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Kurt Wood, Myron R Szewczuk, Dérick Rousseau, Ronald J Neufeld
Pickering emulsions are colloidal dispersions stabilized by particles that either migrate to, or are formed at, the oil-water interface during emulsification. Here, we fabricated and characterized Pickering water-in-oil emulsions where molten glycerol monostearate crystallized at the surface of micron-sized water droplets and formed protective solid shells. We tested this emulsion as a reservoir delivery platform for the sustained release of low molecular weight hydrophilic molecules including sodium chloride (NaCl) and sodium citrate as model compounds, and the therapeutic oseltamivir phosphate (OP), the delivery of which was the ultimate goal of this research...
February 27, 2018: Oncotarget
Noorakmar Jusoh, Hasanuddin Zainal, Azzmer Azzar Abdul Hamid, Noraslinda M Bunnori, Khairul Bariyyah Abd Halim, Shafida Abd Hamid
Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites...
March 15, 2018: Journal of Molecular Modeling
Jiantao Zhang, Yanmei Hu, Christopher Foley, Yuanxiang Wang, Rami Musharrafieh, Shuting Xu, Yongtao Zhang, Chunlong Ma, Christopher Hulme, Jun Wang
Influenza viruses are respiratory pathogens that are responsible for seasonal influenza and sporadic influenza pandemic. The therapeutic efficacy of current influenza vaccines and small molecule antiviral drugs is limited due to the emergence of multidrug-resistant influenza viruses. In response to the urgent need for the next generation of influenza antivirals, we utilized a fast-track drug discovery platform by exploring multi-component reaction products for antiviral drug candidates. Specifically, molecular docking was applied to screen a small molecule library derived from the Ugi-azide four-component reaction methodology for inhibitors that target the influenza polymerase PAC -PB1N interactions...
March 15, 2018: Scientific Reports
Haili Luo, Shaohong Wang, Tongmei Yuan, Jingtao Liu, Ling Yao, Xianguo Pan, Xuemei Long, Juncheng Wu, Feng Shen
BACKGROUND: More and more cases of human infections with avian influenza A H7N9 have been reported since it was first mentioned in 2013 in China, but concurrence of influenza A H7N9 with Mycoplasma pneumoniae, however, has never been described. Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well. CASE PRESENTATION: Our patient was an 80-year-old Chinese woman who presented with fever, cough, chest tightness, and shortness of breath...
March 15, 2018: Journal of Medical Case Reports
Rachel Harrington, Sruthi Adimadhyam, Todd A Lee, Glen T Schumock, James W Antoon
PURPOSE: Studies examining the association between use of oseltamivir and neuropsychiatric events (including suicide) among children have had mixed findings and have been limited by small sample size, reliance on older data, and potential confounding. We undertook an analysis that addresses these limitations. METHODS: Using a national administrative claims database and a case-crossover design that minimized confounding, we analyzed data from 5 contemporary influenza seasons (2009-2013) for individuals aged 1 to 18 years and ascertained oseltamivir exposure from pharmacy dispensing...
March 2018: Annals of Family Medicine
Manoj Kumar, Shanmugasundaram Nagarajan, Harshad V Murugkar, Barnalee Saikia, Bharati Singh, Amit Mishra, Sushil K Tripathi, Sonam Agarwal, Shweta Shukla, Diwakar D Kulkarni, Vijendra Pal Singh, Chakradhar Tosh
H6 subtype avian influenza viruses (AIV), established in terrestrial poultry, have jumped species barriers and caused human infection indicating pandemic potential of the virus. Here, we report isolation, and antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively. Hemagglutination inhibition assay revealed antigenic divergence between the two isolates. This result was corroborated by amino acid differences at 55 positions (15...
March 9, 2018: Infection, Genetics and Evolution
Qinhai Ma, Qingtian Yu, Xuefeng Xing, Sinian Liu, Chunyu Shi, Jiabo Luo
The San Wu Huangqin Decoction (SWHD), a traditional Chinese medicine formula, is used to treat colds caused by exposure to wind-pathogen, hyperpyrexia, infectious diseases and cancer; moreover, it is used for detoxification. The individual herbs of SWHD, such as Sophora flavescens and Scutellaria baicalensis , exhibit a wide spectrum of antiviral, anti-inflammatory, antibacterial, anticancer and other properties. The Chinese compound formula of SWHD is composed of S. flavescens, S. baicalensis and Rehmannia glutinosa ...
March 9, 2018: Viruses
Rami Musharrafieh, Chunlong Ma, Jun Wang
The majority of human influenza A viruses currently in circulation carry the amantadine-resistant AM2-S31N channel mutation. We previously discovered a series of AM2-S31N inhibitors with potent antiviral activity against both oseltamivir-sensitive and -resistant influenza A viruses. To understand the drug-resistance mechanism of AM2-S31N inhibitors, we performed serial viral passage experiments using the influenza virus A/California/07/2009 (H1N1) to select drug-resistant AM2 mutations against two representative AM2-S31N channel blockers (1 and 2)...
March 5, 2018: Antiviral Research
Kathryn B Anderson, Sriluck Simasathien, Veerachai Watanaveeradej, Alden L Weg, Damon W Ellison, Detchvijitr Suwanpakdee, Chonticha Klungthong, Thipwipha Phonpakobsin, Phirangkul Kerdpanich, Danabhand Phiboonbanakit, Robert V Gibbons, Stefan Fernandez, Louis R Macareo, In-Kyu Yoon, Richard G Jarman
Early diagnosis of influenza infection maximizes the effectiveness of antiviral medicines. Here, we assess the ability for clinical characteristics and rapid influenza tests to predict PCR-confirmed influenza infection in a sentinel, cross-sectional study for influenza-like illness (ILI) in Thailand. Participants meeting criteria for acute ILI (fever > 38°C and cough or sore throat) were recruited from inpatient and outpatient departments in Bangkok, Thailand, from 2009-2014. The primary endpoint for the study was the occurrence of virologically-confirmed influenza infection (based upon detection of viral RNA by RT-PCR) among individuals presenting for care with ILI...
2018: PloS One
F Scott Dahlgren, David K Shay, Hector S Izurieta, Richard A Forshee, Michael Wernecke, Yoganand Chillarige, Yun Lu, Jeffrey A Kelman, Carrie Reed
BACKGROUND: Over 34 million residents of the United States aged 65 years old and older are also Medicare prescription drug beneficiaries. Medical claims records for this age group potentially provide a wealth of data for better understanding influenza epidemiology. OBJECTIVE: The purpose of this study was to evaluate data on oseltamivir dispensing extracted from medical claims records as an indicator of influenza activity in the United States for the 2010-11 through 2014-15 influenza seasons...
March 5, 2018: Influenza and Other Respiratory Viruses
Jin Jung Kwon, Won-Suk Choi, Ju Hwan Jeong, Eun-Ha Kim, Ok-Jun Lee, Sun-Woo Yoon, Jungwon Hwang, Richard J Webby, Elena A Govorkova, Young Ki Choi, Yun Hee Baek, Min-Suk Song
The resistance of influenza viruses to neuraminidase (NA) inhibitors (NAIs; i.e. oseltamivir, zanamivir, peramivir and laninamivir) can be associated with several NA substitutions, with differing effects on viral fitness. To identify novel molecular markers conferring multi-NAI resistance, the NA gene of oseltamivir-resistant (H275Y, N1 numbering) 2009 pandemic influenza [A(H1N1)pdm09] virus was enriched with random mutations. This randomly mutated viral library was propagated in Madin-Darby canine kidney (MDCK) cells under zanamivir pressure and gave rise to additional changes within NA, including an I436N substitution located outside the NA enzyme active site...
March 2018: Journal of General Virology
Cinzia Colombo, Črtomir Podlipnik, Leonardo Lo Presti, Masahiro Niikura, Andrew J Bennet, Anna Bernardi
The rise of drug-resistant influenza A virus strains motivates the development of new antiviral drugs, with different structural motifs and substitution. Recently, we explored the use of a bicyclic (bicyclo[3.1.0]hexane) analogue of sialic acid that was designed to mimic the conformation adopted during enzymatic cleavage within the neuraminidase (NA; sialidase) active site. Given that our first series of compounds were at least four orders of magnitude less active than available drugs, we hypothesized that the new carbon skeleton did not elicit the same interactions as the cyclohexene frameworks used previously...
2018: PloS One
Nobuhisa Ishiguro, Naoko Koseki, Miki Kaiho, Tadashi Ariga, Hideaki Kikuta, Koji Oba, Takehiro Togashi, Keisuke Morita, Akira Inagawa, Akiko Okamura, Shigeru Yamazaki, Satoru Shida, Mutsuko Konno, Nobuaki Kawamura, Akihito Ishizaka, Kimihiko Takada, Keiji Tsubakihara, Naoko Nagano, Mutsuo Shibata, Hideto Furuyama, Yoshihiro Matsuzono, Akemi Koike, Mari Murashita, Yoshio Hatae, Hideki Arioka, Tatsuru Yamanaka, Toru Watanabe, Yuuichi Tabata, Yoshihiro Kumita, Kyosuke Hazama, Yasushi Akutsu, Hayato Aoyagi, Chie Tobise, Katsuki Azuma, Kohichi Yasoshima, Yoko Sawada, Kazuyuki Uetsuji, Akira Tsuchida, Akira Tsuchiyama, Kazue Yasuda, Yasuhisa Odagawa, Mikio Yoshioka
The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014-2015 to 2016-2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1...
February 24, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Young-Jun Choi, Hyemin Kim, Ji-Woo Kim, Seokjoo Yoon, Han-Jin Park
OBJECTIVES: The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism. RESULTS: Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (p < 0...
February 20, 2018: Biotechnology Letters
Stephanie L Mitchell, Yeh-Chung Chang, Kristen Feemster, Ana María Cárdenas
PURPOSE: Influenza A virus (FluA), influenza B virus (FluB) and respiratory syncytial virus (RSV) illnesses increase hospitalizations during seasonal epidemics. METHODOLOGY: To determine the utility of the Simplexa FluA/B & RSV Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this assay to emergency department (ED) patients with influenza-like illness. RESULTS: Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours...
January 10, 2018: Journal of Medical Microbiology
E J Growcott, D Bamba, J-R Galarneau, V H J Leonard, W Schul, D Stein, C S Osborne
PURPOSE: Influenza viruses are a common cause of human respiratory infections, resulting in epidemics of high morbidity and mortality. We investigated the effect of a novel mitogen-activated protein kinase (MAPK) inhibitor in vitro and in a murine influenza model to further explore whether p38 MAPK inhibition could reduce viral replication. METHODS: In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38 MAPK inhibitor with an IC50 value of<1 µM, currently in clinical testing), dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection...
January 24, 2018: Journal of Medical Microbiology
Ramona Trebbien, Claus Bohn Christiansen, Thea Kølsen Fischer
BACKGROUND AND OBJECTIVE: Antiviral treatment of influenza virus infections can lead to drug resistance of virus. This study investigates a selection of mutations in the full genome of H3N2 influenza A virus isolated from a patient in treatment with oseltamivir. STUDY DESIGN: Respiratory samples from a patient were collected before, during, and after antiviral treatment. Whole genome sequencing of the influenza virus by next generation sequencing, and low-frequency-variant analysis was performed...
February 11, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
D B C Wu, N Chaiyakunapruk, C Pratoomsoot, K K C Lee, H Y Chong, R E Nelson, P F Smith, C M Kirkpatrick, M A Kamal, K Nieforth, G Dall, S Toovey, D C M Kong, A Kamauu, C R Rayner
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility...
March 2018: Epidemiology and Infection
Hector S Izurieta, Yoganand Chillarige, Jeffrey A Kelman, Richard Forshee, Yandong Qiang, Michael Wernecke, Jill M Ferdinands, Yun Lu, Yuqin Wei, Wenjie Xu, Michael Lu, Alicia Fry, Douglas Pratt, David K Shay
Background: Statins are used to reduce cardiovascular disease risk. Recent studies suggest that statin use may be associated with an increased influenza risk among influenza vaccinees. We used Medicare data to evaluate associations between statins and risks of influenza-related encounters among vaccinees. Methods: In this retrospective cohort study, we identified Medicare beneficiaries aged >65 years who received high-dose (HD) or standard-dose (SD) influenza vaccines at pharmacies from 2010-11 through 2014-15...
February 9, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mark H Ebell
No abstract text is available yet for this article.
December 15, 2017: American Family Physician
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