Publications

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placental transfer of 125 iodinated humanized immunoglobulin g2δa in the cynomolgus monkey.antibody-like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., fcrn receptor). there are limited data evaluating this transfer during organogenesis in any species. understanding placental transfer of antibody-like biopharmaceuticals can help to predict risk of developmental toxicity across species, including humans. to complement previously published placental transfer data in the rat with humanized iggδ2 (higg2), the timing and magnitude of transfer in the c ...202031746560
multi-gene technical assessment of qpcr and nanostring n-counter analysis platforms in cynomolgus monkey cardiac allograft recipients.quantitative gene expression profiling of cardiac allografts characterizes the phenotype of the alloimmune response, yields information regarding differential effects that may be associated with various anti-rejection drug regimens, and generates testable hypotheses regarding the pathogenesis of the chronic rejection lesions typically observed in non-human primate heart transplant models. the goal of this study was to assess interplatform performance and variability between the relatively novel ...202031744596
profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray.engineering of α-galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. overcoming this hurdle revealed the importance of non-α-gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection.202031762117
the role of iron in parkinson's disease monkeys assessed by susceptibility weighted imaging and inductively coupled plasma mass spectrometry.mounting evidences indicated that elevated iron levels in the substantia nigra (sn) have been concerned as the underlying mechanisms of neurodegenerative diseases, including parkinson's disease (pd). the present study used the 1-methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (mptp)-treated cynomolgus monkeys for pd to evaluate the usability of swi for assessing iron deposition in the cerebral nuclei of pd. the results showed that susceptibility-weighted imaging (swi) phase values of the ipsilate ...202031760102
alpha-synuclein oligomerization and dopaminergic degeneration occur synchronously in the brain and colon of mptp-intoxicated parkinsonian monkeys.dopaminergic (daergic) degeneration and abnormal α-synuclein (α-syn) expression, phosphorylation and aggregation are observed in both the nigrostriatal system (nss) and enteric nervous system (ens) of patients with parkinson's disease (pd). whether these alterations in α-syn and daergic neurons occur synchronously in the two nervous systems or follow a process that spreads from the gut to the brain remains a subject of debate. here, in mptp-intoxicated cynomolgus monkeys, we showed a parallel da ...202031759083
identification and characterization of a new carboxylesterase 2 isozyme, mfces2c, in the small intestine of cynomolgus monkeys.in contrast to a single human carboxylesterase 2 (ces2) isozyme (hce2), three ces2 genes have been identified in cynomolgus monkeys: mfces2a, mfces2b, and mfces2c. although mfces2a protein is expressed in several organs, mfces2b is a pseudogene and the phenotype of the mfces2c gene has not yet been clarified in tissues. in previous studies, we detected an unidentified esterase in the region of ces2 mobility upon nondenaturing page analysis of monkey intestinal microsomes, which showed immunoreac ...202031836607
isolation of neutrophils from nonhuman species.the development of new advances in understanding the role of neutrophils in inflammation requires effective procedures for isolating and purifying neutrophils. methods for isolating human neutrophils are fairly standard, and some are covered in other chapters of this volume and previous editions. however, procedures for isolating neutrophils from nonhuman species used to model human diseases vary from those used in isolating human neutrophils and are not as well developed. since neutrophils are ...202031728982
induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeys†.in vitro reconstitution of germ-cell development from pluripotent stem cells (pscs) has created key opportunities to explore the fundamental mechanisms underlying germ-cell development, particularly in mice and humans. importantly, such investigations have clarified critical species differences in the mechanisms regulating mouse and human germ-cell development, highlighting the necessity of establishing an in vitro germ-cell development system in other mammals, such as non-human primates. here, ...202031724030
expression levels of micrornas that are potential cytochrome p450 regulators in cynomolgus macaques.1. although the cynomolgus macaque is an important non-human primate species used in drug metabolism studies, cynomolgus macaque microrna expressions have not been fully investigated.2. the expressions of 11 cynomolgus micrornas, all orthologues of p450 regulators in humans, were measured by quantitative polymerase chain reaction in adrenal gland, brain, heart, jejunum, kidney, liver, ovary, testis and uterus. mfa-mir-122 and mfa-mir-192, potentially important biomarkers for liver toxicity, were ...202031682544
role of p-glycoprotein in the brain disposition of seletalisib: evaluation of the potential for drug-drug interactions.seletalisib is an orally bioavailable selective inhibitor of phosphoinositide 3-kinase delta (pi3kδ) in clinical development for the treatment of immune-mediated inflammatory diseases. the present study investigated the role of p-gp in seletalisib disposition, especially brain distribution, and the associated risks of interactions. seletalisib was found to be actively transported by rodent and human p-gp in vitro (transfected llc-pk1 cells; km of ca. 20 µm), with minimal or no affinity for the o ...202031678424
increased attention to snake images in cynomolgus monkeys: an eye-tracking study.previous studies have revealed faster detection of snake images in humans and non-human primates (nhps), suggesting automatic detection of evolutionary fear-relevant stimuli. furthermore, human studies have indicated that general fear-relevance rather than evolutionary relevance is more effective at capturing attention. however, the issue remains unclarified in nhps. thus, in the present study, we explored the attentional features of laboratory-reared monkeys to evolutionary and general fear-rel ...202031709783
interspecies variation of clopidogrel hydrolysis in liver microsomes from various mammals.clopidogrel, a clinically used antiplatelet agent, can be readily hydrolyzed by human carboxylesterase 1a (ces1a) to release an inactive metabolite clopidogrel carboxylic acid (cca). in this study, clopidogrel was used as a tool substrate to investigate the interspecies variation of clopidogrel hydrolysis in hepatic microsomes from various mammals including human and six laboratory animals (such as mouse, rat, rabbit, beagle dog, minipig and cynomolgus monkey). the results demonstrated that clop ...202031669218
palmoplantar depigmentation in macaca fascicularis following blaschko linear pattern.hypomelanosis of ito is a rare neurocutaneous syndrome, characterized by streaks and swirls of hypopigmentation arranged in a blaschkoid pattern. other associated anomalies are observed. we report a case of a male cynomolgus monkey (macaca fascicularis) who presented the characteristic of hypomelanosis of ito with palmoplantar involvement and polythelia.202031657466
novel highly potent oxe receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys.the 5-lipoxygenase product 5-oxo-6e,8z,11z,14z-eicosatetraenoic acid (5-oxo-ete), acting through the oxe receptor, is a potent eosinophil chemoattractant that may be an important proinflammatory mediator in eosinophilic diseases such as asthma. we previously identified a series of indole-based oxe receptor antagonists that rapidly appear in the blood following oral administration but have limited lifetimes. the objective of this study was to increase the potency and plasma half-lives of these co ...202031655025
inhibition of allergen-induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non-human primates.5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ete), acting via the oxe receptor, is unique among 5-lipoxygenase products in its ability to directly induce human eosinophil migration, suggesting its involvement in eosinophilic diseases. to address this hypothesis, we synthesized selective indole-based oxe receptor antagonists. because rodents lack an oxe receptor orthologue, we sought to determine whether these antagonists could attenuate allergen-induced skin eosinophilia in sensitized monkeys.202031655023
idiopathic chronic diarrhea associated with dysbiosis in a captive cynomolgus macaque (macaca fascicularis).chronic inflammatory enteric diseases occur commonly in humans and animals, especially in captive bred macaques. however, information about the etiology of idiopathic chronic inflammatory diarrhea in cynomolgus monkeys is limited. in this paper, we reported the unusual case of idiopathic chronic diarrhea in a captive cynomolgus monkey based on microbial, imaging, and microbiome examinations.202031642533
nonpyramidal neurons in the primate basolateral amygdala: a golgi study in the baboon (papio cynocephalus) and long-tailed macaque (macaca fascicularis).nonpyramidal gabaergic interneurons in the basolateral nuclear complex (bnc) of the amygdala are critical for the regulation of emotion. remarkably, there have been no golgi studies of these neurons in nonhuman primates. therefore, in the present study we investigated the morphology of nonpyramidal neurons (npns) in the bnc of the baboon and monkey using the golgi technique. npns were scattered throughout all nuclei of the bnc and had aspiny or spine-sparse dendrites. npns were morphologically h ...202031600841
genotyping of enterocytozoon bieneusi among captive long-tailed macaques (macaca fascicularis) in hainan province: high genetic diversity and zoonotic potential.enterocytozoon bieneusi is a potentially important zoonotic pathogen. however, there is no information on e. bieneusi infection of captive long-tailed macaques (macaca fascicularis) in hainan province, china. here 193 fecal specimens of m. fascicularis were collected from a breeding base in hainan province, china, housing non-human primates for experimental use. e. bieneusi was identified and genotyped by nested pcr analysis of the internal transcribed spacer (its) region of the rrna gene. a tot ...202031600522
in vivo characterization of rc28-e, a fusion protein targeting vegf and bfgf: pharmacokinetics and ocular distribution in primates.administration of rc28-e, a vegf/bfgf dual decoy receptor (igg1 fc-fusion protein), have shown relative therapeutic value in ocular in vivo models, including laser-induced choroidal neovascularization (cnv) in monkeys and streptozotocin (stz)-induced diabetic retinopathy (dr) in rats. in the present study, we have elucidated the pharmacokinetics profiles of rc28-e at the systemic, vitreous and aqueous humor after administration in a primate model (macaca fascicularis). moreover, here we tease ou ...202031600485
target-mediated drug disposition pharmacokinetic/pharmacodynamic model-informed dose selection for the first-in-human study of avb-s6-500.avb-s6-500 neutralized growth arrest-specific 6 (gas6) protein and effectively inhibited axl signaling in preclinical cancer models. a target-mediated drug disposition (tmdd) pharmacokinetic/pharmacodynamic (pk/pd) model was used to select first-in-human (fih) doses for avb-s6-500 based on predicted target (gas6) suppression in the clinic. the effect of tmdd on avb-s6-500 clearance was incorporated into a standard two-compartment model, providing parallel linear and nonlinear clearance. observed ...202031599479
sky59, a novel recycling antibody for complement-mediated diseases.the complement system usually helps protect against microbial infection, but it could also be involved in the onset of various diseases. inhibition of complement component 5 (c5) with eculizumab has resulted in a significant reduction of hemolysis, reduction of thromboembolic events, and increased survival in patients with paroxysmal nocturnal hemoglobinuria (pnh). however, eculizumab requires frequent intravenous infusions due to the abundance of c5 in plasma and some patients may still experie ...202031622197
the enhanced immunopharmacology of vib4920, a novel tn3 fusion protein and cd40l antagonist, and assessment of its safety profile in cynomolgus monkeys.inhibition of the t- and b-cell interaction through the cd40/cd40 ligand (l) axis is a favourable approach for inflammatory disease treatment. clinical studies of anti-cd40l molecules in autoimmune diseases have met challenges because of thromboembolic events and adverse haemostasis. vib4920 (formerly medi4920) is a novel cd40l antagonist and tn3 fusion protein designed to prevent adverse haemostasis and immunopharmacology. we evaluated the pharmacokinetics, activity and toxicity of vib4920 in m ...202031648370
ultrasonographic measurement of the renal resistive index in the cynomolgus monkey (macaca fascicularis) under conscious and ketamine-immobilized conditions.measurement of the renal resistive index (rri) is one of the standard diagnostic procedures for assessing kidney disability clinically. this method is expected to be used for the same purpose in many kinds of animals, including monkeys utilized in conventional toxicology studies. to establish a practical rri measurement procedure in cynomolgus monkeys (macaca fascicularis), rri was measured by ultrasonography in the spine position in conscious and ketamine-immobilized monkeys. the rri of conscio ...202031645524
safety and pharmacodynamics of anti-cd2 monoclonal antibody treatment in cynomolgus macaques - an experimental study.anti-cd2 treatment provides targeted immunomodulatory properties that have demonstrated clinical usefulness to condition the immune system and to treat transplant rejection. the treatment is species-specific due to structural cd2 antigen differences between nonhuman primates and humans. herein, we report the safety profile and efficacy of two modifications of the same anti-cd2 monoclonal antibody in cynomolgus macaques. twelve subjects received one i.v. anti-cd2 (of rat or rhesus type) dose each ...202031523849
the nonclinical pharmacokinetics and prediction of human pharmacokinetics of sph3127, a novel direct renin inhibitor.sph3127 is a novel direct renin inhibitor designed as an oral drug for the regulation of blood pressure and body fluid homeostasis via the renin-angiotensin-aldosterone system (raas). this candidate is now being evaluated in a phase i clinical trial in china.202031494843
deposition of aerosolized lucinactant in nonhuman primates.background: lucinactant for inhalation is an investigational noninvasive, aerosolized surfactant replacement therapy for treatment of preterm neonates with respiratory distress syndrome. lucinactant for inhalation consists of lyophilized lucinactant and the aerosurf® delivery system (ads). the objective of this study was to characterize the total and regional pulmonary deposition of lucinactant delivered by the ads in nonhuman primates (nhps). methods: lucinactant was radiolabeled by the additio ...202031436493
impact of cmv reactivation, treatment approaches, and immune reconstitution in a nonmyeloablative tolerance induction protocol in cynomolgus macaques.cytomegalovirus (cmv) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. here, we describe the development and use of an assay to monitor the incidence and treatment of cmv viremia in a cynomolgus macaque model of bone marrow transplantation (bmt) for tolerance induction. we address the correlation between the course of viremia and immune reconstitution.202031385931
in vivo intrathecal tracer dispersion in cynomolgus monkey validates wide biodistribution along neuraxis.it is commonly believed that in intrathecal (it) drug delivery, agent distribution is confined to a narrow region close to the injection site, thereby undermining the efficacy of the method.202031352328
evaluation of the developmental toxicity of vedolizumab, an α4β7 receptor antagonist, in rabbit and nonhuman primate.vedolizumab, a humanized monoclonal antibody approved for the treatment of adults with moderately to severely active ulcerative colitis or crohn disease, targets α4β7 integrin and selectively blocks gut-specific lymphocyte trafficking. the potential effects of vedolizumab on development were assessed by standard preclinical toxicity studies in rabbits and cynomolgus monkeys. a single infusion of vedolizumab (0, 10, 30, or 100 mg/kg) was administered intravenously to pregnant rabbits on gestation ...202031364424
a sensitive and selective immunoassay for the quantitation of serum latent myostatin after in vivo administration of srk-015, a selective inhibitor of myostatin activation.myostatin, a member of the transforming growth factor β (tgfβ) superfamily, is a key regulator of skeletal muscle mass and a therapeutic target for muscle wasting diseases. we developed a human monoclonal antibody, srk-015, that selectively binds to and inhibits proteolytic processing of myostatin precursors, thereby preventing growth factor release from the latent complex. as a consequence of antibody binding, latent myostatin accumulates in the circulation of animals treated with srk-015 or cl ...202031347449
refinement of the primate corticospinal pathway during prenatal development.perturbation of the developmental refinement of the corticospinal (cs) pathway leads to motor disorders. while non-primate developmental refinement is well documented, in primates invasive investigations of the developing cs pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. here, we investigated the developmental changes in the distribution of cs projection neurons in cynomolgus monkey (macaca fascicularis). injections of retrograde tracer at cervi ...202031343065
exposure-response analysis of drug-induced qt interval prolongation in telemetered monkeys for translational prediction to human.the preclinical in vivo assay for qt prolongation is critical for predicting torsadogenic risk, but still difficult to extrapolate to humans. this study ran preclinical tests in cynomolgus monkeys on seven qt reference drugs containing the drugs used in the iq-csrc clinical trial and applied exposure-response (er) analysis to the data to investigate the potential for translational information on the qt effect.202031255745
conjugation of dm1 to anti-cd30 antibody has potential antitumor activity in cd30-positive hematological malignancies with lower systemic toxicity.an anti-cd30 antibody-drug conjugate incorporating the antimitotic agent dm1 and a stable smcc linker, anti-cd30-mcc-dm1, was generated as a new antitumor drug candidate for cd30-positive hematological malignancies. here, the in vitro and in vivo pharmacologic activities of anti-cd30-mcc-dm1 (also known as f0002-adc) were evaluated and compared with adcetris (brentuximab vedotin). pharmacokinetics (pk) and the safety profiles in cynomolgus monkeys were assessed. anti-cd30-mcc-dm1 was effective i ...202031161871
establishment of a new formula for qt interval correction using a large colony of cynomolgus monkeys.the demand for monkeys for medical research is increasing, because their ionic mechanism of repolarization is similar to that of humans. the qt interval is the distance between the q wave and t wave, but this interval is affected by heart rate. therefore, qt correction methods are commonly used in clinical settings. however, an accurate correction formula for the qt interval in cynomolgus monkeys has not been reported. we assessed snapshot electrocardiograms (ecgs) of 353 ketamine-immobilized mo ...202031308302
neuronal loss without amyloid-β deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys.conflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid-β (aβ) deposition, as observed in alzheimer's disease. in this study, we aimed to evaluate the presence of aβ deposits in the ipsilateral thalamus and hippocampus 12 months post-stroke in non-human primates, whose brains are structurally and functionally similar to that of humans. four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (mcao), ...202031278793
autophagy of sensory neurons in the trigeminal and dorsal root ganglia of cynomolgus monkeys (macaca fascicularis).although necrosis and apoptosis are uncommon, autophagy of sensory neurons (asn) in trigeminal and dorsal root ganglia is a very common, spontaneous finding in cynomolgus monkeys (macaca fascicularis). data from one author's (butt) laboratory showed 12 of 22 studies (year range 2017 to 2019) that included the evaluation of sensory ganglia from cynomolgus monkeys had at least one control animal with asn. autophagy of sensory neurons is characterized by a distinct cell membrane, cytoplasm filled w ...202031269872
dissection of the trigeminal ganglion of nonrodent species used in toxicology studies.the ganglion of the trigeminal (v cranial) nerve is generally sampled at necropsy in nonrodent toxicology studies only when somatic or autonomic peripheral nervous system toxicity is suspected. the ganglion is far more difficult to locate in nonrodents than in rats and mice, and suitable methods to dissect it have been described only for swine. the trigeminal nerve caudal to the ganglion passes through a canal, roofed by bone in dogs and rabbits and by a tough layer of dura mater in swine and no ...202031181996
development of tibulizumab, a tetravalent bispecific antibody targeting baff and il-17a for the treatment of autoimmune disease.we describe a bispecific dual-antagonist antibody against human b cell activating factor (baff) and interleukin 17a (il-17). an anti-il-17 single-chain variable fragment (scfv) derived from ixekizumab (taltz®) was fused via a glycine-rich linker to anti-baff tabalumab. the igg-scfv bound both baff and il-17 simultaneously with identical stoichiometry as the parental mabs. stability studies of the initial igg-scfv revealed chemical degradation and aggregation not observed in either parental antib ...202031181988
color perception in protanomalous female macaca fascicularis.protanomalous females with x chromosome-linked color vision deficiency exhibit mild abnormalities, whereas dichromats show a distinct deficiency in discriminating certain color pairs. dichromats have an advantage in detecting a textured target when it is camouflaged by red-green colors, owing to their insensitivity to these colors. however, it is not certain whether protanomalous females possess a similar advantage in breaking camouflage. here, we introduce an animal model of dichromatic macaque ...202031066374
sym021, a promising anti-pd1 clinical candidate antibody derived from a new chicken antibody discovery platform.discovery of therapeutic antibodies is a field of intense development, where immunization of rodents remains a major source of antibody candidates. however, high orthologue protein sequence homology between human and rodent species disfavors generation of antibodies against functionally conserved binding epitopes. chickens are phylogenetically distant from mammals. since chickens generate antibodies from a restricted set of germline genes, the possibility of adapting the symplex antibody discove ...202031046547
a normalization circuit underlying coding of spatial attention in primate lateral prefrontal cortex.lateral prefrontal cortex (lpfc) neurons signal the allocation of voluntary attention; however, the neural computations underlying this function remain unknown. to investigate this, we recorded from neuronal ensembles in the lpfc of two macaca fascicularis performing a visuospatial attention task. lpfc neural responses to a single stimulus were normalized when additional stimuli/distracters appeared across the visual field and were well-characterized by an averaging computation. deploying attent ...202031001577
a unique b cell epitope-based particulate vaccine shows effective suppression of hepatitis b surface antigen in mice.this study aimed to develop a novel therapeutic vaccine based on a unique b cell epitope and investigate its therapeutic potential against chronic hepatitis b (chb) in animal models.202030926653
evaluation of the toxicity and neurological effects of fulranumab in adult cynomolgus monkeys.fulranumab, an anti-human nerve growth factor antibody, was evaluated in a series of nonclinical toxicology studies. no treatment effects were observed in adolescent cynomolgus monkeys in standard design, repeat-dose toxicology studies of up to 6 months. adverse effects on the developing nervous system were observed in offspring of pregnant cynomolgus monkeys treated with fulranumab. subsequent studies including detailed morphologic investigations of the nervous system did reveal fulranumab-rela ...202030852923
preclinical modeling of exposure to a global marine bio-contaminant: effects of in utero domoic acid exposure on neonatal behavior and infant memory.domoic acid (da) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. prenatal da exposure occurs through the maternal consumption of contaminated shellfish/finfish. to better understand the fetal risks associated with da, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral da exposure. to this end, 32 adult female macaca fascicularis monkeys were orally dosed wit ...202030690118
effects of oral domoic acid exposure on maternal reproduction and infant birth characteristics in a preclinical nonhuman primate model.domoic acid (da) is a naturally-occurring excitotoxin, produced by marine algae, which can bioaccumulate in shellfish and finfish. the consumption of seafood contaminated with da is associated with gastrointestinal illness that, in the case of high da exposure, can evolve into a spectrum of responses ranging from agitation to hallucinations, memory loss, seizures and coma. because algal blooms that produce da are becoming more widespread and very little is known about the dangers of chronic, low ...202030615984
administration of recombinant fviia (rfviia) to concizumab-dosed monkeys is safe, and concizumab does not affect the potency of rfviia in hemophilic rabbits.essentials hemophilia patients on concizumab prophylaxis may need rfviia to treat breakthrough bleeds. effect and safety of concizumab + rfviia were tested in vitro and in vivo. concizumab + rfviia had no additive effects on bleeding in hemophilic rabbits. high steady-state levels of concizumab did not affect the safety of rfviia in cynomolgus monkeys. summary: background concizumab is a monoclonal antibody (mab) against tissue factor pathway inhibitor (tfpi), currently in clinical development a ...201930614620
lubricin/proteoglycan 4 detected in vocal folds of humans and five other mammals.lubricin/proteoglycan-4 (prg4) lubricates connective tissues such as joints and tendon sheaths, enabling them to better withstand shearing and frictional forces during motion. we wondered whether prg4 might play a role in phonation, as normal vocal folds withstand repetitive, high-velocity deformations remarkably well. as a first step, we tested whether prg4 is expressed in vocal folds.201930613972
the efficacy of poly-iclc against ebola-zaire virus (ebov) infection in mice and cynomolgus monkeys.the potential protection of poly-iclc (hiltonol®) a double stranded rna (dsrna) against ebov infection was assessed with prophylactic and therapeutic administration to wild type and tlr3-negative mice, and in non-human primates (nhps) by measuring ebol serum titers, survival extension, and serum liver and kidney function markers. various doses of aqueous and liposomal poly-iclc monotherapy provided robust protection in otherwise lethal murine ebov challenge models, when treatment is started on t ...201930611774
effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys.excess energy intake contributes to metabolic disorders. however, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys.201930611256
pain-related behavior and brain activation in cynomolgus macaques with naturally occurring endometriosis.can pain be objectively assessed in macaques with naturally occurring endometriosis?201930597044
regioselective hydroxylation of an antiarrhythmic drug, propafenone, mediated by rat liver cytochrome p450 2d2 differs from that catalyzed by human p450 2d6.1. propafenone, an antiarrhythmic drug, is a typical human cytochrome p450 (p450) 2d6 substrate used in preclinical studies. here, propafenone oxidation by mammalian liver microsomes was investigated in vitro. 2. liver microsomes from humans and marmosets preferentially mediated propafenone 5-hydroxylation, minipig, rat and mouse livers primarily mediated 4'-hydroxylation, but cynomolgus monkey and dog liver microsomes differently mediated n-despropylation. 3. quinine, ketoconazole or anti-p450 ...201930596462
[markers of hepatitis a in the monkeys of the adlers primate center.]hepatitis a is a widespread viral infection. the hav strains of "human" and "monkey" origin are similar in their morphological and antigenic properties, but differ genotypically.201932167690
transmission of a novel genotype of hepatitis e virus from bactrian camels to cynomolgus macaques.hepatitis e virus (hev) is zoonotic and a major cause of acute viral hepatitis worldwide. recently, we identified a novel hev genotype 8 (hev8) in bactrian camels in xinjiang, china. however, the epidemiology, pathogenicity, and zoonotic potential of hev8 are unclear. here, we present the prevalence of hev8 in china and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. fresh fecal and milk samples from bactrian camels collected from four provinces/regions in ch ...201930700602
quantitative contrast-enhanced ultrasound of renal perfusion: a technology for the assessment of early diabetic nephropathy in cynomolgus macaques with type 2 diabetes mellitus.the aim of this study was to investigate the effectiveness of contrast-enhanced ultrasound (ceus) in predicting early nephropathy in cynomolgus macaques with spontaneous type 2 diabetes mellitus (t2dm).201930694370
maa868, a novel fxi antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans.a large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. genetic and pharmacologic evidence in humans and animals suggests that reducing factor xi (fxi) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. we generated a fully human antibody (maa868) that binds the catalytic domain of both fxi (zymogen) and activated fxi ...201930692123
intranodal angiomyomatous hamartoma in a cynomolgus monkey.we describe here an angiomyomatous hamartoma in the right axillary lymph node of a three-year-old male cynomolgus monkey ( macaca fascicularis), used as a control subject in a short-term toxicity study. this is a very rare lesion that has been reported almost exclusively in inguinal lymph nodes, and to date only in human beings. in the present case, light microscopy revealed partial replacement of the lymph node parenchyma by a disorganized, irregular vascular network, sparsely distributed smoot ...201930585127
effects of housing conditions on behaviors and biochemical parameters in juvenile cynomolgus monkeys (macaca fascicularis).to investigate the effects of environmental enrichment on laboratory monkeys, we studied behavioral and physiological differences following changes in housing conditions. ten male and female juvenile cynomolgus monkeys were first housed in pairs for 8 weeks after quarantine/acclimatization (singly housed) and subsequently housed alone for the next 8 weeks. monkeys were subjected to evaluations of body weight gain, stereotypic or affiliative behaviors, cortisol, 4-ethylphenyl sulfate (4eps) and c ...201930584201
intact bioactivities and improved pharmacokinetic of the sl335-ifn-β-1a fusion protein that created by genetic fusion of sl335, a human anti-serum albumin fab, and human interferon-β.recombinant human interferon beta (rifn-β) has long been used as a first-line treatment for multiple sclerosis (ms), and any attempt to develop a long-acting rifn-β is desirable since only one pegylated version of long-acting rifn-β-1a (plegridy) is currently available in clinics. previously, we reported that sl335, a human fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the fcrn recycling mechanism. with the ultimate goal of developing a long-acting ri ...201930684504
multimodal imaging of the retina and choroid in healthy macaca fascicularis at different ages.the aim of this study was to identify the morphological features of the retina and choroid in macaca fascicularis of different ages using multimodal imaging.201930684011
predicting organ carotenoids levels from analysis of plasma could lead to errors: a study in cynomolgus monkeys.carotenoids are phytochemicals with strong antioxidant activity against reactive oxygen species that are widely distributed in fruits and vegetables. the beneficial effects of carotenoids on human health have attracted considerable attention. the plasma carotenoid profile in humans is generally recognized to reflect the dietary carotenoid composition. although carotenoid profile in plasma is believed to correlate well with that in other tissues, the data for tissue accumulation of carotenoids in ...201930683442
the molecular biology and hpv drug responsiveness of cynomolgus macaque papillomaviruses support their use in the development of a relevant in vivo model for antiviral drug testing.due to the extreme tissue and species restriction of the papillomaviruses (pvs), there is a great need for animal models that accurately mimic pv infection in humans for testing therapeutic strategies against human papillomaviruses (hpvs). in this study, we present data that demonstrate that in terms of gene expression during initial viral dna amplification, macaca fascicularis pv (mfpv) types 5 and 8 appear to be similar to mucosal oncogenic hpvs, while mfpv1 (isolated from skin) resembles most ...201930682126
discovery and characterization of potent il-21 neutralizing antibodies via a novel alternating antigen immunization and humanization strategy.interleukin-21 (il-21), a member of the common cytokine receptor γ chain (γc) family, is secreted by cd4+ t cells and natural killer t cells and induces effector function through interactions with the il-21 receptor (il-21r)/γc complex expressed on both immune and non-immune cells. numerous studies suggest that il-21 plays a significant role in autoimmune disorders. therapeutic intervention to disrupt the il-21/il-21r/γc interaction and inhibit subsequent downstream signal transduction could off ...201930682117
steroid-free immune suppression impairs glycemic control in a healthy cynomolgus monkey.the need for chronic immune suppression (is) is one of the hurdles precluding widespread use of islet cell transplantation to restore glycemic control in patients with type 1 diabetes. we report the case of a healthy nonhuman primate (nhp) treated on and off for over 2.5 years with steroid-free is, consisting of daclizumab induction and maintenance therapy with rapamycin and low dose tacrolimus. treatment for 1 year resulted in a striking destabilization of glycemic control, with concomitant dec ...201930675800
in vitro monocyte/macrophage phagocytosis assay for the prediction of drug-induced thrombocytopenia.phagocytosis of platelets by monocytes and macrophages is a primary mechanism of platelet clearance in vivo and has been increasingly implicated in playing an important role in thrombocytopenia mediated by monoclonal antibodies intended for therapeutic purposes. in the present article, we describe an in vitro flow cytometry assay to assess the effect of antibody-mediated platelet phagocytosis by monocytes. freshly isolated platelets were labeled with a fluorescent probe, 5-chloromethylfluorescei ...201930673165
fetoscopic versus ultrasound-guided intravascular delivery of maternal bone marrow cells in fetal macaques: a technical model for intrauterine haemopoietic cell transplantation.significant limitations with existing treatments for major haemoglobinopathies motivate the development of effective intrauterine therapy. we assessed the feasibility of fetoscopic and ultrasound-guided intrauterine haemopoietic cell transplantation (iuhct) in macaque fetuses in early gestation when haemopoietic and immunological ontogeny is anticipated to enable long-term donor cell engraftment.201930661073
homologous recombination-mediated targeted integration in monkey embryos using tale nucleases.non-human primate (nhp) models can closely mimic human physiological functions and are therefore highly valuable in biomedical research. genome editing is now developing rapidly due to the precision and efficiency offered by engineered site-specific endonuclease-based systems, such as transcription activator-like effector nucleases (talens) and the clustered regularly interspaced short palindromic repeats (crispr)/crispr-associated protein-9 nuclease (cas9) system. it has been demonstrated that ...201930646876
histopathological findings in cynomolgus macaques ( macaca fascicularis) consistent with secondary immunological reaction to biotherapeutics with an emphasis on the cns and eye.biotherapeutics are pharmaceutical products derived from or synthesized by biological systems. such molecules carry the potential for immunogenicity which may lead to adverse immune responses. the cynomolgus macaque ( macaca fascicularis) is the species of choice in nonclinical safety assessment of biotherapeutics. the main aim of this study was to confirm whether mononuclear cell infiltrates at specific locations represent a generic effect of biotherapeutics, and therefore the result of their i ...201930636523
both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex.during development of the mammalian cerebral neocortex, postmitotic excitatory neurons migrate toward the outermost region of the neocortex. we previously reported that this outermost region is composed of densely packed relatively immature neurons; we named this region, which is observed during the late stage of mouse neocortical development, the "primitive cortical zone (pcz)." here, we report that postmigratory immature neurons spend about 1-1.5 days in the pcz. an electron microscopic analys ...201930636008
pharmacokinetic properties of arsenic species after intravenous and intragastrical administration of arsenic trioxide solution in cynomolgus macaques using hplc-icp-ms.a rapid and sensitive method was established for arsenic (as) speciation based on high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (hplc-icp-ms). this method was validated for the quantification of four arsenic species, including arsenite (asiii), arsenate (asv), monomethylarsonic acid (mmav) and dimethylarsinic acid (dmav) in cynomolgus macaque plasma. separation was achieved in just 3.7 min with an alkyl reverse phase column and highly aqueous mobi ...201930634677
the immunology of the macaque placenta: a detailed analysis and critical comparison with the human placenta.the cynomolgus monkey is increasingly considered in toxicological research as the most appropriate model for humans due to the species' close physiological contiguity, including reproductive physiology. here, literature on the cynomolgus monkey placenta is reviewed in regards to its similarity to the human placenta and particularly for its immunological role, which is not entirely mirrored in humans. pertinent original data are included in this article. the cynomolgus monkey placenta is evaluate ...201930632863
weekly teriparatide treatment increases vertebral body strength by improving cortical shell architecture in ovariectomized cynomolgus monkeys.weekly teriparatide treatment is reported to reduce the incidence of osteoporotic vertebral fractures. however, the effect of weekly teriparatide on cortical bone has not been clarified. this study aimed to examine the effects of weekly teriparatide treatment on bone mass, intracortical structure, and remodeling of the lumbar vertebral cortical shell and its relation to mechanical properties in ovariectomized cynomolgus monkeys. female monkeys, aged 9 to 15 years, were divided into four groups: ...201930630124
long-tailed macaques (macaca fascicularis) in urban landscapes: gastrointestinal parasitism and barriers for healthy coexistence in northeast thailand.gastrointestinal parasites have diverse life cycles that can involve people, animals, and the environment (e.g., water and soil), demonstrating the utility of one health frameworks in characterizing infection risk. kosumpee forest park (thailand) is home to a dense population of long-tailed macaques (macaca fascicularis) that frequently interact with tourists and local residents. our study investigated the presence of zoonotic parasites, and barriers to healthy coexistence by conducting stool an ...201930628564
genotype 5 hepatitis e virus produced by a reverse genetics system has the potential for zoonotic infection.neither an animal model nor a cell culture system has been established for the genotype 5 hepatitis e virus (g5 hev), and the pathogenicity, epidemiology, and replication mechanism of the virus remain unclear. in this study, we used a reverse genetics system to generate g5 hev and examined the possibility of zoonotic infection. capped and uncapped genomic g5 hev rnas generated by in vitro transcription were transfected into plc/prf/5 cells. infectious g5 hev was recovered from the capped g5 hev ...201930620002
defining the ecological and evolutionary drivers of plasmodium knowlesi transmission within a multi-scale framework.plasmodium knowlesi is a zoonotic malaria parasite normally residing in long-tailed and pig-tailed macaques (macaca fascicularis and macaca nemestrina, respectively) found throughout southeast asia. recently, knowlesi malaria has become the predominant malaria affecting humans in malaysian borneo, being responsible for approximately 70% of reported cases. largely as a result of anthropogenic land use changes in borneo, vectors which transmit the parasite, along with macaque hosts, are both now f ...201930849978
enhanced transduction of macaca fascicularis hematopoietic cells with chimeric lentiviral vectors.recent marketing approval for genetically engineered hematopoietic stem and t cells bears witness to the substantial improvements in lentiviral vectors over the last two decades, but evaluations of the long-term efficacy and toxicity of gene and cell therapy products will, nevertheless, require further studies in nonhuman primate models. macaca fascicularis monkeys from mauritius have a low genetic diversity and are particularly useful for reproducible drug testing. in particular, they have a ge ...201930848170
poor second ovarian stimulation in cynomolgus monkeys (macaca fascicularis) is associated with the production of antibodies against human follicle-stimulating hormone.cynomolgus monkeys (macaca fascicularis) are a valuable model organism for human disease modeling because human physiology and pathology are closer to those of cynomolgus monkeys than rodents. it has been widely reported that mature oocytes can be recovered from cynomolgus monkeys through ovarian stimulation by human follicle-stimulating hormone (hfsh). however, it is unknown whether mature oocytes can be effectively obtained through a second ovarian stimulation by hfsh. here, we report that som ...201930842351
effects of tanezumab on satellite glial cells in the cervicothoracic ganglion of cynomolgus monkeys: a 26-week toxicity study followed by an 8-week recovery period.tanezumab, a humanized monoclonal anti-ngf antibody, has demonstrated efficacy and safety profiles in phase iii clinical trials of chronic pain. in a 24-week study in non-human primates, morphological observations of sympathetic ganglia showed decreased ganglia volume, decreased neuronal size, and increased glial cell density compared with controls after 3 tanezumab treatments. using stereological techniques to quantify glial cells, the present 26-week study found no significant difference after ...201930890348
competition is crucial for social comparison processes in long-tailed macaques.humans modulate their self-evaluations and behaviour as a function of conspecific presence and performance. in this study, we tested for the presence of human-like social comparison effects in long-tailed macaques ( macaca fascicularis). the monkeys' task was to extract food from an apparatus by pulling drawers within reach and we measured latency between drawer pulls. subjects either worked on the task with a partner who could access the apparatus from an adjacent cage, worked in the absence of ...201930890067
an lc-ms/ms approach to assess total and free protein target in the serum of cynomolgus monkey.develop lc-ms/ms-based assays to measure total and free complement c5 in cynomolgus monkey serum as a target engagement biomarker for pharmacokinetic/pharmacodynamic correlation study. materials & methods/results: the c5-specific signature peptide derived from pellet digestion of serum proteins with and without prior immunodepletion of the drug-bound c5 by protein a beads was quantified to assess free and total c5 levels, respectively. conditions for immunodepletion by protein a were optimized t ...201930874444
therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate zt/g4-mmae targeting ron receptor tyrosine kinase for cancer therapy.aberrant expression of the ron receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. currently, therapeutic antibodies targeting ron for cancer therapy are under intensive evaluation. here we report the development and validation of a novel humanized anti-ron antibody-drug conjugate for cancer therapy.201930871619
comprehensive evaluation of ubiquitous promoters suitable for the generation of transgenic cynomolgus monkeys†.nonhuman primates (nhps) are considered to be the most valuable models for human transgenic (tg) research into disease because human pathology is more closely recapitulated in nhps than rodents. previous studies have reported the generation of tg nhps that ubiquitously overexpress a transgene using various promoters, but it is not yet clear which promoter is most suitable for the generation of nhps overexpressing a transgene ubiquitously and persistently in various tissues. to clarify this issue ...201930869744
safety and toxicology of ocular gene therapy with recombinant aav vector raav.hcnga3 in nonhuman primates.the purpose of this study was to examine the toxicity and side effects of a recombinant adeno-associated virus 8 (aav8) vector, aimed to treat cyclic nucleotide gated channel alpha 3 (cnga3)-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. both groups were divided into subgroups receiving either vehicle only, a low (1 × 1011 vector genomes (vg)), or a hi ...201930864850
tak-071, a muscarinic m1 receptor positive allosteric modulator, attenuates scopolamine-induced quantitative electroencephalogram power spectral changes in cynomolgus monkeys.activation of the muscarinic m1 receptor is a promising approach to improve cognitive deficits associated with cholinergic dysfunction in alzheimer's disease, dementia with lewy bodies, and schizophrenia. tak-071 is an m1-selective positive allosteric modulator that improves cognitive deficits induced by scopolamine, a non-selective muscarinic receptor antagonist, with reduced side effects on gastrointestinal function in rats. in this study, we explored changes in quantitative electroencephalogr ...201930856192
immunohistological study of monkey foveal retina.the fovea centralis, an anatomically concave pit located at the center of the macula, is avascular, hypoxic, and characteristic of stem-cell niches of other tissues. we hypothesized that in the fovea, undifferentiated retinal-stem-cell-like cells may exist, and that neurogenesis may occur. hence, we performed an immunohistological study using cynomolgus monkey retinas. after preparing frozen tissue sections of the retina including the foveal pit, immunostaining was performed for glial fibrillary ...201930918305
targeting multiple myeloma with amg 424, a novel anti-cd38/cd3 bispecific t-cell-recruiting antibody optimized for cytotoxicity and cytokine release.despite advances in the treatment of multiple myeloma, new therapies are needed to induce more profound clinical responses. t-cell-redirected lysis triggered by bispecific antibodies recruiting t cells to cancer cells is a clinically validated mechanism of action against hematologic malignancies and cd38 is a tumor-associated antigen with near-universal expression in multiple myeloma. thus, an anti-cd38/cd3 bispecific t-cell-recruiting antibody has the potential to be an effective new therapeuti ...201930918018
effects of the cathepsin k inhibitor ono-5334 and concomitant use of ono-5334 with methotrexate on collagen-induced arthritis in cynomolgus monkeys.we examined whether the cathepsin k inhibitor, ono-5334, administered alone or in combination with methotrexate (mtx), could ameliorate joint destruction evoked by collagen-induced arthritis (cia) in female cynomolgus monkeys. cia was induced by immunizing with bovine type ii collagen. ono-5334 (30 mg/kg/day) was orally administered once daily and mtx (10 mg/body/day) twice weekly for 9 weeks. x-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal ...201930906325
granulovacuolar degeneration in brains of senile cynomolgus monkeys.neurons with histopathological changes consistent with granulovacuolar degeneration (gvd) were found in brain sections from aged cynomolgus monkeys (macaca fascicularis) with clinical and pathological signs of cognitive aging. to our knowledge, this is the first reported description of gvd in non-human primates. gvd-like lesions were found also in age-matched cognitively healthy subjects, albeit in lower numbers, suggesting that they may relate to aging and the increase may have tendency to incr ...201930899220
toxicologic pathology forum*: opinion on sexual maturity and fertility assessment in long-tailed macaques ( macaca fascicularis) in nonclinical safety studies.if nonhuman primates represent the only relevant species for nonclinical safety evaluation of biotechnology-derived products, male and female fertility effects can be assessed in repeat dose toxicity studies given that sexually mature monkeys are used. this opinion piece provides recommendations for determining sexual maturity and when/how fertility assessments should be conducted in the cynomolgus monkey. male sexual maturity should be proven by presence of sperm in a semen sample, female sexua ...201930898082
phenotypic distinctions between the nodose and jugular trpv1-positive vagal sensory neurons in the cynomolgus monkey.vagal capsaicin-sensitive afferent c-fibers play an important role in the maintenance of visceral homeostasis and contribute to symptoms in visceral diseases. based on their developmental origin two functionally distinct types of vagal c-fibers are recognized: those with neurons in the vagal nodose ganglia (derived from epibranchial placodes) and in the vagal jugular ganglia (from neural crest). studies in nonprimate species demonstrated that the vagal nodose and jugular c-fibers differ in activ ...201930896676
functional and molecular characterization of udp-glucuronosyltransferase 2 family in cynomolgus macaques.udp-glucuronosyltransferases (ugts) are essential enzymes metabolizing endogenous and exogenous chemicals. however, characteristics of ugts have not been fully investigated in molecular levels of cynomolgus macaques, one of non-human primates widely used in preclinical drug metabolism studies. in this study, three ugt2a cdnas (ugt2a1, 2a2, and 2a3) were isolated and characterized along with seven ugt2bs previously identified in cynomolgus macaques. several transcript variants were found in cynom ...201930836059
differences in monocyte: lymphocyte ratio and tuberculosis disease progression in genetically distinct populations of macaques.monocyte:lymphocyte ratio (m:l) has been identified as a risk factor in development of tb disease in children and those undergoing treatment for hiv in co-infected individuals. retrospective analysis was performed using m:l data collected from tb modelling studies performed in rhesus macaques of indian genotype (rm), cynomolgus macaque of chinese genotype (ccm) and cynomolgus macaque of mauritian genotype (mcm), which found that the more susceptible populations (rm and mcm) had higher m:l ratios ...201930833652
chronic, low-level oral exposure to marine toxin, domoic acid, alters whole brain morphometry in nonhuman primates.domoic acid (da) is an excitatory neurotoxin produced by marine algae and responsible for amnesiac shellfish poisoning in humans. current regulatory limits (˜0.075-0.1 mg/kg/day) protect against acute toxicity, but recent studies suggest that the chronic consumption of da below the regulatory limit may produce subtle neurotoxicity in adults, including decrements in memory. as da-algal blooms are increasing in both severity and frequency, we sought to better understand the effects of chronic da e ...201930826346
correlation between genotypes and geographic distribution of entamoeba nuttalli isolates from wild long-tailed macaques in central thailand.entamoeba nuttalli found in non-human primates is the phylogenetically closest species to entamoeba histolytica and is potentially pathogenic. however, infection of wild long-tailed macaques (macaca fascicularis) with e. nuttalli has not been found. in this study, the prevalence of entamoeba infections in wild long-tailed macaques was examined in seven locations in six provinces of thailand. the positive rate for e. nuttalli in 214 fecal samples was 43.9% using pcr, but no infection with e. hist ...201930822548
preclinical safety evaluation of the adrenomedullin-binding antibody adrecizumab in rodents, dogs and non-human primates.adrenomedullin (adm) is a vasoactive peptide in sepsis. the non-neutralizing adm-binding antibody adrecizumab improved outcome in animal models of systemic inflammation and sepsis. herein, we evaluated the preclinical safety of adrecizumab in various animal species. first, wistar rats received vehicle, 100, 200 or 400 mg/kg/day of adrecizumab intravenously (n = 20 each) on days 1, 4, 8 and 14. an additional set of rats received vehicle or 400 mg/kg/day (n = 10 each) on the same days and were fol ...201930822437
distinguishing analgesic drugs from non-analgesic drugs based on brain activation in macaques with oxaliplatin-induced neuropathic pain.the antineoplastic agent oxaliplatin is a first-line treatment for colorectal cancer. however, neuropathic pain, characterized by hypersensitivity to cold, emerges soon after treatment. in severe instances, dose reduction or curtailing treatment may be necessary. while a number of potential treatments for oxaliplatin-induced neuropathic pain have been proposed based on preclinical findings, few have demonstrated efficacy in randomized, placebo-controlled clinical studies. this failure could be r ...201930817933
ionis-pkkrx a novel antisense inhibitor of prekallikrein and bradykinin production.kallikrein is the key contact system mediator responsible for the conversion of high-molecular-weight kininogen into the inflammatory vasodilator peptide bradykinin, a process regulated by c1-esterase inhibitor (c1-inh). in hereditary angioedema (hae), genetic mutations result in deficient or dysfunctional c1-inh and dysregulation of the contact system leading to recurrent, sometimes fatal, angioedema attacks. ionis-pkkrx is a second-generation 2'-o-(2-methoxyethyl)-modified chimeric antisense o ...201930817230
pharmacokinetics, tissue distribution, plasma protein binding, and metabolism study of mefunidone, a novel pirfenidone derivative.mefunidone (mfd), a novel derivation of pirfenidone (pfd), exhibits promising anti-renal fibrosis activity. to avoid early development failures and attrition in clinical phase 1, an evaluation of the preclinical pharmacokinetic (pk) properties of mfd was conducted in this study. the absolute bioavailability was evaluated in sprague dawley rats and cynomolgus monkeys, who received an intragastric or intravenous administration at the dose of 31.25 mg/kg and 10 mg/kg, respectively. tissue distribut ...201930815895
paromomycin sulfate is an effective treatment for balantidiasis in captive cynomolgus monkeys.there are few effective antimicrobial agents against balantidium coli infection. the effect of paromomycin sulfate (ps) against b. coli was confirmed in this study of 596 captive cynomolgus monkeys. in several trials, the minimum dose and duration of oral administration of ps were 25 mg/day for 5 + 5 days, with a 2-day withdrawal interval. to facilitate daily ps administration, pumpkin cakes supplemented with ps were made, which not only resulted in precise effects but also increased the efficie ...201930814394
synthesis and evaluation of two new candidate high-affinity full agonist pet radioligands for imaging 5-ht1b receptors.the serotonin 1b receptor subtype is of interest in the pathophysiology and treatment of depression, anxiety, and migraine. over recent years 5-ht1b receptor binding in human brain has been examined with pet using radioligands that are partial but not full agonists. to explore how the intrinsic activity of a pet radioligand may affect imaging performance, two high-affinity full 5-ht1b receptor agonists (az11136118, 4; and az11895987, 5) were selected from a large compound library and radiolabele ...201930811975
characterization of intrathecal cerebrospinal fluid geometry and dynamics in cynomolgus monkeys (macaca fascicularis) by magnetic resonance imaging.recent advancements have been made toward understanding the diagnostic and therapeutic potential of cerebrospinal fluid (csf) and related hydrodynamics. increased understanding of csf dynamics may lead to improved detection of central nervous system (cns) diseases and optimized delivery of csf based cns therapeutics, with many proposed therapeutics hoping to successfully treat or cure debilitating neurological conditions. before significant strides can be made toward the research and development ...201930811449
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