Louise Kenny

Hair Metabolomics: Identification of Fetal Compromise Provides Proof of Concept for Biomarker Discovery

Analysis of the human metabolome has yielded valuable insights into health, disease and toxicity. However, the metabolic profile of complex biological fluids such as blood is highly dynamic and this has limited the discovery of robust biomarkers. Hair grows relatively slowly, and both endogenous compounds and environmental exposures are incorporated from blood into hair during growth, which reflects the average chemical composition over several months. We used hair samples to study the metabolite profiles of women with pregnancies complicated by fetal growth restriction (FGR) and healthy matched controls. We report the use of GC-MS metabolite profiling of hair samples for biomarker discovery. Unsupervised statistical analysis showed complete discrimination of FGR from controls based on hair composition alone. A predictive model combining 5 metabolites produced an area under the receiver-operating curve of 0.998. This is the first study of the metabolome of human hair and demonstrates that this biological material contains robust biomarkers, which may lead to the development of a sensitive diagnostic tool for FGR, and perhaps more importantly, to stable biomarkers for a range of other diseases.

Chapter 18 – Platelets, Coagulation, and the Liver

Publisher Summary Platelets play an important role in hemostasis and clot formation. Various stimuli, including collagen, thrombin, serotonin, epinephrine, and adenosine diphosphate (ADP) can stimulate platelet aggregation. When endothelium is disrupted, platelets adhere to exposed subendothelial collagen. This process requires von Willebrand factor and results in platelet shape changes from a disk to a spiny sphere with fine filopodia. Most platelets that accumulate at a site of injury do not adhere directly to subendothelial surface, but rather aggregate to each other. Such adherence results in the secretion of the contents of dense granules bodies and α-granules that release a host of substances. Further the process of coagulation involves a series of enzymatic reactions that ultimately lead to the conversion of soluble plasma fibrinogen to fibrin clot. Classically, this enzyme sequence is divided into the intrinsic and extrinsic pathways, which both converge in a final common pathway. In the extrinsic pathway, thromboplastin released from damaged cells, together with factor VII and calcium ions, activates factor X. The intrinsic pathway is initiated by activation of factor XII by collagen. This in turn leads to a series of reactions culminating with the activation of factor X. Their extensive autopsy studies, Sheehan and Lynch3 described “toxaemic lesions” that are of two basic types. The first are periportal lesions which begin as localized hemorrhages and which are later replaced by fibrin. The second are various grades of ischemic parenchymal lesions that range in size from microscopic to very large infarcts.