36 research outputs found
Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing
Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit
Variability of solar/stellar activity and magnetic field and its influence on planetary atmosphere evolution
Combination therapy of heparin-bonded covered stent and bare-nitinol stent assessed by intravascular ultrasound
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The Search for Worlds Like Our Own
The direct detection of Earth-like exoplanets orbiting nearby stars and the characterization of such planets -- particularly, their evolution, their atmospheres, and their ability to host life -- constitute a significant problem. The quest for other worlds as abodes of life has been one of mankind's great questions for several millennia. For instance, as stated by Epicurus 300 BC: Other worlds, with plants and other living things, some of them similar and some of them different from ours, must exist. Demokritos from Abdera (460-370 BC), the man who invented the concept of indivisible small parts - atoms - also held the belief that other worlds exist around the stars and that some of these worlds may be inhabited by life-forms. The idea of the plurality of worlds and of life on them has since been held by scientists like Johannes Kepler and William Herschel, among many others. Here, one must also mention Giordano Bruno. Born in 1548, Bruno studied in France and came into contact with the teachings of Nicolas Copernicus. He wrote the book De l'Infinito, Universo e Mondi in 1584, in which he claimed that the Universe was infinite, that it contained an infinite amount of worlds like Earth, and that these worlds were inhabited by intelligent beings. At the time, this was extremely controversial, and eventually Bruno was arrested by the church and burned at the stake in Rome in 1600, as a heretic, for promoting this and other equally confrontational issues (though it is unclear exactly which idea was the one that ultimately brought him to his end). In all the aforementioned cases, the opinions and results were arrived at through reasoning--not by experiment. We have only recently acquired the technological capability to observe planets orbiting stars other than 6our Sun; acquisition of this capability has been a remarkable feat of our time. We show in this introduction to the Habitability Primer that mankind is at the dawning of an age when, by way of the scientific method and 21st-century technology, we will be able to answer this fascinating controversial issue that has persisted for at least 2500 years