Biomarkers in monitoring - a review

Årsliste 2006Biological effects are increasingly used to monitor impacts of contaminants in marine ecosystems. Biomarkers have been defined as ”biochemical, cellular, physiological or behavioural variations in the tissue or body fluids or at the level of whole organism that provide evidence of exposure to chemical pollutants, and may also indicate a toxic effect”. The biomarkers reviewed here were PAH bile metabolites, cytochrome P4501A, glutathione S-transferase, markers for DNA damage (adducts, alkaline unwinding, Comet assay), micronucleus formation, peroxisomal proliferation, acetyl cholinesterase inhibition, metallothionein, vitellogenin and delta-aminolevulinic acid dehydratase. Focus for the review was dose-response relationships, confounding factors, links to population effects, baseline values, assessment criteria and quality assurance for the relevant biomarker. Whereas correlative links to population-relevant effects have been found for some biomarkers, e.g. biomarkers for DNA damage, most biomarkers are generally more useful as markers for possible impacts elsewhere in ecosystems.OL

A Rare Case of Propofol-Induced Acute Liver Failure and Literature Review

The incidence of drug-induced acute liver failure is increasing. A number of drugs can inhibit mitochondrial functions, alter β-oxidation and cause accumulation of free fatty acids within the hepatocytes. This may result in hepatic steatosis, cell death and liver injury. In our case, propofol, an anesthetic drug commonly used in adults and children, is suspected to have induced disturbance of the mitochondrial respiratory chain, which in consequence led to insufficient energy supply and finally liver failure. We report the case of a 35-year-old Caucasian woman with acute liver failure after anesthesia for stripping of varicose veins. Liver histology, imaging and laboratory data indicate drug-induced acute liver failure, presumably due to propofol. Hepatocyte death and microvesicular fatty degeneration of 90% of the liver parenchyma were observed before treatment with steroids. Six months later, a second biopsy was performed, which revealed only minimal steatosis and minimal periportal hepatitis. We suggest that propofol led to impaired fatty acid oxidation possibly due to a genetic susceptibility. This caused free fatty acid accumulation within hepatocytes, which presented as hepatocellular fatty degeneration and cell death. Large scale hepatocyte death was followed by impaired liver function and, consecutively, progressed to acute liver failure

Expression of apoptosis- and vitamin D pathway-related genes in hepatocellular carcinoma

PubMedID: 23635474Background/Aims: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and therapeutic options are scarce. As they might represent future targets for cancer therapy, the expression of apoptosis-related genes in HCC is of particular interest. In this pilot study, we further examined apoptosis-related genes in human HCC and also focused on vitamin D signaling as this might be a regulator of HCC cell apoptosis. Methods: We employed tumor tissue and serum samples from 62 HCC patients as well as 62 healthy controls for these studies. Tissue and serum specimens were analyzed by quantitative RT-PCR, immunohistochemistry and ELISA. Results: In HCC patients the apoptosis marker M30 was found to be elevated and several pro-apoptotic (TRAIL, FasL and FasR) as well as anti-apoptotic genes (Mcl-1 and Bcl-2) were simultaneously upregulated in tumor tissue and especially tumor-surrounding tissue as compared to healthy control livers. Moreover, vitamin D serum levels were decreased in HCC patients whereas vitamin D receptor mRNA expression was increased in tumor tissue and tumor-surrounding tissue as compared to healthy livers. Conclusions: In human HCC, M30 serum levels are elevated indicating an increased cell turnover. Modulation of the vitamin D pathway might be a supportive, pro-apoptotic HCC therapy. Copyright © 2013 S. Karger AG, Basel

Supplementary Material for: Mini-Laparoscopy Guided Liver Biopsy Increases Diagnostic Accuracy in Acute Liver Failure

<p><b><i>Background/Aims:</i></b> For diagnosis, prognosis, and treatment of acute liver failure (ALF), macroscopic evaluation and histological assessment of the liver are important. Due to impaired coagulation in ALF, the risk of bleeding is high after a percutaneous liver biopsy. Our aims were to assess (i) safety and benefit of mini laparoscopy (ML) in patients with ALF and (ii) the potential utility of histological markers in ALF prognosis. <b><i>Methods:</i></b> ML was performed in 39 patients with ALF to assess liver surface and to obtain a liver biopsy. Serological markers of liver injury and immunohistochemical detection of cell death and proliferation were compared to a non-ALF group (n = 10). <b><i>Results:</i></b> Liver biopsies were successfully performed in all patients with no significant complications. All patients had markedly elevated M30 and M65 levels in the serum. In the liver, M30 and Ki67 immune-reactive cells were more abundant in those with ALF. Importantly, there were significantly more Ki67-positive cells but fewer M30-positive cells in livers of ALF patients who recovered spontaneously. <b><i>Conclusion:</i></b> ML with liver biopsy in patients with ALF and severe coagulopathy is safe. Immunohistochemical detection of liver cell death and regeneration may identify individuals who would recover spontaneously or who would need a liver transplant.</p