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https://www.readbyqxmd.com/read/28109707/potential-risk-of-repeated-nasal-vaccination-that-induces-allergic-reaction-with-mucosal-ige-and-airway-eosinophilic-infiltration-in-cynomolgus-macaques-infected-with-h5n1-highly-pathogenic-avian-influenza-virus
#1
Misako Nakayama, Yasushi Itoh, Shintaro Shichinohe, Rumi Nakabayashi, Hirohito Ishigaki, Yoshihiro Sakoda, Quynh Mai Le, Yoshihiro Kawaoka, Hiroshi Kida, Kazumasa Ogasawara
The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma...
January 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28109019/regional-difference-in-sulcal-infolding-progression-correlated-with-cerebral-cortical-expansion-in-cynomolgus-monkey-fetuses
#2
Kazuhiko Sawada, Katsuhiro Fukunishi, Masatoshi Kashima, Noritaka Imai, Shigeyoshi Saito, Ichio Aoki, Yoshihiro Fukui
The present study aimed to specify the cerebral sulci developed by cortical expansion in cynomolgus monkey fetuses. The degree of sulcal infolding was evaluated by the gyrification index (GI), which was quantified using ex vivo MRI. The correlation of cortical volume with the sulcal GI was most frequent during embryonic days (EDs) 100 to 120. Interestingly, the high correlation was marked during EDs 140 to 150 in restricted primary sulci in prefrontal, parietotemporal and medial temporal regions. The present results suggest that cortical expansion is involved in gyral demarcation by sulcal infolding, followed by the sulcal infolding progression in phylogenetically-newer cortices...
January 21, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28102082/characterization-of-the-molecular-mechanisms-underlying-the-chronic-phase-of-stroke-in-a-cynomolgus-monkey-model-of-induced-cerebral-ischemia
#3
Henry C H Law, Samuel S W Szeto, Quan Quan, Yun Zhao, Zaijun Zhang, Olga Krakovska, Leong Ting Lui, Chengyou Zheng, Simon Ming Yuen Lee, K W Michael Siu, Yuqiang Wang, Ivan K Chu
Stroke is one of the main causes of mortality and long-term disability worldwide. The pathophysiological mechanisms underlying this disease are not well understood, particularly in the chronic phase after the initial ischemic episode. In this study, a Macaca fascicularis stroke model consisting of two sample groups, as determined by MRI-quantified infarct volumes as a measure of the stroke severity 28 days after the ischemic episode, was evaluated using qualitative and quantitative proteomics analyses. By using multiple online multidimensional liquid chromatography platforms, 8790 non-redundant proteins that condensed to 5223 protein groups at 1% global false discovery rate (FDR)...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28089936/biodegradable-lipid-nanoparticles-induce-a-prolonged-rna-interference-mediated-protein-knockdown-and-show-rapid-hepatic-clearance-in-mice-and-nonhuman-primates
#4
Yuta Suzuki, Kenji Hyodo, Takuya Suzuki, Yohei Tanaka, Hiroshi Kikuchi, Hiroshi Ishihara
Lipid nanoparticles based on ionizable lipids have been clinically validated as a means of delivery for RNA interference (RNAi) therapeutics. The ideal properties of RNAi carriers are efficient delivery of oligonucleotides into target cells and rapid elimination after the function is performed. Here, we report that degradable lipid nanoparticles are effective carriers of small interfering RNA (siRNA) and have a high therapeutic index. The newly developed degradable lipid nanoparticles carrying siRNA showed potent gene-silencing activity in mouse hepatocytes (ED50≈0...
January 9, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28078358/major-histocompatibility-complex-haplotyping-and-long-amplicon-allele-discovery-in-cynomolgus-macaques-from-chinese-breeding-facilities
#5
Julie A Karl, Michael E Graham, Roger W Wiseman, Katelyn E Heimbruch, Samantha M Gieger, Gaby G M Doxiadis, Ronald E Bontrop, David H O'Connor
Very little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals...
January 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28077441/predicting-ifn-%C3%AE-responses-after-bcg-vaccination-in-humans-from-macaques-a-proof-of-concept-study-of-immunostimulation-immunodynamic-modelling-methods
#6
Sophie J Rhodes, Charlotte Sarfas, Gwenan M Knight, Andrew White, Ansar A Pathan, Helen McShane, Thomas G Evans, Helen Fletcher, Sally Sharpe, Richard G White
INTRODUCTION: Macaques play a central role in human tuberculosis(TB) vaccine development. Immune and challenge responses differ across macaque and human subpopulations. We determined which macaque subpopulations best predicted immune responses in different human subpopulations, using novel immunostimulation/immunodynamic modelling methods in a proof of concept study. METHODS: Data on IFN-γ secreting CD4+ T cells over time after recent BCG vaccination were available for 55 humans and 81 macaques...
January 11, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28077266/asp0028-in-combination-with-suboptimal-dose-of-tacrolimus-in-cynomolgus-monkey-renal-transplantation-model
#7
Hao Dun, Lijun Song, Anlun Ma, Yanxin Hu, Lin Zeng, Jieying Bai, Guangzhou Zhang, Liangyan Zhang, Kumi Koide, Yohei Okada, Kaori Hanaoka, Rie Yamamoto, Jun Hirose, Tatsuaki Morokata, Pierre Daloze, Huifang Chen
FTY720, a S1P-receptor modulator, has shown to be effective in several transplant and autoimmune disease models, via modulating lymphocyte homing into secondary lymphoid organs (SLOs), and thereby reducing these cells in peripheral blood. ASP0028, a newly developed S1P1/S1P5-selective agonist, presented comparable efficacy to FTY720 and wider safety margins than FTY720. In this study, we assessed the efficacy and safety of ASP0028 co-administered with suboptimal-dose of tacrolimus in the Cynomolgus monkey renal transplantation model...
January 7, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28072531/discovery-of-2-1r-4r-4-4-chlorophenyl-phenyl-carbamoyl-oxy-methyl-cyclohexyl-methoxy-acetate-ralinepag-an-orally-active-prostacyclin-receptor-agonist-for-the-treatment-of-pulmonary-arterial-hypertension
#8
Thuy-Anh Tran, Bryan Kramer, Young-Jun Shin, Pureza Vallar, P Douglas Boatman, Ning Zou, Carleton R Sage, Tawfik Gharbaoui, Ashwin Krishnan, Biman Pal, Sagar R Shakya, Antonio Garrido Montalban, John W Adams, Juan Ramirez, Dominic P Behan, Anna Shifrina, Anthony Blackburn, Tina Leakakos, Yunqing Shi, Michael Morgan, Abu Sadeque, Weichao Chen, David J Unett, Ibragim Gaidarov, Xiaohua Chen, Steve Chang, Hsin-Hui Shu, Shiu-Feng Tung, Graeme Semple
The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28071653/prophylactic-orthosteric-inhibition-of-leukocyte-integrin-cd11b-cd18-prevents-long-term-fibrotic-kidney-failure-in-cynomolgus-monkeys
#9
Abbas Dehnadi, A Benedict Cosimi, Rex Neal Smith, Xiangen Li, José L Alonso, Terry K Means, M Amin Arnaout
Ischaemic acute kidney injury (AKI), an inflammatory disease process, often progresses to chronic kidney disease (CKD), with no available effective prophylaxis. This is in part due to lack of clinically relevant CKD models in non-human primates. Here we demonstrate that inhibition of the archetypal innate immune receptor CD11b/CD18 prevents progression of AKI to CKD in cynomolgus monkeys. Severe ischaemia-reperfusion injury of the right kidney, with subsequent periods of the left ureter ligation, causes irreversible right kidney failure 3, 6 or 9 months after AKI...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28070111/a-monkey-model-of-acetaminophen-induced-hepatotoxicity-phenotypic-similarity-to-human
#10
Satoshi Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, Hitomi Shimoda, Wataru Takasaki, Kazuhiko Mori
Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28070055/superovulatory-responses-in-cynomolgus-monkeys-macaca-fascicularis-depend-on-the-interaction-between-donor-status-and-superovulation-method-used
#11
Ji-Su Kim, Seung-Bin Yoon, Kang-Jin Jeong, Bo-Woong Sim, Seon-A Choi, Sang-Il Lee, Yeung Bae Jin, Bong-Seok Song, Sang-Rae Lee, Sun-Uk Kim, Kyu-Tae Chang
The current study was performed to investigate the effect of oocyte donor status, including age and body weight, on metaphase II (MII) oocyte recovery using two superovulation methods in cynomolgus monkeys. The use of Method A [recombinant gonadotrophin (75 IU/kg, 3×, 3-day intervals) and human chorionic gonadotropin (hCG)] led to great increases in ovary size and the mean number of MII oocytes retrieved in age- and body-weight-dependent manner; in contrast, both the parameters were similar in Method B [recombinant gonadotrophin (60 IU, twice daily, 6 days), recombinant gonadotropin and recombinant human luteinizing hormone (rhLH) (60 IU, twice daily, 3 days), and hCG]...
January 9, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28066813/risks-posed-by-reston-the-forgotten-ebolavirus
#12
REVIEW
Diego Cantoni, Arran Hamlet, Martin Michaelis, Mark N Wass, Jeremy S Rossman
Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans...
November 2016: MSphere
https://www.readbyqxmd.com/read/28065822/detecting-drug-induced-changes-in-ecg-parameters-using-jacketed-telemetry-effect-of-different-data-reduction-techniques
#13
Matthew Skinner, Guozhen Xing, Jing Lu, Jin Ren, Karen Oldman
INTRODUCTION: Continuous cardiovascular data is routinely collected during preclinical safety assessment of new medicines. This generates large datasets, which must be summarised to analyse and interpret drug effects. We assessed four methods of data reduction of continuous electrocardiogram (ECG) data and examined the impact on the statistical power of the assay. METHODS: Continuous ECG data were collected from a validation study in 6 cynomolgus monkeys using jacketed telemetry...
January 5, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28062701/widespread-virus-replication-in-alveoli-drives-acute-respiratory-distress-syndrome-in-aerosolized-h5n1-influenza-infection-of-macaques
#14
Elizabeth R Wonderlich, Zachary D Swan, Stephanie J Bissel, Amy L Hartman, Jonathan P Carney, Katherine J O'Malley, Adebimpe O Obadan, Jefferson Santos, Reagan Walker, Timothy J Sturgeon, Lonnie J Frye, Pauline Maiello, Charles A Scanga, Jennifer D Bowling, Anthea L Bouwer, Parichat A Duangkhae, Clayton A Wiley, JoAnne L Flynn, Jieru Wang, Kelly S Cole, Daniel R Perez, Douglas S Reed, Simon M Barratt-Boyes
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28059083/behavioral-determinants-of-cannabinoid-self-administration-in-old-world-monkeys
#15
William S John, Thomas J Martin, Michael A Nader
Reinforcing effects of Δ(9)-tetrahydrocannabinol (THC), the primary active ingredient in marijuana, as assessed with self-administration (SA), has only been established in New World primates (squirrel monkeys). The objective of this study was to investigate some experimental factors that may enhance intravenous SA of THC and the cannabinoid receptor (CBR) agonist CP 55 940 in Old World monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. In one experiment, male rhesus monkeys (N=9) were trained to respond under a fixed-ratio 10 schedule of food presentation...
January 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#16
Rita Bottino, Michael F Knoll, Joshua Graeme-Wilson, Edwin C Klein, David Ayares, Massimo Trucco, David K C Cooper
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months...
January 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28057819/a-new-method-to-evaluate-macaque-health-using-exhaled-breath-a-case-study-of-m-tuberculosis-in-a-bsl-3-setting
#17
Theodore R Mellors, Lionel Blanchet, JoAnne L Flynn, Jaime Tomko, Melanie O'Malley, Charles A Scanga, Philana L Lin, Jane E Hill
Breath is hypothesized to contain clinically relevant information, useful for the diagnosis and monitoring of disease, as well as understanding underlying pathogenesis. Non-human primates, such as the cynomolgus macaque, serve as an important model for the study of human disease, including over 70 different human infections. In this feasibility study, exhaled breath was successfully collected in less than five minutes under Biosafety Level 3 conditions from five anesthetized, intubated cynomolgus and rhesus macaques, before and after lung infection with M...
January 5, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28057078/determinates-of-muscle-precursor-cell-therapy-efficacy-in-a-nonhuman-primate-model-of-intrinsic-urinary-sphincter-deficiency
#18
James Koudy Williams, Ashley Dean, Shannon Lankford, Tracy Criswell, Gopal Badlani, Karl-Erik Andersson
BACKGROUND: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women - and these factors are the focus of this study...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28056568/in-vitro-metabolite-formation-in-human-hepatocytes-and-cardiomyocytes-and-metabolism-and-tissue-distribution-in-monkeys-of-the-2-c-methylguanosine-prodrug-bms-986094
#19
Wenying Li, Kevin J Trouba, Li Ma, Jae Kwagh, Christopher Storck, Yongxin Zhu, Oliver Flint, William G Humphreys, Jian Wang, Ang Liu, Bonnie Wang, Michael J Graziano, Marc H Davies, Thomas P Sanderson
BMS-986094, a 2'-C-methylguanosine prodrug for the treatment of chronic hepatitis C virus infection, was withdrawn from phase 2 clinical trials because of unexpected cardiac and renal toxicities. To better understand these toxicities, the in vitro metabolism of BMS-986094 in human hepatocytes (HHs) and human cardiomyocytes (HCMs) and the measurement of BMS-986094 and selected metabolites in monkey plasma and tissues were assessed. BMS-986094 was extensively metabolized by HHs and HCMs, resulting in more efficient formation and accumulation of the active triphosphorylated metabolite, INX-09114, and less efficient efflux of metabolites in HCMs...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28053621/clinical-and-magnetic-resonance-imaging-features-of-compressive-cervical-myelopathy-with-traumatic-intervertebral-disc-herniation-in-cynomolgus-macaque-macaca-fascicularis
#20
Yun-Jung Choi, Hye-Jin Park, Chul-Ho Sohn, Kyeong Cheon Jung, Seong Hoe Park, Jae-Il Lee
Intervertebral disc herniation (IVDH) with nucleus pulposus extrusion, traumatic or not, is a devastating clinical condition accompanied by neurological problems. Here we report a cynomolgus macaque suffering from acute and progressive neurological dysfunction by a blunt trauma due to neck collar, an animal handling device. Tetraplegia, urinary incontinence, decreased proprioception, and imperception of pain were shown on physical and neurological examinations. MRI sagittal T2 weighted sequences revealed an extensive protrusion of disc material between C2 and C3 cervical vertebra, and this protrusion resulted in central stenosis of the spinal cord...
December 2016: Laboratory Animal Research
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