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https://www.readbyqxmd.com/read/29407773/preclinical-evaluation-of-the-mono-pegylated-recombinant-human-interleukin-11-in-cynomolgus-monkeys
#1
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Suxing Zhang, Peizhen Ye, Kezhi Zhang, Xiaobo Li, Juan Li, Qin Xu, Wing-Tak Wong, Qui-Lim Choo
The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2=6...
February 2, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29395533/immunization-with-phage-virus-like-particles-displaying-zika-virus-potential-b-cell-epitopes-neutralizes-zika-virus-infection-of-monkey-kidney-cells
#2
Rupsa Basu, Lukai Zhai, Alice Contreras, Ebenezer Tumban
Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241-259, 294-315, 317-327, 346-361, 377-388 and 421-437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection...
January 30, 2018: Vaccine
https://www.readbyqxmd.com/read/29348125/metabolism-and-disposition-of-a-novel-selective-%C3%AE-7-neuronal-acetylcholine-receptor-agonist-abt-126-in-humans-characterization-of-the-major-roles-for-flavin-containing-monooxygenases-and-udp-glucuronosyl-transferase-1a4-and-2b10-in-catalysis
#3
Hong Liu, David M Stresser, Melissa J Michmerhuizen, XIaofeng Li, Ahmed A Othman, Aimee D Reed, Michael R Schrimpf, Jens Sydor, Anthony J Lee
Mass balance, metabolism and excretion of ABT-126, an α7 nAChRs agonist, were characterized in healthy male subjects (n=4) following a single 100 mg (100 μCi) oral dose. The total recovery of the administered radioactivity was 94.0% (±2.09%) with 81.5% (± 10.2%) in urine and 12.4% (± 9.3%) in feces. Metabolite profiling indicated that ABT-126 had been extensively metabolized with 6.6% of the dose remaining as unchanged parent drug in urine. Parent drug accounted for 12.2% of the administered radioactivity in feces...
January 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29348093/antifungal-and-cytotoxic-activities-of-selected-medicinal-plants-from-malaysia
#4
Yik Sin Chan, Yit Hong Cheah, Poh Zen Chong, Hui Lai Khor, Wen Siang Teh, Kong Soo Khoo, Hean Chooi Ong, Nam Weng Sit
This study was conducted to investigate the antifungal potential and cytotoxicity of selected medicinal plants from Malaysia. The extracts from the stem of Cissus quadrangularis and the leaves of Asplenium nidus, Pereskia bleo, Persicaria odorata and Sauropus androgynus were assayed against six fungi using p-iodonitrotetrazolium-based on colorimetric broth microdilution method. All the plant extracts were found to be fungicidal against at least one type of fungus. The strongest fungicidal activity (minimum fungicidal concentration=0...
January 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29342972/the-effect-of-combining-natural-terpenes-and-antituberculous-agents-against-reference-and-clinical-mycobacterium-tuberculosis-strains
#5
Elwira Sieniawska, Rafal Sawicki, Marta Swatko-Ossor, Agnieszka Napiorkowska, Agata Przekora, Grazyna Ginalska, Ewa Augustynowicz-Kopec
Background: On account of emergence of multi- and extensively drug-resistant Mycobacterium tuberculosis (Mtb) strains, combinations of drugs with natural compounds were tested to search for antibiotic activity enhancers. In this work we studied terpenes (α-pinene, bisabolol, β-elemene, (R)-limonene, (S)-limonene, myrcene, sabinene), which are the main constituents of essential oil obtained from Mutellina purpurea L., a plant with described antitubercular activity, to investigate their interactions with antibiotics against reference Mtb strains and multidrug-resistant clinical isolates...
January 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29319621/selective-cd28-inhibition-modulates-alloimmunity-and-cardiac-allograft-vasculopathy-in-anti-cd154-treated-monkeys
#6
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade...
January 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29318455/4-6-dimethoxyisoflavone-7-o-%C3%AE-d-glucopyranoside-wistin-is-a-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-agonist-in-mouse-hepatocytes
#7
Misato Suzuki, Fumiya Nakamura, Emi Taguchi, Maho Nakata, Fumi Wada, Momoka Takihi, Tomoyo Inoue, Shinji Ohta, Hiroyuki Kawachi
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that regulate lipid and glucose metabolism. PPARα mainly affects fatty acid metabolism, and its activation lowers lipid levels. PPARγ is involved in the regulation of adipogenesis, insulin sensitivity, energy balance, and lipid biosynthesis. We have previously reported that 4',6-dimethoxyisoflavone-7-O-β-D-glucopyranoside (wistin) can activate PPARγ. The purpose of the present study is to investigate the PPARα agonist activity of wistin...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29300231/long-term-nonhuman-primate-renal-allograft-survival-without-ongoing-immunosuppression-in-recipients-of-delayed-donor-bone-marrow-transplantation
#8
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) following an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine ATG (Atgam) and donor bone marrow transplantation (DBMT). Since these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
January 4, 2018: Transplantation
https://www.readbyqxmd.com/read/29295701/evaluation-of-fibroblasts-cells-viability-and-adhesion-on-six-different-titanium-surfaces-an-in-vitro-experimental-study
#9
Sergio Alexandre Gehrke, Leticia Perez-Diaz, Berenice Anina Dedavid
BACKGROUND: The topographical surficial characteristics and properties of materials can induce different cell reactions regards to the viability and adhesion according to the recent patents. The aim of this in vitro experimental study was to evaluate the viability and adhesion of fibroblastic cells seeded on titanium disks with different surface topography. In addition, we revised all patents relating to sintering process titanium powder surface treatment for a of dental implants. METHODS: Fibroblast cells were cultured on 6 surfaces models: mA disks corresponding to titanium surfaces without additional treatment (machined surface) were compared with mB disks, where surfaces were sandblasting etching using aluminum oxide; mC disks where titanium oxide was used for sandblasting etching; mD disks where triple acid conditioning was used, mE disks with laser treated surface and mF disks which were made of titanium powder by a sintering process...
January 1, 2018: Recent Patents on Biotechnology
https://www.readbyqxmd.com/read/29285901/characterization-of-porcine-sapelovirus-isolated-from-japanese-swine-with-plc-prf-5-cells
#10
H Bai, J Liu, L Fang, M Kataoka, N Takeda, T Wakita, T-C Li
Porcine sapelovirus (PSV) is a causative agent of neurological disorders, fertility disorders and dermal lesions of swine. In this study, we isolated two PSV strains, Jpsv477 and Jpsv1315, from swine faecal specimens using a PLC/PRF/5 cell culture system. The PSV infection of PLC/PRF/5 cells induced a cytopathic effect (CPE). Two types of virus particles with identical diameter (~35 nm) but different densities (1.300 and 1.285 g/cm3 ) were observed in the cell culture supernatants. Analysis of the entire genome sequence of Jpsv477 and Jpsv1315 revealed that both strains possess 7,558 nucleotides and the poly (A) tail and have a typical PSV genome organization consisting of a 5' terminal untranslated region (5'UTR), a large open reading frame (ORF), and a 3' terminal untranslated region (3'UTR)...
December 28, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29282065/pulmonary-edema-following-central-nervous-system-lesions-induced-by-a-non-mouse-adapted-ev71-strain-in-neonatal-balb-c-mice
#11
Yuefei Jin, Chao Zhang, Rongguang Zhang, Jingchao Ren, Shuaiyin Chen, Meili Sui, Guangyuan Zhou, Dejian Dang, Jiehui Zhu, Huifen Feng, Yuanlin Xi, Haiyan Yang, Guangcai Duan
BACKGROUND: Enterovirus (EV) infection has been a serious health issue in Asia-Pacific region. It has been indicated that the occurrence of fatal hand foot and mouth disease (HFMD) cases following EV71 infection is mainly attributed to pulmonary edema. However, the development of pulmonary disorders after EV71 infection remains largely unknown. To establish an EV71-infected animal model and further explore the underlying association of central nervous system (CNS) invasion with pulmonary edema, we isolated a clinical source EV71 strain (ZZ1350) from a severe case in Henan Province...
December 28, 2017: Virology Journal
https://www.readbyqxmd.com/read/29260328/vivo-morpholino-oligomers-strongly-inhibit-dengue-virus-replication-and-production
#12
Patta Phumesin, Mutita Junking, Aussara Panya, Petlada Yongpitakwattana, Sansanee Noisakran, Thawornchai Limjindaporn, Pa-Thai Yenchitsomanus
Dengue virus (DENV) infection is a worldwide public health problem, which can cause severe dengue hemorrhagic fever (DHF) and life-threatening dengue shock syndrome (DSS). There are currently no anti-DENV drugs available, and there has been an intensive search for effective anti-DENV agents that can inhibit all four DENV serotypes. In this study, we tested whether vivo-morpholino oligomers (vivo-MOs), whose effect on DENV infection has not previously been studied, can inhibit DENV infection. Vivo-MOs were designed to target the top of 3' stem-loop (3' SL) in the 3' UTR of the DENV genome and tested for inhibition of DENV infection in monkey kidney epithelial (Vero) cells and human lung epithelial carcinoma (A549) cells...
December 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29235456/infection-via-mosquito-bite-alters-zika-virus-tissue-tropism-and-replication-kinetics-in-rhesus-macaques
#13
Dawn M Dudley, Christina M Newman, Joseph Lalli, Laurel M Stewart, Michelle R Koenig, Andrea M Weiler, Matthew R Semler, Gabrielle L Barry, Katie R Zarbock, Mariel S Mohns, Meghan E Breitbach, Nancy Schultz-Darken, Eric Peterson, Wendy Newton, Emma L Mohr, Saverio Capuano Iii, Jorge E Osorio, Shelby L O'Connor, David H O'Connor, Thomas C Friedrich, Matthew T Aliota
Mouse and nonhuman primate models now serve as useful platforms to study Zika virus (ZIKV) pathogenesis, candidate therapies, and vaccines, but they rely on needle inoculation of virus: the effects of mosquito-borne infection on disease outcome have not been explored in these models. Here we show that infection via mosquito bite delays ZIKV replication to peak viral loads in rhesus macaques. Importantly, in mosquito-infected animals ZIKV tissue distribution was limited to hemolymphatic tissues, female reproductive tract tissues, kidney, and liver, potentially emulating key features of human ZIKV infections, most of which are characterized by mild or asymptomatic disease...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29228714/unique-expression-signatures-of-circular-rnas-in-response-to-dna-tumor-virus-sv40-infection
#14
Jiandong Shi, Ningzhu Hu, Jianfang Li, Zhaoping Zeng, Ling Mo, Jing Sun, Meini Wu, Yunzhang Hu
Circular RNAs (circRNAs), identified as a class of widely expressed endogenous regulatory RNAs, are involved in diverse physiological and pathological processes. However, their role in viral pathogenesis and cellular antiviral response remains unexplored. In this study, a potent DNA tumor virus, simian virus 40 (SV40), was used as a model to investigate the viral influences on cellular circRNA transcriptome. Using RNA-seq, 15,241 putative circRNAs were identified de novo from 5,057 parental genes in monkey kidney-derived Vero cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209895/antiviral-activity-and-metal-ion-binding-properties-of-some-2-hydroxy-3-methoxyphenyl-acylhydrazones
#15
M Carcelli, E Fisicaro, C Compari, L Contardi, D Rogolino, C Solinas, A Stevaert, L Naesens
Here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and African Green monkey kidney cells). Interesting antiviral EC50 values are obtained against herpes simplex virus-1 and vaccinia virus...
December 5, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29190645/cd105-mesenchymal-stem-cells-migrate-into-osteoarthritis-joint-an-animal-model
#16
Pablo Fernandez-Pernas, Iván Rodríguez-Lesende, Alexandre de la Fuente, Jesús Mateos, Isaac Fuentes, Javier De Toro, Fco J Blanco, M C Arufe
Mesenchymal stem cells are being the focus of connective tissue technology and regenerative medicine, presenting a good choice cell source for improving old and well recognized techniques of cartilage defect repair. For instance, the autologous chondrocyte transplantation using new concepts of regenerative medicine. The present study investigated the risk of xenogenicity of human synovial membrane-derived MSCs, injected into the monkeys using intravenous and intra-articular administration. The animal models used were adult monkeys Rhesus which had been injured into the left knee to create an Osteoarthritis (OA) animal model...
2017: PloS One
https://www.readbyqxmd.com/read/29173547/bobcats-lynx-rufus-are-natural-definitive-host-of-besnoitia-darlingi
#17
Shiv K Verma, Camila K Cerqueira-Cézar, Fernando H A Murata, Matthew J Lovallo, Benjamin M Rosenthal, Jitender P Dubey
Bovine besnoitiosis, caused by Besnoitia besnoiti, is an economically important disease of cattle in many countries but its transmission remains a mystery. Wild felids are suspected to be its definitive hosts. The domestic cat (Felis catus) is known experimental definitive host for Besnoitia species of rodents. Here, we report for Besnoitia darlingi the first identification of a natural definitive host, the bobcat (Lynx rufus). Oocysts resembling Toxoplasma gondii (unsporulated; 10.9±0.8×12.1±0.2μm; n=5) were detected microscopically in the feces of two of 25 free ranging wild bobcats from Mississippi, USA...
December 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/29150986/memory-t-cells-are-significantly-increased-in-rejecting-liver-allografts-of-rhesus-monkeys
#18
Hwajung Kim, Hyeyoung Kim, Sun-Kyung Lee, Xue-Li Jin, Tae Jin Kim, Chanho Park, Jae-Il Lee, Hyo-Sin Kim, Suk Kyun Hong, Kyung Chul Yoon, Sung Woo Ahn, Kyoung-Bun Lee, Nam-Joon Yi, Jaeseok Yang, Kwang-Woong Lee, Wayne J Hawthorne, Kyung-Suk Suh
INTRODUCTION: The Rhesus monkey (RM) is an excellent preclinical model in kidney, heart and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of PBMCs and secondary lymphoid organs along with livers of normal rhesus monkeys and compared them to those of rejecting liver transplanted recipient's following withdrawal of immunosuppression...
November 18, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/29150543/toxicokinetics-and-physiologically-based-pharmacokinetic-modeling-of-the-shellfish-toxin-domoic-acid-in-nonhuman-primates
#19
Jing Jing, Rebekah Petroff, Sara Shum, Brenda Crouthamel, Ariel R Topletz, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen
Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA has not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys, following single doses of 5 µg/kg DA iv, 0.075 mg/kg DA po and 0.15 mg/kg DA po. Following iv dosing, DA had a systemic clearance of 124 ± 71 ml/hr/kg, volume of distribution at steady state of 131±71 ml/kg and elimination half-life of 1...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29149329/polymyxin-derivatives-nab739-and-nab815-are-more-effective-than-polymyxin-b-in-murine-escherichia-coli-pyelonephritis
#20
Martti Vaara, Timo Vaara, Carina Vingsbo Lundberg
Objectives: Extremely multiresistant strains of Enterobacteriaceae, such as those of Escherichia coli and Klebsiella pneumoniae, are emerging and spreading at a worrisome speed. Polymyxins (polymyxin B, colistin) are used as last-line therapy against such strains, in spite of their notable nephrotoxicity that may even require discontinuation of the therapy. We have previously developed polymyxin derivatives NAB739 and NAB815 that are better tolerated in cynomolgus monkeys than polymyxin B and are, in contrast to polymyxin B, excreted in the cynomolgus urine to a very significant degree...
November 14, 2017: Journal of Antimicrobial Chemotherapy
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