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Developmental Toxicity

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https://www.readbyqxmd.com/read/28539002/from-in-vivo-to-in-vitro-the-medical-device-testing-paradigm-shift
#1
Dayna Kerecman Myers, Alan M Goldberg, Albrecht Poth, Michael F Wolf, Joseph Carraway, James McKim, Kelly P Coleman, Richard Hutchinson, Ronald Brown, Harald F Krug, Anthony Bahinski, Thomas Hartung
Amid growing efforts to advance the replacement, reduction, and refinement of the use of animals in research, there is a growing recognition that in vitro testing of medical devices can be more effective, both in terms of cost and time, and also more reliable than in vivo testing. Although the technological landscape has evolved rapidly in support of these concepts, regulatory acceptance of alternative testing methods has not kept pace. Despite the acceptance by regulators of some in vitro tests (cytotoxicity, gene toxicity, and some hemocompatibility assays), many toxicity tests still rely on animals (irritation, sensitization, acute toxicity, reproductive/developmental toxicity), even where other industrial sectors have already abandoned them...
May 25, 2017: ALTEX
https://www.readbyqxmd.com/read/28535311/quantification-of-estradiol-uptake-in-zebrafish-embryos-and-larvae
#2
J Paige Souder, Daniel A Gorelick
Zebrafish are a powerful model system to assess the molecular and cellular effects of exposure to toxic chemicals during embryonic development. To study the effects of environmental endocrine disruptors, embryos and larvae are commonly exposed to supraphysiologic concentrations of these compounds in the water, but their bioavailability in zebrafish is largely unknown. One hypothesis is that supraphysiologic concentrations of estrogens in the water are required to achieve physiologic levels in vivo, however this has not been directly tested...
May 23, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28533121/recent-progress-in-hepatocyte-culture-models-and-their-application-to-the-assessment-of-drug-metabolism-transport-and-toxicity-in-drug-discovery-the-value-of-tissue-engineering-for-the-successful-development-of-a-microphysiological-system
#3
REVIEW
Kazuhiro Tetsuka, Masato Ohbuchi, Kenji Tabata
Tissue engineering technology has provided many useful culture models. This article reviews the merits of this technology in a hepatocyte culture system, and describes the applications of the sandwich-cultured hepatocyte model in drug discovery. In addition, we also review recent investigations of the utility of the three-dimensional bioprinted human liver tissue model and spheroid model. Finally, we present the future direction and developmental challenges of a hepatocyte culture model for the successful establishment of a microphysiological system, represented as an organ-on-a-chip and even as a human-on-a-chip...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28531178/zebrafish-exposure-to-environmentally-relevant-concentration-of-depleted-uranium-impairs-progeny-development-at-the-molecular-and-histological-levels
#4
Olivier Armant, Kewin Gombeau, Sophia Murat El Houdigui, Magali Floriani, Virginie Camilleri, Isabelle Cavalie, Christelle Adam-Guillermin
Uranium is an actinide naturally found in the environment. Anthropogenic activities lead to the release of increasing amounts of uranium and depleted uranium (DU) in the environment, posing potential risks to aquatic organisms due to radiological and chemical toxicity of this radionucleide. Although environmental contaminations with high levels of uranium have already been observed, chronic exposures of non-human species to levels close to the environmental quality standards remain scarcely characterized. The present study focused on the identification of the molecular pathways impacted by a chronic exposure of zebrafish to 20 μg/L of DU during 10 days...
2017: PloS One
https://www.readbyqxmd.com/read/28529177/senecio-brasiliensis-impairs-eclosion-rate-and-induces-apoptotic-cell-death-in-larvae-of-drosophila-melanogaster
#5
Giulianna Echeverria Macedo, Karen Kich Gomes, Nathane Rosa Rodrigues, Illana Kemmerich Martins, Gabriel da Luz Wallau, Nélson Rodrigues de Carvalho, Litiele Cezar da Cruz, Dennis Guilherme da Costa Silva, Aline Augusti Boligon, Jeferson Luis Franco, Thaís Posser
Senecio brasilienis (Spreng) Less., is a species native from Brazil, popularly known as "maria mole", and known to induce hepatotoxicity due to its high content of Pyrrolizidine alkaloids. Despite its toxicity, this plant is widely used in Brazilian folk medicine. Considering the antagonizing effects described for S. brasiliensis, we describe here molecular markers involved in the toxicity of hydroalcoholic extract from leaves of S. brasiliensis (HESB) in Drosophila melanogaster. Phytochemical analysis of HESB revealed the presence of phenolic acids and flavonoids...
May 18, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28527947/embryonic-vascular-disruption-adverse-outcomes-linking-high-throughput-signaling-signatures-with-functional-consequences
#6
Robert G Ellis-Hutchings, Raja S Settivari, Alene T McCoy, Nicole Kleinstreuer, Jill Franzosa, Thomas B Knudsen, Edward W Carney
Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay...
May 17, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28521150/the-effects-of-copper-oxide-nanoparticles-on-dorsoventral-patterning-convergent-extension-and-neural-and-cardiac-development-of-zebrafish
#7
Jia Xu, Qiuping Zhang, Xu Li, Sihui Zhan, Lifeng Wang, Dongyan Chen
Currently, nanoparticles are widely used in biomedicine and industry. CuO nanoparticles (CuO-NPs) are versatile materials in our daily life and their toxicity has drawn extensive attention. In this study, we concentrate on the effect of CuO-NPs on early zebrafish development. The results reveal that CuO-NPs can induce abnormal phenotypes of a smaller head and eyes and delayed epiboly. The gene expression pattern shows that CuO-NPs spatially narrow the expression of dorsal genes chordin and goosecoid and alter the expression of dlx3, ntl and hgg which are related to the cell migration of gastrulation...
May 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28518097/light-sheet-based-fluorescence-microscopy-of-living-or-fixed-and-stained-tribolium-castaneum-embryos
#8
Frederic Strobl, Selina Klees, Ernst H K Stelzer
The red flour beetle Tribolium castaneum has become an important insect model organism in developmental genetics and evolutionary developmental biology. The observation of Tribolium embryos with light sheet-based fluorescence microscopy has multiple advantages over conventional widefield and confocal fluorescence microscopy. Due to the unique properties of a light sheet-based microscope, three dimensional images of living specimens can be recorded with high signal-to-noise ratios and significantly reduced photo-bleaching as well as photo-toxicity along multiple directions over periods that last several days...
April 28, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516350/evaluation-of-vascular-effect-of-arsenic-using-in-vivo-assays
#9
Bharat Patel, Rajat Das, Anil Gautam, Mugdha Tiwari, Sukhdev Acharya, Sunil Kumar
Arsenic (As) is an abundant toxicant present in groundwater and soil in various parts of the world including eastern part of India. The epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. Placenta is known to utilize vasculogenesis to develop its vasculature circulation. The effects of four different doses of sodium meta-arsenite (0, 10, 20, 75, and 150 ppm) were assessed on the vascular structure using two different in vivo models, i.e., Matrigel and chorioallantoic membrane (CAM) assay...
May 17, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28516261/-metals-and-their-compounds-as-contaminants-in-food-arsenic-cadmium-lead-and-aluminum
#10
REVIEW
Andrea Hartwig, Gunnar Jahnke
Metals and their compounds are ubiquitously distributed in the environment, thus reaching plant and animal derived food. While actual exposure levels in Europe do not give rise to concern for acute toxicity, chronic toxicity of some metals and metalloids cannot be completely ruled out. Thus, in the case of inorganic arsenic, an elevated risk of carcinogenicity in different organs cannot be excluded even under actual dietary exposure conditions. In the case of cadmium, nephrotoxicity may be a particular problem for certain subgroups, such as children...
May 17, 2017: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
https://www.readbyqxmd.com/read/28511355/identification-of-polar-transformation-products-and-high-molecular-weight-polycyclic-aromatic-hydrocarbons-pahs-in-contaminated-soil-following-bioremediation
#11
Leah Chibwe, Cleo L Davie-Martin, Michael D Aitken, Eunha Hoh, Staci L Massey Simonich
Bioremediation is a technique commonly used to reduce the toxicity associated with polycyclic aromatic hydrocarbons (PAHs) in contaminated soils. However, the efficacy of bioremedial applications is evaluated based on the removal of a subset of parent (or unsubstituted) PAHs and does not incorporate toxic polar transformation products or the more mutagenic high molecular weight PAHs (MW≥302amu or MW302-PAHs). Previously, an effects-directed analysis approach was used to assess the effect of bioremediation on the toxicity of a coal tar-contaminated soil...
May 12, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28507483/effects-of-hesperidin-on-formaldehyde-induced-toxicity-in-pregnant-rats
#12
Sameha Merzoug, Mohamed Lamine Toumi
This experimental study aimed to investigate the protective effect of a bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological and behavioral outcomes in pregnant rats and developmental aspects in their offspring. Female Wistar rats were subjected to perigestational exposure to FA (2 mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os). Pregnant rats were weighed throughout gestation and tested in two behavioral paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and 19 to evaluate the anxiety-like behavior and locomotive alterations...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28503921/fluorescent-nanoparticles-with-tissue-dependent-affinity-for-live-zebrafish-imaging
#13
Deepak Kumar Khajuria, Vijay Bhooshan Kumar, David Karasik, Aharon Gedanken
Carbon-based nanodots (CDs) are widely investigated due to their low toxicity, outstanding water solubility and biocompatibility. Specifically, fluorescent CDs have attracted ever-increasing interest. However, so far, only a few studies have focused on assessing the fluorescence of nitrogen-doped CDs (N@CDs) during in-vivo exposure. Here, we describe a strategy for engineering economically viable non-toxic one-pot hydrothermal synthesized N@CDs. The low toxicity and suitability of the N@CDs for fluorescence imaging are validated using zebrafish (ZF) as a model...
May 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28502309/effects-of-vitrification-of-cumulus-enclosed-porcine-oocytes-at-the-germinal-vesicle-stage-on-cumulus-expansion-nuclear-progression-and-cytoplasmic-maturation
#14
Ruth Appeltant, Tamás Somfai, Elisa C S Santos, Thanh Quang Dang-Nguyen, Takashi Nagai, Kazuhiro Kikuchi
Although offspring have been produced from porcine oocytes vitrified at the germinal vesicle (GV) stage, the rate of embryo development remains low. In the present study, nuclear morphology and progression, cumulus expansion, transzonal projections (TZPs), ATP and glutathione (GSH) levels were compared between vitrified cumulus-oocyte complexes (COCs) and control COCs (no cryoprotectant treatment and no cooling), as well as a toxicity control (no cooling). Vitrification was performed with 17.5% (v/v) ethylene glycol and 17...
May 15, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28500731/alternative-plasticizer-4-cyclohexene-1-2-dicarboxylic-acid-dinonyl-ester-for-blood-containers-with-protective-effects-on-red-blood-cells-and-improved-cold-resistance
#15
Yuki Morishita, Yusuke Nomura, Chie Fukui, Ayano Fujisawa, Kayo Watanabe, Hideo Fujimaki, Hidefumi Kumada, Kaoru Inoue, Tomomi Morikawa, Miwa Takahashi, Tsuyoshi Kawakami, Hideyuki Sakoda, Tomokazu Mukai, Toshiyasu Yuba, Ken-Ichi Inamura, Akito Tanoue, Ken-Ichi Miyazaki, Ung-Il Chung, Kumiko Ogawa, Midori Yoshida, Yuji Haishima
Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl chloride (PVC), is eluted from PVC-made blood containers and protects against red blood cell (RBC) hemolysis. However, concerns have arisen regarding the reproductive and developmental risks of DEHP in humans, and the use of alternative plasticizers for medical devices has been recommended worldwide. In this study, we propose that the use of a novel plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester (DL9TH), could help produce more useful and safe blood containers...
May 13, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28499417/genome-wide-characterization-and-expression-analyses-of-superoxide-dismutase-sod-genes-in-gossypium-hirsutum
#16
Wei Wang, Xiaopei Zhang, Fenni Deng, Rui Yuan, Fafu Shen
BACKGROUND: Superoxide dismutases (SODs) are a key antioxidant enzyme family, which have been implicated in protecting plants against the toxic effects of reactive oxygen species. Despite current studies have shown that the gene family are involved in plant growth and developmental processes and biotic and abiotic stress responses, little is known about its functional role in upland cotton. RESULTS: In the present study, we comprehensively analyzed the characteristics of the SOD gene family in upland cotton (Gossypium hirsutum)...
May 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28498972/development-of-a-combined-in-vitro-physiologically-based-kinetic-pbk-and-monte-carlo-modelling-approach-to-predict-interindividual-human-variation-in-phenol-induced-developmental-toxicity
#17
Marije Strikwold, Bert Spenkelink, Ruud A Woutersen, Ivonne M C M Rietjens, Ans Punt
With our recently developed in vitro physiologically based kinetic (PBK) modelling approach we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol induced developmental toxicity...
May 11, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28498344/mercury-in-children-current-state-on-exposure-through-human-biomonitoring-studies
#18
REVIEW
Flavia Ruggieri, Costanza Majorani, Francesco Domanico, Alessandro Alimonti
Mercury (Hg) in children has multiple exposure sources and the toxicity of Hg compounds depends on exposure routes, dose, timing of exposure, and developmental stage (be it prenatal or postnatal). Over the last decades, Hg was widely recognized as a threat to the children's health and there have been acknowledgements at the international level of the need of a global policy intervention-like the Minamata treaty-aimed at reducing or preventing Hg exposure and protecting the child health. National human biomonitoring (HBM) data has demonstrated that low levels of exposure of Hg are still an important health concern for children, which no one country can solve alone...
May 12, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28494400/maternal-serum-lead-level-during-pregnancy-is-positively-correlated-with-risk-of-preterm-birth-in-a-chinese-population
#19
Jun Li, Hua Wang, Jia-Hu Hao, Yuan-Hua Chen, Lu Liu, Zhen Yu, Lin Fu, Fang-Biao Tao, De-Xiang Xu
Lead (Pb) is a well-known developmental toxicant. The aim of the present study was to analyze the association between maternal serum Pb level and risk of preterm birth in a population-based birth cohort study. The present study analyzed a sub-study of the China-Anhui Birth Cohort that recruited 3125 eligible mother-and-singleton-offspring pairs. Maternal serum Pb level was measured by graphite furnace atomic absorption spectrometry. All subjects were classified into three groups by tertile division according to serum Pb level: Low-Pb (L-Pb, <1...
May 8, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28488132/arsenic-and-immune-response-to-infection-during-pregnancy-and-early-life
#20
REVIEW
Sarah E Attreed, Ana Navas-Acien, Christopher D Heaney
PURPOSE OF REVIEW: Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life...
May 9, 2017: Current Environmental Health Reports
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