Blood-based biomarkers

Hanash, S.M., Balk, C.S., Kallioniemi, O. Emerging molecular biomarkers—blood-based strategies to detect and monitor cancer. Nat. Rev. Clin. Oncol. 8, 142-150 (2011)... 

Blood which contains most of the proteins and biomarkers is one of the most crucial body fluids for the disease diagnostics. Immunoassay is one of the most useful biological detection approaches and medical diagnostic methods due to its high sensitivity and specificity. A whole blood immunoassay test can measure the level or concentration of some substances in blood based on the unique affinity of an antibody. 

Huang, H., Dong, X., Kang, M.X., Xu, B., Chen, Y., Zhang, B., Chen, J., Xie, Q.P., and Wu, Y.L., 2010. Novel blood biomarkers of pancreatic cancer-associated diabetes mellitus identified by peripheral blood-based gene expression profiles. The American Journal of Gastroenterology. 105 1661-1669. 

Kawarabayashi T, Shoji M. Plasma biomarkers of Alzheimer s disease. Curr Opin Psychiatr. 2008 21(3) 260-267. Thambisetty M, Lovestone S. Blood-based biomarkers of Alzheimer s disease challenging but feasible. Biomark Med. 2010 4(l) 65-79. 

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. 

Detection by LDMS and structural elucidation of other secondary metabolite products, generated in the host during the onset of the parasite disease, is discussed. These molecules may serve as additional biomarkers for rapid malaria diagnosis by LDMS. For instance, choline phosphate (CP) is identified as the source of several low-mass ions observed in parasite-infected blood samples in addition to heme biomarker ions. The CP levels track the sample parasitemia levels. This biomarker can provide additional specificity and sensitivity when compared to malaria detection based on heme ion signals alone. Furthermore the observed elevated CP levels are discussed in the context of Plasmodium metabolism during its intra-erythrocytic life cycle. These data can... 

Exposure. Hexachloroethane has been measured in the plasma of occupationally exposed humans (Selden et al. 1993). Because these workers were wearing protective equipment, it is not possible to relate exposure concentrations to plasma levels of hexachloroethane. Based on animal data, exposure to hexachloroethane can be determined by analyzing blood, urine, and fecal matter for the presence of hexachloroethane within 24 hours of exposure (Fowler 1969b). After 24 hours, most of the hexachloroethane has been metabolized to compounds that are not unique to hexachloroethane metabolism. Additional studies of biomarkers of exposure in animals are not needed at this time. 

In the most straightforward risk-based approach, epidemiologic studies have developed exposure-response relationships based on biomarker measurements in hair, blood, urine, or other matrices (e.g., mercury, lead) (see Figure 5-2a). The relationships can be applied directly to new biomonitoring data to determine where on the exposure-response curve any person is. That may facilitate an understanding of risk, but it does not analyze sources of exposure, so other techniques (such as environmental sampling and behavioral surveys) may be needed to assess where the exposure came from. 

The approaches described previously can be used to relate biomonitoring results to a reference population or to workplace exposures, but they do not evaluate the risk associated with the amount of a chemical found in the body. To do that, one needs to develop a relationship between biomarker concentration and toxic response, a relationship that is not commonly derived in standard toxicologic practice. The following sections outline methods for deriving such a relationship. The approaches include the ideal case of existing risk assessments based on biomarker-response relationships established in epidemiologic research. Lead and mercury are used as examples of cases in which exposure was quantified according to hair or blood biomarkers and dose-response associations were developed on this basis. 

One can compare the biomarker-based risk derived for lead with population-based biomonitoring results. Data from NHANES 2000-2001 can be used to estimate the number of children in the United States who have increased blood lead (CDC 2005). Blood lead in U.S. children declined dramatically after the removal of lead from gasoline—from a median of 15 pg/dL in 1978 to 2 pg/dL in 1999 (Rogan and Ware 2003). Nonetheless, an estimated 1.6% of U.S. children 1-5 years old had blood lead greater than 10 pg/dL in 1999-2002, according to NHANES data (CDC 2005). The major exposure sources of lead for U.S. children are deterioration of lead-based paint and the resulting dust and soil contamination (CDC 2005). 

Case Example Pharmacokinetic Calculations to Interpret Phthalate Urinary Biomarker Data. The previous descriptions focused on blood or adipose biomarker concentrations that were converted to body burden to yield estimates of daily dose based on chemical half-life. A modified form of that is conversion of urinary biomarker data to daily exposure dose via simple model calculations as described for phthalates. 

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