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Surendra Kumar
BACKROUND: The outbreak of H1N1 virus had previously reported in India during 2009 flu pandemic. In 2015, the outbreak became widespread throughout India. The states of Gujarat and Rajasthan are severely elected. We studied an outbreak of H1N1 Virus in north-west zone of Rajasthan 2015. OBJECTIVE: To demonstrate the current epidemiological scenario of swine flu (H1N1) in north-west zone of Rajasthan with different demographic factors. METHODS: We screened total 6390 patients...
July 2016: Journal of the Association of Physicians of India
Dalit Talmi-Frank, Zeev Altboum, Inna Solomonov, Yael Udi, Diego Adhemar Jaitin, Mordehay Klepfish, Eyal David, Alina Zhuravlev, Hadas Keren-Shaul, Deborah R Winter, Irit Gat-Viks, Michal Mandelboim, Tamar Ziv, Ido Amit, Irit Sagi
Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage...
October 12, 2016: Cell Host & Microbe
Anna Gillman
Oseltamivir is the best available anti-influenza drug and has therefore been stockpiled worldwide in large quantities as part of influenza pandemic preparedness planning. The active metabolite oseltamivir carboxylate (OC) is stable and is not removed by conventional sewage treatment. Active OC has been detected in river water at concentrations up to 0.86 µg/L. Although the natural reservoir hosts of influenza A virus (IAV) are wild waterfowl that reside in aquatic environments, the ecologic risks associated with environmental OC release and its potential to generate resistant viral variants among wild birds has largely been unknown...
2016: Infection Ecology & Epidemiology
Mimi C Yue, Joel T Collins, Elango Subramoniapillai, Glen A Kennedy
AIM: To describe a nosocomial outbreak of H1N1 influenza A in an inpatient hematology and allogeneic stem cell transplant unit and outcomes of universal oseltamivir prophylaxis. METHODS: Medical records of all patients admitted to the unit were reviewed to define the nosocomial outbreak, commencing 1 week prior to the index case until 4 weeks following institution of oseltamivir prophylaxis. Timelines for clinical symptoms, viral spread, management, patient outcomes and follow up testing were constructed...
October 12, 2016: Asia-Pacific Journal of Clinical Oncology
Hui Wang, XinCai Xiao, Jianyun Lu, Zongqiu Chen, Kuibiao Li, Hui Liu, Lei Luo, Ming Wang, ZhiCong Yang
BACKGROUND: Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014. The fatality rate was much higher than in previous reports. The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate. METHODS: Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research...
October 3, 2016: BMC Infectious Diseases
R Saito, H Akinobu, R A Shaker, I S Akel, A Assaf-Casals, M Lteif, T Odagiri, R Inaba, N Soudani, S Khafaja, S T Ghanem, M Rajab, Y Shobugawa, G S Dbaibo, H Zaraket
Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A(H3N2) was dominant in the 2013/14 season while the A(H1N1)pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors (oseltamivir, zanamivir, peramivir and laninamivir)...
October 2, 2016: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
R El Shesheny, N B Halasa, J V Williams, A A Shehabi, S Faouri, G Kayali, N Khuri-Bulos
Understanding the genetic evolution of A(H1N1)pdm09 and H3N2 viruses can help better select strains to be included in the annual influenza vaccine. There is little information on their evolution in Jordan so this study investigated the genetic and antigenic variability of A(H1N1)pdm09 and H3N2 viruses in Jordan by performing phylogenetic and genetic analyses of the HA and NA genes of A(H1N1)pdm09 and H3N2 viruses between 2011 and 2013. The full HA and NA genes of 16 H1N1-positive samples obtained in our study and 21 published HA sequences and 20 published NA sequences from Jordanian viruses that were available on online gene databases were analysed...
October 2, 2016: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
F Elfalki, H Ihazmad, A Bimouhen, Z Regragui, S Benkaroum, Y Bakri, A Barakat
We monitored phenotypic and genotypic susceptibility of influenza viruses circulating in Morocco during 2014-2015 to oseltamivir and zanamivir. Throat and nasal swab specimens were collected from outpatients (with influenza-like illness) and inpatients (with severe acute respiratory illness) and tested for influenza viruses using real-time reverse transcription polymerase chain reaction. Positive samples were inoculated in MDCK cells and virus phenotypic susceptibility to neuraminidase inhibitors (NAIs) was assessed using fluorescent NA inhibition...
October 2, 2016: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
Akinobu Hibino, Hiroki Kondo, Hironori Masaki, Yoshinari Tanabe, Isamu Sato, Nobuhiro Takemae, Takehiko Saito, Hassan Zaraket, Reiko Saito
We report five cases of community- and hospital-acquired infections with oseltamivir- and peramivir-resistant A(H1N1)pdm09 viruses possessing the neuraminidase (NA) H275Y mutation during January-February 2016 in Japan. One case was hospitalized and was receiving oseltamivir for prophylaxis. The remaining four cases were not taking antiviral drugs at the time of sampling. These cases were geographically distant and epidemiologically unrelated. The five viruses showed ~300-fold rise in IC50 values against oseltamivir and peramivir, defined as highly reduced inhibition according to the WHO definition...
October 6, 2016: Virus Genes
Jiraphorn Phanich, Thanyada Rungrotmongkol, Nawee Kungwan, Supot Hannongbua
The H7N9 avian influenza virus is a novel re-assortment from at least four different strains of virus. Neuraminidase, which is a glycoprotein on the surface membrane, has been the target for drug treatment. However, some H7N9 strains that have been isolated from patient after drug treatment have a R292K mutation in neuraminidase. This substitution was found to facilitate drug resistance using protein- and virus- assays, in particular it gave a high resistance to the most commonly used drug, oseltamivir. The aim of this research is to understand the source of oseltamivir resistance using MD simulations and the MM/PB(GB)SA binding free energy approaches...
October 6, 2016: Journal of Computer-aided Molecular Design
Richard Broadhurst, Anne Mounsey
Treatment of influenza virus infection with oral oseltamivir reduces time to alleviation of symptoms in adults and children by approximately one day compared with placebo. It reduces symptom duration even when initiated more than 2 days after symptom onset.
August 2016: Journal of Family Practice
Anja Hoffmann, Dennis Schade, Johannes Kirchmair, Bernd Clement, Andreas Sauerbrei, Michaela Schmidtke
Efforts to develop novel neuraminidase inhibitors (NAIs) for the treatment of influenza are ongoing. Novel NAIs should in particular be also effective against seasonal and/or pandemic N1 that carry a H274Y or N294S substitution (N2 numbering), which are most commonly linked to oseltamivir resistance. Here we report a platform for profiling the efficacy of novel NAIs in the N1 genetic background of influenza A virus. Employing reverse genetics, a set of influenza virus variants containing an amino acid substitution associated with oseltamivir resistance in N1 isolates (H274Y, N294S, Y155H or Q136L) was generated...
November 2016: Journal of Virological Methods
Kayoko Ohura, Hikaru Nishiyama, Saori Saco, Keisuke Kurokawa, Teruko Imai
Caco-2 cells predominantly express human carboxylesterase 1 (hCE1), unlike the human intestine which predominantly expresses human carboxylesterase 2 (hCE2). Transport experiments using Caco-2 cell monolayers often lead to mis-estimation of the intestinal absorption of prodrugs because of this difference, as prodrugs designed to increase the bioavailability of parent drugs are made to be resistant to hCE2 in the intestine, so that they can be hydrolyzed by hCE1 in the liver. In the present study, we tried to establish a new Caco-2 subclone, with a similar pattern of carboxylase expression to human intestine, to enable a more accurate estimation of the intestinal absorption of prodrugs...
September 16, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Xian-Ying Yang, Ai-Lin Liu, Shu-Jing Liu, Xiao-Wei Xu, Lin-Fang Huang
To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from 113 TCM. The medicine extracts were then reacted with oseltamivir, using 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) as the substrate, to determine influenza virus neuraminidase activity using a standard fluorimetric assay...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Vladimir Rafalsky, Alexander Averyanov, Boris Bart, Elena Minina, Mikhail Putilovskiy, Elena Andrianova, Oleg Epstein
OBJECTIVES: Ergoferon is an antiviral complex drug containing released-active forms of antibodies to interferon gamma, CD4, and histamine. Its efficacy and safety in the treatment of acute respiratory viral infections has been reported previously. The aim of this study was to compare Ergoferon with oseltamivir. METHODS: A multicenter, open-label, randomized controlled trial of patients aged 18 to 65 years, who had tested positive for influenza A or B antigens, was performed...
September 8, 2016: International Journal of Infectious Diseases: IJID
Kana Tokuda, Chiduru Watanabe, Yoshio Okiyama, Yuji Mochizuki, Kaori Fukuzawa, Yuto Komeiji
The fragment molecular orbital (FMO) method was applied to quantum chemical calculations of neuramic acid, the natural substrate of the influenza virus neuraminidase, and two of its competitive inhibitors, Oseltamivir (Tamiful(®)) and Zanamivir (Relenza(®)), to investigate their hydrated structures and energetics. Each of the three ligands was immersed in an explicit water solvent, geometry-optimized by classical MM and QM/MM methods, and subjected to FMO calculations with 2-, 3-, and 4-body corrections under several fragmentation options...
September 2016: Journal of Molecular Graphics & Modelling
Roman Akasov, Sabah Haq, Fiona Haxho, Vanessa Samuel, Sergey V Burov, Elena Markvicheva, Ronald J Neufeld, Myron R Szewczuk
Multicellular tumor spheroids (MTS) have been at the forefront of cancer research, designed to mimic tumor-like developmental patterns in vitro. Tumor growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS formation are not well defined. Matrix-free spheroids from breast MCF-7 and pancreatic PANC1 cancer cell lines and their respective tamoxifen (TMX) and gemcitabine (Gem) resistant variants were generated using the RGD platform of cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK (TPP))...
September 6, 2016: Oncotarget
Yacine Abed, Julie Carbonneau, Arnaud G L'Huillier, Laurent Kaiser, Guy Boivin
The H275Y and E119D neuraminidase (NA) mutations constitute important molecular markers of resistance to NA inhibitors in A(H1N1)pdm09 viruses. We used reverse transcriptase-droplet digital PCR amplification (RT-ddPCR) to analyze quasi-species at codons 275 and 119 of the NA in A(H1N1)pdm09 viruses recovered from an immuncompromised patient who received oseltamivir and zanamivir therapies. RT-ddPCR assays detected and quantified H275Y and E119D mutations with an efficiency that was comparable to that of high throughput sequencing (HiSeq 2500 Illumina) technology...
September 7, 2016: Journal of Medical Virology
Daniel B Hawcutt, Nicki-Jayne Russell, Hannah Maqsood, Koushan Kouranloo, Simon Gomberg, Catriona Waitt, Andrew Sharp, Andrew Riordan, Mark A Turner
AIMS: The UK Medicines and Healthcare products Regulatory Agency (MHRA) runs a national spontaneous reporting system (Yellow Card [YC] Scheme) to collect 'suspected' adverse drug reaction (ADR) data. We aim to describe the content and utility of YC reports received for patients aged <2 years. METHODS: Data on all ADRs reported using YC in Infants aged <2 years from the years 2001-10 were supplied by the MHRA. RESULTS: For infants age <2 years, 3496 suspected ADRs were reported using YC (Paternal medication pre-conception n = 3, transplacental n = 246, transmammary n = 30, neonates n = 97, infant n = 477, and vaccinations n = 2673), averaging 0...
September 6, 2016: British Journal of Clinical Pharmacology
Rashmi Dixit, Slade Matthews, Gulam Khandaker, Karen Walker, Marino Festa, Robert Booy
BACKGROUND: Oseltamivir is the only antiviral treatment recommended for influenza in young children over the age of 1 year. There is scant data on oseltamivir pharmacokinetics (PK) in infants <1 year. We set out to perform PK measurements in infants who received oseltamivir. METHODS: This study was a prospective, uncontrolled, open label evaluation of the pharmacokinetics of oseltamivir metabolism, safety of oseltamivir, viral clearance in infants <12 months diagnosed with influenza by nasopharyngeal influenza nucleic acid antigen test (NAAT)...
December 2016: Clinical and Translational Medicine
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