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https://www.readbyqxmd.com/read/28654865/molecular-effects-of-doxorubicin-on-choline-metabolism-in-breast-cancer
#1
Menglin Cheng, Asif Rizwan, Lu Jiang, Zaver M Bhujwalla, Kristine Glunde
Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS) detected total choline (tCho) signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC), phosphocholine (PC) and free choline (Cho), before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells...
June 24, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28654711/addressing-the-immunopathogenesis-of-atopic-dermatitis-advances-in-topical-and-systemic-treatment
#2
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/28652963/switching-from-sildenafil-to-riociguat-for-the-treatment-of-pah-and-inoperable-cteph-real-life-experiences
#3
Asger Andersen, Kasper Korsholm, Søren Mellemkjær, Jens Erik Nielsen-Kudsk
Riociguat is a novel soluble guanylate cyclase stimulator that is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA). As riociguat is a relatively new drug, experience of its use in clinical practice is limited, especially in patients who would not have met the inclusion criteria for the pivotal Phase III clinical trials, PATENT-1 and CHEST-1...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28652311/a-nutrient-regulated-cyclic-diguanylate-phosphodiesterase-controls-clostridium-difficile-biofilm-and-toxin-production-during-stationary-phase
#4
Erin B Purcell, Robert W McKee, David S Courson, Elizabeth M Garrett, Shonna M McBride, Richard E Cheney, Rita Tamayo
The signaling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen Clostridium difficile, c-di-GMP inhibits flagellar motility and toxin production, and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases...
June 26, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28652301/stand-alone-eal-domain-proteins-form-a-distinct-subclass-of-eal-proteins-involved-in-regulation-of-cell-motility-and-biofilm-formation-in-enterobacteria
#5
Youssef El Mouali, Hyunhee Kim, Irfan Ahmad, Annelie Brauner, Ying Liu, Mikael Skurnik, Michael Y Galperin, Ute Römling
The second messenger cyclic di-GMP is almost ubiquitous among bacteria and so are the cyclic di-GMP turnover proteins, which mediate the transition between motility and sessility. EAL domain proteins have been characterized as cyclic di-GMP-specific phosphodiesterases. While most EAL domain proteins contain additional, usually N-terminal, domains, there is a distinct family of proteins within stand-alone EAL domains, exemplified by Salmonella enterica serovar Typhimurium proteins STM3611 (YhjH/PdeH), a c-di-GMP-specific phosphodiesterase, and the enzymatically inactive STM1344 (YdiV/CdgR) and STM1697, which regulate bacterial motility through interaction with the flagella master regulator FlhDC...
June 26, 2017: Journal of Bacteriology
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
#6
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/28651482/modulation-of-some-markers-of-erectile-dysfunction-and-malonaldehyde-levels-in-isolated-rat-penile-tissue-with-unripe-and-ripe-plantain-peels-identification-of-the-constituents-of-the-plants-using-hplc
#7
Ganiyu Oboh, Adedayo Oluwaseun Ademiluyi, Sunday Idowu Oyeleye, Tosin Abiola Olasehinde, Aline Augusti Boligon
CONTEXT: Plantain fruit pulp has been used as a natural remedy to manage erectile dysfunction (ED) in traditional medicine. However, the potency of the peel has not been examined with respect to ED management. OBJECTIVE: This study investigated and compared the inhibitory potential of unripe (UPP) and ripe (RPP) plantain peels on some enzymes associated with ED and Fe(2+)-induced oxidative stress in albino rat penile homogenate in vitro. MATERIALS AND METHOD: Aqueous extract of the peels was prepared and the effect on phosphodiesterase-5 (PDE-5), arginase, acetylcholinesterase (AChE), angiotensin-I converting enzyme (ACE) and Fe(2+)-induced malonyladehyde in isolated albino rat penile homogenate were investigated...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28650427/roflumilast-reverses-polymicrobial-sepsis-induced-liver-damage-by-inhibiting-inflammation-in-mice
#8
Hongfang Feng, Jiajia Chen, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Qiuping Zhong, Jiangping Xu
Sepsis is a life-threatening syndrome accompanied by an overwhelming inflammatory response and organ dysfunction. Selective targeting of phosphodiesterase 4 (PDE4) is currently being investigated as an effective therapeutic approach for inflammation-associated diseases. Roflumilast is a selective PDE4 inhibitor, used for the treatment of severe chronic obstructive pulmonary disease in clinic. However, its role in the treatment of sepsis-induced liver damage remains unclear. In the present study, we evaluated the effects of roflumilast in mice with cecal ligation and puncture-induced sepsis, and investigated the underlying mechanism...
June 26, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28649129/c33-s-a-novel-pde9a-inhibitor-protects-against-rat-cardiac-hypertrophy-through-upregulating-cgmp-signaling
#9
Pan-Xia Wang, Zhuo-Ming Li, Si-Dong Cai, Jing-Yan Li, Ping He, Yi Huang, Guo-Shuai Feng, Hai-Bin Luo, Shao-Rui Chen, Pei-Qing Liu
Phosphodiesterase-9A (PDE9A) expression is upregulated during cardiac hypertrophy and heart failure. Accumulating evidence suggests that PDE9A might be a promising therapeutic target for heart diseases. The present study sought to investigate the effects and underlying mechanisms of C33(S), a novel selective PDE9A inhibitor, on cardiac hypertrophy in vitro and in vivo. Treatment of neonatal rat cardiomyocytes (NRCMs) with PE (100 μmol/L) or ISO (1 μmol/L) induced cardiac hypertrophy characterized by significantly increased cell surface areas and increased expression of fetal genes (ANF and BNP)...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28648986/segmentation-of-medical-images-using-mean-value-guided-contour
#10
Ali A Kiaei, Hassan Khotanlou
Partial differential equation-based (PDE-based) methods are extensively used in image segmentation, especially in contour models. Difficulties associated with the boundaries, namely troubles with developing initialization, inadequate convergence to boundary concavities, and difficulties connected to saddle points and stationary points of active contours make the contour models suffer from a feeble performance of referring to complex geometries. The present paper is designed to take advantage of mean value theorem rather than minimizing energy function for contours...
June 13, 2017: Medical Image Analysis
https://www.readbyqxmd.com/read/28648945/phosphodiesterase-5-inhibition-as-a-therapeutic-target-for-ischemic-stroke-a-systematic-review-of-preclinical-studies
#11
Joakim N E Ölmestig, Ida R Marlet, Atticus H Hainsworth, Christina Kruuse
Phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil (Viagra®) are widely used for erectile dysfunction and pulmonary hypertension. Preclinical studies suggest that PDE5i may improve functional outcome following ischemic stroke. In this systematic review we aimed to evaluate the effects of selective PDE5i in animal models of brain ischaemia. A systematic search in Medline, Embase, and The Cochrane Library was performed including studies in English assessing the effects of selective PDE5i. 32 publications were included describing outcome in 3646 animals...
June 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28643344/optimization-and-transferability-of-non-electrostatic-repulsion-in-the-polarizable-density-embedding-model
#12
Dalibor Hršak, Jógvan Magnus Haugaard Olsen, Jacob Kongsted
Embedding techniques in combination with response theory represent a successful approach to calculate molecular properties and excited states in large molecular systems such as solutions and proteins. Recently, the polarizable embedding model has been extended by introducing explicit electronic densities of the molecules in the nearest environment, resulting in the polarizable density embedding (PDE) model. This improvement provides a better description of the intermolecular interactions at short distances...
June 22, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28643292/-avanafil-for-the-treatment-of-erectile-dysfunction-in-practice-non-interventional-study-avanti
#13
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/28642047/erectile-dysfunction-in-young-men-a-review-of-the-prevalence-and-risk-factors
#14
REVIEW
Hoang Minh Tue Nguyen, Andrew T Gabrielson, Wayne J G Hellstrom
INTRODUCTION: Erectile dysfunction (ED) is an important health concern that can significantly affect a man's psychosocial well-being. ED has traditionally been considered a disease of old age; however, contemporary evidence suggests a growing incidence of ED in men younger than 40 years. The process of achieving an erection is multifaceted; there are many potential mechanisms that can be disrupted. It is critical to identify the specific causes of ED before proceeding with potentially costly and invasive therapeutic options...
June 19, 2017: Sexual Medicine Reviews
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/28640077/improvement-of-peripheral-artery-disease-with-sildenafil-and-bosentan-combined-therapy-in-a-patient-with-limited-cutaneous-systemic-sclerosis-a-case-report
#16
Loukman Omarjee, Cedric Fontaine, Guillaume Mahe, Vincent Jaquinandi
RATIONALE: Sildenafil, a phosphodiesterase-5-inhibitor and Bosentan, an endothelin-1-receptor antagonist combined therapy could have beneficial effect in systemic sclerosis (SSc) patients with peripheral artery disease. PATIENT CONCERNS: We report a case of a 48-year-old Black woman, who developed severe left limb claudication and walking limitation following a left femoropopliteal bypass occlusion in 2014. She was a heavy smoker and had a history of right middle cerebral artery ischemic stroke and bilateral Raynaud phenomenon...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28638635/crystal-structure-of-an-apremilast-ethanol-hemisolvate-hemihydrate-solvatomorph
#17
Yun-Deng Wu, Xiao-Hong Liu, Jian Xu, Si-Han Zhang, Kun Shen, Ling Sun, Yong-Mei He, Yan Ma, Ai-Hua Zhang
The title compound, C22H24N2O7S·0.5C2H5OH·0.5H2O {systematic name: (S)-4-acetamido-2-[1-(3-eth-oxy-4-meth-oxy-phen-yl)-2-(methyl-sulfon-yl)eth-yl]iso-indo-line-1,3-dione ethanol hemisolvate hemihydrate}, is a novel solvatomorph of apremilast (AP), which is an inhibitor of phosphodiesterase 4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The asymmetric unit contains one mol-ecule of AP and disordered mol-ecules of ethanol and water, both with half occupancy. The dihedral angle between the planes of the phenyl ring and the iso-indole ring is 67...
June 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28637505/human-lung-and-monocyte-derived-macrophages-differ-with-regard-to-the-effects-of-%C3%AE-2-adrenoceptor-agonists-on-cytokine-release
#18
Tatiana Victoni, Hélène Salvator, Charlotte Abrial, Marion Brollo, Luis Cristovão Sobrino Porto, Vincent Lagente, Emmanuel Naline, Stanislas Grassin-Delyle, Philippe Devillier
BACKGROUND: β2-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β2-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs. METHODS: LMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF...
June 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28636912/channeling-of-camp-in-pde-pka-complexes-promotes-signal-adaptation
#19
Nikhil Kumar Tulsian, Srinath Krishnamurthy, Ganesh Srinivasan Anand
Spatiotemporal control of the cAMP signaling pathway is governed by both hormonal stimulation of cAMP generation by adenylyl cyclases (activation phase) and cAMP hydrolysis by phosphodiesterases (PDEs) (termination phase). The termination phase is initiated by PDEs actively targeting the protein kinase A (PKA) R-subunit through formation of a PDE-PKAR-cyclic adenosine monophosphate (cAMP) complex (the termination complex). Our results using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP bound to its receptor RIα by enhancing the enzymatic activity...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28634298/analyses-of-pde-regulated-phosphoproteomes-reveal-unique-and-specific-camp-signaling-modules-in-t-cells
#20
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
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