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correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the av7909 anthrax vaccine candidate.the anthrax vaccine candidate av7909 is being developed as a next generation vaccine for a post-exposure prophylaxis (pep) indication against anthrax. av7909 consists of the anthrax vaccine adsorbed (ava, biothrax®) bulk drug substance adjuvanted with the immunostimulatory oligodeoxynucleotide (odn) compound, cpg 7909. the addition of cpg 7909 to ava enhances both the magnitude and the kinetics of antibody responses in animals and human subjects, making av7909 a suitable next-generation vaccine ...201728774566
systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.characterization of adeno-associated viral vector (aav) mediated gene delivery to the enteric nervous system (ens) was recently described in mice and rats. in these proof-of-concept experiments, we show that intravenous injections of clinically relevant aavs can transduce the ens in guinea pigs and non-human primates. neonatal guinea pigs were given intravenous injections of either aav8 or aav9 vectors that contained a green fluorescent protein (gfp) expression cassette or phosphate-buffered sal ...201728771235
pharmacodynamic monitoring of ro5459072, a small molecule inhibitor of cathepsin s.major histocompatibility complex class ii (mhcii)-restricted antigen priming of cd4(+) t cells is both involved in adaptive immune responses and the pathogenesis of autoimmune diseases. degradation of invariant chain ii, a protein that prevents premature peptide loading, is a prerequisite for nascent mhcii-peptide complex formation. a key proteolytic step in this process is mediated by cathepsin s. inhibition of this cysteine protease is known to result in the intracellular accumulation of lip10 ...201728769925
characterization and reliability of [(18)f]2fnq1p in cynomolgus monkeys as a pet radiotracer for serotonin 5-ht6 receptors.brain serotonin-6 receptor (5-ht6r) is the one of the most recently identified serotonin receptors. accumulating evidence suggests that it is a potent therapeutic target for psychiatric and neurological diseases. since [(18)f]2fnq1p was recently proposed as the first fluorinated positron emission tomography (pet) radioligand for this receptor, the objective of the present study was to demonstrate its suitability for 5-ht6r neuroimaging in primates. [(18)f]2fnq1p was characterized by in vitro aut ...201728769801
development of genotyping method for functionally relevant variants of cytochromes p450 in cynomolgus macaques.in cynomolgus macaques (macaca fascicularis), widely used in drug metabolism studies, cyp2c9, cyp2c76, cyp2d6, cyp3a4, and cyp3a5, important drug-metabolizing enzymes, are abundantly expressed in liver and metabolize cytochrome p450 substrates. cyp2c9 (c.334a>c), cyp2c76 (c.449tg>a), cyp2d6 (c.891a>g), cyp3a4 (ivs3 + 1g>del), and cyp3a5 (c.625a>t) substantially influence metabolic activity of enzymes, and thus are important variants in drug metabolism studies. in this study, a real-time pcr meth ...201728752932
increased functional connectivity after stroke correlates with behavioral scores in non-human primate model.here we characterized the functional connectivity (fc) changes occurring after a controlled mca stroke in a primate model. we hypothesize that if fc can inform about the neural changes after a stroke in the non-human primate (nhp) stroke model, then significant fc changes after the stroke would have to correlate with the remaining behavioral capacities. eleven cynomolgus monkeys underwent an experimental middle cerebral artery occlusion while five monkeys remained as the control group. one month ...201728751636
new insights into the factors affecting synonymous codon usage in human infecting plasmodium species.codon usage bias is due to the non-random usage of synonymous codons for coding amino acids. the synonymous sites are under weak selection, and codon usage bias is maintained by the equilibrium in mutational bias, genetic drift and selection pressure. the differential codon usage choices are also relevant to human infecting plasmodium species. recently, p. knowlesi switches its natural host, long-tailed macaques, and starts infecting humans. this review focuses on the comparative analysis of cod ...201728751162
mauritian cynomolgus macaques with m3m4 mhc genotype control sivmac251 infection.understanding natural hiv control may lead to new preventative or therapeutic strategies. several protective major histocompatibility complex (mhc) genotypes were found in humans and rhesus macaques. here, we report a simian immunodeficiency virus (siv) controller mhc genotype in mauritian cynomolgus macaques (mcms).201728748659
next-generation sequencing to investigate urinary micrornas from macaca fascicularis (cynomolgus monkey).advanced sequencing technologies like next-generation sequencing (ngs) not only detect micrornas (mirnas) in biological samples but also facilitate de novo identification of mirnas. using an ion torrent's ion proton system, here we described mirnas sequencing of urine samples collected from macaca fascicularis (cynomolgus monkey) to investigate mirnas as potential novel biomarkers of nephrotoxicity in this species. urinary mirna sequencing methodologies described here include (a) urinary exosoma ...201728748475
quantitative prediction of therapeutic antibody pharmacokinetics after intravenous and subcutaneous injection in human.prediction of the plasma/serum mab concentration-time profile in human is important to determine the required dose regime. this study proposes an approach for predicting the plasma/serum mab concentration-time profile after intravenous and subcutaneous injection in human based on comprehensive analysis of reported pharmacokinetic data. optimal scaling exponents from cynomolgus monkey to human for cl, q, vc, and vp were estimated as 0.8, 0.75, 1.0, and 0.95, respectively. the estimated exponents ...201728734646
cross-validation of commercial enzyme-linked immunosorbent assay and radioimmunoassay for porcine c-peptide concentration measurements in non-human primate serum.c-peptide concentration is widely used as a marker of insulin secretion and is especially relevant in evaluating islet graft function following transplantation, because its measurement is not confounded by the presence of exogenous insulin. to address the shortage of human islet donors, the use of porcine islets has been proposed as a possible solution and the stringent pig-to-non-human primate (nhp) model is often the most relevant for pre-clinical evaluation of the potential for diabetes rever ...201728731212
chikungunya virus infection in cynomolgus macaques following intradermal and aerosol exposure.chikungunya virus (chikv) is transmitted via mosquito bite and potentially by aerosol, causing chikungunya fever and arthritic disease in humans. there are currently no licensed vaccines or antiviral therapeutics to protect against chikv infection in humans. animal models recapitulating human disease, especially for transmission by aerosol, are needed for licensure of such medical countermeasures.201728728590
clinical laboratory values as early indicators of ebola virus infection in nonhuman primates.the ebola virus (ebov) outbreak in west africa during 2013-2016 demonstrated the need to improve ebola virus disease (evd) diagnostics and standards of care. this retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal evd to assess associations with improved survival time. in addition, the study identified laboratory values useful as predictors of survival, surrogates for ebov viral loads, and triggers for initiation of therapeutic interventio ...201728726603
isolation of a monoclonal antibody from a phage display library binding the rhesus macaque mhc class i allomorph mamu-a1*001.monoclonal antibodies that bind to human leukocyte antigen (hla) are useful tools for hla-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (mhc) on cell surfaces. unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. to address this deficiency, we isolated an antibody that recognizes the common i ...201728719653
evaluation of drug-induced hematotoxicity using novel in vitro monkey cfu-gm and bfu-e colony assays.in order to evaluate drug-induced hematotoxicity in monkey cells in vitro, colony-forming unit-granulocyte, macrophage (cfu-gm), and burst-forming unit-erythroid (bfu-e) colony assays were established using mononuclear cells in the bone marrow collected from male cynomolgus monkeys. furthermore, the effects of doxorubicin, chloramphenicol, and linezolid on cfu-gm and bfu-e colony formation were investigated using established monkey cfu-gm and bfu-e colony assays in comparison with those on human ...201728717098
preclinical safety and efficacy of andexanet alfa in animal models.essentials there is currently no approved reversal agent for factor xa (fxa) inhibitors andexanet alfa has been developed to reverse the anticoagulant effects of fxa inhibitors andexanet reduced blood loss and anticoagulation markers in rivaroxaban-anticoagulated rabbits andexanet was well tolerated in monkeys and rats, with no evidence of prothrombotic activity summary: background andexanet alfa is a recombinant modified form of factor xa (fxa), designed to bind to and reverse the anticoagulant ...201728682477
generation of macaca fascicularis ips cell line atci-mf1 from adult skin fibroblasts using non-integrative sendai viruses.we generated atci-mf1 induced pluripotent stem (ips) cell line from macaca fascicularis adult skin fibroblasts using non-integrative sendai viruses carrying oct3/4, klf4, sox2 and c-myc. once established, atci-mf1 cells present a normal karyotype, are sendai virus-free and express pluripotency associated markers. microsatellite markers analysis confirmed the origin of the ips cells from the parental fibroblasts. pluripotency was tested with the in vivo teratoma formation assay. atci-mf1 cell lin ...201728677526
identification and optimization of pyrrolo[3,2-d]pyrimidine toll-like receptor 7 (tlr7) selective agonists for the treatment of hepatitis b.pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective tlr7 agonists. compounds were optimized for their activity and selectivity over tlr8. this presents an advantage over recently described scaffolds that have residual tlr8 activity, which may be detrimental to the tolerability of the candidate drug. oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (isg) response in mice and cynomolgus monkeys. we aimed for a high ...201728671847
single-cell transcriptome of early embryos and cultured embryonic stem cells of cynomolgus monkeys.in mammals, the development of pluripotency and specification of primordial germ cells (pgcs) have been studied predominantly using mice as a model organism. however, divergences among mammalian species for such processes have begun to be recognized. between humans and mice, pre-implantation development appears relatively similar, but the manner and morphology of post-implantation development are significantly different. nevertheless, the embryogenesis just after implantation in primates, includ ...201728649393
post-exposure treatment of non-human primates lethally infected with ebola virus with ebotab, a purified ovine igg product.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 strin ...201728642489
role of social interaction, exercise, diet, and age on developing and untreated diabetes in cynomolgus monkeys.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 untre ...201728625601
comparative assessment of immune complex-mediated hypersensitivity reactions with biotherapeutics in the non-human primate: critical parameters, safety and lessons for future studies.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 ...201728624430
bpi-3016, a novel long-acting hglp-1 analogue for the treatment of type 2 diabetes mellitus.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 ...201728619366
early paradoxical increase of dopamine: a neurochemical study of olfactory bulb in asymptomatic and symptomatic mptp treated monkeys.parkinson's disease (pd) is a neurodegenerative disease with both motor and non-motor manifestations. hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. the relationship between hyposmia and pd remains elusive. olfactory bulb (ob) pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. in this study we examined tissue levels of dopamine (da) and serotonin (5-hydroxytrypta ...201728611598
long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates.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.201728609387
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.cynomolgus monkey cytochrome p450 2c9 (formerly known as p450 2c43) variation was reportedly associated with metabolic clearance of the antiretroviral drug efavirenz in vivo (in 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 signifi ...201728608515
effects of social reorganization on dopamine d2/d3 receptor availability and cocaine self-administration in male cynomolgus monkeys.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.201728608008
rapid focal cooling attenuates cortical seizures in a primate epilepsy model.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 ...201728601605
nonclinical pharmacokinetic and pharmacodynamic characterisation of somapacitan: a reversible non-covalent albumin-binding growth hormone.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.201728595133
surgical techniques of allogeneic liver transplantation in a nonhuman primate model.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 ...201728583546
simultaneous subtotal pancreatectomy and streptozotocin injection for diabetes modeling in cynomolgus monkeys.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.201728583545
chronic ketamine exposure causes white matter microstructural abnormalities in adolescent cynomolgus monkeys.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 ...201728579941
translational research in the nonhuman primate model of tuberculosis.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 ...201728575319
testicular fibrous hypoplasia in cynomolgus monkeys ( macaca fascicularis): an incidental, congenital lesion.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 betw ...201728573934
obiltoxaximab: adding to the treatment arsenal for bacillus anthracis infection.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.201728573869
characterization of a pristane-induced lupus-associated model in the non-human primate cynomolgus monkey.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.201728573661
relationship between elevated intraocular pressure and divided peripapillary sector retinal nerve fiber layer thickness in a cynomolgus monkey laser-induced ocular hypertension model.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.201728564657
the fluorocycline tp-271 is efficacious in models of aerosolized francisella tularensis schu s4 infection in balb/c mice and cynomolgus macaques.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 mics against 50% and 90% of isolates of 0.25 and 0.5 μg/ml, respectively. in a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (ld50)/mouse of f. tularensis schu s4. following 21 days of once-daily intraperitoneal dosing with tp-271 at 3, 6, 1 ...201728559261
comparative evaluation of αcd40 (2c10r4) and αcd154 (5c8h1 and idec-131) in a nonhuman primate cardiac allotransplant model.specific blockade of t cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. the goal of this study is to compare results associated with 3 monoclonal antibodies directed against the cd40/cd154 t cell costimulation pathway.201728557955
morphological evaluation of retinal ganglion cells expressing the l132c/t159c chr2 mutant transgene in young adult cynomolgus monkeys.to characterize recombinant aav2 (raav2)-mediated expression of l132c/t159c chr2 mutant in retinal ganglion cells (rgcs) of young adult cynomolgus monkeys. raav2 vectors carrying a fusion construct of the chr2 mutant and gfp (chr2-gfp) were delivered to the vitreous chamber by intravitreal injection. expression patterns of the chr2 mutant in rgcs were examined by immunohistochemical methods three months after injection. the rna-binding protein with multiple splicing (rbpms) was used as an rgc sp ...201728550523
prolonged deficits of associative motor learning in cynomolgus monkeys after long-term administration of phencyclidine.phencyclidine (pcp) is a potent drug of abuse that induces sustained schizophrenia-like symptoms in humans by blocking neurotransmission at n-methyl-d-aspartate (nmda)-type glutamate receptors. alterations in nmda receptor function have been linked to numerous behavioral deficits and cognitive dysfunction. classical eye-blink conditioning (ebc), including delay (debc) and trace (tebc) paradigms, provides an effective means to study the neurobiology of associative motor learning in rodents, mamma ...201728549649
high infection rates for adult macaques after intravaginal or intrarectal inoculation with zika virus.unprotected sexual intercourse between persons residing in or traveling from regions with zika virus transmission is a risk factor for infection. to model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with zika virus by intravaginal or intrarectal routes. in macaques inoculated intravaginally, we detected viremia and virus rna in 50% of macaques, followed by seroconversion. in macaques inoculated intrarectally, we detected viremia, virus rna, or both, ...201728548637
insights into reston virus spillovers and adaption from virus whole genome sequences.reston virus (family filoviridae) is unique among the viruses of the ebolavirus genus in that it is considered non-pathogenic in humans, in contrast to the other members which are highly virulent. the virus has however, been associated with several outbreaks of highly lethal hemorrhagic fever in non-human primates (nhps), specifically cynomolgus monkeys (macaca fascicularis) originating in the philippines. in addition, reston virus has been isolated from domestic pigs in the philippines. to bett ...201728542463
discovery of clinical candidate 2-((2s,6s)-2-phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [bms-816336], an orally active novel selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor.bms-816336 (6n-2), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-hsd1) enzyme (ic50 3.0 nm) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-hsd2). 6n-2 exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ed50 0.12 mg/kg) and in dio mice. it is orally bioavailable (%f ranges from 20 to 72% in preclinical species) and has a predicted pharma ...201728537398
discovery of n-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (vu0424238): a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5 selected for clinical evaluation.preclinical evidence in support of the potential utility of mglu5 nams for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. despite some promising results from clinical studies, no small molecule mglu5 nam has yet to reach market. here we present the discovery and evaluation of n-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, vu0424238), a compound selected for clinical evalua ...201728530802
septicemic invasive klebsiella pneumoniae infection in a cynomolgus monkey (macaca fascicularis) with severe diffused suppurative meningoencephalitis.a 2-year-old male cynomolgus monkey (macaca fascicularis) showed neurological symptoms during quarantine for importation into japan, and was euthanized due to poor prognosis. gross anatomical examination revealed a hemorrhagic lesion around the lateral ventricle in the cerebrum. histologically, severe diffused suppurative meningitis and ventriculitis were detected with numerous gram-negative bacilli in the cerebrum. immunohistochemically, the bacilli were positively stained with an antibody agai ...201728529273
discovery of bi 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor.a potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β hsd1) inhibitor (11j) has been identified. compound 11j inhibited 11β hsd1 activity in human adipocytes with an ic50 of 4.3nm and in primary human adipose tissue with an ic80 of 53nm. oral administration of 11j to cynomolgus monkey inhibited 11β hsd1 activity in adipose tissue. compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered huma ...201728528082
modeling rett syndrome using talen-edited mecp2 mutant cynomolgus monkeys.gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. here, we report detailed genotypes and phenotypes of talen-edited mecp2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, rett syndrome (rtt), which is caused by loss-of-function mutations in the human mecp2 gene. male mutant monkeys were embryonic lethal, reiterating that rtt is a disease of females. through a battery of behavioral analyses, including prim ...201728525759
from the cover: evaluation of the effects of tanezumab, a monoclonal antibody against nerve growth factor, on the sympathetic nervous system in adult cynomolgus monkeys (macaca fascicularis): a stereologic, histomorphologic, and cardiofunctional assessment.tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (sns) of adult nonhuman primates. study 1 evaluated potential effects of subcutaneous (sc) tanezumab (1.2 mg/kg every 8 weeks [q8w]) on sns in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a no ...201728525647
effects of olanexidine gluconate on preoperative skin preparation: an experimental study in cynomolgus monkeys.to determine the bactericidal efficacy of a new topical antiseptic for preoperative skin preparation, olanexidine gluconate (development code: opb-2045g), against transient or resident bacterial flora on the skin of cynomolgus monkeys.201728516852
mechanistic modeling of the pharmacodynamic and pharmacokinetic relationship of tissue factor pathway inhibitor-neutralizing antibody (bay 1093884) in cynomolgus monkeys.bay 1093884 is a fully human monoclonal antibody against the tissue factor pathway inhibitor (tfpi) in development as prophylaxis in patients with hemophilia with or without inhibitors. in vitro, bay 1093884 binds to human, mouse, and monkey tfpi. the objective of this study was to find a pharmacodynamic (pd) biomarker after administration of bay 1093884 to normal monkeys. in monkey plasma, bay 1093884 exhibited an ic50 (concentration that inhibits 50%) of 4.65 and 6.19 nm for free tfpi and dilu ...201728516358
intergroup variation in robbing and bartering by long-tailed macaques at uluwatu temple (bali, indonesia).robbing and bartering (rb) is a behavioral practice anecdotally reported in free-ranging commensal macaques. it usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. while extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. during a 4-month study in 2010, we used both focal and ...201728516338
a neutralizing anti-g-csfr antibody blocks g-csf-induced neutrophilia without inducing neutropenia in nonhuman primates.neutrophils are the most abundant wbcs and have an essential role in the clearance of pathogens. tight regulation of neutrophil numbers and their recruitment to sites of inflammation is critical in maintaining a balanced immune response. in various inflammatory conditions, such as rheumatoid arthritis, vasculitis, cystic fibrosis, and inflammatory bowel disease, increased serum g-csf correlates with neutrophilia and enhanced neutrophil infiltration into inflamed tissues. we describe a fully huma ...201728515226
effects of sa237, a humanized anti-interleukin-6 receptor monoclonal antibody, on pre- and postnatal development in cynomolgus monkey.sa237 is a humanized anti-interleukin-6 receptor (il-6r) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. according to literature, blocking of il-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth.201728504465
investigating biogeographic boundaries of the sunda shelf: a phylogenetic analysis of two island populations of macaca fascicularis.cyclical submergence and re-emergence of the sunda shelf throughout the pleistocene served as a dynamic biogeographic landscape, across which long-tailed macaques (macaca fascicularis) have migrated and evolved. here, we tested the integrity of the previously reported continental-insular haplotype divide reported among y and mitochondrial dna lineages across multiple studies.201728500747
first molecular identification and genetic diversity of strongyloides stercoralis and strongyloides fuelleborni in human communities having contact with long-tailed macaques in thailand.the parasitic nematodes, strongyloides stercoralis and strongyloides fuelleborni, can infect humans and non-human primates. we amplified and sequenced a portion of the 18s ribosomal rna gene (rrna) and of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of strongyloides from humans in the study area in thailand, where people have frequent contact with long-tailed macaques. fresh stool samples were obtained from 213 people and were examined using the agar plate culture method. the ove ...201728500375
comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (hiv) prevention strategies. however, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study.201728488364
interplay between grip and vision in the monkey medial parietal lobe.we aimed at understanding the relative contribution of visual information and hand shaping to the neuronal activity of medial posterior parietal area v6a, a newly added area in the monkey cortical grasping circuit. two macaca fascicularis performed a reach-to-grasp task in the dark and in the light, grasping objects of different shapes. we found that v6a contains visual cells, activated only during grasping in the light; motor neurons, equally activated during grasping in the dark and in the lig ...201728472262
low potential for mechanical transmission of ebola virus via house flies (musca domestica).ebola virus (ebov) infection results in high morbidity and mortality and is primarily transmitted in communities by contact with infectious bodily fluids. while clinical and experimental evidence indicates that ebov is transmitted via mucosal exposure, the ability of non-biting muscid flies to mechanically transmit ebov following exposure to the face had not been assessed.201728468673
activation of skeletal muscle ampk promotes glucose disposal and glucose lowering in non-human primates and mice.the amp-activated protein kinase (ampk) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. we evaluated two distinct direct activators of ampk: a non-selective activator of all ampk complexes, pf-739, and an activator selective for ampk β1-containing complexes, pf-249. in cells and animals, both compounds were effective at activating ampk in hepatocytes, but only pf-739 was capable of activating ampk in skeletal muscle. in dia ...201728467931
pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates.pharmacokinetic studies play an important role in all stages of drug discovery and development. recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advanci ...201728463063
in utero transfer of adeno-associated viral vectors produces long-term factor ix levels in a cynomolgus macaque model.the safe correction of an inherited bleeding disorder in utero prior to the onset of organ damage is highly desirable. here, we report long-term transgene expression over more than 6 years without toxicity following a single intrauterine gene transfer (iugt) at 0.9g using recombinant adeno-associated vector (aav)-human factor ix (hfix) in the non-human primate model we have previously described. four of six treated animals monitored for around 74 months expressed hfix at therapeutic levels (3.9% ...201728462816
a simple way to eradicate methicillin-resistant staphylococcus aureus in cynomolgus macaques (macaca fascicularis).our investigation of indoor-housed cynomolgus macaques (macaca fascicularis) by using automated identification followedbyantibiotic susceptibility testing revealed 1 of 7 immunocompetent animals and 2 of 9 immunosuppressed monkeys as carriers ofmethicillin-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 n ...201728462776
nonuniform moving boundary method for computational fluid dynamics simulation of intrathecal cerebrospinal flow distribution in a cynomolgus monkey.a detailed quantification and understanding of cerebrospinal fluid (csf) dynamics may improve detection and treatment of central nervous system (cns) diseases and help optimize csf system-based delivery of cns therapeutics. this study presents a computational fluid dynamics (cfd) model that utilizes a nonuniform moving boundary approach to accurately reproduce the nonuniform distribution of csf flow along the spinal subarachnoid space (sas) of a single cynomolgus monkey. a magnetic resonance ima ...201728462417
comprehensive analysis of circulating microrna specific to the liver, heart, and skeletal muscle of cynomolgus monkeys.circulating micrornas (mirnas) could represent sensitive and specific biomarkers for tissue injury. however, their utility as biomarkers in nonclinical toxicological studies using nonhuman primates is limited by a lack of information on their organ specificity and circulating levels under resting condition of the animals. herein, liver, heart, and skeletal muscle-specific expression patterns of mirnas were determined in 27 tissues/organs from male and female monkeys (n =2/sex) by next-generation ...201728460582
localization of zinc transporters in the spinal cord of cynomolgus monkey.zinc is abundant in the spinal cord, where it participates in several physiological and pathophysiological processes, including neurotransmission, spinal cord injury, and amyotrophic lateral sclerosis. however, the mechanisms underlying zinc homeostasis in the spinal cord are largely unknown. zinc transporters (znts) are responsible for transporting zinc from the cytoplasm to the extracellular space or to intracellular compartments. in the present study, we examined the distribution of znt1-10 p ...201728455213
role of regional absorption and gastrointestinal motility on variability in oral absorption of a model drug.variability in oral absorption in pre-clinical species makes human dose projection challenging. in this study, we investigated the mechanistic basis of variability in oral absorption of a model hydrophobic compound with ph-dependent solubility, bms-955829, after oral dosing in rats, dogs, and cynomolgus monkeys. the contribution of regional absorption to pharmacokinetic variability was assessed in ported monkeys by direct intraduodenal and intraileal administration. the effect of bms-955829 on g ...201728455207
in depth comparative phenotyping of blood innate myeloid leukocytes from healthy humans and macaques using mass cytometry.comparative immune-profiling of innate responses in humans and non-human primates is important to understand the pathogenesis of infectious and chronic inflammatory diseases as well as for the preclinical development of vaccines and immune therapies. however, direct comparisons of the two species are rare and were never performed using mass cytometry. here, whole-blood-derived leukocytes from healthy humans and cynomolgus macaques were analyzed with mass cytometry. two similar panels of around 3 ...201728444973
iohexol clearance for determination of glomerular filtration rate in cynomolgus monkeys (macaca fascicularis).the purpose of this study was to validate a method for determine the glomerular filtration rate (gfr) in healthy cynomolgus monkeys by using iohexol. eighteen healthy cynomolgus macaque monkeys (age, 4 to 6 y [mean, 5 y]; weight, 2 to 6 kg [mean, 4 kg]) were randomly entered into 3 different doses groups (3 male and 3 female macaques per group) of 30, 60, 90 mg i/kg to receive an intravenous bolus injection of iohexol. serum iohexol concentrations were determined by using liquid chromatography-t ...201728443538
effects of an ep2 and ep3 receptor dual agonist, ono-8055, on a radical hysterectomy-induced underactive bladder model in monkeys.the objective was to develop an underactive bladder (uab) model in primates and to evaluate the potential of prostanoid ep2 and ep3 receptor dual agonist ono-8055 to become a therapeutic agent for uab.201728439968
herpes b virus replication and viral lesions in the liver of a cynomolgus macaque which died from severe disease with rapid onset.herpes b virus (bv, macacine alphaherpesvirus 1) infects macaques asymptomatically, with rare exceptions, but can cause fatal encephalitis in humans. here, we report disseminated bv infection in a cynomolgus macaque that had died within 12 hour after the onset of unspecific symptoms. multifocal lesions surrounded by viral antigen were detected in liver while other organs remained inconspicuous, indicating that the liver is a major target. moreover, high copy numbers of viral dna were found in fe ...201728439900
long lasting neutralization of c5 by sky59, a novel recycling antibody, is a potential therapy for complement-mediated diseases.dysregulation of the complement system is linked to the pathogenesis of a variety of hematological disorders. eculizumab, an anti-complement c5 monoclonal antibody, is the current standard of care for paroxysmal nocturnal hemoglobinuria (pnh) and atypical hemolytic uremic syndrome (ahus). however, because of high levels of c5 in plasma, eculizumab has to be administered biweekly by intravenous infusion. by applying recycling technology through ph-dependent binding to c5, we generated a novel hum ...201728439081
pharmacokinetic and toxicology comparator testing of biosimilar drugs - assessing need.a key element in the development of a biosimilar molecule is the comparability of the biological activity/nonclinical similarity to the innovator drug. although some regulatory guidelines are encouraging little or no in vivo testing, currently a common practice is to perform at least one toxicology and/or one pharmacokinetic (pk) study to assess if any different findings occur for in-life, clinical pathology and histopathological parameters or in exposure. an exercise was performed in which the ...201728433587
preclinical study of raav2-strail: pharmaceutical efficacy, biodistribution and safety in animals.the recombinant strail has been in clinical trial for various human malignancies. however, the half-life time of strail is very short, which might be an important factor influencing its clinical efficacy for cancer therapy. we previously reported the recombinant adeno-associated virus (aav)-encoding strail95-281-mediated strail expression in vivo up to 8 months and suppressed tumor growth markedly in mouse xenografts. in the present study, we further evaluated the clinical potency for cancer gen ...201728429751
kinetic reconstruction reveals time-dependent effects of romosozumab on bone formation and osteoblast function in vertebral cancellous and cortical bone in cynomolgus monkeys.romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption. the effects on bone formation are transient, eliciting a rapid increase in bone formation that attenuates with continued treatment. although bone formation attenuates, bone mineral density (bmd) continues to increase. to explore potential tissue-level mechanisms that could contribute to a pr ...201728428078
alveolar ridge dimensional changes following ridge preservation procedure with novel devices: part 3 - histological analysis in non-human primate model.this study sought to investigate the histological changes following tooth extraction, ridge preservation and augmentation, using novel devices designed to obturate the oral orifice of extraction sockets (socketkap™) and provide structural support for sockets with defective bony walls (socketkage™) in a non-human primate model.201728422326
pharmacokinetics of monoclonal antibodies and fc-fusion proteins.there are many factors that can influence the pharmacokinetics (pk) of a mab or fc-fusion molecule with the primary determinant being fcrn-mediated recycling. through fab or fc engineering, igg-fcrn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. glycosylation of a mab or fc-fusion protein can have a significant impact on the pk of these molecules. mab charge can be important and ...201728421387
urban primate ranging patterns: gps-collar deployments for macaca fascicularis and m. sylvanus.the global increase in urbanization is leading to heavier interface between humans and wildlife. within these anthropogenic landscapes, little is known about ranging patterns, particularly with regard to urban primates. here we present the results of the first long-term deployment of multiple gps collars on two species of macaques to investigate the impacts of urbanization on urban primate ranging patterns in singapore and gibraltar. collars data acquisition were excellent with respect to the am ...201728419550
evaluation of the physiotel™ digital m11 cardiovascular telemetry implant in socially housed cynomolgus monkeys up to 16weeks after surgery.the novel physiotel™ digital m11 telemetry implant was evaluated in socially housed monkeys with respect to both safety pharmacological cardiovascular (arterial blood pressure (bp), heart rate (hr) and electrocardiogram (ecg)) and toxicological (clinical pathology and histopathology) endpoints.201728416413
distribution of fcrn across species and tissues.the neonatal fc receptor (fcrn) is a major histocompatibility complex class i type molecule that binds to, transports, and recycles immunoglobulin g (igg) and albumin, thereby protecting them from lysosomal degradation. therefore, besides the knowledge of fcrn affinity, fcrn protein expression is critical in understanding the pharmacokinetic behavior of fc-containing biotherapeutics such as monoclonal antibodies. the goal of this investigation was to achieve for the first time a comparative asse ...201728402755
collagen sponge functionalized with chimeric anti-bmp-2 monoclonal antibody mediates repair of critical-size mandibular continuity defects in a nonhuman primate model.antibody-mediated osseous regeneration (amor) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mabs) immobilized on a scaffold. specifically, anti-bone morphogenetic protein- (bmp-) 2 mabs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. the present study sought to investigate the application of amor for repair of mandibular co ...201728401163
leveraging of rifampicin-dosed cynomolgus monkeys to identify bile acid 3-o-sulfate conjugates as potential novel biomarkers for organic anion-transporting polypeptides.in the search for novel bile acid (ba) biomarkers of liver organic anion-transporting polypeptides (oatps), cynomolgus monkeys received oral rifampicin (rif) at four dose levels (1, 3, 10, and 30 mg/kg) that generated plasma-free cmax values (0.06, 0.66, 2.57, and 7.79 µm, respectively) spanning the reported in vitro ic50 values for oatp1b1 and oatp1b3 (≤1.7 μm). as expected, the area under the plasma concentration-time curve (auc) of an oatp probe drug (i.v. (2)h4-pitavastatin, 0.2 mg/kg) was i ...201728396527
identification of human igg1 variant with enhanced fcrn binding and without increased binding to rheumatoid factor autoantibody.various studies have demonstrated that fc engineering to enhance neonatal fc receptor (fcrn) binding is effective for elongating half-life or increasing cellular uptake of igg. a previous study has shown that a n434h mutation to enhance fcrn binding resulted in increased binding to rheumatoid factor (rf) autoantibody, which is not desirable for therapeutic use in autoimmune disease. in this study, we first showed that all the existing fc variants with enhanced fcrn binding also show increased rf ...201728387635
establishment of reference values for complete blood count and blood gases in cynomolgus monkeys (macaca fascicularis).cynomolgus monkeys are closely related to humans phylogenetically, and this has resulted in their widespread use as a preclinical model. hematological data with regard to these monkeys are thus important. although reference values for blood components and sex hormones have been established for cynomolgus monkeys, those for arterial blood gases have not. the arterial blood gases quickly reflect respiratory and circulatory dynamics, and are thus useful for animal management and safe general anesth ...201728381665
evidence of simian retrovirus type d by polymerase chain reaction.over the past few years, there have been reports of finding simian retrovirus type d (srv) in macaque colonies where some animals were characterized as antibody positive but virus negative raising questions about how srv was transmitted or whether there is a variant strain detected by antibody but not polymerase chain reaction (pcr) in current use.201728370081
long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. nonhuman primate (nhp) is an excellent model for metabolic research, because nhps can naturally develop type 2 diabetes mellitus (t2dm) similarly to humans. this study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (macaca fascicularis) during circadian, meal, stress and drug exposure.201728365864
establishing a large-animal model for in vivo reprogramming of bile duct cells into insulin-secreting cells to treat diabetes.type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. both of these approaches have severe limitations. repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures. islet transplantation, while highly effective, i ...201728363269
long noncoding rna mantis facilitates endothelial angiogenic function.the angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding rnas (lncrnas) has hardly been studied. we set out to identify novel and functionally important endothelial lncrnas.201728351900
discrimination of stem cell status after subjecting cynomolgus monkey pluripotent stem cells to naïve conversion.experimental animal models have played an indispensable role in the development of human induced pluripotent stem cell (ipsc) research. the derivation of high-quality (so-called "true naïve state") ipscs of non-human primates enhances their application and safety for human regenerative medicine. although several attempts have been made to convert human and non-human primate pscs into a truly naïve state, it is unclear which evaluation methods can discriminate them as being truly naïve. here we a ...201728349944
adipokines (leptin, adiponectin, resistin) differentially regulate all hormonal cell types in primary anterior pituitary cell cultures from two primate species.adipose-tissue (at) is an endocrine organ that dynamically secretes multiple hormones, the adipokines, which regulate key physiological processes. however, adipokines and their receptors are also expressed and regulated in other tissues, including the pituitary, suggesting that locally- and at-produced adipokines might comprise a regulatory circuit that relevantly modulate pituitary cell-function. here, we used primary pituitary cell-cultures from two normal nonhuman-primate species [papio-anubi ...201728349931
improved full-length killer cell immunoglobulin-like receptor transcript discovery in mauritian cynomolgus macaques.killer cell immunoglobulin-like receptors (kirs) modulate disease progression of pathogens including hiv, malaria, and hepatitis c. cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens, and so, considerable effort has been put into characterizing their kir genetics. however, previous studies have relied on cdna cloning and sanger sequencing that lack the throughput of current sequencing platforms. in this study, we present a high throughput, full-len ...201728343239
preclinical development of a humanized neutralizing antibody targeting hgf.hepatocyte growth factor (hgf) and its receptor, cmet, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. we therefore examined the anti-tumor activity of the humanized monoclonal anti-hgf antibody, yyb-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. hgf neutralization, the extracellular signal-related kinases 1 and 2 (erk1/2) phosphorylation, and hgf-induced scattering were assessed in ...201728336956
social setting, social rank and hpa axis response in cynomolgus monkeys.hypothalamic-pituitary-adrenal (hpa) axis activity under different social settings in non-human primates is understudied.201728332004
a novel fc-fgf21 with improved resistance to proteolysis, increased affinity toward β-klotho, and enhanced efficacy in mice and cynomolgus monkeys.fibroblast growth factor (fgf) 21 is a natural hormone that modulates glucose, lipid, and energy metabolism. previously, we engineered an fc fusion fgf21 variant with two mutations, fc-fgf21(rg), to extend the half-life and reduce aggregation and in vivo degradation of fgf21. we now describe a new variant developed to reduce the extreme c-terminal degradation and improve the binding affinity to β-klotho. we demonstrate, by introducing one additional mutation located at the c terminus of fgf21 (a ...201728324011
immunolocalization of novel corticomedullary tubule injury markers in cynomolgus monkeys treated with amphotericin b.amphotericin b (ampb) nephrotoxicity was used to assess the utility of drug‑induced kidney injury (diki) biomarkers in an exploratory study in male cynomolgus monkeys. all animals had quantifiable levels of ampb in plasma on days 1 and 4. there were no clinical signs of ampb‑induced toxicity in this study. the gold standard method used to confirm ampb‑induced diki was anatomic pathology which revealed microscopic lesions with varying grades of severity. immunolocalization of alpha‑1 microglobuli ...201728321043
decoding information for grasping from the macaque dorsomedial visual stream.neurodecoders have been developed by researchers mostly to control neuroprosthetic devices, but also to shed new light on neural functions. in this study, we show that signals representing grip configurations can be reliably decoded from neural data acquired from area v6a of the monkey medial posterior parietal cortex. two macaca fascicularis monkeys were trained to perform an instructed-delay reach-to-grasp task in the dark and in the light toward objects of different shapes. population neural ...201728320845
from play to proficiency: the ontogeny of stone-tool use in coastal-foraging long-tailed macaques (macaca fascicularis) from a comparative perception-action perspective.macaques crack shellfish in coastal environments with specialized stone-hammering techniques. i provide the first examination of skill development from 866 object-manipulation and 7,400 tool-use bouts, collected over 15 months, using longitudinal analyses of infants' object manipulation (n = 7) and cross-sectional comparisons of manipulative and tool-use behavior (n = 69). i adopt a perception-action approach, examining how the emergence of actions on objects relate to the spatial-relational and ...201728318292
preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of js-001, a programmed cell death protein-1 (pd-1) monoclonal antibody.js-001 is the first monoclonal antibody (mab) against programmed cell death protein-1 (pd-1) approved by the china food and drug administration (cfda) into the clinical trails. to date, however, no pre-clinical pharmacological and pharmacokinetic (pk) data are available. in this study, we investigated the efficacy of js-001 and conducted a preclinical pk study, including the monitoring of anti-drug antibodies (adas). we found that js-001 specifically bound to pd-1 antigen with an ec50 of 21 nmol ...201728317872
radiological and microsurgical anatomy for variation of the mandible: comparative study of human and macaca fascicularis.recent studies using cone-beam computer tomography (cbct) have added to our understanding of anatomical variation in the mandible of humans. however, the distribution of nerves cannot be revealed by cbct. there have been investigations of the distribution of nerves relating to the mandible, but some proposed causes of these variations remain controversial. in this study, we observed a total of 10 sides from five mandibles of macaca fascicularis of unknown age and sex using cbct and dissection un ...201728317283
morphologic and doppler findings from hepatic ultrasonography of normal cynomolgus monkeys (macaca fascicularis).the present study evaluated the anatomic and ultrasonographic features of the liver in normal cynomolgus monkeys (macaca fascicularis). healthy, male, cynomolgus monkeys from cambodia (n = 25; mean age, 58.1 mo) were sedated with ketamine (7 mg/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. vesse ...201728315648
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