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https://www.readbyqxmd.com/read/28500071/activated-microglia-desialylate-and-phagocytose-cells-via-neuraminidase-galectin-3-and-mer-tyrosine-kinase
#1
Koji Nomura, Anna Vilalta, David H Allendorf, Tamara C Hornik, Guy C Brown
Activated microglia can phagocytose dying, stressed, or excess neurons and synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal-3) can cross-link surface glycoproteins by binding galactose residues that are normally hidden below terminal sialic acid residues. Gal-3 was recently reported to opsonize cells via activating MerTK. We found that LPS-activated BV-2 microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors. Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and it increased microglial phagocytosis of PC12 cells or primary neurons, which was blocked by inhibition of MerTK...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28457075/comparative-characteristics-of-the-2009-pandemic-influenza-a-h1n1-virus-and-2010-2011-seasonal-influenza-in-pediatric-patients
#2
Najwan Nasrallah, Yael Shachor-Meyouhas, Zipi Kra-Oz, Tania Mashiach, Moran Szwarcwort-Cohen, Eynat Shafran, Imad Kassis
BACKGROUND: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2. OBJECTIVES: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic. METHODS: A retrospective observational study was conducted at a tertiary hospital...
December 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28433777/design-and-expeditious-synthesis-of-organosilanes-as-potent-antivirals-targeting-multidrug-resistant-influenza-a-viruses
#3
Yanmei Hu, Yuanxiang Wang, Fang Li, Chunlong Ma, Jun Wang
The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28416546/anti-influenza-activity-of-bacillus-subtilis-probiotic-strain
#4
Darya Starosila, Svetlana Rybalko, Ludmila Varbanetz, Naila Ivanskaya, Iryna Sorokulova
Among Bacillus bacteria, B. subtilis is the most productive species of antimicrobial compounds. In this study, we analyzed the activity of probiotic strain B. subtilis 3 against influenza virus. The antiviral effect of this strain has been demonstrated in vitro and in vivo New peptide P18 produced by probiotic strain was isolated, purified, chemically synthesized, and characterized. Cytotoxicity studies demonstrated no toxic effect of P18 on Madin-Darby canine kidney (MDCK) cells, even in the highest tested concentration (100 μg/mL)...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28377100/the-mek-inhibitor-ci-1040-displays-a-broad-anti-influenza-virus-activity-in%C3%A2-vitro-and-provides-a-prolonged-treatment-window-compared-to-standard-of-care-in%C3%A2-vivo
#5
Emanuel Haasbach, Christin Müller, Christina Ehrhardt, Andre Schreiber, Stephan Pleschka, Stephan Ludwig, Oliver Planz
Influenza viruses (IV) continue to pose an imminent threat to human welfare. Yearly re-occurring seasonal epidemic outbreaks and pandemics with high mortality can occur. Besides vaccination against a limited number of viral strains only a few antiviral drugs are available, which are losing their effectiveness as more and more IV strains become resistant. Thus, new antiviral approaches that omit IV resistance are urgently needed. Here, the dependency on the cellular Raf/MEK/ERK signaling pathway for IV replication opens a new perspective...
June 2017: Antiviral Research
https://www.readbyqxmd.com/read/28337082/pharmacokinetics-of-peramivir-in-an-adolescent-patient-receiving-continuous-venovenous-hemodiafiltration
#6
Ryan C Dillon, Robert Witcher, Jeffrey J Cies, Wayne S Moore, Arun Chopra
Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration-approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia...
January 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28315686/crystal-structure-of-the-catalytic-domain-of-clostridium-perfringens-neuraminidase-in-complex-with-a-non-carbohydrate-based-inhibitor-2-cyclohexylamino-ethanesulfonic-acid
#7
Youngjin Lee, Hyung-Seop Youn, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Jung Youn Kang, Young Bae Ryu, Mi Sun Jin, Ki Hun Park, Soo Hyun Eom
Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28188897/survival-biases-lead-to-flawed-conclusions-in-observational-treatment-studies-of-influenza-patients
#8
Martin Wolkewitz, Martin Schumacher
BACKGROUND AND OBJECTIVE: Several observational studies reported that Oseltamivir (Tamiflu) reduced mortality in infected and hospitalized patients. Because of the restriction of observation to hospital stay and time-dependent treatment assignment, such findings were prone to common types of survival bias (length, time-dependent and competing risk bias). METHODS: British hospital data from the Influenza Clinical Information Network (FLU-CIN) study group were used which included 1,391 patients with confirmed pandemic influenza A/H1N1 2009 infection...
February 7, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28155963/stereoisomers-of-oseltamivir-synthesis-in-silico-prediction-and-biological-evaluation
#9
Viktória Hajzer, Roman Fišera, Attila Latika, Július Durmis, Jakub Kollár, Vladimír Frecer, Zuzana Tučeková, Stanislav Miertuš, František Kostolanský, Eva Varečková, Radovan Šebesta
Oseltamivir is an important antiviral drug, which possess three chirality centers in its structure. From eight possible stereoisomers, only two have been synthesized and evaluated so far. We describe herein the stereoselective synthesis, computational activity prediction and biological testing of another three diastereoisomers of oseltamivir. These isomers have been synthesized using stereoselective organocatalytic Michael addition, cyclization and reduction. Their binding to viral neuraminidase N1 of influenza A virus was evaluated by quantum-chemical calculations and their anti-influenza activities were tested by an in vitro virus-inhibition assay...
February 3, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#10
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/27997573/genetic-characterization-of-circulating-2015-a-h1n1-pdm09-influenza-viruses-from-eastern-india
#11
Anupam Mukherjee, Mukti Kant Nayak, Shanta Dutta, Samiran Panda, Biswa Ranjan Satpathi, Mamta Chawla-Sarkar
In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015...
2016: PloS One
https://www.readbyqxmd.com/read/27966711/development-of-a-point-of-care-diagnostic-for-influenza-detection-with-antiviral-treatment-effectiveness-indication
#12
Richard C Murdock, Karen M Gallegos, Joshua A Hagen, Nancy Kelley-Loughnane, Alison A Weiss, Ian Papautsky
Currently, diagnosis of influenza is performed either through tedious polymerase chain reaction (PCR) or through rapid antigen detection assays. The rapid antigen detection assays available today are highly specific but not very sensitive, and most importantly, lack the ability to show if the strain of influenza detected is susceptible to antiviral agents, such as Tamiflu and Relenza. The ability to rapidly determine if a patient has an infectious disease and what type of treatment the infection will respond to, would significantly reduce the treatment decision time, shorten the impact of symptoms, and minimize transfer to others...
January 17, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/27924780/activity-of-ergoferon-against-lethal-influenza-a-h3n2-virus-infection-in-mice
#13
Maria A Skarnovich, Alexandra G Emelyanova, Nataliia V Petrova, Alena A Borshcheva, Evgeniy A Gorbunov, Oleg Yu Mazurkov, Maksim O Skarnovich, Sergey A Tarasov, Larisa N Shishkina, Oleg I Epstein
BACKGROUND: The Influenza A virus accounts for serious annual viral upper respiratory tract infections. It is constantly able to modify its antigenic structure, thus evading host defence mechanisms. Moreover, currently available anti-influenza agents have a rather limited application, emphasising the further need for new effective treatments. One of them is Ergoferon, a drug, containing combined polyclonal antibodies - anti-interferon gamma, anti-CD4 receptor, and anti-histamine - in released-active form...
December 7, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27800573/pharmacokinetic-modeling-and-monte-carlo-simulation-to-predict-interindividual-variability-in-human-exposure-to-oseltamivir-and-its-active-metabolite-ro-64-0802
#14
Mototsugu Ito, Hiroyuki Kusuhara, Atsushi Ose, Tsunenori Kondo, Kazunari Tanabe, Hideki Nakayama, Shigeru Horita, Takuya Fujita, Yuichi Sugiyama
Oseltamivir (Tamiflu®) is a prodrug of Ro 64-0802, a selective inhibitor of influenza virus neuraminidase. There is a possible relationship between oseltamivir treatment and neuropsychiatric adverse events; although this has not been established, close monitoring is recommended on the prescription label. The objective of this study was to predict interindividual variability of human exposure to oseltamivir and its active metabolite Ro 64-0802. By leveraging mathematical models and computations, physiological parameters in virtual subjects were generated with population means and coefficient of variations collected from the literature or produced experimentally...
January 2017: AAPS Journal
https://www.readbyqxmd.com/read/27567070/fda-approves-first-generic-version-of-tamiflu
#15
Patricia Lobo
No abstract text is available yet for this article.
October 2016: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27522128/an-evaluation-of-the-use-of-short-message-service-during-an-avian-influenza-outbreak-on-a-poultry-farm-in-young
#16
Lisa M Stephenson, Janice S Biggs, Vicky Sheppeard, Tracey L Oakman
In 2013 an avian influenza outbreak occurred in a large poultry farm in Young (approximately 2 hours north-west of Canberra.) The responsible strain was H7N2, which is highly pathogenic and can affect humans. Daily surveillance was required for those individuals who were possibly exposed. This was conducted through the use of daily message through the short message service (SMS). A total of 55 people were identified as having had high risk exposure and requiring monitoring during the surveillance period from 16 to 25 October 2013...
June 30, 2016: Communicable Diseases Intelligence Quarterly Report
https://www.readbyqxmd.com/read/27490658/patient-perceptions-of-oseltamivir-for-the-treatment-of-influenza
#17
Steven G Schauer, Shawn M Varney, James K Aden, Vikhyat S Bebarta
OBJECTIVES: Oseltamivir (Tamiflu) is approved by the Food and Drug Administration and is advertised for the treatment of influenza types A and B. Patient perceptions of its efficacy have not been adequately studied. Recent systematic reviews have called the benefits of this drug into question relative to the cost and adverse effect profile. We hypothesized that most people would be unaware of the efficacy, cost, or adverse effect profile of the drug. Our objective was to determine patient perceptions of efficacy, cost, and adverse effect profile of oseltamivir for the treatment of influenza...
August 2016: Southern Medical Journal
https://www.readbyqxmd.com/read/27454847/shikimic-acid-inhibits-lps-induced-cellular-pro-inflammatory-cytokines-and-attenuates-mechanical-hyperalgesia-in-mice
#18
Thallita Kelly Rabelo, Adriana Gibara Guimarães, Marlange Almeida Oliveira, Juciano Gasparotto, Mairim Russo Serafini, Adriano Antunes de Souza Araújo, Lucindo José Quintans-Júnior, José Cláudio Fonseca Moreira, Daniel Pens Gelain
BACKGROUND AND AIMS: Shikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA. METHODS: RAW 264.7 macrophage cells were treated with bacterial LPS (1μg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1β content and MAPK (ERK1/2 and p38) activation was evaluated...
October 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27351973/two-escape-mechanisms-of-influenza-a-virus-to-a-broadly-neutralizing-stalk-binding-antibody
#19
Ning Chai, Lee R Swem, Mike Reichelt, Haiyin Chen-Harris, Elizabeth Luis, Summer Park, Ashley Fouts, Patrick Lupardus, Thomas D Wu, Olga Li, Jacqueline McBride, Michael Lawrence, Min Xu, Man-Wah Tan
Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking virus infection both in vitro and in vivo. The highly conserved epitopes recognized by these antibodies are critical for the membrane fusion function of HA and therefore less likely to be permissive for virus mutational escape. Here we report three resistant viruses of the A/Perth/16/2009 strain that were selected in the presence of a broadly neutralizing stalk-binding antibody...
June 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27339308/studies-on-the-production-of-shikimic-acid-using-the-arok-knockout-strain-of-bacillus-megaterium
#20
Saptarshi Ghosh, Utpal Mohan, Uttam Chand Banerjee
Shikimic acid has various pharmaceutical and industrial applications. It is the sole chemical building block for the antiviral drug oseltamivir (Tamiflu(®)) and one of the potent pharmaceutical intermediates with three chiral centres. Here we report a modified strain of Bacillus megaterium with aroK (shikimate kinase) knock out to block the aromatic biosynthetic pathway downstream of shikimic acid. Homologous recombination based gene disruption approach was used for generating aroK knock out mutant of B. megaterium...
August 2016: World Journal of Microbiology & Biotechnology
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