Biomarker Type 0 marker

Three biomarker types are the most critical, these are surrogate (disease management), stratification (companion), and early detection. The semantics is somewhat confusing as the same types of markers used during a drug trial may have different names compared to the use in clinical practice here the naming used in clinical practice is in parentheses. 

Results obtained in in vivo and ex vivo experiments are of various types. Some studies have found positive effects of the consumption of carotenoids or foods containing carotenoids on the markers of in vivo oxidative stress, even in smokers. Other studies demonstrated no effects of carotenoid ingestion on oxidative stress biomarkers of lipid peroxidation. " It should be noted that for studies using food, the activity observed may also be partly due to other antioxidant molecules in the food (phenols, antioxidant vitamins) or to the combination of actions of all the antioxidants in the food. 

A number of biochemical markers not associated with the cell envelope allow the specific detection of individual microorganisms in environmental samples. These include secondary alcohols. For example, Mycobacterium xenopi can be detected through the hydrolysis of wax ester mycolates, which liberates 2-docosanol, a characteristic and dominant secondary alcohol, which can be detected at low levels by GC-MS. This biomarker was found to be very useful for the rapid detection of M. xenopi in drinking water (159,160). Results from the GC-MS detection of 2-docosanol were obtained within 2 days compared to the 12 weeks required for culturable detection of M. xenopi. The detection limit for this type of approach was found to be 10 colony-forming units (CFU) ml" drinking water. 

In the present chapter we will first review basic concepts of epidemiological research and follow with a discussion of different types of biomarkers used in molecular epidemiology, and finally we will concentrate on the study of genetic susceptibility. In our discussion we will put special emphasis in the challenges that using such markers introduce when used at the population level. 

Biomarkers are generally divided into three categories markers of exposure, markers of effects, and markers of susceptibility. Each of these types of biomarkers is described below, along with how they may be used in risk assessment. 

Many commonly measured pharmacokinetic values can be used as biomarkers of exposure. Examples include parent compound or metabolites in exhaled breath, blood, or urine and macromolecular adducts or their degradation products that appear in urine. To make quantitative assessments of the relationship of such markers to prior exposures, it is necessary to determine the rate of formation and removal (clearance) of the marker. From this information it is possible to predict the steady-state concentrations of the marker following various exposure scenarios. In addition, with information on the rate of formation and removal of a marker and knowledge of the factors that influence those rates (such as gender, dose, repeated exposures, route of exposure, rate of exposure), a mathematical model that describes the concentration of the marker under different exposure conditions can be developed. While the concentration of the marker cannot be used to identify a unique exposure scenario, the marker can indicate the types of exposure regimens that would produce the measured level of the biomarker. 

It is often possible to address function more specifically in in vitro assays, where functional parameters are usually very sensitive readouts of adverse effects. For example trans-epithelial electrical resistance (TEER) is a very sensitive marker of epithelial disturbances. TEER measures the barrier function of the entire mono-layer and is utilized to study functional disturbances of many epithelial/endothelial cell types including blood-brain barrier, pulmonary, renal, and gastrointestinal cells. Its sensitivity lies in the fact that only a small proportion of cell death has a very large impact on barrier function. Additionally, cell stress can interfere with the arrangement and population of tight junction proteins [16] thus, TEER can in certain conditions measure functional disturbances in the absence of cell death [13]. Also since TEER can be measured noninvasively, it is nondestructive and can be used to monitor the effects of treatment over days and weeks [13, 17]. For excitable cells, electrical activity has also been proven to be an extremely sensitive parameter of adverse drug reactions and microelectrode arrays have been employed successfully to monitor neurotoxicity in vitro [18]. Also, for contractile cells, such as cardiomyocytes, the use of impedance measurements to measure the effects of compounds on spontaneous contraction has been demonstrated to be a very sensitive functional monitoring parameter in vitro [19, 20], Admittedly, none of the aforementioned techniques are true biomarkers per se however, such measurements illustrate the fact that in vitro techniques allow certain possibilities that are not practically tenable in the whole body. 

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