Biomarkers methods

L. Zclles and K. Alef, Biomarkers, Methods in Applied Soil Microbiology and Biochemistry (K. Alef, P. Nannipieri, eds.). Academic Press, New York, 1995, p. 422. 

Philp RP (ed) (1985) Fossil fuel biomarkers methods in geochemistry and geophysics, vol 23. Elsevier, New York, p 292... 

Cummings J, Ward TH, Greystoke A, et al. Biomarker method validation in anticancer drug development. Br. J. Pharmacol. 2008 153 646-656. 

In recent years there have been significant improvements in our ability to distinguish between organic matter sources in estuaries using tools such as elemental, isotopic (bulk and compound/class specific), and chemical biomarker methods. 

FIGURE 6.1 Conceptual diagram of fit for purpose biomarkers method validation. The method validation processes include four activity circles prevalidation (preanalytical consid eration and method development), exploratory method validation, in study method validation and advanced method validation. The processes are continuous and iterative, dictated by the purpose of the biomarker application. The solid arrows depict the normal flow of biomarker development (prevalidation), method validation (exploratory or advanced), and application (in study method validation). The process could include moving the chosen biomarkers from exploratory mechanistic pilot studies to advanced validation and confirmatory studies, or from exploratory validation to advanced validation after changes in critical business decision. The broken arrows represent scenarios where validation data do not satisfy study requirements, necessitating assay refinement or modification. 

Some biomarker methods may require the evaluation of additional performance measures. The performance measures are generally conducted on a case-by-case basis and are evaluated based on laboratory experience with the tech-nology/platform or with the species and sample type being studied. Some common performance measurements include but are not limited to ... 

Section 3.8 Biomarkers of E osure and Effect Section 3.11 Methods for Reducing Toxic Effects... 

The purpose of this chapter is to describe the analytical methods that are available for detecting, measuring, and/or monitoring methyl parathion, its metabolites, and other biomarkers of exposure and effect to methyl parathion. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to identify well-established methods that are used as the standard methods of analysis. Many of the analytical methods used for environmental samples are the methods approved by federal agencies and organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by groups such as the Association of Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). Additionally, analytical methods are included that modify previously used methods to obtain lower detection limits and/or to improve accuracy and precision. 

Agarwal et al. 1978), the quantification of these specific enzymes may indicate that exposure to endosulfan has occurred. Blood tests, such as decay curves for aminopyrine in plasma, which are semiquantitative indices of liver enzyme induction, have been used successfully in the past to demonstrate enzyme induction in pesticide-exposed workers. Because numerous chemicals found at hazardous waste sites also induce these hepatic enzymes, these measurements are not specific for endosulfan exposure. However, measurements of enzyme activity, together with the detection of the parent compound or its metabolites in tissue or excreta, can be useful indicators of exposure. All of these potential biomarkers require further verification in epidemiological studies. Further studies with focus on the development of methods to separate and measure the estrogenicity of endosulfan in in vitro assays would be valuable since these assays are more sensitive and discriminative than other conventional biomarkers. Preliminary results have been presented by Sonnenschein et al. (1995). 

Methods for Determining Biomarkers of Exposure and Effect. GC/ECD, GC/MS, and GC/MC are analytical techniques used for measuring endosulfan in blood, urine, hand rinses, and various biological tissues and excreta at low- and sub-ppb levels (Coutselinis et al. 1976 Demeter and Heyndrickx 1978 Demeter et al. 1977 Griffith and Blanke 1974 Guardino et al. 1996 Kazen et al. 

Recently, there has been a growth of interest in the development of in vitro methods for measuring toxic effects of chemicals on the central nervous system. One approach has been to conduct electrophysiological measurements on slices of the hippocampus and other brain tissues (Noraberg 2004, Kohling et al. 2005). An example of this approach is the extracellular recording of evoked potentials from neocortical slices of rodents and humans (Kohling et al. 2005). This method, which employs a three-dimensional microelectrode array, can demonstrate a loss of evoked potential after treatment of brain tissue with the neurotoxin trimethyltin. Apart from the potential of in vitro methods such as this as biomarkers, there is considerable interest in the use of them as alternative methods in the risk assessment of chemicals, a point that will be returned to in Section 16.8. 

THE DEVELOPMENT OF MORE SOPHISTICATED METHODS OF TOXICITY TESTING MECHANISTIC BIOMARKERS... 

Nikolsky Y, Ekins S, Nikolskaya T, Bugrim A. A novel method for generation of signature networks as biomarkers from complex high throughput data. Toxicol Lett 2005 158 20-9. 

Experimental evidence in humans is based upon intervention studies with diets enriched in carotenoids or carotenoid-contaiifing foods. Oxidative stress biomarkers are measured in plasma or urine. The inhibition of low density lipoprotein (LDL) oxidation has been posmlated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Since carotenoids are transported mainly via LDL in blood, testing the susceptibility of carotenoid-loaded LDL to oxidation is a common method of evaluating the antioxidant activities of carotenoids in vivo. This type of smdy is more precisely of the ex vivo type because LDLs are extracted from plasma in order to be tested in vitro for oxidative sensitivity after the subjects are given a special diet. 

Ponce RA, BarteU SM, Kavanagh TJ, Woods JS, Griffith WC, Lee RC, Takaro TK, Faustman EM. 1998. Uncertainty analysis methods for comparing predictive models and biomarkers a case study of dietary methyl mercury exposure. Regulatory Toxicol Pharmacol 28 96-105. 

Microbes of differing physiologic types, acting in consortia, appear to be more destructive than monocultures. Methods for examining consortia are based on the detection of lipid biomarkers that are characteristic for different classes of microbes. These can be analyzed by gas chromatography coupled with mass spectrometry [512]. 

A range of biomarkers (biological markers) have been developed for the detection of microorganisms using both their genetic (DNA and RNA) and biochemical components. Most methods have originated from studies on pure isolates and have been adapted to identify and quantify either the total or a sub.set of the microbial biomass in a sample. In these methods,. specific taxonomic or pheno-... 

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