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Transplant Spectroscopy

=Yellow and black bile were considered by the ancients as two of the four vital humours of the human body along with phlegm and blood. Ancient and mediaeval Greco-Roman alternative medicine. Imbalances in these humours caused illness. The Greek names for the terms gave rise to the words “choler” (bile) [the prefix in cholesterol, of course] and “melancholia” (black bile). Excessive bile was supposed to produce an aggressive temperament, known as “choleric” and cause “biliousness.” Depression and other mental illnesses (melancholia) were ascribed to a bodily surplus of black bile.

We now know that bile is far more complex than that. The liver secretes bile into the gall bladder, which concentrates it and releases it into the duodenum. It is mainly composed of bile acids, which are an essential component of the digestive juices needed to absorb fats, proteins and fat-soluble vitamins. Bile also plays an excretory role in getting rid of cholesterol, bilirubin and worn out proteins, eliminating drugs, metabolites, toxins and heavy metals.

Bile also contains phospholipids (predominantly phosphatidylcholine), proteins, amino acids, nucleotides, vitamins, bilirubin and other organic anions and various inorganic substances. The overall composition is regulated by the liver but liver disease and malignancy of the biliary system can disrupt its chemical makeup. Now, researchers are looking at the NMR spectra of bile and other bodily fluids to help them diagnose and monitor illness and potentially to improve the outcome for liver transplant surgery.

I report details of the study in the new issue of SpectroscopyNOW’s NMR ezine.

The study is just a small part of a much bigger project where we are examining the usefulness of metabonomics to monitor the outcome of liver transplants,” team member John Lindon of Imperial College London told me. “We have already published a paper on using NMR spectroscopy of intact human liver tissue biopsies in Analytical Chemistry (using high resolution magic-angle-spinning proton NMR) and we have several more publications submitted and in preparation,” he added.

The bile research is part of a collaboration between Lindon’s team at IC, Elaine Holmes and her team and the Liver Transplant team at King’s College Hospital, London. Colleagues from Portugal, with funding from the British Council, visited IC and also worked on the project there, as well as doing some of the analysis back in Portugal.

This particular study provides a baseline so that researchers know precisely what constitutes bile. “We plan to look for differences between biles from livers before transplantation and after transplantation,” adds Lindon, “knowing clinically what the liver status is.” This work could reveal biomarkers that could be used to distinguish between good graft function and poor function.

The metabolic profile of any biofluid is very complex and changes in this can be used for disease diagnosis or for looking at the beneficial effects of drugs or the detrimental effects of toxins. The changes can be subtle and complex and so the researchers use cheminformatics, in the form of multivariate statistics, to tease out the most significant effects. They are also studying the liver tissue itself and blood plasma.

Research Blogging IconIola F. Duarte, Cristina Legido-Quigley, David A. Parker, Jonathan R. Swann, Manfred Spraul, Ulrich Braumann, Ana M. Gil, Elaine Holmes, Jeremy K. Nicholson, Gerard M. Murphy, Hector Vilca-Melendez, Nigel Heaton, John C. Lindon (2009). Identification of metabolites in human hepatic bile using 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS Molecular BioSystems DOI: 10.1039/b814426e

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