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https://www.readbyqxmd.com/read/28197304/ester-prodrugs-of-ihvr-19029-with-enhanced-oral-exposure-and-prevention-of-gastrointestinal-glucosidase-interaction
#1
Julia Ma, Shuo Wu, Xuexiang Zhang, Fang Guo, Katherine Yang, Jia Guo, Qing Su, Huagang Lu, Patrick Lam, Yuhuan Li, Zhengyin Yan, William Kinney, Ju-Tao Guo, Timothy M Block, Jinhong Chang, Yanming Du
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28194016/modelling-filovirus-maintenance-in-nature-by-experimental-transmission-of-marburg-virus-between-egyptian-rousette-bats
#2
Amy J Schuh, Brian R Amman, Megan E B Jones, Tara K Sealy, Luke S Uebelhoer, Jessica R Spengler, Brock E Martin, Jo Ann D Coleman-McCray, Stuart T Nichol, Jonathan S Towner
The Egyptian rousette bat (ERB) is a natural reservoir host for Marburg virus (MARV); however, the mechanisms by which MARV is transmitted bat-to-bat and to other animals are unclear. Here we co-house MARV-inoculated donor ERBs with naive contact ERBs. MARV shedding is detected in oral, rectal and urine specimens from inoculated bats from 5-19 days post infection. Simultaneously, MARV is detected in oral specimens from contact bats, indicating oral exposure to the virus. In the late study phase, we provide evidence that MARV can be horizontally transmitted from inoculated to contact ERBs by finding MARV RNA in blood and oral specimens from contact bats, followed by MARV IgG antibodies in these same bats...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179007/global-research-trends-of-world-health-organization-s-top-eight-emerging-pathogens
#3
Waleed M Sweileh
BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS)...
February 8, 2017: Globalization and Health
https://www.readbyqxmd.com/read/28167534/detection-of-lipid-induced-structural-changes-of-the-marburg-virus-matrix-protein-vp40-using-hydrogen-deuterium-exchange-mass-spectrometry
#4
Kaveesha J Wijesinghe, Sarah Urata, Nisha Bhattarai, Edgar E Kooijman, Bernard S Gerstman, Prem P Chapagain, Sheng Li, Robert V Stahelin
Marburg virus (MARV) is a lipid-enveloped virus from the Filoviridae family containing a negative sense RNA genome. One of the seven MARV genes encodes the matrix protein VP40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. MARV VP40 (mVP40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. While a number of mVP40 cationic residues have been shown to facilitate binding to membranes containing anionic lipids, much less is known on how mVP40 assembles to form the matrix layer following membrane binding...
February 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28155588/friedrich-august-genth-aus-w%C3%A3-chersbach-und-die-entdeckung-der-ersten-nio-kristalle-am-marburger-chemischen-institut-unter-robert-wilhelm-bunsen
#5
https://www.readbyqxmd.com/read/28135118/ebola-virus-and-marburg-virus-in-human-milk-are-inactivated-by-holder-pasteurization
#6
Erin Hamilton Spence, Monica Huff, Karen Shattuck, Amy Vickers, Nadezda Yun, Slobodan Paessler
BACKGROUND: Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. METHODS: Milk samples were obtained from a nonprofit milk bank...
January 1, 2017: Journal of Human Lactation: Official Journal of International Lactation Consultant Association
https://www.readbyqxmd.com/read/28130780/membrane-insertion-of-fusion-peptides-from-ebola-and-marburg-viruses-studied-by-replica-exchange-molecular-dynamics-simulations
#7
Mark A Olson, Michael S Lee, In-Chul Yeh
This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale...
January 28, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28122983/innate-immune-response-of-bat-and-human-cells-to-filoviruses-commonalities-and-distinctions
#8
Ivan V Kuzmin, Toni M Schwarz, Philipp A Ilinykh, Ingo Jordan, Thomas G Ksiazek, Ravi Sachidanandam, Christopher F Basler, Alexander Bukreyev
: Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28109709/the-effect-of-gamma-irradiation-conditions-on-the-immunogenicity-of-whole-inactivated-influenza-a-virus-vaccine
#9
Shannon C David, Josyane Lau, Eve V Singleton, Rachelle Babb, Justin Davies, Timothy R Hirst, Shaun R McColl, James C Paton, Mohammed Alsharifi
Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL)...
January 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28076420/chaperone-mediated-autophagy-protein-bag3-negatively-regulates-ebola-and-marburg-vp40-mediated-egress
#10
Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty
Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28074834/corrigendum-differential-transcriptional-responses-to-ebola-and-marburg-virus-infection-in-bat-and-human-cells
#11
Martin Hölzer, Verena Krähling, Fabian Amman, Emanuel Barth, Stephan H Bernhart, Victor A O Carmelo, Maximilian Collatz, Gero Doose, Florian Eggenhofer, Jan Ewald, Jörg Fallmann, Lasse M Feldhahn, Markus Fricke, Juliane Gebauer, Andreas J Gruber, Franziska Hufsky, Henrike Indrischek, Sabina Kanton, Jörg Linde, Nelly Mostajo, Roman Ochsenreiter, Konstantin Riege, Lorena Rivarola-Duarte, Abdullah H Sahyoun, Sita J Saunders, Stefan E Seemann, Andrea Tanzer, Bertram Vogel, Stefanie Wehner, Michael T Wolfinger, Rolf Backofen, Jan Gorodkin, Ivo Grosse, Ivo Hofacker, Steve Hoffmann, Christoph Kaleta, Peter F Stadler, Stephan Becker, Manja Marz
No abstract text is available yet for this article.
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070675/-refeeding-syndrome-in-geriatric-patients-a-frequently-overlooked-complication
#12
Rainer Wirth, Rebecca Diekmann, Olga Fleiter, Leonhardt Fricke, Annika Kreilkamp, Mirja Katrin Modreker, Christian Marburger, Stefan Nels, Rolf Schaefer, Heinz-Peter Willschrei, Dorothee Volkert
The refeeding syndrome is a life-threatening complication that can occur after initiation of a nutrition therapy in malnourished patients. If the risk factors and pathophysiology are known, the refeeding syndrome can effectively be prevented and treated, if recognized early. A slow increase of food intake and the close monitoring of serum electrolyte levels play an important role. Because the refeeding syndrome is not well known and the symptoms may vary extremely, this complication is poorly recognized, especially against the background of geriatric multimorbidity...
January 9, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28069021/preoperative-optimization-of-patient-expectations-improves-long-term-outcome-in-heart-surgery-patients-results-of-the-randomized-controlled-psy-heart-trial
#13
Winfried Rief, Meike C Shedden-Mora, Johannes A C Laferton, Charlotte Auer, Keith J Petrie, Stefan Salzmann, Manfred Schedlowski, Rainer Moosdorf
BACKGROUND: Placebo effects contribute substantially to outcome in most fields of medicine. While clinical trials typically try to control or minimize these effects, the potential of placebo mechanisms to improve outcome is rarely used. Patient expectations about treatment efficacy and outcome are major mechanisms that contribute to these placebo effects. We aimed to optimize these expectations to improve outcome in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: In a prospective three-arm randomized clinical trial with a 6 month follow-up, 124 patients scheduled for CABG surgery were randomized to either a brief psychological pre-surgery intervention to optimize outcome expectations (EXPECT); or a psychological control intervention focusing on emotional support and general advice, but not on expectations (SUPPORT); or to standard medical care (SMC)...
January 10, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28050052/the-hematologic-definition-of-monoclonal-gammopathy-of-undetermined-significance-in-relation-to-paraproteinemic-keratopathy-an-american-ophthalmological-society-thesis
#14
Walter Lisch, Joanna Wasielica-Poslednik, Tero Kivelä, Ursula Schlötzer-Schrehardt, Jens M Rohrbach, Walter Sekundo, Uwe Pleyer, Christina Lisch, Alexander Desuki, Heidi Rossmann, Jayne S Weiss
PURPOSE: To determine if paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of undetermined significance (MGUS) causes distinct patterns of corneal opacification that can be distinguished from hereditary, immunologic, or inflammatory causes. METHODS: A retrospective, interventional study of patients showed distinct bilateral opacity patterns of the cornea at the eye clinics of Hanau, Mainz, Helsinki, Marburg, and Berlin between 1993 and 2015...
August 2016: Transactions of the American Ophthalmological Society
https://www.readbyqxmd.com/read/28027897/relevance-of-dihydropyrimidine-dehydrogenase-and-thymidylate-synthase-in-patients-with-pancreatic-neuroendocrine-neoplasms-treated-with-5-fu-based-chemotherapy
#15
S Krug, M Boch, W Nimphius, T M Gress, P Michl, A Rinke
BACKGROUND: Chemotherapy with 5-FU and Streptozotocin (STZ) is recommended as first-line treatment in patients with metastatic pancreatic neuroendocrine neoplasms (PNEN). However, data about biomarkers involved in the 5-FU metabolism to predict response are still limited. OBJECTIVES: Evaluation of clinicopathological features and potential predictive and prognostic markers of patients with PNEN treated with 5-FU based regimens. PATIENTS AND METHODS: We retrospectively analyzed 41 patients with PNEN who were treated at the University Hospital Marburg between 2000 and 2013...
December 22, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28012899/corning-hyperflask-%C3%A2-for-viral-amplification-and-production-of-diagnostic-reagents
#16
Brian J Kearney, Matthew A Voorhees, Priscilla L Williams, Scott P Olschner, Cynthia A Rossi, Randal J Schoepp
Viral preparations are essential components in diagnostic research and development. The production of large quantities of virus traditionally is done by infecting numerous tissue culture flasks or roller bottles, which require large incubators and/or roller bottle racks. The Corning HYPERFlask(®) is a multilayer flask that uses a gas permeable film to provide gas exchange between the cells and culture medium and the atmospheric environment. This study evaluated the suitability of the HYPERFlask for production of Lassa, Ebola, Bundibugyo, Reston, and Marburg viruses and compared it to more traditional methods using tissue culture flasks and roller bottles...
December 21, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/28007224/efficacy-of-surgical-safety-checklist-assessing-orthopaedic-surgical-implant-readiness
#17
Benjamin G Thomasson, David Fuller, John Mansour, Robert Marburger, Erin Pukenas
INTRODUCTION: Our institution employs a Surgical Universal Protocol Preoperative Checklist in accordance with World Health Organization guidelines to promote patient safety. It is used in part to evaluate orthopaedic surgical equipment and implant readiness prior to the initiation of each surgical case. Our goal is to measure the preoperative checklist's efficacy in assessing orthopaedic equipment readiness preoperatively and its ability to prevent orthopaedic equipment failures (OEF)...
December 2016: Healthcare
https://www.readbyqxmd.com/read/27979676/ebola-virus-derived-g-quadruplexes-thiazole-orange-interaction
#18
Petra Krafčíková, Erika Demkovičová, Viktor Víglaský
The Ebola and Marburg viruses are some of the deadliest viruses in the world. In this study a series of G-rich DNA sequences derived from these types of viruses which possess the potential to form G-quadruplex structures are analyzed. A set of DNA oligonucleotides derived from original viral isolates was used as a representative modeling sequence with which to demonstrate the influence of thiazole orange on circular dichroism (CD) spectral profiles. The results show the unique profile of the induced CD (ICD) signal in the visible region caused by interactions between the ligand and G-quadruplexes...
December 13, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27976688/a-hamster-model-for-marburg-virus-infection-accurately-recapitulates-marburg-hemorrhagic-fever
#19
Andrea Marzi, Logan Banadyga, Elaine Haddock, Tina Thomas, Kui Shen, Eva J Horne, Dana P Scott, Heinz Feldmann, Hideki Ebihara
Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27930961/novel-activities-by-ebolavirus-and-marburgvirus-interferon-antagonists-revealed-using-a-standardized-in-vitro-reporter-system
#20
Jonathan C Guito, César G Albariño, Ayan K Chakrabarti, Jonathan S Towner
Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected...
January 15, 2017: Virology
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