Effect of brain cortex phospholipids on adenylate-cyclase activity of mouse brain.
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Biomedical subjects
Publications and source records attributed to G Toffano.
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Concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were investigated by lumbar cerebrospinal fluid (CSF) of 21 patients with partial and total spinal subarachnoid block. HVA levels in CSF below a complete block were significantly lower and 5-HIAA levels were signigicantly higher than controls. Below a partial block, HVA levels were normal; 5-HIAA levels were higher than in patients with complete block. Possible explanations for these findings are discussed.
21 cases of hypertensive hydrocephalus were investigated for lumbar 5-HIAA before and after operation. Seven groups (posterior fossa tumors) of patients aged between 2 and 12 years were tested after tumor removal; the others (nontumorous hydrocephalus) after ventricular shunting. This last group included 8 patients with noncommunicating hydrocephalus aged between 15 days and 12 years and 6 with communicating hydrocephalus aged between 6 months and 9 years. At the time of the second determination all patients presented an improvement of clinical signs of intracranial hypertension. A correlative analysis of 5-HIAA values before and after operation is made. In tumor cases, preoperative levels were higher than controls, and a significant decrease was found after operation in comparison with preoperative levels. In nontumor cases, a significant decrease was also observed in noncommunicating hydrocephalus, confirming clinical usefulness of the results for controlling the degree of the intracranial hypertension and, in consequence, shunt performance. In communicating cases the results were disappointing, because almost always postoperative levels did not differ from the preoperative ones. Possible interpretations of the data are analyzed.
Two types of crude synaptic membranes have been prepared which differ in their kinetic properties to bind 3H-GABA in a Na+-free medium. One type (B) has one type of receptor (affinity or KD about 0.2 micrometer), the other type (A) has two populations of receptors which have a high (0.16 micrometer) and a low ((.02 micrometer) KD for GABA binding. This difference is due to the presence of a selective endogenous inhibitor of the high affinity receptor for GABA, a thermostable protein of about 15,000 molecular weight. Inhibitor action is counteracted by diazepam (7 X 10(-7) M), competitively. Clonazepam is more active but chlordiazepoxide is less active than diazepam. Two enantiomers of a benzodiazepine were studied. One of them is endowed with anxiolytic activity and nullifies the action of the endogenous inhibitor on high affinity GABA binding, the other is devoid of anxiolytic activity and is inactive against the inhibitor. The endogenous protein inhibitor also competitively blocks the high affinity binding of 3H-diazepam to Type A membranes. It is concluded that the endogenous inhibitor and diazepam act on the same receptor; and suggested that the endogenous inhibitor may be the natural ligand for the brain receptors that bind benzodiazepines with high affinity.
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Mice on an atherogenic diet for 40 days show a decrease in brain content of catecholamines, cyclic AMP and in dopamine degradation, and modification of the glycolytic pathway. The metabolic changes are paralleled by changes in behaviour, i.e. decrease in spontaneous motor activity and in conditioning avoidance response. The decrease in dopamine degradation and in behaviour parameters is partly due to the propylthiouracil present in the diet. Endovenous treatment with sonicated dispersions of bovine brain phospholipids induces a modification in the parameters of behaviour and metabolism. The possibility is discussed that some of the defects arising during the atherogenic diet are related with the establishment of a hypoxic state.
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1) Cholesterol - enriched diet induces changes in the phospholipid fatty acids of particulate fractions and modifications in the membrane-bound enzyme: 2) BC-PL (100 mg/kg i.p., as shown in rabbits) prevent cholesterol-induced modifications at brain level: 3)BC-PL (100 mg/kg i.v., as shown in mice) have a recovery effect on the cholesterol-induced modification at brain level; 4) It is suggested that some atherosclerotic lesions are analogous to those reproduced by anoxia; 5) It is suggested that the effect of BC-PL is a direct action at the level of the brain cellular membranes.
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