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https://www.readbyqxmd.com/read/28094956/radiolabeled-r954-derivatives-for-imaging-bradykinin-b1-receptor-expression-with-positron-emission-tomography
#1
Hsiou-Ting Kuo, Jinhe Pan, Joseph Lau, Chengcheng Zhang, Jutta Zeisler, Nadine Colpo, Francois Benard, Kuo-Shyan Lin
Peptide receptors have emerged as promising targets for diagnosis and therapy. The aberrant overexpression of these receptors in different cancer subtypes allows for the adoption of new treatment strategies that complement conventional chemotherapies. Bradykinin B1 receptor (B1R) is a G protein-coupled receptor that is overexpressed in many cancers, with limited expression in healthy tissues. Previously, we developed 68Ga- and 18F-labeled derivatives of B1R antagonist peptides B9858 and B9958, and successfully targeted B1R-expressing tumor xenografts in vivo...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28088526/subcutaneous-immunization-with-streptococcus-pneumoniae-gapdh-confers-effective-protection-in-mice-via-tlr2-and-tlr4
#2
Xiaoyu Sun, Jichao Wang, Jie Zhou, Hong Wang, Xiaofang Wang, Jingwen Wu, Yujuan He, Yibing Yin, Xuemei Zhang, Wenchun Xu
The surface localized Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Streptococcus pneumoniae is best known as housekeeping protein. Currently, GAPDH has been recognized as moonlighting protein and virulent factor. Therefore, we investigate whether GAPDH can act as a suitable vaccine candidate protein to prevent pneumococcal infection. In this study, mice received subcutaneous vaccination with recombinant GAPDH followed by challenge with D39 and 19F showing higher survival rate and lower bacterial loads in nasal washes and lung homogenates than control...
January 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28087317/acute-otitis-media-caused-by-streptococcus-pneumoniae-serotype-19a-st320-clone-epidemiological-and-clinical-characteristics
#3
Hsin Chi, Nan-Chang Chiu, Fu-Yuan Huang, Chyong-Hsin Hsu, Kuo-Sheng Lee, Li-Min Huang, Yu-Chia Hsieh
BACKGROUND: Streptococcus pneumoniae serotype 19A ST320, a highly multiresistant and virulent clone, has emerged as a common pathogen causing acute otitis media (AOM) in children. METHODS: Patients aged 0-18 years with AOM who presented at Mackay Memorial Hospital, Taipei, Taiwan were prospectively enrolled between December 1, 2009, and November 30, 2012. For each patient, a specimen of middle-ear fluid was obtained and cultured. S. pneumoniae isolates were tested by serotyping, antibiotic-resistance profiling, and multilocus sequence typing...
December 19, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28069358/pneumococcal-polysaccharide-vaccination-administered-early-after-neurotrauma-or-neurosurgery
#4
Anna Ljunghill Hedberg, Karlis Pauksens, Per Enblad, Jessika Söderberg, Björn Johansson, Helena Käyhty, Jan Sjölin
OBJECTIVES: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune-suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). METHODS: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10days after neurotrauma or neurosurgery...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28062125/propensity-of-pneumococcal-carriage-serotypes-to-infect-the-lower-airways-of-children-with-chronic-endobronchial-infections
#5
Kim M Hare, Heidi C Smith-Vaughan, Anne B Chang, Susan Pizzutto, Helen L Petsky, Gabrielle B McCallum, Amanda J Leach
BACKGROUND: Chronic endobronchial infections in children are responsible for a high disease burden. Streptococcus pneumoniae is frequently isolated; however, few publications have described serotypes associated with non-invasive lower airway infection. METHODS: Paired nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids were collected from children undergoing bronchoscopy for chronic cough. NP swabs were also collected from asymptomatic children in otitis media surveillance studies (controls)...
January 3, 2017: Vaccine
https://www.readbyqxmd.com/read/28039377/detection-of-serotype-distribution-and-drug-resistance-of-streptococcus-pneumoniae-isolated-from-pediatric-patients
#6
Junrong Wang, Fenqin Liu, Peiran Ao, Xianneng Li, Haixiao Zheng, Di Wu, Nina Zhang, Junping Yu, Junhui Yuan, Xiuying Wu
OBJECTIVE: To analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from pediatric patients in a Chinese hospital. METHODS: From October 2011 to May 2014, we collected 284 isolates (including 217 noninvasive and 67 invasive strains). We tested the antimicrobial susceptibility of these specimens using the Epsilomer test and disk diffusion method, and the expression of macrolide resistant genes ermB and mefA by polymerase chain reaction...
December 29, 2016: Laboratory Medicine
https://www.readbyqxmd.com/read/28002967/discovery-of-1s-2r-3s-4s-5r-6r-2-amino-3-3-4-difluorophenyl-sulfanylmethyl-4-hydroxy-bicyclo-3-1-0-hexane-2-6-dicarboxylic-acid-hydrochloride-ly3020371%C3%A2-hcl-a-potent-metabotropic-glutamate-2-3-receptor-antagonist-with-antidepressant-like-activity
#7
Mark D Chappell, Renhua Li, Stephon C Smith, Bruce A Dressman, Eric G Tromiczak, Allie E Tripp, Maria-Jesus Blanco, Tatiana Vetman, Steven J Quimby, James Matt, Thomas C Britton, Adam M Fivush, Jeffrey M Schkeryantz, Daniel Mayhugh, Jon A Erickson, Mark G Bures, Carlos Jaramillo, Mercedes Carpintero, José Eugenio de Diego, Mario Barberis, Susana Garcia-Cerrada, José F Soriano, Stephen Antonysamy, Shane Atwell, Iain MacEwan, Bradley Condon, Christine Sougias, Jing Wang, Aiping Zhang, Kris Conners, Chris Groshong, Stephen R Wasserman, John W Koss, Jeffrey M Witkin, Xia Li, Carl Overshiner, Keith A Wafford, Wesley Seidel, Xu-Shan Wang, Beverly A Heinz, Steven Swanson, John T Catlow, David W Bedwell, James A Monn, Charles H Mitch, Paul L Ornstein
As part of our ongoing efforts to identify novel ligands for the metabotropic glutamate 2 and 3 (mGlu2/3) receptors, we have incorporated substitution at the C3 and C4 positions of the (1S,2R,5R,6R)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid scaffold to generate mGlu2/3 antagonists. Exploration of this structure-activity relationship (SAR) led to the identification of (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride (LY3020371·HCl, 19f), a potent, selective, and maximally efficacious mGlu2/3 antagonist...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28000669/a-live-rsv-vaccine-with-engineered-thermostability-is-immunogenic-in-cotton-rats-despite-high-attenuation
#8
Christopher C Stobart, Christina A Rostad, Zunlong Ke, Rebecca S Dillard, Cheri M Hampton, Joshua D Strauss, Hong Yi, Anne L Hotard, Jia Meng, Raymond J Pickles, Kaori Sakamoto, Sujin Lee, Michael G Currier, Syed M Moin, Barney S Graham, Marina S Boukhvalova, Brian E Gilbert, Jorge C G Blanco, Pedro A Piedra, Elizabeth R Wright, Martin L Moore
Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27998266/impact-of-pneumococcal-conjugate-vaccines-on-pneumococcal-meningitis-cases-in-france-between-2001-and-2014-a-time-series-analysis
#9
Anna Alari, Hélène Chaussade, Matthieu Domenech De Cellès, Lénaig Le Fouler, Emmanuelle Varon, Lulla Opatowski, Didier Guillemot, Laurence Watier
BACKGROUND: Pneumococcal meningitis (PM) is a major invasive pneumococcal disease. Two pneumococcal conjugate vaccines (PCVs) have been introduced in France: PCV7 was recommended in 2003 and replaced in 2010 by PCV13, which has six additional serotypes. The impact of introducing those vaccines on the evolution of PM case numbers and serotype distributions in France from 2001 to 2014 is assessed herein. METHODS: Data on 5166 Streptococcus pneumoniae strains isolated from cerebrospinal fluid between 2001 and 2014 in the 22 regions of France were obtained from the National Reference Center for Pneumococci...
December 21, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27973447/anti-inflammatory-effects-of-vitamin-d-on-human-immune-cells-in-the-context-of-bacterial-infection
#10
Edwin Hoe, Jordan Nathanielsz, Zheng Quan Toh, Leena Spry, Rachel Marimla, Anne Balloch, Kim Mulholland, Paul V Licciardi
Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)₂D₃, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS)...
December 12, 2016: Nutrients
https://www.readbyqxmd.com/read/27960627/comparative-evaluation-of-a-newly-developed-13-valent-pneumococcal-conjugate-vaccine-in-a-mouse-model
#11
Chulmin Park, Eun-Young Kwon, Su-Mi Choi, Sung-Yeon Cho, Ji-Hyun Byun, Jung Yeon Park, Dong-Gun Lee, Jin Han Kang, Jinhwan Shin, Hun Kim
Animal models facilitate evaluation of vaccine efficacy at relatively low cost. This study was a comparative evaluation of the immunogenicity and protective efficacy of a new 13-valent pneumococcal conjugate vaccine (PCV13) with a control vaccine in a mouse model. After vaccination, anti-capsular antibody levels were evaluated by pneumococcal polysaccharide (PnP) enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA). Also, mice were challenged intraperitoneally with 100-fold of the 50% lethal dose of Streptococcus pneumoniae...
December 14, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27956163/invasive-pneumococcal-disease-in-children-aged-younger-than-5-years-in-india-a-surveillance-study
#12
Anand Manoharan, Vikas Manchanda, Sundaram Balasubramanian, Sanjay Lalwani, Meera Modak, Sushama Bai, Ajith Vijayan, Anita Shet, Savitha Nagaraj, Sunil Karande, Gita Nataraj, Vijay N Yewale, Shrikrishna A Joshi, Ranganathan N Iyer, Mathuram Santosham, Geoffrey D Kahn, Maria Deloria Knoll
BACKGROUND: Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due to Streptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India. METHODS: In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India...
December 9, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27905836/invasive-pneumococcal-disease-from-a-tertiary-care-hospital-in-the-post-vaccine-era
#13
Sevgen Tanır Basaranoglu, Eda Karadag Oncel, Kubra Aykac, Yasemin Ozsurekci, Ali Bulent Cengiz, Ates Kara, Mehmet Ceyhan
A breakthrough infection occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in Turkey are previously described. A breakthrough infection is defined as IPD in a child who had received ≥ 1 PCV-7 or PCV-13 and for which the pneumococcal isolate was a vaccine serotype. During one year period, among 6 patients with invasive pneumococcal infection, 2 patients were considered to have a vaccine failure with serotype 19F. Antibiotic resistance results were remarkable; macrolide resistance were observed in all strains except one, and high and intermediate penicillin resistance were determined in 2 strains...
December 1, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27879152/preparation-and-immunogenicity-of-gold-glyco-nanoparticles-as-antipneumococcal-vaccine-model
#14
Maria Vetro, Dodi Safari, Silvia Fallarini, Korrie Salsabila, Martina Lahmann, Soledad Penadés, Luigi Lay, Marco Marradi, Federica Compostella
AIM: Nanotechnology-based fully synthetic carbohydrate vaccines are promising alternatives to classic polysaccharide/protein conjugate vaccines. We have prepared gold glyco-nanoparticles (GNP) bearing two synthetic carbohydrate antigens related to serotypes 19F and 14 of Streptococcus pneumoniae and evaluated their immunogenicity in vivo. RESULTS: A tetrasaccharide fragment of serotype 14 (Tetra-14), a trisaccharide fragment of serotype 19F (Tri-19F), a T-helper peptide and d -glucose were loaded onto GNP in different ratios...
January 2017: Nanomedicine
https://www.readbyqxmd.com/read/27831604/-epidemiologic-clinical-and-bacteriologic-characteristics-of-pneumococcal-meningitis-in-pediatric-patients-from-lima-peru
#15
Long Davalos, Yessica Terrazas, Ana Quintana, Martha Egoavil, Katherine Sedano, María E Castillo, Isabel Reyes, Eduardo Chaparro, Wilda Silva, Francisco Campos, Andrés Saenz, Roger Hernandez, Olguita Del Águila, Daniel Guillén Pinto, Theresa J Ochoa
Objectives.: To describe the clinical characteristics, lethality, antibiotic susceptibility, and serotype distribution of pneumococcal meningitis in pediatric patients in Lima, Peru. Materials and Methods.: A case series of pneumococcal meningitis in children less than 16 years of age from two prospective, multicenter, passive surveillance studies of invasive pneumococcal diseases held in Lima-Peru from 2006 to 2008 and 2009 to 2011. Results.: We report 44 pneumococcal meningitis episodes; 68...
July 2016: Revista Peruana de Medicina Experimental y Salud Pública
https://www.readbyqxmd.com/read/27829063/pneumococcal-carriage-in-children-under-five-years-in-uganda-will-present-pneumococcal-conjugate-vaccines-be-appropriate
#16
Ann Lindstrand, Joan Kalyango, Tobias Alfvén, Jessica Darenberg, Daniel Kadobera, Freddie Bwanga, Stefan Peterson, Birgitta Henriques-Normark, Karin Källander
BACKGROUND: Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission...
2016: PloS One
https://www.readbyqxmd.com/read/27819116/safety-and-immunogenicity-of-pneumococcal-conjugate-vaccine-in-preterm-infants-a-meta-analysis
#17
Kai Duan, Jin Guo, Ping Lei
OBJECTIVE: To assess the safety and immunogenicity of pneumococcal conjugate vaccine (PCVs) in preterm infants. METHODS: In accordance with the PRISM (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement (as of May 2015), a meta-analysis was conducted to evaluate the safety and immunogenicity of PCVs in preterm infants. RESULTS: Ten thousand nine hundred sixty full-term infants and 2131 preterm infants with 344 preterm infants of <2500 g birth weight [low-birth weight (LBW)] were included, and all the subjects were immunized with either PCV-7, PCV-10 or PCV-13 in this random-effects meta-analysis...
February 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/27798547/streptococcus-pneumoniae-serotypes-and-antibiotic-susceptibility-patterns-in-middle-ear-fluid-isolates-during-acute-otitis-media-and-nasopharyngeal-isolates-during-community-acquired-alveolar-pneumonia-in-central-romania
#18
Raluca-Ileana Lixandru, Cristian Falup-Pecurariu, Laura Bleotu, Alice Mercas, Eugene Leibovitz, Ron Dagan, David Greenberg, Oana Falup-Pecurariu
INTRODUCTION: Streptococcus pneumoniae is a common cause of community-acquired alveolar pneumonia (CAAP) and acute otitis media (AOM) in children. Romania has high rates of S. pneumoniae antibiotic resistance. The pneumococcal conjugated vaccines (PCVs) are not being used routinely in this country. The aims of the study were: 1) To compare pneumococcal antibiotic resistance patterns in AOM and CAAP in children from central Romania; and 2) to compare differences in the distribution of pneumococcal serotypes isolated from the middle ear fluid (MEF) of children with AOM and from the nasopharynx (NP) of children with CAAP...
October 25, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27788227/perfluorocarbon-loaded-lipid-nanocapsules-to-assess-the-dependence-of-u87-human-glioblastoma-tumor-po2-on-in-vitro-expansion-conditions
#19
Laurent Lemaire, Janske Nel, Florence Franconi, Guillaume Bastiat, Patrick Saulnier
Growing tumor cell lines, such as U87-MG glioma cells, under mild hypoxia (3% O2) leads to a ca. 40% reduction in growth rate once implanted in the brain of nude mice, as compared to normoxia (21% O2) grown cells, wherein the former over-express HIF-1 and VEGF-A. Despite developing differently, the tumors have similar: blood perfusion, oxygen consumption, and vascular surface area parameters, whereas the number of blood vessels is nearly doubled in the tumor arising from normoxia cultured cells. Interestingly, tumor oxygen tension, measured using 19F-oximetry, showed that the normoxia grown cells led to tumors characterized by mild hypoxic environment (approximately 4%) conditions, whilst the hypoxia grown cells led to tumors characterized by physioxic environment (approximately 6%) conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27783520/probing-the-complex-binding-modes-of-the-ppar%C3%AE-partial-agonist-2-chloro-n-3-chloro-4-5-chlorobenzo-d-thiazol-2-yl-thio-phenyl-4-trifluoromethyl-benzenesulfonamide-t2384-to-orthosteric-and-allosteric-sites-with-nmr-spectroscopy
#20
Travis S Hughes, Jinsai Shang, Richard Brust, Ian Mitchelle S de Vera, Jakob Fuhrmann, Claudia Ruiz, Michael D Cameron, Theodore M Kamenecka, Douglas J Kojetin
In a previous study, a cocrystal structure of PPARγ bound to 2-chloro-N-(3-chloro-4-((5-chlorobenzo[d]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide (1, T2384) revealed two orthosteric pocket binding modes attributed to a concentration-dependent biochemical activity profile. However, 1 also bound an alternate/allosteric site that could alternatively account for the profile. Here, we show ligand aggregation afflicts the activity profile of 1 in biochemical assays. However, ligand-observed fluorine ((19)F) and protein-observed NMR confirms 1 binds PPARγ with two orthosteric binding modes and to an allosteric site...
November 23, 2016: Journal of Medicinal Chemistry
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