CYP1A Expression in Caged Rainbow Trout Discriminates Among Sites with Various Degrees of Polychlorinated Biphenyl Contamination

It has become increasingly apparent that resident fish can develop resistance to chemicals in their environment, thus compromising their usefulness as sentinels of site-specific pollution. By using a stream system whose resident fish appear to have developed pollutant resistance (Brammell et al., Mar Environ Res 58:251–255, 2005), we tested the hypothesis that the pollutant-inducible biomarker, cytochrome P4501A (CYP1A), as measured in field-caged juvenile rainbow trout (Oncorhynchus mykiss), would reflect relative pollution differences between reference and polychlorinated biphenyl (PCB)-contaminated sites. Trout were caged in the Town Branch/Mud River system (Logan County, KY), a stream system undergoing remediation for PCBs. Fish were held in remediated (Town Branch), unremeditated (Mud River), and reference sites for 2 weeks during spring 2002. At the end of this period, gill and hepatic CYP1A expression were measured. To evaluate the relative PCB exposure of caged trout and provide a reference point against which to calibrate CYP1A response, PCB levels were quantified in sediments from each site. Hepatic CYP1A expression in caged trout clearly detected the presence of PCBs in the Town Branch/Mud River stream system. Sediment PCB levels and hepatic CYP1A expression in caged trout produced identical pollution rankings for the study sites. Gill CYP1A expression, although suggestive of site differences, was not statistically different among sites. Unlike resident fish, which failed to show site differences in hepatic CYP1A expression in this waterway (Brammell et al. 2005), caged fish proved to be a sensitive discriminator of relative PCB contamination in this system. In summary, we determined that CYP1A expression in caged fish reflected relative in situ pollutant exposure. The exposure paradigm confirmed that 2 weeks was a sufficient caging period for evaluating CYP1A response in this species at these temperatures (13–19°C). In addition, these studies demonstrate that tissue-specific CYP1A expression can provide insights into likely routes of exposure. We conclude that CYP1A expression in caged trout is a reliable and inexpensive first-pass determination of relative environmental pollutant exposure and bioavailability in aqueous systems.     

The liver slice system: A rapid in vitro acute toxicity test for primary screening of hepatotoxic agents

A simple method for the rapid screening of hepatotoxic agents is described. Liver slice systems were prepared from rats and mice, and incubated in Krebs-Ringer-Hepes medium with different concentrations of the test compounds. Hepatotoxicity was monitored by determination of liver enzymes in the slice medium. Enzyme leakage was dose- and time-dependent. Histopathological changes in the hepatotoxin-treated slices were well correlated with the extent of enzyme leakage. Species differences in susceptibility to various hepatotoxins could be easily detected by this in vitro system: the dose-toxicity curves revealed that the mouse is more vulnerable than the rat to acetaminophen and furosemide. These findings are well correlated with those of in vivo experiments. A preliminary study showed that, in the same species, the relative toxicities of various chemicals in the liver slice system were similar to those reported in vivo. In summary, these results on the tissue slice system are encouraging. However, much more work will have to be done before the system can be considered sufficiently well validated for routine use.     

Phagocyte function and cytokine production in community acquired pneumonia.

BACKGROUND--It is possible that many deaths from pneumonia may involve the generation of inflammatory mediators and tissue damage by activated phagocytes. To test this hypothesis phagocyte function, plasma levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), and soluble interleukin 2 receptor (IL-2R), disease severity, and outcome have been examined in 46 patients with community acquired pneumonia. METHODS--Polymorphonuclear leucocyte (PMNL) and monocyte function were measured daily by chemiluminescence in these patients during the first week of admission, and cytokine levels were subsequently determined by ELISA. A series of 61 healthy individuals were used as a control group for the chemiluminescence results. RESULTS--There was evidence of phagocyte, particularly PMNL, activation on admission in 76% of the patients. Most patients (86%) also had raised IL-2R levels on admission. IL-6 and unbound TNF alpha were present in 23% and 41% of patients at varying times during the course of the disease. There was little correlation between measurements of cytokine or phagocyte levels and outcome or indicators of disease severity, although this may be because of the small number of patients included in this preliminary study. CONCLUSIONS--These results are consistent with the hypothesis that activated phagocyte function and raised levels of circulating cytokines may contribute to the pathogenesis of community acquired pneumonia. There are striking similarities in this respect between pneumonia, adult respiratory distress syndrome, and sepsis.     

Mutation analysis of Jewish hunter patients in Israel

We have performed molecular and mutation analyses on 14 unrelated Israeli Hunter families and have identified the IDS mutation in 8 of them. Three unrelated Ashkenazi patients had the same previously reported mutation (1246 C→T). Based on the haplotypes of the mutation-bearing chromosomes, we concluded that this is a recurrent mutation. In two patients, we identified a deletion spanning exons V–VII. Three novel mutations were observed in different patients: L410P, 717del4, and 244del3. In addition, the silent mutation (562 C→T) was observed in one patient. © 1994 Wiley-Liss, Inc.