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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 451 records · Page 25Linked to original sources

The modification of the ethanol withdrawal syndrome in rats by di-n-propylacetate.

Di-n-propylacetate (DPA), a drug known to increase brain gamma-aminobutyric acid (GABA) levels and to inhibit GABA-transamine (GABA-T) activity, was administered during the ethanol withdrawal period to rats made physically dependent upon ethanol. Under all conditions tested, 400 mg DPA/kg injected i.p. significantly reduced the withdrawal hyperexcitable state induced by acoustic stimulation. The effect was seen as early as 30 min after the administration of DPA and lasted for at least 2 hrs. Readministration of the same dose of DPA 6.5 hrs after its initial injection again mitigated withdrawal symptoms. A 200 mg/kg dose of DPA was significantly effective for only 1 hr after its administration. Neither dose led to mortality or observable tranquilization. The results suggest that DPA may be a useful agent in the control of the hyperexcitable state induced by ethanol withdrawal and that the GABA system may be involved in this state.

Acoustic Stimulation↗

Properties of ecto-(inoganic) pyrophosphatase of nervous system cells in culture. Activation upon partial release of sialic acid from the cell surface.

Clonal line NN hamster astroblasts and clonal line N18 neuroblasts were treated with phospholipase C-free, protease-free, and hemolysin-free Clostridium perfringens sialidase, at a low level (5 X 10(-3) units/ml) so as to maintain cell intactness and to avoid spurious protein effects. A rapid, regular release of sialic acid was achieved. An approximately 9-fold increase in ecto-pyrophosphatase activity could be brought about by action of C. perfringens sialidase for 10 min. Since the sialidase preparations were employed at a level which gave a very low concentration of extraneous protein, and the preparations were free of demonstrable phospholipase C and protease activities, these effects appear to relate specifically to removal of cell surface sialic acid. Neutral p-nitrophenyl phosphatase was activated under the same conditions, but activity remained low compared with pyrophosphatase. Progress curves for activation of the two enzymes were dissimilar. Ecto-pyrophosphatase of NN and N18 cells had an absolute requirement for Mg2+ both before and after removal of cell surface sialic acid. In the presence of near optimum Mg2+ (5 mM), other divalent cations were inhibitory at a low level (10(-1)mM). The effect of Mg2+ concentration, as well as inorganic pyrophosphate concentration, upon ecto-pyrophosphatase activity was shown to obey Michaelis-Menten kinetics for the control activity and for the sialidase-enhanced activity of both cell types. Km for Mg2+ and for pyrophosphate remained constant upon ecto-pyrophosphatase enhancement by sialic acid removal; increase in enzymatic activity was accounted for entirely by an increase in Vmax.

Cell Line↗

The (Na+ + K+)-ATPase activity in brain of Quaking mice.

The (Na+ 4 K+)- and Mg2+-dependent ATPase distribution in several brain areas has been investigated in Quaking mutant mice characterized by myelin deficiency. A marked decrease of (Na+ + K+)-ATPase activity has been found in limbic structures, hypothalamus and cerebellum. The Mg2+-dependent activity did not change. A possible involvement of the impairment of the (Na+ + K+)-ATPase activity in the seizure susceptibility of this mice is discussed.

Adenosine Triphosphatases↗

The chronic and acute effects of ethanol on adenosine triphosphatase activity in cultured astroblast and neuroblastoma cells.

Mg2+ATPase and (Na+ + K+)ATPase activities were measured in clonal line NN hamster astroblasts and in clonal lines M1 and N1E-115 mouse neuroblastoma cells after the cells had been subjected to the acute and chronic actions of 100 mM ethanol. Exposure of the astroblasts to ethanol for periods as long as 68 days produced an increase in total cellular Mg2+ ATPase activity, as measured in cell homogenates; however, activity reverted to control levels upon withdrawal of ethanol. Chronic exposure of clonal line N1E-115 neuroblastoma cells to ethanol produced an increase in Mg2+ATPase and (Na+ +K+)ATPase activities. In contrast, the activities of both ATPases of clonal line M1 neuroblasts were unaffected by chronic exposure to ethanol. Acute exposure of cell homogenates to 100 mM ethanol inhibited Mg2+ ATPase and (Na+ + K+)ATPase of astroblasts but not that of neublastoma cells. These findings suggest that neural cells in culture may serve as useful models for studying the effects of ethanol on specific cell types.

Adenosine Triphosphatases↗

Changes of CTP synthetase activity during postnatal rat brain development.

The activity of CTP synthetase (UTP: ammonia ligase (ADP, EC. 6.3.4.2.) was determined in rat cerebral hemispheres and cerebellum during postnatal development. It was found that enzyme activity, when expressed per unit of protein or wet tissue weight, in both parts of the brain decreased with age, the diminution proceeding more rapidly in the cerebellum than in the hemispheres. When CTP synthetase was expressed on the basis of DNA an activity peak in the hemispheres with a maximum on the 5th day after birth was observed. The enzyme content per cell was several times lower in the cerebellum than in the hemispheres at each age studied, with the exception of 1-day-old animals, in which both tissues displayed similar activity. The results obtained were compared with literature data for the intensity of RNA synthesis in the developing brain. The conclusion was reached that the changes of CTP synthetase activity were closely related to the RNA metabolism. Therefore the enzyme under study may be one of the factors involved in cell control of RNA synthesis.

Age Factors↗

Inhibition of high affinity uptake of GABA by branched fatty acids.

Several branched fatty acids including an antiepileptic agent nDPA were tested as potential inhibitors of high affinity uptake of GABA by brain slices and synaptosomes. Only three compounds (2-butyl-3-propylhexanoic acid, 5-propyloctanoic acid, 2-propylpenten-2-oic acid) were found to be relatively weak inhibitors of the uptake system. There was no correlation between anticonvulsant properties of the branched fatty acids and their potencies as inhibitors of high affinity uptake of GABA.

Aminobutyrates↗

Lipid composition of rat sciatic nerve.

In the course of our study on the lipids of the rat sciatic nerve, the analysis of the neutral lipids allowed us to detect and characterize cholesteryl esters present at a relatively high level (5%). Among the phospholipids, ethanolamine phosphoglyceride is the most abundant fraction and contains neraly all the plasmalogens (20% of total lipid phosphorus). The glycolipids consist of five different fractions; the cerebrosides with hydroxy fatty acids account for 38% of total glycolipids. Monogalactosyl diglyceride represents 7% of total glycolipids.

Animals↗