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Rasha Swadi, Grace Mather, Barry L Pizer, Paul D Losty, Violaine See, Diana Moss
BACKGROUND: Neuroblastoma is a paediatric cancer that despite multimodal therapy still has a poor outcome for many patients with high risk tumours. Retinoic acid (RA) promotes differentiation of some neuroblastoma tumours and cell lines, and is successfully used clinically, supporting the view that differentiation therapy is a promising strategy for treatment of neuroblastoma. To improve treatment of a wider range of tumour types, development and testing of novel differentiation agents is essential...
January 4, 2018: BMC Cancer
Thalita Boldrin Zanoni, Tatiana Nascimento Pedrosa, Carolina Motter Catarino, Sander W Spiekstra, Danielle Palma de Oliveira, Gertjan Den Hartog, Aalt Bast, Geja Hagemann, Susan Gibbs, Silvia Berlanga de Moraes Barros, Silvya Stuchi Maria-Engler
Allergic and irritant skin reactions caused by topical exposure to permanent hair dyes are a common problem. For regulatory and ethnical purposes, it is required to perform chemical safety assessment following the replacement, reduction, and refinement of animal testing (3Rs). Permanent hair dyes are formed by a mixture of ingredients that vary from low to extreme skin sensitizing potency and that inter-react to form unknown by-products. Because of the complex reaction, this cytotoxic mechanism has not yet been elucidated and is the subject of this study...
December 19, 2017: Food and Chemical Toxicology
Helinor J Johnston, Rachel Verdon, Suzanne Gillies, David M Brown, Teresa F Fernandes, Theodore B Henry, Adriano G Rossi, Lang Tran, Carl Tucker, Charles R Tyler, Vicki Stone
Assessing the safety of engineered nanomaterials (NMs) is paramount to the responsible and sustainable development of nanotechnology, which provides huge societal benefits. Currently, there is no evidence that engineered NMs cause detrimental health effects in humans. However, investigation of NM toxicity using in vivo, in vitro, in chemico, and in silico models has demonstrated that some NMs stimulate oxidative stress and inflammation, which may lead to adverse health effects. Accordingly, investigation of these responses currently dominates NM safety assessments...
December 14, 2017: Critical Reviews in Toxicology
Maria G Varrica, Chiara Zagni, Placido G Mineo, Giuseppe Floresta, Giulia Monciino, Venerando Pistarà, Antonio Abbadessa, Angelo Nicosia, Rogerio M Castilho, Emanuele Amata, Antonio Rescifina
((3RS,5SR)- and ((3RS,5RS)-2-(2-methoxybenzyl)-3-(1,10-phenanthrolin-2-yl)isoxazolidin-5-yl)methanol have been synthesized, according to 1,3-dipolar cycloaddition methodology, as DNA intercalating agents and evaluated for their anticancer activity against human cervical carcinoma HeLa and head and neck squamous cells carcinoma cell lines. The synthesized compounds exhibited good cytotoxic activity with IC50 better than cisplatin, used as the main and effective treatment for HNSCC, and a 24.3-72.0-fold selectivity respect to the 184B5 non-cancerous immortalized breast epithelial cell lines...
November 26, 2017: European Journal of Medicinal Chemistry
Caralyn Kemp, Harriet Thatcher, David Farningham, Claire Witham, Ann MacLarnon, Amanda Holmes, Stuart Semple, Emily J Bethell
There has been increased recognition of the 3Rs in laboratory animal management over the last decade, including improvements in animal handling and housing. For example, positive reinforcement is now more widely used to encourage primates to cooperate with husbandry procedures, and improved enclosure design allows housing in social groups with opportunity to escape and avoid other primates and humans. Both practices have become gold standards in captive primate care resulting in improved health and behavioural outcomes...
December 2017: Applied Animal Behaviour Science
Katy Taylor, Laura Rego, Tilo Weber
Under the new Directive 2010/63/EC, member states have to publish non-technical summaries (NTS) of the projects involving animals that they authorise. These summaries must include information on the objectives of the project including the predicted harm and benefits and the number and types of animals to be used. Summaries should also demonstrate compliance with the 3Rs. The intention was that NTS would help increase the transparency of animal research in the EU. In this article, we review the status of the publication of NTS across member states and give some general observations on publication speed, identification, accessibility and quality...
November 29, 2017: ALTEX
Aleksander Rust, Ciara Doran, Rosalyn Hart, Thomas Binz, Paul Stickings, Dorothea Sesardic, Andrew A Peden, Bazbek Davletov
Botulinum neurotoxins (BoNTs) type A and type B are commonly used as biopharmaceutics for neurological diseases, uniquely allowing months-long paralysis of target muscles. Their exquisite neuronal specificity is conferred by a multistep process of binding, internalization, cytosolic escape and cleavage of the neuron-specific proteins, SNAP-25 and vesicle-associated membrane proteins (VAMPs), ultimately to inhibit secretion of neurotransmitters. Currently the mouse lethality bioassay is the only available method for quality control testing of VAMP-cleaving botulinum products...
2017: Frontiers in Pharmacology
Le Tuan Anh, Alexander A Titov, Maxim S Kobzev, Leonid G Voskressensky, Alexey V Varlamov, Pavel V Dorovatovskii, Victor N Khrustalev
The title compound, C25H27NO4 (I), the product of the unusual thermolysis of aza-cyclic allene methyl 10,11-dimeth-oxy-3,8-dimethyl-6-phenyl-3-aza-benzo[d]cyclo-deca-4,6,7-triene-5-carboxyl-ate, represents a bicyclic heterosystem and crystallizes in the monoclinic space group P21/c with three crystallographically independent mol-ecules in the unit cell. These independent mol-ecules adopt very similar geometries and differ only in the conformations of the two meth-oxy substituents on the benzene ring. In two of the three independent mol-ecules, both meth-oxy groups are almost coplanar with the benzene ring [the C-C-O-Me torsion angles are 10...
November 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
Monika Nendza, Ralph Kühne, Anna Lombardo, Sebastian Strempel, Gerrit Schüürmann
Aquatic bioconcentration factors (BCFs) are critical in PBT (persistent, bioaccumulative, toxic) and risk assessment of chemicals. High costs and use of more than 100 fish per standard BCF study (OECD 305) call for alternative methods to replace as much in vivo testing as possible. The BCF waiving scheme is a screening tool combining QSAR classifications based on physicochemical properties related to the distribution (hydrophobicity, ionisation), persistence (biodegradability, hydrolysis), solubility and volatility (Henry's law constant) of substances in water bodies and aquatic biota to predict substances with low aquatic bioaccumulation (nonB, BCF<2000)...
November 3, 2017: Science of the Total Environment
Dion Garrett, Fernando Montesso, Stéphanie Fougerolle, Maria R Lopez-Alvarez, Ilhan Birand, Manuelle De Bock, Chengjin M Huang, Loïc Legrand, Stéphane Pronost, Romain Paillot
Equine Influenza (EI) is an important respiratory disease of horses caused by H3N8 equine influenza viruses (EIV). Vaccination is a key strategy to prevent or control this disease. However, EIV undergoes continuous antigenic drift and whilst numerous EI vaccines are commercially available worldwide, an accurate evaluation of their efficacy is frequently required through clinical trials conducted in the natural host. Room nebulisation is one of the chosen methods to challenge horses during EI vaccine studies...
November 2017: Veterinary Microbiology
Anja Beierfuß, Hermann Dietrich, Christian Kremser, Monika Hunjadi, Andreas Ritsch, Thomas Rülicke, Claudius Thomé, Demissew Shenegelegn Mern
Intervertebral disc (IVD) degeneration that accelerates the loss of disc structural and functional integrities is recognized as one of the major factors of chronic back pain. Cardiovascular risk factors, such as deficits of apolipoproteins that elevate the levels of cholesterol and triglycerides, are considered critical for the progress of atherosclerosis; notably in the abdominal aorta and its lumbar branching arteries that supply lumbar vertebrae and IVDs. Obstruction of the lumbar arteries by atherosclerosis is presumed to promote lumbar disc degeneration and low back pain...
2017: PloS One
Judy MacArthur Clark
First promulgated in 1959, the 3Rs of Replacement, Reduction and Refinement have evolved as fundamental principles underlying the use of animals and alternatives in science throughout the modern world. This review describes a contemporary approach to delivering the 3Rs through acknowledging the contribution of new technologies and emphasising that applying the 3Rs can be beneficial to good science as well as to animal welfare. This science-led approach moves the concept of the 3Rs out of an ethical silo where they were often considered by scientists to be an inconvenient obligation...
October 30, 2017: British Journal of Nutrition
Natalie Burden, Karin Aschberger, Qasim Chaudhry, Martin J D Clift, Paul Fowler, Helinor Johnston, Robert Landsiedel, Joanna Rowland, Vicki Stone, Shareen H Doak
Nanomaterials convey numerous advantages, and the past decade has seen a considerable rise in their development and production for an expanse of applications. While the potential advantages of nanomaterials are clear, concerns over the impact of human and environmental exposure exist. Concerted, science-led efforts are required to understand the effects of nanomaterial exposure and ensure that protection goals are met. There is much on-going discussion regarding how best to assess nanomaterial risk, particularly considering the large number of tests that may be required...
October 22, 2017: Regulatory Toxicology and Pharmacology: RTP
Donato Traversa, Anja Joachim
Experimental infections are required by current guidelines for investigating the efficacy of anthelmintics in dogs and cats. Recently, alternatives to experimental infections and the sacrificing of research dogs and cats have been evaluated, and novel conceptual investigations and methods of examination have been explored. Several of these approaches could potentially be used in efficacy studies for anthelmintics in dogs and cats. Here, we provide food for thought towards using new tools for evaluating the efficacy of anthelmintics in companion animals, for promoting the value of field trials, and for updating the existing guidelines for the efficacy testing of anthelmintics in dogs and cats...
October 4, 2017: Trends in Parasitology
Viviana Cuartas, Braulio Insuasty, Justo Cobo, Christopher Glidewell
The reaction of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde and N-benzylmethylamine under microwave irradiation gives 5-[benzyl(methyl)amino]-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, C19H19N3O, (I). Subsequent reactions under basic conditions, between (I) and a range of acetophenones, yield the corresponding chalcones. These undergo cyclocondensation reactions with hydrazine to produce reduced bipyrazoles which can be N-formylated with formic acid or N-acetylated with acetic anhydride. The structures of (I) and of representative examples from this reaction sequence are reported, namely the chalcone (E)-3-{5-[benzyl(methyl)amino]-3-methyl-1-phenyl-1H-pyrazol-4-yl}-1-(4-bromophenyl)prop-2-en-1-one, C27H24BrN3O, (II), the N-formyl derivative (3RS)-5'-[benzyl(methyl)amino]-3'-methyl-1',5-diphenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole]-2-carbaldehyde, C28H27N5O, (III), and the N-acetyl derivative (3RS)-2-acetyl-5'-[benzyl(methyl)amino]-5-(4-methoxyphenyl)-3'-methyl-1'-phenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole], which crystallizes as the ethanol 0...
October 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
Almut Köhler, Chereen Collymore, Karin Finger-Baier, Robert Geisler, Larissa Kaufmann, Kieran C Pounder, Stefan Schulte-Merker, Ana Valentim, Zoltan M Varga, Jürgen Weiss, Uwe Strähle
The increasing importance of zebrafish as a biomedical model organism is reflected by the steadily growing number of publications and laboratories working with this species. Regulatory recommendations for euthanasia as issued in Directive 2010/63/EU are, however, based on experience with fish species used for food production and do not take the small size and specific physiology of zebrafish into account. Consequently, the currently recommended methods of euthanasia in the Directive 2010/63/EU are either not applicable or may interfere with research goals...
October 2, 2017: Zebrafish
Deepak Gola, Anushree Malik, Maneesh Namburath, Shaikh Ziauddin Ahammad
Presence of industrial dyes and heavy metal as a contaminant in environment poses a great risk to human health. In order to develop a potential technology for remediation of dyes (Reactive remazol red, Yellow 3RS, Indanthrene blue and Vat novatic grey) and heavy metal [Cu(II), Ni(II), Cd(II), Zn(II), Cr(VI) and Pb(II)] contamination, present study was performed with entomopathogenic fungi, Beauveria bassiana (MTCC no. 4580). High dye removal (88-97%) was observed during the growth of B. bassiana while removal percentage for heavy metals ranged from 58 to 75%...
October 1, 2017: Environmental Science and Pollution Research International
Malgorzata Kucinska, Marek Murias, Patrycja Nowak-Sliwinska
The proper design of experiments is a critical step for each study in order to obtain reproducible and reliable data. Taking into account constant competitiveness in the quickly developing biomedical sciences and the availability of sophisticated techniques, the choice and establishment of an experimental model system are essential for a successful research project. Currently, various sophisticated in vitro and in vivo models are being designed and developed in order to replace the use of mammalian models to investigate the mechanisms of action, activity and properties of novel compounds or treatment modalities...
July 2017: Mutation Research
Laura Domicevica, Heidi Koldsø, Philip C Biggin
P-glycoprotein (P-gp) can transport a wide range of very different hydrophobic organic molecules across the membrane. Its ability to extrude molecules from the cell creates delivery problems for drugs that target proteins in the central nervous system (CNS) and also causes drug-resistance in many forms of cancer. Whether a drug will be susceptible to export by P-gp is difficult to predict and currently this is usually assessed with empirical and/or animal models. Thus, there is a need to better understand how P-gp works at the molecular level in order to fulfil the 3Rs: Refinement, reduction and replacement of animals in research...
September 2, 2017: Journal of Molecular Graphics & Modelling
Marieke Hoonakker, Juan Arciniega, Coenraad Hendriksen
The current test of acellular Bordetella pertussis (aP) vaccines for residual pertussis toxin (PTx) is the Histamine Sensitization test (HIST), based on the empirical finding that PTx sensitizes mice to histamine. Although HIST has ensured the safety of aP vaccines for years, it is criticized for the limited understanding of how it works, its technical difficulty, and for animal welfare reasons. To estimate the number of mice used worldwide for HIST, we surveyed major aP manufacturers and organizations performing, requiring, or recommending the test...
November 2, 2017: Human Vaccines & Immunotherapeutics
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