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https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#1
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27872007/the-role-of-pde5-inhibitors-and-the-no-cgmp-pathway-in-cancer
#2
REVIEW
Taylor C Peak, Ashley Richman, Serap Gur, Faysal A Yafi, Wayne J G Hellstrom
INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Simultaneously, researchers have elucidated the roles that this pathway plays in the regulation of cell proliferation, tumor development, and progression. As a result, our knowledge of PDE5i and cancer biology has expanded and provides an integration that holds great promise for some, but concern for others...
January 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27860834/regulation-of-mammalian-oocyte-meiosis-by-intercellular-communication-within-the-ovarian-follicle
#3
Laurinda Jaffe, Jeremy R Egbert
Meiotic progression in mammalian preovulatory follicles is controlled by the granulosa cells around the oocyte. Cyclic GMP (cGMP) generated in the granulosa cells diffuses through gap junctions into the oocyte, maintaining meiotic prophase arrest. Luteinizing hormone then acts on receptors in outer granulosa cells to rapidly decrease cGMP. This occurs by two complementary pathways: cGMP production is decreased by dephosphorylation and inactivation of the NPR2 guanylyl cyclase, and cGMP hydrolysis is increased by activation of the PDE5 phosphodiesterase...
November 14, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27855624/the-women-s-heart-insights-into-new-potential-targeted-therapy
#4
Daniele Gianfrilli, Ricardo Pofi, Tiziana Feola, Andrea Lenzi, Elisa Giannetta
Cardiovascular disease represents an increasing cause of death in women. The analysis of cardiovascular risk factors in women has not reached a consensus with respect to a specific and personalized treatment designed in pre-menopausal and post-menopausal phases. Clinically significant cardioprotective and antiremodeling effects were detected in animal and human study exploring chronic inhibition of Phosphodiesterase type 5 (PDE5). The relationship between heart, estrogens and PDE5 inhibitors (PDE5i) remains unclear...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27843073/off-target-effect-of-sildenafil-on-postsurgical-erectile-dysfunction-alternate-pathways-and-localized-delivery-system
#5
Amirali Salmasi, Geun Taek Lee, Neal Patel, Ritu Goyal, Michael Dinizo, Young Suk Kwon, Part K Modi, Izak Faiena, Nara Lee, Johanna L Hannan, Joachim Kohn, Isaac Yi Kim
INTRODUCTION: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. AIM: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). METHODS: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H2O2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures...
November 11, 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27836585/neuroprotective-effects-of-sildenafil-against-oxidative-stress-and-memory-dysfunction-in-mice-exposed-to-noise-stress
#6
Hu Erxidan Sikandaner, So Young Park, Min Jung Kim, Shi Nae Park, Dong Won Yang
Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level...
November 9, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27813474/-cyclic-nucleotide-phosphodiesterases-role-in-the-heart-and-therapeutic-perspectives
#7
Ibrahim Bedioune, Pierre Bobin, Sarah Karam, Marta Lindner, Delphine Mika, Patrick Lechêne, Jérôme Leroy, Rodolphe Fischmeister, Grégoire Vandecasteele
Cyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating multiple aspects of cardiac function. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families that are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP, controlling specific cell functions in response to various neurohormonal stimuli...
2016: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/27785815/characterisation-of-pomegranate-juice-effects-on-human-corpus-cavernosum
#8
S Gur, B M Rezk, Z Y Abd Elmageed, P J Kadowitz, S C Sikka, W J G Hellstrom
Pomegranate (POM) juice may benefit the erectile process, but the scientific evidence is lacking. This study evaluates the molecular characterisation and confirmation of POM's action on human corpus cavernosum (HCC) obtained from patients (n = 16) undergoing penile prosthesis implantation. After phenylephrine contraction, the relaxant effects of POM with various inhibitors in the presence and absence of palmitic acid (PA)-induced acute oxidative stress were investigated. Electrical field stimulation (EFS)- and acetylcholine (ACh)-induced relaxation were performed using organ bath preparation...
October 26, 2016: Andrologia
https://www.readbyqxmd.com/read/27785443/dr-bang-ping-jiann-pde5-inhibitors-in-erectile-dysfunction
#9
Lucine M Gao
No abstract text is available yet for this article.
October 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/27784679/hydrogen-sulfide-an-enhancer-of-vascular-nitric-oxide-signalling-mechanisms-and-implications
#10
Csaba Szabo
Nitric oxide (NO) vascular signalling has long been considered an independent, self-sufficient pathway. However, recent data indicate that the novel gaseous mediator, hydrogen sulfide (H2S), serves as an essential enhancer/stimulator of vascular NO signalling. The current article overviews the multiple levels at which this enhancement/stimulation takes place. The first level of interaction relates to the formation of biologically active hybrid S/N species and the stimulation of NO release from its various stable "pools" (e...
October 26, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27763717/additive-effects-of-the-rho-kinase-inhibitor-y-27632-and-vardenafil-on-relaxation-of-the-corpus-cavernosum-tissue-of-patients-with-erectile-dysfunction-and-clinical-phosphodiesterase-type-5-inhibitor-failure
#11
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk J M K De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR])...
October 20, 2016: BJU International
https://www.readbyqxmd.com/read/27747306/chemotherapeutic-efficacy-of-phosphodiesterase-inhibitors-in-chagasic-cardiomyopathy
#12
Jian-Jun Wen, Xianxiu Wan, John Thacker, Nisha Jain Garg
BACKGROUND: Chagasic cardiomyopathy (CCM) caused by Trypanosoma cruzi (Tc) infection is prevalent in Latin America and recognized as an emerging infectious heart disease in the US. The NO-cGMP-PKG1α pathway maintains cardiac homeostasis and inotropy and may be disturbed due to phosphodiesterase (PDE5) mediated cGMP catabolism in CCM. METHODS AND RESULTS: C57BL/6 mice were infected with Tc, and at the end of acute parasitemia (i.e. 45 days post-infection), treated with sildenafil (SIL, 1 mg/kg) twice per week for 3 weeks...
June 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/27711090/penile-vascular-diagnostic-categorization-using-penile-duplex-doppler-ultrasound-differences-in-vascular-hemodynamics-parameters-by-differences-in-anatomic-sampling-location
#13
Fabio Pezzoni, Fabrizio Ildefonso Scroppo
OBJECTIVES: In 2013 the International Society for Sexual Medicine(ISSM) published the guidelines regarding the standard operating procedure (SOP) for penile duplex Doppler ultrasound (PDDU). Although ISSM-SOP have given important strides in reducing interobserver variability in PDDU by procedural protocol and parameters these guidelines do not address the anatomic location along the penis at which hemodynamic measurements have to be done. In our opinion a "double sampling" may be interesting to detect the arteriogenic or venogenic nature of the erectile dysfunction (ED)...
October 5, 2016: Archivio Italiano di Urologia, Andrologia
https://www.readbyqxmd.com/read/27705730/erectile-function-recovery-after-robotic-assisted-radical-prostatectomy-rarp-long-term-exhaustive-analysis-across-all-preoperative-potency-categories
#14
Abdullah M Alenizi, Kevin C Zorn, Marc Bienz, Emad Rajih, Pierre Alain Hueber, Naif Al-Hathal, Serge Benayoun, Thierry Lebeau, Assaad El-Hakim
INTRODUCTION: To evaluate erectile function recovery following robotic-assisted radical prostatectomy (RARP) according to preoperative sexual health inventory for men (SHIM) score stratification. MATERIALS AND METHODS: We prospectively collected data on 250 consecutive patients who underwent RARP by a single surgeon between October 2006 and October 2012. Thirty-six patients were excluded because of lack of preoperative SHIM score. All patients had a minimum follow up of 2 years...
October 2016: Canadian Journal of Urology
https://www.readbyqxmd.com/read/27701772/effects-of-an-alpha1a-d-adrenoceptor-antagonist-naftopidil-and-a-phosphodiesterase-type-5-inhibitor-tadalafil-on-urinary-bladder-remodeling-in-rats-with-spinal-cord-injury
#15
Katsumi Kadekawa, Tsuyoshi Majima, Naoki Kawamorita, Hiroki Okada, Tsuyoshi Yoshizawa, Kenichi Mori, Pradeep Tyagi, Kimio Sugaya, Naoki Yoshimura
AIMS: In order to clarify whether an alpha1A/D-adrenoceptor (α1 A/D-AR) antagonist, naftopidil, or a phosphodiesterase type 5 (PDE5) inhibitor, tadalafil, prevents bladder wall remodeling after spinal cord injury (SCI), we examined the bladder and urethral activity as well as ischemic and fibrotic changes in the bladder using SCI rats with or without naftopidil or tadalafil treatment. METHODS: Adult female Sprague-Dawley rats were divided into four groups: (1) normal (spinal cord intact); (2) vehicle SCI; (3) naftopidil SCI; and (4) tadalafil SCI groups...
October 4, 2016: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/27693738/labelling-molecular-modelling-and-biological-evaluation-of-vardenafil-a-potential-agent-for-diagnostic-evaluation-of-erectile-dysfunction
#16
O A El-Kawy, J A García-Horsman, R K Tuominen
(99m)Tc-tricarbonyl-vardenafil was specifically radiosynthesized for diagnostic evaluation of erectile dysfunction with a radiochemical yield ~97.2%. It was stable in saline up to 15h and in serum for more than 6h. The radiocomplex was lipophilic with a partition coefficient ~1.32 and plasma protein binding 72-76%. Its structure was determined using molecular mechanics and confirmed by NMR. In-silico docking to its target PDE5 enzyme was performed. The radiocomplex inhibitory activity was assessed and its IC50 was 0...
September 21, 2016: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/27686568/expressions-of-vaginal-endothelial-nitric-oxide-synthase-and-phosphodiesterase-5-in-female-sexual-dysfunction-a-pilot-study
#17
Kang Jun Cho, Kyu-Sung Lee, Myung-Soo Choo, Ju Tae Seo, Jang Hwan Kim, Jong Bo Choi, Seung-June Oh, Joon Chul Kim
INTRODUCTION AND HYPOTHESIS: The objective was to investigate the expression of endothelial nitric oxide synthase (eNOS) and phosphodiesterase (PDE) 5 in vaginal tissue of premenopausal women experiencing stress urinary incontinence (SUI) with and without sexual dysfunction. METHODS: Women presenting for treatment of SUI were screened using the Female Sexual Function Index (FSFI) and 10 were selected who met the criteria for female sexual dysfunction (FSD) and 10 asymptomatic controls...
September 29, 2016: International Urogynecology Journal
https://www.readbyqxmd.com/read/27685753/inhibition-of-phosphodiesterase-3-4-and-5-induces-endolymphatic-hydrops-in-mouse-inner-ear-as-evaluated-with-repeated-9-4t-mri
#18
Eva Degerman, Rene In 't Zandt, Annki Pålbrink, Lena Eliasson, Per Cayé-Thomasen, Måns Magnusson
CONCLUSION: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. OBJECTIVE: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling...
August 15, 2016: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/27658991/-efficacy-and-tolerance-of-pde-5%C3%A2-in-the-treatment-of-erectile-dysfunction-in-schizophrenic-patients-a-literature-review
#19
L Bacconi, F Gressier
INTRODUCTION: Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients...
September 19, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27611008/comparisons-of-regular-and-on-demand-regimen-of-ped5-is-in-the-treatment-of-ed-after-nerve-sparing-radical-prostatectomy-for-prostate-cancer
#20
Shi Qiu, Zhuang Tang, Linghui Deng, Liangren Liu, Ping Han, Lu Yang, Qiang Wei
Phosphodiesterase type-5 inhibitors (PDE5-Is) have been recommended as first line therapy for erectile dysfunction for patients received nerve-sparing radical prostatectomy for prostate cancer. We examed the efficiency of PDE5-Is and considered the optimal application. Systematic search of PubMed, Embase and the Cochrane Library was performed to identify all the studies. We identified 103 studies including 3175 patients, of which 14 were recruited for systematic review. Compared with placebo, PDE5-Is significantly ameliorated the International Index of Erectile Function-Erectile Function domain score (IIEF) scores (MD 4...
September 9, 2016: Scientific Reports
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