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https://www.readbyqxmd.com/read/28642489/post-exposure-treatment-of-non-human-primates-lethally-infected-with-ebola-virus-with-ebotab-a-purified-ovine-igg-product
#1
Stuart D Dowall, Frédéric Jacquot, John Landon, Emma Rayner, Graham Hall, Caroline Carbonnelle, Hervé Raoul, Delphine Pannetier, Ian Cameron, Ruth Coxon, Ibrahim Al Abdulla, Roger Hewson, Miles W Carroll
Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625601/role-of-social-interaction-exercise-diet-and-age-on-developing-and-untreated-diabetes-in-cynomolgus-monkeys
#2
Feng Yue, Guodong Zhang, Jorge E Quintero, Don M Gash, Zhiming Zhang
Type 2 diabetes mellitus is the most common form of diabetes that occurs in both human and nonhuman primates. Although spontaneously diabetic nonhuman primates are used extensively in diabetic related research and are a proven valuable tool for the study of the natural history of diabetes, little is known about the key factors that can cause this metabolic disorder and the preventative measures that could be employed to minimize the consequences of diabetes. Using a model of developing and untreated diabetes, this study describes the effects of housing arrangement (socially group- versus individually single-housed), exercise, diet, age, and sex on fasting plasma glucose, key lipids associated with diabetes, and bodyweight in two large cohorts of nonhuman primates...
June 15, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28624430/comparative-assessment-of-immune-complex-mediated-hypersensitivity-reactions-with-biotherapeutics-in-the-non-human-primate-critical-parameters-safety-and-lessons-for-future-studies
#3
Sven Kronenberg, Elisabeth Husar, Christine Schubert, Christian Freichel, Thomas Emrich, Martin Lechmann, Anna Maria Giusti, Franziska Regenass
With the emergence of novel biotherapeutic formats and immunostimulatory biotherapeutics in cancer immunotherapy, an understanding of immune-complex (IC) mediated hypersensitivity reactions in toxicology studies - and their differentiation from pharmacology - remains key to the preclinical evaluation of these drugs. In this review we provide an in-depth evaluation and comparison of case examples where IC-mediated hypersensitivity reactions were observed in cynomolgus monkeys. We provide details of the parameters evaluated in each study to substantiate and guide the interpretation of these findings...
June 15, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28619366/bpi-3016-a-novel-long-acting-hglp-1-analogue-for-the-treatment-of-type-2-diabetes-mellitus
#4
Lieming Ding, Sisi Lu, Yanping Wang, Haibo Chen, Wei Long, Cunbo Ma, Erlong He, Dan Yan, Fenlai Tan
Glucagon-like peptide-1 (GLP-1) analogues have been commonly used as add-on medications for patients with Type 2 diabetes mellitus (T2DM). Currently, the development of long-acting GLP-1 analogues which allow the freedom and flexibility of once-weekly injections while maintaining their potency for a relatively long period has become the mainstream. Here, we successfully developed a long-acting human GLP-1(7-37) analogue (BPI-3016) with significantly extended half-life and increased resistance to dipeptidyl peptidase IV (DPP-IV) cleavage by structural modifications of human GLP-1...
June 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#5
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28609387/long-term-sertraline-treatment-and-depression-effects-on-carotid-artery-atherosclerosis-in-premenopausal-female-primates
#6
Marnie G Silverstein-Metzler, Jamie N Justice, Susan E Appt, Leanne Groban, Dalane W Kitzman, John Jeffrey Carr, Thomas C Register, Carol A Shively
OBJECTIVE: Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. Selective serotonin reuptake inhibitor (SSRI) antidepressants, recently approved for hot flushes, have been associated with increased ischemic stroke risk in several observational studies; however, effects on carotid artery atherosclerosis, a strong predictor of future vascular events, are unknown. METHODS: The effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on atherosclerosis in the carotid artery was assessed in a placebo-controlled, longitudinal, randomized study of premeonopausal depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n = 42)...
June 12, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28608515/efavirenz-clearances-in-vitro-and-in-vivo-in-six-cynomolgus-monkeys-associated-with-polymorphic-cytochrome-p450-2c9-and-simulated-by-individual-physiologically-based-pharmacokinetic-models
#7
Masahiro Utoh, Tomonori Miura, Takashi Kusama, Shotaro Uehara, Makiko Shimizu, Yasuhiro Uno, Hiroshi Yamazaki
Cynomolgus monkey cytochrome P450 2C9 (formerly known as P450 2C43) variation was reportedly associated with metabolic clearance of the antiretroviral drug efavirenz in vivo (of three wild-type, one heterozygote, and two homozygote animals), being unlikely in the case of human P450 2B6-dependent efavirenz clearance. In this study, the liver microsomal elimination rates of efavirenz for the same individual animals previously treated with intravenous/oral administrations of efavirenz showed significant reductions associated with the P450 2C9 p...
June 13, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28608008/effects-of-social-reorganization-on-dopamine-d2-d3-receptor-availability-and-cocaine-self-administration-in-male-cynomolgus-monkeys
#8
P W Czoty, R W Gould, H D Gage, M A Nader
RATIONALE: Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. OBJECTIVE: In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. METHODS: Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule...
June 12, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28601605/rapid-focal-cooling-attenuates-cortical-seizures-in-a-primate-epilepsy-model
#9
Guoping Ren, Jiaqing Yan, Guoxian Tao, Yunmeng Gan, Donghong Li, Xi Yan, Yongjuan Fu, Leiming Wang, Weimin Wang, Zhiming Zhang, Feng Yue, Xiaofeng Yang
Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys...
June 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28595133/nonclinical-pharmacokinetic-and-pharmacodynamic-characterisation-of-somapacitan-a-reversible-non-covalent-albumin-binding-growth-hormone
#10
Peter Thygesen, Henrik Sune Andersen, Carsten Behrens, Johannes Josef Fels, Leif Nørskov-Lauritsen, Christian Rischel, Nils Langeland Johansen
OBJECTIVE: Somapacitan is an albumin-binding growth hormone derivative intended for once weekly administration, currently in clinical development for treatment of adult as well as juvenile GH deficiency. Nonclinical in vivo pharmacological characterisation of somapacitan was performed to support the clinical trials. Here we present the pharmacokinetic and pharmacodynamic effects of somapacitan in rats, minipigs, and cynomolgus monkeys. METHODS: Pharmacokinetic studies investigating exposure, absorption, clearance, and bioavailability after single intravenous (i...
May 24, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28583546/surgical-techniques-of-allogeneic-liver-transplantation-in-a-nonhuman-primate-model
#11
H Kim, H Kim, J-I Lee, S W Ahn, S K Hong, K C Yoon, H-S Kim, J-Y Choi, D Oh, N-J Yi, J Yang, K-W Lee, K-S Suh
Herein, we report our experience of performing allogeneic orthotopic liver transplantation (LT) in nonhuman primates. We designed an allogeneic ABO-compatible orthotopic LT model in monkeys in a manner similar to that used in humans. We applied almost the same surgical procedures used for human conventional deceased donor LT. A total of 6 monkeys underwent allogeneic LT. One cynomolgus monkey aged 45 months (3.4 kg) and 5 rhesus macaque monkeys aged 50.2 ± 14.8 months (5.40 ± 0.33 kg) were used as recipients...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28583545/simultaneous-subtotal-pancreatectomy-and-streptozotocin-injection-for-diabetes-modeling-in-cynomolgus-monkeys
#12
H Park, J B Park, J H Kim, K W Lee, H S Lee, G-S Kim, D-Y Shin, S-H Oh, S-M Jin, S J Kim
BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28583039/experimental-models-of-autoimmune-demyelinating-diseases-in-nonhuman-primates
#13
Lev Stimmer, Claire-Maëlle Fovet, Ché Serguera
Human idiopathic inflammatory demyelinating diseases (IIDD) are a heterogeneous group of autoimmune inflammatory and demyelinating disorders of the central nervous system (CNS). These include multiple sclerosis (MS), the most common chronic IIDD, but also rarer disorders such as acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO). Great efforts have been made to understand the pathophysiology of MS, leading to the development of a few effective treatments. Nonetheless, IIDD still require a better understanding of the causes and underlying mechanisms to implement more effective therapies and diagnostic methods...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28579941/chronic-ketamine-exposure-causes-white-matter-microstructural-abnormalities-in-adolescent-cynomolgus-monkeys
#14
Qi Li, Lin Shi, Gang Lu, Hong-Luan Yu, Fu-Ki Yeung, Nai-Kei Wong, Lin Sun, Kai Liu, David Yew, Fang Pan, De-Feng Wang, Pak C Sham
Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28575319/translational-research-in-the-nonhuman-primate-model-of-tuberculosis
#15
Taylor W Foreman, Smriti Mehra, Andrew A Lackner, Deepak Kaushal
Infection with Mycobacterium tuberculosis predominantly establishes subclinical latent infection over the lifetime of an individual, with a fraction of infected individuals rapidly progressing to active disease. The immune control in latent infection can be perturbed by comorbidities such as diabetes mellitus, obesity, smoking, and coinfection with helminthes or HIV. Modeling the varying aspects of natural infection remains incomplete when using zebrafish and mice. However, the nonhuman primate model of tuberculosis offers a unique and accurate model to investigate host responses to infection, test novel therapeutics, and thoroughly assess preclinical vaccine candidates...
May 31, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28573934/testicular-fibrous-hypoplasia-in-cynomolgus-monkeys-macaca-fascicularis-an-incidental-congenital-lesion
#16
Marcia E Pereira Bacares, Vimala Vemireddi, Dianne Creasy
Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28573869/obiltoxaximab-adding-to-the-treatment-arsenal-for-bacillus-anthracis-infection
#17
Audrey W Hou, Amanda M Morrill
OBJECTIVE: To review the safety and efficacy of obiltoxaximab, a monoclonal antibody indicated for the treatment of Bacillus anthracis inhalational anthrax in adult and pediatric patients. DATA SOURCES: A MEDLINE (1946 to May, week 1, 2017) and EMBASE (1980 to 2017, week 19) search was performed using the search terms obiltoxaximab OR ETI-204 OR Anthim AND anthrax. STUDY SELECTION AND DATA EXTRACTION: All English-language clinical studies in both animal and human models assessing the safety and efficacy of obiltoxaximab were included...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28573661/characterization-of-a-pristane-induced-lupus-associated-model-in-the-non-human-primate-cynomolgus-monkey
#18
Jing Wang, Hui Shen, Yuqiang Zhu, Ying Zhu, Lei Cai, Zhiyao Wang, Qin Shi, Yuhua Qiu
BACKGROUND: Lupus is an autoimmune disease with complex syndrome. Rodent models have limitations for recapitulating the spectrum of the disease. A more powerful translational model is desirable. METHOD: Lupus-associated model in cynomolgus monkeys was induced by two intraperitoneal injections of 2, 6, 10, 14-tetramethylpentadecane (PRISTANE). Lupus-specific biomarkers and manifestations over a 246-day period were observed at multilevel. To visualize and quantify kidney function in real time, contrast-enhanced ultrasound was used...
June 2, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28564657/relationship-between-elevated-intraocular-pressure-and-divided-peripapillary-sector-retinal-nerve-fiber-layer-thickness-in-a-cynomolgus-monkey-laser-induced-ocular-hypertension-model
#19
Tetsuro Noguchi, Masamitsu Shimazawa, Koji Hamaguchi, Tomoaki Araki, Naoto Horai, Hideaki Hara
AIMS: We investigated the relationship between elevated intraocular pressure (IOP) and changes in global and peripapillary sector retinal nerve fiber layer (RNFL) thickness around the optic nerve head (ONH) in the laser-induced ocular hypertension monkey model. METHODS: To induce high IOP, green laser photocoagulation burns were applied around the trabecular meshwork of 1 eye from each of 12 cynomolgus monkeys. The animals had been acclimated to IOP measurement under conscious conditions for more than 2 months, and IOP was chronologically measured...
June 1, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28559261/the-fluorocycline-tp-271-is-efficacious-in-models-of-aerosolized-francisella-tularensis-schu-s4-infection-in-balb-c-mice-and-cynomolgus-macaques
#20
Trudy H Grossman, Michael S Anderson, David Christ, Melanie Gooldy, Lisa N Henning, Henry S Heine, M Victoria Kindt, Winston Lin, Kaylyn Siefkas-Patterson, Anne K Radcliff, Vincent H Tam, Joyce A Sutcliffe
TP-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. TP-271 was active in vitro against a panel of 29 Francisella tularensis isolates, showing minimal inhibitory concentrations against 50% and 90% of isolates of 0.25 and 0.5μg/mL, respectively. In a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 LD50/mouse of F. tularensis SCHU S4. Following 21 days of once-daily intraperitoneal dosing of 3, 6, 12 and 18 mg/kg/day TP-271, initiating at 24 hours post-challenge, survival was 80%, 100%, 100%, and 100%, respectively...
May 30, 2017: Antimicrobial Agents and Chemotherapy
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