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functional neurotoxicity evaluation of noribogaine using video-eeg in cynomolgus monkeys.continuous video-electroencephalographic (eeg) monitoring remains the gold standard for seizure liability assessments in preclinical drug safety assessments. eeg monitored by telemetry was used to assess the behavioral and eeg effects of noribogaine hydrochloride (noribogaine) in cynomolgus monkeys. noribogaine is an iboga alkaloid being studied for the treatment of opioid dependence.201727126304
mixed body/hand reference frame for reaching in 3d space in macaque parietal area pec.the neural correlates of coordinate transformations from vision to action are expressed in the activity of posterior parietal cortex (ppc). it has been demonstrated that among the medial-most areas of the ppc, reaching targets are represented mainly in hand-centered coordinates in area pe, and in eye-centered, body-centered, and mixed body/hand-centered coordinates in area v6a. here, we assessed whether neurons of area pec, located between v6a and pe in the medial ppc, encode targets in body-cen ...201726941385
predicting pharmacokinetic profile of therapeutic antibodies after iv injection from only the data after sc injection in cynomolgus monkey.1. the number of developed therapeutic monoclonal antibodies (mabs) has increased in this decade. this study aims to predict their pharmacokinetic profiles after intravenous (iv) injection using only the data taken after subcutaneous (sc) injection in cynomolgus monkey. 2. two-compartment model parameters, q, vc and vp, were collected from the published data after iv injection in cynomolgus monkey for 21 mabs (group a). bioavailability after sc injection (f), cl and serum/plasma concentration af ...201727151820
cardiovascular safety assessments in the cynomolgus monkey: unmasking potential background arrhythmias in general toxicity studies.we describe experience with an unexpectedly high background incidence of atrioventricular block (avb) observed in mauritian cynomolgus monkeys (mcm) during preclinical safety assessment for bitopertin, a glycine-transporter-1 inhibitor.201726957141
correction: temporal expression of peripheral blood leukocyte biomarkers in a macaca fascicularis infection model of tuberculosis; comparison with human datasets and analysis with parametric/non-parametric tools for improved diagnostic biomarker identification.[this corrects the article doi: 10.1371/journal.pone.0154320.].201727428353
voluntary ethanol consumption reduces gabaergic neuroactive steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-thp) in the amygdala of the cynomolgus monkey.neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-thp, allopregnanolone) enhance the gamma-aminobutyric acid (gaba)-ergic effects of ethanol and modulate excessive drinking in rodents. moreover, chronic ethanol consumption reduces 3α,5α-thp levels in human plasma, rat hippocampus and mouse limbic regions. we explored the relationship between 3α,5α-thp levels in limbic brain areas and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of et ...201726625954
tactical deception to hide sexual behaviour: macaques use distance, not visibility.although tactical deception (td) may be employed to hide sexual behaviour, there is as yet no firm evidence for it. hiding may be guided by cognitive mechanisms consistent with either no, low or high level td, such as exploiting male peripheral positions (no td), creating distance (td level 1) or hiding behind screens (td level 1.5 which involves visual perspective taking (vpt)). macaques are capable of vpt in a food context, suggesting that they may employ td level 1.5. we investigated, in an o ...201726246655
evaluation of cardiovascular parameters in cynomolgus monkeys following iv administration of lbr-101, a monoclonal antibody against calcitonin gene-related peptide.calcitonin gene-related peptide (cgrp) is a well-validated target for migraine therapy and a known potent systemic vasodilator. lbr-101 is a monoclonal antibody against cgrp in clinical development for the preventive treatment of episodic and chronic migraine. understanding the hemodynamic and cardiovascular consequences of chronic cgrp inhibition is therefore warranted. given the conservation in cgrp sequence between monkeys and humans, addressing this question in monkeys is ideal as it allows ...201724866108
characterization and screening of igg binding to the neonatal fc receptor.the neonatal fc receptor (fcrn) protects immunoglobulin g (igg) from degradation and increases the serum half-life of igg, thereby contributing to a higher concentration of igg in the serum. because altered fcrn binding may result in a reduced or prolonged half-life of igg molecules, it is advisable to characterize fc receptor binding of therapeutic antibody lead candidates prior to the start of pre-clinical and clinical studies. in this study, we characterized the interactions between fcrn of d ...201724802048
morphologic manifestations of testicular and epididymal toxicity.histopathologic examination of the testis is the most sensitive means to detect effects on spermatogenesis; however, the complexity of testicular histology, interrelatedness of cell types within the testis, and long duration of spermatogenesis can make assessment of a testicular toxicant challenging. a thorough understanding of the histology and morphologic manifestations of response to injury is critical to successfully identify a testicular effect and to begin to understand the underlying mech ...201726413388
comparative reactivity of human ige to cynomolgus monkey and human effector cells and effects on ige effector cell potency.due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. ige therapeutics in development depend upon engagement with the fcεri and fcεrii receptors on immune effector cells for their function. only limited knowledge of the primate ige immune system is available to inform the choice of models for mechanistic and safety evaluations.201724492303
argx-110, a highly potent antibody targeting cd70, eliminates tumors via both enhanced adcc and immune checkpoint blockade.overexpression of cd70 has been documented in a variety of solid and hematological tumors, where it is thought to play a role in tumor proliferation and evasion of immune surveillance. here, we describe argx-110, a defucosylated igg1 monoclonal antibody (mab) that selectively targets and neutralizes cd70, the ligand of cd27.   argx-110 was generated by immunization of outbred llamas. the antibody was germlined to 95% human identity, and its anti-tumor efficacy was tested in several in vitro assa ...201724492296
application of canaloplasty in glaucoma gene therapy: where are we?schlemm's canal (sc) inner wall is adjacent to the juxtacanalicular trabecular meshwork (tm) over their entire circumference. we seek to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys.201724512297
minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration.subcutaneous (sc) delivery is a common route of administration for therapeutic monoclonal antibodies (mabs) with pharmacokinetic (pk)/pharmacodynamic (pd) properties requiring long-term or frequent drug administration. an ideal in vivo preclinical model for predicting human pk following sc administration may be one in which the skin and overall physiological characteristics are similar to that of humans. in this study, the pk properties of a series of therapeutic mabs following intravenous (iv) ...201722453096
pharmacokinetics of engineered human monomeric and dimeric ch2 domains.therapeutic monoclonal antibodies have several advantages over small molecule drugs and small proteins and peptides, including a long serum half-life. the long serum half-life of igg is due, in part, to its molecular weight (150kda) and its ability to bind fcrn. both the ch2 and ch3 domains of fc are involved in fcrn binding. antibody fragments and antibody-like scaffolds have improved penetration into tissues due to their small size, yet suffer from a short serum half-life of less than one hour ...201622699277
effect of dioxin on ovarian function in the cynomolgus macaque (m. fascicularis).ovarian function was evaluated in mature female cynomolgus macaques 443 to 625 days following a single oral exposure (1, 2, or 4 microg/kg bw) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd). urinary estrone conjugates (e1c), pregnanediol-3-glucuronide (pdg), and follicle stimulating hormone (fsh) were measured. three of four animals in the high dose group had no evidence of menstrual cycles while animals in the low and medium dose groups plus one from the high dose group had cycles that were simi ...201611489593
clinicopathological findings in non-human primate recipients of porcine renal xenografts: quantitative and qualitative evaluation of proteinuria.immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. in human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. the detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential gr ...201624112104
platelet aggregation in humans and nonhuman primates: relevance to xenotransplantation.platelet activation/aggregation plays a key role in the dysregulation of coagulation and the development of thrombotic microangiopathy in nonhuman primate recipients of pig xenografts. as a preliminary to the study of anti-platelet therapy in vitro and in vivo, the present study aimed to compare platelet aggregation in whole blood from humans, baboons, and cynomolgus monkeys.201622909136
preclinical evaluation of 89zr-labeled anti-cd44 monoclonal antibody rg7356 in mice and cynomolgus monkeys: prelude to phase 1 clinical studies.rg7356 is a humanized antibody targeting the constant region of cd44. rg7356 was radiolabeled with (89)zr for preclinical evaluations in tumor xenograft-bearing mice and normal cynomolgus monkeys to enable study of its biodistribution and the role of cd44 expression on rg7356 uptake.   studies with (89)zr-rg7356 were performed in mice bearing tumor xenografts that differ in the level of cd44 expression (cd44(+) or cd44(-)) and rg7356 responsiveness (resp or non-resp): mda-mb-231 (cd44(+), resp), ...201624492295
a review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a "humanized" tilapia insulin.most islet xenotransplantation laboratories have focused on porcine islets, which are both costly and difficult to isolate. teleost (bony) fish, such as tilapia, possess macroscopically visible distinct islet organs called brockmann bodies which can be inexpensively harvested. when transplanted into diabetic nude mice, tilapia islets maintain long-term normoglycemia and provide human-like glucose tolerance profiles. like porcine islets, when transplanted into euthymic mice, they are rejected in ...201625040337
thalamic projections to visual and visuomotor areas (v6 and v6a) in the rostral bank of the parieto-occipital sulcus of the macaque.the medial posterior parietal cortex of the primate brain includes different functional areas, which have been defined based on the functional properties, cyto- and myeloarchitectural criteria, and cortico-cortical connections. here, we describe the thalamic projections to two of these areas (v6 and v6a), based on 14 retrograde neuronal tracer injections in 11 hemispheres of 9 macaca fascicularis. the injections were placed either by direct visualisation or using electrophysiological guidance, a ...201625633471
method validation and reference range values for a peripheral blood immunophenotyping assay in non-human primates.a peripheral blood immunophenotyping assay was developed and validated for determination of total t-lymphocytes, helper t-lymphocytes, cytotoxic t-lymphocytes, b-lymphocytes, and natural killer cells in cynomolgus monkeys. validation parameters included assessment of precision, linearity, antibody optimization, stability of peripheral blood samples, and stability of fixed immunophenotyping samples. total lymphocyte populations were determined using a heterogeneous lymphocyte gating strategy cons ...201625600312
chronic ethanol self-administration in macaques shifts dopamine feedback inhibition to predominantly d2 receptors in nucleus accumbens core.given the high level of homology between nonhuman primates and humans in regard to anatomy, physiology and ethanol drinking patterns, nonhuman primates represent an unparalleled preclinical model for examining the neurobiological basis of ethanol abuse.201626627912
fully human anti-baff inhibitory monoclonal antibody tabalumab does not adversely affect t-dependent antibody responses in cynomolgus monkey (macaca fasicularis): a summary of three pre-clinical immunotoxicology evaluations.the potential immunotoxicity of tabalumab was assessed as a component of standard pre-clinical toxicology studies in cynomolgus monkeys. to evaluate potential tabalumab-associated immunosuppression after antigen challenge, cynomolgus monkeys were administered placebo control or tabalumab in three immunotoxicological safety studies. study 1, a 4-week pilot study, evaluated biweekly intravenous (iv) control, and 0.3, 1.0, 5.0, and 15.0 mg/kg tabalumab doses. study 2 evaluated iv control, and 0.1, ...201625585959
cynomolgus monkey induced pluripotent stem cells generated by using allogeneic genes.induced pluripotent stem (ips) cells that are potentially similar to embryonic stem (es) cells can be artificially established by introduction into somatic cells of the transgenes pou5f1 (also known as oct3/4), sox2, klf4, and c-myc. in cynomolgus monkeys (macaca fascicularis), ips cells generated by using these four allogeneic transgenes should be an important resource for various types of biomedical research because the use of xenogeneic transgenes may cause complications. to establish such ip ...201625410287
congenital foot deformation alters the topographic organization in the primate somatosensory system.limbs may fail to grow properly during fetal development, but the extent to which such growth alters the nervous system has not been extensively explored. here we describe the organization of the somatosensory system in a 6-year-old monkey (macaca radiata) born with a deformed left foot in comparison to the results from a normal monkey (macaca fascicularis). toes 1, 3, and 5 were missing, but the proximal parts of toes 2 and 4 were present. we used anatomical tracers to characterize the patterns ...201625326245
inhibition of crac with a human anti-orai1 monoclonal antibody inhibits t-cell-derived cytokine production but fails to inhibit a t-cell-dependent antibody response in the cynomolgus monkey.orai1 is the pore-forming component of calcium release-activated calcium (crac) channels. crac channels are the primary route for calcium ion (ca(2+)) entry into t-cells following antigen stimulation. this ca(2+) entry induces proliferation and cytokine production through activation of calcineurin and the nuclear factor of activated t-cells (nfat) transcription factor along with subsequent cytokine-related genes. it was hypothesized that the in vivo inhibition of t-cell function by blocking orai ...201624990272
biodistribution study of intravenously injected cetuximab-irdye700dx in cynomolgus macaques.the use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. to facilitate clinical testing, we evaluated cetuximab conjugated to irdye700dx (ir700) in cynomolgus macaques.201626335283
multiplexing of receptor occupancy measurements for pharmacodynamic biomarker assessment of biopharmaceuticals.receptor occupancy (ro) assays measure drug target engagement, and are used as pharmacodynamic (pd) biomarkers. ro assays are commonly performed by flow cytometry and often require multiplexing for assessment of multiple pd biomarkers when specimen volumes are limited. we present multiplexed ro assays for an igf1r-egfr bispecific antibody (bs-ab) and a ctla4-ig recombinant fusion protein to demonstrate key considerations for accurate ro assessment.201626332491
development of a genotyping tool for a functionally relevant cyp2c19 allele (phe100asn, ala103val and ile112leu) in cynomolgus macaques..in cynomolgus macaques, which are widely used in drug metabolism studies, cyp2c19 (formerly known as cyp2c75) is abundantly expressed in liver, metabolizes human cyp2c substrates and is thus an important drug-metabolizing enzyme. one of the cynomolgus cyp2c19 alleles (p.phe100asn, p.ala103val and p.ile112leu) results in substantially reduced metabolic activity and thus is an important allele in drug metabolism studies. for this allele, a genotyping tool was developed using allele-specific taqma ...201626300440
a method for estimating the glomerular filtration rate in conscious monkeys.to establish a method for estimating the glomerular filtration rate (gfr) in conscious monkeys, the radiographic contrast medium iodixanol and the standard agent inulin were coadministered as tracers to male cynomolgus monkeys (macaca fascicularis) as a bolus injection; blood was collected after 60, 90 and 120 min. an equation based on a single-blood-sample method derived from jacobsson's formula was prepared using the data from healthy and saline- and gentamicin-treated monkeys by a multisample ...201625994107
single- and repeat-dose toxicity of idx14184, a nucleotide prodrug with antiviral activity for hepatitis c viral infection, in mice, rats, and monkeys.the single- and repeat-dose toxicity profile of idx14184, a novel guanosine nucleotide prodrug with antiviral activity against hepatitis c viral infection, was characterized following once daily oral administration for durations up to 13, 26, and 32 weeks in mouse, rat, and cynomolgus monkey, respectively. the heart, liver, kidney, skeletal muscles, and lower gastrointestinal tract (cecum, colon, and/or rectum) were identified as the primary toxicity targets in these nonclinical species. the mou ...201626138064
receptor occupancy and blocking of stat5 signaling by an anti-il-7 receptor α antibody in cynomolgus monkeys.interleukin-7 receptor α (il-7rα) is associated with autoimmune disease. blocking its activation by interleukin-7 (il-7) with a therapeutic monoclonal antibody may reduce pathogenic t cells and effectively control the autoimmune response in these disorders.201625914284
distribution of topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye.nepafenac ophthalmic suspensions, 0.1% (nevanac(®)) and 0.3% (ilevro™), are topical nonsteroidal anti-inflammatory drug (nsaid) products approved in the united states, europe and various other countries to treat pain and inflammation associated with cataract surgery. nevanac is also approved in europe for the reduction in the risk of postoperative macular edema (me) associated with cataract surgery in diabetic patients. the efficacy against me suggests that topical administration leads to distri ...201626474497
kidney versus islet allograft survival after induction of mixed chimerism with combined donor bone marrow transplantation.we have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in mhc mismatched nonhuman primates. in this study, we attempted to extend this tolerance induction approach to islet allografts. a total of eight recipients underwent mhc mismatched combined islet and bone marrow (bm) transplantation after induction of diabetes by streptozotocin. three recipients were treated after a nonmyeloablative conditioning regimen that included low-d ...201626337731
a central mesencephalic reticular formation projection to the supraoculomotor area in macaque monkeys.the central mesencephalic reticular formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system's premotor circuitry. this study in macaca fascicularis monkeys investigates the pattern of central mesencephalic reticular formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. it also examines the location of the cells responsible for this projection. inj ...201625859632
evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate.quantitative analysis of the orientational distribution of biological apatite (bap) crystals is proposed as a new index of bone quality. this study aimed to analyze bap c-axis orientation in ovariectomized (ovx) monkeys treated with amino-bisphosphonates minodronic acid and alendronate as reference. sixty female monkeys aged 9-17 years were divided into five groups: one sham group and four ovx groups. the sham group and one ovx group were treated daily with vehicle for 17 months. the other three ...201625837430
long-term effects of castration on the skeleton of male rhesus monkeys (macaca mulatta).while osteopenia (ope) and osteoporosis (opo) have been studied in various species of aging nonhuman primates and extensively in ovariectomized rhesus and cynomolgus macaques, there is virtually no information on the effects of castration on the skeleton of male nonhuman primates. most information on castrated male primates comes from a few studies on the skeletons of eunuchs. this report used a subset of the caribbean primate research center's (cprc) cayo santiago (cs) rhesus macaque skeletal c ...201625771746
a central mesencephalic reticular formation projection to the edinger-westphal nuclei.the central mesencephalic reticular formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. the edinger-westphal nucleus is found within the supraoculomotor area. it has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iri ...201626615603
do monkeys compare themselves to others?social comparisons are a fundamental characteristic of human behaviour, yet relatively little is known about their evolutionary foundations. adapting the co-acting paradigm from human research (seta in j pers soc psychol 42:281-291, 1982. doi: 10.1037//0022-3514.42.2.281), we examined how the performance of a partner influenced subjects' performance in long-tailed macaques (macaca fascicularis). using parallel testing in touch screen setups in which subjects had to discriminate familiar and nove ...201626615416
cynomolgus monkey as a clinically relevant model to study transport involving renal organic cation transporters: in vitro and in vivo evaluation.organic cation transporter (oct) 2, multidrug and toxin extrusion protein (mate) 1, and mate2k mediate the renal secretion of various cationic drugs and can serve as the loci of drug-drug interactions (ddi). to support the evaluation of cynomolgus monkey as a surrogate model for studying human organic cation transporters, monkey genes were cloned and shown to have a high degree of amino acid sequence identity versus their human counterparts (93.7, 94.7, and 95.4% for oct2, mate1, and mate2k, res ...201626608080
investigating the effect of autoinduction in cynomolgus monkeys of a novel anticancer mdm2 antagonist, idasanutlin, and relevance to humans.1. idasanutlin (rg7388) is a potent p53-mdm2 antagonist currently in clinical development for treatment of cancer. the purpose of the present studies was to investigate the cause of marked decrease in plasma exposure after repeated oral administration of rg7388 in monkeys and whether the autoinduction observed in monkeys is relevant to humans. 2. in monkey liver and intestinal microsomes collected after repeated oral administration of rg7388 to monkeys, significantly increased activities of homo ...201626586447
in vivo and in vitro characterization of a novel mao-b inhibitor radioligand, 18f-labeled deuterated fluorodeprenyl.the aim of this study was to radiolabel a novel bis-deuterium substituted l-deprenyl analog (fluorodeprenyl-d2) with (18)f and to evaluate its potential to visualize and quantify monoamine oxidase (mao) b activity in vivo.201626585057
identification of putative substrates for cynomolgus monkey cytochrome p450 2c8 by substrate depletion assays with 22 human p450 substrates and inhibitors.cynomolgus monkeys are widely used in drug developmental stages as non-human primate models. previous studies used 89 compounds to investigate species differences associated with cytochrome p450 (p450 or cyp) function that reported monkey specific cyp2c76 cleared 19 chemicals, and homologous cyp2c9 and cyp2c19 metabolized 17 and 30 human cyp2c9 and/or cyp2c19 substrates/inhibitors, respectively. in the present study, 22 compounds selected from viewpoints of global drug interaction guidances and ...201626581561
metabolism and metabolite profiles in vitro and in vivo of ospemifene in humans and preclinical species.metabolite profiles of ospemifene, a novel nonsteroidal selective estrogen receptor modulator, were surveyed as part of its development.201626581074
identification and function probing of an antithrombin iiiβ conformation-specific antibody.essentials: antithrombin iii (at)β binds heparin with higher affinity than atα. a conformation-specific antibody against atβ, tpp2009, was made to investigate atβ in hemostasis. tpp2009 bound specifically to heparin-atβ and greatly reduced the anticoagulant effect of at. this antibody was effective in elucidating the importance of atβ in hemostasis.201626581031
chemically modified interleukin-6 aptamer inhibits development of collagen-induced arthritis in cynomolgus monkeys.interleukin-6 (il-6) is a potent mediator of inflammatory and immune responses, and a validated target for therapeutic intervention of inflammatory diseases. previous studies have shown that sl1026, a slow off-rate modified aptamer (somamer) antagonist of il-6, neutralizes il-6 signaling in vitro. in the present study, we show that sl1026 delays the onset and reduces the severity of rheumatoid symptoms in a collagen-induced arthritis model in cynomolgus monkeys. sl1026 (1 and 10 mg/kg), administ ...201626579954
a novel allosteric insulin receptor-activating antibody reduces hyperglycemia without hypoglycemia in diabetic cynomolgus monkeys.xmeta is a fully human, allosteric monoclonal antibody that binds the insulin receptor with high affinity and mimics the glucoregulatory, but not the mitogenic, actions of insulin. here we evaluated the efficacy of both single and repeat s.c. administrations of xmeta in reducing hyperglycemia in obese cynomolgus monkeys with naturally developed type 2 diabetes, a model that shares many features of human diabetes. the data show that a single s.c. administration of xmeta at dose levels ranging fro ...201626578267
evaluation of 6-11c-methyl-m-tyrosine as a pet probe for presynaptic dopaminergic activity: a comparison pet study with β-11c-l-dopa and 18f-fdopa in parkinson disease monkeys.we recently developed a novel pet probe, 6-(11)c-methyl-m-tyrosine ((11)c-6memtyr), for quantitative imaging of presynaptic dopamine synthesis in the living brain. in the present study, (11)c-6memtyr was compared with β-(11)c-l-dopa and 6-(18)f-fluoro-l-dopa ((18)f-fdopa) in the brains of normal and parkinson disease (pd) model monkeys (macaca fascicularis).201626564319
agonistic human antibodies binding to lecithin-cholesterol acyltransferase modulate high density lipoprotein metabolism.drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. however, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. ...201626644477
treg depletion in non-human primates using a novel diphtheria toxin-based anti-human ccr4 immunotoxin.regulatory t cells (treg) play an important role in modulating the immune response and has attracted increasing attention in diverse fields such as cancer treatment, transplantation and autoimmune diseases. cc chemokine receptor 4 (ccr4) is expressed on the majority of tregs, especially on effector tregs. recently we have developed a diphtheria-toxin based anti-human ccr4 immunotoxin for depleting ccr4(+) cells in vivo. in this study, we demonstrated that the anti-human ccr4 immunotoxin bound an ...201626643572
pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cgmp levels.sildenafil (viagra) is a selective inhibitor of phosphodiesterase type 5 (pde5), which degrades cyclic guanosine monophosphate to the linear nucleotide. sildenafil is acutely used in erectile dysfunction and chronically in pulmonary hypertension. evidence in the last decade shows that sildenafil may have potential as a therapeutic option for alzheimer's disease or other neurodegenerative disorders. the purpose of this work was to explore whether sildenafil crosses the blood-brain barrier. pharma ...201626641206
assessment of interspecies differences in drug-induced qtc interval prolongation in cynomolgus monkeys, dogs and humans.the selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidate molecules. the objective of this investigation was to assess quantitatively the differences in the qtc prolonging effects of moxifloxacin between cynomolgus monkeys, dogs and humans. the impact of interspecies differences is also illustrated for a new candidate molecule.201626553352
using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic c3 inhibitor cp40.simple and reliable methods for evaluating the inhibitory effects of drug candidates on complement activation are essential for preclinical development. here, using an immortalized porcine aortic endothelial cell line (ipec) as target, we evaluated the feasibility and effectiveness of an in vitro xenoantibody-mediated complement-dependent cytotoxicity (cdc) model for evaluating the complement inhibitory activity of cp40, a potent analog of the peptidic c3 inhibitor compstatin. the binding of hum ...201626548839
antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans.epidemiological, genetic association, and mendelian randomization studies have provided strong evidence that lipoprotein (a) [lp(a)] is an independent causal risk factor for cvd, including myocardial infarction, stroke, peripheral arterial disease, and calcific aortic valve stenosis. lp(a) levels >50 mg/dl are highly prevalent (20% of the general population) and are overrepresented in patients with cvd and aortic stenosis. these data support the notion that lp(a) should be a target of therapy fo ...201626538546
advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.radiation therapy is a major treatment regimen for more than 50% of cancer patients. the collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (sigdnp) provide simultaneous mr contrast and radiation dose enhancement. the high atomic number of gadolinium provides a large photoelectric cross-section for increased phot ...201627423325
regulatory t cell infusion can enhance memory t cell and alloantibody responses in lymphodepleted nonhuman primate heart allograft recipients.the ability of regulatory t cells (treg) to prolong allograft survival and promote transplant tolerance in lymphodepleted rodents is well established. few studies, however, have addressed the therapeutic potential of adoptively transferred, cd4(+) cd25(+) cd127(-) foxp3(+) (treg) in clinically relevant large animal models. we infused ex vivo-expanded, functionally stable, nonselected treg (up to a maximum cumulative dose of 1.87 billion cells) into antithymocyte globulin-lymphodepleted, mhc-mism ...201626700196
biib042, a novel γ-secretase modulator, reduces amyloidogenic aβ isoforms in primates and rodents and plaque pathology in a mouse model of alzheimer's disease.reducing the production of larger aggregation-prone amyloid β-peptides (aβ) remains an untested therapeutic approach for reducing the appearance and growth of aβ plaques in the brain, which are a hallmark pathological feature of alzheimer's disease. γ-secretase modulators (gsms) are therapeutics that impact γ-secretase-dependent cleavage of amyloid precursor protein to promote the production of shorter aβ peptides that are less prone to aggregation and plaque deposition. this is accomplished wit ...201626690893
safety and biodistribution evaluation in cynomolgus macaques of raav2tyf-pr1.7-hcngb3, a recombinant aav vector for treatment of achromatopsia.agtc is developing raav2tyf-pr1.7-hcngb3, a recombinant adeno-associated virus (raav) vector expressing the human cngb3 gene, for treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity and absence of color discrimination. we report here results of a study evaluating the safety and biodistribution of raav2tyf-pr1.7-hcngb3 in cynomolgus macaques. three groups of animals (n=2 males and 2 females per group) received a subr ...201626956923
joint degradation in a monkey model of collagen-induced arthritis: role of cathepsin k based on biochemical markers and histological evaluation.the role of cathepsin k in joint degradation in a model of collagen-induced arthritis (cia) in cynomolgus monkey was examined using biochemical markers and histology. joint swelling, urinary c-telopeptide of type ii collagen (ctx-ii), deoxypyridinoline (dpd), and n- and c-telopeptides of type i collagen (ntx and ctx-i, resp.) were analyzed. immunohistochemistry of type ii collagen, cathepsin k, and ctx-ii were performed using joints. joint swelling reached peak on day 42 and continued at this le ...201626949397
immunogenicity screening assay development for a novel human-mouse chimeric anti-cd147 monoclonal antibody (metuzumab).the clinical effect of patient immune responses to therapeutic antibodies affect product safety and efficacy, which makes the development of valid, sensitive immune assays a key aspect of antibody drug development. in this paper, we reported the generations of mouse monoclonal and cynomolgus monkey polyclonal antibodies against the anti-cd147 antibody (metuzumab) as the internal standards and the positive controls. seven mouse monoclonal antibodies were shown to recognize both (fab)2 and full le ...201626944771
knee osteoarthritis pain following medial meniscectomy in the nonhuman primate.a number of promising compounds developed for osteoarthritic pain have failed to demonstrate clinical efficacy. to enhance preclinical translational research for osteoarthritis, a model of knee osteoarthritis pain was developed in macaca fascicularis and the effects of two distinct pharmacological classes of drugs were tested on pain-related behavior.201626944197
2-chloro-4-[[(1r,2r)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: a transdermal selective androgen receptor modulator (sarm) for muscle atrophy.a transdermal sarm has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (bph) and liver-mediated decrease in hdl-c. 2-chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical orx rat model. compound 6 had minimal effect on hdl-c levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective ...201626683992
marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier.the proteasome plays a vital role in the physiology of glioblastoma (gbm), and proteasome inhibition can be used as a strategy for treating gbm. marizomib is a second-generation, irreversible proteasome inhibitor with a more lipophilic structure that suggests the potential for penetrating the blood-brain barrier. while bortezomib and carfilzomib, the 2 proteasome inhibitors approved for treatment of multiple myeloma, have little activity against malignant gliomas in vivo, marizomib could be a no ...201626681765
changes in bone mass during the perimenopausal transition in naturally menopausal cynomolgus monkeys.this study measured the differences in bone mineral density and content in relation to changes in serum hormone and bone marker levels during the perimenopausal transition in naturally menopausal cynomolgus monkeys.201626671190
an snp marker at the stat6 locus can identify the hybrids between rhesus (macaca mulatta) and long-tailed macaques (m. fascicularis) in thailand: a rapid and simple screening method and its application.a polymerase chain reaction-restriction fragment length polymorphism (pcr-rflp) assay was developed to genetically discriminate rhesus (macaca mulatta) macaques from long-tailed (m. fascicularis) macaques. the 745 bp pcr amplicon of the stat6 locus that spans a potentially species-diagnostic single nucleotide polymorphism (snp) marker was digested with apai and gel electrophoresed to give (1) two (234 and 511 bp), (2) one (745 bp) and (3) three (234, 511 and 745 bp) band patterns that correspond ...201626660683
the p2y1 receptor antagonist mrs2500 prevents carotid artery thrombosis in cynomolgus monkeys.adenosine diphosphate directly induces platelet aggregation via the g-protein coupled p2y1 and p2y12 receptors. p2y12, but not p2y1, receptor antagonists are available in the clinic. the relevance of the p2y1 receptor as an antiplatelet target has been studied in rodents, but not in higher species. we therefore examined effects of the pharmacological blockade of the p2y1 receptor with its selective antagonist mrs2500 in monkey models of electrolytic-mediated arterial thrombosis (ecat) and kidney ...201626660522
characterization of the ph and temperature in the rabbit, pig, and monkey eye: key parameters for the development of long-acting delivery ocular strategies.many long-acting delivery strategies for ocular indications rely on ph- and/or temperature-driven release of the therapeutic agent and degradation of the drug carrier. yet, these physiological parameters are poorly characterized in ocular animal models. these strategies aim at reducing the frequency of dosing, which is of particular interest for the treatment of chronic disorders affecting the posterior segment of the eye, such as macular degeneration that warrants monthly or every other month i ...201626655747
human plasma concentrations of five cytochrome p450 probes extrapolated from pharmacokinetics in dogs and minipigs using physiologically based pharmacokinetic modeling.the pharmacokinetics of cytochrome p450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys using simplified physiologically based pharmacokinetic (pbpk) modeling. in the current study, despite some species difference in drug clearances, this modeling methodology was adapted to estimate human plasma concentrations of p450 probes based on data from commonly used medium-sized experimental animals, namely dogs and minipigs. using known species allometric scaling facto ...201626652678
single-trial decoding of intended eye movement goals from lateral prefrontal cortex neural ensembles.neurons in the lateral prefrontal cortex (lpfc) encode sensory and cognitive signals, as well as commands for goal-directed actions. therefore, the lpfc might be a good signal source for a goal-selection brain-computer interface (bci) that decodes the intended goal of a motor action previous to its execution. as a first step in the development of a goal-selection bci, we set out to determine if we could decode simple behavioral intentions to direct gaze to eight different locations in space from ...201626561608
pharmacologic characterization of amg 334, a potent and selective human monoclonal antibody against the calcitonin gene-related peptide receptor.therapeutic agents that block the calcitonin gene-related peptide (cgrp) signaling pathway are a highly anticipated and promising new drug class for migraine therapy, especially after reports that small-molecule cgrp-receptor antagonists are efficacious for both acute migraine treatment and migraine prevention. using xenomouse technology, we successfully generated amg 334, a fully human monoclonal antibody against the cgrp receptor. here we show that amg 334 competes with [(125)i]-cgrp binding t ...201626559125
evaluation of early fetal exposure to vaginally-administered metronidazole in pregnant cynomolgus monkeys.given concern about potential embryo-fetal harm following seminal exposure to drugs with teratogenic potential, pharmaceutical companies use theoretical calculations to estimate seminal concentrations, maternal exposure, and distribution across the placenta to the embryo-fetal compartment for risk assessment. however, it is plausible that there are additional mechanisms whereby the conceptus is exposed. in order to determine if theoretical calculations are sufficiently conservative to predict em ...201626524246
comparison of the superagonist complex, alt-803, to il15 as cancer immunotherapeutics in animal models.il15, a potent stimulant of cd8(+) t cells and natural killer (nk) cells, is a promising cancer immunotherapeutic. alt-803 is a complex of an il15 superagonist mutant and a dimeric il15 receptor αsu/fc fusion protein that was found to exhibit enhanced biologic activity in vivo, with a substantially longer serum half-life than recombinant il15. a single intravenous dose of alt-803, but not il15, eliminated well-established tumors and prolonged survival of mice bearing multiple myeloma. in this st ...201626511282
intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.object convection-enhanced delivery (ced) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. however, the drug distribution attained using ced has not satisfactorily covered the entire targeted lesion in tumors such as glioma. recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. the authors developed a new ultrasound-facilitated drug delivery (ufd) system ...201626495939
effective use of the tspy gene-specific copy number in determining fetal dna in the maternal blood of cynomolgus monkeys.since the available concentration of single-copy fetal genes in maternal blood dna is sometimes lower than detection limits by pcr methods, the development of specific and quantitative pcr detection methods for fetal dna in maternal blood is anticipated, which may broaden the methods that can be used to monitor pregnancy. we used the taqman qpcr amplification for dys14 multi-copy sequence and the sry gene in maternal blood plasma (cell-free dna) and fractional precipitated blood cells (cellular ...201626420680
comparison of radiographic and histological assessment of peri-implant bone around oral implants.the aim of this study was to compare the radiographic bone mineral density and the histological assessment of relative volume density of bone and bone-to-implant contact (bic) of single implants placed in the posterior mandible of monkeys.201626407918
shedding light on minipig drug metabolism - elevated amide hydrolysis in vitro.1. in recent years, the minipig is increasingly used as a test species in non-clinical assessment of drug candidates. while there is good scientific evidence available concerning cytochrome p450-mediated metabolism in minipig, the knowledge of other metabolic pathways is more limited. 2. the aim of this study was to provide an understanding of when, why, and how drug metabolism in minipig differs from other species commonly used in non-clinical studies. in-house cross-species metabolite profile ...201626405846
evaluation of assay interference and interpretation of cxcr4 receptor occupancy results in a preclinical study with medi3185, a fully human antibody to cxcr4.receptor occupancy (ro) assays provide a means to measure the direct interaction of therapeutics with their cell surface targets. free receptor assays quantify cell-surface receptors not bound by a therapeutic while total receptor assays quantify the amount of target on the cell surface.201626384735
preclinical pharmacokinetics evaluation of anti-heparin-binding egf-like growth factor (hb-egf) monoclonal antibody using cynomolgus monkeys via (89)zr-immuno-pet study and the determination of drug concentrations in serum and cerebrospinal fluid.heparin-binding egf-like growth factor (hb-egf) is a member of the egf family and is an important therapeutic target in some types of human cancers. khk2866 is a humanized anti-hb-egf monoclonal antibody igg that neutralizes hb-egf activity by inhibiting the binding of hb-egf to its receptors. the phase i study of khk2866 was discontinued because of neuropsychiatric toxicity. in this study, the pharmacokinetics of khk2866 was evaluated by (89)zr-immuno-pet study and the determination of drug con ...201626464296
serotonin hyperinnervation of the striatum with high synaptic incidence in parkinsonian monkeys.the chronic use of l-dopa for alleviating the motor symptoms of parkinson's disease often produces adverse effects such as dyskinesia. unregulated release of dopamine by serotonin axons following l-dopa administration is a major presynaptic determinant of these abnormal involuntary movements. the present study was designed to characterize the reorganization of serotonin striatal afferents following dopaminergic denervation in a primate model of parkinson's disease. our sample comprised eight cyn ...201626462663
assessment of the hybridization between rhesus (macaca mulatta) and long-tailed macaques (m. fascicularis) based on morphological characters.hybridization between rhesus (macaca mulatta) and long-tailed (m. fascicularis) macaques has become a focal point of interest. the majority of such studies have evaluated their genetics, but not their morphological characters.201626354607
alterations in high-frequency neuronal oscillations in a cynomolgus macaque test of sustained attention following nmda receptor antagonism.a growing body of evidence indicates that neuronal oscillations in the gamma frequency range (30-80 hz) are disturbed in schizophrenic patients during cognitive processes and may represent an endophenotype of the disease. n-methyl-d-aspartate (nmda) receptor antagonists have been used experimentally to induce schizophrenia-like symptoms including cognitive deficits in animals and humans. here we characterized neuronal oscillations and event-related potentials (erps) in cynomolgus macaques fully ...201626354045
finite element analysis of denosumab treatment effects on vertebral strength in ovariectomized cynomolgus monkeys.finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (sham- ...201627149403
on the role of the pedunculopontine nucleus and mesencephalic reticular formation in locomotion in nonhuman primates.the mesencephalic reticular formation (mrf) is formed by the pedunculopontine and cuneiform nuclei, two neuronal structures thought to be key elements in the supraspinal control of locomotion, muscle tone, waking, and rem sleep. the role of mrf has also been advocated in modulation of state of arousal leading to transition from wakefulness to sleep and it is further considered to be a main player in the pathophysiology of gait disorders seen in parkinson's disease. however, the existence of a me ...201627147647
generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17a.interleukin (il)-17a exists as a homodimer (a/a) or as a heterodimer (a/f) with il-17f. il-17a is expressed by a subset of t-cells, called th17 cells, at inflammatory sites. most cell types can respond to the local production of il-17a because of the near ubiquitous expression of il-17a receptors, il-17ra and il-17rc. il-17a stimulates the release of cytokines and chemokines designed to recruit and activate both neutrophils and memory t-cells to the site of injury or inflammation and maintain a ...201627143947
effects of repeated complement activation associated with chronic treatment of cynomolgus monkeys with 2'-o-methoxyethyl modified antisense oligonucleotide.the effects of repeated complement activation in cynomolgus monkeys after chronic antisense oligonucleotide (aso) treatment were evaluated by using isis 104838, a representative 2'-o-methoxyethyl (2'-moe) modified aso. the treatment was up to 9 months with a total weekly dose of 30 mg/kg, given either as daily [4.3 mg/kg/day, subcutaneous (s.c.) injection] or once weekly [30 mg/kg, either as s.c. injection or 30-min intravenous (i.v.) infusion]. acute elevations of complement split products (bb ...201627140858
mapping of mitochondrial ferritin in the brainstem of macaca fascicularis.mitochondrial ferritin (ftmt), a recently-studied iron storage protein, which we suspect is an important defense against oxidative stress in neurons and elsewhere. the 242-amino acid ftmt precursor protein is cleaved to mature protein (of molecular weight about 22-kda) in the mitochondrial matrix. compared with the ubiquitously expressed traditional ferritin (h-ferritin and l-ferritin), ftmt has been found in fewer locations including the testis, heart and brain. previous studies have reported t ...201627133573
cardiac-specific epi64c blunts pressure overload-induced cardiac hypertrophy.the calcium-responsive molecule, calcineurin, has been well characterized to play a causal role in pathological cardiac hypertrophy over the past decade. however, the intrinsic negative regulation of calcineurin signaling during the progression of cardiomyocyte hypertrophy remains enigmatic. herein, we explored the role of epi64c, a dual inhibitor of both ras and calcineurin signaling during t-cell activation, in pressure overload-induced cardiac hypertrophy. we generated a cardiac-specific epi6 ...201627021007
a novel sample processing method for rapid detection of tuberculosis in the stool of pediatric patients using the xpert mtb/rif assay.tuberculosis (tb) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples. stool could replace sputum for diagnostic tb testing if adequate sample processing techniques were available.201627007974
effects of pubertal exposure to dietary soy on estrogen receptor activity in the breast of cynomolgus macaques.endogenous estrogens influence mammary gland development during puberty and breast cancer risk during adulthood. early-life exposure to dietary or environmental estrogens may alter estrogen-mediated processes. soy foods contain phytoestrogenic isoflavones (if), which have mixed estrogen agonist/antagonist properties. here, we evaluated mammary gland responses over time in pubertal female cynomolgus macaques fed diets containing either casein/lactalbumin (n = 12) or soy protein containing a human ...201627006379
safety and biodistribution evaluation in cynomolgus macaques of raav2tyf-pr1.7-hcngb3, a recombinant aav vector for treatment of achromatopsia.applied genetic technologies corporation (agtc) is developing raav2tyf-pr1.7-hcngb3, a recombinant adeno-associated viral (raav) vector expressing the human cngb3 gene, for treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. we report here results of a study evaluating the safety and biodistribution of raav2tyf-pr1.7-hcngb3 in cynomolgus macaques. three groups of animals (n = 2 ...201627003753
malaria in cynomolgus monkeys used in toxicity studies in japan.plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. here we report both our experience with malaria recrudescence in cynomolgus monkeys (macaca fascicularis) in a toxicity study and the results of a survey on plasmodium infection in cynomolgus monkeys imported to japan for laboratory use. a cynomolgus monkey from the toxicity study presented with severe anemia and plasmodium protozoa in erythrocytes on a thin blood smea ...201626989299
pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin-induced neuropathic cold hypersensitivity.oxaliplatin is a first-line treatment for colorectal cancer. however, shortly following treatment, cold-evoked hypersensitivity appears in the extremities and over time, the pain is such that oxaliplatin dosing may need to be markedly reduced or even terminated. there is currently a lack of efficacious treatments for oxaliplatin-induced peripheral neuropathy, which is due in part to the difficulty in translating findings obtained from preclinical rodent models of chemotherapy-induced peripheral ...201626977304
a long-acting fgf21 molecule, pf-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects.fgf21 plays a central role in energy, lipid, and glucose homeostasis. to characterize the pharmacologic effects of fgf21, we administered a long-acting fgf21 analog, pf-05231023, to obese cynomolgus monkeys. pf-05231023 caused a marked decrease in food intake that led to reduced body weight. to assess the effects of pf-05231023 in humans, we conducted a placebo-controlled, multiple ascending-dose study in overweight/obese subjects with type 2 diabetes. pf-05231023 treatment resulted in a signifi ...201626959184
fibroblast activation protein cleaves and inactivates fibroblast growth factor 21.fgf21 is a stress-induced hormone with potent anti-obesity, insulin-sensitizing, and hepatoprotective properties. although proteolytic cleavage of recombinant human fgf21 in preclinical species has been observed previously, the regulation of endogenously produced fgf21 is not well understood. here we identify fibroblast activation protein (fap) as the enzyme that cleaves and inactivates human fgf21. a selective chemical inhibitor, immunodepletion, or genetic deletion of fap stabilized recombinan ...201626797127
low birth weight associates with hippocampal gene expression.birth weight predicts the lifetime risk for psychopathology suggesting that the quality of fetal development influences the predisposition for mental disorders. the connectivity and synaptic network of the hippocampus are implicated in depression, schizophrenia and anxiety. we thus examined the underlying molecular adaptations in the hippocampus as a function of the fetal conditions associated with low birth weight. we used tissues from the non-human primate, macaca fascicularis, to identify cha ...201626791528
immunization against an il-6 peptide induces anti-il-6 antibodies and modulates the delayed-type hypersensitivity reaction in cynomolgus monkeys.interleukin-6 (il-6) overproduction has been involved in the pathogenesis of several chronic inflammatory diseases and the administration of an anti-il-6 receptor monoclonal antibody has been proven clinically efficient to treat them. however, the drawbacks of monoclonal antibodies have led our group to develop an innovative anti-il-6 strategy using a peptide-based active immunization. this approach has previously shown its efficacy in a mouse model of systemic sclerosis. here the safety, immuno ...201626782790
immunogenicity, inflammation, and lipid accumulation in cynomolgus monkeys infused with a lipidated tetranectin-apoa-i fusion protein.high density lipoprotein (hdl)-targeted therapies, which promote cholesterol efflux from cells, are currently in development for reducing cardiovascular events in acute coronary syndrome. human apolipoprotein a-i (apoa-i), the major hdl protein, was fused to the trimerization domain of tetranectin (tn) and complexed with phospholipids to generate a hdl mimetic (lipidated tn-apoa-i) with reduced renal clearance and enhanced efficacy. cynomolgus monkeys received 24-h intravenous infusions of contr ...201626781512
nonhuman primate ocular biometry.to examine ocular growth in nonhuman primates (nhps) from measurements on ex vivo eyes.201626780314
expression of a hyaluronic acid-binding proteoglycan (versican) in the cynomolgus monkey eye.the expression of versican, a hyaluronic acid (ha)-binding protein, during the development and differentiation of the retina has been reported. in this study, we performed histochemical and immunohistological analysis of ha and versican from the ciliary body to the retina in cynomolgus monkey eyes. paraffin-embedded sections of cynomolgus monkey eyes, including from the ciliary body to the macular region, were prepared. the distribution of versican and ha was examined by histochemical and immuno ...201626780096
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