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https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#1
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27855358/phytosynthesized-gold-nanoparticles-from-c-roxburghii-dc-leaf-and-their-toxic-effects-on-normal-and-cancer-cell-lines
#2
Pannerselvam Balashanmugam, Prabhu Durai, Manickam Dakshinamoorthi Balakumaran, Pudupalayam Thangavelu Kalaichelvan
Gold nanoparticles are considered of great importance compared to other noble metal nanoparticles and its wide range of applications like pharmaceutics, therapeutics and diagnostics etc. During the past decade, phytosynthesized gold nanoparticles (AuNPs) are more focused in in vitro and in vivo study. The present study was focused on the gold chloride and phytosynthesized gold nanoparticles from aqueous leaf extract of Cassia roxburghii and their toxic effects on African green monkey normal kidney Vero cell line and three different cancer cell lines such as HepG2, MCF7 and HeLa...
October 17, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27846155/effect-of-ex-vivo-expanded-recipient-regulatory-t-cells-on-hematopoietic-chimerism-and-kidney-allograft-tolerance-across-mhc-barriers-in-cynomolgus-macaques
#3
Raimon Duran-Struuck, Hugo P Sondermeijer, Leo Bühler, Paula Alonso-Guallart, Jonah Zitsman, Yojiro Kato, Anette Wu, Alicia N McMurchy, David Woodland, Adam Griesemer, Mercedes Martinez, Svetlan Boskovic, Tatsuo Kawai, A Benedict Cosimi, Cheng-Shie Wuu, Andrea Slate, Markus Mapara, Sam Baker, Rafal Tokarz, Vivette Dʼ Agati, Scott Hammer, Marcus Pereira, W Ian Lipkin, Thomas Wekerle, Megan Levings, Megan Sykes
BACKGROUND: Infusion of recipient regulatory T cells (Treg) promotes durable mixed hematopoietic chimerism and allograft tolerance in mice receiving allogeneic BMT with minimal conditioning. We applied this strategy in a Cynomolgus macaque model. METHODS: CD4+CD25high Treg that were polyclonally expanded in culture were highly suppressive in vitro and maintained high expression of FoxP3. Eight monkeys underwent nonmyeloablative conditioning and MHC-mismatched BMT with or without Treg infusion...
November 15, 2016: Transplantation
https://www.readbyqxmd.com/read/27816641/development-and-evaluation-of-topotecan-loaded-solid-lipid-nanoparticles-a-study-in-cervical-cancer-cell-lines
#4
Zhao-Jie Chen, Zhen Zhang, Bei-Bei Xie, Hai-Yan Zhang
The study aims at statistical development of solid lipid nanoparticles (SLNs) loaded with topotecan hydrochloride for avoiding the drawbacks of conventional drug therapies used in cervical cancer. Twenty SLN batches were prepared using organic solvent evaporation method to provide response surface curves. Thereafter, optimized SLNs were obtained using numeric method based on desirability functions providing maximum drug loading and appropriate particle size. Physical characterization of optimized TPH loaded SLNs was performed in terms of particle size, zeta potential, transmission and scanning electron microscopic evaluation...
October 18, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27795414/identification-of-novel-kshv-orf50-transcripts-discovery-of-new-rta-isoforms-with-variable-transactivation-potential
#5
Brian S Wakeman, Yoshihiro Izumiya, Samuel H Speck
: Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma, multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50. RTA is a known transactivator of multiple viral genes allowing for it to control the switch between latency and virus replication...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27764180/biodistribution-of-idursulfase-formulated-for-intrathecal-use-idursulfase-it-in-cynomolgus-monkeys-after-intrathecal-lumbar-administration
#6
Jou-Ku Chung, Eilish Brown, Bob Crooker, Kathleen J Palmieri, Thomas G McCauley
Enzyme replacement therapy with intravenous idursulfase (recombinant iduronate-2-sulfatase) is approved for the treatment of Hunter syndrome. Intravenous administration does not, however, treat the neurological manifestations, due to its low central nervous system bioavailability. Using intrathecal-lumbar administration, iduronate-2-sulfatase is delivered directly to the central nervous system. This study investigates the central nervous system biodistribution of intrathecal-lumbar administered iduronate-2-sulfatase in cynomolgus monkeys...
2016: PloS One
https://www.readbyqxmd.com/read/27738905/tanapoxvirus-lacking-a-neuregulin-like-gene-regresses-human-melanoma-tumors-in-nude-mice
#7
Tiantian Zhang, Yogesh R Suryawanshi, Dennis H Kordish, Helene M Woyczesczyk, David Jeng, Karim Essani
Neuregulin (NRG), an epidermal growth factor is known to promote the growth of various cell types, including human melanoma cells through ErbB family of tyrosine kinases receptors. Tanapoxvirus (TPV)-encoded protein TPV-15L, a functional mimic of NRG, also acts through ErbB receptors. Here, we show that the TPV-15L protein promotes melanoma proliferation. TPV recombinant generated by deleting the 15L gene (TPVΔ15L) showed replication ability similar to that of wild-type TPV (wtTPV) in owl monkey kidney cells, human lung fibroblast (WI-38) cells, and human melanoma (SK-MEL-3) cells...
October 13, 2016: Virus Genes
https://www.readbyqxmd.com/read/27701856/protective-effects-of-degraded-soybean-polysaccharides-on-renal-epithelial-cells-exposed-to-oxidative-damage
#8
Xin-Yuan Sun, Jian-Ming Ouyang, Poonam Bhadja, Qin Gui, Hua Peng, Jie Liu
This study aimed to investigate the protective effects of degraded soybean polysaccharides (DSP) on oxidatively damaged African green monkey kidney epithelial (Vero) cells. Low DSP concentration (10 μg/mL) elicited an evident protective effect on H2O2-induced cell injury (0.3 mmol/L). The cell viabilities of the H2O2-treated group and the DSP-protected group were 57.3% and 93.1%, respectively. The cell viability decreased to 88.3% when the dosage was increased to 100 μg/mL. DSP protected Vero cells from H2O2-mediated oxidative damage by enhancing cellular superoxide dismutase activity and total antioxidant capacity and by decreasing malonaldehyde content and lactate dehydrogenase release...
October 5, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27695060/correction-identification-of-micrornas-in-macaca-fascicularis-cynomolgus-monkey-by-homology-search-and-experimental-validation-by-small-rna-seq-and-rt-qpcr-using-kidney-cortex-tissues
#9
Yaligara Veeranagouda, Pierrick Rival, Catherine Prades, Claire Mariet, Jean-François Léonard, Jean-Charles Gautier, Xiaobing Zhou, Jufeng Wang, Bo Li, Marie-Laure Ozoux, Eric Boitier
[This corrects the article DOI: 10.1371/journal.pone.0142708.].
2016: PloS One
https://www.readbyqxmd.com/read/27684193/epa-method-1615-measurement-of-enterovirus-and-norovirus-occurrence-in-water-by-culture-and-rt-qpcr-ii-total-culturable-virus-assay
#10
G Shay Fout, Jennifer L Cashdollar
A standardized method is required when national studies on virus occurrence in environmental and drinking waters utilize multiple analytical laboratories. The U.S Environmental Protection Agency's (USEPA) Method 1615 was developed with the goal of providing such a standard for measuring Enterovirus and Norovirus in these waters. Virus is concentrated from water using an electropositive filter, eluted from the filter surface with beef extract, and then concentrated further using organic flocculation. Herein we present the protocol from Method 1615 for filter elution, secondary concentration, and measurement of total culturable viruses...
September 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27666430/matrix-metalloproteinase-20-co-expression-with-dentin-sialophosphoprotein-in-human-and-monkey-kidneys
#11
Kalu U E Ogbureke, Komal Koli, Geetu Saxena
We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively...
October 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27648636/reassortment-of-high-yield-influenza-viruses-in-vero-cells-and-safety-assessment-as-candidate-vaccine-strains
#12
Jian Zhou, Fan Yang, Jinghui Yang, Lei Ma, Yina Cun, Shaohui Song, Guoyang Liao
Vaccination is the practiced and accessible measure for preventing influenza infection. Because chicken embryos used for vaccine production have various insufficiencies, more efficient methods are needed. African green monkey kidney (Vero) cells are recommended by the World Health Organization (WHO) as a safe substitute for influenza vaccine production for humans. However, the influenza virus usually had low-yield in Vero cells, which limits the usage of Vero cellular vaccines. This study used two high-yield influenza viruses in Vero cells: A/Yunnan/1/2005Va (H3N2) and B/Yunnan/2/2005Va (B) as donor viruses...
September 20, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27647649/-patient-information-before-bladder-wall-injection-of-botulinum-toxin-a-botox-%C3%A2-which-essential-items-results-of-delphi-consensus-from-genulf-experts
#13
I Dominique, A Bourmaud, B Tamarelle, J E Terrier, A Ruffion
INTRODUCTION: Preoperative information before bladder wall injection of botulinum toxin A (Botox(®)) holds several essential facts to understand and retain by the patients. The aim of this study was a review of essential preoperative information items according to GENULF medical experts. METHOD: It was a prospective review from December 2015 to April 2016. Three Delphi rounds had been done from the Survey Monkey(®) software. The initial questionnaire was composed of items from the patient information sheet edited by the GENULF...
December 2016: Progrès en Urologie
https://www.readbyqxmd.com/read/27630227/the-presumed-polyomavirus-viroporin-vp4-of-simian-virus-40-or-human-bk-polyomavirus-is-not-required-for-viral-progeny-release
#14
Stian Henriksen, Terkel Hansen, Jack-Ansgar Bruun, Christine Hanssen Rinaldo
: The minor capsid protein of human BK polyomavirus (BKPyV), VP2, and its N-terminally truncated form, VP3, are both important for viral entry. The closely related simian virus 40 (SV40) reportedly produces an additional truncated form of VP2/3, denoted VP4, apparently functioning as a viroporin promoting progeny release. The VP4 open reading frame is conserved in some polyomaviruses, including BKPyV. In this study, we investigated the role of VP4 in BKPyV replication. By transfecting viral genomes into primary human renal proximal tubule epithelial cells, we demonstrated that unaltered BKPyV and mutants with start codon substitutions in VP4 (VP2M229I and VP2M229A) abolishing putative VP4 production were released at the same level to supernatants...
November 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27598231/asp2409-a-next-generation-ctla4-ig-versus-belatacept-in-renal-allograft-survival-in-cynomolgus-monkeys
#15
L Song, A Ma, H Dun, Y Hu, Y Fujii, F Kinugasa, S Oshima, Y Higashi, P Daloze, H Chen
Belatacept is the first costimulatory blockade agent approved for maintenance immunosuppression in kidney transplant recipients. Clinical results have indicated that belatacept is associated with superior renal function and improved metabolic profile. However, higher incidence of acute rejection and PTLD are the shortcomings of this agent. In this study, ASP2409, a new CTLA4-Ig possessing 14-fold higher in vitro CD86 binding affinity than belatacept, was tested for renal allograft survival in cynomolgus monkeys...
September 6, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27588895/altered-gene-expression-of-glycosyltransferases-and-sialyltransferases-and-total-amount-of-glycosphingolipids-following-herpes-simplex-virus-infection
#16
Kazuki Miyaji, Jun-Ichi Furukawa, Youichi Suzuki, Naoki Yamamoto, Yasuro Shinohara, Nobuhiro Yuki
There is a case report of a patient with overlapping Guillain-Barré syndrome and Bickerstaff brainstem encephalitis after infection with herpes simplex virus type 1 (HSV-1), who carried high titers of serum anti-GQ1b IgG antibodies. Several studies have linked viral infection to the modulation of ganglioside expression such as human T-lymphotropic virus to GD2 and simian virus 40 to GM3. Also, enhancement of the expression of GM2 on the cell membrane after cytomegalovirus infection has been reported. The objective of this study was to unveil the relationship between HSV-1 infection and the alteration of cellular ganglioside expression in neuronal and glial cell lines...
August 18, 2016: Carbohydrate Research
https://www.readbyqxmd.com/read/27576736/filaricidal-activities-on-onchocerca-ochengi-and-loa-loa-toxicity-and-phytochemical-screening-of-extracts-of-tragia-benthami-and-piper-umbellatum
#17
Fidelis Cho-Ngwa, Elvis Monya, Boris K Azantsa, Faustin Pascal T Manfo, Smith B Babiaka, James A Mbah, Moses Samje
BACKGROUND: Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L...
2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27569095/in-vitro-anticancer-and-cytotoxic-activities-of-some-plant-extracts-on-hela-and-vero-cell-lines
#18
Fulya Tugba Artun, Ali Karagoz, Gul Ozcan, Gulay Melikoglu, Sezin Anil, Sukran Kultur, Nurhayat Sutlupinar
PURPOSE: The aim of our study was to evaluate the effect of in vitro anticancer and cytotoxic activity of the methanolic extracts of 14 medicinal plants, 8 of which are endemic species in Anatolia, against the human HeLa cervical cancer cell line and to compare to the normal African green monkey kidney epithelial cell line (Vero) using the MTT colorimetric assay. METHODS: Values for cytotoxicity measured by MTT assay were expressed as the concentration that causes 50% decrease in cell viability (IC50, μg/mL)...
May 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/27543393/genomic-changes-detected-after-serial-passages-in-cell-culture-of-virulent-human-g1p-8-rotaviruses
#19
Takeshi Tsugawa, Hiroyuki Tsutsumi
Serial passages of a virulent mouse rotavirus in cell cultures caused a loss of virulence in mice. To gain insight into the genomic mutations in human rotavirus during cell culture and its attenuation in humans, we serially passaged three wild type human G1P[8] rotavirus strains (Wa, DC3695, DC5685) derived from diarrheal stool samples up to 60 times in two different cell cultures (human colon adenocarcinoma cell line: HT29, and primary African green monkey kidney cells: primary AGMK). We sequenced the whole genomes of 60 times-passaged strains and compared them with those of the original viruses...
August 16, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27518791/-the-history-of-kidney-transplantation
#20
M Hatzinger, M Stastny, P Grützmacher, M Sohn
The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861-1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed...
October 2016: Der Urologe. Ausg. A
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