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Kornelia Johann, Marlen Colleen Reis, Lisbeth Harder, Beate Herrmann, Sogol Gachkar, Jens Mittag, Rebecca Oelkrug
Stimulation of thermogenic pathways appears to be a promising approach to find new ways of tackling metabolic diseases like obesity and diabetes mellitus type 2. Thermogenic, weight reducing and insulin sensitizing effects of phosphodiesterase 5 (PDE 5) inhibitors have recently been postulated, suggesting that modulators of endogenous cGMP signaling have the therapeutic potential to treat metabolic disorders. However, most studies have been performed in vitro or in animals that were not glucose intolerant. We, thus, aimed to test the metabolic effects of the PDE 5 inhibitor sildenafil by treating diet-induced obese (DIO) mice orally for 8 days...
March 13, 2018: Nutrition & Diabetes
D Valenzuela, F Moya, M Luco, J L Tapia
50 years ago, Northway described Broncopulmonary Dysplasia (BPD) in preterm infants exposed to mechanical ventilation. Since then, their survival has increased, nevertheless a "new BPD" has appeared and its incidence has not diminished. One of the characteristics of this pathology is the the abnormal vascular remodeling, which in its most severe expression is known as Pulmonary Hyper tension (PH); with an incidence of 17% in patients with BPD, which is proportional to the severity of the disease (33% in severe BPD), and as mortality factor (up to 48% 2-year mortality in PH-BPD)...
December 2017: Revista Chilena de Pediatría
Taishi Nakamura, Guangshuo Zhu, Mark J Ranek, Kristen Kokkonen-Simon, Manling Zhang, Grace E Kim, Kenichi Tsujita, David A Kass
BACKGROUND: Stimulation of sGC (soluble guanylate cyclase) or inhibition of PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression of pathological cardiac stress. Because PDE5 and sGC reside in separate microdomains, we speculated that PKG1α oxidation might also differentially influence the effects from their pharmacological modulation...
March 2018: Circulation. Heart Failure
Claudia Miranda, Zenia Pérez-Rodríguez, Rosario Hernández-Armengol, Yaidel Quiñones-García, Tania Betancourt-Purón, Miguel Ángel Cabrera-Pérez
The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1...
March 12, 2018: AAPS PharmSciTech
Jinglan Zhang, Jiakai Lu, Xiaorui Zhou, Xuefeng Xu, Qing Ye, Qitan Ou, Yanna Li, Jiapeng Huang
OBJECTIVES: The mortality of pregnant women with idiopathic pulmonary arterial hypertension (PAH) is very high. There are limited data on the management of idiopathic PAH during pregnancy. The authors aimed to examine systematically the characteristics of parturient women with idiopathic PAH, to explore the adverse effects of idiopathic PAH on pregnancy outcomes, and to report the multidisciplinary perioperative management strategy from the largest comprehensive cardiac hospital in China...
March 7, 2018: Journal of Cardiothoracic and Vascular Anesthesia
Teemu T Turunen, Ari Koskelainen
Cyclic nucleotide phosphodiesterases (PDEs) hydrolyze the second messengers cAMP and cGMP. PDEs control numerous cellular processes making them promising targets for the development of therapeutic agents. Unfortunately, many PDE inhibitor molecules are non-selective among PDE classes and efficient methods for quantitative studies on the isoform-specificity of PDE inhibitors in the natural environments of PDEs are unavailable. The PDE in photoreceptors, PDE6, mediates the conversion of photon information into electrical signals making the retina an exceptional model system for examinations of the pharmacological effects of PDE inhibitors on PDE6...
March 5, 2018: Toxicology and Applied Pharmacology
Nabham Rai, Swathi Veeroju, Yves Schymura, Wiebke Janssen, Astrid Wietelmann, Baktybek Kojonazarov, Norbert Weissmann, Johannes-Peter Stasch, Hossein Ardeschir Ghofrani, Werner Seeger, Ralph Theo Schermuly, Tatyana Novoyatleva
Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and a rise in right ventricular (RV) afterload. The increased RV afterload leads to right ventricular failure (RVF) which is the reason for the high morbidity and mortality in PAH patients. The objective was to evaluate the therapeutic efficacy and antiremodeling potential of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the soluble guanylate cyclase stimulator riociguat in a model of pressure overload RV hypertrophy induced by pulmonary artery banding (PAB)...
2018: BioMed Research International
Mervat Z Mohamed, Heba M Hafez, Nagwa M Zenhom, Hanaa Hassanein Mohammed
AIMS: Male infertility prevalence is higher in diabetic patients. Those patients exhibit testicular oxidative damage due to sustained hyperglycemia and inflammation. The study has investigated the efficacy of cilostazol, a phosphodiesterase 3 inhibitor, on testicular damage of diabetic rats. MAIN METHODS: Streptozotocin-induced diabetes in rats was used as a model. Six control male rats and 24 diabetic male rats were divided into the following: diabetic, cilostazol at low dose, cilostazol at high dose, and sildenafil treated rat groups...
February 26, 2018: Life Sciences
Joseph C Cappelleri, Li-Jung Tseng, Vera J Stecher, Stanley E Althof
AIM: To determine what constitutes a clinically important difference (CID) on the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), an 11-item validated questionnaire assessing treatment satisfaction used in clinical trials for patients with erectile dysfunction (ED). METHODS: Erectile Dysfunction Inventory of Treatment Satisfaction data were evaluated from a double-blind, fixed-dose trial of 279 men aged 18-65 years with ED who were treated with sildenafil 50 or 100 mg or placebo...
March 1, 2018: International Journal of Clinical Practice
Fatoumata Yanoga, Ronald C Gentile, Toco Y P Chui, K Bailey Freund, Millie Fell, Rosa Dolz-Marco, Richard B Rosen
BACKGROUND/PURPOSE: To report a case of persistent retinal toxicity associated with a high dose of sildenafil citrate intake. METHODS: Single retrospective case report. RESULTS: A 31-year-old white man with no medical history presented with complaints of bilateral multicolored photopsias and erythropsia (red-tinted vision), shortly after taking sildenafil citrate-purchased through the internet. Patient was found to have cone photoreceptor damage, demonstrated using electroretinogram, optical coherence tomography, and adaptive optics imaging...
February 27, 2018: Retinal Cases & Brief Reports
Yun-Yun Li, Ya-Jie Yu, Xi-Pu Liu, Ning-Pu Liu
No abstract text is available yet for this article.
2018: International Journal of Ophthalmology
Diego Moura Soares, Flávia Maria de Moraes Ramos-Perez, Samuel Silva de Araújo, Priscylla Gonçalves Correia Leite de Marcelos, Andrea Dos Anjos Pontual, Danyel Elias da Cruz Perez
OBJECTIVE: To investigate the effect of sildenafil citrate on the prevention and progression of experimental periodontitis (EP) in rats. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly assigned into 2 groups: Group 1 (preventive) and Group 2 (progression). In Group 1, the animals received daily doses of sildenafil (10 mg/Kg) or vehicle for 30 days, and EP was induced on the 15th day. In Group 2, the EP was induced on the first day, and the animals received daily doses of sildenafil (10 mg/Kg) or vehicle from the 15th day...
February 26, 2018: Oral Diseases
Lennart van der Veeken, Francesca M Russo, Johannes van der Merwe, David Basurto, Dyuti Sharma, Tram Nguyen, Marie P Eastwood, Namesh Khoshgoo, Jaan Toelen, Karel Allegaert, Philip Dekoninck, Stuart B Hooper, Richard Keijzer, Paolo DE Coppi, Jan Deprest
Congenital diaphragmatic hernia is rare birth defect, which can be easily corrected after birth. The main problem is that herniation of viscera during fetal development impairs lung development, leading to a 30 % mortality and significant morbidity. In isolated cases the outcome can be accurately predicted prenatally by medical imaging. Cases with a poor prognosis can be treated before birth; clinically this is by fetoscopic endoluminal tracheal occlusion. Obstruction of the airways triggers lung growth. This procedure and is currently being evaluated in a global clinical trial for left sided cases; right sided cases with poor prognosis are offered the procedure clinically...
February 23, 2018: Minerva Pediatrica
Nathani Minaz, Rema Razdan, Lokesh Pathak
BACKGROUND: Well known risk factors for diabetic erectile dysfunction include impaired nitric oxide synthesis and endothelial dysfunction. We proposed to evaluate the efficacy of nitric oxide donor, molsidomine in rat model of diabetic erectile dysfunction. METHODS: Streptozotocin (52 mg/kg, ip) induced diabetic male rats were treated with molsidomine (5 and 10 mg/kg, po) for 8 weeks. The sexual behaviour of male rat in presence of the female rat in oestrous phase was observed at the end of study...
September 4, 2017: Pharmacological Reports: PR
Henning Gall, Jean-Luc Vachiéry, Nobuhiro Tanabe, Michael Halank, Mauricio Orozco-Levi, Lisa Mielniczuk, MiKyung Chang, Kai Vogtländer, Ekkehard Grünig
PURPOSE: A proportion of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) do not achieve treatment goals or experience side effects on their current therapy. In such cases, switching patients to a new drug while discontinuing the first may be a viable and appropriate treatment option. CAPTURE was designed to investigate how physicians manage the switching of patients to riociguat in real-world clinical practice. Observations from the study were used to assess whether recommendations in the riociguat prescribing information are reflected in clinical practice...
February 22, 2018: Lung
Luca De Toni, Maurizio De Rocco Ponce, Erica Franceschinis, Stefano Dall'Acqua, Roberto Padrini, Nicola Realdon, Andrea Garolla, Carlo Foresta
Objective: Type 5 phosphodiesterase inhibitors (PDE5i) are efficient drugs used for treatment of erectile dysfunction (ED); however, a large discontinuation rate due to major side effects is reported. The aim of this study was to evaluate the possible improvement of sildenafil (Sild) pharmacokinetics associated to the sublingual administration of the new available oro-dispersible film (ODF), compared to both the oro-dispersible tablet (ODT) and the film-coated tablet (FCT) as original per os formulation. Methods: In vitro disaggregation test, dissolution test, and permeation test in specific devices to estimate the trans-mucosal absorption...
2018: Frontiers in Pharmacology
C Bereket, I Sener, N Cakir-Özkan, M E Önger, A V Polat
Objectives: The purpose of the present study was to evaluate the effects of sildenafil on mandibular fracture healing in animals treated with zoledronic acid by using histologic, histomorphometric, immunohistochemical, and radiodensitometric methods. Materials and Methods: A total of 36 Sprague-Dawley rats (3 months old) were used. All animals were treated intraperitoneally with 0.1 mg/kg zoledronate three times per week, for a total of 8 weeks. Postoperatively, the animals were divided into two groups: zoledronate group (Z), which had no treatment applied (n = 18), and zoledronate + sildenafil (ZS), which were treated daily with 10 mg/kg sildenafil (n = 18)...
February 2018: Nigerian Journal of Clinical Practice
Christian Apitz, Dietmar Schranz
No abstract text is available yet for this article.
February 16, 2018: Respiration; International Review of Thoracic Diseases
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles-E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary vasculature constriction and remodeling, involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT 2/2B/7 . In a rat model of monocrotaline (MCT)-induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor modulator, was evaluated as monotherapy and as an adjunct to standard PAH treatments. After a single 60mg/kg dose of MCT, rats received vehicle (MCT+Veh; gavage twice-daily [b.i.d.]), RP (10mg/kg; gavage b...
February 14, 2018: European Journal of Pharmacology
Sandra Frankenreiter, Dieter Groneberg, Anna Kuret, Thomas Krieg, Peter Ruth, Andreas Friebe, Robert Lukowski
Aims: It has been suggested that the nitric oxide-sensitive guanylyl cyclase (NO-GC)/cGMP-dependent signaling pathway affords protection against cardiac damage during acute myocardial infarction (AMI). It is, however, not clear whether the NO-GC/cGMP system confers its favorable effects through a mechanism located in cardiomyocytes (CMs). The aim of this study was to evaluate the infarct-limiting effects of the endogenous NO-GC in CMs in vivo. Methods and Results: Ischemia/reperfusion (I/R) injury was evaluated in mice with a cardiomyocyte-specific deletion of NO-GC (CM NO-GC KO) and in control siblings (CM NO-GC CTR) subjected to an in vivo model of AMI...
February 9, 2018: Cardiovascular Research
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