Demographics, Glasgow Coma Scale (GCS), ICH volume, ICH location, and 30-day case fatality rates were determined. Total WBC count, ANC, AMC, and hemoglobin concentration were determined. Linear and logistic regressions were used to evaluate factors associated with baseline ICH volume (log transformed) and 30-day case fatality, respectively. Results: Of the 186 patients, mean
(+/- SD) age was 67.3 +/- 14.8 years; 51% were men and 22% were black. Median (interquartile range) ICH volume was 12.8 (4.9, 29.4) mL. After adjusting for patient age and initial hemoglobin, higher initial WBC count (P = .0009) and higher ANC (P = .006) were associated with higher ICH volume, whereas AMC was not (P = .4). After adjusting for patient age, GCS, intraventricular hemorrhage (+/-), stroke location, and ICH volume, baseline AMC was associated with greater odds of Bafilomycin A1 30-day Wnt/beta-catenin inhibitor case fatality (odds ratio 2.26, 95% confidence interval 1.10-4.65, P = .03). Conclusions: The association of AMC with higher 30-day case fatality after ICH is hypothesis generating. Given the lack of association between presenting AMC and ICH volume, AMC may contribute to secondary injury after ICH (hematoma expansion and/or cerebral edema).”
“Introduction: Numerous studies have confirmed that zebrafish and mammalian toxicity profiles are strikingly similar and the transparency of larval zebrafish permits direct in vivo assessment
of drug toxicity including hepatotoxicity in zebrafish. Methods: Hepatotoxicity of 6 known mammalian hepatotoxic drugs (acetaminophen [APAP], aspirin, tetracycline HCl, sodium valproate, cyclophosphamide and erythromycin) and 2 non-hepatotoxic compounds (sucrose and biotin) were quantitatively assessed in larval zebrafish using three specific phenotypic endpoints of hepatotoxicity: liver degeneration, changes in liver size and yolk sac retention. Zebrafish liver degeneration was originally screened
visually, quantified using an image-based morphometric analysis and confirmed by histopathology. Results: All the tested mammalian hepatotoxic drugs induced liver degeneration, reduced liver size and delayed yolk sac absorption in larval zebrafish, whereas the non-hepatotoxic compounds did not have observable adverse effect on zebrafish liver. The overall prediction success rate for hepatotoxic LCL161 in vivo drugs and non-hepatotoxic compounds in zebrafish was 100% (8/8) as compared with mammalian results, suggesting that hepatotoxic drugs in mammals also caused similar hepatotoxicity in zebrafish. Discussion: Larval zebrafish phenotypic assay is a highly predictive animal model for rapidly in vivo assessment of compound hepatotoxicity. This convenient, reproducible animal model saves time and money for drug discovery and can serve as an intermediate step between cell-based evaluation and conventional animal testing of hepatotoxicity. (c) 2012 Elsevier Inc.