Metabolic Profiling: Disease and Xenobiotics.pdf
After graduating in Chemistry/Statistical Analysis at Birkbeck College, University of London in 1981, Prof. Grootveld completed his Ph.D on bioanalytical chemistry and metallodrugs in 1985 at the same institution and then conducted post-doctoral work on the analysis of 'markers' of free radical activity in biofluids at King's College, University of London. He then spent 2 1/2 years lecturing and conducting research work at the Polytechnic of North London prior to taking up a Lectureship in Clinical Chemistry at St. Bartholomews and the Royal London School of Medicine and Dentistry in 1989, where he subsequently became Senior Lecturer and then Reader in Chemical Pathology. Later, he transferred to London South Bank University where he was also Reader in Chemical Pathology, and Director of their M.Sc Forensic Science course. He is now Professor of Chemical Pathology and Biomedical Materials at the University of Bolton where he has established and now directs a Master's course in Medical and Healthcare Devices which is the first of its kind available in the UK. He was Visiting Professor of Clinical Chemistry at Queen's University Belfast from 2001-2005. Prof. Grootveld is the author of almost 100 full, refereed research publications in reputable international scientific and/or clinical journals, 20 reviews and more than 160 refereed conference contributions.
Preface; Introduction to the Applications of Chemometric Techniques in 'Omics' Research; Common Pitfalls, Misconceptions and 'Rights and Wrongs' in Metabolomics Research; Experimental Design: Sample Collection, Sample Size, Power Calculations, Molecular Analysis-Of-Variance etc.; Exploratory Data Analysis and Pattern Recognition Techniques: State-of-the-Art; Applications to the Diagnosis and Prognosis of Diseases; Early Disease Diagnosis; Mass Spectrometric Evaluations of Microbial, Plant and Mammalian Metabolomes; Biomarkers for Cancer; Multiple Biomarkers in Molecular Oncology; Mass Spectrometric-Based Metabolomics in Breast Cancer Diagnosis; Obesity; Type II Diabetes; Vascular Injury; Metabolomic Approaches to the Investigation of Cardiovascular Diseases; Disease-Related Urinary Metabolic Patterns for Osteoarthritis; Infectious Diseases; 1H NMR-Linked Metabonomics in the Oral Sciences: Evaluations of Oral Health Status and Dentifrice Product Intervention; Testing and Evaluation of Oral Health Care Products; Drug Toxicity; Toxicogenomics; Drug-Induced Hepatotoxicity; Drug Discovery; Index
Multivariate (MV) analysis of the multi-component analytical profiles of carefully collected biofluid and/or tissue biopsy specimens provides a 'fingerprint' of their biomolecular/metabolic status and hence, when correctly applied, much valuable information regarding disease indicators, disease strata and sub-strata, and disease activities. These techniques serve as powerful tools for clinical and toxicological research, including drug development, early disease detection, and the stratification of patients into disease or treatment/treatment response sub-classes. They also serve as an extremely valuable means of providing pre-clinical biomarkers of the therapeutic and/or toxicological capacity of newly-developed drugs. Currently, the most informative techniques utilised in such research investigations are high-resolution biomedical Nuclear Magnetic Resonance (NMR) analysis, and both gas- and liquid-chromatography coupled with mass spectrometry (GC/MS and LC/MS respectively), although vibrational spectroscopy (NIR, MIR and Raman) have also been successfully employed in this area. Such techniques can be employed for the delineation of biomarkers which reflect deviations from 'normal' or healthy metabolism, information which serves to improve our understanding of the toxicological actions of xenobiotics, together with the aetiology and development of a range of disease processes. In this exemplary new book applications of these techniques in the areas of drug therapy and toxicology, cancer, obesity, diabetes and cardiovascular, infectious, inflammatory and oral diseases are outlined in detail, with particular reference to cautionary measures which must be applied to the diagnosis and classification of these conditions or physiological criteria.