摘要:

Abstract—Experiments have been performed to study the effect of gamma‐hydroxybutyric acid (GHB) on glucose metabolismin vivoandin vitro.1Administration of GHB (500 mg/kg) is followed by sleep in rats and mice.2GHB is shown to increase the 1‐14C/6‐14C ratio in expired CO2in micein vivoby 300 per cent.3The same effect is obtained with slices of cerebral cortical grey matter from GHB‐treated rats, where the 1‐14C/6‐14C ratio is increased from 1.72 to 3.63, but not with homogenates of cerebral cortex, nor with slices of kidney or diaphragm.4GHB (500 mg/kg, intrapentoneally) specifically increases the activity of glucosed‐6‐phosphate dehydrogenasein vivoin rat and mouse whole brain by 27 per cent. The time course of this effect correlates with the sleeping time in both species.5The activity of glucose‐6‐phosphate dehydrogenase is not alteredin vitroby high concentrations of GHB.6GHB stimulates O2uptake by slices of cerebral cortical grey matter by 24 per cent, but it is not itself able to support respiration by the tissue.7It is proposed that GHB specifically increases the activity of the pentose phosphate pathway in brain, and that this effect is mediated by an increase in glucose‐6‐phospha

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01334.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Following intracerebral inoculation of mouse adapted scrapie agent into mice, polyamine concentration in the brain decreases to about 75 per cent of the normal level during the first 2 months after intracerebral inoculation of the agent. Between 2 and 4 months after infection thelevel of spermidine and spermineincreased by 80 and 40 percent respectively to reach concentrations of 25 and 20 per cent higher than controls of the same age. During the same period the rate of incorporation of [14C]putrescine into spermidine is increased four‐fold as compared with controls. The changes in polyamine levels correlate well with the pattern of astrocyte hypertrophy and are similar to those reported for human brain tumours. The concentration of polyamines in spleen increases soon after inoculation. Whilst changes in brain polyamines might be referred to the hypertrophic growth of astrocytes those in spleen are perhaps due to an increased metabolic activity of spleen cells associated with the replication of the agent. These results are derived from experimental mouse scrapie and not naturally occurring disease in sh

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01335.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—5‐Hydroxytryptamine (5‐HT) synthesis has been determined in the rat brain by measuring the 5‐[3H]HT formed from [3H]tryptophan in the presence of monoamine oxidase inhibitor. Electrical stimulation in the region of the midbrain raphe nucleus increased formation of 5‐[3H]HT by over 100 per cent, although the level of endogenous 5‐HT and the concentration and specific activity of tryptophan were unchanged; the results are interpreted in terms of a two‐compartment model. The optimum stimulation parameters were determined. Three days after a single dose of the tryptophan hydroxylase inhibitorp‐chlorophenylalanine, stimulation increased 5‐HT synthesis by the same percentage as in untreated animals. It was also found that after the end of an hour's stimulation, synthesis returned to control values in under an hour. These results suggest that the rise in synthesis of the amine on stimulation is not due to induction of tryptophan hydroxylase, but more likely to an increase in the activity o

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01336.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—The enzymes catalysing ethanol metabolism, alcohol dehydrogenase (EC 1.l.1.1) and aldehyde dehydrogenase (EC 1.2.1.3), were assayed in a variety of neural and somatic tissues of the rat, the human counterparts of which are known to be vulnerable to excessive ethanol. The activity of alcohol dehydrogenase was assayed by the coupled oxidation of ethanol and reduction of lactaldehyde, a method which we have recently found to be sufficiently sensitive and specific to measure the relatively low levels of activity in whole brain. Detectable activities of these enzymes were found in peripheral nerve, skeletal muscle, retina, optic nerve and various regions of brain, as well as in a variety of non‐neural tissues. The levels of the enzymic activities in all tissues were markedly lower than those of liver, but probably sufficient to perform a local function in the metabolism of ethanol or other endogenous substrates. The activity of alcohol dehydrogenase in the various tissues, like that of liver, was confined to the cytosol and exhibited kinetic properties and responses to inhibitors almost identical to those of the liver enzyme. We consider the results to be consistent with the hypothesis that the pathological effects of alcohol may be related, at least in part, to local mechanisms for the metabolism of alco

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01337.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Sciatic nerves from 18‐day‐old chick embryos incorporated35SO4into myelin sulphatidein vitro. Sulphatide in a microsomal subfraction of the nerve was rapidly labelled with35SO4, and a lipoprotein fraction in the nerve served to transfer the [35S]sulphatide from the microsomal subfraction to myelin. Puromycin and cycloheximide inhibited the incorporation of [35S]sulphatide into myelin after a lag period of about 2 h. These agents did not alter the rate of appearance of [35S]sulphatide in the microsomal subfraction, and did not diminish the capacity of myelin to take up [35S]sulphatide from the lipoprotein fraction; instead, they appeared to interfere with the incorporation of [35S]sulphatide into myelin by decreasing the available pool of the transport lipoprotein. Partial characterization of the [35S]labelled lipoprotein fraction indicated that it had a density of 1.06–1.08. The lipoprotein was highly aggregated, but, after incubation with SDS and mercaptoethanol, it was dissociated into sulphatide‐containing micelles and

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01338.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—DNA synthesis in methylazoxymethanol (MAM)‐treated foetal brain was reduced during the first 3 days after the injection of the compound into the mother rat. The MAM‐treated brain grew at almost the normal rate after this period, but the reduction in DNA persisted through maturity of the animal. This difference in DNA content between normal and microencephalic brain was restricted to the cerebral hemispheres. The major increase in DNA content of prenatal brain occurred in the cerebrum, whereas the postnatal increase took place in the cerebellum. jH‐Labelled MAM was incorporated more extensively into foetal brain DNA than into RNA. The half‐life of the MAM‐modified nucleic acids was 4–5 days. We suggest that removal of necrotic cells from the brain may account for the rapid loss of label from

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01339.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—The fatty acid composition of cerebrosides, sulphatides and ceramides has been determined at 20 days postpartum in the brains of Quaking mutant mice and of littermate controls. There was a significant deficit in the proportion of long‐chain fatty acids (C22‐C24) affecting both normal and a‐hydroxy fatty acids of the cerebrosides. The proportion of normal but not the a‐hydroxy long‐chain fatty acids of the sulphatides was also decreased. Striking and disproportionate deficits of the C24:1and C24 h:1fatty acids of cerebrosides, sulphatides and ceramides characterized the brain of the Quaking mutant, and an increased proportion of C23 h:Ofatty acid was found in the cerebrosides and sulphatides of the brain of this mutant. We compared these data with findings on the Jimpy mutant which has been examined by the same techniques. The deficiency of long‐chain fatty acids which was found in the cerebrosides and sulphatides of both mutants was less extensive but more selective in the Q

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01340.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Abstract‐Tumors of the human nervous system were utilized to investigate the cellular distribution of N‐acetyl‐L‐aspartic acid (NAA). Astroglial tumours contained about 0.144 μmol/g. Oligodendrogliomas and medulloblastomas contained somewhat larger amounts. However, the level of NAA in all gliomas studied was less than that of normal human white matter. NAA was undetectable in meningiomas and acoustic neurinomas. If these results may be taken as representative of normal tissue, they imply a predominantly neuronal localization for NAA.Substantial amounts of NAA were found in peripheral nervous tissues and retina. Neurons seem to vary widely in N

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01341.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—[U‐14C]Glucose was given to dogs by intravenous infusion to maintain a fixed level of specific radioactivity of the plasma glucose. The time course of incorporation of14C into free amino acids, proteins and lipids of the cerebrum was observed for periods up to 2 h. Labelling of amino acids closely related to the tricarboxylic acid cycle increased progressively throughout the infusion, approaching specific radioactivities per μg‐atom of carbon equal to that of the plasma glucose. No significant dilution by unlabelled carbon entering the metabolic pathways was apparent.In dogs subjected to profound insulin hypoglycaemia, [U‐14C]glucose mixed with unlabelled glucose was given to bring about recovery. The incorporation of14C into glutamate, glutamine and aspartate during a 40‐min period was greater than during a comparable period in control animals, whereas the incorporation into serine was reduced. When considered in relation to alterations in amino acid levels, the data suggest that during recovery from hypoglycaemia the rates of synthesis of amino acids related to the tricarboxylic acid cycle are increased. During the period of recovery the rates of incorporation of14C from glucose into proteins exceeded the pre‐insulin rates to a degree surpassing the increased incorporation into free amino acids. The labelling of the ganglioside, cerebroside‐sulphatide and cephalin fractions was also increased, The rates of incorporation into the lecithin‐sphin‐gomyelin and cholesterol fractions during recovery were the same as in the pre‐insulin period. Hypoglycaemia decreased the cerebral content of the phospholipid fractions; the lecithin‐sphingomyelin fraction returned toward normal during recovery, whereas the cephalins did not increase significantly.The electrographic patterns and the occurrence of convulsive activity are discussed, both in insulin hypoglycaem

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01342.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Preparations of phospholipase Az have been obtained from human cerebral cortex. The enzyme was extracted from acetone‐dried tissue and purified by heat‐treatment and gel filtration on Sephadex.Although heating at 65°C or 70°C destroys most of the phospholipase A1activity that is present in crude extracts, a small proportion remains associated with the A2activity during these procedures. The heat‐treated extracts hydrolyse lecithin in preference to phosphatidyl‐ethanolamine but have no action on lysolecithin or neutral lipids. The results suggest that A2activity and the heat‐stable component of A1may both be due to a single phospholipase A that can hydrolyse diacylglycerophosphatides at either the 2‐or the 1‐position, to form a mixture of isomeric lysoderivatives.A molecular weight of 55,000 was calculat

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01343.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY