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https://www.readbyqxmd.com/read/28225764/cynomolgus-macaques-naturally-infected-with-trypanosoma-cruzi-i-exhibit-an-overall-mixed-pro-inflammatory-modulated-cytokine-signature-characteristic-of-human-chagas-disease
#1
Danielle Marquete Vitelli-Avelar, Renato Sathler-Avelar, Armanda Moreira Mattoso-Barbosa, Nicolas Gouin, Marcelo Perdigão-de-Oliveira, Leydiane Valério-Dos-Reis, Ronaldo Peres Costa, Silvana Maria Elói-Santos, Matheus de Souza Gomes, Laurence Rodrigues do Amaral, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Edward J Dick, Gene B Hubbard, Jane F VandeBerg, John L VandeBerg
BACKGROUND: Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28223455/acute-fetal-demise-with-first-trimester-maternal-infection-resulting-from-listeria-monocytogenes-in-a-nonhuman-primate-model
#2
Bryce Wolfe, Gregory J Wiepz, Michele Schotzko, Gennadiy I Bondarenko, Maureen Durning, Heather A Simmons, Andres Mejia, Nancy G Faith, Emmanuel Sampene, Marulasiddappa Suresh, Sophia Kathariou, Charles J Czuprynski, Thaddeus G Golos
Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28220108/adaptations-in-basal-and-hypothalamic-pituitary-adrenal-activated-deoxycorticosterone-responses-following-ethanol-self-administration-in-cynomolgus-monkeys
#3
Vanessa A Jimenez, Patrizia Porcu, A Leslie Morrow, Kathleen A Grant
Acute ethanol activates the hypothalamic-pituitary-adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28215474/establishment-of-disseminated-intravascular-coagulation-dic-model-by-a-single-iv-administration-of-escherichia-coli-derived-lipopolysaccharide-lps-to-cynomolgus-monkeys-and-evaluation-of-its-pathophysiological-status
#4
Hirofumi Minomo, Kengo Inoue, Shuko Sakaki, Takanobu Okazaki, Kinji Kobayashi, Kazuhiko Inoue, Atsuro Miyata
We prepared a DIC model by administrating LPS to cynomolgus monkeys, and investigated its potential for evaluations of new medicines for DIC therapy. Peripheral blood mononuclear cells (PBMC) collected from cynomolgus monkeys were incubated with LPS (8 types), and TNF-α levels in the media were measured. LPS from Escherichia coli (K-235) was most appropriate in terms of larger increases and smaller variation in TNF-α levels. PBMC from rats, cynomolgus monkeys or humans were incubated with LPS (K-235), and the TNF-α response to LPS was investigated...
February 2, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28211310/morphologic-and-doppler-findings-from-hepatic-ultrasonography-of-normal-cynomolgus-monkeys-macaca-fascicularis
#5
Kyo Won Lee Chan Woo Cho Ji Eun Lee Hyojun Park Gyu-Seong Choi Woo Kyoung Jeong Jae Berm Park And Sungjoo Kim
The present study evaluated the anatomic and ultrasonographic features of the liver in normal cynomolgus monkeys (Macacafascicularis). Healthy, male, cynomolgus monkeys from Cambodia (n = 25; mean age, 58.1 mo) were sedated with ketamine (7mg/kg) and examined by using 2D and Doppler ultrasonography. We measured the diameters of the vascular structures and bile duct, determined the velocities of the hepatic artery and portal vein, and calculated the resistance index of the hepatic artery. Vessel diameters were: proper hepatic artery, 1...
February 16, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28203239/sublingual-priming-with-a-hiv-gp41-based-subunit-vaccine-elicits-mucosal-antibodies-and-persistent-b-memory-responses-in-non-human-primates
#6
Selma Bekri, Pierre Bourdely, Carmelo Luci, Nathalie Dereuddre-Bosquet, Bin Su, Frédéric Martinon, Véronique M Braud, Irene Luque, Pedro L Mateo, Sara Crespillo, Francisco Conejero-Lara, Christiane Moog, Roger Le Grand, Fabienne Anjuère
Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28196829/marmoset-cytochrome-p450-3a4-expressed-in-liver-and-small-intestine-tissues-efficiently-metabolizes-midazolam-alprazolam-nifedipine-and-testosterone
#7
Shotaro Uehara, Yasuhiro Uno, Kazuyuki Nakanishi, Sakura Ishii, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
Common marmosets (Callithrix jacchus), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has remained in marmosets. In this study, sequence homology, tissue distribution, and enzymatic property of marmoset P450 3A4 orthologue, 3A5 orthologue, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologues and evolutionary closeness to human and cynomolgus monkey P450 3A orthologues, compared with other P450 3A enzymes...
February 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28195359/sodium-taurocholate-cotransporting-polypeptide-is-the-limiting-host-factor-of-hepatitis-b-virus-infection-in-macaque-and-pig-hepatocytes
#8
Florian A Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W R Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
: Infections with the human Hepatitis B (HBV) and Hepatitis D Virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide hNTCP. Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV indicating the requirement of additional HBV-specific factors. As an essential premise towards the establishment for an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194148/animal-models-of-emerging-tick-borne-phleboviruses-determining-target-cells-in-a-lethal-model-of-sftsv-infection
#9
Keita Matsuno, Yasuko Orba, Kimberly Maede-White, Dana Scott, Friederike Feldmann, Mifang Liang, Hideki Ebihara
The pathogenesis of clinical manifestations caused by newly emerging tick-borne phleboviruses [i.e., Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV)], such as severe thrombocytopenia and lymphocytopenia, are not yet fully understood. In the present study, to establish an animal model mimicking the profile of fatal human cases, we examined the susceptibilities of adult mice from 12 strains, aged mice from two strains, and cynomolgus macaques to SFTSV and/or HRTV infections...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28188299/novel-mechanism-of-decyanation-of-gdc-0425-by-cytochrome-p450
#10
Ryan H Takahashi, Jason S Halladay, Michael Siu, Yuan Chen, Cornelis Eca Hop, Siamak Cyrus Khojasteh, Shuguang Ma
GDC-0425 is an orally bioavailable small molecule inhibitor of checkpoint kinase 1 (Chk1) that was investigated as a novel co-therapy to potentiate chemotherapeutic drugs such as gemcitabine. In the radiolabeled ADME study in Sprague-Dawley rats, trace level but long-lived 14C-labeled plasma thiocyanate was observed. This thiocyanate originated from metabolic decyanation of GDC-0425 and rapid conversion of cyanide to thiocyanate. Excretion studies indicated decyanation was a minor metabolic pathway, but placing 14C at nitrile magnified its observation...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28186423/translational-repression-of-a-splice-variant-of-cynomolgus-macaque-cxcl1l-by-its-c-terminal-sequence
#11
Hisayuki Nomiyama, Naoki Osada, Ichiro Takahashi, Keiji Terao, Kazuya Yamagata, Osamu Yoshie
We previously isolated a cDNA clone from cynomolgus macaque encoding a novel CXC chemokine that we termed CXCL1L from its close similarity to CXCL1. However, the cDNA consisted of 3 exons instead of 4 exons that were typically seen in other CXC chemokines. Here, we isolated a cDNA encoding the full-length variant of CXCL1L that we termed CXCL1Lβ. CXCL1Lβ is 50 amino acids longer than the original CXCL1L, which we now term CXCL1Lα. The CXCL1Lβ mRNA is much more abundantly expressed in the cynomolgus macaque tissues than CXCL1Lα mRNA...
February 10, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28183275/diversity-and-regulatory-impact-of-copy-number-variation-in-the-primate-macaca-fascicularis
#12
Andreas R Gschwind, Anjali Singh, Ulrich Certa, Alexandre Reymond, Tobias Heckel
BACKGROUND: Copy number variations (CNVs) are a significant source of genetic diversity and commonly found in mammalian genomes. We have generated a genome-wide CNV map for Cynomolgus monkeys (Macaca fascicularis). This crab-eating macaque is the closest animal model to humans that is used in biomedical research. RESULTS: We show that Cynomolgus monkey CNVs are in general much smaller in size than gene loci and are specific to the population of origin. Genome-wide expression data from five vitally important organs demonstrates that CNVs in close proximity to transcription start sites associate strongly with expression changes...
February 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28170376/corrigendum-zika-viral-dynamics-and-shedding-in-rhesus-and-cynomolgus-macaques
#13
Christa E Osuna, So-Yon Lim, Claire Deleage, Bryan D Griffin, Derek Stein, Lukas T Schroeder, Robert Omage, Katharine Best, Ma Luo, Peter T Hraber, Hanne Andersen-Elyard, Erwing Fabian Cardozo Ojeda, Scott Huang, Dana L Vanlandingham, Stephen Higgs, Alan S Perelson, Jacob D Estes, David Safronetz, Mark G Lewis, James B Whitney
No abstract text is available yet for this article.
February 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28160080/genome-wide-mining-and-comparative-analysis-of-microsatellites-in-three-macaque-species
#14
Sanxu Liu, Wei Hou, Tianlin Sun, Yongtao Xu, Peng Li, Bisong Yue, Zhenxin Fan, Jing Li
Microsatellites are found in taxonomically different organisms, and such repeats are related with genomic structure, function and certain diseases. To characterize microsatellites for macaques, we searched and compared SSRs with 1-6 bp nucleotide motifs in rhesus, cynomolgus and pigtailed macaque. A total of 1395671, 1284929 and 1266348 perfect SSRs were mined, respectively. The most frequent perfect SSRs were mononucleotide SSRs. The most GC-content was in dinucleotide SSRs and the least was in the mononucleotide SSRs...
February 3, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28155869/successful-post-exposure-prophylaxis-of-ebola-infected-non-human-primates-using-ebola-glycoprotein-specific-equine-igg
#15
Oleg V Pyankov, Yin Xiang Setoh, Sergey A Bodnev, Judith H Edmonds, Olga G Pyankova, Stepan A Pyankov, Gabor Pali, Shane Belford, Louis Lu, Mylinh La, George Lovrecz, Valentina A Volchkova, Keith J Chappell, Daniel Watterson, Glenn Marsh, Paul R Young, Alexander A Agafonov, Jillann F Farmer, Victor E Volchkov, Andreas Suhrbier, Alexander A Khromykh
Herein we describe production of purified equine IgG obtained from horses immunized with plasmid DNA followed by boosting with Kunjin replicon virus-like particles both encoding a modified Ebola glycoprotein. Administration of the equine IgG over 5 days to cynomolgus macaques infected 24 hours previously with a lethal dose of Ebola virus suppressed viral loads by more than 5 logs and protected animals from mortality. Animals generated their own Ebola glycoprotein-specific IgG responses 9-15 days after infection, with circulating virus undetectable by day 15-17...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154890/single-nucleotide-polymorphisms-in-the-fc%C3%AE-r3a-and-tap1-genes-impact-adcc-in-cynomolgus-monkey-pbmcs
#16
Jonathan C Sanford, Hong Wu, Yasmina Abdiche, Julie A Harney, Javier Chaparro-Riggers, Karissa Adkins
Phenotypic variability is often observed in cynomolgus monkeys on preclinical studies and may, in part, be driven by genetic variability. However, the role of monkey genetic variation remains largely unexplored in the context of drug response. This study evaluated genetic variation in cynomolgus monkey FcγR3A and TAP1 genes and the potential impact of identified polymorphisms on antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Studies in humans have demonstrated that a single nucleotide polymorphism (SNP), F158V, in FcγR3A can influence response to rituximab through altered ADCC and that SNPs in TAP1/2 decrease natural killer (NK) cell activity against major histocompatibility complex (MHC) class I deficient cells, potentially through altered ADCC...
February 3, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28153493/cyp2c76-deficiency-is-embryonic-lethal-in-cynomolgus-macaques-the-potential-role-of-cyp2c76-in-early-embryogenesis
#17
Shuzo Koyama, Koji Fukuda, Sho Watanabe, Akinori Matsushita, Hideaki Tsuchiya, Nahoko Fujinami, Sakae Kohara, Norie Murayama, Masashi Nagano, Hiroshi Yamazaki, Koichiro Fukuzaki, Yasuhiro Uno, Yoshihiko Hosoi
Cynomolgus macaques are an important primate species for drug metabolism studies; however cynomolgus CYP2C76, an important drug-metabolizing enzyme, accounts for drug metabolism differences to humans, so that CYP2C76-null animals might show drug-metabolizing properties more similar to humans. In this study, attempts were made to produce CYP2C76-null animals by assisted reproduction technology. Oocytes and sperm collected from the heterozygotes for the null allele (c.449TG > A) were subjected to intracytoplasmic sperm injection, and the embryos produced were cultured in vitro through the blastocyst stage...
October 27, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28137817/pharmacokinetics-of-the-novel-echinocandin-cd101-in-multiple-animal-species
#18
Voon Ong, Kenneth D James, Steven Smith, B Radha Krishnan
CD101 is a novel semi-synthetic echinocandin with antifungal activity against Candida and Aspergillus spp. The PK of CD101 administered intravenously to mice, rats, dogs, cynomolgus monkeys, and chimpanzees are presented. CD101 consistently exhibited very low clearance, modest volume of distribution, and long half-life across all species tested. In mouse, rat, dog, cynomolgus monkey, and chimpanzee, CD101 clearance [mL/min/kg] was 0.10, 0.47, 0.30, 0.41, and 0.06; Vss [mL/kg] was 206, 1390, not determined, 597, and 400; and t1/2 [h] was 25, 39, 53, 40, and 81, respectively...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28136132/r-warfarin-clearances-from-plasma-associated-with-polymorphic-cytochrome-p450-2c19-and-simulated-by-individual-physiologically-based-pharmacokinetic-models-for-11-cynomolgus-monkeys
#19
Masahiro Utoh, Takashi Kusama, Tomonori Miura, Marina Mitsui, Mirai Kawano, Takahiro Hirano, Makiko Shimizu, Yasuhiro Uno, Hiroshi Yamazaki
1. Cynomolgus monkey cytochrome P450 2C19 (formerly known as P450 2C75), homologous to human P450 2C19, has been identified as R-warfarin 7-hydroxylase. In this study, simulations of R-warfarin clearance in individual cynomolgus monkeys genotyped for P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling. 2. Pharmacokinetic parameters and absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances for individual PBPK models were estimated for eleven cynomolgus monkeys...
January 30, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28132865/implementation-of-a-non-human-primate-model-of-ebola-disease-infection-of-mauritian-cynomolgus-macaques-and-analysis-of-virus-populations
#20
Géraldine Piorkowski, Frédéric Jacquot, Gilles Quérat, Caroline Carbonnelle, Delphine Pannetier, France Mentré, Hervé Raoul, Xavier de Lamballerie
Ebola virus (EBOV) haemorrhagic fever remains a threat to global public health with an urgent need for an effective treatment. In order to achieve these goals, access to non-human primate (NHP) laboratory models is an essential requirement. Here, we present the first NHP-EBOV laboratory model readily available to the European scientific community, based on infection of Mauritian cynomolgus macaques using a Central-African EBOV strain and increasing virus challenge dose (10, 100, or 1000 focus forming units per animal)...
January 26, 2017: Antiviral Research
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