[An experimental study on the mechanism of the protective action of pentobarbital and Y-9179 against cerebral ischemia (author's transl)].
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Biomedical subjects
Publications and source records attributed to A Tamura.
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The effect of intracarotid prostacyclin (PGI2) on cerebral blood flow (CBF) was measured by the 133xenon intracarotid injection technique in 8 baboons. Intracarotid prostacyclin increased CBF by 22% at 10(-7) g/kg/min and by 71% at 5 x 10(-6) g/kg/min, accompanied by systemic hypotension and tachycardia. The effects of PGI2 (10(-7) g/kg/min) were not potentiated by transient opening of the blood-brain barrier with the intracarotid hypertonic urea technique. At hypercapnia, the vasoconstrictor effect of indomethacin on the cerebral circulation was reversed by PGI2. These results support our suggestion that a prostaglandin, in particular PGI2, is required for hypercapnia to produce full cerebral vasodilatation. In separate experiments, following craniectomy in 5 cats, PGI2, but not its stable metabolite 6-keto-PGF1 alpha, dilated pial arterioles when locally injected into the mock CSF overlying the arteriole.
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In 22 subjects, selective venous sampling from the inferior petrosal sinus was performed under provocative tests along with simultaneous sampling of pituitary blood from the antecubital vein, after retrograde cavernous sinography. The difference of hormonal levels between sinus blood (Bs) and peripheral blood (Bv) was measured by two antibody radioimmunoassay. Most extreme difference of hormonal levels was observed in acromegalic subjects, where Bs/Bv ratio of GH was 6.0 in the basal value and 4.9 in the peak value, and that of PRL 3.5 and 4.6, respectively. In subjects who reacted to provocative tests, the average ratio of Bs/Bv ranged from 6.9 to 1.1 in the order of GH, PRL, LH, TSH and FSH. Non-reactive subjects showed no significant difference in the hormonal levels between Bs and Bv. From the results obtained above, we assume a possible relationship between Bs/Bv ratio and metabolic clearance rate and between difference of Bs-Bv and basal production. The integral of Bs-Bv difference measured from time zero to the time returned to the basal value under provocative tests represents the sum of basal production and pituitary reserve according to compartment analysis.
A new antibiotic designated tendomycin was isolated from the culture of Streptomyces No. 9034. The antibiotic is active against Gram-positive bacteria, fungi and cultured cancer cells, and shows an inhibitory effect of EHRLICH carcinoma in mice.
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A new multifunctional protein kinase, which normally exists as an inactive form in the soluble fraction in mammalian tissues, attaches to membranes to exhibit full enzymatic activity. A low concentration of Ca2+ is absolutely necessary for this activation. This process is reversible. cAMP shows no effect. The active factors in membranes are phosphatidylinositol, phosphatidylserine, phosphatidic acid, diphosphatidylglycerol, and phosphatidylethanolamine in that order. Phosphatidylcholine and sphingomyelin are far less effective. Cytoplasmic as well as other membrane fractions from various tissues are active in supporting the enzymatic activity. A possible role of this Ca2+ and phospholipid-activated protein kinase system in transmembrane control is proposed.
Changes in the membrane morphology and phospholipid content of human erythrocytes were determined after incubation of intact cells with each of various exogeneous phospholipases (PLases). PLase A2 from Naja naja or bee venom induced crenation of the cells in parallel with hydrolysis of the membrane phosphatidylcholine (PC). This crenated cell shape was reversed to a biconcave disc or cup-like form by a further treatment with lysophospholipase. In contrast, bacterial PLase C from Clostridium perfringens and Pseudomonas aureofaciens or fungal PLase D from Streptomyces chromofuscus induced invagination of the cells in parallel with hydrolysis of the PC. The action of the latter group of PLases on the membrane morphology was counteracted by PLase A2, and vice versa. Thus, participation of the membrane lipid bilayer in the induction of membrane conformational change and hence cell shape change was demonstrated.
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Two penicillins and 5 cephalosporins were evaluated for their ability to pass through the outer-membranes of Proteus morganii, Citrobacter freundii and Escherichia coli. Cefazolin, ceftezole and cephaloridine showed high permeability through the outer-membranes of these Gram-negative bacteria. Benzylpenicillin and cephalothin, on the contrary, showed low permeability. The outer-membrane permeability of ampicillin and cephalexin varied from species to species. C. freundii was found to have the highest barrier against both the penicillins and the cephalosporins, and E. coli appeared to have a low barrier against the cephalosporins. The hydrophobic character of the beta-lactam antibiotics, which was estimated by a reversed-phase thin-layer chromatography was closely related to the outer-membrane permeability. In general, the more hydrophilic antibiotic showed the higher outer-membrane permeability. However, cephaloridine, the most lipophilic compound among the antibiotics tested, showed good permeability.
The correlation between the changes of regional cerebral blood flow (rCBF) and the histological changes were examined using the middle cerebral arterial (MCA) occlusion model in cats. A total of 24 adult cats were tracheostomized and anesthetized by inhalation of halothane. The right MCA was clipped by the transorbital approach. Two hours after the application, the clip was removed and the brain was recirculated for two hours. Then, the brain was perfusion-fixated and the histological studies were carried out. The animals were separated into two groups according to the severity of histological damages using light and electron microscope. Severe cortical damage was present in 8 cats (Group A). In the remaining 16 cats, little or no cortical damage was found (Group B). The averaged rCBF values before occlusion were 45.4 +/- 2.3 ml/100 gm/min in group A and 46.5 +/- 1.6 in group B, showing no statistically significant difference. Between these two groups, however, there was a statistically significant difference in the averaged rCBF values during the ischemic period. In group A, the averaged rCBF values during MCA occlusion was only 6.8 +/- 0.9 and in group B, it was 25.3 +/- 0.8. In the recirculation period, there was a prompt and uniform recovery of rCBF in group B. Whereas in group A, a marked diversity of rCBF ranging from oligemia to hyperemia ensued. This is presumably a reflection of inhomogeneous blood flow, or patchy non-filling of the cerebral cortex. The critical values of rCBF as to the occurrence of severe cortical damage in two-hours MCA occlusion is considered to lie between the lowest value of group B and the highest value of group A, i.e., around 12--15 ml/100 gm/min.
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