Electroencephalographic study of naloxone effects in the recovery of an acute alcoholic intoxication

Experimental assays analysing EEG changes during the recovery of an acute alcoholic intoxication were carried out in three groups of cats: 1) Recovery of acute alcoholic intoxication produced by continuous intravenous perfusion of ethanol, 0.06 g/kg/min, during 20 minutes. 2) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), just after finishing alcohol perfusion. 3) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), 15 min after finishing perfusion. Naloxone administered after an acute alcoholic intoxication worsens the recovery of EEG parameters; 1-2 (p less than 0.05), 1-3 (p less than 0.05).     

Effect of alcoholic intoxication on the body's natural resistance to exposure to infectious and toxic agents]

The influence of alcoholic intoxication on the resistance of albino mice to bacterial toxins and staphylococcus cultures was investigated. Five-day administration of 40% ethyl alcohol to the animals was accompanied by a significant increase of their resistance to the intoxication caused by C1. perfringens toxins and staphylococcus. Thirty-day alcoholic intoxication promoted a marked reduction of albino mice resistance to the both toxins used and the staphylococcus cultures.     

Effect of supplemental magnesium on the kidney levels of cadmium, zinc, and copper of mice exposed to toxic levels of cadmium

In this report, we present the results of our investigations on the effect of Mg pretreatment on Cd and bioelements (Cu and Zn) contents in kidney of mice exposed to acute and subacute Cd intoxication. Acute intoxication was performed on male Swiss mice given a single oral dose of 20 mg Cd/kg body weight and mice given the same dose of Cd but pretreated with 40 mg Mg/kg body weight. For subacute intoxication one group of mice was given 10 mg Cd/kg body weight every day, for 2 wk, and the other one received the same dose of Cd after oral Mg intake of 20 mg/kg body weight. Cd, Cu, and Zn content was determined in kidney by atomic absorption spectrophotometry. In acute Cd intoxication, Mg pretreatment resulted in significant decrease of Cd in kidney after 4 and 6 h, compared with animals given only Cd. Under the condition of subacute Cd intoxication, Mg supplementation reduced Cd kidney content after 2 wk for about 30%, compared with animals treated with Cd only. The effect of Mg on Cu and Zn kidney content was also beneficial.     

Acute alcoholic intoxication and naloxone. Effects on visual evoked potential.

Experimental assays analyzing visual evoked potential (VEP) changes during an acute alcoholic intoxication were carried out in two groups of cats: One with continuous ethanol (0.06 g/kg.min) i.v. perfusion. Another one with a naloxone (400 micrograms/kg) i.v. injection 10 min before ethylic perfusion. Naloxone potentiates alcohol effects on VEP parameters, and on the appearance of isoelectric postpotential and flat VEP.     

Gamma-L-glutamyl-taurine (Litoralon) affects conditioned taste aversion in rats

The dipeptide gamma-L-glutamyl-taurine (Litoralon) reduced neophobia of rats at a dose of 5.0 mg/kg (i.p.) in a "one-bottle forced choice paradigm" for conditioned taste aversion (CTA), but did not significantly affect the rats' "memory" of intoxication following chronic treatment at doses of 0.05, 0.50 and 5.00 mg/kg (i.p.). Acute treatment with Litoralon (10-1000 micrograms/kg, i.p.) did not affect CTA checked in a "two-bottle test", when administered immediately following the unconditioned stimulus (LiCl injection). In contrast, when given 90 min prior to the retention test, the injection of Litoralon (50.0 micrograms/kg) and gamma-aminobutyryl ethanolamine phosphate (100 and 500 micrograms/kg) resulted in a significantly higher intake of saccharin solution by the rats. This effect is comparable to the action of diazepam tested in the same experimental procedure. The results support our hypothesis about the anti-conflict potencies of these dipeptides, exerted by reducing aversion of phobia and/or the anxiety level of the animals in the experimental situation.     

Ultrastructure of the nuclei of neurons and glial cells of the cerebral cortex during experimental alcoholic intoxication

Nuclear ultrastructure of neurons and glial cells of the rat sensomotor cortex was studied under chronic alcoholic intoxication. During 24 h the animals drank up about 10 ml of 20 degrees alcohol. In the course of prolonged alcoholic intoxication there occurred processes leading to deformation of the nuclei of neurons and glial cells and to the deficiency of nuclear and cytoplasmic substances. These changes are regarded as an atrophic process responsible for the corrugation of the nucleus and diminution of the cell size.     

Effect of the destruction of the brain serotoninergic system on the alcohol consumption by rats in the early periods of experimental alcoholism

Albino noninbred rats were divided into groups, according to the duration of alcoholic anesthesia (4.5 g/kg i.p.), of predisposed (195.6 min) and non-predisposed (69.1 min) to voluntary intake of alcohol. Another group included animals screened for 21 days according to the level of intake of 15% ethanol under the conditions of free choice between alcohol and water (6.15 and 2.62 g/kg pure ethanol per day, respectively). The animals were subjected to electro-coagulation of the dorsal or magnus raphe nucleus or were injected with 5,6-dihydroxytryptamine--DNT (75 micrograms/microliters) into the ventricles of the brain. It was established that in rats non-predisposed to alcohol intake, the destruction of the raphe nuclei, of the dorsal in particular, or injection of DOT to animals with a weak alcoholic motivation produces a dramatic increase in alcohol intake. In alcohol intake predisposed rats and in animals with a high level of alcohol use, analogous exposures do not bring about any significant differences in alcohol intake. The data obtained indicate that the reduced serotonin content in the brain is associated with an increase in the level of alcoholic motivation.     

Subacute alcoholic intoxication in rats: effect of an intravenous injection of glucagon or adrenaline]

We have studied the hyperglycemic effect of glucagon (20 microgram/kg) and adrenaline (5 microgram/kg/mn/3 mn) on the rat subjected to a subacute alcoholic intoxication (6,4 g/kg by day during 12 days). The hyperglycemic action of the glucagon is increased while that of the adrenaline slightly decreased. So, the alcoholic intoxication allows to dissociate the both mechanisms of the glycogenolytic action of both hormones. Two hypothesis are brought forward in the discussion.     

Comparison of the incidence of 5-azacytidine-induced exencephaly between MT/HokIdr and Slc:ICR mice.

The incidence of 5-azacytidine-induced exencephaly was compared between MT/HokIdr strain (MT) and Slc:ICR strain (ICR) mice. MT mice have a genetic predisposition for exencephaly, but ICR mice do not. Pregnant mice were given 5-azacytidine (1 mg/kg to 100 micrograms/kg) injected intraperitoneally on Day 7.5 of gestation (vaginal plug day = Day 0.5), and fetuses were observed for external malformations on Day 18.5 of gestation. One hundred micrograms/kg 5-azacytidine induced exencephaly in MT mice but not in ICR mice, and 1 mg/kg 5-azacytidine resulted in resorptions in MT mice but caused exencephaly in ICR mice. These results indicated that MT mice had 10-fold more sensitivity to 5-azacytidine than ICR mice. It seems likely that less than effective doses of teratogens for animals without genetic predispositions are still effective in inducing malformations in animals with a genetic predisposition for malformations. When 4-somite-stage embryos of both MT and ICR mice were cultured in rat serum supplemented with 5-azacytidine, 0.02 micrograms/ml 5-azacytidine induced the failure of closure of cephalic neural tube in MT embryos but not in ICR embryos, and 0.2 micrograms/ml 5-azacytidine induced severe growth retardation in MT embryos but in ICR embryos it only induced embryos with smaller heads and fewer somites than in control. These results indicated that MT mouse embryos in culture also had a 10-fold-increased sensitivity to 5-azacytidine compared with ICR mouse embryos, suggesting maternal effects play no significant role in their increased sensitivity to 5-azacytidine.     

Forensic considerations on the comparison of “serum γ-glutamyltranspeptidase” (“γ-GT”) activity in experimental acute alcoholic intoxication and in alcoholic car drivers who caused road accidents

The authors studied blood alcohol levels and serum γ-GT activity in 18 drivers who caused car accidents while intoxicated, and in 20 young volunteer subjects without any hepatic damage, in which an acute alcoholic intoxication was present.In most of the drivers the serum γ-GT activity was significantly higher than in the volunteers, which strongly suggests a chronic alcoholic intoxication.In the 20 volunteers, who were occasional drinkers, the serum γ-GT activity did not show pathological values even in a state of heavy intoxication.According to the authors, the serum γ-GT determination could be made obligatory by law, in order to differentiate between acute or chronic alcoholic intoxication. Should an intoxicated driver be found guilty of an offence, this fact could aggravate the circum-stances. Furthermore serum γ-GT activity determination could be used as an evaluating parameter in granting driving licences.     

Protective action of rifampicin in experimental rabies infection of albino mice

The paper presents the results of the experimental study of the action of rifampicin on the process of rabies infection in albino mice contaminated with 1-10 LD50 of the fixed rabies virus. Exposure to rifampicin in doses of 250 and 500 micrograms/mouse (35-70 mg/kg) resulted in survival of 66.7 and 83.4 per cent of the animals respectively while in the controls it did not exceed 16.6 and 25.0 per cent. The average life-span of the albino mice treated with the antibiotic increased 1.6-2.4-fold in comparison with the controls. The chemotherapeutic index of rifampicin representing the ratio of the maximum tolerance dose to the minimum dose providing the protective action was equal to 20. The protective action was observed either after administration of the antibiotic according to the treatment-and-prophylaxis scheme or after administration of its 2- or 3-fold dose once a day immediately after the contamination.     

Contractile function, glucose consumption and lactate release by the isolated rat heart during different regimens of alcohol administration and after discontinuation of ethanol

Acute or chronic intoxication of rats with ethanol (intragastric administration at a dose of 8 g/kg or free-choice drinking of 10% ethanol for 3 months) produced no significant changes in contractile function, glycogen content, glucose uptake and lactate release in isolated hearts. Withdrawal syndrome simulated in rats following a short period of severe intoxication with ethanol at a dose of 4-5 g/kg twice daily has demonstrated a 15 and 28% decrease in peak systolic pressure and tension time index, respectively. In this case glucose uptake and lactate release were 2 times higher. Changes in glycogen level were observed three days after the last ethanol administration. The rats, survived after the abstinence period, revealed areas of perivascular myocardial necrosis. It is concluded that withdrawal syndrome plays an important role in pathogenesis of alcoholic cardiomyopathy.     

Antibodies to catecholamines and serotonin during alcoholic intoxication in animals with different predispositions to the development of experimental alcoholism

Experiments on C57Bl/6, CBA and DBA/2 mice characterized by different preferences for ethanol have shown that during chronic administration of alcohol to animals with natural ethanol motivation (strain C57Bl/6) the level of antibodies to catecholamines and serotonin was increased on the 3rd month of ethanol intoxication, with the voluntary alcohol consumption in mice decreased by this time. On the contrary in mice rejecting alcohol (strains DBA/2, CBA) no antibodies to catecholamines and serotonin have been found.     

Retinol/ethanol drug interaction during acute alcohol intoxication in mice involves inhibition of retinol metabolism to retinoic acid by alcohol dehydrogenase

Substantial evidence indicates that one consequence of alcohol intoxication is a reduction in retinoic acid (RA) levels. Studies on the mechanism have shown that chronic ethanol consumption induces P450 enzymes that increase RA degradation, thus accounting for much but not all of the observed decrease in RA. A reduction in RA synthesis may also be involved as ethanol competitively inhibits retinol oxidation catalyzed by alcohol dehydrogenase (ADH) in vitro. This may be important during acute ethanol intoxication and may contribute to adverse retinol/ethanol drug interactions. Here we have examined mice for the effect of either acute ethanol intoxication or Adh1 gene disruption on RA synthesis and degradation. RA produced following a dose of retinol (50 mg/kg) was reduced 87% by pretreatment with an intoxicating dose of ethanol (3.5 g/kg). RA produced in Adh1-null mutant mice following a 50-mg/kg dose of retinol was reduced 82% relative to wild-type mice, thus similar to wild-type mice pretreated with ethanol. Reduced RA production was associated with increased retinol levels in both ethanol-treated wild-type mice and Adh1-null mutant mice, indicating reduced clearance of the retinol dose. RA degradation following a dose of RA (10 mg/kg) was increased only 42% by ethanol pretreatment (3.5 g/kg) and only 26% in Adh1-null mutant mice relative to wild-type mice. These findings demonstrate that the reduced RA levels observed during acute retinol/ethanol drug interaction are due primarily to a decrease in ADH-catalyzed RA synthesis and secondarily to an increase in RA degradation.     

Placental changes due to administration of diethylstilbestrol (DES)

Pregnant mice were injected with 12.5 micrograms DES/kg body weight or 25 micrograms DES/kg body weight daily from gestation day 9 through day 12 or 16 and sacrificed on day 13 or 17. Placentas of DES treated animals were smaller than controls, the effect being dose dependent. Histologic changes in 13 gestation day placentas regional thinning of the labyrinth associated with an apparent inhibition of trophoblast maturation and development of fetal blood vessels. Knots of mononuclear cells form in the labyrinthine region of 13 day placentas exposed to the higher dose of DES. By 17 days gestation, coagulative necrosis is common in the decidua basalis, being most severe in those animals receiving 25 micrograms DES/kg. In many placentas the labyrinthine region is absent. The only remaining elements are trophoblast cells, giant cells and glycogen-containing cells. Fetal deaths associated with the lower dose of DES increased with time whereas 100% fetal mortality was associated with the higher dose.     

Mutagenic activity of propylene oxide in bacterial and mammalian systems.

Propylene oxide is used extensively in the chemical and food manufacturing industries, but relatively little is known of its ability to interact with genetic material. Studies were undertaken to investigate its ability to induce gene mutations and primary DNA damage in bacteria and chromosomal damage in mammalian cells. The induction of base-substitution mutations was demonstrated in spot tests with strains of Salmonella typhimurium and Escherichia coli at 700 micrograms/plate of propylene oxide; inclusion of a preparation of rat-liver microsomes and cofactors (S9 mix) was without significant effect on this response. A linear dose--response relationship was recorded in plate tests with S. typhimurium strains TA100 and TA1535 over the range 100--750 micrograms/plate. After addition to dividing lymphocytes in cultures established from human peripheral blood, propylene oxide caused dose-related chromosomal damage, detected at 1.85 and 9.25 micrograms/ml. Oral administration of propylene oxide at 2 x 100, 2 x 250 or 2 x 500 mg/kg to male mice produced no detectable increases in the incidence of micronucleated, polychromatic erythrocytes in bone marrow. A male mouse dominant lethal test employing oral doses of 50 or 250 mg/kg/day for 14 days gave no evidence of mutagenic action on sperm. Intraperitoneal injections of propylene oxide at 2 x 300 mg/kg induced increased numbers of micronucleated erythrocytes in mice, but lower doses given by this route had no such effect. Possible reasons for the contrasting findings in vitro and in vivo are discussed.     

Effect of chronic alcoholism on the state of the microcirculatory bed of the myocardium

Ultrastructure of myocardial capillaries of rats was studied in cases of chronic alcohol intoxication, experimental alcoholic cardiomyopathy (ACM) and its correction with antioxidants (vitamin E, dibunol). Alterations in the microcirculatory bed were similar in all groups of animals irrespective of disturbances in cardiomyocytes. Cardiomyocyte ultrastructure was improved after treatment with antioxidants, but capillary bed was the same as in untreated animals. High dibunol doses caused the onset of perivascular sclerosis. Disturbances in the microcirculatory bed are, probably, the first step in the determination of ACM pathogenesis and therapy of ACM must be directed at the correction of both alterations of cardiomyocytes and capillary bed.     

Glutamyl transferase and acetylcholinesterase activity in various areas of the rat brain in alcoholic intoxication

Albino mongrel rats were used for the determination of the gamma-glutamyl transferase (gamma-GTF) and acetylcholine esterase (AChE) activities in various brain areas (cerebral hemispheres, cerebellum, hippocampus, brain stem) during acute (1.5; 4 and 6 g/kg i. p.) and chronic (15 months) alcoholic intoxication and alcohol withdrawal (24-48 h, 4 and 8 days). An increase or a decrease in the activity of these two enzymes in the various rat brain areas depends on the dose of ethanol and the time of its action. The activity of gamma-GTF grew in all brain areas during chronic ethanol intoxication; the activity of AChE was also enhanced in three brain areas but it was diminished in cerebral hemispheres. Alcohol withdrawal caused diverse changes in the activities of these two enzymes in various areas of the brain. A tendency to normalization of the gamma-GTF and AChE activities is manifested 4-8 days after alcohol withdrawal.     

Fluorodeoxyuridine-induced sex differences in baseline sister-chromatid exchanges in C57BL/6 mice and Chinese hamsters

The baseline sister-chromatid exchanges (SCEs) and the percentage of first (M1), second (M2) and third or higher metaphase (M3+) chromosomes were analysed in bone-marrow cells of male and female C57BL/6 mice and Chinese hamsters following serial intraperitoneal injections of 40 micrograms/g body weight (b.w.) of 5-bromo-2'-deoxyuridine (BrdUrd) and 2 micrograms/g b.w. of 5-fluorodeoxyuridine (FdUrd) or 40 micrograms/g b.w. of BrdUrd and 10 micrograms/g b.w. of deoxycytidine (dC). Female animals receiving BrdUrd/FdUrd showed significantly higher (P less than 0.01) baseline SCEs compared to the other groups. No sex difference in the baseline SCEs was found in animals treated with BrdUrd/dC. The distribution patterns of M1, M2 and M3+ metaphases in BrdUrd/FdUrd-treated animals differ significantly from those in BrdUrd/dC-treated animals.     

Development of nanostructured phosphorite: Study of the safety of application

A nanostructured mineral food supplement with a particle size of 60.0–120.0 nm was manufactured from phosphorite by ultrasonic dispersion. It was found that intragastric administration of nanostructures phosphorite to mice is relatively safe: clinical signs of intoxication appeared after a single administration of the preparation only at a dose of 90 mg/kg; a dose of 150 mg/kg caused death of 8% of mice, in which injuries of organs of the gastrointestinal tract were observed. When the preparation was administered subcutaneously, intramuscularly, or intraperitoneally, small phosphorite conglomerates and inflammation of the surrounding tissues and organs were observed at the injection site. Death of 25% of animals was observed in the group of mice which received intraperitoneal injections of nanophosphorite at a dose of 200 mg/kg.