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- Flu-like Symptoms and Associated Immunological Response Following Therapy with Botulinum Toxins. [JOURNAL ARTICLE]
- Neurotox Res 2013 May 16.
We aimed to define the frequency and risk factors associated with flu-like symptoms (FLS) and other systemic symptoms following treatment with botulinum toxins (BoNT) and correlate them with the immunological response as determined by blood cytokines. The study involved prospective clinical and serological evaluation for cytokine analysis in patients receiving BoNT for movement disorders. We interviewed 218 patients about FLS following BoNT injections and prospectively studied 117 patients (females 67.5 %; mean age 59.74 ± 12.39 years) treated with BoNT in a total of 143 treatment cycles. While no patient reported any FLS at baseline, the symptom complex was subsequently reported in 19 patients (16.3 %) and in 20 (14 %) treatment cycles, with at least one systemic symptom reported in 49 (42 %) patients in 59 (41.3 %) treatment cycles. FLS and at least one symptom were reported more frequently by women (P = 0.006 and P = 0.049, respectively) and by younger patients: 55.6 versus 61.7 years (P = 0.022). Although the symptoms were usually considered mild, they were rated as moderate to serious after 18 (12 %) cycles. The following interleukins showed increased levels at 7-10 days after the BoNT injections: IL-1β, IL-8, GROα, eotaxin, MCP-1 and 2, RANTES, TARC, and inducible protein 10 (IP10), but only the latter showed significantly increased levels in patients with FLS: 69 versus 3 pg/ml (P = 0.007). FLS and other systemic symptoms occur after about 14 % of treatment visits in patients receiving BoNT. IP10 levels correlate with the presence and severity of FLS.
- [Chile between pandemic: the influenza of 1918, globalization and the new medicine]. [English Abstract, Journal Article]
- Rev Chilena Infectol 2013 Apr; 30(2):206-15.
In 1918 Chile met the deadly presence of the Spanish influenza pandemic twentieth century's most important. For many historians, this event is an important milestone in the historical process of the unification of the world through sickness and in which our country has been involved. In this context, this paper aims to examine how the flu broke into Chilean society and how that situation helped give new impetus to the modernization of the Chilean public health and the establishment in the 1920s to model new medicine or preventive medicine.
- Attomolar Detection of Influenza A Virus Hemagglutinin Human H1 and Avian H5 Using Glycan-blotted Field Effect Transistor Biosensor. [JOURNAL ARTICLE]
- Anal Chem 2013 May 15.
Influenza virus, through the cell invasion and propagation with the interaction between hemagglutinin (HA) present on its surface and glycans on the host cell, causes a rapidly spreading infection throughout the world. In the present investigation, we succeeded for the first time in the attomolar-level sensing and discrimination of influenza A viral HA molecules H1 and H5 by using a glycan-immobilized field effect transistor (FET) biosensor. The small ligand glycans immobilized on the FET device, which make effective use of the charge-detectable region for FET-based detection in terms of Debye length, gave an advantage in the highly-sensitive detection of the proteins. Two kinds of trisaccharides receptors terminating in sialic acid-α2,6-galactose (6'-sialyllactose) and in sialic acid-α2,3-galactose (3'-sialyllactose) were conjugated directly with the SiO2 surface of FET devices by a simple glycoblotting method using the self-assembled monolayer (SAM) of aminooxy terminated silane-coupling reagent, 3-aminooxypropyltriethoxysilane. Furthermore, it was demonstrated that the FETs with densely-immobilized glycans, which possess the high capture ability by achieving the glycoside cluster effect, clearly distinguish HA molecules between their subtypes H1 (human) and H5 (avian) at the attomolar level, while the conventional method based on HA antibodies achieves only picomolar-level detection. Our findings indicate that the glycan-immobilized FET is a promising device to detect various pathogenic bacteria and viruses through glycan-protein interaction found ubiquitously in many infectious diseases.
- Proceedings of the Fourth ESWI Influenza Conference, September 11-14, 2011, Malta. [Congresses, Overall]
- Vaccine 2012 Dec 7; 30(51):7343-438.
- Isolation of influenza A(H3N2)v virus from pigs and characterization of its biological properties in pigs and mice. [JOURNAL ARTICLE]
- Arch Virol 2013 May 15.
Recently, a novel reassortant virus, influenza A(H3N2)v [A(H3N2)v], was identified as the causative pathogen in 307 human cases of influenza in the United States. A(H3N2)v contains the matrix gene from the 2009 pandemic H1N1 (pH1N1) virus, while its other genes originate from H3N2 viruses with triple-reassorted internal genes. In this study, we isolated three A(H3N2)v viruses from commercial pigs in Korea that showed similarities with published human A(H3N2)v viruses in eight segment sequence alignments. After genetic characterization, the pathogenicity of one of these viruses was assessed in pigs and mice. Infection of pigs with this novel virus resulted in mild interstitial pneumonia with marked oronasal shedding of viral RNA for about 14 days. In mice, the virus replicated efficiently in the lungs; viral RNA was detected up to 9 days post-inoculation. However, the virus did not cause severe disease or death in mice, despite the administration of a high infectious dose (10(5.2) TCID50). This study demonstrates that A(H3N2)v causes a high morbidity rate with low virulence; however, global monitoring of A(H3N2)v outbreaks in mammals will be needed to determine whether this novel subtype will shift to a highly pathogenic virus.
- Human monoclonal ScFv that bind to different functional domains of M2 and inhibit H5N1 influenza virus replication. [JOURNAL ARTICLE]
- Virol J 2013 May 14; 10(1):148.
BACKGROUND:Novel effective anti-influenza agent that tolerates influenza virus antigenic variation is needed. Highly conserved influenza virus M2 protein has multiple pivotal functions including ion channel activity for vRNP uncoating, anti-autophagy and virus assembly, morphogenesis and release. Thus, M2 is an attractive target of anti-influenza agents including small molecular drugs and specific antibodies.
METHODS:Fully human monoclonal single chain antibodies (HuScFv) specific to recombinant and native M2 proteins of A/H5N1 virus were produced from huscfv-phagemid transformed E. coli clones selected from a HuScFv phage display library using recombinant M2 of clade 1 A/H5N1 as panning antigen. The HuScFv were tested for their ability to inhibit replication of A/H5N1 of both homologous and heterologous clades. M2 domains bound by HuScFv of individual E. coli clones were identified by phage mimotope searching and computerized molecular docking.
RESULTS:HuScFv derived from four huscfv-phagemid transformed E. coli clones (no. 2, 19, 23 and 27) showed different amino acid sequences particularly at the CDRs. Cells infected with A/H5N1 influenza viruses (both adamantane sensitive and resistant) that had been exposed to the HuScFv had reduced virus release and intracellular virus. Phage peptide mimotope search and multiple alignments revealed that conformational epitopes of HuScFv2 located at the residues important for ion channel activity, anti-autophagy and M1 binding; epitopic residues of HuScFv19 located at the M2 amphipathic helix and cytoplasmic tail important for anti-autophagy, virus assembly, morphogenesis and release; epitope of HuScFv23 involved residues important for the M2 activities similar to HuScFv2 and also amphipathic helix residues for viral budding and release while HuScFv27 epitope spanned ectodomain, ion channel and anti-autophagy residues. Results of computerized homology modelling and molecular docking conformed to the epitope identification by phages.
CONCLUSIONS:HuScFv that bound to highly conserved epitopes across influenza A subtypes and human pathogenic H5N1clades located on different functional domains of M2 were produced. The HuScFv reduced viral release and intracellular virus of infected cells. While the molecular mechanisms of the HuScFv await experimental validation, the small human antibody fragments have high potential for developing further as a safe, novel and mutation tolerable anti-influenza agent especially against drug resistant variants.
- Knowledge, Attitudes, and Practices Regarding Pandemic H1N1 Influenza Among Medical and Dental Residents and Fellowships in Shiraz, Iran. [Journal Article]
- Int J Prev Med 2013 Apr; 4(4):396-403.
Influenza disease is one of the oldest medical problems that can cause severe illness and high mortality rates, worldwide. In flu pandemics, medical and dental students' knowledge, attitudes, and practices (KAP) is critical to save patients life. The aim of this study was to determine the score of KAP toward the Pandemic H1N1 and their predictor factors among the medical and dental residents and fellowships of Shiraz University of Medical Sciences, Iran.In 2009, 125 participants were recruited in a convenient sampling cross-sectional survey. Self-reported questionnaire were used and results were analyzed applying appropriate statistical tests.The mean score of participants' knowledge, attitude and practice were 22.6, 21.1 and 26.5 respectively. Participants practice had significant linear positive correlation with knowledge and attitude. Also, their age was significantly and directly correlated to knowledge and practice. The educational major, age, and sex were significant predictors of responder's knowledge score and age was the only significant predictor of both attitude and practice scores.High knowledge is not sufficient lonely for improve attitude and practices. It seems that traditional educational models are not efficient and governments should emphasize to advanced and motivational education methods including health belief model and motivational interview at postgraduate levels. Perhaps younger students, dentists and males have less motivation to change their attitude and behavior, so we can focuses our interventions in these groups.
- Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model. [Journal Article]
- PLoS Pathog 2013 May; 9(5):e1003354.
Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.
- A cure for the Flu? [Journal Article]
- Nat Rev Microbiol 2013 Jun; 11(6):361.