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https://www.readbyqxmd.com/read/28731212/cross-validation-of-commercial-enzyme-linked-immunosorbent-assay-and-radioimmunoassay-for-porcine-c-peptide-concentration-measurements-in-non-human-primate-serum
#1
Sarah C Gresch, Lucas A Mutch, Jody L Janecek, Rebecca L Hegstad-Davies, Melanie L Graham
BACKGROUND: C-peptide concentration is widely used as a marker of insulin secretion and is especially relevant in evaluating islet graft function following transplantation, because its measurement is not confounded by the presence of exogenous insulin. To address the shortage of human islet donors, the use of porcine islets has been proposed as a possible solution and the stringent pig-to-non-human primate (NHP) model is often the most relevant for pre-clinical evaluation of the potential for diabetes reversal resulting from an islet xenograft...
July 21, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28642489/post-exposure-treatment-of-non-human-primates-lethally-infected-with-ebola-virus-with-ebotab-a-purified-ovine-igg-product
#2
Stuart D Dowall, Frédéric Jacquot, John Landon, Emma Rayner, Graham Hall, Caroline Carbonnelle, Hervé Raoul, Delphine Pannetier, Ian Cameron, Ruth Coxon, Ibrahim Al Abdulla, Roger Hewson, Miles W Carroll
Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28545034/characterization-of-sudan-ebolavirus-infection-in-ferrets
#3
Andrea Kroeker, Shihua He, Marc-Antoine de La Vega, Gary Wong, Carissa Embury-Hyatt, Xiangguo Qiu
Sudan virus (SUDV) outbreaks in Africa are highly lethal; however, the development and testing of novel antivirals and vaccines for this virus has been limited by a lack of suitable animal models. Non-human primates (NHP) remain the gold standard for modeling filovirus disease, but they are not conducive to screening large numbers of experimental compounds and should only be used to test the most promising candidates. Therefore, other smaller animal models are a valuable asset. We have recently developed a guinea-pig adapted SUDV virus that is lethal in guinea pigs...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28542463/insights-into-reston-virus-spillovers-and-adaption-from-virus-whole-genome-sequences
#4
César G Albariño, Lisa Wiggleton Guerrero, Harley M Jenks, Ayan K Chakrabarti, Thomas G Ksiazek, Pierre E Rollin, Stuart T Nichol
Reston virus (family Filoviridae) is unique among the viruses of the Ebolavirus genus in that it is considered non-pathogenic in humans, in contrast to the other members which are highly virulent. The virus has however, been associated with several outbreaks of highly lethal hemorrhagic fever in non-human primates (NHPs), specifically cynomolgus monkeys (Macaca fascicularis) originating in the Philippines. In addition, Reston virus has been isolated from domestic pigs in the Philippines. To better understand virus spillover events and potential adaption to new hosts, the whole genome sequences of representative Reston virus isolates were obtained using a next generation sequencing (NGS) approach and comparative genomic analysis and virus fitness analyses were performed...
2017: PloS One
https://www.readbyqxmd.com/read/28503733/long-term-safety-from-transmission-of-porcine-endogenous-retrovirus-after-pig-to-non-human-primate-corneal-transplantation
#5
Hyuk Jin Choi, Jiyeon Kim, Jae Young Kim, Hyun Ju Lee, Won Ryang Wee, Mee Kum Kim, Eung Soo Hwang
BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. Accordingly, an investigation was performed to analyze the infectivity of PERVs from porcine keratocytes to human cells, and the long-term risk of transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal transplantation models...
May 14, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28487309/molecular-cloning-and-characterization-of-marmoset-aldehyde-oxidase
#6
Shotaro Uehara, Yasuhiro Uno, Eriko Okamoto, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
Common marmosets (Callithrix jacchus), New world monkeys, are a promising primate model for preclinical drug metabolism studies due to the similarities of cytochrome P450 (P450) enzyme function to those of humans. Despite an increasing number of drug candidates catalyzed by non-P450 enzymes, drug metabolizing enzymes other than P450s have been hardly identified or characterized in marmosets. In this study, we identified aldehyde oxidase (AOX) 1 gene by marmoset genome analysis. AOX1 cDNA was cloned from marmoset livers by reverse transcription-polymerase chain reaction...
May 9, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28483459/animal-models-of-atherosclerosis
#7
Besa Emini Veseli, Paola Perrotta, Gregory R A De Meyer, Lynn Roth, Carole Van der Donckt, Wim Martinet, Guido R Y De Meyer
An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain results that can be extrapolated to human medicine. Moreover, it must be easy to acquire, can be maintained at a reasonable cost, is easy to handle and shares the topography of the lesions with humans. In general, animal models of atherosclerosis are based on accelerated plaque formation due to a cholesterol-rich/Western-type diet, manipulation of genes involved in the cholesterol metabolism, and the introduction of additional risk factors for atherosclerosis...
May 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28472809/developmental-changes-in-expression-of-gabaa-receptor-subunits-%C3%AE-1-%C3%AE-2-and-%C3%AE-3-in-the-pig-brain
#8
Stephanie M Miller, Viskasari P Kalanjati, Paul B Colditz, Stella Tracey Björkman
GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABAA receptor (GABAAR); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABAA α-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97, 100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days)...
May 5, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28471371/the-reversal-of-direct-oral-anticoagulants-in-animal-models
#9
Markus Honickel, Necib Akman, Oliver Grottke
Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity)...
August 2017: Shock
https://www.readbyqxmd.com/read/28464334/high-prevalence-of-hepatitis-e-virus-infection-in-goats
#10
Feiyan Long, Wenhai Yu, Chenchen Yang, Jue Wang, Yunlong Li, Yi Li, Fen Huang
Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide, primarily transmitted by fecal-oral route. Zoonotic transmission of HEV from HEV-infected pigs (pork) or cows (milk) to human or non-human primate has been confirmed, but the risk of HEV in goat is still rarely assessed. In the present study, stool, blood, tissues and milk of goat were collected for HEV infection investigation from Dali City of Yunnan Province in China, where raw mutton and goat milk are traditionally consumed. Surprisingly, a high prevalence of HEV infection in goat was found...
May 2, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28447999/exposure-of-the-pig-cns-for-histological-analysis-a-manual-for-decapitation-skull-opening-and-brain-removal
#11
Carsten R Bjarkam, Dariusz Orlowski, Laura Tvilling, Johannes Bech, Andreas N Glud, Jens-Christian H Sørensen
Pigs have become increasingly popular in large-animal translational neuroscience research as an economically and ethically feasible substitute to non-human primates. The large brain size of the pig allows the use of conventional clinical brain imagers and the direct use and testing of neurosurgical procedures and equipment from the human clinic. Further macroscopic and histological analysis, however, requires postmortem exposure of the pig central nervous system (CNS) and subsequent brain removal. This is not an easy task, as the pig CNS is encapsulated by a thick, bony skull and spinal column...
April 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28417501/d-dimer-level-in-association-with-humoral-responses-negatively-correlates-with-survival-of-porcine-islet-grafts-in-non-human-primates-with-immunosuppression
#12
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Byoung-Hoon Min, Chung-Gyu Park
BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft survival in non-human primates (NHPs) after porcine islet transplantation (PITx), but their success rates vary. To understand the mechanism of graft loss, we investigated the relationships between graft survival and humoral or inflammatory responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from adult wild-type pigs were intraportally transplanted into streptozotocin-induced diabetic rhesus monkeys...
April 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28397982/generation-of-chimeric-minipigs-by-aggregating-4-to-8-cell-stage-blastomeres-from-somatic-cell-nuclear-transfer-with-the-tracing-of-enhanced-green-fluorescent-protein
#13
Huili Ji, Chuan Long, Chong Feng, Ningning Shi, Yingdi Jiang, Guomin Zeng, Xirui Li, Jingjing Wu, Lin Lu, Shengsheng Lu, Dengke Pan
BACKGROUND: Blastocyst complementation is an important technique for generating chimeric organs in organ-deficient pigs, which holds great promise for solving the problem of a shortage of organs for human transplantation procedures. Porcine chimeras have been generated using embryonic germ cells, embryonic stem cells, and induced pluripotent stem cells; however, there are no authentic pluripotent stem cells for pigs. In previous studies, blastomeres from 4- to 8-cell-stage parthenogenetic embryos were able to generate chimeric fetuses efficiently, but the resulting fetuses did not produce live-born young...
April 11, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28393447/anti-cd40-antibody-mediated-costimulation-blockade-promotes-long-term-survival-of-deep-lamellar-porcine-corneal-grafts-in-non-human-primates
#14
Jaeyoung Kim, Dong Hyun Kim, Hyuk Jin Choi, Hyun Ju Lee, Hee Jung Kang, Chung-Gyu Park, Eung-Soo Hwang, Mee Kum Kim, Won Ryang Wee
BACKGROUND: Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model...
May 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28389406/simultaneous-overexpression-of-human-e5nt-and-entpd1-protects-porcine-endothelial-cells-against-h2o2-induced-oxidative-stress-and-cytotoxicity-in-vitro
#15
Elisa Chisci, Marco De Giorgi, Elisa Zanfrini, Angela Testasecca, Elena Brambilla, Alessandro Cinti, Laura Farina, Barbara Kutryb-Zajac, Cristina Bugarin, Chiara Villa, Emanuela Grassilli, Romina Combi, Giuseppe Gaipa, Maria Grazia Cerrito, Ilaria Rivolta, Ryszard Tomasz Smolenski, Marialuisa Lavitrano, Roberto Giovannoni
Ischemia-reperfusion injury (IRI) and oxidative stress still limit the survival of cells and organs in xenotransplantation models. Ectonucleotidases play an important role in inflammation and IRI in transplantation settings. We tested the potential protective effects derived by the co-expression of the two main vascular ectonucleotidases, ecto-5'-nucleotidase (E5NT) and ecto nucleoside triphosphate diphosphohydrolase 1 (ENTPD1), in an in vitro model of H2O2-induced oxidative stress and cytotoxicity. We produced a dicistronic plasmid (named pCX-DI-2A) for the co-expression of human E5NT and ENTPD1 by using the F2A technology...
April 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28379031/experimental-models-of-hyperlipoproteinemia-and-atherosclerosis
#16
R Poledne, L Jurčíková-Novotná
The first experimental model of atherosclerosis (in rabbits) is more than hundred years old. Several animal species have been used to produce hyperlipoproteinemia and possible atherosclerosis. The gene manipulation produced the most used models recently. This review acknowledges the extensive study of atherosclerotic changes in experimental models of hyperlipoproteinemia and atherosclerosis to come to light thus far and the purpose here is not only to summarize the published data but also to try to add some details of our experience in using these models...
April 5, 2017: Physiological Research
https://www.readbyqxmd.com/read/28271465/porcine-islet-xenografts-a-clinical-source-of-%C3%A3-cell-grafts
#17
REVIEW
Bassem F Salama, Gregory S Korbutt
PURPOSE OF REVIEW: Diabetes is medical and social burden affecting millions around the world. Despite intensive therapy, insulin fails to maintain adequate glucose homeostasis and often results in episodes of hypoglycemic unawareness. Islet transplantation is a propitious replacement therapy, and incremental improvements in islet isolation and immunosuppressive drugs have made this procedure a feasible option. Shortage of donors, graft loss, and toxic immunosuppressive agents are few of many hurdles against making human allogenic islet transplantation a routine procedure...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#18
Hayato Iwase, Hong Liu, Eva Schmelzer, Mohamed Ezzelarab, Martin Wijkstrom, Hidetaka Hara, Whayoung Lee, Jagjit Singh, Cassandra Long, Eric Lagasse, Jörg C Gerlach, David K C Cooper, Bruno Gridelli
BACKGROUND: Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28068870/induced-remodeling-of-porcine-tendons-to-human-anterior-cruciate-ligaments-by-%C3%AE-gal-epitope-removal-and-partial-cross-linking
#19
Kevin R Stone, Ann Walgenbach, Uri Galili
This review describes a novel method developed for processing porcine tendon and other ligament implants that enables in situ remodeling into autologous ligaments in humans. The method differs from methods using extracellular matrices (ECMs) that provide postoperative orthobiological support (i.e., augmentation grafts) for healing of injured ligaments, in that the porcine bone-patellar-tendon-bone itself serves as the graft replacing ruptured anterior cruciate ligament (ACL). The method allows for gradual remodeling of porcine tendon into autologous human ACL while maintaining the biomechanical integrity...
February 14, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#20
Rita Bottino, Michael F Knoll, Joshua Graeme-Wilson, Edwin C Klein, David Ayares, Massimo Trucco, David K C Cooper
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months...
January 2017: Xenotransplantation
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