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Sunil Ghatge, Youri Yang, Woo-Young Song, Tae-Young Kim, Hor-Gil Hur
In the present study, the gene encoding a multicopper oxidase, more precisely a laccase from the thermoalkaliphilic aerobic bacterium Caldalkalibacillus thermarum strain TA2.A1 (CtLac), was cloned and expressed in Escherichia coli. CtLac is a monomeric protein with a molecular weight of 57 kDa as determined by native polyacrylamide gel electrophoresis. The optimum pH and temperature for 2,6-dimethoxyphenol (2,6-DMP) oxidation were 8.0 and 70 °C, respectively. The kinetic constants Km and kcat for 2,6-DMP were of 200 μM and 23 s-1 , respectively...
March 19, 2018: Applied Microbiology and Biotechnology
Hélène Chapy, Leonid Kagan
With a long half-life, pharmacokinetic evaluation of monoclonal antibodies in rodents lasts multiple weeks during which the animals may grow significantly. We evaluated the impact of weight, age and previous drug exposure on the pharmacokinetics of rituximab. Serum concentrations of rituximab were measured after intravenous and subcutaneous dosing, in Sprague-Dawley rats between 7 to 21 weeks old and weighing between 200 to 600 g. The growth of rats during the study was incorporated into the model through the increase of the volumes of compartments in relation to the rats total body weight...
March 15, 2018: Journal of Pharmaceutical Sciences
Mona Jasmine R Ahonen, Dakota J Suchyta, Huanyu Zhu, Mark H Schoenfisch
Low and high molecular weight alginate biopolymers were chemically modified to store and release potentially therapeutic levels of nitric oxide (NO). Carbodiimide chemistry was first used to modify carboxylic acid functional groups with a series of small molecule alkyl amines. The resulting secondary amines were subsequently converted to N-diazeniumdiolate NO donors via reaction with NO gas under basic conditions. NO donor-modified alginates stored between 0.4-0.6 µmol NO•mg-1. In aqueous solution, the NO-release kinetics was diverse (0...
March 19, 2018: Biomacromolecules
Wataru Ochiai, Hiroko Kobayashi, Satoshi Kitaoka, Mayumi Kashiwada, Yuya Koyama, Saho Nakaishi, Tomomi Nagai, Masaki Aburada, Kiyoshi Sugiyama
5,7-Dimethoxyflavone (5,7-DMF), one of the major components of Kaempferia parviflora, has anti-obesity, anti-inflammatory, and antineoplastic effects. On the other hand, in vitro studies have reported that it directly inhibits the drug metabolizing enzyme family cytochrome P450 (CYP) 3As. In this study, its safety was evaluated from a pharmacokinetic point of view, based on daily ingestion of 5,7-DMF. Midazolam, a substrate of CYP3As, was orally administered to mice treated with 5,7-DMF for 10 days, and its pharmacokinetic properties were investigated...
March 17, 2018: Journal of Natural Medicines
H Zatorski, P Mosinska, M Storr, J Fichna
There is an unmet need for effective pharmacological therapies for the treatment of gastroparesis and other upper gastrointestinal (GI) motility disorders, which reduce patients' quality of life and are a burden to the healthcare system. Ghrelin is an endogenous growth hormone secretagogue receptor ligand and has been shown to exert prokinetic effects on GI motility. Nevertheless, considering the short half-life of ghrelin its use in clinical practice is limited. Thus, ghrelin receptor agonists with enhanced pharmacokinetics were developed; they accelerate gastric emptying and improve symptoms of gastroparesis in animal models and humans...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Qiang Hao, Lei He, Jiming Zhou, Yuan Yuan, Xiaowen Ma, Zhijun Pang, Weina Li, Yingqi Zhang, Wei Zhang, Cun Zhang, Meng Li
BACKGROUND: Thymosin beta 4 (Tβ4) is a 43-amino-acid peptide with protective properties in myocardium injury. Previously, we produced a recombinant human dimeric Tβ4 (DTβ4). Here, the cardioprotective effects of DTβ4 and the molecular mechanisms underlying its enhanced activity were investigated. METHODS AND RESULTS: Echocardiography measurements showed that the cardioprotective effect of DTβ4 in myocardial infarction mice was significantly higher than that of wild-type Tβ4...
March 14, 2018: International Journal of Cardiology
Qing Cao, Alan D Steinman, Lei Yao, Liqiang Xie
An experiment was conducted to investigate the effect of farming activities on microcystin-LR (MC-LR) degradation in soils. Three farming activities were assessed: 1) fertilization via addition of different nitrogen sources and organic matter; 2) pesticide application by addition of different commercial pesticides; and 3) irrigation by addition of different amount of water. The contribution of the two major degradation processes of MC-LR in soils, photodegradation and biodegradation, were also evaluated. MC-LR was added into the soil samples to create a concentration of 500 μg kg-1 for each treatment...
March 14, 2018: Ecotoxicology and Environmental Safety
Kristen Healy
The goal of this study was to evaluate the use of stable isotope labeled compounds to better understand factors influencing energy turnover in larval Culex quinquefasciatus (Say; Diptera: Culicidae). Three isotope labeled compounds were evaluated in this study, including 15N-labeled potassium nitrate, 13C-labeled glucose, and 13C-labeled leucine. Conditions were first optimized in the laboratory to determine the most appropriate concentration of isotope, as well as the half-life of enrichment. Once optimum conditions were established we used standard equations to predict and determine temperature and density-dependent energy turnover rates...
March 14, 2018: Journal of Medical Entomology
Debasis Banerjee, Xianyin Chen, Sergey Lobanov, Anna M Plonka, Xiaojun Chan, John Daly, Taejin Kim, Praveen K Thallapally, John Parise
Used nuclear fuel reprocessing represents a unique challenge when dealing with radionuclides such as isotopes of85 Kr and129 I2 due to their volatility and long half-life. Efficient capture of129 I2 (t1/2 = 15.7 ×106 million years) from the nuclear waste stream can help reduce the risk of releasing I2 radionuclide into the environment and/or potential incorporation into the human thyroid. Metal organic frameworks have the reported potential to be I2 adsorbents but the effect of water vapor, generally present in the reprocessing off-gas stream, is rarely taken into account...
March 16, 2018: ACS Applied Materials & Interfaces
Sophie Poty, Lynn C Francesconi, Michael R McDevitt, Michael J Morris, Jason S Lewis
With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their wide-spread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters...
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
Michael M Linden, J Philipp Wagner, Bastian Bernhardt, Marcus A Bartlett, Wesley D Allen, Peter R Schreiner
Disentangling internal and external effects is a key requirement for understanding conformational tunneling processes. Here we report the s-trans/s-cis tunneling rotamerization of carbonic acid monomethyl ester (1) under matrix isolation conditions and make comparisons to its parent carbonic acid (3). The observed tunneling rate of 1 is temperature independent in the 3-20 K range and accelerates when using argon instead of neon as the matrix material. The methyl group increases the effective half-life (τeff) of the energetically disfavored s-trans-conformer from 3-5 h for 3 to 11-13 h for 1...
March 15, 2018: Journal of Physical Chemistry Letters
Wenge Chen, Yunlong Cheng, Jianzhong Chen, Jiahang Chen, Kai Jiang, Yuyang Zhou, Lee Jia
Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes...
March 8, 2018: Journal of Pharmaceutical and Biomedical Analysis
Y Dargaud, X Delavenne, D P Hart, S Meunier, P Mismetti
Over the past decades, haemophilia management has continually evolved, with prophylaxis now considered the treatment of choice. Prophylaxis primarily seeks to prevent bleeding and haemarthrosis episodes from occurring and avert the otherwise inevitable haemophilic arthropathy. Yet, numerous unanswered issues remain. These concern dose levels, dosing intervals, ways of integrating variability in bleeding phenotype, patient age, joint status, lifestyle, physical activity, treatment adherence and individual responses to FVIII or FIX concentrates...
March 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
J B Albert, G Anton, I Badhrees, P S Barbeau, R Bayerlein, D Beck, V Belov, M Breidenbach, T Brunner, G F Cao, W R Cen, C Chambers, B Cleveland, M Coon, A Craycraft, W Cree, T Daniels, M Danilov, S J Daugherty, J Daughhetee, J Davis, S Delaquis, A Der Mesrobian-Kabakian, R DeVoe, T Didberidze, J Dilling, A Dolgolenko, M J Dolinski, W Fairbank, J Farine, S Feyzbakhsh, P Fierlinger, D Fudenberg, R Gornea, K Graham, G Gratta, C Hall, E V Hansen, J Hoessl, P Hufschmidt, M Hughes, A Jamil, M J Jewell, A Johnson, S Johnston, A Karelin, L J Kaufman, T Koffas, S Kravitz, R Krücken, A Kuchenkov, K S Kumar, Y Lan, D S Leonard, G S Li, S Li, C Licciardi, Y H Lin, R MacLellan, T Michel, B Mong, D Moore, K Murray, R Nelson, O Njoya, A Odian, I Ostrovskiy, A Piepke, A Pocar, F Retière, P C Rowson, J J Russell, S Schmidt, A Schubert, D Sinclair, V Stekhanov, M Tarka, T Tolba, R Tsang, P Vogel, J-L Vuilleumier, M Wagenpfeil, A Waite, T Walton, M Weber, L J Wen, U Wichoski, G Wrede, L Yang, Y-R Yen, O Ya Zeldovich, J Zettlemoyer, T Ziegler
Results from a search for neutrinoless double-beta decay (0νββ) of ^{136}Xe are presented using the first year of data taken with the upgraded EXO-200 detector. Relative to previous searches by EXO-200, the energy resolution of the detector has been improved to σ/E=1.23%, the electric field in the drift region has been raised by 50%, and a system to suppress radon in the volume between the cryostat and lead shielding has been implemented. In addition, analysis techniques that improve topological discrimination between 0νββ and background events have been developed...
February 16, 2018: Physical Review Letters
Karolina Pierzynowska, Lidia Gaffke, Zuzanna Cyske, Michał Puchalski, Estera Rintz, Michał Bartkowski, Marta Osiadły, Michał Pierzynowski, Jagoda Mantej, Ewa Piotrowska, Grzegorz Węgrzyn
Autophagy is a process of degradation of macromolecules in the cytoplasm, particularly proteins of a long half-life, as well as whole organelles, in eukaryotic cells. Lysosomes play crucial roles during this degradation. Autophagy is a phylogenetically old, and evolutionarily conserved phenomenon which occurs in all eukaryotic cells. It can be found in yeast Saccharomyces cerevisiae, insect Drosophila melanogaster, and mammals, including humans. Its high importance for cell physiology has been recognized, and in fact, dysfunctions causing impaired autophagy are associated with many severe disorders, including cancer and metabolic brain diseases...
March 14, 2018: Metabolic Brain Disease
Homa Torabizadeh, Asieh Mahmoudi
Inulinase can produce a high amount of fructose syrup from inulin in a one-step enzymatic process. Inulinase from Aspergillus niger was immobilized covalently on Fe3 O4 magnetic nanoparticles functionalized with wheat gluten hydrolysates (WGHs). Wheat gluten was enzymatically hydrolyzed by two endopeptidases Alcalase and Neutrase and related nanoparticles were prepared by desolvation method. Magnetite nanoparticles were coated with WGHs nanoparticles and then inulinase was immobilized onto it using glutaraldehyde as crosslinking agent...
March 2018: Biotechnology Reports
Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
G F Pierce, A Haffar, G Ampartzidis, F Peyvandi, S Diop, M El-Ekiaby, H M van den Berg
INTRODUCTION: The gaps in haemophilia treatment around the world are enormous; approximately 60% of an estimated 475 000 individuals are not identified. Of the 187 000 diagnosed, 30% (57 000) access clotting factor replacement therapy. Since 1996, humanitarian aid distributed by the World Federation of Hemophilia (WFH) has played a minor, yet vital role providing life-saving clotting factor to countries in emergency situations. Donated amounts have been small and sporadic, often salvaging short-dated products, providing little opportunity to leverage donations with governments...
March 14, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
A Bar-Ilan, T Livnat, M Hoffmann, L Binder, M Zakar, R Guy, Y Felikman, L Moschcovich, B Shenkman, D Monroe, O Hershkovitz, G Kenet, G Hart
INTRODUCTION: Recombinant FVIIa (rFVIIa) is an effective treatment for haemophilia through frequent administration. However, the short half-life of rFVIIa decreases its prophylactic ability to reduce bleeding. Carboxy-terminal peptide (CTP)-modified FVIIa (MOD-5014) is a long-acting rFVIIa developed for on-demand treatment of haemophilia using either an intravenous or subcutaneous injection with the aim of less frequent administrations, as well as for prophylactic use. AIM: The comprehensive evaluation of the activity MOD-5014 vs commercially available rhFVIIa, as well as their interaction with cofactors and inhibitors...
March 14, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
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