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https://www.readbyqxmd.com/read/28730281/pk-pd-studies-on-non-selective-pde-inhibitors-in-rats-using-camp-as-a-marker-of-pharmacological-response
#1
Artur Świerczek, Elżbieta Wyska, Sebastian Baś, Marta Woyciechowska, Jacek Mlynarski
In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1 mg kg(-1), i...
July 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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
#2
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
#3
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/28709222/population-density-equations-for-stochastic-processes-with-memory-kernels
#4
Yi Ming Lai, Marc de Kamps
We present a method for solving population density equations (PDEs)--a mean-field technique describing homogeneous populations of uncoupled neurons-where the populations can be subject to non-Markov noise for arbitrary distributions of jump sizes. The method combines recent developments in two different disciplines that traditionally have had limited interaction: computational neuroscience and the theory of random networks. The method uses a geometric binning scheme, based on the method of characteristics, to capture the deterministic neurodynamics of the population, separating the deterministic and stochastic process cleanly...
June 2017: Physical Review. E
https://www.readbyqxmd.com/read/28707220/application-of-quasi-steady-state-methods-to-nonlinear-models-of-intracellular-transport-by-molecular-motors
#5
Cole Zmurchok, Tim Small, Michael J Ward, Leah Edelstein-Keshet
Molecular motors such as kinesin and dynein are responsible for transporting material along microtubule networks in cells. In many contexts, motor dynamics can be modelled by a system of reaction-advection-diffusion partial differential equations (PDEs). Recently, quasi-steady-state (QSS) methods have been applied to models with linear reactions to approximate the behaviour of the full PDE system. Here, we extend this QSS reduction methodology to certain nonlinear reaction models. The QSS method relies on the assumption that the nonlinear binding and unbinding interactions of the cellular motors occur on a faster timescale than the spatial diffusion and advection processes...
July 13, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28707032/receptor-heterogeneity-in-optical-biosensors
#6
Ryan M Evans, David A Edwards
Scientists measure rate constants associated with biochemical reactions in an optical biosensor-an instrument in which ligand molecules are convected through a flow cell over a surface to which receptors are immobilized. We quantify transport effects on such reactions by modeling the associated convection-diffusion equation with a reaction boundary condition. In experimental situations, the full PDE model reduces to a set of unwieldy integrodifferential equations (IDEs). Employing common physical assumptions, we may reduce the system to an ODE model, which is more useful in practice, and which can be easily adapted to the inverse problem of finding rate constants...
July 13, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28706457/relaxant-and-anti-inflammatory-effect-of-two-thalidomide-analogs-as-pde-4-inhibitors-in-pregnant-rat-uterus
#7
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
#8
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/28702541/enhanced-polarization-sensitive-terahertz-emission-from-vertically-grown-graphene-by-a-dynamical-photon-drag-effect
#9
L Zhu, Y Huang, Z Yao, B Quan, L Zhang, J Li, C Gu, X Xu, Z Ren
Improving terahertz (THz) emission from graphene is a challenge for graphene-based THz photonics as graphene demonstrates a weak light-matter interaction. With a unique ultra-black surface structure, vertically grown graphene (VGG) is proposed to enhance the light-matter interaction and further enhance THz emission. Herein, enhanced THz radiation is observed by THz time-domain emission spectroscopy from VGG compared with single-layer graphene. The radiated THz amplitude shows a linear dependence on pump power, which demonstrates a second order nonlinear effect...
July 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/28701798/cognitive-behavioral-therapy-as-an-adjunct-treatment-for-pakistani-men-with-ed
#10
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/28698725/plasma-pyridoxal-5%C3%A1-phosphate-level-in-children-with-intractable-and-controlled-epilepsy
#11
Zahra Pirzadeh, Mohammad Ghofrani, Mohsen Mollamohammadi
OBJECTIVE: Intractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy. MATERIALS & METHODS: This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age...
2017: Iranian Journal of Child Neurology
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
#12
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/28691859/preliminary-studies-of-berberine-and-its-semi-synthetic-derivatives-as-a-promising-class-of-multi-target-anti-parkinson-agents
#13
Giovanni Ribaudo, Enrico Zanforlin, Marcella Canton, Sergio Bova, Giuseppe Zagotto
Parkinson's disease (PD) is a neurodegenerative disorder bearing motor and nonmotor symptoms. The treatment today is symptomatical rather than preventive or curative and this leaves the field open for the search of both novel molecular targets and drug candidates. Interference with α-synuclein fibrillation, monoamine oxidase (MAO) inhibition, modulation of adenosine receptors and the inhibition of specific phosphodiesterase (PDE) isoforms are some of the currently pursued strategies. We synthesised and studied some semi-synthetic berberine derivatives using a set of in silico tools...
July 10, 2017: Natural Product Research
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
#14
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/28688490/a-fourth-order-pde-based-fuzzy-c-means-approach-for-segmentation-of-microscopic-biopsy-images-in-presence-of-poisson-noise-for-cancer-detection
#15
Rajesh Kumar, Subodh Srivastava, Rajeev Srivastava
BACKGROUND AND OBJECTIVE: For cancer detection from microscopic biopsy images, image segmentation step used for segmentation of cells and nuclei play an important role. Accuracy of segmentation approach dominate the final results. Also the microscopic biopsy images have intrinsic Poisson noise and if it is present in the image the segmentation results may not be accurate. The objective is to propose an efficient fuzzy c-means based segmentation approach which can also handle the noise present in the image during the segmentation process itself i...
July 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28687756/john-s-equation-based-consistency-condition-and-corrupted-projection-restoration-in-circular-trajectory-cone-beam-ct
#16
Jianhui Ma, Shuyu Wu, Hongliang Qi, Bin Li, Hao Yan, Linghong Zhou, Yuan Xu
In transmitted X-ray tomography imaging, the acquired projections may be corrupted for various reasons, such as defective detector cells and beam-stop array scatter correction problems. In this study, we derive a consistency condition for cone-beam projections and propose a method to restore lost data in corrupted projections. In particular, the relationship of the geometry parameters in circular trajectory cone-beam computed tomography (CBCT) is utilized to convert an ultra-hyperbolic partial differential equation (PDE) into a second-order PDE...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687079/expression-and-function-of-phosphodiesterases-pdes-in-the-rat-urinary-bladder
#17
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/28682259/inverse-diffusion-curves-using-shape-optimization
#18
Shuang Zhao, Fredo Durand, Changxi Zheng
The inverse diffusion curve problem focuses on automatic creation of diffusion curve images that resemble user provided color fields. This problem is challenging since the 1D curves have a nonlinear and global impact on resulting color fields via a partial differential equation (PDE). We introduce a new approach complementary to previous methods by optimizing curve geometry. In particular, we propose a novel iterative algorithm based on the theory of shape derivatives. The resulting diffusion curves are clean and well-shaped, and the final image closely approximates the input...
June 29, 2017: IEEE Transactions on Visualization and Computer Graphics
https://www.readbyqxmd.com/read/28681318/phosphodiesterase-4-inhibitor-therapies-for-atopic-dermatitis-progress-and-outlook
#19
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
#20
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
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