Biomarkers study

Bioanalytical resources (including bioanalytical methods to support PK studies), biomarker studies... 

There is also effort to develop practical ways of measuring intake of additives. The direct measurement of intake continues to be problematical. Duplicate diet studies require a lot of resources, and there are not enough analytical methods available to test for all the additives of interest. Total diet studies, also known as market basket studies, provide a very general picture which can be a useful start to more detailed work on intake, but they too suffer from the same shortage of analytical methods. Biomarker studies are currently problematical. It is difficult to identify metabolites that are both unique to particular additives and can be readily measured in urine. The estimation of additive intake by calculation is still the preferred method, although it requires a large amount of information on both additive levels in food and much data on food consumption. The latter is difficult to obtain without using a lot of resources - many of us have very varied diets ... 

Intake estimates and calculations have been performed repeatedly for intense sweeteners for which probably the most extensive database among food additives exists. All studies and all calculations starting from reasonable assumptions indicate that only a minute proportion of consumers may come close to the ADI which may only seldom be exceeded by persons having food habits substantially different from the majority of the population. The best available data originate from a biomarker study on acesulfame and saccharin in which even the highest consumers among children consumed only a fraction of the ADI.29 Several intake studies were carried out on aspartame with the uniform result that no appreciable risk to exceed the ADI was found.14... 

Collaboration Between Basic Researchers, Clinicians, Pathologists, and Industry is Critical in Biomarker Studies... 

Solvents are typically not targeted for biomonitoring in general population studies, because their rapid clearance by exhalation or metabolism results in a transient biomarker that does not reach steady state. However, analysis of such rapidly cleared chemicals may be possible, as exemplified in a trichloroethylene (TCE) biomarker study (Sohn et al. 2004), which constitutes another case study of pharmacokinetic modeling of human biomonitoring data under non-steady-state conditions. 

In 1991 the UK Committee on Toxicology (COT) set a tolerable daily intake value (TDI) of 0.3 mg/kg body weight/day for DEHA. One year later, in 1992, a urinary biomarker study was reported for DEHA in a limited population exercise in the UK. A skewed distribution was determined with a median value of 2.7 mg/day and this confirmed by an independent route, the earlier estimates of DEHA intake made using dietary survey data. 

L. Sewell. 2003. Synovial biomarker study of ISIS 104838, an antisense oligodeoxy-nucleotide targeting TNF-alpha, in rheumatoid arthritis. In 67th Annual Meeting of the American College of Rheumatology (ACR). October 23-28, Orlando, Florida, USA. 

Albrethsen J, Bogebo R, Gammeltoft S, Olsen J, Winther B, Raskov H. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours A biomarker study. BMC Cancer 2005 5 8. 

Yeung, R, Ding, L., and Casley, W.L. HPLC assay with UV detection for determination of RBC purine nucleotide concentrations and application for biomarker study in vivo. J. Pharm. Biomed. 2008,47, 377-382. 

Forman, M.R. et al.. The fluctuation of plasma carotenoid concentrations by phase of the menstrual cycle a controlled diet study. Am. J. Clin. Nutr., 64, 559, 1996. Lipkin, M., Summary of recommendations for colonic biomarker studies of candidate chemopreventive compounds in phase II clinical trials, J. Cell. Biochem., Suppl. 19, 94, 1994. 

Dunn DS, Sridhar N, Miller MA, Price KT, Pabalan R, Abrajano TA Jr (2007) Development of a surface-enhanced Raman technique for biomarker studies on Mars. Appl Spectrosc 61 25-31... 

The molecular distribution and compound-specific carbon-isotopic composition of hydrocarbons can be used to qualify and quantify their sources and pathways in the environment. Molecular source apportionment borrows from molecular methods that were developed and applied extensively for fundamental oil biomarker studies, oil-oil and oil source rock correlation analysis. Additionally, petroleum refinement produces well-defined mass and volatility ranges that are used as indicators of specific petroleum product sources in the environment. Compound-specific carbon-isotopic measurement is a more recent addition to the arsenal of methods for hydrocarbon source apportionment. Carbon isotopic discrimination of i-alkanes, biomarkers, and PAHs has shown that the technique is highly complementary to molecular apportionment methods. 

Li M, Zeng T, Liu R, Chen L (2014) Detecting tissue-specific early warning signals for complex diseases based on dynamical network biomarkers study of type 2 diabetes by cross-tissue analysis. Brief Bioinform 15(2) 229-243... 

Blaise, C., Gagne, F., Pellerin, J., Hansen, P.-D. and Trottier, S. (2002b) Molluscan shellfish biomarker study of the Quebec, Canada, Saguenay fjord with the softshell clam Mya... 

Gagne, F., Blaise, C., Aoyama, I., Luo, R., Gagnon, C., Couillard, Y., Campbell, P. and Salazar, M. (2002b) Biomarker study of a municipal effluent dispersion plume in two species of freshwater mussels. Environ. Toxicol., 17, 149-159. 

Kobel M, Kalloger SE, Boyd N, et al. Ovarian carcinoma sub-types are different diseases implications for biomarker studies. PLoS Med. 2008 5 e232. 

Ray-Coquard IL, Blay J, Italiano A et al (2011) Neoadjuvant MDM2 antagonist RG7112 for well-differentiated and dedifferentiated liposarcomas (WD/DD LPS) a pharmacodynamic (PD) biomarker study. Abstract 10007b. 2011 ASCO annual meeting, Chicago, IL... 

Assay Qualification for a Quasi-Quantitative Ligand-Binding Assay Used in Exploratory Biomarker Studies... 

Determination of the appropriate level of documentation for an exploratory or advanced biomarker application is made by the organization or laboratory responsible for the biomarker study. In general, an analytical procedure and a validation memo containing the summary data should be adequate for exploratory application. For an advanced validation, the record keeping and reporting may be similar to that of the methods for PK support. The basic idea is that the data should be traceable and subjected to QC and QA review. The final method should be documented in an analytical procedure and the results presented in a validation report. 

Biomarker studies provided evidence of increased cadmium exposure. There were small but measurable increases in cadmium levels in urine and blood samples in Shipham compared with a control population but in most cases such measurements fell between accepted normal ranges. Despite such increases, there was no evidence that exposure had been sufficient to elicit a measurable effect. For example, there was no significant excess of symptoms in Shipham compared with a control area and no significant differences in blood pressure (cadmium has been linked to hypertension).41 In addition an analysis of hospital admissions and cancer registrations revealed that any effect of cadmium was considered unlikely. 

Nielsen SE. Metabolism and biomarker studies of dietary flavonoids, Ph.D. dissertation. Danish Veterinary and Food Administration, Denmark, 1998. 

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