Alteration of water-soluble S-100 protein content in microembolized rat brain.

The amount of S-100 protein in rat brain embolized with carbon microspheres decreased in parallel with the development of cerebral edema as judged by water content, recovering to the normal range by 24h after embolization. These results suggest the participation of S-100 protein in the permeability characterisitics of nervous system capillaries known as the blood-brain barrier.</p

Experimental and clinical studies on the catecholamine metabolism 1. Studies on the determination of catecholamines in tissues, serum, urine and cerebrospinal fluid by gas chromatography (ECD).

Catecholamine in tissue, serum and urine has been determined by the fluorometric method. It still remains some problems, especially sensitivity in the measurement and purification of catecholamines according to this method. Therefore, I determined by a gas chromatographic method (using an Electron Capture Detector: ECD) modified from the method of Imai (1971). Catecholamines in cerebrospinal fluid (CSF) have not been determined by gas chromatographic method so far. A new technique for the determination of catecholamine in CSF of human will be presented in this paper. The results are as follows, 1) According to the gas chromatography, 20mg of tissue, 2.5ml of serum and 3.0ml of CSF are enough to determine with the grade of one nanogram. 2) Dopamine, norepinephrine, epinephrine, 3, 4-dihydroxyphenylalanine (DOPA), tyramine, octopamine, metanephrine, normetanephrine and synephrine were determined. Retention time of gas chromatography for these substances was decided. Heptachlor epoxide or dieldrin were available to the internal standard substances. 3) Dopamine was determined in serum of normal human subjects and in experimental animals (rat and cat). 4) Epinephrine was detected in brain tissue of rats and cats. This evidence will show that the central nervous system contains enough epinephrine to evaluate. 5) Micro-quantitative analysis of catecholamine and its derivatives in various samples will contribute to the neurochemical researches and to the clinical works in the central nervous system

Experimental and clinical studies on the catecholamine metabolism 3. Experimental and clinical studies on the peripheral aromatic amino acid decarboxylase inhibitor and catecholamine metabolism

Combined effects by L-DOPA and peripheral decarboxylase inhibitor (L-alpha-hydrazinomethyldopa: MK486) were studied in cats and eighteen parkinsonian patients, with special reference to catecholamines and amino acids metabolism. Catecholamine levels in brain tissues and plasma were measured in cats following the intraperitoneal injection of L-DOPA alone (100mg/kg b. w.) or combined with MK486 (10mg/kg b. w.) by gas chromatographic method (using an Electron Capture Detector). 1) DOPA level in cat plasma in the combination with MK486 was three-fold as high as in L-DOPA alone. Dopamine levels in caudate nucleus of cats were increased up to about six-fold in the combination. Dopamine level in plasma was markedly decreased in the combination with MK486. Norepinephrine and epinephrine levels in cat plasma were no significant change in both L-DOPA alone and combination with MK486. Norepinephrine level in the brain was no significant change except slight increase in pallidum and caudate nucleus. 2) After oral administration of L-DOPA in combination with MK486, DOPA level in plasma of the patients with parkinsonism was maintained at a higher level and for longer than after the oral administration of L-DOPA alone. Plasma dopamine level with the combination was markedly lower than with L-DOPA alone. Dopamine level in plasma at three hours after the administration tended to be decreased at a 1:5 ratio of MK486 to L-DOPA in dosage. Plasma epinephrine level was not significant change at all. Dopamine level in cerebrospinal fluid was maintained at a higher level and for longer than the oral administration of L-DOPA alone. 3) Urinary homovanillic acid level in parkinsonism was lower in the combination of MK486. 4) Plasma amino acids which might affect catecholamines metabolism was not significant change following the administration of L-DOPA alone as well as L-DOPA plus MK486. 5) In clinical studies of 18 patients with parkinsonism, the effectiveness of the combination therapy with L-DOPA and MK486 (mean dosage of L-DOPA: 750mg/day and MK486: 75mg/day) was observed in all cases. Marked improvement was noted in 10 cases out of 18 (56%) with akinesia, in 12 cases out of 18 (67%) with rigidity and in 6 cases out of 18 (33%) with tremor. Maximum plasma DOPA levels were higher in cases with marked improvement than the other, and were highest in patients with dyskinesias of a side effect. 6) Nausea and vomiting of the side effect, which were less severe than those experienced with L-DOPA alone, were noted in 5 cases (28%). Dyskinesias in extremities, face, mouth and tongue were observed in 6 cases (33%)

Experimental and clinical studies on the catecholamine metabolism 2. Experimental and clinical studies on the catecholamine metabolism in epilepsy.

Catecholamine and its metabolites level in cerebrospinal fluid (CSF), serum and urine of the 62 patients with epilepsy (38 males and 24 females, 12 cases of Lennox's syndrome, 48 cases of centrencephalic epilepsy, one case of focal cortical epilepsy and one case of temporal lobe epilepsy) were determined by gas chromatographic method (using an Electron Capture Detector) and fluorometric method. Studies on the epilepsy was performed with a special reference to catecholamine metabolism. As the results, 1) 3, 4-dihydroxyphenylalanine (DOPA) and dopamine in CSF of the epileptics were significantly lower than in the control group. 2) Homovanillic acid (HVA: end-product of dopamine) in CSF of the epileptics was also significantly lower than in the control group. 3) In epileptics tyramine, octopamine and synephrine were detected in CSF. 4) It is speculated in epileptics that the suppression of the pathway from tyrosine to dopamine may act to enhance the side pathway from tyrosine to tyramine followed by octopamine, synephrine and epinephrine. 5) Serum DOPA levels of epileptics being treated with anticonvulsants were abnormal in about half of the cases. 6) Serum MAO activity of epileptics was significantly lower than in the control group. 7) HVA in urine of epileptics tended to increase, but its level was changeable. Based on these clinical studies of epileptics, a penicillin focus was made on the cortex of cats. And effects of the catecholamines to penicillin focus were electroencephalographically examined. 8) Penicillin spikes were strongly inhibited by topical application of dopamine. 9) When octopamine was injected into cisterna magna after the appearance of penicillin spikes, spike frequency increased and abnormal spike discharges were observed