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Background: Disrupted bile secretion leads to liver damage characterized by inflammation, fibrosis, eventually cirrhosis, and hepatocellular cancer. As obstructive cholestasis often progresses insidiously, markers for the diagnosis and staging of the disease are urgently needed. To this end, we compiled a comprehensive data set of serum markers, histological parameters and transcript profiles at 8 time points of disease progression after bile duct ligation (BDL) in mice, aiming at identifying a set of parameters that could be used as robust biomarkers for transition of different disease progression phases. Results: Statistical analysis of the more than 6,000 data points revealed distinct temporal phases of disease. Time course correlation analysis of biochemical, histochemical and mRNA transcript parameters (=factors) defined 6 clusters for different phases of disease progression. The number of CTGF-positive cells provided the most reliable overall measure for disease progression at histological level, bilirubin at biochemical level, and metalloproteinase inhibitor 1 (Timp1) at transcript level. Prominent molecular events exhibited by strong transcript peaks are found for the transcriptional regulator Nr0b2 (Shp) and 1,25-dihydroxyvitamin D(3) 24-hydroxylase (Cyp24a1) at 6 h. Based on these clusters, we constructed a decision tree of factor combinations potentially useful as markers for different time intervals of disease progression. Best prediction for onset of disease is achieved by fibronectin (Fn1), for early disease phase by Cytochrome P450 1A2 (Cyp1a2), passage to perpetuation phase by collagen1α-1 (Col1a1), and transition to the progression phase by interleukin 17-a (Il17a), with early and late progression separated by Col1a1. Notably, these predictions remained stable even for randomly chosen small sub-sets of factors selected from the clusters. Conclusion: Our detailed time-resolved explorative study of liver homogenates following BDL revealed a wellcoordinated response, resulting in disease phase dependent parameter modulations at morphological, biochemical, metabolic and gene expression levels. Interestingly, a small set of selected parameters can be used as diagnostic markers to predict disease stages in mice with cholestatic liver disease. [ABSTRACT FROM AUTHOR]

Mature specimens of the isopod Oniscus asellus were maintained on soil and leaf litter to which was added different concentrations of either benzo[a]pyren (B[a]P), 2,2',5,5'-tetrachlorobiphenyl (PCB52), gamma-hexachlorocyclohexane (gamma-HCH), or pentachlorophenol (PCP) for a maximum of 14 days. Time-dependent investigation of the body level of the 70 kD stress protein group (hsp70) in the isopods revealed a significant but transient induction of the hsp70 response after about 24 h of exposure to PCB52 or B[a]P. Despite continuous exposure, the hsp70 level decreased subsequently and ended up close to or below thecontrol level independent of the concentration of PCB52 or B[a]P in the substrate. All applied PCP or gamma-HCH concentrations also resulted in an initial peak of hsp70 response after 24 h of exposure and asecond peak after several days of exposure, as well as an elevated hsp70 level throughout the period of exposure. Although acute stress conditions posed by all four organic chemicals were monitored by stress protein induction, hsp70 can act as a biomarker of chronic exposureand effect for PCP and gamma-HCH only. [ABSTRACT FROM AUTHOR]

Abstract During investigations on the induction of the 70 kD stress protein family (hsp70, stress-70) in Julus scandinavius following exposure to different biohazards, the colour of the supernatant of the homogenate was closely correlated to the hsp70 level. Hsp70 has recently been shown to be a suitable biomarker for sublethal toxicity in soil animals. Control millipedes typically exhibited red or red-orange supernatants whilst the supernatant of starved or toxin-exposed diplopods was orange, orange-yellow, or even bright yellow. Based on these observations, a quantitative colour test was established which was found to be able to indicate the degree of stress situations caused by exposure to heavy metals (cadmium, zinc), organic pollutants (lindane, PCB 52), or by food deprivation in laboratory tests. It is suggested that this is caused by a breakdown of the red-orange bilirubins into orange-yellow urobilins.