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https://www.readbyqxmd.com/read/28713578/retrospective-evaluation-of-pimobendan-and-sildenafil-therapy-for-severe-pulmonary-hypertension-due-to-lung-disease-and-hypoxia-in-28-dogs-2007-2013
#1
Lisa A Murphy, Nicholas Russell, Domenico Bianco, Reid K Nakamura
Pulmonary hypertension (PH) is the persistent abnormal increase in pulmonary artery (PA) pressure and in dogs is usually secondary to congenital disease causing pulmonary over circulation, chronic respiratory disease and elevated left atrial pressure. Sildenafil (SF) is a phosphodiesterase (PDE) V inhibitor that causes pulmonary artery (PA) vasodilation by increasing pulmonary vascular concentrations of cyclic guanosine monophosphate which subsequently increases the activity of endogenous nitric oxide. Pimobendan (PB) is a PDE III inhibitor with calcium sensitizing effects thereby exerting positive inotropy and vasodilation...
May 2017: Veterinary Medicine and Science
https://www.readbyqxmd.com/read/28709568/current-and-emerging-topical-therapies-for-atopic-dermatitis
#2
Jeremy Udkoff, Andrea Waldman, Jusleen Ahluwalia, Jenna Borok, Lawrence F Eichenfield
The pathogenesis of atopic dermatitis (AD) involves epidermal barrier dysfunction and T helper cell type 2 (Th2) lymphocyte-driven inflammation. Cytokines, such as interleukin 4 (IL-4) and IL-13, are important in this reaction. They stimulate B cells to produce immunoglobulin E, causing atopic disease. This process has been well characterized, and new therapies for AD, such as phosphodiesterase 4 (PDE-4) inhibitors, Th2-expressed chemoattractant receptor-homologous molecule antagonists, and Janus kinase inhibitors, work by antagonizing this cellular pathway...
July 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28706457/relaxant-and-anti-inflammatory-effect-of-two-thalidomide-analogs-as-pde-4-inhibitors-in-pregnant-rat-uterus
#3
Víctor Manuel Muñoz-Pérez, Eduardo Fernández-Martínez, Héctor Ponce-Monter, Mario I Ortiz
The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy. Uterine samples were used in functional studies to evaluate the inhibitory effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-F2α (PGF2α)-induced phasic, K(+)-induced tonic, and Ca(2+)-induced contractions...
July 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28702718/single-center-experience-using-selexipag-in-a-pediatric-population
#4
Roberto Gallotti, Diana E Drogalis-Kim, Gary Satou, Juan Alejos
Pulmonary arterial hypertension (PAH) is a rare and progressive disorder. Current treatment in the pediatric population includes phosphodiesterase 5 inhibitors (PDE-5i), endothelin receptor antagonists (ERA), and both inhaled and intravenous prostacyclin pathway agonists. As of December 22, 2015 the first oral prostacyclin pathway agonist, selexipag (Uptravi(®)), was FDA approved in the US. In this case series, we discuss our single-center experience using selexipag in a pediatric population, composed of both patients with idiopathic PAH, and patients with congenital heart disease and PAH...
July 13, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28701798/cognitive-behavioral-therapy-as-an-adjunct-treatment-for-pakistani-men-with-ed
#5
S Khan, A Amjad, D Rowland
The goal of this study was to determine potential positive effects of cognitive behavioral therapy (CBT) on Pakistani men with ED who were undergoing treatment with a PDE-5 inhibitor. We used a pre-post research design comparing men with and without adjunctive CBT. Men in the two groups were compared to determine whether CBT improved sexual function, as measured by the International Index of Erectile Function (IIEF). A total of 60 individuals diagnosed with ED completed the study. Participants were systematically assigned to one of two groups, the CBT group or the control group...
July 13, 2017: International Journal of Impotence Research
https://www.readbyqxmd.com/read/28697992/pde3-inhibition-by-c-type-natriuretic-peptide-induced-cgmp-enhances-camp-mediated-signaling-in-both-non-failing-and-failing-hearts
#6
Silja Meier, Kjetil Wessel Andressen, Jan Magnus Aronsen, Ivar Sjaastad, Karina Hougen, Tor Skomedal, Jan-Bjørn Osnes, Eirik Qvigstad, Finn Olav Levy, Lise Román Moltzau
We have previously shown that the natriuretic peptide receptor B (NPR-B) agonist C-type natriuretic peptide (CNP) enhances cyclic adenosine 3´,5´-monophosphate (cAMP)-mediated signaling in failing hearts, through cyclic guanosine 3´,5´-monophosphate (cGMP)-mediated phosphodiesterase (PDE) 3 inhibition. As several signaling pathways are importantly changed in failing hearts, it could not be taken for granted that this crosstalk would be the same in non-failing hearts. Thus, we wanted to clarify to which extent this effect of CNP occurred also in non-failing hearts...
July 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28689812/ibmx-protects-human-proximal-tubular-epithelial-cells-from-hypoxic-stress-through-suppressing-hypoxia-inducible-factor-1%C3%AE-expression
#7
Arif Ul Hasan, Wararat Kittikulsuth, Fuminori Yamaguchi, Tuba Musarrat Ansary, Asadur Rahman, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Masaaki Tokuda, Akira Nishiyama
Hypoxia predisposes renal fibrosis. This study was conducted to identify novel approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated hypoxia-inducible factor 1α (HIF-1α) mRNA expression, which was further augmented by addition of a transcriptional inhibitor, actinomycin D. IBMX also increased the cellular cyclic adenosine monophosphate (cAMP) level...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28687079/expression-and-function-of-phosphodiesterases-pdes-in-the-rat-urinary-bladder
#8
Xiaofei Zhu, Kui Zhai, Yue Mi, Guangju Ji
BACKGROUND: It has been shown that hosphodiesterases (PDEs) play an important role in mediating the smooth muscle tone of rat urinary bladder. However, the gene expression profiles of them were still unknown. METHODS: Urinary bladder Strips were obtained from both neonatal and adult Sprague-Dawley rats. RT-PCR/western blot and organ bath were used to measure the expression and function of PDEs. RESULTS: Adult rat urinary bladder expressed various PDE mRNA with the following rank order: PDE5A ≈ PDE9A ≈ PDE10A > PDE2A ≈ PDE4A ≈ PDE4D > PDE4B ≈ PDE3B ≈ PDE8B ≈ PDE7A ≈ PDE7B > PDE1A...
July 7, 2017: BMC Urology
https://www.readbyqxmd.com/read/28681318/phosphodiesterase-4-inhibitor-therapies-for-atopic-dermatitis-progress-and-outlook
#9
Jusleen Ahluwalia, Jeremy Udkoff, Andrea Waldman, Jenna Borok, Lawrence F Eichenfield
Phosphodiesterase 4 (PDE4) is a cyclic AMP degrading enzyme in leukocytes. Several decades ago, increased PDE activity was demonstrated in patients with atopic dermatitis (AD). Currently, several PDE4 inhibitors in both topical and oral formulation have been developed to target the inflammatory cascade of AD. This review shows the pathogenic rationale behind these inhibitors, and discusses multiple PDE4 inhibitors that are under evaluation or in the market. PDE4 inhibitors may be considered as favorable agents in the repertoire of current interventions for AD...
July 5, 2017: Drugs
https://www.readbyqxmd.com/read/28675791/olprinone-protects-liver-from-ischemia-reperfusion-injury-through-oxidative-stress-prevention-and-protein-kinase-akt-activation
#10
Mohamed Bejaoui, Mohamed Amine Zaouali, Rim Sakly, Hassen Ben Abdennebi
Liver ischemia reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary non function after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to one hour of partial warm ischemia (70%) followed by six hours of reperfusion...
July 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28656504/can-dehydrated-human-amnion-chorion-membrane-accelerate-the-return-to-potency-after-a-nerve-sparing-robotic-assisted-radical-prostatectomy-propensity-score-matched-analysis
#11
Gabriel Ogaya-Pinies, Hariharan Palayapalam-Ganapathi, Travis Rogers, Eduardo Hernandez-Cardona, Bernardo Rocco, R F Coelho, Cathy Jenson, Vipul R Patel
The objective of this study is to determine if the use of dehydrated human amnion/chorion membrane (dHACM) allograft wrapped around the NVB during a robotic-assisted radical prostatectomy (RARP) accelerates the return to potency. 940 patients with preoperative SHIM >20 underwent RARP with some degree of bilateral NS. Of these, 235 patients underwent RARP, with bilateral placement of dHACM graft around the NVBs. They were matched in a 1:3 proportion with a similar group of patients (n = 705) who did not receive the allograft (control group or group 2)...
June 27, 2017: Journal of Robotic Surgery
https://www.readbyqxmd.com/read/28654711/addressing-the-immunopathogenesis-of-atopic-dermatitis-advances-in-topical-and-systemic-treatment
#12
Lawrence F Eichenfield, Linda F Stein Gold
Several immunologic mediators-phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase-have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA-15406...
March 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28651653/influence-of-nitric-oxide-and-phosphodiesterases-during-in-vitro-maturation-of-bovine-oocytes-on-meiotic-resumption-and-embryo-production
#13
Ramon Cesar Botigelli, Katia Lancellotti Schwarz, Fabiane Gilli Zaffalon, Maite Del Collado, Fernanda Cavallari Castro, Hugo Fernandes, Claudia Lima Verde Leal
This study aimed to examine the effects of nitric oxide (NO) and different phosphodiesterase (PDE) families on meiosis resumption, nucleotides levels and embryo production. Experiment I, COCs were matured in vitro with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) associated or not with the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), meiotic resumption and nucleotides levels were assessed. SNAP delayed germinal vesicle breakdown (GVBD) (53.4 ± 1.2 versus 78...
June 27, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28643292/-avanafil-for-the-treatment-of-erectile-dysfunction-in-practice-non-interventional-study-avanti
#14
Richard Berges, Dieter Schremmer, Roger Limberg
OBJECTIVE AND METHOD: In the prospective, multicentric, non-interventional AVANTI study, the selection criteria for the PDE-5 inhibitor Avanafil were evaluated and it's acceptance in the treatment of patients with erectile dysfunction was investigated. Data from 1,804 probands with an average age of 58.0 years were analyzed. RESULTS: Doctors and patients most commonly referred to Avanafil as a fast-acting substance (70.6% and 78.6%, respectively). A favorable side-effect profile was more focused when the patient co-decided (62...
June 2017: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/28641524/the-bio-psycho-social-dimension-in-women-s-sexual-desire-argumentum-ad-novitatem
#15
Nur Syazwani Roslan, Nik Ruzyanei Nik Jaafar, Hatta Sidi, Najwa Baharuddin, Jaya Kumar, Srijit Das, Nik Hazlina Nik Hussein
Sexual desire includes complex motivation and drive. In the context of biological and cognitive-emotive state art of science, it is often a neglected field in medicine. With regard to the treatment, study on women's sexual function received less attention compared to the men's sexuality. In the past, this endeavor was relatively not well disseminated in the scientific community. Recently, there was a revolutionized surge of drug targets available to treat women with low sexual desire. It is timely to review the relevant biological approach, especially in the context of pharmacotherapy to understand this interesting clinical entity which was modulated by numerous interactive psychosocial inter-play and factors...
June 21, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28634298/analyses-of-pde-regulated-phosphoproteomes-reveal-unique-and-specific-camp-signaling-modules-in-t-cells
#16
Michael-Claude G Beltejar, Ho-Tak Lau, Martin G Golkowski, Shao-En Ong, Joseph A Beavo
Specific functions for different cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types. Conventional approaches to study PDE function typically rely on measurements of global cAMP, general increases in cAMP-dependent protein kinase (PKA), or the activity of exchange protein activated by cAMP (EPAC). Although newer approaches using subcellularly targeted FRET reporter sensors have helped define more compartmentalized regulation of cAMP, PKA, and EPAC, they have limited ability to link this regulation to downstream effector molecules and biological functions...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28618988/synthesis-docking-and-anti-inflammatory-activity-of-triazole-amine-derivatives-as-potential-phosphodiesterase-4-inhibitors
#17
Ajmer Singh Grewal, Viney Lather, Deepti Pandita, Ruchi Dalal
BACKGROUND: Phosphodiesterase 4 (PDE4), one of the member of PDE superfamily catalyzes, the hydrolysis of cyclic adenosine monophosphate to adenosine monophosphate in pro-inflammatory and immunomodulatory cells leading to increased inflammatory processes. PDE4 has been reported as an attractive therapeutic target involved in various inflammatory disorders. OBJECTIVE: The present work was designed to synthesize and evaluate the anti-inflammatory activity of some new triazole amine derivatives as potential PDE4 inhibitors...
June 16, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28613871/discovery-of-n-4-5-4-fluorophenyl-3-methyl-2-methylsulfanyl-3h-imidazol-4-yl-pyridin-2-yl-acetamide-cbs-3595-a-dual-p38%C3%AE-mapk-pde-4-inhibitor-with-activity-against-tnf%C3%AE-related-diseases
#18
Wolfgang Albrecht, Anke Unger, Silke M Bauer, Stefan A Laufer
The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release...
June 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28597753/circulatory-power-and-ventilatory-power-over-time-under-goal-oriented-sequential-combination-therapy-for-pulmonary-arterial-hypertension
#19
Akihiro Hirashiki, Shiro Adachi, Yoshihisa Nakano, Yoshihiro Kamimura, Shigetake Shimokata, Kyosuke Takeshita, Atsuya Shimizu, Kenji Toba, Toyoaki Murohara, Takahisa Kondo
Many therapeutic options are available for patients with pulmonary arterial hypertension (PAH). However, little is known about the effects of sequential combination therapy on exercise capacity. Here we monitored exercise capacity by cardiopulmonary exercise testing (CPX) and observed the benefit of using a peak VO2 cutoff of 15 mL/kg/min to guide combination therapy. Thirty patients newly diagnosed with PAH were treated with goal-oriented sequential combination therapy. Endothelin receptor antagonists (ERA) were the first-line treatment, with phosphodiesterase type 5 inhibitors (PDE-5i) as the preferred combination partner...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28590829/aging-and-sexual-health-getting-to-the-problem
#20
Ecem Kaya, Suresh C Sikka, Philip J Kadowitz, Serap Gur
Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis. This review aims to identify the mechanisms of ED in the penile aging process in experimental and clinical data...
June 2017: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
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