Byington C.L.,University of Utah |
Ampofo K.,University of Utah |
Stockmann C.,University of Utah |
Adler F.R.,Biology |
And 7 more authors.
Clinical Infectious Diseases | Year: 2015
Background. This study: (1) describes the viral etiology of respiratory illness by prospectively collecting weekly symptom diaries and nasal swabs from families for 1 year, (2) analyzed data by reported symptoms, virus, age, and family composition, and (3) evaluated the duration of virus detection. Methods. Twenty-six households (108 individuals) provided concurrent symptom and nasal swab data for 4166 person-weeks. The FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC) was used to detect 16 respiratory viruses. Viral illnesses were defined as ?1 consecutive weeks with the same virus detected with symptoms reported in ?1 week. Results. Participants reported symptoms in 23% and a virus was detected in 26% of person-weeks. Children younger than 5 years reported symptoms more often and were more likely to have a virus detected than older participants (odds ratio [OR] 2.47, 95% confidence interval [CI], 2.08-2.94 and OR 3.96, 95% CI, 3.35-4.70, respectively). Compared with single person households, individuals living with children experienced 3 additional weeks of virus detection. There were 783 viral detection episodes; 440 (56%) associated with symptoms. Coronaviruses, human metapneumovirus, and influenza A detections were usually symptomatic; bocavirus and rhinovirus detections were often asymptomatic. The mean duration of PCR detection was ≤2 weeks for all viruses and detections of ?3 weeks occurred in 16% of episodes. Younger children had longer durations of PCR detection. Conclusions. Viral detection is often asymptomatic and occasionally prolonged, especially for bocavirus and rhinovirus. In clinical settings, the interpretation of positive PCR tests, particularly in young children and those who live with them, may be confounded. © The Author 2015. Source
Pharmacokinetic and pharmacodynamic properties of gs-9620, a novel toll-like receptor 7 agonist, demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral dosess
Zheng J.,Drug Metabolism |
Pflanz S.,Biology |
Frey C.R.,Biology |
Hesselgesser J.,Clinical Virology and Medicinal Chemistry |
And 2 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2014
GS-9620 [8-(3-(pyrrolidin-1-ylmethyl)benzyl)-4-amino-2-butoxy-7,8- dihydropteridin-6(5H)-one] is a potent, orally bioavailable small-molecule agonist of Toll-like receptor 7 (TLR7) developed for finite treatment of chronic hepatitis B viral (HBV) infection, with the goal of inducing a liver-targeted antiviral effect without inducing the adverse effects associated with current systemic interferon-a (IFN-a) therapies. We characterized the pharmacodynamic response of GS-9620 in CD-1 mice and cynomolgus monkeys following intravenous or oral administration and showed that GS-9620 induces the production of select chemokines and cytokines, including IFN-a and interferon-stimulated genes (ISGs). It is noteworthy that we also demonstrated that, in animals and healthy human volunteers, oral administration of GS-9620 can induce a type I interferon-dependent antiviral innate immune response, as measured by whole-blood mRNA of the ISGs 2959-oligoadenylate synthetase 1 (OAS1) and myxovirus resistance 1 (MX1), without the induction of detectable systemic IFN-a, i.e., a presystemic response. Additionally, presystemic induction of hepatic OAS1 and MX1 mRNA was observed in CD-1 mice in the absence of detectable systemic IFN-a. We propose that the mechanism of this presystemic response is likely its high intestinal absorption,which facilitates localized activation of TLR7, probably in plasmacytoid dendritic cells at the level of gut-associated lymphoid tissue and/or the liver. This localized response is further supported by data that indicate onlyminimal contributions of systemic immune stimulation to the overall pharmacodynamic response to orally administered GS-9620. These data demonstrate that GS-9620 can induce an antiviral innate immune response without inducing a systemic IFN-a response and thus suggest the therapeutic potential of this approach in the treatment of chronic HBV infection. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics. Source
Prates J.,Sao Paulo State University |
Franco-Salla G.B.,Sao Paulo State University |
Dinarte dos Santos A.R.,University of Sao Paulo |
da Silva W.A.,University of Sao Paulo |
And 4 more authors.
Gene | Year: 2015
Cervical cancer is the second most frequent cancer in women worldwide and is associated with genetic alterations, infection with human papilloma virus (HPV), angiogenesis and inflammatory processes. The idea that inflammation is involved in tumorigenesis is supported by the frequent appearance of cancer in areas of chronic inflammation. On the other hand, the inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1), a 37. kDa protein was detected as a modulator of inflammatory processes and is expressed by tumor cells.The study was carried out on the epithelial cancer cell line (SiHa) treated with the peptide of annexin A1 (ANXA1Ac2-26). We combined subtraction hybridization approach, Ingenuity Systems software and quantitative PCR, in order to evaluate gene expression influenced by ANXA1.We observed that ANXA1Ac2-26 inhibited proliferation in SiHa cells after 72h. In these cells, 55 genes exhibited changes in expression levels in response to peptide treatment. Six genes were selected and the expression results of 5 up-regulated genes (TPT1, LDHA, NCOA3, HIF1A, RAB13) and one down-regulated gene (ID1) were research by real time quantitative PCR. Four more genes (BMP4, BMPR1B, SMAD1 and SMAD4) of the ID1 pathway were investigated and only one (BMPR1B) shows the same down regulation.The data indicate the involvement of ANXA1Ac2-26 in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of cervical cancer. © 2015 Elsevier B.V. Source
Chimia | Year: 2014
Winning in the global market place with brilliant innovations is the recipe for success for the Swiss economy. Indeed, Switzerland always stands out in the global rankings when it comes to innovation. Yet there is nothing as dangerous as to rest on one's laurels, and this is particularly true for R&D-based businesses. For this reason CTI, the Commission for Technology and Innovation, offers Swiss companies quick and effective access to knowledge available at Swiss public research institutions, and to international R&D programs promoting application-oriented research. Knowledge and technology transfer are promoted - via its KTT support - through National Thematic Networks (NTNs), Innovation Mentors and information platforms. The following article highlights the activities of the National Thematic Networks and invites Swiss companies and research institutes to benefit from the multiple offers and services available. © Schweizerische Chemische Gesellschaft. Source
Atamanyuk D.,Medicinal Chemistry |
Faivre F.,Medicinal Chemistry |
Oxoby M.,Medicinal Chemistry |
Ledoussal B.,Medicinal Chemistry |
And 3 more authors.
Journal of Medicinal Chemistry | Year: 2013
In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their Gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies. © 2013 American Chemical Society. Source