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Biomedical subjects

B Djuricic

Publications and source records attributed to B Djuricic.

23 records · Page 2Linked to original sources

Polyamine metabolism in reversible cerebral ischemia: effect of alpha-difluoromethylornithine.

Severe forebrain ischemia was produced in rats by occluding both carotid and vertebral arteries. Following 30 min ischemia brains were recirculated for 8 or 24 h. Twelve animals subjected to 8 or 24 h recirculation (n = 6, each group) were given alpha-difluoromethylornithine (DFMO; injected intraperitoneally) immediately before recirculation. At the end of the experiments brains were frozen and samples were taken from the cerebellum, cortex, caudatoputamen and hippocampus. Samples from the left hemisphere were used for measuring ornithine decarboxylase (ODC) activity, and those from the right hemisphere for determining putrescine profiles. During recirculation ODC activity increased markedly in all brain structures, the most pronounced change being in the caudatoputamen after 8 h recirculation. Putrescine increased drastically after 8 h and even more after 24 h recirculation. DFMO-treatment significantly reduced ODC activity after 8 h recirculation and following 24 h recirculation. Putrescine, however, was significantly reduced following 24 h but not after 8 h recirculation. The discrepancy between reduction in ODC activity and putrescine levels in DFMO-treated animals was most prominent in the hippocampus after 8 h recirculation: here DFMO reduced ODC activity to control values without affecting putrescine levels. The results suggest that the observed overshoot in putrescine formation following ischemia is only partly caused by activation of ODC.

Animals↗

Hemiballismus: changes in cerebrospinal fluid.

Concentrations of serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and dopamine metabolites, homovanillic acid (HVA) and 3,4-dihydroxy-phenylacetic acid (DOPAC), were measured in the samples of cerebrospinal fluid of 5 patients with acute hemiballismus. The only significant change was the increased content of HVA compared to controls. This finding support the hypothesis on the increased dopamine turnover in hemiballismus and provide a rational basis for the present treatment with antidopaminergic agents.

3,4-Dihydroxyphenylacetic Acid↗

Polyamine changes in reversible cerebral ischemia.

Putrescine, spermidine, and spermine levels were measured in the cortex, caudoputamen, and hippocampus of rats during 30 min of severe forebrain ischemia (induced by occlusion of both carotid and vertebral arteries) and subsequent recirculation. During ischemia, polyamine levels did not change significantly. During postischemic recirculation, however, putrescine levels dramatically increased whereas those of spermine and spermidine did not change, with the exception of the severely damaged caudoputamen, where the concentration declined after 24 h. The increase of putrescine is explained by postischemic activation of ornithine decarboxylase and inhibition of S-adenosylmethionine decarboxylase. It is suggested that the accumulation of putrescine during postischemic recirculation may be responsible for the delayed neuronal death occurring after ischemia.

Animals↗

Lactate and pH in the brain: association and dissociation in different pathophysiological states.

Brain tissue pH and lactate content were measured in rats under three different experimental conditions, namely: during complete global cerebral ischemia; after reversible near-complete cerebral ischemia; and in experimental brain tumors. At the end of the experiments brains were frozen with liquid nitrogen. A series of 20-microns thick coronal sections was prepared in a cryostat and then used for the regional determination of tissue pH (umbelliferone technique) and tissue lactate (bioluminescent technique). In addition, tissue samples were taken for the quantitative measurement of brain lactate (enzymatic fluorometric technique). The relationship between lactate content and tissue pH was different for each of the three experimental models studied: only after short-term global cerebral ischemia did an increase in the lactate content correlate with a decrease in tissue pH (r = 0.94; p less than 0.001). A highly significant increase in the lactate content (p less than 0.001) was accompanied by physiological pH values (6.96 +/- 0.08 in comparison to 6.97 +/- 0.04 in controls) during recirculation after transient cerebral ischemia and in brain tumors even by an alkaline pH shift. In view of these observations the term "lactacidosis" should not be used without measuring both the lactate content and the pH. The observed dissociation between pH and lactate is due to the fact that both parameters are regulated independently. During anaerobiosis the main source of proton production is ATP hydrolysis rather than glycolysis. It is, therefore, suggested that the terms "acidosis" and "lactosis" should be used instead of "lactacidosis."

Animals↗

Polyamines in cerebral ischemia.

The present series of experiments was designed to study regional profiles of polyamines (putrescine, spermidine, and spermine) in reversible cerebral ischemia produced in rats and Mongolian gerbils. Polyamine profiles did not change during ischemia, but did following recirculation. The most prominent changes were a dramatic postischemic increase in putrescine and a marked decrease in spermine in severely damaged regions. Within a given brain structure, the postischemic putrescine levels correlated closely with the density of ischemic cell injury and the time period of cerebral ischemia. Furthermore, putrescine was already considerably increased in the CA1-subfield of the hippocampus of gerbils after 8 h recirculation, i.e., at a time when the cells are still intact. The results indicate that putrescine may be viewed as an excellent biochemical correlate of ischemic cell injury. The postischemic changes in putrescine levels are discussed in relation to the known activities of this compound.

Animals↗