Accessible biomarkers

An integrated Omics approach increases confidence in study by bridging gene expression to intra- or extracellular protein or metabolites in bodily fluid at the pathway or network level. Proteomics or metabolomics can also help identify accessible biomarkers, and their data are often easy to interpret. 

NTE has also been found in circulating lymphocytes and platelets [77-80], and lymphocyte NTE has been used or proposed for use as an accessible biomarker of animal and human exposure to neuropathic OP compounds [25,80-84], Furthermore, lymphocyte NTE inhibition has been suggested as a predictor of OPIDN or an adjunct for its early diagnosis [5,80,85-87],... 

The problem is nobody is in charge of doing fhis. Is if academia Is if fhe FDA People come to FDA and say, "Why aren t you using this biomarker " And the people at FDA say, "We don t have the data nobody s analyzed the data." Private companies may try to synthesize the data and present it to the agency, but usually they do not have access to all the datasets. Those datasets reside in different companies and different hands aroxmd the country. 

US Food and Drug Administration (2011) Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels http // www.fda.gov/Drugs/ScienceResearch/ ResearchAreas/Pharmacogenetics/ ucm083378.htm (last accessed 12 September 2011). 

WHO (World Health Organization). 2001. Biomarkers in Risk Assessment Validity and Validation. Environmental Health Criteria 222. Geneva World Health Organization. 238pp [online]. Available http //www.inchem.org/documents/ehc/ehc/ehc222.htm [accessed Nov. 21, 2005]. 

Hughes, M.F. In press. Biomarkers of exposure A case study with inorganic arsenic. Environ. Health Perspect [online]. Available http //ehp.niehs.nih.gov/docs/2006/9058/abstract. html [accessed Aug. 21, 2006]. 

Ideally, biomarkers should be measurable in a versatile and easily accessible body fluid, such as serum or urine, to maximize clinical use in terms of patient compliance and readiness to interface with the diagnostic... 

Table of pharmacogenomic biomarkers in drug labels. Last accessed 5 Jan 2012... 

Validation The use of TMAs enables analysis of large data sets, however this does not by any means suggest that the data set is not skewed. This skewing may be the result of the institution s location (population distributions with regards to race, ethnicity, access to health care), type of practice (community hospital versus referral center). These collectively might influence the tumor size, grade and subtype composition of the cases in the dataset. Such abnormalities of the dataset need to be compensated the involvement of a biostatistician from the start (i.e from case selection) helps to prevent the creation of biased TMAs. It is useful to perform common biomarker analysis on sections from the created TMA to confirm the normal distribution of known parameters. Comparison of this data with prior clinical data (e.g. ER analysis) obtained from whole section analysis is particularly useful to validate utility of the TMA. Alternatively the incidence of expression of a number of biomarkers in the TMA should be compared to that in published literature (using whole sections). 

Clinical diagnosis is relatively simple and is based on medical history, circumstances of exposure, and the presence of clinical symptoms of poisoning. Confirmation of diagnosis can be made by measurement of red blood cell AChE or plasma ChE. Activities of these enzymes are accepted as biomarkers of exposure and/or toxicity of OPs and carbamates. Red blood cell AChE is identical to the enzyme present in the target synapses and its levels are assumed to reflect the effects in target organs. Thus, red blood cell AChE is regarded as a biomarker of toxicity of these compounds. However, it must be kept in mind that the above assumption is only correct when the inhibitor has equal access to blood and synapses. It is difficult to know... 

Phospholipids, which are responsible for the structure of the cell membrane, are easily accessed through simple extraction procedures providing a useful biomarker for microbial detection and identification. However, they are influenced by the growth conditions, nutritional status, and history of a microorganism. These factors cause changes in the phospholipid (phosphoglyceride) profile as the microbe changes its membrane composition in response to its environmental requirements. 

Biomarker analysis Sulfodipeptide Leukotrienes Urine, human cell culture extract Untreated antibodies and fluorescence-labeled ligand, reversed-phase restricted-access chromatography 0.4 nmol/L 15... 

NTE has also been found in circulating lymphocytes and platelets, where its inhibition has found some use as a biomarker of exposure to neuropathic OP compounds. There is a reasonably good correlation between inhibition of NTE in leukocytes and brain when the measurements are carried out within 24 h of an acute exposure. However, a good correlation might not be found later (even by 48 h) or under conditions of repeated exposures. Nevertheless, leukocytes provide an accessible source of NTE for detection of inhibition by neuropathic OP compounds. Currently, there is considerable interest in using protein mass spectrometry to detect OP adducts on NTE as sensitive and specific biomarkers of exposure to neuropathic OP compounds. 

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