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https://www.readbyqxmd.com/read/28109128/population-pharmacokinetics-and-pharmacodynamics-of-benralizumab-in-healthy-volunteers-and-patients-with-asthma
#1
B Wang, L Yan, Z Yao, L K Roskos
Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG) 1 κ monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N = 48) and four studies in patients with asthma (N = 152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the central compartment and first-order absorption from the subcutaneous dosing site...
January 21, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28109094/-lactobacillus-rhamnosus-gg-conditioned-medium-prevents-e-coli-meningitis-by-inhibiting-nuclear-factor-%C3%AE%C2%BAb-pathway
#2
Qing Zeng, Xiao-Long He, Han-Sheng Xiao, Lei DU, Yu-Jing Li, Le-Cheng Chen, Hui-Wen Tian, Sheng-He Huang, Hong Cao
OBJECTIVE: To investigate whether Lactobacillus rhamnosus GG conditioned medium(LGG-CM)has preventive effect against E. coli K1-induced neuropathogenicity in vitro by inhibiting nuclear factor-κB (NF-κB) signaling pathway. METHODS: An in vitro blood-brain barrier (BBB) model was constructed using human brain microvascular endothelial cells (HBMECs). The effect of LGG-CM on E. coli-actived NF-κB signaling pathway was assayed using Western blotting. Invasion assay and polymorphonuclear leukocyte (PMN) transmigration assay were performed to explore whether LGG-CM could inhibit E...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28108766/immunosuppressive-myeloid-derived-suppressor-cells-are-increased-in-splenocytes-from-cancer-patients
#3
Kimberly R Jordan, Puja Kapoor, Eric Spongberg, Richard P Tobin, Dexiang Gao, Virginia F Borges, Martin D McCarter
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice...
January 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28108746/myeloid-derived-suppressor-cells-can-be-efficiently-generated-from-human-hematopoietic-progenitors-and-peripheral-blood-monocytes
#4
Sílvia Casacuberta-Serra, Marta Parés, Arantxa Golbano, Elisabet Coves, Carmen Espejo, Jordi Barquinero
Myeloid-derived suppressor cells (MDSCs) play an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex-vivo-generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34(+) hematopoietic progenitors from apheresis products and CD14(+) cells isolated from buffy coats were cultured in the presence of different combinations of cytokines...
January 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28108645/whole-body-hyperthermia-but-not-skin-hyperthermia-accelerates-brain-and-locomotor-limb-circulatory-strain-and-impairs-exercise-capacity-in-humans
#5
Steven J Trangmar, Scott T Chiesa, Kameljit K Kalsi, Niels H Secher, José González-Alonso
Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans, however, the contribution of elevations in skin (Tsk) versus whole body temperatures on exercise capacity has not been characterized. To ascertain their relationships with exercise capacity, blood temperature (TB), oxygen uptake (V̇O2), brain perfusion (MCA Vmean), locomotor limb hemodynamics, and hematological parameters were assessed during incremental cycling exercise with elevated skin (mild hyperthermia; HYPmild), combined core and skin temperatures (moderate hyperthermia; HYPmod), and under control conditions...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28108611/reversal-of-diabetes-in-nod-mice-by-clinical-grade-proinsulin-and-il-10-secreting-lactococcus-lactis-in-combination-with-low-dose-anti-cd3-depends-on-the-induction-of-foxp3-positive-t-cells
#6
Tatiana Takiishi, Dana Paulina Cook, Hannelie Korf, Guido Sebastiani, Francesca Mancarella, João Paulo Monteiro Carvalho Mori Cunha, Clive Wasserfall, Noelia Casares, Juan José Lasarte, Lothar Steidler, Pieter Rottiers, Francesco Dotta, Conny Gysemans, Chantal Mathieu
The introduction of β-cell autoantigens via the gut through Lactococcus lactis (L. lactis) has been demonstrated to be a promising approach for diabetes reversal in NOD mice. Here we show that a combination therapy of low-dose anti-CD3 with a clinical-grade self-containing L. lactis, appropriate for human application, secreting human proinsulin and interleukin-10, cured 66% of mice with new-onset diabetes, which is comparable to therapy results with plasmid-driven L. lactis Initial blood glucose concentrations (<350 mg/dL) and insulin autoantibody positivity were predictors of the stable reversal of hyperglycemia, and decline in insulin autoantibody positivity was an immune biomarker of therapeutic outcome...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108610/circulating-cxcr5-pd-1-icos-follicular-t-helper-cells-are-increased-close-to-the-diagnosis-of-type-1-diabetes-in-children-with-multiple-autoantibodies
#7
Tyyne Viisanen, Emmi-Leena Ihantola, Kirsti Näntö-Salonen, Heikki Hyöty, Noora Nurminen, Jenni Selvenius, Auni Juutilainen, Leena Moilanen, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108544/the-interplay-between-neutrophils-and-cd8-t-cells-improves-survival-in-human-colorectal-cancer
#8
Valeria Governa, Emanuele Trella, Valentina Mele, Luigi Tornillo, Francesca Amicarella, Eleonora Cremonesi, Maunele Giuseppe Muraro, Hui Xu, Raoul Droeser, Silvio Raffael Däster, Martin Bolli, Raffaele Rosso, Daniel Oertli, Serenella Eppenberger-Castori, Luigi Terracciano, Giandomenica Iezzi, Giulio C Spagnoli
PURPOSE: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer (CRC). Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes and functional features of CRC infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells. EXPERIMENTAL DESIGN: CD66b+ and CD8+ cell infiltration was analyzed by immunohistochemistry on a tissue microarray including >650 evaluable CRC samples...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108516/fibrinolytic-enzyme-co-therapy-improves-tumor-perfusion-and-therapeutic-efficacy-of-anticancer-nanomedicine
#9
Ameya R Kirtane, Tanmoy Sadhukha, Hyunjoon Kim, Vidhi Khanna, Brenda Koniar, Jayanth Panyam
Elevated interstitial fluid pressure and solid stress within tumors contribute to poor intratumoral distribution of nanomedicine. In this study, we hypothesized that the presence of fibrin in tumor extracellular matrix contributes to hindered intratumoral distribution of nanocarriers and that this can be overcome through the use of a fibrinolytic enzyme such as tissue plasminogen activator (tPA). Analysis of fibrin expression in human tumor biopsies showed significant fibrin staining in nearly all tumor types evaluated...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108228/a-preliminary-study-of-endocannabinoid-system-regulation-in-psychosis-distinct-alterations-of-cnr1-promoter-dna-methylation-in-patients-with-schizophrenia
#10
Claudio D'Addario, Vincenzo Micale, Martina Di Bartolomeo, Tibor Stark, Mariangela Pucci, Alexandra Sulcova, Mariacarlotta Palazzo, Zuzana Babinska, Laura Cremaschi, Filippo Drago, A Carlo Altamura, Mauro Maccarrone, Bernardo Dell'Osso
Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1, the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients (N=25) with no changes in any other disorder...
January 17, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28108093/source-apportionment-of-lead-in-the-blood-of-women-of-reproductive-age-living-near-tailings-in-taxco-guerrero-mexico-an-isotopic-study
#11
Analine Berenice Vázquez Bahéna, Oscar Talavera Mendoza, Ma Elena Moreno Godínez, Sergio Adrián Salgado Souto, Joaquín Ruiz, Gerardo Huerta Beristain
The concentration and isotopic composition of lead in the blood of forty seven women of reproductive age (15-45y) exposed to multiple sources in two rural communities of the mining region of Taxco, Guerrero in southern Mexico were determined in order to identify specific contributing sources and their apportionment and to trace probable ingestion pathways. Our data indicate that >36% of the studied women have blood lead concentrations above 10μgdL(-1) and up to 87% above 5μgdL(-1). Tailings contain between 2128 and 5988mgkg(-1) of lead and represent the most conspicuous source in the area...
January 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28107977/ultrasensitive-detection-of-mucin-1-biomarker-by-immuno-loop-mediated-isothermal-amplification
#12
Hongmei Cao, Xueen Fang, Haipeng Li, Hua Li, Jilie Kong
Mucin 1 (MUC-1), a glycoprotein over-expressed on most malignant epithelial cell surfaces, such as colorectal, lung, prostate, pancreatic, ovarian, and bladder carcinomas, has been confirmed as a useful biomarker for the diagnosis of early cancers. Therefore, it is very important for early cancer diagnoses to develop the sensitive and specific detection approach of MUC-1. In this paper, we report a novel technique of aptamer-based Immuno-Loop-Mediated Isothermal Amplification (Im-LAMP) for the quantitative detection of MUC-1 by MUC-1 aptamer with high affinity for MUC-1...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107976/sensitive-fluorescent-detection-of-h2o2-and-glucose-in-human-serum-based-on-inner-filter-effect-of-squaric-acid-iron-iii-on-the-fluorescence-of-upconversion-nanoparticle
#13
Hongyu Chen, Aijin Fang, Li He, Youyu Zhang, Shouzhuo Yao
Diabetes mellitus is an epidemic disease that it has became a worldwide public health problem. Thus, blood glucose monitoring has attracted extensive attention. Here, we report a nanosensor based on inner filter effect (IFE) between upconversion nanoparticles (UCNPs) and squaric acid (SQA)-iron(III) for the highly sensitive and selective detection of glucose levels in human serum. In this assay, GOx-catalyzed oxidization of glucose produces gluconic acid and hydrogen peroxide (H2O2). The latter can catalytically oxidize iron(II) to iron(III) which can rapidly (<1min) coordinate with the SQA to produce (SQA)-iron(III)...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107860/the-role-of-heme-oxygenase-1-in-pathogenesis-of-cerebral-malaria-in-the-co-culture-model-of-human-brain-microvascular-endothelial-cell-and-itg-plasmodium-falciparum-infected-red-blood-cells
#14
Pimwan Thongdee, Kesara Na-Bangchang
OBJECTIVE: To investigate the role of human host heme-oxygenase-1 (HO-1) in pathogenesis of cerebral malaria in the in vitro model. METHODS: The effect of human host HO-1 [human brain microvascular endothelial cell (HBMEC)] on hemoglobin degradation in the co-culture model of HBMEC and ITG Plasmodium falciparum-infected red cells (iRBC) through measurement of the enzymatic products iron and bilirubin. RESULTS: Following exposure to the HO-1 inducer CoPPIX at all concentrations, the HBMEC cells apoptosis occurred, which could be prominently observed at 15 μM of 3 h exposure...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28107829/high-throughput-online-solid-phase-extraction-ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-polyfluoroalkyl-phosphate-esters-perfluoroalkyl-phosphonates-and-other-perfluoroalkyl-substances-in-human-serum-plasma-and-whole-blood
#15
Somrutai Poothong, Elsa Lundanes, Cathrine Thomsen, Line Småstuen Haug
A rapid, sensitive and reliable method was developed for the determination of a broad range of poly- and perfluoroalkyl substances (PFASs) in various blood matrices (serum, plasma, and whole blood), and uses only 50 μL of sample material. The method consists of a rapid protein precipitation by methanol followed by high throughput online solid phase extraction (SPE), ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), and negative electrospray ionization detection...
March 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28107816/the-time-course-of-erythrocyte-membrane-fatty-acid-concentrations-during-and-after-treatment-of-non-human-primates-with-increasing-doses-of-an-omega-3-rich-phospholipid-preparation-derived-from-krill-oil
#16
Petter-Arnt Hals, Xiaoli Wang, Fabiana Piscitelli, Vincenzo Di Marzo, Yong-Fu Xiao
BACKGROUND: A commonly used measure to reflect the intake of the long-chain omega-3 fatty acids EPA and DHA is the omega-3 index, defined as the sum of EPA + DHA as % of total fatty acids in erythrocyte membrane. When the omega-3 index changes it follows that the relative fractions of other fatty acids in the membrane are also changed. In the present study, increasing doses of a preparation of omega-3 rich phospholipids extracted from krill oil were administered orally to non-human primates for 12 weeks and the time course of EPA, DHA and 22 other fatty acids in erythrocytes was determined bi-weekly during treatment and for 8 weeks after cessation of treatment...
January 21, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28107779/effects-of-mineralocorticoid-receptor-antagonists-on-the-progression-of-diabetic-nephropathy
#17
Li-Jing Sun, Yan-Ni Sun, Jian-Ping Shan, Geng-Ru Jiang
AIMS: We aimed to evaluate the potential benefits and adverse effects of adding a mineralocorticoid receptor antagonist (MRA) to angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), as standard treatment in patients with DN. MATERIALS AND METHODS: We scanned the Embase, PubMed, and Cochrane Central Register of Controlled Trials databases for human clinical trials published in English until June 2016, evaluating renal outcomes in patients with DN...
January 20, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28107695/antibacterial-activity-computational-analysis-and-host-toxicity-study-of-thymol-sulfonamide-conjugates
#18
Shasank S Swain, Sudhir K Paidesetty, Rabindra N Padhy
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE) are notorious pathogenic multidrug resistant (MDR) bacteria in both hospital and community sectors, and today the first antibacterial drug sulfamethoxazole is ineffective. The monoterpene phenol, thymol was conjugated with seven sulfa drug derivatives individually, adopting the dye-azo synthesis protocol, and conjugates were characterized using spectral analysis techniques such as, UV, FTIR, MS, HPLC, (1)H NMR, (13)C NMR and SEM...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107484/resveratrol-co-treatment-attenuates-the-effects-of-hiv-protease-inhibitors-on-rat-body-weight-and-enhances-cardiac-mitochondrial-respiration
#19
Burger Symington, Rudo F Mapanga, Gavin R Norton, M Faadiel Essop
Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months)...
2017: PloS One
https://www.readbyqxmd.com/read/28107457/novel-analysis-of-immune-cells-from-nasal-microbiopsy-demonstrates-reliable-reproducible-data-for-immune-populations-and-superior-cytokine-detection-compared-to-nasal-wash
#20
Simon P Jochems, Katherine Piddock, Jamie Rylance, Hugh Adler, Beatriz F Carniel, Andrea Collins, Jenna F Gritzfeld, Carole Hancock, Helen Hill, Jesus Reiné, Alexandra Seddon, Carla Solórzano, Syba Sunny, Ashleigh Trimble, Angela D Wright, Seher Zaidi, Stephen B Gordon, Daniela M Ferreira
The morbidity and mortality related to respiratory tract diseases is enormous, with hundreds of millions of individuals afflicted and four million people dying each year. Understanding the immunological processes in the mucosa that govern outcome following pathogenic encounter could lead to novel therapies. There is a need to study responses at mucosal surfaces in humans for two reasons: (i) Immunological findings in mice, or other animals, often fail to translate to humans. (ii) Compartmentalization of the immune system dictates a need to study sites where pathogens reside...
2017: PloS One
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