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https://www.readbyqxmd.com/read/28918011/nucleic-acid-polymers-with-accelerated-plasma-and-tissue-clearance-for-chronic-hepatitis-b-therapy
#1
Ingo Roehl, Stephan Seiffert, Celia Brikh, Jonathan Quinet, Catherine Jamard, Nadine Dorfler, Jennifer A Lockridge, Lucyna Cova, Andrew Vaillant
REP 2139 is a nucleic acid polymer (NAP) currently under clinical development for chronic hepatitis B (HBV) therapy. This preclinical study investigated different REP 2139 analogs that would display reduced accumulation in the serum and tissues, while retaining an antiviral effect against HBV infection. REP 2139 analogs were evaluated in human plasma, CD-1 mice, cynomolgus monkeys, and Pekin ducks. Discrete ribose transformation to 2'OH in selected riboadenosines resulted in a slow degradation in acidified human plasma that plateaued after 48 hr...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916921/potential-effect-of-prolonged-sevoflurane-anesthesia-on-the-kinetics-of-11-c-raclopride-in-non-human-primates
#2
Ryosuke Arakawa, Lars Farde, Junya Matsumoto, Naoki Kanegawa, Igor Yakushev, Kai-Chun Yang, Akihiro Takano
PURPOSE: Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BPND) of [(11)C]raclopride in NHP...
September 15, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28916434/effects-of-icos-t-cell-depletion-via-afucosylated-monoclonal-antibody-medi-570-on-pregnant-cynomolgus-monkeys-and-the-developing-offspring
#3
Simone M Nicholson, Gianluca Carlesso, Lily I Cheng, Halie Cook, Karma DaCosta, Joel Leininger, Kathleen McKeever, Stephen Weasel Scott, Devon Taylor, Katie Streicher, Steve Eck, Molly Reed, Raffaella Faggioni, Ronald Herbst, Rakesh Dixit, Patricia C Ryan
MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology...
September 12, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28910279/longitudinal-multiparameter-single-cell-analysis-of-macaques-immunized-with-pneumococcal-protein-conjugated-or-unconjugated-polysaccharide-vaccines-reveals-distinct-antigen-specific-memory-b-cell-repertoires
#4
Bin Jia, Lisa K McNeil, Christopher D Dupont, Konstantinos Tsioris, Rachel M Barry, Ingrid L Scully, Adebola O Ogunniyi, Christopher Gonzalez, Michael W Pride, Todd M Gierahn, Paul A Liberator, Kathrin U Jansen, J Christopher Love
BACKGROUND: The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae. METHODS: We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC) or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS) using microengraving (a single-cell analysis method) and single-cell RT-PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28905721/using-a-cageside-device-for-testing-glycosylated-hemoglobin-in-cynomolgus-macaques-macaca-fascicularis
#5
Jessica M Johnston, Jolaine M Wilson, Abigail L Smith, John T Farrar, Michael J Kallan, Christin L Veeder
Nonhuman primates naturally develop type 2 diabetes mellitus and exhibit clinical features that are similar to those observed in humans, including obesity, insulin resistance, dyslipidemia, and pancreatic pathology. The glycosylated hemoglobin (HbA1C) test is the primary test used for diabetes management in humans because it reflects the average blood glucose levels over the previous 3 mo. The HbA1C results are a better predictor of potential risk of complications than are single or episodic measures of glucose levels...
January 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28905720/evaluation-of-infrared-thermometry-in-cynomolgus-macaques-macaca-fascicularis
#6
Michael M Laffins, Nacera Mellal, Cynthia L Almlie, Douglas E Regalia
Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations...
January 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28904298/usefulness-of-urinary-biomarkers-for-nephrotoxicity-in-cynomolgus-monkeys-treated-with-gentamicin-cisplatin-and-puromycin-aminonucleoside
#7
Hiroshi Uchino, Junko Fujishima, Kaori Fukuoka, Teppei Iwakiri, Akira Kamikuri, Hidenori Maeda, Kazuhiro Nakama
The objective of this study was to investigate the availability of novel urinary biomarkers (BMs) such as total protein, albumin, β2-microglobulin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute nephrotoxicity in cynomolgus monkeys. Animals (total 9 males/3 groups) were administered gentamicin (GM) subcutaneously at 40 mg/kg for 7 days, cisplatin (CDDP) intravenously at 3 mg/kg once and puromycin aminonucleoside (PAN) intravenously at 20 mg/kg for 7 days...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28903943/therapeutic-potential-of-sgn-cd19b-a-pbd-based-anti-cd19-drug-conjugate-for-treatment-of-b-cell-malignancies
#8
Maureen C Ryan, Maria Corinna Palanca-Wessels, Brian Schimpf, Kristine A Gordon, Heather Kostner, Brad Meyer, Changpu Yu, Heather Van Epps, Dennis Benjamin
Patients with relapsed/refractory B-cell malignancies such as non-Hodgkin lymphoma (B-NHL) or acute lymphoblastic leukemia (B-ALL) have a poor prognosis. Despite measurable clinical activity with new targeted therapies, many patients do not achieve a complete or durable response suggesting an opportunity to improve upon existing therapies. Here we describe SGN-CD19B, a pyrrolobenzodiazepine (PBD)-based anti-CD19 antibody drug conjugate (ADC) being investigated for treatment of B-cell malignancies, which has improved potency compared to other ADCs...
September 13, 2017: Blood
https://www.readbyqxmd.com/read/28895785/preclinical-pharmacokinetic-characterization-of-an-adipose-tissue-targeting-monoclonal-antibody-in-obese-and-non-obese-animals
#9
Sharmila Rajan, Danielle Mandikian, Amos Baruch, Thomas R Gelzleichter, Dale Stevens, Junichiro Sonoda, Kyra Cowan, C Andrew Boswell, Eric Stefanich
Target receptor levels can influence pharmacokinetics (PK) or pharmacodynamics (PD) of monoclonal antibodies (mAbs), and can affect drug development of this class of molecules. We generated an effector-less humanized bispecific antibody that selectively activates fibroblast growth factor receptor (FGFR)1 and βKlotho receptor, a FGF21 receptor complex highly expressed in both white and brown adipocytes. The molecule shows cross-species binding with comparable equilibrium binding affinity (Kd) for human, cynomolgus monkey, and mouse FGFR1/βKlotho...
September 12, 2017: MAbs
https://www.readbyqxmd.com/read/28885626/evidence-for-a-primate-origin-of-zoonotic-helicobacter-suis-colonizing-domesticated-pigs
#10
Bram Flahou, Mirko Rossi, Jaco Bakker, Jan Am Langermans, Edwin Heuvelman, Jay V Solnick, Miriam E Martin, Jani O'Rourke, Le Duc Ngoan, Nguyen Xuan Hoa, Masahiko Nakamura, Anders Øverby, Hidenori Matsui, Hiroyoshi Ota, Takehisa Matsumoto, Dennis L Foss, Laurice A Kopta, Oladipo Omotosho, Maria Pia Franciosini, Patrizia Casagrande Proietti, Aizhen Guo, Han Liu, Gabriela Borilova, Ana Paula Bracarense, Sara K Lindén, Sofie De Bruyckere, Guangzhi Zhang, Chloë De Witte, Annemieke Smet, Frank Pasmans, Richard Ducatelle, Jukka Corander, Freddy Haesebrouck
Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig- or non-human primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H...
September 8, 2017: ISME Journal
https://www.readbyqxmd.com/read/28882438/biodistribution-and-safety-of-a-live-attenuated-tetravalent-dengue-vaccine-in-the-cynomolgus-monkey
#11
Guillaume Ravel, Nathalie Mantel, Jeremy Silvano, Alexandra Rogue, Bruno Guy, Nicholas Jackson, Nicolas Burdin
BACKGROUND: The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. METHODS: Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log10 CCID50/serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology...
September 4, 2017: Vaccine
https://www.readbyqxmd.com/read/28869611/human-monoclonal-antibody-therapy-protects-nonhuman-primates-against-advanced-lassa-fever
#12
Chad E Mire, Robert W Cross, Joan B Geisbert, Viktoriya Borisevich, Krystle N Agans, Daniel J Deer, Megan L Heinrich, Megan M Rowland, Augustine Goba, Mambu Momoh, Mathew L Boisen, Donald S Grant, Mohamed Fullah, Sheik Humarr Khan, Karla A Fenton, James E Robinson, Luis M Branco, Robert F Garry, Thomas W Geisbert
There are no approved treatments for Lassa fever, which is endemic to the same regions of West Africa that were recently devastated by Ebola. Here we show that a combination of human monoclonal antibodies that cross-react with the glycoproteins of all four clades of Lassa virus is able to rescue 100% of cynomolgus macaques when treatment is initiated at advanced stages of disease, including up to 8 d after challenge.
September 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28861030/coding-of-velocity-storage-in-the-vestibular-nuclei
#13
Sergei B Yakushin, Theodore Raphan, Bernard Cohen
Semicircular canal afferents sense angular acceleration and output angular velocity with a short time constant of ≈4.5 s. This output is prolonged by a central integrative network, velocity storage that lengthens the time constants of eye velocity. This mechanism utilizes canal, otolith, and visual (optokinetic) information to align the axis of eye velocity toward the spatial vertical when head orientation is off-vertical axis. Previous studies indicated that vestibular-only (VO) and vestibular-pause-saccade (VPS) neurons located in the medial and superior vestibular nucleus could code all aspects of velocity storage...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28859225/widespread-brain-distribution-and-activity-following-anti-bace1-intracerebroventricular-infusion-in-nonhuman-primates
#14
Daniela Bumbaca Yadav, Janice A Maloney, Kristin R Wildsmith, Reina N Fuji, William J Meilandt, Hilda Solanoy, Yanmei Lu, Kun Peng, Blair Wilson, Pamela Chan, Kapil Gadkar, Andrew Kosky, Marisa Goo, Ann Daugherty, Jessica A Couch, Thomas Keene, Karen Hayes, Lisa Jungbauer Nikolas, Deanna Lane, Robert Switzer, Eric Adams, Ryan J Watts, Kimberly Scearce-Levie, Saileta Prabhu, Lisa Shafer, Deepak R Thakker, Keith Hildebrand, Jasvinder K Atwal
BACKGROUND AND PURPOSE: The potential for therapeutic antibody treatment of neurological diseases is limited by poor penetration across the blood-brain barrier. Intracerebroventricular (i.c.v.) delivery is a promising route to the brain, however it is unclear how efficiently i.c.v - delivered antibodies penetrate the cerebrospinal fluid (CSF)-brain barrier and distribute throughout the brain parenchyma. EXPERIMENTAL APPROACH: We evaluated the pharmacokinetics and pharmacodynamics of an inhibitory monoclonal antibody against β-site amyloid precursor protein cleaving enzyme 1 (anti-BACE1) following continuous infusion into the left lateral ventricle of healthy adult cynomolgus monkeys...
August 31, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28855711/potential-antigens-involved-in-delayed-xenograft-rejection-in-a-ggta1-cmah-dko-pig-to-monkey-model
#15
Junfang Zhang, Chongwei Xie, Ying Lu, Ming Zhou, Zepeng Qu, Da Yao, Chuanghua Qiu, Jia Xu, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Shanshan Ma, Mingtao Li, Zhiming Cai, Lisha Mou
When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate the potential antigens involved in DXR. We isolated primary renal microvascular endothelial cells (RMEC) and aortic endothelial cells (AEC) from a GGTA1/CMAH double-knockout (DKO) pig (and a GGTA1-KO pig) and immunized cynomolgus monkeys with both of these cells. After sensitization, monkey serum antibody binding and cytotoxicity to RMEC was significantly higher than to AEC(p < 0...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855509/mhc-matching-improves-engraftment-of-ipsc-derived-neurons-in-non-human-primates
#16
Asuka Morizane, Tetsuhiro Kikuchi, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Hisashi Doi, Aya Mawatari, Matthew F Glasser, Takashi Shiina, Hirohito Ishigaki, Yasushi Itoh, Keisuke Okita, Emi Yamasaki, Daisuke Doi, Hirotaka Onoe, Kazumasa Ogasawara, Shinya Yamanaka, Jun Takahashi
The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28852031/infection-with-the-makona-variant-results-in-a-delayed-and-distinct-host-immune-response-compared-to-previous-ebola-virus-variants
#17
Krista Versteeg, Andrea R Menicucci, Courtney Woolsey, Chad E Mire, Joan B Geisbert, Robert W Cross, Krystle N Agans, Daniel Jeske, Ilhem Messaoudi, Thomas W Geisbert
Zaire Ebolavirus (ZEBOV) continues to pose a significant threat to human health as highlighted by the recent epidemic that originated in West Africa and the ongoing outbreak in the Democratic Republic of the Congo. Although the ZEBOV variant responsible for this epidemic (Makona) shares significant genetic similarity with previously identified variants (Kikwit and Mayinga), recent reports suggest slower disease progression in nonhuman primates. However, the pathogenesis caused by the new variant is not fully understood...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838069/genomic-tools-for-the-use-of-nonhuman-primates-in-translational-research
#18
John D Harding
Nonhuman primates (NHPs) are important preclinical models for understanding the etiology of human diseases and for developing therapies and vaccines to cure or eliminate disease. Most human diseases have genetic components. Therefore, to be of maximal utility, the NHP species used for translational science should be as well characterized in regard to their genome and transcriptome as possible. This article reviews the current status of genomic information for the five NHP species used most often in translational research: rhesus macaque, cynomolgus macaque, vervet (African green) monkey, baboon, and marmoset NHP...
July 1, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28830583/a-simple-way-to-eradicate-methicillin-resistant-staphylococcus-aureus-in-cynomolgus-macaques-macaca-fascicularis
#19
Tae M Kim, Hyojun Park, Kyo W Lee, Eun W Choi, Sang H Moon, Yong S Lee, Kahee Cho, Wan J Park, Jae B Park, Sung J Kim
Our investigation of indoor-housed cynomolgus macaques (Macaca fascicularis) by using automated identification followed by antibiotic susceptibility testing revealed 1 of 7 immunocompetent animals and 2 of 9 immunosuppressed monkeys as carriers of methicillin-resistant Staphylococcus aureus (MRSA). Follow-up management involving mupirocin treatment resulted in the conversion of the 3 MRSA carriers into MRSA-negative cases. Prospective assessment of newly imported monkeys involving 24-h culture of nasal swabs on chromogenic agar revealed that 22% (18 of 82 animals) were MRSA-positive...
August 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28830332/hypersensitivity-reactions-to-obinutuzumab-in-cynomolgus-monkeys-and-relevance-to-humans
#20
Elisabeth Husar, Maria Solonets, Olaf Kuhlmann, Eginhard Schick, Hanna Piper-Lepoutre, Thomas Singer, Gaurav Tyagi
Obinutuzumab (GA101, Gazyva™, Gazyvaro®, F. Hoffmann-La Roche AG, Basel, Switzerland) is a humanized, glycoengineered type II antibody targeted against CD20. The preclinical safety evaluation required to support clinical development and marketing authorization of obinutuzumab included repeat-dose toxicity studies in cynomolgus monkeys for up to 6-month dosing with a 9-month recovery period. Results from those studies showed decreases in circulating B cells and corresponding B-cell depletion in lymphoid tissues, consistent with the desired pharmacology of obinutuzumab...
July 2017: Toxicologic Pathology
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