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The levels of the antioxidants ascorbic acid, cysteine, reduced glutathione and a-tocopherol, of the free-radical marker uric acid and of the amino acids tyrosine and tryptophan were measured by means of high-pressure liquid chromatography in plaques, adjacent white matter and distant white matter from patients with multiple sclerosis, and in central nervous system tissue from patients without neurological diseases. Cholesterol and DNA were also determined, to check demyelination and cellularity. Uric acid was increased and glutathione correspondingly decreased in plaques; α-tocopherol was lowest in plaques and highest in distant white matter in all cases. Ascorbic acid, cysteine, tyrosine and tryptophan were not significantly changed in any tissue. The results provide evidence supporting the involvement of free radicals in multiple sclerosis.

The aim of this study was to use quantitative microdialysis to estimate the true extracellular concentrations of glucose and lactate in minimally disturbed human brain. These values are important as criteria for microdialytical monitoring in critical care patients and for determining therapy. Microdialysis procedures were carried out during tumor operations, the probe being inserted distant from the site of manipulation in minimally disturbed tissue. Two methods were used: 1. The zero net flux method of Lönnroth. 2. The low flow method (10 mm membrane length, flow rate 0.3 microliter min-1, high in vivo recovery). Both methods gave similar values of about 2000 microM for lactate and slightly less for glucose (1700 microM). Glucose levels correspond with those measured by other methods in humans, allowing for the fact that our patients were anesthetised. Extracellular glucose levels were positively correlated with blood glucose values measured before the operation, and with extracellular lactate. Results confirm that extracellular glucose is zero when blood glucose is about 2 mM.

Ascorbic acid, cysteine, glutathione and uric acid were determined by reverse-phase high-pressure liquid chromatography (HPLC) in 46 breast tissue samples [neoplastic (C) and non-neoplastic (N) from the same patient]. Cholesterol, alpha-tocopherol and gamma-tocopherol were quantified in 64 similar samples by extraction into heptane followed by direct-phase HPLC. DNA was measured in all samples and the percentages of epithelium, fat and connective tissue were estimated in sections adjacent to the sample. Results confirm previous findings that ascorbic acid and glutathione, expressed as mumol/g DNA, were greatly increased in the epithelium of neoplastic tissue. Similar increases in cysteine could be accounted for by the presence of inflammatory cells. Although values of alpha- and gamma-tocopherol correlated with the percentage of fat in both types of tissue, these compounds were also present in the epithelium. Because of the varying amounts of fat in the samples, no significant difference could be found between N and C values. Cholesterol correlated with fat in N and epithelium in C. Consideration of 10 cases with equal amounts of fat in C and N tissue suggests that cholesterol is reduced in C in the epithelial cells.

Summary: Extracellular concentrations of ascorbic acid, glutathione, cysteine, uric acid, tyrosine, and tryptophan were monitored using intracerebral microdialysis in the left frontoparietal cortex of spontaneous hypertensive rats before, and for 3 h after, either focal ischemia [left middle cerebral artery occlusion (MCAO)] or sham oper ation. The size of the ischemic area and the position of the microdialysis probe were checked using the enzyme his totopochemical acid phosphatase reaction. The probe was always located in the cortex inside the stained area. Ascorbic acid levels rose immediately after MCAO and remained at about 12-fold for 3 h. There was a transient Microdialysis (Tossman and V ngerstedt, 1986; Benveniste and Huttemeier, 1990) provides a mini mally invasive method for continuously monitoring changes in concentrations of low-molecular-weight substances in the extracellular (EC) fluid of various organs. It has been used to study cerebral ischemia in the rat, measurements being made mainly in the striatum, one of the areas most susceptible to isch emic damage. Changes have been found in this re gion at the onset of cerebral ischemia in the EC concentrations of various parameters, e. g. , ascor bic acid (Hillered et aI. , 1988), lactate (Hillered et aI., 1989), purine metabolites (Hagberg et aI. , 1987),

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The current study determined the extracellular content of glutamate, 10 additional amino acids, lactate, glucose and some antioxidants in a rodent model of malignant glioma, its peritumoral space and the adjacent cortex. RG2 tumors were induced in the right frontal cortex of Fischer-344 rats (n = 10) by a standardized procedure to obtain a maximum sagittal tumor width of 3-4 mm diameter. After confirmation of tumor growth and localization by contrast enhanced MRI three microdialysis probes were implanted simultaneously in the cortex: at the tumor implantation site (tumor), 2 mm caudally, brain around tumor (BAT) and 4 mm caudally (cortex) to the site of implantation. Dialysate concentrations of glutamate were increased 3.9-fold in tumor and 2-fold in BAT compared with cortex. Glycine was elevated 11.4-fold in tumor and 2.6-fold in BAT. Lactate was increased 1.7-fold in tumor, 1.2-fold in BAT. Levels of glucose, ascorbic acid and uric acid were not significantly different in tumor, BAT and cortex. The increased dialysate levels of glutamate and glycine in the peritumoral space may contribute to impaired neuronal function and epileptiform activity associated with this tumor type in humans.

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