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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
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
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
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
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
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
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
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
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...
2016: Scientific Reports
Obdulia Rabal, Juan A Sánchez-Arias, Mar Cuadrado-Tejedor, Irene de Miguel, Marta Pérez-González, Carolina García-Barroso, Ana Ugarte, Ander Estella-Hermoso de Mendoza, Elena Sáez, Maria Espelosin, Susana Ursua, Tan Haizhong, Wu Wei, Xu Musheng, Ana Garcia-Osta, Julen Oyarzabal
Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). To further extend this concept, we designed and synthesized the first chemical series of dual acting PDE5 and HDAC inhibitors, and we validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate our hypothesis of dual in vitro inhibition...
October 13, 2016: Journal of Medicinal Chemistry
Sakura Morishita, Maki Hagihara, Megumi Itabashi, Yoshimi Ishii, Wataru Yamamoto, Ayumi Numata, Kenji Motohashi, Kenji Matsumoto, Shin Fujisawa, Hideaki Nakajima
We present a 36-year-old woman who had been taking oral dasatinib for 3 years for the treatment of chronic myelogenous leukemia (CML). Although adverse events such as thrombocytopenia and pleural effusion developed, she showed a major molecular response (MMR) 22 months after the initiation of oral dasatinib administration, and the therapy was thus continued. Approximately 34 months after oral dasatinib initiation, she developed severe exertional dyspnea and had to be urgently hospitalized. There was no apparent pleural effusion increase, and neither imaging nor blood test results suggested pneumonia or other infections...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Gülru Kayık, Nurcan Ş Tüzün, Serdar Durdagi
Cyclic nucleotide phosphodiesterase enzymes (PDEs) have functions in regulating the levels of intracellular second messengers, 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), via hydrolysis and decomposing mechanisms in cells. They take essential roles in modulating various cellular activities such as memory and smooth muscle functions. PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction...
October 6, 2016: Journal of Biomolecular Structure & Dynamics
E Onal, D Yilmaz, E Kaya, T Bastaskın, N Bayatlı, S Gur
Erectile dysfunction (ED) is associated with diabetes mellitus (DM). Pomegranate juice (PJ) is a potent antioxidant in diabetes induced oxidative stress. The aim of this study was to evaluate whether the administration of PJ ameliorates ED in streptozotocin (STZ)-diabetic rat model. Adult male Sprague-Dawley rats were divided into three groups (n=10-12, each): (1) Control, (2) STZ (25-35 mg kg(-1), intravenously, 10 weeks) induced DM, and (3) PJ (100 mg kg(-1) day(-1), 10 weeks) treated DM rats. The in vivo erectile [a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP)] and ex vivo corpus cavernosum (CC) responses were evaluated...
September 1, 2016: International Journal of Impotence Research
Asger Andersen, Jonas Agerlund Povlsen, Jacob Johnsen, Nichlas Riise Jespersen, Hans Erik Bøtker, Jens Erik Nielsen-Kudsk
BACKGROUND: To investigate whether modulation of the sGC-cGMP-PKG pathway protects against ischemia and reperfusion injury in the healthy and the failing right ventricle (RV). METHODS: Hearts from male Wistar rats with a healthy RV (n=39) or a hypertrophic and failing RV induced by pulmonary trunk banding (n=57) were isolated and perfused in a pressure-controlled modified Langendorff setup. The isolated hearts were randomized to control, ischemic preconditioning (IPC, 2×5min of global ischemia), a phosphodiesterase-5 (PDE5) inhibitor vardenafil (66nM) alone and in combination with a cGMP-dependent protein kinase (PKG) blocker KT 5823 (1μM)...
November 15, 2016: International Journal of Cardiology
Kátia R L Schwarz, Ramon Cesar Botigelli, Maite Del Collado, Fernanda Cavallari de Castro, Hugo Fernandes, Daniela M Paschoal, Cláudia Lima Verde Leal
Intracellular levels of cyclic nucleotides, such as cGMP, are involved in the regulation of adipocyte lipolysis. Cumulus-oocyte complexes (COCs) express enzymes that both synthesise (guanylate cyclase) and degrade (phosphodiesterase (PDE) 5A) cGMP. Because serum interferes with lipid metabolism, its effects on the cGMP pathway and lipid content in bovine COCs were examined. COCs were matured in medium containing fetal calf serum (FCS; 2% or 10%) or 0.4% bovine serum albumin (BSA; control). At both 2% and 10%, FCS decreased cGMP levels in COCs compared with BSA (0...
August 24, 2016: Reproduction, Fertility, and Development
Mar Cuadrado-Tejedor, Carolina Garcia-Barroso, Juan A Sánchez-Arias, Obdulia Rabal, Marta Pérez-González, Sara Mederos, Ana Ugarte, Rafael Franco, Victor Segura, Gertrudis Perea, Julen Oyarzabal, Ana Garcia-Osta
The targeting of two independent but synergistic enzymatic activities, histone deacetylases (HDACs, class I and HDAC6) and phosphodiesterase 5 (PDE5), has recently been validated as a potentially novel therapeutic approach for Alzheimerś disease (AD). Here we report the discovery of a new first-in-class small-molecule (CM-414) that acts as a dual inhibitor of PDE5 and HDACs. We have used this compound as a chemical probe to validate this systems therapeutics strategy, where an increase in the activation of cAMP/cGMP responsive element binding protein (CREB) induced by PDE5 inhibition, combined with moderate HDAC class I inhibition, leads to efficient histone acetylation...
August 23, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Fábio H Silva, Serkan Karakus, Biljana Musicki, Hotaka Matsui, Trinity J Bivalacqua, Jean L Dos Santos, Fernando F Costa, Arthur L Burnett
Patients with sickle cell disease (SCD) display priapism, and dysregulated nitric oxide (NO) pathway may contribute to this condition. However, current therapies offered for the prevention of priapism in SCD are few. The 3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate (compound 4C) was synthesized through molecular hybridization of hydroxyurea and thalidomide, which displays an NO-donor property. This study aimed to evaluate the effects of compound 4C on functional and molecular alterations of erectile function in murine models that display low NO bioavailability, SCD transgenic mice, and endothelial NO synthase and neuronal NO synthase double gene-deficient (dNOS(-/)) mice, focusing on the dysregulated NO-cGMP- phosphodiesterase type 5 (PDE5) pathway and oxidative stress in erectile tissue...
November 2016: Journal of Pharmacology and Experimental Therapeutics
James Anaissie, Wayne Jg Hellstrom
Erectile dysfunction (ED) is a common and debilitating disorder seen in over 50% of men older than 70 years. Oral phosphodiesterase type 5 (PDE5) inhibitors are the mainstay of treatment for ED, but cannot be used by a significant subset of patients due to systemic side effects and drug-drug interactions. Second-line therapy may include intracavernosal therapies, but are associated with poor compliance due to their invasive nature. Alprostadil has a mechanism of action different from that of PDE5 inhibitors...
2016: Research and Reports in Urology
Mahmoud Benatta, Nassim Kazi Tani, Sataa Sallami, K Belayachi, M Mahdid, M Lakli, Mohamed Amin Djazouli
AIM: to make an inventory of the prevalence, the severity, the reasons for the patient's consultation and the therapeutic measures indicated by urologists for erectile dysfunction (ED) in the west of Algeria. METHODS: This survey was conducted among 4 urologists. All male patients, aged over 18 years, presenting to clinics during the study period of 2 months were included. Data collection was based on a self-administered questionnaire on socio-demographic data, comorbidities especially urological and sexual health history...
February 2016: La Tunisie Médicale
Xiao-Hui Li, Yuan-Yuan Deng, Fei Li, Jing-Shan Shi, Qi-Hai Gong
Alzheimer's disease (AD) is known to be caused by the accumulation of amyloid-β peptide (Aβ). The accumulation of Aβ has been shown to cause learning and memory impairment in rats, and it has been shown that hydrogen sulfide donors, such as sodium hydrosulfide (NaHS) can attenuate these effects. However, the underlying mechanisms have not yet been fully eludicated. This study was designed to investigate whether NaHS attenuates the inflammation and apoptosis induced by Aβ. We demonstrated that NaHS attenuated Aβ25‑35-induced neuronal reduction and apoptosis, and inhibited the activation of pro-caspase-3...
October 2016: International Journal of Molecular Medicine
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