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https://www.readbyqxmd.com/read/29346838/first-in-human-study-to-assess-safety-pharmacokinetics-and-pharmacodynamics-of-bms-962212-a-direct-reversible-small-molecule-factor-xia-inhibitor-in-non-japanese-and-japanese-healthy-subjects
#1
Vidya Perera, Joseph M Luettgen, Zhaoqing Wang, Charles E Frost, Cynthia Yones, Cesare Russo, John Lee, Yue Zhao, Frank P LaCreta, Xuewen Ma, Robert M Knabb, Dietmar Seiffert, Mary DeSouza, Pierre Mugnier, Brenda Cirincione, Takayo Ueno, Robert J A Frost
AIMS: To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1.5, 4, 10, and 25 mg h-1 ) assigned to BMS-962212 or placebo in a 3:1 ratio per dose. Part B used 4 doses (1, 3, 9, and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese subjects (n = 4 active, n = 1 placebo) per dose...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29346627/severe-and-protracted-sleep-disruptions-in-mouse-model-of-post-traumatic-stress-disorder
#2
Rishi Sharma, Pradeep Sahota, Mahesh M Thakkar
Increasing evidences suggest that the predator threat model is a valid animal model of post-traumatic stress disorder (PTSD). However, sleep has never been examined in this model. Since sleep disturbances, including insomnia and excessive daytime sleepiness, are severe and protracted symptoms of PTSD, we hypothesized that mice exposed to predator odor trauma (POT) will display contextual fear conditioning along with severe and protracted sleep disruptions.Adult male C57BL/6J mice, instrumented with wire electrodes [to record hippocampal field potentials (LFP) and nuchal muscle (EMG) activity], were exposed to contextual conditioning using soiled cat litter as unconditional stimulus (US)...
January 13, 2018: Sleep
https://www.readbyqxmd.com/read/29346585/maternal-vaccination-with-a-mono-component-pertussis-toxoid-vaccine-is-sufficient-to-protect-infants-in-a-baboon-model-of-whooping-cough
#3
Parul Kapil, James F Papin, Roman F Wolf, Lindsey I Zimmerman, Leslie D Wagner, Tod J Merkel
Background: Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at six to eight weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease...
January 15, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29346443/exposure-to-previous-cart-is-associated-with-significant-liver-fibrosis-and-cirrhosis-in-human-immunodeficiency-virus-infected-patients
#4
Evrim Anadol, Kristina Lust, Christoph Boesecke, Carolynne Schwarze-Zander, Raphael Mohr, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh, Jonel Trebicka
INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. METHODS: This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE)...
2018: PloS One
https://www.readbyqxmd.com/read/29346367/assessment-of-serum-pharmacokinetics-and-urinary-excretion-of-albendazole-and-its-metabolites-in-human-volunteers
#5
Laura Ceballos, Alejandro Krolewiecki, Marisa Juárez, Laura Moreno, Fabian Schaer, Luis I Alvarez, Rubén Cimino, Judd Walson, Carlos E Lanusse
BACKGROUND: Soil Transmitted Helminth (STH) infections negatively impact physical and mental development in human populations. Current WHO guidelines recommend morbidity control of these infections through mass drug administration (MDA) using albendazole (ABZ) or mebendazole. Despite major reductions in STH associated morbidity globally, not all programs have demonstrated the expected impact on prevalence of parasite infections. These therapeutic failures may be related to poor programmatic coverage, suboptimal adherence or the exposure of parasites to sub-therapeutic drug concentrations...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29346316/chronic-dietary-intake-of-enniatin-b-in-broiler-chickens-has-low-impact-on-intestinal-morphometry-and-hepatic-histology-and-shows-limited-transfer-to-liver-tissue
#6
Sophie Fraeyman, Siska Croubels, Mathias Devreese, Richard Ducatelle, Michael Rychlik, Gunther Antonissen
The Fusarium mycotoxin enniatin B (ENN B) is a so-called emerging mycotoxin frequently contaminating poultry feed. To investigate the impact of chronic ENN B exposure on animal health, broiler chickens were fed either a diet naturally contaminated with ENN B (2352 µg/kg) or a control diet (135 µg/kg) for 2, 7, 14, or 21 days. ENN B concentrations were determined in plasma and liver using a validated ultra-high performance liquid chromatography-tandem mass spectrometry UHPLC-MS/MS method. Liver was evaluated histologically, and the villus length and crypt depth of the duodenum, jejunum, and ileum were measured...
January 18, 2018: Toxins
https://www.readbyqxmd.com/read/29346307/knowledge-and-attitudes-of-general-practitioners-and-sexual-health-care-professionals-regarding-human-papillomavirus-vaccination-for-young-men-who-have-sex-with-men
#7
Samuel W D Merriel, Carrie Flannagan, Joanna M Kesten, Gilla K Shapiro, Tom Nadarzynski, Gillian Prue
Men who have sex with men (MSM) may be at higher risk for human papillomavirus (HPV)-associated cancers. Healthcare professionals' recommendations can affect HPV vaccination uptake. Since 2016, MSM up to 45 years have been offered HPV vaccination at genitourinary medicine (GUM) clinics in a pilot programme, and primary care was recommended as a setting for opportunistic vaccination. Vaccination prior to potential exposure to the virus (i.e., sexual debut) is likely to be most efficacious, therefore a focus on young MSM (YMSM) is important...
January 18, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29346280/a-multi-band-body-worn-distributed-radio-frequency-exposure-meter-design-on-body-calibration-and-study-of-body-morphology
#8
Reza Aminzadeh, Arno Thielens, Sam Agneessens, Patrick Van Torre, Matthias Van den Bossche, Stefan Dongus, Marloes Eeftens, Anke Huss, Roel Vermeulen, René de Seze, Paul Mazet, Elisabeth Cardis, Hendrik Rogier, Martin Röösli, Luc Martens, Wout Joseph
A multi-band Body-Worn Distributed exposure Meter (BWDM) calibrated for simultaneous measurement of the incident power density in 11 telecommunication frequency bands, is proposed. The BDWM consists of 22 textile antennas integrated in a garment and is calibrated on six human subjects in an anechoic chamber to assess its measurement uncertainty in terms of 68% confidence interval of the on-body antenna aperture. It is shown that by using multiple antennas in each frequency band, the uncertainty of the BWDM is 22 dB improved with respect to single nodes on the front and back of the torso and variations are decreased to maximum 8...
January 18, 2018: Sensors
https://www.readbyqxmd.com/read/29345613/comparative-transcriptomics-of-aspergillus-fumigatus-strains-upon-exposure-to-human-airway-epithelial-cells
#9
Tonya N Watkins, Hong Liu, Matthew Chung, Tracy H Hazen, Julie C Dunning Hotopp, Scott G Filler, Vincent M Bruno
Aspergillus fumigatus is an opportunistic, ubiquitous, saprophytic mould that can cause severe allergic responses in atopic individuals as well as life-threatening infections in immunocompromised patients. A critical step in the establishment of infection is the invasion of airway epithelial cells by the inhaled fungi. Understanding how A. fumigatus senses and responds to airway cells is important to understand the pathogenesis of invasive pulmonary aspergillosis. Here, we analysed the transcriptomes of two commonly used clinical isolates, Af293 and CEA10, during infection of the A549 type II pneumocyte cell line in vitro...
January 18, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29345424/a-fluorescence-based-sensor-assay-that-monitors-general-protein-aggregation-in-human-cells
#10
Marisa Pereira, Diogo Tomé, Ana S Domingues, Ana S Varanda, Cristiana Paulo, Manuel A S Santos, Ana R Soares
Protein conformational disorders are characterized by disruption of protein folding and toxic accumulation of protein aggregates. Here we describe a sensitive and simple method to follow and monitor general protein aggregation in human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock protein that binds and keeps unfolded proteins in a folding competent state. This high specificity of HSP27 for aggregated proteins can be explored to monitor aggregation in living cells by fusing it to a fluorescent protein as Green Fluorescent Protein (GFP)...
January 18, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29345412/wnt5a-promotes-migration-and-invasion-of-human-osteosarcoma-cells-via-src-erk-mmp-14-pathway
#11
Xingwen Wang, Xin Zhao, Zhigang Yi, Bing Ma, Hong Wang, Yanchuan Pu, Jing Wang, Shuanke Wang
WNT5A, a representative ligand of activating several non-canonical Wnt signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5A-induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings...
January 18, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29345363/effects-of-il-10-and-th-2-cytokines-on-human-m%C3%AF-phenotype-and-response-to-csf1r-inhibitor
#12
Leon P Pradel, Andreas Franke, Carola H Ries
Tumor-associated Mφs display a plastic phenotype that is regulated by the local tumor milieu. Gene expression analysis and functional characterization of Mφs exposed in vitro to individual cytokines aids to delineate the cross-talk between defined cytokines shaping the complex Mφ phenotype. Human monocyte-derived Mφs can be differentiated in vitro with the T helper cell type 2 response cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking antibody emactuzumab...
January 4, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345335/heat-shock-protein-70-modulates-neural-progenitor-cells-dynamics-in-human-neuroblastoma-sh-sy5y-cells-exposed-to-high-glucose-content
#13
Leila Salimi, Reza Rahbarghazi, Vahab Jafarian, Çıgır Biray Avci, Bakiye Goker Bagca, Neslihan Pinar Ozates, Majid Khaksar, Alireza Nourazarian
BACKGROUND: In the current experiment, detrimental effects of high glucose condition were investigated on human neuroblastoma cells. METHODS: Human neuroblastoma cell line SH-SY5Y were exposed to 5, 40 and 70 mM glucose over a period of 72 h. Survival rate and the proliferation of cells were analyzed by MTT and BrdU incorporation assays. Apoptosis was studied by the assays of flow cytometry and PCR array. In order to investigate the trans-differentiation capacity of the cell into mature neurons, we used immunofluorescence imaging to follow NeuN protein level...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345311/calcium-sensing-receptor-activates-the-nlrp3-inflammasome-in-ls14-preadipocytes-mediated-by-erk1-2-signaling
#14
Amanda D'Espessailles, Yuly A Mora, Cecilia Fuentes, Mariana Cifuentes
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29345269/tributyltin-induces-epigenetic-changes-and-decreases-the-expression-of-nuclear-respiratory-factor-1
#15
Saki Hanaoka, Keishi Ishida, Saki Tanaka, Shuichiro Sakamoto, Katsuhiro Okuda, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Tributyltin (TBT), a common organotin environmental pollutant, has been widely used as a component of marine antifouling paints. We previously reported that exposure to TBT inhibits the expression and DNA binding of nuclear respiratory factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on the epigenetic effects of TBT and investigated whether TBT decreases NRF-1 expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells. First, we found that exposure to 300 nM TBT decreases NRF-1 expression...
January 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29345156/pharmacokinetic-drug-evaluation-of-opicapone-for-the-treatment-of-parkinson-s-disease
#16
M Svetel, A Tomić, N Kresojević, V S Kostić
Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa treated patients with PD and motor fluctuations. Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert commentary: Oral OPC exhibits linear, dose-dependent absorption. However, following concomitant ingestion of a high-fat, high-calorie meal, the maximum plasma concentration will be decreased...
January 18, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29344966/quorum-sensing-molecule-dihydroxy-2-3-pentanedione-and-its-analogs-as-regulators-of-epithelial-integrity
#17
S Elmanfi, X Ma, H O Sintim, E Könönen, S Syrjänen, U K Gursoy
BACKGROUND AND OBJECTIVE: Quorum-sensing molecules regulate the behavior of bacteria within biofilms and at the same time elicit an immune response in host tissues. Our aim was to investigate the regulatory role of dihydroxy-2,3-pentanedione (DPD), the precursor of universal autoinducer-2 (AI-2), and its analogs (ethyl-DPD, butyl-DPD and isobutyl-DPD) in the integrity of gingival epithelial cells. MATERIAL AND METHODS: Human gingival keratinocytes were incubated with four concentrations (10 μmol L-1 , 1 μmol L-1 , 100 nmol L-1 and 10 nmol L-1 ) of DPD and its analogs for 24 hours...
January 17, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29344636/analysis-of-the-prolonged-infusion-of-dfp-10917-a-deoxycytidine-analog-as-a-therapeutic-strategy-for-the-treatment-of-human-tumor-xenografts-in-vivo
#18
Kenzo Iizuka, Chun Zhang, Kokoro Eshima, Cheng Jin, Kiyoshi Eshima, Masakazu Fukushima
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofranocyl-cytosine (DFP-10917, CNDAC) is a 2'-deoxycytidine analog with antitumor activity against various tumor cells. However, a clinically available therapeutic regimen for this compound needs to be established and its functional mechanisms in relation to the dosing schedule need to be clarified. In this study, we evaluated the antitumor activity and toxicity of DFP-10917 by varying the dose and administration schedule in human solid tumor and leukemia xenografts in vivo...
January 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344587/an-exploratory-study-of-red-raspberry-rubus-idaeus-l-poly-phenols-metabolites-in-human-biological-samples
#19
Xuhuiqun Zhang, Amandeep Sandhu, Indika Edirisinghe, Britt Burton-Freeman
Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different forms (parent compounds, degradants or microbial metabolites) are subject to xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate, glucuronide, and sulfate conjugated metabolites. Upon acute exposure, (poly)phenol/metabolite presence in the blood depends mainly on intestinal absorption, enterohepatic circulation, and metabolism by resident microbiota...
January 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29344203/mucin-1-promotes-radioresistance-in-hepatocellular-carcinoma-cells-through-activation-of-jak2-stat3-signaling
#20
Feng-Tao Yi, Qi-Ping Lu
Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types, including hepatocellular carcinoma (HCC) and contributes to chemoresistance of tumor cells. The aim of the present study was to evaluate the possible implication of MUC1 in radioresistance of HCC cells and the underlying mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC cells following irradiation exposure, which was coupled with increased phosphorylation of signal transducer and activator of transcription 3 (STAT3)...
December 2017: Oncology Letters
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