Effects Of Acute Intoxication Research Articles

THE GAMMA‐AMINOBUTYRIC ACID (GABA) SYSTEM IN BRAIN DURING ACUTE AND CHRONIC ETHANOL INTOXICATION

Abstract— The effects of acute and chronic ethanol intoxication on the GAGA system of rats have been investigated. Under the terminal conditions provoked. by ethanol (6–8 g/kg, i.p.) the brain GABA content sharply increased. There was a simultaneous decrease of 35–40% in the glutamate decarboxylase (GAD) activity of the cerebellum and cerebral hemispheres. In contrast, the transaminase, GABA‐T was either unchanged, or it increased: by 28% only in cerebellum and by 1.5–2.0–fold in liver and kidney. It is suggested that effects of acute ethanol intoxication at different doses (2–8 g/kg) on the brain GABA system is connected with the phases of the functional condition of the CNS and a disturbance of homeostatic function. Chronic ethanol consumption caused a decrease in brain GABA. an increase of GAD activity in cerebellum and cerebral hemispheres, and no change in GABA‐T activity. The activity of this last enzyme was increased 1.5–2.0‐fold in liver and kidneys of rats consuming a diet containing 10% ethanol daily. A 50‐fold purified preparation of GABA‐T obtained from pig brain was inhibited by butanol‐l and propanol‐1 (0.03–0.6m) with no effect of ethanol. It is suggested that the mechanisms involved in the ethanol effect on nervous cells are linked with the GABA system and the phases of the functional condition of the CNS.

The effects of acute ethanol intoxication on cerebral energy metabolism.

It has long been known that anesthetics inhibit respiration in many tissues including brain and can, in yeast or heart extracts, lead to a reduction of cytochrome b while cytochromes c and a remain oxidized (Keilin, D. 1925 & 1929).

Effects of 3-acetylpyridine on the central nervous system of the rat, as demonstrated by silver methods

The effects of acute intoxication by 3-acetylpyridine on the central nervous system of rats were investigated by means of the so-called suppressive silver impregnation methods. Consequential to a single intraperitoneal injection of this nicotinamide antagonist, partial degeneration of the facial and hypoglossal nuclei was observed, as well as total destruction of the inferior olivary complex and an almost complete destruction of the nucleus ambiguus. Accordingly, the fiber tracts originating in these structures contained degenerating fibers. All the degenerating fibers originating in the inferior olives were found to take the course of the olivo-cerebellar tracts. Degenerating fibers were also found in the solitary tracts, indicating lesions in the ganglia of origin of the visceral afferent components of the cranial nerves VII, IX and X. Discrete lesions were also detected in the substantia nigra, the nucleus of the basal optic root, and the nucleus dorsalis of the raphe in the midbrain. These observations were discussed in the light of previous data from the literature. It was concluded that the clinical symptoms observed in the treated animals were due mainly to cerebellar function impairment following inferior olive destruction.

Abnormal orotic acid metabolism associated with acute hyperammonaemia in the rat

The effect of acute ammonium acetate intoxication upon orotic acid-6- 14C urinary excretion, distribution between blood and liver, and its incorporation into acid-soluble liver nucleotides, was studied in rats. Increased urinary orotic acid excretion was demonstrated following ammonium acetate treatment. In the first series of experiments, the rats pretreated with ammonium acetate were sacrificed at various time intervals after 14C-OA injection ranging from 1 to 60 min. The radioactivity content of the acid-soluble liver fraction 30–60 min following ammonium acetate treatment showed values lower by a factor of 1.5-2 when compared with saline or sodiumacetate-treated controls. The clearance of the label from blood was slower than in controls. In vivo, 14C-OA conversion to uracil nucleotides in the liver was decreased, falling to 50% 15 min after ammonium acetate treatment. In control animals 1 min after orotic acid injection, all the radioactivity recovered from the acid-soluble liver fraction was in the form of uracil nucleotides (100% conversion). In the second series of experiments, the rats were injected with ammonium acetate followed by 14C-OA at various time intervals from 1 min to 3 hr and sacrificed 5 min later. The most marked decrease in the liver radioactivity content was reached 20 min following ammonium acetate injection. The highest degree of 14C-OA accumulation in the acid-soluble liver fraction was shown 20 min after ammonium acetate treatment. A transient accumulation of endogenously produced orotic acid in the livers of rats treated with ammonium acetate was demonstrated. The rats treated with ammonium acetate showed a twofold increase in the liver acid-soluble uracil nucleotide content. The effect of acute ammonia intoxication on orotic acid formation and disposal is discussed.

Counteracting depressant effects of alcohol by psychological stress.

Interaction between effects of acute alcohol intoxication and psychological stress was examined in 8 male and 8 female students. Alcohol was given as whisky, 2 ml/kg body wt to males and 1.7 ml/kg body wt to females. Psychological stress was induced by applying electric shocks of a moderate intensity to two fingers of one of the subject's hands. Performance in reaction-time tasks representing different levels of complexity, self-estimates of wakefulness and mood, measurements of catecholamine excretion and of heart rate, were used as indices of the effects caused by alcohol and shock, singly and in combination. Among these variables, only performance was selectively sensitive to the different experimental treatments. Thus, shocks and alcohol had opposite effects, shocks decreasing and alcohol increasing reaction time. When the subjects were simultaneously exposed to both influences, the impairment produced by alcohol was significantly reduced by shock at all levels of task complexity. No sex differences could be detected.

Fetal Brain Damage Following Maternal Carbon Monoxide Intoxication: An Experimental Study

Abstract. Techniques of fetal monitoring, including fetal blood sampling in utero, were employed to study the physiological effects of acute maternal carbon monoxide intoxication upon the fetal rhesus monkey. Nine term‐pregnant female monkeys were exposed to 0.1‐0.3 % inspired CO over 1‐3 hours. The mothers tolerated car‐boxyhemoglobin (COHb) levels exceeding 60 % without clinical sequelae. The fetuses promptly developed profound hypoxia upon exposure of the mothers to CO. However, the fetal COHb levels rose only gradually over the 1‐3 hours and thus contributed only slightly to the development of the early fetal hypoxia. Fetal hypoxia was associated with bradycardia, hypotension, and metabolic and, later, respiratory acidosis. A close correlation was noted between the severity of intrauterine hypoxia and the appearance of brain damage. Severe brain damage (brain swelling associated with hemorrhagic necrosis of the cerebral hemispheres) appeared only in those fetuses whose arterial O2 content had fallen below 2.0 ml/100 ml for at least 45 min during the maternal CO intoxication.

The effect of acute ammonia intoxication upon the brain energy state in rats pretreated with L-methionine D-L-sulphoximine.

The effects of ammonium acetate upon the brain energy state in MSO-pretreated animals were evaluated in lightly anesthetized normocapnic rats. Ammonia intoxication was associated with increased lactate contents, raised lactate/pyruvate ratios. With high ammonia contents inconsistent changes in the energy state occurred in both supratentorial and infratentorial structures, indicating a labile energy homeostasis. It was concluded that inhibition of glutamine synthetase is of minor importance for maintaining energy balance and probably could not account for the protective effect of MSO against acute ammonia intoxication.

Effect of acute ethanol intoxication on the distribution of dieldrin in mice

Ethanol (6.3 g/kg) or a calorically equivalent quantity of glucose was administered po to groups of adult male Swiss-Webster mice previously given a single po dose of dieldrin (16 mg/kg). Dieldrin levels were significantly elevated in plasma and liver 16 hr after ethanol administration. There was also an increase in total liver lipids 8 and 16 hr after ethanol. Although ethanol decreased the urine volume, there was no significant reduction in the total dieldrin excreted in the urine during the first 16 hr after ethanol. There was no difference between ethanol and glucose treated animals in respect to dieldrin levels in epididymal fat at 8, 16 and 24 hr after ethanol or glucose. Since ethanol did not decrease the concentration of dieldrin in epididymal fat, it appears that mobilization of dieldrin from storage sites in adipose tissue may not be primarily responsible for the observed increase in dieldrin levels in plasma and liver after ethanol. It is suggested that a decrease in urinary excretion of dieldrin following ethanol accounts for the increase in dieldrin levels in the tissues.

Effects of acute and chronic amphetamine intoxication on brain catecholamines in the guinea pig.

The effects of amphetamine on central and peripheral catecholamines have been studied in guinea pigs, since in this species, unlike several others, amphetamine is not metabolized by p‐hydroxylation. Twenty mg/kg of dl‐amphe‐tamine‐sulphate given intraperitoneally caused a 40 % decrease in brain and heart noradrenaline, a 13 % decrease in brain dopamine and a 60 % decrease in homo‐vanillic acid in the caudate nucleus, four hours after its administration. The changes in tissue catecholamine levels and the increase in motor activity followed the time‐course of the amphetamine concentrations both in the brain and plasma. After chronic administration of amphetamine at 12 hourly intervals for 7 or 18 days, there was a further decrease in brain and heart catecholamine and homovanillic acid levels. A 4‐fold increase in the 3‐O‐methylated metabolites of noradrenaline and dopamine in brain after the administration of amphetamine to guinea pigs pretreated with nialamide and an increase in the urinary excretion of NA (13‐fold) and adrenaline (3‐fold) provided evidence for an amphetamine induced release of central and peripheral catecholamines as has previously been reported in rats and cats. Amphetamine disappeared from brain and plasma with an apparent half‐life of 2.5–3.1 hours. Only amphetamine and hippuric acid were recovered in the urine after the administration of radioactively labelled amphetamine. No p‐ or βhydroxylated metabolites of amphetamine were present in the brain or heart tissues in the guinea pig. The results show that acute and chronic amphetamine administration causes changes in endogenous catecholamines in guinea pigs similar to those found previously in rats in spite of differences in the metabolism of amphetamine between the two species.

Cerebral effects of acute ammonia intoxication. I. The influence on intracellular and extracellular acid-base parameters.

The effect of acute ammonia intoxication upon extra- and intracellular acid-base parameters in the brain was evaluated in lightly anesthetized normocapnic rats after intraperitoneal injection of ammonium acetate. The ammonia loads were unassociated with any significant changes in the CSF pH in spite of a progressive accumulation of lactate in the CSF. Comparable results were obtained for the intracellular space, which showed small decreases in pH' in spite of a substantial increase in the intracellular lactate concentration. It is concluded that the lactacidosis developing during am monia intoxication is balanced by an influx of basic equivalents from the blood. These basic equivalents may be represented by nonionic diffusion of NH3.

Inhibition of drug metabolism by acute ethanol intoxication: A hepatic microsomal mechanism

The effects of acute ethanol intoxication on drug metabolism were studied in man and rats. Ethanol ingestion significantly retarded the disappearance of pentobarbital and meprobamate from the blood in human volunteer subjects and rats. This was not due to altered compartmentalization, since total body disappearance of pentobarbital in rats was also delayed. In vitro, ethanol inhibited the metabolism of meprobamate by rat liver slices, which indicates a direct effect on hepatic drug metabolism. This effect was shown to involve inhibition of hepatic microsomal drug-metabolizing enzymes by ethanol, which was competitive or partially competitive. In addition ethanol decreased the activity of cytochrome P450 reductase, a rate limiting step in the electron transport chain of microsomal drug detoxification. The inhibition of drug metabolism demonstrated in this study may be due to the binding of ethanol to hepatic microsomes and its oxidation at this site.

The effects of acute chloroquine poisoning with special reference to the heart

The cardiovascular effects of acute chloroquine intoxication have been described in three patients and in five animal experiments. The drug appears to act as a potent myocardial poison, reducing the output of the heart and causing disturbances of conduction bradycardia, and arrhythmias. As far as we know, the first two human cases ever, which illustrate the electrocardiographic changes induced by acute chloroquine poisoning, are the ones presented (Patients 1 and 3). The sequence of changes in the electrocardiogram in acute poisoning in dogs is described. Adrenaline was found to be an effective antidote, as well as a preventive drug. Appropriate precautions are suggested to prevent the occurrence of accidental death or induced poisoning. These emphasize the administration of the drug on a weight rather than an age basis. The use of small doses similar to quinidine may prevent drug idiosyncrasy but does not seem to be practical. Considering the widespread use of chloroquine and its increasing administration, it is necessary to consider the precautionary measures outlined on an international scale.

1707. Effect of cyanide on amino-acid transport in brain slices: Levi, G. & Amaducci, L. (1968). Effect of acute cyanide intoxication on the active transport of amino acids in brain slices. J. Neurochem.15, 459

1707. Effect of cyanide on amino-acid transport in brain slices: Levi, G. & Amaducci, L. (1968). Effect of acute cyanide intoxication on the active transport of amino acids in brain slices. J. Neurochem.15, 459

MESENCHYMAL-CELL PROLIFERATION IN LIVER DISEASE OF THE ALCOHOLIC.

AVAILABLE INFORMATION suggests that ethanol-induced hepatic necrosis in the setting of fatty liver initiates a regenerative reaction which ultimately leads to lobular distortion and cirrhosis. 1 Further research is now desirable to elucidate mechanisms responsible for the hepatic cell damage, to discover initiating and controlling factors in regeneration, and to determine the contribution of various cell types to liver repair. The present investigation was undertaken to delineate the degree, localization, and effect of cellular proliferation which accompanies liver injury due to alcoholism. Autoradiographic techniques employing tritiated thymidine (H 3 T) were utilized 2 to evaluate the influence of ethanol intoxication on hepatic deoxyribonucleic acid (DNA) synthesis and regeneration in experimental animals and man. Materials and Methods Animal experiments were conducted to determine the effect of acute ethanol intoxication on hepatic DNA synthesis. A single or divided oral dose of 0.6 gm of ethanol per 100 gm weight, each day for 3

Effect of acute alcohol intoxication on steroid output of rat adrenals in vitro.

Ethyl alcohol, 2 g/kg in 20% solution, was given to rats by gavage and the adrenals were removed 1 1/2 hr later and incubated in vitro. Their corticosteroid production was not significantly different from that of glands from water-treated or untreated controls. However, when this dose of alcohol was administered by intraperitoneal injection, a significant elevation in adrenal steroid output was observed. Increasing the dose of alcohol to 4 g/kg by stomach tube also evoked an increased adrenocortical response, but when this total dose was divided into two spaced doses, each one of 2 g/kg by stomach tube, 1 1/2 hr apart, no significant alteration in adrenocortical production was observed, despite higher blood alcohol levels and equally deep intoxication. Thus, although the blood alcohol level attained may influence the activity of the adrenal cortex, the rate of change in blood and tissue alcohol levels also seems to be a significant factor in determining whether adrenal cortical stimulation will occur. None of the treatments appeared to modify the relative proportions of the various steroids released.

Studies in Neuromuscular Transmission

The effect of acute potassium intoxication on the neuromuscular transmission was studied in rabbits. The sciatic nerve was stimulated through bipolar electrode pairs and the electrical response of the gastrocnemius muscle was recorded. The stimulus necessary to evoke a maximal response, neuromuscular conduction time, nerve conduction time, amplitude and duration of response, refractory and irresponsive periods were measured as was the response to repeated stimulation at a rate of 3 per second. Hyperpotassemia was produced by i. v. infusion (1/2‐1 1/2 ml per min.) of isotonic solution of potassium chloride over 1/2–3 1/2 hours. The observed changes were: Prolonged neuromuscular conduction time, decreased amplitude and prolonged duration of response, prolonged refractory and irresponsive periods. These findings can be explained by a slowing of depolarization and re‐polarization near, at or distal to the neuromuscular junction. They were not caused by the metabolic acidosis nor by the hyponatremia which in some of the experiments accompanied the hyperpotassemia.

Effect of Acute Ethanol Intoxication on Liver and Plasma Lipid Fractions of the Rat

Effect of Acute Ethanol Intoxication on Liver and Plasma Lipid Fractions of the Rat

Effect of acute ethanol intoxication on liver and plasma lipid fractions of the rat.

Plasma and liver lipid fractions of rats were studied 8 and 16 hours after administration of a single oral intoxicating dose of ethanol. When compared to rats which received an isocaloric amount of glucose, no differences were noted in plasma phosphatide, cholesterol or triglyceride concentrations. Liver weight and triglyceride concentrations were significantly elevated 8 and 16 hours after ethanol administration. The increase in liver neutral fat was not prevented by the simultaneous administration of choline and was not associated with alterations in liver or plasma phospholipid metabolism. The possible mechanisms of the development of a fatty liver following acute ethanol intoxication are discussed with particular reference to its possible hepatotoxic action.

The effect of acute alcoholic intoxication on the blood-brain barrier.

Journal Article The Effect of Acute Alcoholic Intoxication on the Blood-Brain Barrier, Get access William J. Horsey, M.D. William J. Horsey, M.D. Baltimore, Md. ***International Fellow, W. K. Kellogg Foundation. Now at the Department of Surgery, Division of Neurosurgery, University of Toronto and Toronto General Hospital, Toronto, Ontario. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Neuropathology & Experimental Neurology, Volume 12, Issue 4, October 1953, Pages 368–372, https://doi.org/10.1097/00005072-195312040-00004 Published: 01 October 1953

The Effect of Acute Alcohol Intoxication on the Adrenal Glands of Rats and Guinea Pigs

The Effect of Acute Alcohol Intoxication on the Adrenal Glands of Rats and Guinea Pigs