Abstract
The radioanalytical techniques of particle induced X-ray emission (PIXE), Rutherford Backscattering (RBS) and instrumental neutron activation (INA) are outlined and associated experimental equipment described. Initial work presented includes the calibration of the new atmosphere thin window (ATW) Si(Li) low energy photon detector. Preliminary investigations on porcine brain tissue allowed development of sample handling and preparation techniques as well as determination of sampling factors, a study of the effects of sample heating on element concentrations and rejection of particle induced gamma ray emission (PIGE) analysis as being too time consuming to be incorporated into the analytical procedures employed. Studies conducted on 13 brain regions from both hemispheres of 19 ’normal’ ageing subjects found that the brain has a heterogeneous distribution of elements. Also, that brain regions can be clustered into groups according to their elemental compositions and these groups correspond to the approximate percentage composition of grey and white matter of the region. Differences in concentrations were also found between the two brain hemispheres, possibly reflecting the different functions. Potassium and calcium concentrations were found to increase with age in the subjects and potassium concentrations were found to be higher in females than males. The samples were provided by the Pathology Department, Royal Surrey County Hospital. Studies on samples taken from the frontal, occipital, parietal and temporal cortex of both hemispheres of 'normal' ageing subjects and sporadic Alzheimer cases showed that the dry to fresh weight ratio was decreased in Alzheimer cases compared to ’normals’ by an amount which was dependant upon the brain region studied and the duration of Alzheimer disease (AD). The regional variation in the decrease of water ratio was in rough agreement with the pattern of anatomical and histological abnormalities seen throughout the cortex of Alzheimer subjects, i.e. the occipital lobe being the least affected. The water ratio was found to be lower in Alzheimer patients of long disease duration than those of short disease duration, as may be expected. In terms of the concentrations of minor and trace elements determined, Na, Cl, Br and Zn were found to be increased in the Alzheimer brain compared to 'normals’ and K, Rb and Se decreased. No significant difference in elemental concentrations was found between 'normal’ and Alzheimer tissue for Al, Mg, P, S, Ca, Fe, Cd, Cs, Sc and Cu. The change in elemental concentration from the ’normal' was dependant on the brain region studied and the recorded duration of the disease. In particular, the bromine concentrations of samples affected by Alzheimer’s disease were found to reflect the degree of anatomical and histological abnormalities of the region. The dependence of Na, Cl, Br and K concentrations on the duration of the disease, were not as may be expected. The high concentrations of Na, Cl and Br in Alzheimer brain tissue were found to decrease with increasing duration of disease and the low concentrations of K to increase. Therefore in the brain tissue of long term sufferers the elemental concentrations determined were more representative of 'normal' elemental concentrations than elemental levels obtained in the brain tissue of short term sufferers. All samples used for the study of Alzheimer’s disease were provided by the Alzheimer’s Disease Brain Bank, Institute of Psychiatry, London. The possible role that free radicals play in Alzheimer's disease is discussed and a study of antioxidant therapy conducted in another disease thought to be free radical mediated, ulcerative colitis. The trial included seven active UC patients and three quiescent patients. Active UC patients were found to have low blood plasma concentrations of selenium and high concentrations of iron, both of which would be believed to increase the number of free radicals. Daily supplements of antioxidants were given to the active patients and blood plasma selenium concentrations were found to increase whilst iron concentrations were found to decrease. There was also an associated betterment in patient condition with improvements in the number of stools passed and the histological score. On removal of the supplements selenium concentrations were found to decrease and iron concentrations to increase. However, patient health continued to improve. No adverse effects to the large daily doses of selenium administered were observed. Samples for this work were provided by the Gastrointestinal Science Research Unit, The London Hospital Medical College.