme (ACE), as well as improving right ventricle function in rabbit models with heart failure. We hypothesize that AU may mitigate cardiovascular damage caused by pulmonary arterial hypertension (PAH) and has value in the supplementary treatment of the complications of the disease...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28648945/phosphodiesterase-5-inhibition-as-a-therapeutic-target-for-ischemic-stroke-a-systematic-review-of-preclinical-studies
#18
Joakim N E Ölmestig, Ida R Marlet, Atticus H Hainsworth, Christina Kruuse
Phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil (Viagra®) are widely used for erectile dysfunction and pulmonary hypertension. Preclinical studies suggest that PDE5i may improve functional outcome following ischemic stroke. In this systematic review we aimed to evaluate the effects of selective PDE5i in animal models of brain ischaemia. A systematic search in Medline, Embase, and The Cochrane Library was performed including studies in English assessing the effects of selective PDE5i. 32 publications were included describing outcome in 3646 animals...
June 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28626017/amyloid-%C3%AE-peptide-is-needed-for-cgmp-induced-long-term-potentiation-and-memory
#19
Agostino Palmeri, Roberta Ricciarelli, Walter Gulisano, Daniela Rivera, Claudia Rebosio, Elisa Calcagno, Maria Rosaria Tropea, Silvia Conti, Utpal Das, Subhojit Roy, Maria Adelaide Pronzato, Ottavio Arancio, Ernesto Fedele, Daniela Puzzo
High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28623462/in-silico-investigations-of-chemical-constituents-of-clerodendrum-colebrookianum-in-the-anti-hypertensive-drug-targets-rock-ace-and-pde5
#20
Hemant Arya, Safiulla Basha Syed, Sorokhaibam Sureshkumar Singh, Dinakar R Ampasala, Mohane Selvaraj Coumar
Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5)...
June 16, 2017: Interdisciplinary Sciences, Computational Life Sciences
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