Biomarkers, circulating

Erdely, A. et al. (2009) Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure. Potential biomarkers. Nano Letters, 9 (1), 36-43. 

Because cholinesterase inhibition is a very sensitive biomarker for other chemicals, it is not always conclusive evidence of disulfoton exposure. However, depression of cholinesterase activity can alert a physician to the possibility of more serious neurological effects. Erythrocyte acetylcholinesterase activity more accurately reflects the degree of synaptic cholinesterase inhibition in nervous tissue, while serum cholinesterase activity may be associated with other sites (Goldfrank et al. 1990). In addition, a recent study showed that after rats received oral doses of disulfoton for 14 days, acetylcholinesterase levels in circulating lymphocytes correlated better with brain acetylcholinesterase activity than did erythrocyte cell cholinesterase activities during exposure (Fitzgerald and Costa 1993). However, recovery of the activity in lymphocytes was faster than the recovery of activity in the brain, which correlated better with the activity in erythrocytes. Animal studies have also demonstrated that brain acetylcholinesterase depression is a sensitive indicator of neurological effects (Carpy et al. 1975 Costa et al. 1984 Schwab and Murphy 1981 Schwab et al. 1981, 1983) however, the measurement of brain acetylcholinesterase in humans is too invasive to be practical. 

This preliminary evidence suggests a possible role of circulating stem cell subpopulations as biomarkers. EPCs might provide a unique window into patients vascular health. Moreover, functional studies, such as stromal-derived factor 1... 

Shin BK, Wang H, Hanash S. (2002) Proteomics approaches to uncover the repertoire of circulating biomarkers for breast cancer. J Mammary Gland Biol Neoplasia 7, 407-13. 

Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation 2003 108 2054-2059. 

A different study purely focused on isolating carrier molecules and their bound proteins to search for biomarkers of clinical interest. It was not only found that circulating carrier proteins were reservoirs for the accumulation and amplification of putative disease markers but also that the low molecular mass proteins that bound to albumin were distinct from those bound to nonalbumin carriers. Using SELDI-TOF, it was further verified that albumin bound peptides associated with ovarian cancer. This demonstrated that albumin capture was an effective method for harvesting disease-relevant biomarkers [66]. 

Ridker PM, Brown NJ, Vaughan DE, Harrison DG, MehtaJL. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events, Circulation 2004 109(25 suppl I) IV6—IVI 9,... 

Graphs of the differences in the coagulation cascade and circulating biomarkers and unstable angina (open bars) and peripheral arterial disease (.shaded boxes). 

Wiviott SD, Cannon CR Morrow DA, et al. Differential expression of cardiac biomarkers by gender in patients with unstable angina/non-ST elevation myocardial infarction. Circulation 2004 109 580-586. 

MPs (also called microvesicles) are present in the blood of healthy individuals and are increased in various diseases including CVD. They are small membrane vesicles derived from activated and apoptotic cells. Importantly, MPs have been proposed to play roles in thrombosis, inflammation, and angiogenesis (103). MPs are also released in the circulation (104), and ever since their potent procoagulatory properties were first recognized in the field of homeostasis (105), the interest in their potential pathophysiological importance has increased (106). MP metabolome may be a useful and reliable source of biologically relevant disease biomarkers. 

The third group is patients who present still later, more than 48 hours after the onset of chest pain, and also lack diagnostic ECG changes. The ideal biomarker of myocardial injury for this group would have to be one that persists in the circulation for several days to provide a late diagnostic time window. The shortfall of such a marker might be its inability to distinguish recurrent injury from the prior, older injury. 

As increases in cardiac troponin detect any form of myocardial injury, nonischemic mechanisms of injury are also responsible for cardiac troponin release from the heart, causing increases in circulating troponin. Table 5-3 shows a list of potential etiologies that have been responsible for increases in non-ischemic damage to the heart. Thus, whenever cardiac troponin is monitored, it is important to follow the serial pattern of a rising or a falling pattern of the biomarker. An increased cTn pattern that remains relatively unchanged and is not indicative of this serial trend is likely not an MI. 

Pentraxins as a key component on innate immunity, Cum Opin. Immunol. 18,10-15,2006 Vidt, D.G., Inflammation in renal disease. Am. J. Cardiol. 97, 20A-27A, 2006 Armstrong, E.J., Morrow, D.A., and Sabatine, M.S., Inflammatory biomarkers in acute coronary syndromes. Part 11 acute-phase reactants and biomarkers of endothelial cell activation. Circulation 113, el52-el55, 2006. See also Heat-Shock Proteins. 

Roussel R, Mentre F, Bouchemal N, Hadjadj S, Lievre M, Chatel-lier G, Menard J, Panhard X, Le H6nanff A, Marre M, and Le Moyec L. DIABHYCAR Study Group. NMR-based prediction of cardiovascular risk in diabetes. Nat. Med. 2007 13 399 00. Sabatine MS, Liu E, Morrow DA, Heller E, McCarroll R, Wie-gand R, Berriz GF, Roth FP, Gerszten RE. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation 2005 112 3868-3875. 

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