Introduction to biomedical literature text mining: context and objectives.

INFORMATION: If you are reading this, you know how important it is and almost certainly look to the biomedical literature for a large part of the information you need. We work hard to find more and more biomedical literature, seeking new content from multiple sources. But, can there be too much of a good thing? Most science is reductionist by nature. It is difficult enough finding the relevant nuggets of information from 1,000 documents. It is at least ten times harder to do so from 10,000 documents. And, with 25 million biomedical journal articles and many times that of other textual information sources, we are faced with significant challenges. In this introduction, we identify some of those challenges to prepare you for the remaining chapters.

Toxicokinetic, toxicodynamic, and toxicoproteomic aspects of short-term exposure to trenbolone in female fish.

The toxicokinetics of trenbolone was characterized during 500 ng/l water exposures in female rainbow trout (Oncorhynchus mykiss) and fathead minnows (Pimephales promelas). Related experiments measured various toxicodynamic effects of exposure. In both species, trenbolone was rapidly absorbed from the water and reached peak plasma levels within 8h of exposure. Afterwards, trenbolone concentrations in trout (66-95 ng/ml) were 2-6 times higher compared with minnows (15-29 ng/ml), which was attributable to greater plasma binding in trout. During water exposures, circulating levels of estradiol (E2) rapidly decreased in both species to a concentration that was 25%-40% of control values by 8-24h of exposure and then remained relatively unchanged for the subsequent 6 days of exposure. In trout, changes in circulating levels of follicle-stimulating hormone were also significantly greater after trenbolone exposure, relative to controls. In both species, the pharmacokinetics of injected E2-d3 was altered by trenbolone exposure with an increase in total body clearance and a corresponding decrease in elimination half-life. The unbound percentage of E2 in trout plasma was 0.25%, which was similar in pre- or postvitellogenic female trout. Subsequent incubation with trenbolone caused the unbound percentage to significantly increase to 2.4% in the previtellogenic trout plasma. iTRAQ-based toxicoproteomic studies in minnows exposed to 5, 50, and 500 ng/l trenbolone identified a total of 148 proteins with 19 downregulated including vitellogenin and 18 upregulated. Other downregulated proteins were fibrinogens, α-2-macroglobulin, and transferrin. Upregulated proteins included amine oxidase, apolipoproteins, parvalbumin, complement system proteins, and several uncharacterized proteins. The results indicate trenbolone exposure is a highly dynamic process in female fish with uptake and tissue equilibrium quickly established, leading to both rapid and delayed toxicodynamic effects.

Biomarker analysis of Morquio syndrome: identification of disease state and drug responsive markers.

BACKGROUND: This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA. METHODS: Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS) levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance. RESULTS: Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a), matrix metalloprotein (MMP)-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P. CONCLUSIONS: Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.