Biomarkers materials

One other important aspect of the definition of biomarkers is beyond the scope of the actual analytical measurement of an individual sample (from an individual patient), but rather refers to the biological variabihty and mutual interference of biomolecular effectors. Only if a certain biomolecule (or labeled compound) is found in an indicative concentration in not only one or a few patient samples but in perhaps 99% of samples in a statistically sufficient cohort, can it be denoted as a candidate for a useable biomarker. Moreover, only if this substance is found, in a statistically broad study, to be independent in either appearance or concentration of other non-disease-related effectors, can the targeted disease indeed be assumed to be indicated by the detection of this biomarker material. 

Ronkainen, N.J., Okon, S.L., 2014. Nanomaterial-based electrochemical immunosensors for clinically significant biomarkers. Materials 7, 4669 709. 

At the practical level, an ideal mechanistic biomarker should be simple to use, sensitive, relatively specific, stable, and usable on material that can be obtained by nondestructive sampling (e.g., blood or skin). A tall order, no doubt, and no biomarker yet developed has all of these attributes. However, the judicious use of combinations of biomarkers can overcome the shortcomings of individual assays. The main point to emphasize is that the resources so far invested in the development of biomarker technology for environmental risk assessment has been very small (cf the investment in biomarkers for use in medicine). Knowledge of toxic mechanisms of organic pollutants is already substantial (especially of pesticides), and it grows apace. The scientific basis is already there for technological advance it all comes down to a question of investment. 

Pentachlorophenol concentrations in urine and serum can be used as biomarkers of internal dose (Colosio et al., 1993a). PCP concentrations up to about 30 mg/L were detected in urine samples of exposed workers, while concentrations lower than 0.3 mg/L were detected in the general population. The presence of PCP in biological samples of the general population is attributable to indoor exposure to the compound released from treated materials (furniture, leather, paints, etc.). 

Evershed, R. P. and P. H. Bethell (1996), Application of Multi-molecular Biomarker Techniques to the Identification of Faecal Material in Archaeological Soils and Sediments, ACS Symposium Series, Vol. 625, pp. 157-172. 

Until now, the composition of positive IHC controls resemble that of the patient sample. Pathologic discard tissue sections that express the biomarker in question are almost universally used as positive controls. Clinical laboratories bear the responsibility for identifying and validating the controls, typically from previous cases. An alternative QC material, which is especially popular for HER2 testing, is to use cell lines expressing the biomarker in question (as described in Chapter 6). Positive controls comprised of tissue sections or cell lines resemble patient samples in that they are cellular in nature. 

In the present chapter, we first provide some general information concerning the chemistry of waxes and lipids currently encountered in various items from our cultural heritage and we detail the main protocols based on direct mass spectrometry that have been developed so far. We then discuss the mass spectra obtained by EI-MS on a range of reference substances and materials sampled from museum and archaeological artefacts. We then focus on the recent possibilities supplied by electrospray ionisation for the elucidation of the structure of biomarkers of beeswax and animal fats. 

Global proteomic profiling by MS is gaining significant attention as a tool for discovering disease biomarkers. Two basic approaches have been explored. With the first, MS analysis is performed with a material from a specific disease condition and the mass spectra are compared to those of normal individuals or related disease conditions. SELDI-TOF MS gained popularity in this area because of its simplicity and the requirement for only small amounts of samples.38"13 In MS-pattem based disease categorization, the mass spectral patterns are considered reflective of the proteins present in samples from distinct clinical conditions. 

Blood is a better indicator of exposure to chlordecone than is saliva (Borzelleca and Skalsky 1980 Skalsky et al. 1980). Chlordecone has been detected in saliva of humans only in trace amounts and in rats at concentrations three to four times lower than in blood (Guzelian et al. 1981 Skalsky et al. 1980). Peak chlordecone concentrations occurred within the first 24 hours of exposure therefore, the period of utility of saliva as a biomarker is limited. The movement of chlordecone from the blood into the saliva is one of passive diffusion and is not concentration dependent (Borzelleca and Skalsky 1980 Skalsky et al. 1980). Thus, blood is a better biological material than saliva for monitoring exposure. 

The understanding of bio- and chemo-catalytic functionalities, their integration in recognizing materials (doped materials, membranes, tubes, conductive materials, biomarker detection, etc.) and the development of smart composite materials (e.g., bio-polymer-metal) are all necessary elements to reach above objectives. It is thus necessary to create the conditions to realize a cross-fertilization between scientific areas such as catalysis, membrane technology, biotech materials, porous solids, nanocomposites, etc., which so far have had limited interaction. Synergic interactions are the key factor to realizing the advanced nanoengineered devices cited above. 

The application of biomarker research in the geologic record has dealt with the derivative hydrocarbons as found in petroleum, coals, and sedimentary rocks. Reports on biomarkers in discrete fossils compared to the host rocks are sparse because (1) previous studies focused on the highly degraded geoterpenoids, i.e. saturated and aromatic hydrocarbons, and (2) the preservation potential of polar compounds (natural product bioterpenoids ) was believed to be low. Flowever, recent investigations of conifer fossils demonstrated that unaltered natural product terpenoids can be preserved in resin material.This will be illustrated here with an example. 

No information was located concerning on-going studies for improving methods of analysis of hexachlorobutadiene, its metabolites, or other biomarkers of exposure and effect to hexachlorobutadiene in biological materials or environmental samples. 

The sediment from Amerikahaven (site 10) was found to contain unexpectedly low contaminant levels during sampling in 1996 (see also De Boer et al., 2001). This was attributed to repeated dredging activity. The sediment was therefore sampled a second time in September 1997 at a non-dredged site. Analysis of this sediment showed considerably higher contaminant levels. These results are considered more representative of this location and were therefore used instead of the 1996 data in the multivariate statistical analysis of biomarker data. Sediment bioassays were however conducted with the material collected in 1996 and these data for location no. 10 were used for multivariate analysis when sediment chemistry was included. 

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