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PDE5 Inhibitors

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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
#1
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
#2
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
#3
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...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28398017/differential-effects-of-phosphodiesterase-5-inhibition-in-chronic-cardiac-decompensation-depending-on-the-type-whether-hfref-or-hfpef-of-heart-failure-a-meta-analysis
#4
Renato DE Vecchis, Arturo Cesaro, Carmelina Ariano
INTRODUCTION: According to 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension(PH), no specific drug is currently indicated for PH related to left heart disease( PH-LDH), i.e., the one secondary to left chronic heart failure (CHF), which coincides with the group 2 of the PH classification endorsed by the above-mentioned guidelines. In fact, adoption of therapies that specifically apply for so-called pulmonary arterial hypertension (group 1 of the PH classification) has been regarded as substantially contraindicated in patients with PH- LHD, according to current ESC/ERS guidelines...
April 10, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/28394522/-the-role-of-waterjet-dissection-in-improving-erectile-function-and-continence-after-nerve-sparing-prostatectomy
#5
P V Glybochko, Yu G Alyaev, L M Rapoport, N A Grigorev, E A Bezrukov, D G Tsarichenko, E S Sirota, G A Martirosyan
INTRODUCTION: Erectile dysfunction (ED) and urinary incontinence (UI) following radical prostatectomy (RP) adversely impact patients psycho-emotional status reducing the quality of life and treatment satisfaction. AIM: To investigate the rates of regaining continence and erectile function (EF) after nerve-sparing radical retropubic prostatectomy (NS-RRP) and nerve-sparing laparoscopic radical prostatectomy (NS-LRP) in the early postoperative period. MATERIALS AND METHODS: The study comprised 116 patients who preserved sexual activity and the ability to have sex...
April 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28337142/icariside-ii-effectively-reduces-spatial-learning-and-memory-impairments-in-alzheimer-s-disease-model-mice-targeting-beta-amyloid-production
#6
Lingli Yan, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Fei Li, Jingshan Shi, Qihai Gong
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28335220/pde5-inhibitors-loaded-nanovesicles-physico-chemical-properties-and-in-vitro-antiproliferative-activity
#7
Roberta F De Rose, Maria Chiara Cristiano, Marilena Celano, Valentina Maggisano, Ada Vero, Giovanni Enrico Lombardo, Martina Di Francesco, Donatella Paolino, Diego Russo, Donato Cosco
Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP). Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase...
May 18, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28316997/sildenafil-can-affect-innate-and-adaptive-immune-system-in-both-experimental-animals-and-patients
#8
REVIEW
Monika Kniotek, Agnieszka Boguska
Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28294194/phosphodiesterase-5-inhibition-preserves-renal-hemodynamics-and-function-in-mice-with-diabetic-kidney-disease-by-modulating-mir-22-and-bmp7
#9
Riccardo Pofi, Daniela Fiore, Rita De Gaetano, Giuseppe Panio, Daniele Gianfrilli, Carlotta Pozza, Federica Barbagallo, Yang Kevin Xiang, Konstantinos Giannakakis, Susanna Morano, Andrea Lenzi, Fabio Naro, Andrea M Isidori, Mary Anna Venneri
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P < 0.001), the increase of urine albumin creatinine ratio (P < 0...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283895/influence-of-the-pde5-inhibitor-tadalafil-on-redox-status-and-antioxidant-defense-system-in-c2c12-skeletal-muscle-cells
#10
Guglielmo Duranti, Roberta Ceci, Paolo Sgrò, Stefania Sabatini, Luigi Di Luigi
Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism...
March 11, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28260869/efficacy-and-safety-of-short-and-long-term-regular-and-on-demand-regimens-of-phosphodiesterase-type-5-inhibitors-in-treating-erectile-dysfunction-after-nerve-sparing-radical-prostatectomy-a-systematic-review-and-meta-analysis
#11
Daxue Tian, Xiao-Yan Wang, Huan-Tao Zong, Yong Zhang
BACKGROUND: We performed a meta-analysis to evaluate the efficacy and safety of short-term (≤6 months) and long-term (>6 months), regular (OaD) and on-demand (PRN) regimens of phosphodiesterase type 5 inhibitors (PDE5-Is) in treating erectile dysfunction (ED) after nerve-sparing radical prostatectomy (NSRP). METHODS: We conducted a literature search in August 2016. Sources included PubMed, EMBASE, and MEDLINE databases. The main outcome was International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, and the secondary outcome was treatment-emergent adverse events (TEAEs)...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28259808/the-effect-of-oral-phosphodiesterase-5-inhibitors-on-sperm-parameters-a-meta-analysis-and-systematic-review
#12
Ping Tan, Liangren Liu, Shiyou Wei, Zhuang Tang, Lu Yang, Qiang Wei
OBJECTIVE: To perform a systematic review and meta-analysis to evaluate the effect of phosphodiesterase-5 (PDE5) inhibitors on sperm parameters. METHODS: A systematic literature search was performed. Mean value and its standard deviation (mean ± standard deviation) were used to perform quantitative analysis. Statistic heterogeneity scores were assessed with the standard Cochran Q test and I(2) statistic. All statistical analyses were conducted by RevMan 5.3...
March 1, 2017: Urology
https://www.readbyqxmd.com/read/28251255/-side-effects-of-erectile-dysfunction-drug-treatment
#13
H Sperling
Due to the large number of drugs now available, the therapy of erectile dysfunction has changed profoundly in recent decades. The phosphodiesterase type 5 inhibitors (PDE5-i): sildenafil, taldalafil, vardenafil, and avanafil are EMA European Medicines Agency approved and show similar adverse events and success rates. The absolute contraindication is the simultaneous use of nitrates. Despite this wide variety of options, therapy of erectile dysfunction should be performed in an individually adapted manner. The exact patient's history, physical examination, collaboration of medical disciplines, and choice of therapy will offer every patient the possibility to achieve or regain a satisfying sexual life...
March 1, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28243299/assessment-of-the-role-of-no-cgmp-pathway-in-orthodontic-tooth-movement-using-pde5-inhibitors-an-animal-study
#14
Amir Hossein Mirhashemi, Mohammad Sadegh Ahmad Akhoundi, Rezvaneh Ghazanfari, Shahroo Etemad-Moghadam, Mojgan Alaeddini, Azam Khorshidian, Ahmad Reza Dehpour, Nafiseh Momeni
OBJECTIVES: Nitric oxide (NO) is a signaling molecule that mediates mechanical bone loading. Cyclic guanosine 3', 5' monophosphate (cGMP) is a NO-induced effector molecule. The aim of this study was to assess the effect of NO-cGMP pathway on orthodontic tooth movement (OTM) in rats by use of two phosphodiesterase 5 (PDE5) inhibitors namely sildenafil and tadalafil as chemical tools. MATERIALS AND METHODS: Forty-five male Wistar rats were divided into three equal groups (n=15) based on the substance they received...
November 2016: Journal of Dentistry of Tehran University of Medical Sciences
https://www.readbyqxmd.com/read/28238269/long-acting-pde5-inhibitor-tadalafil-prevents-early-doxorubicin-induced-left-ventricle-diastolic-dysfunction-in-juvenile-mice-potential-role-of-cytoskeletal-proteins
#15
Mohamed Nagiub, Scott Filippone, David Durrant, Anindita Das, Rakesh C Kukreja
The chemotherapeutic use of doxorubicin (Dox) is hindered due to the development of irreversible cardiotoxicity. Specifically, childhood cancer survivors are at greater risk of Dox-induced cardiovascular complications. Because of the potent cardioprotective effect of phosphodiesterase 5 (PDE5) inhibitors, we examined the effect of long-acting PDE5 inhibitor tadalafil (Tada) against Dox cardiotoxicity in juvenile mice. C57BL/6J mice (6 weeks old) were treated with Dox (20 mg/kg, i.v.) and (or) Tada (10 mg/kg daily for 14 days, p...
March 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28235796/pulmonary-hypertension-therapy-and-a-systematic-review-of-efficacy-and-safety-of-pde-5-inhibitors
#16
REVIEW
Chinwe Unegbu, Corina Noje, John D Coulson, Jodi B Segal, Lewis Romer
Pulmonary hypertension (PH) is a syndrome that is of growing concern to pediatricians worldwide. Recent data led to concerns about the safety of phosphodiesterase type 5 (PDE5) inhibitors in children and a US Food and Drug Administration safety advisory. Our objective is to provide insight into therapies for PH in children and to systematically review the comparative effectiveness and safety of PDE5 inhibitors in the management of pediatric patients with PH. We searched the following databases through February 2015: Medline, Embase, SCOPUS, and the Cochrane Central Register of Controlled Trials...
March 2017: Pediatrics
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#17
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28196856/vardenafil-reduces-macrophage-pro-inflammatory-overresponses-in-cystic-fibrosis-through-pde5-and-cftr-dependent-mechanisms
#18
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type littermates...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28155571/the-augmentation-of-bk-channel-activity-by-nitric-oxide-signaling-in-rat-cerebral-arteries-involves-co-localized-regulatory-elements
#19
Barry D Kyle, Ramesh C Mishra, Andrew P Braun
Large conductance, Ca(2+)-activated K(+) (BK) channels control cerebrovascular tone; however, the regulatory processes influencing these channels remain poorly understood. Here, we investigate the cellular mechanisms underlying the enhancement of BK current in rat cerebral arteries by nitric oxide (NO) signaling. In isolated cerebral myocytes, BK current magnitude was reversibly increased by sodium nitroprusside (SNP, 100 μM) and sensitive to the BK channel inhibitor, penitrem-A (100 nM). Fostriecin (30 nM), a protein phosphatase type 2A (PP2A) inhibitor, significantly prolonged the SNP-induced augmentation of BK current and a similar effect was produced by sildenafil (30 nM), a phosphodiesterase 5 (PDE5) inhibitor...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28150511/investigation-of-pde5-pde6-and-pde5-pde11-selective-potent-tadalafil-like-pde5-inhibitors-using-combination-of-molecular-modeling-approaches-molecular-fingerprint-based-virtual-screening-protocols-and-structure-based-pharmacophore-development
#20
Gülru Kayık, Nurcan Ş Tüzün, Serdar Durdagi
The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3',5'-cyclic guanosine monophosphate (cGMP) and/or 3',5'-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction. Due to the amino acid sequence and the secondary structural similarity of PDE6 and PDE11 with the catalytic domain of PDE5, first-generation PDE5 inhibitors (i...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
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