Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| vp1 amino acid residue 145 of enterovirus 71 is a key residue for its receptor attachment and resistance to neutralizing antibody during cynomolgus monkey infection. | enterovirus 71 (ev71) is a causative agent of hand, foot, and mouth disease and sometimes causes severe or fatal neurological complications. the amino acid at vp1-145 determines the virological characteristics of ev71. viruses with glutamic acid (e) at vp1-145 (vp1-145e) are virulent in neonatal mice and transgenic mice expressing human scavenger receptor b2, whereas those with glutamine (q) or glycine (g) are not. however, the contribution of this variation to pathogenesis in humans is not full ... | 2018 | 29848582 |
| investigation into the mechanism(s) that leads to platelet decreases in cynomolgus monkeys during administration of isis 104838, a 2'-moe-modified antisense oligonucleotide. | isis 104838, a 2'-o-methoxyethyl (2'-moe)-modified antisense oligonucleotide (aso), causes a moderate, reproducible, dose-dependent, but selflimiting decrease in platelet (plt) counts in monkeys and humans. to determine the etiology of plt decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of isis 104838 (30-60 mg/kg/week). monkeys were also injected intravenously with 111indium(in)-oxine-labeled plts to investigate plt se ... | 2018 | 29846725 |
| superparamagnetic iron oxide-enhanced magnetic resonance imaging of spontaneous hepatic neoplasia in a cynomolgus macaque (macaca fascicularis). | although the number of reports describing tumors in aged nhp has increased, spontaneous neoplasias in nhp are extremely rare, with the notable exception of prosimians, in which spontaneous hepatic neoplasms arise. in addition to radiography and ultrasonography, superparamagnetic iron oxide (spio)-enhanced mri tends to be applied in human practice to non-invasively locate, identify, and size liver tumors and to define the border between neoplastic and normal tissues. here we report a 13-y-old fem ... | 2018 | 29843863 |
| performance assessment of new urinary translational safety biomarkers of drug-induced renal tubular injury in tenofovir-treated cynomolgus monkeys and beagle dogs. | newer urinary protein kidney safety biomarkers can outperform the conventional kidney functional biomarkers blood urea nitrogen (bun) and serum creatinine (scr) in rats. however, there is far less experience with the relative performance of these biomarkers in dogs and nonhuman primates. here, we report urine protein biomarker performance in tenofovir-treated cynomolgus monkeys and beagle dogs. tenofovir intravenous daily dosing in monkeys for 2 or 4 weeks at 30 mg/kg/day resulted in minimal to ... | 2018 | 29807506 |
| nonclinical safety and pharmacokinetics of miglyol 812: a medium chain triglyceride in exenatide once weekly suspension. | exenatide, a glucagon-like peptide-1 receptor agonist was originally developed as either a twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. exenatide qw suspension was developed for use with an autoinjector device, in which the microspheres are suspended in miglyol 812, a mixture of medium chain triglycerides (mcts). mcts are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or mcfas). while mcts are edible ... | 2018 | 29806696 |
| disposition and metabolism of [14c]lemborexant, a novel dual orexin receptor antagonist, in rats and monkeys. | the disposition and metabolism of lemborexant, a novel dual orexin receptor antagonist currently under development as a therapeutic agent for insomnia disorder, were evaluated after a single oral administration of [14c]lemborexant in sprague-dawley rats (10 mg/kg) and cynomolgus monkeys (3 mg/kg). in both species, [14c]lemborexant was rapidly absorbed: radioactivity concentration in blood peaked at 0.83-1.8 h, and decreased with elimination half-life of 110 h. the radioactivity administered was ... | 2019 | 29806508 |
| unprecedented symbiont eukaryote diversity is governed by internal trophic webs in a wild non-human primate. | research on host-associated microbiomes has highlighted major divisions between the role of eukaryotes in free-living and symbiont systems. these trends call into question the relevance of macroecological processes to host-associated systems and the relative importance of parasitism, commensalism, and mutualism as evolutionary patterns across the domains of life. however, it is unclear as to whether these apparent differences reflect biological realities or methodologies in community characteriz ... | 2018 | 29803114 |
| effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome. | methamphetamine (ma), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. the cellular and molecular mechanisms associated with hippocampal impairments due to ma remain unknown. the aim of this study was to investigate the effects of ma on structural alterations and gene expressions in the hippocampus. we analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imagi ... | 2018 | 29802913 |
| engineered fcrn binding fusion peptides significantly enhance the half-life of a fab domain in cynomolgus monkeys. | there is a rapidly growing reinvigoration of the investigation of small proteins, cyclic peptides, and mab derived domains as biotherapies. the drugability of these structures are challenged by fast peripheral clearance properties that can reduce their potential to be realized as medicines. engineering strategies have been of limited value because mechanistically the half-life benefit is manifested by increasing the molecular weight and/or the hydrodyanimc radius which slows the molecule's renal ... | 2019 | 29802766 |
| peripheral defocus of the monkey crystalline lens with accommodation in a lens stretcher. | to characterize the peripheral defocus of the monkey crystalline lens and its changes with accommodation. | 2018 | 29801154 |
| a macaca fascicularis knee osteoarthritis model developed by modified hulth combined with joint scratches. | background osteoarthritis is a common degenerative disease of joints, and animal models have important significance in the investigation of this disease. the aim of this study was to develop a better method for developing osteoarthritis models in primates by comparing the modified hulth score combined with joint scratches modeling method with others. material and methods we randomly divided 15 young male macaca fascicularis and 3 old male macaca fascicularis into 6 groups (n=3). knee osteoarthri ... | 2018 | 29789519 |
| [experimental study on lentivirus-mediated multi-genes co-transfection in bone marrow mesenchymal stem cells for treatment of knee osteoarthritis in cynomolgus monkey]. | to observe the effect of lentivirus-mediated cyclooxygenase 2 (cox-2) and aggrecanase-1 silencing and insulin-like growth factor 1 (igf-1) in bmscs after injecting into the knee joint cavity in cynomolgus monkeys with knee osteoarthritis (oa). | 2016 | 29786374 |
| methylprednisolone inhibits the proliferation of endogenous neural stem cells in nonhuman primates with spinal cord injury. | objective the aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (enscs) in nonhuman primates with spinal cord injury (sci). methods a total of 14 healthy cynomolgus monkeys ( macaca fascicularis) (4-5 years of age) were randomly divided into 3 groups: the control group (n = 6), sci group (n = 6), and methylprednisolone therapy group (n = 2). only laminectomy was performed in the control animals at t-10. sci was induced in m ... | 2018 | 29775163 |
| discovery of a novel il-15 based protein with improved developability and efficacy for cancer immunotherapy. | interleukin-15 (il-15) can promote both innate and adaptive immune reactions by stimulating cd8+/cd4+ t cells and natural killer cells (nk) while showing no effect in activating t-regulatory (treg) cells or inducing activation-associated death among effector t cells and nk cells. thus, il-15 is considered as one of the most promising molecules for antitumor immune therapy. to improve the drug-like properties of natural il-15, we create an il-15-based molecule, named p22339, with the following ch ... | 2018 | 29769573 |
| effects of monoclonal antibodies against nerve growth factor on healthy bone and joint tissues in mice, rats, and monkeys: histopathologic, biomarker, and microcomputed tomographic assessments. | tanezumab, an anti-nerve growth factor (ngf) antibody, is in development for management of chronic pain. during clinical trials of anti-ngf antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all ngf inhibitors. three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor mumab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, spragu ... | 2018 | 29768985 |
| pain-related behavior and brain activation in a cynomolgus macaque model of postoperative pain. | inadequate postoperative pain management could lead to persistent pain and this is, in part, due to incomplete understanding of the mechanism of postoperative pain. currently available rodent models may have limited translatability to clinical postoperative pain. thus, a preclinical model of postoperative pain was developed in the cynomolgus macaque, a species that is phylogenetically closer to humans than rodents. | 2018 | 29766827 |
| are monkeys intuitive aristotelians? associations between target size and vertical target position in long-tailed macaques. | different hypotheses have been put forward to explain the interaction between size perception and spatial position. to explore the evolutionary roots of these phenomena, we tested long-tailed macaques' performance in a two-choice discrimination task on a touchscreen and contrasted two hypotheses. first, a hierarchy association in which large objects are associated with top positions, due to a link between power, dominance and importance with top position. second, a naive aristotelian association ... | 2018 | 29765622 |
| cochlear implant electrode array from partial to full insertion in non-human primate model. | to determine the feasibility of progressive insertion (two sequential surgeries: partial to full insertion) of an electrode array and to compare functional outcomes. | 2018 | 29764773 |
| prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (adc) when evaluation of higher doses in animals is limited by tolerability: case study with an anti-cd33 adc. | for antibody-drug conjugates (adcs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. for molecules with non-linear pharmacokinetics (pk), this limited dose range may be insufficient to fully characterize the pk of the adc and limits translation to humans. mathematical pk models are frequently used for molecule selection during preclinical drug development and for translatio ... | 2018 | 29757698 |
| metabolism of an oxime-linked antibody drug conjugate, ags62p1, and characterization of its identified metabolite. | ags62p1 is an antibody drug conjugate (adc) composed of a human igg1κ monoclonal antibody against flt3 (fms-like tyrosine kinase 3) with a p-acetyl phenylalanine (paf) residue inserted at position 124 of each heavy chain linked to the proprietary microtubule disrupting agent agl-0182-30 via an alkoxyamine linker that forms an oxime upon conjugation to the antibody. ags62p1 is currently in phase i human clinical trials for acute myelogenous leukemia (aml). the identified primary metabolite of an ... | 2018 | 29757653 |
| regulated intratumoral expression of il-12 using a rheoswitch therapeutic system® (rts®) gene switch as gene therapy for the treatment of glioma. | the purpose of this study was to determine if localized delivery of il-12 encoded by a replication-incompetent adenoviral vector engineered to express il-12 via a rheoswitch therapeutic system® (rts®) gene switch (ad-rts-il-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. mice bearing 5-10-day-old intracranial gl-261 gliomas were intratumorally administered ad-rts-mil-12 in which il-12 protein expression is ... | 2018 | 29755109 |
| discovery of benzimidazole derivatives as orally active renin inhibitors: optimization of 3,5-disubstituted piperidine to improve pharmacokinetic profile. | we previously identified 2-tert-butyl-4-[(3-methoxypropyl)amino]-n-(2-methylpropyl)-n-[(3s,5r)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]pyrimidine-5-carboxamide 3 as a potent renin inhibitor. since 3 showed unacceptably low bioavailability (ba) in rats, structural modification, using sbdd and focused on physicochemical properties was conducted to improve its pk profile while maintaining renin inhibitory activity. conversion of the amino group attached at the 4-position of pyrimidine to methylene ... | 2018 | 29754833 |
| young macaques (macaca fascicularis) preferentially bias attention towards closer, older, and better tool users. | examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. we studied a population of macaques on koram island, thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. we first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity ... | 2018 | 29754253 |
| persistence of vertebral growth plate cartilage in aged cynomolgus monkeys. | growth plates at each end of vertebral bodies play a pivotal role in longitudinal spinal growth. epiphyseal closures are formed in adult humans. although monkeys are frequently employed in bone and disc research, the age of epiphyseal closure has not been well documented. in this study, histological analyses of lumbar vertebral end plates and the surrounding tissue were performed in 11 normal cynomolgus monkeys aged approximately 9 to 15 years, and unclosed growth plate cartilage was detected in ... | 2018 | 29750005 |
| testicular microlithiasis in a clinically healthy cynomolgus monkey (macaca fascicularis). | the present article describes an occurrence of testicular microlithiasis in a cynomolgus monkey from a routine regulatory toxicology study. the monkey was from a negative control group. microscopically, the lesion was characterized by multiple extracellular mineralized calculi within seminiferous tubular epithelia of both testes without any tissue reaction or abnormal condition such as cryptorchidism, testicular neoplasm, or hypogonadism. the present case is remarkable in that there is a paucity ... | 2018 | 29750004 |
| a novel neural prosthesis providing long-term electrocorticography recording and cortical stimulation for epilepsy and brain-computer interface. | objectivewireless technology is a novel tool for the transmission of cortical signals. wireless electrocorticography (ecog) aims to improve the safety and diagnostic gain of procedures requiring invasive localization of seizure foci and also to provide long-term recording of brain activity for brain-computer interfaces (bcis). however, no wireless devices aimed at these clinical applications are currently available. the authors present the application of a fully implantable and externally rechar ... | 2018 | 29749917 |
| chitinase mrna levels determined by qpcr in crab-eating monkey (macaca fascicularis) tissues: species-specific expression of acidic mammalian chitinase and chitotriosidase. | mice and humans express two active chitinases: acidic mammalian chitinase (amcase) and chitotriosidase (chit1). both chitinases are thought to play important roles in specific pathophysiological conditions. the crab-eating monkey (macaca fascicularis) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chai ... | 2018 | 29747453 |
| hepatic histopathological changes and dysfunction in primates following exposure to organic arsenic diphenylarsinic acid. | organic arsenic diphenylarsinic acid (dpaa[v]) accumulates at high concentrations in the liver of primates after its subchronic administration. however, no studies on the hepatic effects of organic arsenic compounds, including dpaa(v), on primates have been reported to date. to clarify the toxicokinetics of dpaa(v) in the liver of primates, hepatic tissue specimens were collected from cynomolgus monkeys (n = 32) at 5, 29, 170, and 339 days after repeated administration of dpaa(v) for 28 days. fo ... | 2018 | 29743440 |
| nonclinical and clinical pharmacological characterization of the potent and selective cathepsin k inhibitor miv-711. | cathepsin k is an attractive therapeutic target for diseases in which bone resorption is excessive such as osteoporosis and osteoarthritis (oa). the current paper characterized the pharmacological profile of the potent and selective cathepsin k inhibitor, miv-711, in vitro and in cynomolgus monkeys, and assessed translation to human based on a single dose clinical study in man. | 2018 | 29743078 |
| efficient generation of cynomolgus monkey induced pluripotent stem cell-derived intestinal organoids with pharmacokinetic functions. | in preclinical studies, the cynomolgus monkey (cm) model is frequently used to predict the pharmacokinetics of drugs in the human small intestine, because of its evolutionary closeness to humans. intestinal organoids that mimic the intestinal tissue have attracted attention in regenerative medicine and drug development. in this study, we generated intestinal organoids from cm induced pluripotent stem (cmips) cells and analyzed their pharmacokinetic functions. cmips cells were induced into the hi ... | 2018 | 29742964 |
| safety of intra-articular transplantation of lentivirally transduced mesenchymal stromal cells for haemophilic arthropathy in a non-human primate. | joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. we previously developed a mesenchymal stromal cell (msc)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia a. here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous mscs in non-human primates. autologous bone-marrow-derived mscs transduced with a lentiviral vector expressing coagulation factor viii (fvii ... | 2018 | 29737459 |
| seven years of experiences of preclinical experiments of xeno-heart transplantation of pig to non-human primate (cynomolgus monkey). | the absolute shortage of donors compared with patients requiring transplantation is currently an unsolved problem, and the only possible solution may be xenotransplantation. to establish a successful clinical trial, a preclinical study using nonhuman primates is essential. starting in november 2011, our team initiated heterotopic abdominal heart xenotransplantation, the first in the republic of korea. we present here the initial 7-year results. | 2018 | 29731087 |
| a big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans. | although lack of efficacy is an important cause of late stage attrition in drug development the shortcomings in the translation of toxicities observed during the preclinical development to observations in clinical trials or post-approval is an ongoing topic of research. the concordance between preclinical and clinical safety observations has been analyzed only on relatively small data sets, mostly over short time periods of drug approvals. we therefore explored the feasibility of a big-data anal ... | 2018 | 29730448 |
| translational pk-pd modeling analysis of mcla-128, a her2/her3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose. | introduction mcla-128 is a bispecific monoclonal antibody targeting the her2 and her3 receptors. pharmacokinetics (pk) and pharmacodynamics (pd) of mcla-128 have been evaluated in preclinical studies in cynomolgus monkeys and mice. the aim of this study was to characterize the pk and pd of mcla-128 and to predict a safe starting dose and efficacious clinical dose for the first-in-human study. methods a pk-pd model was developed based on pk data from cynomolgus monkeys and tumor growth data from ... | 2018 | 29728897 |
| species-specific involvement of integrin αiibβ3 in a monoclonal antibody ch12 triggers off-target thrombocytopenia in cynomolgus monkeys. | ch12 is a novel humanized monoclonal antibody against epidermal growth factor receptor variant iii (egfrviii) for cancer treatment. unfortunately, in pre-clinical safety evaluation studies, acute thrombocytopenia was observed after administration of ch12 in cynomolgus monkeys, but not rats. more importantly, in vitro experiments found that ch12 can bind and activate platelets in cynomolgus monkey, but not human peripheral blood samples. cynomolgus monkey-specific thrombocytopenia has been report ... | 2018 | 29724685 |
| fc engineering of anti-nectin-2 antibody improved thrombocytopenic adverse event in monkey. | nectin-2 is a transmembrane glycoprotein which is involved in the process of ca2+-independent cell-cell adhesion. in our previous study, we have demonstrated that nectin-2 is over-expressed in breast and ovarian cancer tissues by using gene expression analysis and immunohistochemistry. furthermore, we discovered multiple anti-nectin-2 fully human monoclonal antibodies which inhibited tumor growth in in vivo subcutaneous xenograft models with antibody-dependent cellular cytotoxicity (adcc) as the ... | 2018 | 29723247 |
| seminal simian immunodeficiency virus in chronically infected cynomolgus macaques is dominated by virus originating from multiple genital organs. | the sexual transmission of viruses is responsible for the spread of multiple infectious diseases. although the human immunodeficiency virus (hiv)/aids pandemic remains fueled by sexual contacts with infected semen, the origin of virus in semen is still unknown. in a substantial number of hiv-infected men, viral strains present in semen differ from the ones in blood, suggesting that hiv is locally produced within the genital tract. such local production may be responsible for the persistence of h ... | 2018 | 29720516 |
| molecular mechanisms for species differences in organic anion transporter 1, oat1: implications for renal drug toxicity. | species differences in renal drug transporters continue to plague drug development with animal models failing to adequately predict renal drug toxicity. for example, adefovir, a renally excreted antiviral drug, failed clinical studies for human immunodeficiency virus due to pronounced nephrotoxicity in humans. in this study, we demonstrated that there are large species differences in the kinetics of interactions of a key class of antiviral drugs, acyclic nucleoside phosphonates (anps), with orga ... | 2018 | 29720497 |
| predicting human clearance of organic anion transporting polypeptide substrates using cynomolgus monkey: in vitro-in vivo scaling of hepatic uptake clearance. | this work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (oatp) transporters. nine oatp substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan, and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence ... | 2018 | 29720472 |
| effect of ex vivo-expanded recipient regulatory t cells on hematopoietic chimerism and kidney allograft tolerance across mhc barriers in cynomolgus macaques: erratum. | 2018 | 29702539 | |
| collection and culture of primordial germ cells from cynomolgus monkeys (macaca fascicularis). | aim: to clarify the location of primordial germ cells (pgc) in an embryo of target-age and to examine the culture environment of the pcg. methods: the days of ovulation and fertilization were estimated by measuring the serum concentration of estrogen. pregnancy was confirmed by measurement of the serum concentration of the beta subunit of macaque chorionic gonadotropin and by ultrasonography. we also examined the location of pgc in the embryo at the time of retrieval. results: results showed ... | 2007 | 29699279 |
| polymeric nano-shielded islets with heparin-polyethylene glycol in a non-human primate model. | intraportal pancreatic islet transplantation incurs huge cell losses during its early stages due to instant blood-mediated inflammatory reactions (ibmirs), which may also drive regulation of the adaptive immune system. therefore, a method that evades ibmir will improve clinical islet transplantation. we used a layer-by-layer approach to shield non-human primate (nhp) islets with polyethylene glycol (nano-shielded islets, nsis) and polyethylene glycol plus heparin (heparin nano-shielded islets; h ... | 2018 | 29698867 |
| lack of transmission of chronic wasting disease to cynomolgus macaques. | chronic wasting disease (cwd) is a fatal prion disease that can infect deer, elk, and moose. cwd was first recognized in captive deer kept in wildlife facilities in colorado from 1967 to 1979. cwd has now been detected in 25 u.s. states, 2 canadian provinces, south korea, norway, and finland. it is currently unknown if humans are susceptible to cwd infection. understanding the health risk from consuming meat and/or products from cwd-infected cervids is a critical human health concern. previous r ... | 2018 | 29695429 |
| virus-encoded mirnas in ebola virus disease. | ebola virus (ebov) is a negative-strand rna virus that replicates in the cytoplasm and causes an often-fatal hemorrhagic fever. ebov, like other viruses, can reportedly encode its own micrornas (mirnas) to subvert host immune defenses. mirnas are short noncoding rnas that can regulate gene expression by hybridizing to multiple mrnas, and viral mirnas can enhance viral replication and infectivity by regulating host or viral genes. to date, only one ebov mirna has been examined in human infection. ... | 2018 | 29691416 |
| lack of human-like extracellular sortilin neuropathology in transgenic alzheimer's disease model mice and macaques. | alzheimer's disease (ad) is a devastating neurodegenerative disorder bearing multiple pathological hallmarks suggestive of complex cellular/molecular interplay during pathogenesis. transgenic mice and nonhuman primates are used as disease models for mechanistic and translational research into ad; the extent to which these animal models recapitulate ad-type neuropathology is an issue of importance. putative c-terminal fragments from sortilin, a member of the vacuolar protein sorting 10 protein (v ... | 2018 | 29690919 |
| spontaneous endometriosis in cynomolgus monkeys as a clinically relevant experimental model. | does spontaneous endometriosis in cynomolgus monkeys have the characteristics required of a good experimental model? | 2018 | 29684118 |
| activation of liver ampk with pf-06409577 corrects nafld and lowers cholesterol in rodent and primate preclinical models. | dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (nash). therapeutic activators of the amp-activated protein kinase (ampk) have been proposed as a treatment for metabolic diseases; we show that the ampk β1-biased activator pf-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclini ... | 2018 | 29673898 |
| nonclinical comparability studies of recombinant human arylsulfatase a addressing manufacturing process changes. | recombinant human arylsulfatase a (rhasa) is in clinical development for the treatment of patients with metachromatic leukodystrophy (mld). manufacturing process changes were introduced to improve robustness and efficiency, resulting in higher levels of mannose-6-phosphate and sialic acid in post-change (process b) compared with pre-change (process a) rhasa. a nonclinical comparability program was conducted to compare process a and process b rhasa. all doses were administered intrathecally. phar ... | 2018 | 29672630 |
| inhibition of sperm motility in male macaques with ep055, a potential non-hormonal male contraceptive. | men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. new male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. one particular target is the sperm protein eppin, which is present on the surface of human spermatozoa. ep055 is a small organic compound that targets eppin on the surface of sperm and inhibits motility. ep055 was tested in ... | 2018 | 29672554 |
| the cynomolgus macaque natural history model of pneumonic tularemia for predicting clinical efficacy under the animal rule. | francisella tularensis is a highly infectious gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a tier 1 select agent. the natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (mcm) in human populations. development and licensure of tularemia therapeutics and vaccines need to occur under the food and drug administration's (fda's) animal rule ... | 2018 | 29670861 |
| successful application of human-based methyl capture sequencing for methylome analysis in non-human primate models. | the characterization of genomic or epigenomic variation in human and animal models could provide important insight into pathophysiological mechanisms of various diseases, and lead to new developments in disease diagnosis and clinical intervention. the african green monkey (agm; chlorocebus aethiops) and cynomolgus monkey (cm; macaca fascicularis) have long been considered important animal models in biomedical research. however, non-human primate-specific methods applicable to epigenomic analyses ... | 2018 | 29669513 |
| investigation of the mechanism of therapeutic protein-drug interaction between methotrexate and golimumab, an anti-tnfα monoclonal antibody. | a prominent example of human therapeutic protein-drug interaction (tp-di) is between methotrexate (mtx) and anti-tnfα mabs. one plausible mechanism for this tp-di is through the pharmacodynamic effect of mtx on immunogenicity. however, there is no definitive evidence to substantiate this mechanism, and other competing hypotheses, such as mtx suppressing fcγri expression thereby affecting mab pk, have also been proposed. in order to understand this mechanism, a cynomolgus monkey study was conduct ... | 2018 | 29667047 |
| questioning the extreme neurovirulence of monkey b virus (macacine alphaherpesvirus 1). | monkey b virus (macacine alphaherpesvirus 1; bv) occurs naturally in macaques of the genus macaca, which includes rhesus and long-tailed (cynomolgus) monkeys that are widely used in biomedical research. bv is closely related to the human herpes simplex viruses (hsv), and bv infections in its natural macaque host are quite similar to hsv infections in humans. zoonotic bv is extremely rare, having been diagnosed in only a handful of north american facilities with the last documented case occurring ... | 2018 | 29666644 |
| review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by fda in 2016 and 2017. | details of embryo-fetal development (efd) studies were compiled for all fda drug approvals in 2016-17. rats and rabbits were used for 63% of small molecule (sm) drugs. the cynomolgus monkey was used for 47% of biopharmaceuticals. rodent studies using the clinical mab or animal homologue replaced monkey studies under some circumstances. efd studies were not required for anti-cancer drugs when the mode of action was associated with known developmental risk. one quarter of sm non-oncology drugs and ... | 2018 | 29660390 |
| analysis of wild macaque stone tools used to crack oil palm nuts. | the discovery of oil palm (elaeis guineensis) nut-cracking by wild long-tailed macaques (macaca fascicularis) is significant for the study of non-human primate and hominin percussive behaviour. up until now, only west african chimpanzees (pan troglodytes verus) and modern human populations were known to use stone hammers to crack open this particular hard-shelled palm nut. the addition of non-habituated, wild macaques increases our comparative dataset of primate lithic percussive behaviour focus ... | 2018 | 29657792 |
| transplantation of neural progenitor cells expressing glial cell line-derived neurotrophic factor into the motor cortex as a strategy to treat amyotrophic lateral sclerosis. | early dysfunction of cortical motor neurons may underlie the initiation of amyotrophic lateral sclerosis (als). as such, the cortex represents a critical area of als research and a promising therapeutic target. in the current study, human cortical-derived neural progenitor cells engineered to secrete glial cell line-derived neurotrophic factor (gdnf) were transplanted into the sod1g93a als rat cortex, where they migrated, matured into astrocytes, and released gdnf. this protected motor neurons, ... | 2018 | 29656478 |
| importance of cynomolgus monkeys in development of monoclonal antibody drugs. | animal species used in the preclinical studies for development of monoclonal antibody (mab) drugs are surveyed in this review. relevant animal species for preclinical studies of mab candidates are those express desired epitope of mab candidates. cynomolgus monkeys cross-react with mab drugs much higher than other animal species commonly used in preclinical studies such as absorption, distribution, metabolism and excretion (adme), efficacy, and toxicity studies, for development of new drugs. more ... | 2019 | 29655914 |
| labyrinthitis ossificans in a cynomolgus macaque (macaca fascicularis). | labyrinthitis is inflammation of the membranous and bony labyrinth of the inner ear. typical portals of entry includehematogenous spread from the cochlear vasculature, passage of otitis media pathogens through the round window, and mostcommonly, meningogenic spread from the subarachnoid space. the sequela of chronic inner ear inflammation is labyrinthitisossificans, in which inner ear structures are replaced by fibrous and osseous tissues. labyrinthitis in humans has been reportedconcurrently wi ... | 2018 | 29650059 |
| in vitro-in vivo extrapolation of oatp1b-mediated drug-drug interactions in cynomolgus monkey. | hepatic organic anion-transporting polypeptides (oatp) 1b1 and 1b3 are clinically relevant transporters associated with significant drug-drug interactions (ddis) and safety concerns. given that oatp1bs in cynomolgus monkey share >90% degree of gene and amino acid sequence homology with human orthologs, we evaluated the in vitro-in vivo translation of oatp1b-mediated ddi risk using this preclinical model. in vitro studies using plated cynomolgus monkey hepatocytes showed active uptake km values o ... | 2018 | 29643253 |
| [shaoyangzhugu formula regulates p19arf-p53-p21cip1 signaling pathway to ameliorate cartilage degeneration in aged cynomolgus monkeys with knee osteoarthritis]. | to study the effect of shaoyangzhugu (syzg) formula (a formula consisting of 9 traditional chinese drugs) in delaying the degeneration of articular cartilage and the role p19arf-p53-p21cip1 signaling pathway in mediating this effect. | 2018 | 29643043 |
| comparative study of three xenic media culture for cultivation of balantidium coli strains. | the aim of the present study was to evaluate the growth rate of balantidium coli in three xenic media cultures. between 2013 and 2015, 10 b. coli isolates obtained from feces of cynomolgus macaques, and 30 isolates from feces of pigs were studied. an inoculum of 500 trophozoites was transferred to tubes containing les, tysgm-9 and pavlova media. these cultures were evaluated at incubation times of 24, 48, 72 and 96 hours. in most of strains analyzed wasn't showed significant difference in the gr ... | 2018 | 29641791 |
| malaria parasites of long-tailed macaques in sarawak, malaysian borneo: a novel species and demographic and evolutionary histories. | non-human primates have long been identified to harbour different species of plasmodium. long-tailed macaques (macaca fascicularis), in particular, are reservoirs for p. knowlesi, p. inui, p. cynomolgi, p. coatneyi and p. fieldi. a previous study conducted in sarawak, malaysian borneo, however revealed that long-tailed macaques could potentially harbour novel species of plasmodium based on sequences of small subunit ribosomal rna and circumsporozoite genes. to further validate this finding, the ... | 2018 | 29636003 |
| linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: a comparison between human, cynomolgus monkey and hfcrn tg32 transgenic mouse using a population-modeling approach. | the linear pharmacokinetics (pk) of therapeutic monoclonal antibodies (mabs) can be considered a class property with values that are similar to endogenous igg. knowledge of these parameters across species could be used to avoid unnecessary in vivo pk studies and to enable early pk predictions and pharmacokinetic/pharmacodynamic (pk/pd) simulations. in this work, population-pharmacokinetic (poppk) modeling was used to determine a single set of 'typical' poppk parameters describing the linear pk o ... | 2018 | 29634430 |
| a cynomolgus macaque model for crimean-congo haemorrhagic fever. | crimean-congo haemorrhagic fever (cchf) is the most medically significant tick-borne disease, being widespread in the middle east, asia, africa and parts of europe 1 . increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of cchf as a public health threat. ixodid ticks of the genus hyalomma are the vector for cchf virus (cchfv), an arbovirus in the genus orthonairovirus of the family nairoviridae. cchfv naturally infects numerous wild and dom ... | 2018 | 29632370 |
| an anatomic characterization of the midbrain near response neurons in the macaque monkey. | these experiments were designed to reveal the location of the premotor neurons that have previously been designated physiologically as the midbrain near response cells controlling vergence, lens accommodation, and pupillary constriction in response to target distance. | 2018 | 29625471 |
| hypothetical endogenous siv-like antigens in mauritian cynomolgus macaques. | simian immunodeficiency virus (siv) infection of mauritian cynomolgus macaques (mcms) is an increasingly important nonhuman primate model for hiv vaccine research. we previously reported that in mcms anti-siv antibodies can be naturally developed without exogenous infection or vaccination, and that a vaccine targeting siv protease cleavage sites (pcs) can cross-induce antibodies to non-pcs siv antigens. we speculate that this is potentially caused by the existence of endogenous siv-like antigens ... | 2018 | 29618899 |
| fgf21 acts as a negative regulator of bile acid synthesis. | fibroblast growth factor 21 (fgf21) is a potent regulator of glucose and lipid homeostasis in vivo; its most closely related subfamily member, fgf19, is known to be a critical negative regulator of bile acid synthesis. to delineate whether fgf21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native fgf21 and long-acting fgf21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary he ... | 2018 | 29615519 |
| refinement of in vitro methods for identification of aldehyde oxidase substrates reveals metabolites of kinase inhibitors. | to identify aldehyde oxidase (ao) substrates, an assay procedure was developed that leverages the capabilities of high-resolution mass spectrometry to simultaneously monitor parent loss and formation of hydroxylated metabolite over time in incubations with liver cytosol. by incorporating metabolite monitoring, false positives resulting from metabolism by other cytosolic enzymes or processes were decreased. a diverse set of 34 kinase inhibitors containing ao-substrate motifs was screened, and 35% ... | 2018 | 29615437 |
| a novel selective soluble guanylate cyclase activator, mgv354, lowers intraocular pressure in preclinical models, following topical ocular dosing. | the nitric oxide/soluble guanylate cyclase/protein kinase g (no/sgc/pkg) is known to be involved in the regulation of intraocular pressure (iop) and may be dysregulated in glaucoma. the purpose is to demonstrate that the sgc activator mgv354 lowers iop in a monkey model of glaucoma and could be considered as a possible new clinical drug candidate. | 2018 | 29610853 |
| pre-clinical and translational pharmacology of a human interleukin-22 igg fusion protein for potential treatment of infectious or inflammatory diseases. | interleukin (il)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. il-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. uttr1147a is a recombinant fusion protein that links the human cytokine il-22 with the fc portion of human immunoglobulin (ig) g4. here, we report extensive in vitro and in vivo nonclinical studies that were conducted t ... | 2018 | 29608910 |
| molecular cytogenetic analysis of one african and five asian macaque species reveals identical karyotypes as in mandrill. | the question how evolution and speciation work is one of the major interests of biology. especially, genetic including karyotypic evolution within primates is of special interest due to the close phylogenetic position of macaca and homo sapiens and the role as in vivo models in medical research, neuroscience, behavior, pharmacology, reproduction and acquired immune deficiency syndrome (aids). | 2018 | 29606908 |
| a new telemetry-based system for assessing cardiovascular function in group-housed large animals. taking the 3rs to a new level with the evaluation of remote measurement via cloud data transmission. | a newly developed total implant telemetry system for cardiovascular (cv), electrophysiological and body temperature measurement was evaluated. a cloud-based transmission of the physiological signals allowed an assessment of the quality of the physiological signals despite the physical separation between the instrumented animals and the evaluating home laboratory. the new system is intended to be used for safety pharmacological evaluations of drug candidates in various species. | 2019 | 29597013 |
| a conserved transcriptional response to intranasal ebola virus exposure in nonhuman primates prior to onset of fever. | ebola virus disease (evd), caused by ebola virus (ebov), is a severe illness characterized by case fatality rates of up to 90%. the sporadic nature of outbreaks in resource-limited areas has hindered the ability to characterize the pathogenesis of evd at all stages of infection but particularly early host responses. pathogenesis is often studied in nonhuman primate (nhp) models of disease that replicate major aspects of human evd. typically, nhp models use a large infectious dose, are carried ou ... | 2018 | 29593102 |
| abt-165, a dual variable domain immunoglobulin (dvd-ig) targeting dll4 and vegf, demonstrates superior efficacy and favorable safety profiles in preclinical models. | antiangiogenic therapy is a clinically validated modality in cancer treatment. to date, all approved antiangiogenic drugs primarily inhibit the vegf pathway. delta-like ligand 4 (dll4) has been identified as a potential drug target in vegf-independent angiogenesis and tumor-initiating cell (tic) survival. a dual-specific biologic targeting both vegf and dll4 could be an attractive strategy to improve the effectiveness of anti-vegf therapy. abt-165 was uniquely engineered using a proprietary dual ... | 2018 | 29592882 |
| generation and characterization of a potent fully human monoclonal antibody against the interleukin-23 receptor. | interleukin (il)-12 and il-23 share a common subunit (p40) and function in t-helper (th) 1 and th17 immunity, respectively. anti-il-12/23p40 and specific anti-il-23 antibodies are currently in clinical use for psoriasis and undergoing trials for autoimmune diseases. since expression levels of the il-23 receptor are likely to be much lower than those of il-23, an anti-il-23 receptor antibody might offer greater promise in inhibiting the il-23-il-17 pathways involved in inflammatory disorders. to ... | 2018 | 29588152 |
| antiviral efficacy of favipiravir against ebola virus: a translational study in cynomolgus macaques. | despite repeated outbreaks, in particular the devastating 2014-2016 epidemic, there is no effective treatment validated for patients with ebola virus disease (evd). among the drug candidates is the broad-spectrum polymerase inhibitor favipiravir, which showed a good tolerance profile in patients with evd (jiki trial) but did not demonstrate a strong antiviral efficacy. in order to gain new insights into the antiviral efficacy of favipiravir and improve preparedness and public health management o ... | 2018 | 29584730 |
| preclinical pharmacokinetics and biodistribution of subcutaneously administered glycopegylated recombinant factor viii (n8-gp) and development of a human pharmacokinetic prediction model. | essentials n8-gp is an extended half-life recombinant factor viii (fviii) for the treatment of hemophilia a. subcutaneous (sc) fviii dosing might reduce the treatment burden of prophylaxis. sc n8-gp has a favorable pk profile in animal models and disappears from skin injection sites. combined animal (sc) and clinical (iv) data suggest that daily sc dosing may provide prophylaxis. | 2018 | 29582559 |
| immune molecular profiling of whole blood drawn from a non-human primate cardiac xenograft model treated with anti-cd154 monoclonal antibodies. | most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. here, we performed immune molecular profiling following anti-cd154 monoclonal antibody (mab) treatment in heterotopic abdominal cardiac xenografts from α-1,3-galactosyltransferase-knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. ... | 2018 | 29582477 |
| mechanism of activating the proprioceptive nt-3/trkc signalling pathway by reverse intervention for the anterior cruciate ligament-hamstring reflex arc with electroacupuncture. | the anterior cruciate ligament (acl) is an important structure maintaining stability of the knee joints. deficits in physical stability and the proprioceptive capabilities of the knee joints are observed, when the acl is damaged. additionally, a unilateral acl injury can affect bilateral knee proprioception; therefore, proprioception of the acl may play a key role in stability. electroacupuncture therapy has a definite effect nerve regeneration. in this study, cynomolgus monkeys were randomly di ... | 2018 | 29581981 |
| the anatomy of the foveola reinvestigated. | in the foveola of the eye, photoreceptors and müller cells with a unique morphology have been described, but little is known about their 3d structure and orientation. considering that there is an angle-dependent change in the foveolar photoreceptor response for the same light beam, known as the stiles crawford effect of the first kind (sce i), which is still not fully understood, a detailed analysis of the anatomy of the foveolar cells might help to clarify this phenomenon. | 2018 | 29576957 |
| nonclinical assessments of the potential biosimilar pf-06439535 and bevacizumab. | bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (vegf), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney cancer, and glioblastoma. to support clinical development of the potential bevacizumab biosimilar pf-06439535, nonclinical studies evaluated structural, functional, toxicological, and toxicokinetic similarity to bevacizumab sourced from the european union (bevacizumab-eu) ... | 2018 | 29574193 |
| molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques. | butyrylcholinesterase (bche), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. bche polymorphisms partly account for variable bche activities among individuals in humans, but have not been investigated in cynomolgus macaques. | 2018 | 29573432 |
| morphological integration of anatomical, developmental, and functional postcranial modules in the crab-eating macaque (macaca fascicularis). | integration and modularity reflect the coordinated action of past evolutionary processes and, in turn, constrain or facilitate phenotypic evolvability. here, we analyze magnitudes of integration in the macaque postcranium to test whether 20 a priori defined modules are (1) more tightly integrated than random sets of postcranial traits, and (2) are differentiated based on mode of definition, with developmental modules expected to be more integrated than functional or anatomical modules. | 2018 | 29566426 |
| preclinical pharmacokinetics, interspecies scaling, and pharmacokinetics of a phase i clinical trial of ttac-0001, a fully human monoclonal antibody against vascular endothelial growth factor 2. | vegf is a highly selective mitogen that serves as the central regulator of tumor angiogenesis by mediating endothelial proliferation, permeability, and survival. tanibirumab (ttac-0001) is a fully human igg1 monoclonal antibody derived from a fully human naïve single-chain variable fragment (scfv) phage library that was developed to inhibit the effects of vegf in the treatment of solid tumors, especially those of the brain. | 2018 | 29563774 |
| monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration. | many studies have focused on the challenges of small molecule uptake across the blood-brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central nervous system (cns). in drug development, cerebrospinal fluid (csf) sampling is routinely used as a surrogate for assessing cns drug exposure and biomarker levels. in this report, we have studied the kinetic correlation between csf and serum drug concentration-time profiles for five humanized ... | 2018 | 29558954 |
| histopathologic characterization of mifepristone-induced ovarian toxicity in cynomolgus monkeys. | mifepristone, which is an orally active synthetic steroid with antiprogesterone activity, is known as an ovarian toxicant. because the available data regarding the histopathologic characteristics of ovarian toxicity in nonhuman primates are limited, the present study was undertaken in order to investigate detailed histopathologic changes accompanying mifepristone-induced ovarian toxicity and its relationship to changes in menstrual cycle and circulating sex steroid hormone. twenty mg/kg of mifep ... | 2018 | 29558845 |
| experimental infection of cynomolgus macaques with highly pathogenic h5n1 influenza virus through the aerosol route. | several animal models are used to study influenza viruses. intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (nhp) ... | 2018 | 29556081 |
| porches as enrichment for singly housed cynomolgus macaques (macaca fascicularis). | effective environmental enrichment is used by animals, promotes species-typical behavior, and decreases abnormal behavior. porches attached to the front of an animal's cage provide additional space, perching opportunities, and a better view of the surroundings. here we assessed the effectiveness of porches as a form of enrichment and identified characteristics of the animals most likely to use the porches. we videorecorded and scored the behavior of 18 (9 male, 9 female) singly housed cynomolgus ... | 2018 | 29555002 |
| absolute quantification of plasma microrna levels in cynomolgus monkeys, using quantitative real-time reverse transcription pcr. | rt-qpcr is one of the most common methods to assess individual target mirnas. mirnas levels are generally measured relative to a reference sample. this approach is appropriate for examining physiological changes in target gene expression levels. however, absolute quantification using better statistical analysis is preferable for a comprehensive assessment of gene expression levels. absolute quantification is still not in common use. this report describes a protocol for measuring the absolute lev ... | 2018 | 29553521 |
| rd-05, a novel anti-cd154 antibody, efficiently inhibits generation of anti-drug antibody without the risk of thrombus formation in non-human primates. | antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and factor viii, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. it is well known that anti-cd154 antibodies have the highest potential to inhibit these types of adverse immune responses. nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-cd154 blocking antibodies. for this, we attempt ... | 2018 | 29550477 |
| practical strategies when using a stable isotope labeled microtracer for absolute bioavailability assessment: a case study of a high oral dose clinical candidate gdc-0810. | the ph labile metabolite, hydrophobicity, high oral dose and systematic exposure of gdc-0810 posed tremendous challenges to develop a lc-ms method for a stable isotope labeled aba study. in this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high cp.o. to ci.v. ratio on the labeling selection and assay dynamic range. a [13c9] gdc-0810 was synthesized to minimize the isotopic interference between po dose, internal standard and i.v. micro ... | 2018 | 29549853 |
| raman micro-spectroscopy analysis of different sperm regions: a species comparison. | is raman micro-spectroscopy a valid approach to assess the biochemical hallmarks of sperm regions (head, midpiece and tail) in four different species? | 2018 | 29528451 |
| glyco-engineered long acting fgf21 variant with optimal pharmaceutical and pharmacokinetic properties to enable weekly to twice monthly subcutaneous dosing. | pharmacological administration of fgf21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. here we report the design, optimization, and characterization of a long acting glyco-variant of fgf21. using a combination of n-glycan engineering for enhanced protease resistance and improved solubility, fc fusion for further half-life extension, and a single point mutation for improving manufacturability in chi ... | 2018 | 29523796 |
| development of a non-human primate bcg infection model for the evaluation of candidate tuberculosis vaccines. | the lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. using intradermal bacille calmette-guréin (bcg) as a surrogate for aerosol mycobacterium tuberculosis (m.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. non-human primates (nhps) may provide the best model in which to do this. cynomolgus and rhesus macaques were infected with bcg by intraderm ... | 2018 | 29523335 |
| pharmacokinetics and toxicology of the neuroprotective e,e,e-methanofullerene(60)-63-tris malonic acid [c3] in mice and primates. | fullerene-based compounds are a novel class of molecules being developed for a variety of biomedical applications, with nearly 1000 publications in this area in the last 4 years alone. one such compound, the e,e,e-methanofullerene(60)-63-tris malonic acid (designated c3), is a potent catalytic superoxide dismutase mimetic which has shown neuroprotective efficacy in a number of animal models of neurologic disease, including parkinsonian macaca fascicularis monkeys. the aim of this study was to ch ... | 2018 | 29520718 |
| alleviating cyp and herg liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series - potent, selective and orally efficacious microsomal prostaglandin e synthase-1 (mpges-1) inhibitors: part-2. | in an effort to identify cyp and herg clean mpges-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (sar) studies were performed. optimization of a, d and e-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nm. selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against cox-enzymes and mpges-1 isoforms (mpges-2 and cpges) along with sufficient selecti ... | 2018 | 29519738 |
| a safety and immunogenicity study of immunization with hvegf26-104/rfase in cynomolgus monkeys. | vascular endothelial growth factor (vegf) is pivotal in tumor angiogenesis and therapies targeting the vegf axis are widely used in the clinic for the treatment of cancer. we have developed a therapeutic vaccine targeting human (h)vegf165. hvegf26-104/rfase is based on the truncated protein hvegf26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide rfase as adjuvant. here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomol ... | 2018 | 29519591 |
| lesions of the female reproductive tract in japanese macaque ( macaca fuscata) from two captive colonies. | reproductive lesions have been described in various nonhuman primate species, including rhesus macaques ( macaca mulatta), cynomolgus macaques ( macaca fascicularis), baboons ( papio spp.), squirrel monkeys ( saimiri sciureus), and chimpanzees ( pan spp.); however, there are few publications describing reproductive disease and pathology in japanese macaques ( macaca fuscata). a retrospective evaluation of postmortem reports for two captive m. fuscata populations housed within zoos from 1982 thro ... | 2018 | 29517447 |
| a sensitive method for the quantitation of the peptide-based glucagon-like peptide-1 receptor agonist liraglutide in plasma using microfluidics chromatography tandem ms. | an lc-ms/ms assay for the quantitation of liraglutide, a peptide-based injectable glucagon-like peptide-1 receptor agonist, has been developed as a convenient alternative to the enzyme-linked immunosorbent assay, and used to characterize liraglutide pharmacokinetics in cynomolgus monkeys. | 2018 | 29516741 |
| tool-use training temporarily enhances cognitive performance in long-tailed macaques (macaca fascicularis). | tool use relies on numerous cognitive functions, including sustained attention and understanding of causality. in this study, we investigated the effects of tool-use training on cognitive performance in primates. specifically, we applied the primate cognition test battery to three long-tailed macaques (macaca fascicularis) at different stages of a training procedure that consisted of using a rake to retrieve out-of-reach food items. in addition, we evaluated a control group (n = 3) performing a ... | 2018 | 29502167 |