Increased BAEP latency and reduced brain cytochrome c oxidase activity observed in the Suzuki model of Alzheimer's disease [abstract]

Cytochrome c oxidase (COX), the terminal respiratory enzyme, is reported to be deficient and to exhibit reduced activity in a number of neurodegenerative disorders. The Alzheimer's rabbit model is based on the intracerebral injection of Holt's adjuvant, an aluminum salt solution. This model was used to compare the brain activity and the activity of brain COX in treated and controlled rabbits. Of a total of 26 New Zealand white rabbits, thirteen were injected intracerebrally with Holt's adjuvant solution, five with physiologically saline solution and the remainder were kept as controls. The auditory responses (BAEP) of the rabbits were monitored for 14 days before injections and 14 days thereafter. The animals were then sacrificed and brain mitochondrial extracts were used for SDS-PAGE analysis, difference spectra spectrophotometry and polarographic assays. The results of SDS-PAGE showed that there were no differences in the protein composition of the brain mitochondria of the three groups. Similarly, difference spectra (reduced minus oxidized, 400-630 nm) from both treated groups were identical to that of the control with characteristic maxima centered around 434, 550 and 604 nm. Polarographic assays, however, showed that while the enzyme from both treated groups displayed the characteristic biphasic kinetics, there was reduced activity in the enzymes from the brain of rabbits receiving the adjuvant but not the saline solution. This result is significant in light of the fact that several researchers have reported reduced activity of COX from Alzheimer's disease (AD) patients. Of particular significance, BAEP results reveal an increase in the interpeak latency between peaks III and V of the Holt's injected but not the saline injected or control rabbits. This latter result suggests that monitoring the BAEP might provide a simple non-invasive method for confirming AD. (AU)

A method for the isolation of the amide nitrogen of glutamine from biological samples for mass spectrometry

The amide nitrogen from L-glutamine has been isolated from an artificial plasma, in a form suitable for mass spectrometry, by a macromodification of the glutaminase reaction. The prior removal of free ammonia was carried out by alkaline aeration. When this was performed at 0§C for 3 h, spontaneous hydrolysis of glutamine was 1.4 percent. Cross-contamination with nitrogen liberated from the amide group of asparagine can be avoided by preincubation with asparaginase for 2h and removal of the freed ammonia prior to reacting with glutaminase. Hydrolysis of glutamine during this step is 12 percent. Measurements of enrichment can be made on samples yielding more than 1 æmol of glutamine amide-derived ammonia.(AU)

Chemical composition of organs of children who died from malnutrition

Chemical analysis was carried out on samples of brain, liver, skeletal muscle, heart and kidney obtained from children who died of malnutrition. Total body potassium was measured before autopsy by the 'whole body counting' technique. There was a marked increase in liver fat, and the brain contributed a higher percentage of the body-weight in the more severely malnourished children. All the organs had approximately the same concentrations of non-collagen nitrogen. The proportion of collagen was highest in muscle. All organs were depleted of potassium, but the muscle was most severely affected. Brain potassium as a percentage of total body potassium was higher than normal in the most severely potassium depleted children. Measurements of tissue magnesium showed that there was no difference in magnesium content of tissue when expressed in terms of non-collagen nitrogen. When compared with normal values, muscle was magnesium depleted. The potassium to magnesium ratio was lowest in muscle. (AU)

Loss of brain potassium in kwashiorkor

Change of mental state is a characteristic of severely malnourished children, in whom the usual sequence is irritablility, apathy, stupor, coma, and death. These mental changes tend to be more pronounced in kwashiorkor than in marasmus. Total body potassium is also more reduced in kwashiorkor than in marasmus, and in children who die with kwashiorkor a very low concentration of potassium has been found in the brain postmortem. A method is described by which the potassium content of the head of a human infant can be estimated during life. This method has given low values for the potassium content of the head of malnourished children, in whom the total body potassium was also low. The conclusion is that in children with kwashiorkor the composition of the brain is not as well preserved as it is in malmourished laboratory animals, and that the mental changes in kwashiorkor may be associated with loss of brain potassium. The loss of potassium is not due to a deficiency of dietary potassium, but is probably secondary to some metabolic disturbance caused by severe protein malnutrition (AU)