Ethanol diminishes the toxicity of the mushroomAmanita phalloides

Summary Survival of mice after lethal doses of a lyophilizate fromAmanita phalloides (death cap) was markedly increased by single doses of ethanol applied 30 min before or 5 min after the mushroom. Hepatic histopathological damage (confluent necrosis) was largley prevented. Acute, but not chronic, consumption of ethanol may thus influence favorably the outcome of death cap poisoning and should be taken into consideration in the evaluation of therapeutic measures.     

Dexamethasone protection against the acute lethality of ethanol in mice

Summary The administration of dexamethasone (DXM, 2.00 mg/kg) 1 h prior to the injection of lethal doses of ethanol was found to offer complete protection against ethanol toxicity at doses up to 5.25 g/kg and partial protection using higher doses. It is suggested that DXM central action might be involved in the protection against ethanol toxicity.Supported by a grant from U.S. National Aeronautics and Space Administration.     

Changes in the activities of protein kinase modulators in the cerebellum of mice due to ethanol, caffeine, or phenobarbital administration.

Decreased activities of both the inhibitory modulator of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (A-PK) as well as the stimulatory modulator of guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase (G-PK) from the mouse cerebellum were noted due to the administration of excessive doses of ethanol, caffeine, and phenobarbital for up to 28 days. The dose-dependent of the inhibition of A-PK or the stimulation of G-PK was observed as a function of the amount of protein kinase modulators in the cerebellum of mice receiving different doses of ethanol.     

Effect of glucagon on ethanol oxidation in isolated rat liver cells

Summary Addition of glucagon 5 min after ethanol was found to stimulate the rate of ethanol oxidation in hepatocytes isolated from starved rats. This stimulation is of the same order of magnitude as that mediated by asparagine. The glucagon effect is suppressed by antiproteolytic agents such as insulin or NH₄Cl. The stimulatingeffect of glucagon on ethanol oxidation is probably liked to enhanced proteolysis andan elevated glutamate level in the hepatocytes.Acknowledgments. this investigation was supported by grants from the Institut de la Santé de la Recherche Médicale, the Scientific Council of the Faculté de Médecine Paris-Ouest and the Ecole Pratique des Hautes Etudes (3rd section).     

Protection of rat gastric mucosa against ethanol injury by the new synthetic prostaglandin MDL 646

Oral administration to fasted rats of absolute ethanol produces extensive necrotic lesions of gastric mucosa as well as a massive leakage of proteins and mucus glycoproteins into gastric lumen. When the new synthetic prostaglandin MDL 646, belonging to the PGE1 series, is administered intragastrically (2 or 10 micrograms/kg) 30 min before ethanol administration, a significant protection of rat gastric mucosa against alcohol injury is observed.     

Protection of rat gastric mucosa against ethanol injury by the new synthetic prostaglandin MDL 646

Summary Oral administration to fasted rats of absolute ethanol produces extensive necrotic lesions of gastric mucosa as well as a massive leakage of proteins and mucus glycoproteins into gastric lumen. When the new synthetic prostaglandin MDL 646, belonging to the PGE₁ series, is administered intragastrically (2 or 10 g/kg) 30 min before ethanol administration, a significant protection of rat gastric mucosa against alcohol injury is observed.This work was supported in part by a contribution from Ministero della Pubblica Istruzione (MPI), Rome, Italy.     

Changes in the activities of protein kinase modulators in the cerebellum of mice due to ethanol,caffeine, or phenobarbital administration

Summary Decreased activities of both the inhibitory modulator of adenosine 35-monophosphate (cAMP)-dependent protein kinase (A-PK) as well as the stimulatory modulator of guanosine 35-monophosphate (cGMP)-dependent protein kinase (G-PK) from the mouse cerebellum were noted due to the administration of excessive doses of ethanol, caffeine, and phenobarbital for up to 28 days. The dose-dependence of the inhibition of A-PK or the stimulation of G-PK was observed as a function of the amount of protein kinase modulators in the cerebellum of mice receiving different doses of ethanol.Acknowledgments. This work was supported by a grant (RR 08119-06-PK modulator project) from NIH, USA. J.L. Williams, T. Floyd-Jones, C.F. Duggans, D.L. Boone, and S.O. Smith were prebaccalaureate trainees of MBS program. Authors thank Dr J.F. Kuo of Emory University for encouragement in this project.     

Behavior and endocrine effects of 3,4,5-trimethoxyamphetamine in male mice

Summary Effects of single doses of 50 and 100 mg/kg of TMA given i.p. were noted in male albino mice after 40 min and 2 1/2 h. Locomotor activity was significantly altered and biochemical tests indicated stimulatory effects on adrenocortical and adrenomedullary functions due to TMA.     

Effect of vincristine on glucose-induced insulin secretion in man

Summary 60 min after the injection of therapeutic doses of vincristine for cancer chemotherapy, there is a reduction of the total (40%) and of the acute phase (43%) areas of insulin secretion induced by a 5-g i.v. glucose load, and the constant of glucose utilization is reduced by 25%. No differences are observed after 3 5-g i.v. glucose loads given at hourly intervals in control subjects.Acknowledgment. The authors are grateful to Mr S. Castiglioni and to Miss Maria Luisa Fuser for their skillful technical assistance.     

Behavior and endocrine effects of 3,4,5-trimethoxyamphetamine in male mice.

Effects of single doses of 50 and 100 mg/kg of TMA given i.p. were noted in male albino mice after 40 min and 2 1/2 h. Locomotor activity was significantly altered and biochemical tests indicated stimulatory effects on adrenocortical and adrenomedullary functions due to TMA.     

Kinetics of BRCA1 regulation in response to UVC radiation

To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to increasing doses of ultraviolet C. We observed an increase in BRCA1 protein levels above 78 J/m². This increase was observed as early as 5 min after irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent with the previously published data. By pretreating with cycloheximide prior to irradiation, we observed a decrease in the protein half-life, from 3.5 h to 53 min, suggesting that a decrease in protein half-life may cause the lower levels of BRCA1 after irradiation. We also observed an increase in BRCA1 mRNA within 15 min of irradiation, followed by a decrease after 4 h. These data suggest that newly translated protein may contribute to increases in BRCA1 protein levels. The very rapid changes in BRCA1 support its role as a sensor of DNA damage, as opposed to being a repair gene. Received 6 April 2000; received after revision 23 May 2000; accepted 23 May 2000     

Ethanol and liver protein synthesis in vivo

Summary Ethanol was administered i.p. to adult roosters during hormonally induced vitellogenin synthesis. At moderate doses, ethanol had no influence on the synthesis of vitellogenin nor did it cause alterations in the size distribution of liver polyribosomes.This was supported in part by a grant from the Foundation for Alcohol Studies, Finland.     

Effect of ethanol on taurine concentration in the brain

Summary The taurine concentration in the brain was decreased in ethanol-dependent rats, but returned to normal soon after withdrawal of ethanol. It was not affected by acute ethanol administration.This research was supported by a grant from the Taisho Pharmaceutical Co., Ltd., Tokyo.     

Effects of ethanol and acetaldehyde on cultured pre-implantation mouse embryos

Pre-implantation 2-cell stage mouse embryos, obtained from superovulated CF-1 mice, were exposed to ethanol and acetaldehyde through the culture medium for 60 min followed by a 105-h incubation period. Control and ethanol exposed embryos survived equally well in ethanol concentrations as high as 800 mg/100 ml medium and acetaldehyde levels up to 10 mg/100 ml medium.     

Effects of ethanol and acetaldehyde on cultured pre-implantation mouse embryos

Summary Pre-implantation 2-cell stage mouse embryos, obtained from superovulated CF-1 mice, were exposed to ethanol and acetaldehyde through the culture medium for 60 min followed by a 105-h incubation period. Control and ethanol exposed embryos survived equally well in ethanol concentrations as high as 800mg/100 ml medium and acetaldehyde levels up to 10 mg/100 ml medium.     

Effect of ethanol intake on phenytoin metabolism in volunteers.

Ingestion of ethanol, 1 g/kg, did not influence the phenytoin half-life in 5 volunteers after single i.v. administration of 3 mg/kg phenytoin. The control phenytoin half-life was 12.4 h (SD +/- 4.4); with ethanol ingestion it was 12.3 h (SD +/- 5.2).     

Possible role of intestinal alkaline phosphatase activity in thiamine transport.

Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca++-ATPase activity and Ca++-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg++-, Ca++-and (Na+ + K+)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca++-ATPase activity, is not related to Ca++-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Effects of C1-C8 n-alcohols on the growth of 3T3 mouse fibroblasts]

The effect of C1-C8 n-alcohols on 3T3 cell growth is studied using flow cytofluorometry. Methanol and ethanol markedly lengthen either the duration of G1, or that of G2+ M when present in relatively higher doses. The effect of longer chains is always to increase G2+M significantly. This may be due to deviations depending on alcoholic chain length in membrane lipid fluidity.     

Time courses and refractoriness of enhanced vascular permeability induced by histamine,serotonin and bradykinin in synovialis of the rat

Summary Enhanced vascular permeability induced in synovialis of the rat by histamine and serotonin lasts 5–15 min and that induced by bradykinin less than 5 min. Synovialis of the rat becomes refractory to the permeability effects of repeated doses of each of these substances in the hour following initial application.This work was carried out while L.P.B. was supported by a Medical Postgraduate Scholarship from the National Health and Medical Research Council of Australia.     

Stress-induced increase in noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis

Summary The hypothalamic microdialysis of conscious rats was used to investigate the effects of immobilization stress (20 min) on extracellular noradrenaline(NA) levels. The stress significantly increased NA levels relative to basal efflux by 106% and this elevation continued for 40 min after release from stress.