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Direct Analytical Sample Quality Assessment (DASQ) for Biomarker Investigation: Qualifying CSF Samples

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Cerebrospinal fluid (CSF) surrounds the brain and spinal column and contains small molecules, peptides, proteins etc., which play critical roles in many physiological processes in the central nervous system (CNS). CSF is considered a prime reservoir for neurological studies because the content of proteins and metabolites and the changes in their concentrations directly reflect the internal milieu of the brain: it offers a unique window to search for new biomarkers and to improve early diagnosis of neurological diseases [1-3]. However, the complexities of the brain and human neurological disorders represent a severe roadblock to identify novel neurological biomarkers. A biomarker can be defined as a biochemical, pharmacological or physiological, indicator of a specific biological state or of a defined biological stage of an organism as represented in its characteristic specific sample. Such an indicator should be measurable and possible useful for diagnostic and/or prognostic purposes such as the prediction of disease progression, disease activity and targeted therapy efficacy. The identification of specific biomarkers is essential for the realization of personalized medicine, in terms of better-estimate disease risk, personalized therapies and improve the disease outcome [4]. Fundamental to biomarker research is access to quality biospecimens that have to be carefully annotated with clinical, molecular and collection data. In fact, sample collection has to be based on well defined protocols which provide the fundamental standard operative procedures (SOPs) for workflow certification.
The National Health and Medical Research Council (NHMRC) has recognized biobanks as essential tools for research and biomedical sciences. Large biob...


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...e been widely described to be associated with non optimal sample collection and storage [8, 9]. Several different proteins have been proposed as an index of correct storage of the sample. Bearing in mind all the literature to date, we review these proteins useful for CSF quality control [10-12]. We propose the direct assessment of sample quality (DASQ) by applying a fast MALDI-TOF-MS methodology to evaluate molecular features of sample degradation and oxidation that have been often correlated with a sub-optimal pre-analytical and storage phases of CSF. This approach will provide a direct and analytical evaluation of the proper collection and storage phases of CSF samples. Such an analysis will check for the presence of blood contamination (e.g. haemoglobin chains), molecular truncated isoforms (e.g. Cystatin C) and oxidized proteins (e.g Transthyretin) [8, 12, 13].



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