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https://www.readbyqxmd.com/read/28626017/amyloid-beta-peptide-is-needed-for-cgmp-induced-long-term-potentiation-and-memory
#1
Agostino Palmeri, Roberta Ricciarelli, Walter Gulisano, Daniela Rivera, Claudia Rebosio, Elisa Calcagno, Maria Rosaria Tropea, Silvia Conti, Utpal Das, Subhojit Roy, Maria A Pronzato, Ottavio Arancio, Ernesto Fedele, Daniela Puzzo
High levels of amyloid-beta 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 (PDE5-Is) 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 (BACE1)...
June 16, 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
#2
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
https://www.readbyqxmd.com/read/28603047/tadalafil-induces-antiproliferation-apoptosis-and-phosphodiesterase-type-5-downregulation-in-idiopathic-pulmonary-arterial-hypertension-in-vitro
#3
Aya Yamamura, Eri Fujitomi, Naoki Ohara, Kikuo Tsukamoto, Motohiko Sato, Hisao Yamamura
Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease of the pulmonary artery resulting from a currently unidentified etiology. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. Vascular remodeling is mediated by enhanced proliferation and reduced apoptosis in pulmonary arterial smooth muscle cells (PASMCs). Based on its pathological mechanism, specific phosphodiesterase type 5 (PDE5) inhibitors have been used in the treatment of IPAH...
June 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28600399/validation-of-pde5-as-a-chemoprevention-target
#4
EDITORIAL
Gary A Piazza
No abstract text is available yet for this article.
June 9, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28597769/a-systematic-review-of-transition-studies-of-pulmonary-arterial-hypertension-specific-medications
#5
Avraham Sofer, Michael J Ryan, Ryan J Tedford, Joel A Wirth, Wassim H Fares
Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28596298/sex-differences-in-pulmonary-vascular-control-focus-on-the-nitric-oxide-pathway
#6
Daphne P M de Wijs-Meijler, A H Jan Danser, Irwin K M Reiss, Dirk J Duncker, Daphne Merkus
Although the incidence of pulmonary hypertension is higher in females, the severity and prognosis of pulmonary vascular disease in both neonates and adults have been shown to be worse in male subjects. Studies of sex differences in pulmonary hypertension have mainly focused on the role of sex hormones. However, the contribution of sex differences in terms of vascular signaling pathways regulating pulmonary vascular function remains incompletely understood. Consequently, we investigated pulmonary vascular function of male and female swine in vivo, both at rest and during exercise, and in isolated small pulmonary arteries in vitro, with a particular focus on the NO-cGMP-PDE5 pathway...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28548953/from-rapalogs-to-anti-aging-formula
#7
Mikhail V Blagosklonny
Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor...
May 30, 2017: Oncotarget
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
#8
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/28540228/research-in-pharmacotherapy-for-erectile-dysfunction
#9
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
#10
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/28515348/relation-of-phosphodiesterase-type-5-inhibitors-and-malignant-melanoma-a-meta-analysis-and-systematic-review
#11
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/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#12
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
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
#13
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/28483482/-sexual-consequences-after-treatment-of-prostate-cancer-inquiry-among-members-of-the-association-nationale-des-malades-du-cancer-de-la-prostate
#14
D Girier, A Chevrot, P Costa, R Thuret, A Faix, A Mestre, S Droupy
INTRODUCTION: Complications of prostate cancer treatments are responsible of a lower quality of life. We evaluated the prevalence and the perceptions of sexual consequences of prostate cancer treatments. MATERIALS AND METHODS: A retrospective self-administered questionnaire was sent to all the members of the Association Nationale des Malades du Cancer de la Prostate (ANAMACAP). All the answers were analyzed. RESULTS: 226 questionnaires were analyzed, the average age was 67...
May 2017: Progrès en Urologie
https://www.readbyqxmd.com/read/28469435/inhibition-of-phosphodiesterase-5-and-increasing-the-level-of-cyclic-guanosine-3-5-monophosphate-by-hydroalcoholic-achillea-wilhelmsii-c-koch-extract-in-human-breast-cancer-cell-lines-mcf-7-and-mda-mb-468
#15
Ramin Saravani, Hamid Reza Galavi, Ali Shahraki
This study aimed to investigate the effect of hydroalcoholic Achillea wilhelmsii C. Koch extract (HAWE) on phosphodiesterase 5 (PDE5) gene expression and cyclic guanosine 3',5' monophosphate (cGMP) signaling in the MCF-7 and MDA-Mb-468 cell lines. The effective dose (ED50) of HAWE was examined in both cell lines using a 3-(4,5-dimethylhiazol-2-yl)-2,5-diphenyltetrazolium bromide viability test, and the type of cell death was detected by flow cytometry. The expression of PDE5 and the concentration of cGMP were measured in a time-dependent manner in the ED50 by real-time polymerase chain reaction and a colorimetric assay, respectively...
2017: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/28468928/sildenafil-suppresses-inflammation-driven-colorectal-cancer-in-mice
#16
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
https://www.readbyqxmd.com/read/28458371/synthesis-and-structure-revision-of-dimeric-tadalafil-analogue-adulterants-in-dietary-supplements
#17
Suresh Mandava, Bogonda Ganganna, Jungjoong Hwang, Younchang Jang, Jiho Hwang, Mallesham Samala, Ki-Bbeum Kim, Haeil Park, Ji Hyun Lee, Sun Young Baek, Jongkook Lee
A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28414103/apoptosis-induction-of-poly-s-nitrosated-human-serum-albumin-in-resistant-solid-tumor-under-hypoxia-can-be-restored-by-phosphodiesterase-5-inhibition
#18
Mayumi Ikeda, Yu Ishima, Victor T G Chuang, Tsuyoshi Ikeda, Ryo Kinoshita, Hiroshi Watanabe, Tatsuhiro Ishida, Masaki Otagiri, Toru Maruyama
Poly-S-nitrosated human serum albumin (Poly-SNO-HSA) delivered and accumulated nitric oxide (NO) in tumors and induces apoptosis. Tumor hypoxia is strongly associated with malignant progression and tumor resistance to therapy. In this study, we examined the cytotoxic effect of Poly-SNO-HSA under hypoxia on the murine colon 26 adenocarcinoma (C26) cells in vitro and in vivo. Under hypoxia, at about 4 times LD50 dose of Poly-SNO-HSA in vitro, the reactive oxygen species production was hindered but apoptotic cells were induced via cGMP pathway as the effect was suppressed by a soluble guanylate cyclase inhibitor, NS2028...
April 13, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28400802/pde5-inhibitors-promote-recovery-of-peripheral-neuropathy-in-diabetic-mice
#19
Lei Wang, Michael Chopp, Zheng Gang Zhang
No abstract text is available yet for this article.
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28399643/the-effect-of-pde5-inhibitors-on-bone-and-oxidative-damage-in-ovariectomy-induced-osteoporosis
#20
Hamit H Alp, Zübeyir Huyut, Serkan Yildirim, Yıldıray Başbugan, Levent Ediz, Mehmet R Şekeroğlu
Osteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3',5'-cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy...
May 2017: Experimental Biology and Medicine
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