Sildenafil Administration in Dogs Heterozygous for a Functional Null Mutation in Pde6a: Suppressed Rod-Mediated ERG Responses and Apparent Retinal Outer Nuclear Layer Thinning.

Abstract:

:This study was designed to assess risk for retinal toxicity associated with administration of high-dose sildenafil citrate to dogs heterozygous for a functionally null mutation in Pde6a over a 4-month period. Three Pde6a +/- dogs were administered 14.3 mg/kg sildenafil per os and two Pde6a +/- dogs placebo once daily for 16 weeks. Three Pde6a +/+ dogs were administered sildenafil for 7 days. Ophthalmic examination, vision testing, and electroretinography (ERG) were regularly performed. At study termination, dogs were euthanized and globes collected. Retinal layer thickness and photoreceptor nuclei counts were determined from plastic sections. In both Pde6a +/- and Pde6a +/+ sildenafil-treated (ST) dogs, elevation of dark-adapted b-wave threshold and unmasking of the scotopic threshold response (STR) were observed. Sildenafil treated Pde6a +/- dogs had significantly thinner ONL (24.90 +/-1.88 μm, p = 0.004) and lower photoreceptor nuclei counts (273.6 +/- 29.3 cells/100 μm, p = 0.008) compared to measurements (35.90 +/- 1.63 μm) and counts (391.5 +/-27.0 cells/100 μm) from archived untreated Pde6a +/- dogs.

journal_name

Adv Exp Med Biol

authors

Pierce KE,Curran PG,Zelinka CP,Fischer AJ,Petersen-Jones SM,Bartoe JT

doi

10.1007/978-3-030-27378-1_61

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

371-376

eissn

0065-2598

issn

2214-8019

journal_volume

1185

pub_type

杂志文章
  • Fat content and fatty acid composition of fresh, pasteurized, or sterilized human milk.

    abstract::In hospitals, human milk is subjected to heat treatment to reduce risk of transmission of infectious agents such as human immunodeficiency virus (HIV), hepatitis B, cytomegalovirus, and bacterial contamination, especially during feeding of banked milk to preterm infants. Fat losses due to heat treatment have been exte...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-1371-1_60

    authors: Fidler N,Sauerwald TU,Demmelmair H,Koletzko B

    更新日期:2001-01-01 00:00:00

  • Kinetic properties of the ATP-dependent actin-myosin sliding as revealed by the force-movement assay system with a centrifuge microscope.

    abstract::To study the kinetic properties of the ATP-dependent actin-myosin sliding responsible for muscle contraction, we developed an in vitro force-movement assay system, in which centrifugal forces were applied to myosin-coated polystyrene beads sliding along actin cables of giant algal cells in the presence of ATP. Under c...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-2872-2_34

    authors: Chaen S,Oiwa K,Kobayashi T,Gross T,Kamitsubo E,Shimmen T,Sugi H

    更新日期:1993-01-01 00:00:00

  • Reconstructing virus structures from nanometer to near-atomic resolutions with cryo-electron microscopy and tomography.

    abstract::The past few decades have seen tremendous advances in single-particle electron -cryo-microscopy (cryo-EM). The field has matured to the point that near-atomic resolution density maps can be generated for icosahedral viruses without the need for crystallization. In parallel, substantial progress has been made in determ...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-1-4614-0980-9_4

    authors: Chang J,Liu X,Rochat RH,Baker ML,Chiu W

    更新日期:2012-01-01 00:00:00

  • Dose effects of raw soybean flour on pancreatic growth.

    abstract::Raw soya flour (RSF) feeding to rats produces pancreatic hypertrophy and hyperplasia, and, if sufficiently prolonged, the spontaneous development of pancreatic neoplasms and the potentiation of pancreatic carcinogens. With continuous exposure to RSF the threshold dose for pancreatic growth is approximately 20% RSF, bu...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4757-0022-0_4

    authors: Morgan RG,Crass RA,Oates PS

    更新日期:1986-01-01 00:00:00

  • Endogenous hormone levels and risk of breast, endometrial and ovarian cancers: prospective studies.

    abstract::Multiple lines of evidence support a central role of hormones in the etiology of breast, endometrial and ovarian cancers. Evidence of an association between circulating hormones and these cancers varies by both hormone and cancer site, with the most consistent associations observed for sex steroid hormones and breast ...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:

    authors: Eliassen AH,Hankinson SE

    更新日期:2008-01-01 00:00:00

  • Isolation of [hydroxyproline3]Lysyl-bradykinin formed by kallikrein from human plasma protein.

    abstract::[Hydroxyproline3]Lysyl-bradykinin ([Hyp3]Lys-BK), a new kinin was isolated, besides Lysyl-bradykinin (Lys-BK), from the reaction mixture of human plasma protein Cohn's fraction IV-4 with hog pancreatic kallikrein. The liberated kinins were isolated by procedures including ethanol extraction, Sephadex G-15, CM cellulos...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-9543-4_83

    authors: Sasaguri M,Ikeda M,Ideishi M,Arakawa K

    更新日期:1989-01-01 00:00:00

  • Taurine Chloramine Suppresses LPS-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglial Cells.

    abstract::The brain is sensitive to the inflammation and oxidative stress that can cause the aging or neurodegenerative diseases. We investigated the anti-neuroinflammatory activities of taurine chloramine (TauCl) on lipopolysaccharide (LPS)-treated mouse BV2 microglia mediated through heme oxygenase (HO)-1 expression. TauCl in...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-94-024-1079-2_12

    authors: Lee DS,Kwon KH,Cheong SH

    更新日期:2017-01-01 00:00:00

  • The effect of IABP ventricular contractility of the normal and ischemic canine heart assessed in situ by T-Emax.

    abstract::The effects of IABP on the contractile state of the in situ canine heart was evaluated under control conditions and conditions of regional ischemia by determining the transient slope of the end-systolic pressure-volume line, T-Emax. For comparison, the conventional index reflecting contractility, dP/dtmax and other re...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:

    authors: Chen J,Jiang YS,Fang FZ,Zeng J,Zhao M,Zhang WL,Zhang LF

    更新日期:1989-01-01 00:00:00

  • Cellular origin of mucins of the ocular surface tear film.

    abstract::In summary, we have demonstrated that the ocular surface epithelia express at least three mucin genes. We suggest that the gel-forming mucin MUC5AC is a major mucin forming the mucus gel of the tear film. We further suggest that MUC1 facilitates the spread of the MUC5-containing mucus on the ocular surface and, along ...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-1-4615-5359-5_32

    authors: Gipson IK,Inatomi T

    更新日期:1998-01-01 00:00:00

  • The use of genomics in model in vitro systems.

    abstract::Traditional toxicological tests generally provide descriptive information regarding the potential toxicity of chemicals, drugs and physical agents and are limited in their ability to assess risk to humans because they use model systems that are nonhuman in origin. Upon completion of the sequencing of the human genome,...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-1-4614-3055-1_12

    authors: Casciano DA

    更新日期:2012-01-01 00:00:00

  • Genetic variation in thymidylate synthase confers resistance to 5-fluorodeoxyuridine.

    abstract::The human colorectal tumor cell line HCT 116 was resident to the cytotoxic effects of 5-fluorodeoxyuridine (FdUrd). The response to FdUrd was increased only slightly by the presence of 10 microM folinic acid (CF). HCT 116 formed FdUMP and CH2H4PteGlu polyglutamates after exposure to FdUrd and CF. The sensitivity to Fd...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-2488-5_8

    authors: Hughey CT,Barbour KW,Berger FG,Berger SH

    更新日期:1993-01-01 00:00:00

  • Endosome acidification and the pathways of receptor-mediated endocytosis.

    abstract::Acidification of endocytic compartments occurs within 2-3 minutes following internalization. In CHO cells, three kinetically and morphologically distinct endocytic or recycling compartments can be identified. Measurements of the pH in these compartments show that the acidity of the compartments is regulated independen...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-1-4684-5442-0_16

    authors: Maxfield FR,Yamashiro DJ

    更新日期:1987-01-01 00:00:00

  • Formation of the comutagenic beta-carboline norharman in a simple tryptophan-containing model system at low temperature (40 degrees C-80 degrees C).

    abstract::The formation of the comutagenic tryptophan derivate norharman in heat-processed food is a well known phenomenon. As a first step to investigate the possible formation of norharman during food storage particularly in regard to fortified food we developed a model system and studied the non-enzymatic formation of the co...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-4709-9_89

    authors: Ziegenhagen R,Boczek P,Viell B

    更新日期:1999-01-01 00:00:00

  • Impact of modulators of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) on hypoxic pulmonary vasoconstriction.

    abstract::Previously, we demonstrated that hypoxic pulmonary vasoconstriction (HPV) of intra-acinar arteries (IAA) requires mitochondrial complex II (= succinate dehydrogenase, SDH) activity (citeauthor ch41:paddenberg2006, Respir Res, 7:93, citeyear ch41:paddenberg2006). Interestingly, SDH subunits A and B have recently been d...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-90-481-2259-2_41

    authors: Paddenberg R,Faulhammer P,Goldenberg A,Gries B,Heinl J,Kummer W

    更新日期:2009-01-01 00:00:00

  • Curcumin and Its Role in Chronic Diseases.

    abstract::Curcumin, a yellow pigment from the spice turmeric, is used in Indian and Chinese medicine since ancient times for wide range of diseases. Extensive scientific research on this molecule performed over the last 3 to 4 decades has proved its potential as an important pharmacological agent. The antioxidant, anti-inflamma...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-319-41334-1_1

    authors: Kunwar A,Priyadarsini KI

    更新日期:2016-01-01 00:00:00

  • Platelet-activating factor receptor. Gene structure and tissue-specific regulation.

    abstract::The human platelet-activating factor receptor gene exists as a single copy on chromosome 1. Two 5'-noncoding exons (Exon 1 and 2) has distinct transcription initiation sites and promoters. These exons are alternatively spliced to a common splice acceptor site on exon 3 that contains a total coding regions. The transcr...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:

    authors: Shimizu T,Mutoh H,Kato S

    更新日期:1996-01-01 00:00:00

  • Cardiovascular flow velocity measurements by 2D Doppler imaging for assessment of vascular function.

    abstract::Clinical two-dimensional (2D) Doppler ultrasound flow velocity measurement is important for determination of arterial wall shear stress, blood-tissue exchange, myocardial and valvular function. Such 2D Doppler flow velocity images are usually displayed in color, superimposed on the gray-scale, cross-section structural...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-2946-0_38

    authors: Adam DR,Kempner KM,Vivino MA,Tucker EE,Jones M

    更新日期:1993-01-01 00:00:00

  • Noncoding RNAs Regulating Cancer Signaling Network.

    abstract::The cellular signaling network plays a fundamental role during development and disease, especially cancer progression. By deregulating signaling pathways, cancer cells acquire hallmarks of the disease including uncontrolled proliferation, evasion from cell death, activation of angiogenesis, invasion, and metastasis. N...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-981-10-1498-7_11

    authors: Hu J,Markowitz GJ,Wang X

    更新日期:2016-01-01 00:00:00

  • Estrogens influence growth, maturation, and amyloid beta-peptide production in neuroblastoma cells and in a beta-APP transfected kidney 293 cell line.

    abstract::During development in vivo and in vitro, estrogens: a) increase brain excitability, particularly in limbic structures; b) are responsible for the maturation and cyclicity of limbic-hypothalamic interrelations; c) enhance myelinogenesis; and d) may act with NGF to stimulate neurite formation. In senescence, estrogen ad...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4757-9551-6_19

    authors: Chang D,Kwan J,Timiras PS

    更新日期:1997-01-01 00:00:00

  • The Production of a Rat Model That Inhibits Phosphoenolpyruvate Carboxykinase (PEPCK), a Rate-Limiting Enzyme of Hepatic Gluconeogenesis.

    abstract::We previously showed that taurine administration contributed to the extension of time to exhaustion through exercise-induced hypoglycemia restraint, and we suggested that the activation of hepatic gluconeogenesis was initiated before the exercise with the taurine administration. We hypothesize that the extension effec...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-981-13-8023-5_10

    authors: Ohmori H,Matsumura M,Komine S,Kobayashi H,Kobayashi Y,Shiromoto J,Miyakawa S

    更新日期:2019-01-01 00:00:00

  • Multimodal Learning in Health Sciences and Medicine: Merging Technologies to Enhance Student Learning and Communication.

    abstract::Advances in consumer-level educational technologies show great promise for enhancing the learning experiences of students in health and medicine. There are particular benefits to using a combination of various devices and technologies when teaching challenging concepts. These include augmented reality-enabled devices ...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-3-030-31904-5_5

    authors: Moro C,Smith J,Stromberga Z

    更新日期:2019-01-01 00:00:00

  • The locus for enterocyte effacement (LEE) of enteropathogenic Escherichia coli (EPEC) from dogs and cats.

    abstract::Enteropathogenic Escherichia coli (EPEC) produce attaching and effacing lesions. The genes responsible for this lesion are clustered on the chromosome forming a 35.5 kilobase pathogenesis island called LEE. The LEE was identified, characterized and completely sequenced from the human EPEC strain E2348/69. The LEE carr...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-4143-1_11

    authors: Goffaux F,China B,Janssen L,Pirson V,Mainil J

    更新日期:1999-01-01 00:00:00

  • 1,25-Dihydroxyvitamin D3 receptors: altered functional domains are associated with cellular resistance to vitamin D3.

    abstract::1,25-Dihydroxyvitamin D3 receptors are cytosoluble proteins detectable in a variety of tissues responsive to 1,25(OH)2D3. They are DNA binding-proteins analogous to other steroid receptors and it is this functional property which is likely involved in the activation of hormone-sensitive genes. Utilizing 1,25(OH)2D3 an...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-1-4684-5101-6_25

    authors: Pike JW,Allegretto EA,Kelly MA,Donaldson CA,Marion SL,Mangelsdorf DJ,Haussler MR

    更新日期:1986-01-01 00:00:00

  • Mitochondrial and Metabolic Drivers of Pulmonary Vascular Endothelial Dysfunction in Pulmonary Hypertension.

    abstract::Pulmonary hypertension (PH) is a deadly and increasingly prevalent vascular disease characterized by excessive pulmonary vascular remodeling and right ventricular dysfunction which leads to right heart failure, multiorgan dysfunction, and premature death. The cause of the vascular remodeling in PH remains elusive, and...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-319-63245-2_24

    authors: Yu Q,Chan SY

    更新日期:2017-01-01 00:00:00

  • Functional oxygen-17 magnetic resonance imaging and localized spectroscopy.

    abstract::Functional oxygen-17 magnetic resonance (MR) imaging and localized spectroscopy is defined as the ensemble of MR measurements aiming at in vivo, noninvasive characterization of oxygen transport and utilization. After a brief description of the present status of in vivo 17O-MR, preliminary results are reported on oxyge...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-0205-0_35

    authors: Mateescu GD

    更新日期:2003-01-01 00:00:00

  • Monitoring Intracellular Oxygen Concentration: Implications for Hypoxia Studies and Real-Time Oxygen Monitoring.

    abstract::The metabolic properties of cancer cells have been widely accepted as a hallmark of cancer for a number of years and have shown to be of critical importance in tumour development. It is generally accepted that tumour cells exhibit a more glycolytic phenotype than normal cells. In this study, we investigate the bioener...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4939-3023-4_32

    authors: Potter M,Badder L,Hoade Y,Johnston IG,Morten KJ

    更新日期:2016-01-01 00:00:00

  • Structural Insights into IP3R Function.

    abstract::Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed intracellular ligand-gated Ca2+ channels present on the endoplasmic reticulum of virtually all eukaryotic cells. These channels mediate the Ca2+ release from intracellular stores in response to activation by the signaling molecule IP3, which fun...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-3-319-55858-5_6

    authors: Serysheva II,Baker MR,Fan G

    更新日期:2017-01-01 00:00:00

  • Roles of transient receptor potential proteins (TRPs) in epidermal keratinocytes.

    abstract::Epidermal keratinocytes are the epithelial cells of mammalian skin. At the basal layer of the epidermis, these cells proliferate strongly, and as they move towards the skin surface, differentiation proceeds. At the uppermost layer of the epidermis, keratinocytes undergo apoptosis and die, forming a thin, water-imperme...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-94-007-0265-3_44

    authors: Denda M,Tsutsumi M

    更新日期:2011-01-01 00:00:00

  • Degradation of tryptophan in neurodegenerative disorders.

    abstract::In patients with neurodegenerative disorders, namely Alzheimer's disease and Huntington's disease, we compared serum concentrations of tryptophan, kynurenine and the kynurenine per tryptophan ratio with concentrations of soluble immune activation markers. Significantly lower tryptophan concentrations were observed in ...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章

    doi:10.1007/978-1-4615-4709-9_19

    authors: Widner B,Leblhuber F,Walli J,Tilz GP,Demel U,Fuchs D

    更新日期:1999-01-01 00:00:00

  • Cyanobacteria blooms: effects on aquatic ecosystems.

    abstract::Cyanobacteria become increasingly dominant as concentrations of TP and TN increase during eutrophication of lakes, rivers and estuaries. Temporal dynamics of cyanobacteria blooms are variable--in some systems persistent blooms occur in summer to fall, whereas in other systems blooms are more sporadic. Cyanobacteria bl...

    journal_title:Advances in experimental medicine and biology

    pub_type: 杂志文章,评审

    doi:10.1007/978-0-387-75865-7_33

    authors: Havens KE

    更新日期:2008-01-01 00:00:00