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Miwa Isshiki, Satoshi Hirayama, Tsuyoshi Ueno, Masayuki Ito, Ayaka Furuta, Kouji Yano, Kotoko Yamatani, Masami Sugihara, Mayumi Idei, Takashi Miida
BACKGROUND: Rapid turnover proteins (RTPs), such as transthyretin (TTR), retinol binding protein (RBP), and transferrin (Tf), provide an accurate assessment of nutritional status but are susceptible to inflammation. Lipid-related markers, which have short half-lives in serum, may be better suited for nutritional assessment. We sought to identify sensitive nutritional markers unaffected by inflammation. METHODS: Fasting serum samples were collected from 30 malnourished inpatients and 25 healthy volunteers...
March 11, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Yang Bai, Hannelore Bové, Tim S Nawrot, Benoit Nemery
BACKGROUND: Carbon load in airway macrophages (AM) has been proposed as an internal marker to assess long-term exposure to combustion-derived pollutant particles. However, it is not known how this biomarker is affected by changes in exposure. We studied the clearance kinetics of black carbon (BC) in AM, obtained by sputum induction, in a one-year panel study. METHODS: AM BC was measured 8 times with 6 weeks intervals in healthy young subjects: 15 long-term residents in Leuven, Belgium (BE, mean annual PM10 20-30 μg/m3 ) and 30 newcomers having arrived recently (< 3 weeks) in Leuven from highly polluted cities (mean annual PM10  > 50 μg/m3 ) in low and middle-income countries (LMIC, n = 15), or from low to moderately polluted cities in high-income countries (HIC, n = 15)...
March 14, 2018: Particle and Fibre Toxicology
Tomoya Maeda, Yuya Tanaka, Masayuki Inui
The Corynebacterium glutamicum R grtA (cgR_2936), grtB (cgR_2934), and grtC (cgR_2933) genes were identified as paralogs encoding glutamine-rich toxic proteins. We also identified a new antisense small RNA AsgR (antisense sRNA for grtA) that overlaps the 3' end of the grtA gene. Single over-expressions of grtA, grtB, and grtC resulted in complete inhibition of Escherichia coli cell growth. This growth was rescued by co-expression of AsgR. Similar effects were observed in C. glutamicum, although the toxicities of these proteins were moderate...
March 14, 2018: Molecular Microbiology
Xizhen Lian, Yanyan Huang, Yuanyuan Zhu, Yu Fang, Rui Zhao, Elizabeth Joseph, Jialuo Li, Jean-Phillipe Pellois, Hongcai Zhou
Prodrug activation by exogenously administered enzymes for cancer therapy is an approach to achieve better selectivity and less systemic toxicity than conventional chemotherapy. However, the short half-lives of the activating enzymes in bloodstream has limited its success. Here, we demonstrate that a tyrosinase-MOF nanoreactor activates the prodrug paracetamol in cancer cells in a long-lasting manner. By generating reactive oxygen species (ROS) and depleting glutathione (GSH), the product of enzymatic conversion of paracetamol is toxic to drug-resistant cancer cells...
March 13, 2018: Angewandte Chemie
Ines Greco, Bernard D Hummel, Jaspreet Vasir, Jeffrey L Watts, Jason Koch, Johannes E Hansen, Hanne Mørck Nielsen, Peter Damborg, Paul R Hansen
Antimicrobial peptides (AMPs) hold promise as the next generation of antimicrobial agents, but often suffer from rapid degradation in vivo. Modifying AMPs with non-proteinogenic residues such as peptoids (oligomers of N -alkylglycines) provides the potential to improve stability. We have identified two novel peptoid-based compounds, B1 and D2 , which are effective against the canine skin pathogen Staphylococcus pseudintermedius , the main cause of antibiotic use in companion animals. We report on their potential to treat infections topically by characterizing their release from formulation and in vitro ADME properties...
March 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Charlotte H Maden, David Fairman, Michelle Chalker, Maria J Costa, William A Fahy, Nadia Garman, Pauline T Lukey, Tim Mant, Simon Parry, Juliet K Simpson, Robert J Slack, Stuart Kendrick, Richard P Marshall
PURPOSE: Inhaled drug delivery is an attractive route by which to deliver drugs to lungs of patients with idiopathic pulmonary fibrosis (IPF). GSK3008348 is a potent and selective small molecule being developed as the first inhaled inhibitor of the αvβ6 integrin for the treatment of IPF. The phase 1 first-time-in-human clinical trial (NCT02612051) presented here was designed to investigate the safety, tolerability and pharmacokinetic (PK) profile of single doses of GSK3008348 in healthy participants...
March 12, 2018: European Journal of Clinical Pharmacology
Amanda A Pierce, Steven W Chapman, Laura K Zimmerman, Jennifer C Hurley, Ramon Aravena, John A Cherry, Beth L Parker
Plumes of trichloroethene (TCE) with degradation products occur at a large industrial site in California where TCE as a dense non-aqueous phase liquid (DNAPL) entered the fractured sandstone bedrock at many locations beginning in the late 1940s. Groundwater flows rapidly in closely spaced fractures but plume fronts are strongly retarded relative to groundwater flow velocities owing largely to matrix diffusion in early decades and degradation processes in later decades and going forward. Multiple data types show field evidence for both biotic and abiotic dechlorination of TCE and its degradation products, resulting in non-chlorinated compounds...
March 3, 2018: Journal of Contaminant Hydrology
Jing Lu, Haipu Li, Yi Tu, Zhaoguang Yang
Parabens are preservatives widely used in foodstuffs, cosmetics and pharmaceuticals, which have led to elevated paraben concentrations in wastewater and receiving waters. Laboratory-scale batch experiments were conducted to investigate the adsorption and degradation of parabens in an aerobic activated sludge system. Results show that biodegradation plays a key role in removing parabens from the aerobic system of wastewater treatment plants, while adsorption on the sludge is not significant. The effects of parent paraben concentration, concentration of mixed liquor suspended solids (MLSS), initial pH and temperature on degradation were investigated using kinetic models...
March 9, 2018: Ecotoxicology and Environmental Safety
Na Liu, Xinglu Pan, Shuang Zhang, Mingshan Ji, Zhihong Zhang
The fate of tetraconazole enantiomers in strawberries during wine-making process was studied. The residues were determined by ultra-performance convergence chromatography tandem triple quadrupole mass spectrometry after each process steps. Results indicated that there was significant enantioselective dissipation of tetraconazole enantiomers during the fermentation process. And (-)-tetraconazole degraded faster than (+)-tetraconazole. The half-lives of (-)-tetraconazole and (+)-tetraconazole were 3.12, 3.76 days with washing procedure and 3...
March 12, 2018: Chirality
Tomas Majtan, Erez M Bublil, Insun Park, Erland Arning, Teodoro Bottiglieri, Frank Glavin, Jan P Kraus
AIMS: PEGylated human truncated cystathionine beta-synthase, lacking the C-terminal regulatory domain (PEG-CBS), is a promising preclinical candidate for enzyme replacement therapy in homocystinuria (HCU). It was designed to function as a metabolic sink to decrease the severely elevated plasma and tissue homocysteine concentrations. Here we evaluated pharmacokinetics (PK), pharmacodynamics (PD) and sub-chronic toxicity of PEG-CBS in homocystinuric mice and wild type rats and monkeys to estimate the minimum human efficacious dose for clinical trials...
March 8, 2018: Life Sciences
Marycarmen Cruz-Hurtado, Ma de Lourdes López-González, Derly Constanza Escobar-Wilches, Adolfo Sierra-Santoyo
Vinclozolin (V) is a fungicide with anti-androgenic properties whose metabolism is not fully understood, and data on urinary elimination of either V or its metabolites are limited. Therefore the kinetics of urinary elimination of V and its metabolites, after an oral dose in adult male rats were investigated. A single oral dose of V (100 mg/kg) suspended in corn oil was administered to male adult Wistar rats, and urine was collected at different times after dosing. V and its metabolites were extracted from urine, then enzymatically hydrolyzed using β-glucuronidase/sulfatase of H...
March 8, 2018: Toxicology and Applied Pharmacology
Paul Gavra, André Y Denault, Yves Théoret, Louis P Perrault, France Varin
OBJECTIVES: Milrinone pulmonary administration is used currently for the treatment of pulmonary hypertension. Several methods are available: simple jet nebulization, vibrating mesh nebulization, intratracheal instillation, and intratracheal atomization. The aim of this study was to explore the concentration-effect relationship of milrinone for each of these methods. DESIGN: Observational open-label pharmacokinetic/pharmacodynamics cohort study. SETTING: Single-center, hospital animal laboratory...
January 31, 2018: Journal of Cardiothoracic and Vascular Anesthesia
Monica Galan, Martin Kalinowski, Abdelhakim Gheddou, Kassoum Yamba
This work presents the last updated evaluations of the nuclear and decay data of the four radioxenon isotopes of interest for the Comprehensive Nuclear-Test-Ban Treaty (CTBT): Xe-131 m, Xe-133, Xe-133 m and Xe-135. This includes the most recent measured values on the half-lives, gamma emission probabilities (Pγ) and internal conversion coefficients (ICC). The evaluation procedure has been made within the Decay Data Evaluation Project (DDEP) framework and using the latest available versions of nuclear and atomic data evaluation software tools and compilations...
March 7, 2018: Journal of Environmental Radioactivity
Isaac R Melamed, Michael Borte, Laurenz Trawnicek, Ai-Lan Kobayashi, Roger H Kobayashi, Alan Knutsen, Sudhir Gupta, William Smits, Anna Pituch-Noworolska, Magdalena Strach, Grazyna Pulka, Hans D Ochs, James N Moy
Intravenous immunoglobulin (IVIG) therapy is commonly used to treat patients with primary antibody deficiency. This prospective, open-label, non-randomised, multicentre, phase III trial investigated the pharmacokinetics of a new 10% liquid IVIG product (panzyga®; Octapharma) in 51 patients aged 2-75 years with common variable immunodeficiency (n = 43) or X-linked agammaglobulinaemia (n = 8). Patients were treated with IVIG 10% every 3 (n = 21) or 4 weeks (n = 30) at a dose of 200-800 mg/kg for 12 months...
March 6, 2018: European Journal of Pharmaceutical Sciences
Shima Gholizadeh, Emmy M Dolman, Rebecca Wieriks, Rolf W Sparidans, Wim E Hennink, Robbert J Kok
PURPOSE: Sepantronium bromide (YM155) is a hydrophilic quaternary compound that cannot be administered orally due to its low oral bioavailability; it is furthermore rapidly eliminated via the kidneys. The current study aims at improving the pharmacokinetic profile of YM155 by its formulation in immunoliposomes that can achieve its enhanced delivery into tumor tissue and facilitate uptake in neuroblastoma cancer cells. METHODS: PEGylated YM155 loaded liposomes composed of DPPC, cholesterol and DSPE-PEG2000 were prepared via passive film-hydration and extrusion method...
March 7, 2018: Pharmaceutical Research
Rongjun Liu, Liangliang Zhang, Yunyun Chen, Zirong Huang, Yong Huang, Shulin Zhao
Superoxide anion (O2•-) and hydroxyl radical (•OH) are important reactive oxygen species (ROS) used as biomarkers in physiological and pathological processes. The ROS generation is closely related to the development of a variety of inflammatory diseases. However, in situ tracing inflammation process by real time monitoring the changes of ROS is difficult owing to short half-lives of ROS and high tissue autofluorescence in vivo. Here we developed a new near-infrared (NIR) ratiometric fluorescence imaging approach by using a förster resonance energy transfer (FRET)-base ratiometric fluorescent nanoprobe for real-time monitoring O2•- and •OH generation, and in situ tracing inflammation process in vivo...
March 7, 2018: Analytical Chemistry
Mayur Doke, Vincent Avecilla, Quentin Felty
The rising global incidence of obesity cannot be fully explained within the context of traditional risk factors such as an unhealthy diet, physical inactivity, aging, or genetics. Adipose tissue is an endocrine as well as a metabolic organ that may be susceptible to disruption by environmental estrogenic chemicals. Since some of the endocrine disruptors are lipophilic chemicals with long half-lives, they tend to bioaccumulate in the adipose tissue of exposed populations. Elevated exposure to these chemicals may predispose susceptible individuals to weight gain by increasing the number and size of fat cells...
2018: BioMed Research International
Nathalie Hill-Kapturczak, Donald M Dougherty, John D Roache, Tara E Karns-Wright, Martin A Javors
BACKGROUND: The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers. METHODS: A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in15 min. Blood and breath samples were collected before, at various times up to 360 min post-consumption, and 2, 4, 7, 11 and 14 days after alcohol consumption...
March 5, 2018: Alcoholism, Clinical and Experimental Research
Runan Li, Zenglong Chen, Fengshou Dong, Jun Xu, Xingang Liu, Xiaohu Wu, Xinglu Pan, Yan Tao, Yongquan Zheng
A rapid, sensitive and effective supercritical fluid chromatographic-tandem mass spectrometry (SFC-MS/MS) method was developed to analyze thiacloprid for the first time. The SFC-MS/MS conditions were optimized with the ultra-performance convergence chromatography (UPC2 ) BEH column (100 mm × 3.0 mm, 1.7 μm particle size) and thiacloprid was eluted at 1.22 min in gradient mode with CO2 /methanol as mobile phase. The 0.1% formic acid in methanol (v/v) was used as postcolumn compensation solution to improve sensitivity...
February 16, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Wenxi Li, Jia Mao, Xuefang Dai, Xin Zhao, Chengkui Qiao, Xueyan Zhang, Entang Pu
In this study, a new method for the simultaneous quantitative determination of triclopyr and aminopyralid in forage grass, hay, and soil was developed and validated using gas chromatography coupled with electron capture detector (GC-ECD). In this method, a simple and maneuverable esterification reaction was applied to convert the two acidic herbicides into their ester form with methanol. The target compounds were extracted with 1% hydrochloric acid-acetonitrile, esterified, purified by florisil solid-phase extraction cartridge, and detected in a single run by the GC-ECD...
February 26, 2018: Ecotoxicology and Environmental Safety
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