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Biomedical subjects

E Majchrowicz

Publications and source records attributed to E Majchrowicz.

At least 37 records · Page 2Linked to original sources
PubMed1981

Reversal in central nervous system function during ethanol withdrawal in humans and experimental animals.

The ultimate objective in devising animal analogs of physical dependence on ethanol is to obtain meaningful imitations that have behavioral and biological similarities to human subjects during the ethanol withdrawal syndrome. The natural history of alcoholic disease in human subject and in experimental animals involves three periods, each characterized on the basis of temporal relationships, pattern of ethanol intake, blood ethanol concentrations, and/or a typical sequence in the onset and decay of the characteristic spectrum and continuum of overt behavioral, neurological, and biological signs and responses. These characteristics are expressions of different functional states of the central nervous system (CNS): 1) the baseline period or predrinking period reflects normal function of the CNS; 2) the induction period or drinking period is characterized by overt signs and responses of nonspecific, long-term CNS depression; and 3) the withdrawal period is characterized by a relatively rapid transition in the CNS function from depression during the prodromal detoxication phase to hyperexcitability observed during the withdrawal syndrome (dependence phase). The rapid transition from overt depression to overt hyperexcitability is a consequence of rapid removal of the drug from the system, and constitutes the basis of the reversal in the CNS function in both humans and experimental animals.

Alcoholism↗
PubMed1981

Effect of chronic ethanol administration on plasma levels of LH and the estrous cycle in the female rat.

Intragastric intubation of 4 or 8 g/kg of body weight of ethanol per day for 12 consecutive days disrupted the normal estrous cycle in female rats as monitored by vaginal epithelial cell changes. Plasma luteinizing hormone levels were unchanged suggesting that blood ethanol in the 50--100 mg/100 ml range acted as a direct gonadal toxin and not at the hypothalamic-pituitary gland level.

Alcoholism↗
PubMed1980

Suppression of the ethanol withdrawal syndrome by aliphatic diols.

Considerable evidence both in vitro and in vivo suggests that alcohols exert their intoxicating properties through an interaction with membranes. A wide range of alcohols and diols with divergent structures induce a virtually identical spectrum of intoxication signs. Because of their pharmacological similarities to ethanol, a number of aliphatic diols were tested to determine whether this class of compounds may have efficacy in suppressing the ethanol withdrawal syndrome in rats. All of the diols tested, when administered intragastrically, were effective without inducing intoxication. Furthermore, the withdrawal-suppressing potencies of these drugs were related to their ability to partition into membranes, the same property that determines their potency as depressants. Two halogenated hydrocarbons, which are amphiphiles like alcohols and diols, were both able to suppress the withdrawal syndrome, although several aliphatic hydrocarbons could not. The data suggest that short-chain aliphatic alcohols and diols may have a common site of action, possibly in a region in membranes near the aqueous membrane interphase.

Alcoholism↗
PubMed1979

Alterations in neurotransmitter activity after acute and chronic ethanol treatment: studies of transmitter interactions.

Acute and chronic ethanol treatment has multiple effects on the neurotransmitter systems in the nigrostriatal complex. A single dose of ethanol increases striatal dopamine release at low doses, but depresses it at high doses. In ethanol-dependent rats, dopamine release is accelerated during intoxication, but is reduced during a withdrawal syndrome. Concomitantly, high-affinity choline uptake, an index of cholinergic activity, is elevated at times when dopamine release is depressed. Changes in dopaminergic or cholinergic receptor activity do not induce or result from these effects. Neither has a role for GABA or substance P yet been implicated. The data suggest that interactions between at least two trasmitters in the caudate nucleus may occur after acute and chronic ethanol treatment.

Acetylcholine↗
PubMed1978

Sleep during chronic ethanol administration and withdrawal in rats.

After a priming dose, ethanol was administered at a rate relative to behavioral impairment for 4 days and its effects on sleep were monitored by EEG. EEG's during withdrawal indicated an initial sleep loss followed by a return of total sleep and a REM sleep rebound several days later.

Alcoholic Intoxication↗
PubMed1977

Comparison of ethanol withdrawal syndrome in humans and rats.

Physical dependence upon ehtanol induced in rats is in several respects similar to the tremulous and convulsive components of the ethanol withdrawal syndrome observed in man. These include short duration of the induction period, pattern of continuous ethanol consumption, rectilinear clearance of blood ethanol during prodromal detoxication phase and the onset of the ethanol dependence phase at relatively high blood ethanol concentrations. During the ethanol withdrawal period two phases are distinguished in both species: (1) Prodromal detoxication phase characterized by a spectrum of signs and responses of ethanol intoxication. (2) Ethanol dependence phase characterized by a spectrum of withdrawal signs and reactions. The successive onset and disappearance of the two sets of signs and reactions during both phases of the ethanol withdrawal period constitute a continuum of effects and responses and represent a reversal in the CNS function from the extremes of ethanol depression to the extremes of hyperexcitability.

Alcoholism↗
PubMed1977

The metabolism of biogenic amines in experimental animals and in human subjects during acute and chronic administration of ethanol.

Ethanol has been shown to induce a shift in catecholamine metabolism peripherally from normally oxidative pathways to reductive pathways. The mechanisms of this effect may result from competitive inhibition of aldehyde dehydrogenase by acetaldehyde. The shift in metabolism cannot be found in brain and alterations in catecholamine function may reflect changes in the turnover of these amines.

Acetaldehyde↗
PubMed1976

Suppression by 1,3-butanediol of the ethanol withdrawal syndrome in rats.

1,3-Butanediol was tested for its ability to suppress an ethanol with drawal syndrome. Male Sprague-Dawley rats were rendered physically dependent on ethanol by intragastric administration of ethanol at a dosage of 9 to 15 grams per kilogram per day over a 4-day period. A nonintoxicating oral dose of 1,3-butanediol at 4 grams per kilogram administered after elimination of ethanol from the blood was effective against the tremulous and conbulsive components of the ethanol withdrawal syndrome in all animals for 1 to 5 hours. This period coincided with the time of maximum severity of the withdrawal syndrome, as seen in the control animals.

Animals↗
PubMed1976

Temporal relationship of the induction of tolerance and physical dependence after continuous intoxication with maximum tolerable doses of ethanol in rats.

Rats were treated by intragastric intubation of a 20% ethanol solution in doses of 9-15 g/kg in 3-5 fractions for 1-7 days. Both tolerance and physical dependence were demonstrated after this treatment with the maximum tolerable doses to only a few days. Tolerance was assessed by signs of severity of intoxication: coma, loss of righting reflex, ataxia-3, ataxia-2, ataxia-1, sedation, and neutrality. During withdrawal, as blood ethanol concentrations approached 100 mg/dl the ethanol dependence phase was characterized by the onset of signs and responses of progressive severity: hyperactivity, tremors, spastic rigidity, and spontaneous convulsive seizures. A significant degree of tolerance was demonstrated for all signs of intoxication after 4 days of treatment, but did not reach maximum level even after 7 days. The severity of the withdrawal reactions intensified progressively to a maximum intensity after 4 days of treatment when as many as 72% of animals exhibited severe withdrawal signs and reactions including convulsive seizures. These different time courses suggest that tolerance and physical dependence are mediated through different mechanisms.

Alcoholism↗
PubMed1976

Brain concentrations of biogenic amine metabolites in acutely treated and ethanol-dependent rats.

1 Mass fragmentography was used to measure whole brain concentrations of some of the major metabolites of tyramine, octopamine, dopamine and noradrenaline in acutely treated and in ethanol-dependent rats. 2 Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p-hydroxphenylacetic and p-hydroxymandelic acid (metabolites derived from tyramine and octopamine respectively). The effect on catecholamine metabolites was marked and therefore suggests that ethanol is selective in its effect on central metabolism of biogenic amines. 3 Acute ethanol treatment significantly increased brain concentration of homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Vanilmandelic acid (VMA) was not affected. All four metabolites (HVA, DOPAC, MHPG and VMA) were increased in the brains of rats rendered dependent on ethanol while still intoxicated (blood ethanol levels above 200 mg/dl). In ethanol-dependent rats undergoing ethanol withdrawal syndrome (no ethanol present in blood), the brain concentrations of HVA and DOPAC were normal while those of MHPG and VMA continued to be elevated. 4 From the decline in the concentrations of HVA and DOPAC after 50 mg pargyline/kg in control rats and rats acutely treated with ethanol, it was concluded that ethanol has no effect on the transport of phenolic acids across the blood brain barrier. 5 No reversal in the metabolism of catecholamines from an oxidative to a reductive pathway, analogous to that produced by ethanol in the periphery, could be established in the brain. 6 The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.

Animals↗
PubMed1975

Induction of physical dependence upon ethanol and the associated behavioral changes in rats.

This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9-15 g/kg in 3-5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, greater than 640; coma, 780-460; loss of righting reflex, 640-400; ataxia 3-1, 570-250; sedation 340-190; neutrality, 220-130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.

Alcoholic Intoxication↗
PubMed1975

Metabolic correlates of ethanol, acetaldehyde, acetate and methanol in humans and animals.

Following the administration of alcoholic beverages, ethanol exerts a number of direct and indirect effects on the body and in turn, ethanol is itself metabolized. Liver and brain are twomajor organs which are immediately concerned with the effects of ethanol. Ethanol acts as CNS depressant and as a source of energy. Since the metabolism of ethain the liver proceeds at a constant rate until completion,acetate is produced regardless of energy requirements of the body. Thus, ethanol plays the role of an aberrant nutrient. Although ethanol has no effect on oxygen consumption in the liver, it severely suppresses the productionof carbon dioxide in the Krebs cycle resulting in the corresponding suppressionof respiratory quotient. This indicates that ethanol diverts the utilizationof oxygen for the oxidationof reducing, equivalents which accumulate as a consequence of increased formation of NADH. This is reflected in the shift from the oxidative to reductive components of a number of oxido-reductive couples, e.g.: pyruvate-lactate, oxaloacetate-malate and acetoacetate-beta-hydroxybutyrate. These actions of ethanol are exarcerbated by the fact that the metabolism of ethanol is also associated with the diversion of the availability of a number of enzymes and coenzymes from the metabolism of endogenous substrates towards the metabolism of metabolites of ethanol, thus resulting in the competitive inhibitionof a number of enzyme catalyzed reactions, e.g., inhibition of methanol metabolism during long-term consumption resulting in the acumulation of methanol in body fluids; shift in the peripheral metabolism of biogenic amines from oxidative to reductive pathways; and formation of aberrant neurotransmitters (in vitro); inhibition of the oxidation of fatty acids in the liver...

Acetaldehyde↗
PubMed1975

Effect of peripheral ethanol metabolism on the central nervous system.

The main symptoms of ethanol intoxication, tolerance, and physical dependence presumably, derive from the effects of ethanol on the central nervous system. It is not known clearly how and to what extent these effects are caused by ethanol itself or by its metabolic derivatives, chiefly acetaldehyde, formed in the liver, and transported into the brain through the blood stream. Since the concentrations of acetaldehyde found in the blood and brain of human subjects and experimental animals are approximately 44 times lower than the lowest effective concentrations found in in vitro experiments, it remains to be established whether acetaldehyde derived under in vivo conditions from the oxidation of ethanol in the liver plays any significant role in suppressing the respiratory metabolism or other metabolic pathways in the brain. It is concluded that the site of ethanol effects on the central nervous system is probably associated with that part of the metabolic system that is dependent on normal functioning of the neuronal cell membrane and probably has little relation to the peripheral or central metabolism of ethanol.

Acetates↗