More on the costs of beta-lactam antibiotics.
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Ceftizoxime↗
Biomedical subjects
R D Malcolm
Publications and source records attributed to R D Malcolm.
Ethanol withdrawal in mice precipitated and exacerbated by hyperbaric exposure.
Mice were fed an ethanol-containing liquid diet for 9 days. On removal of the diet, exposure to 12 atmospheres absolute of a mixture of helium and oxygen precipitated earlier withdrawal, increased withdrawal scores for the first 6 hours, and increased the peak withdrawal intensity compared to dependent animals exposed to control conditions. The enhanced withdrawal did not appear to reflect alterations in ethanol elimination, oxygen or helium partial pressures, body temperature, or general excitability. These results extend to chronically treated animals the evidence that hyperbaric exposure antagonizes the membrane actions of ethanol.
Animals↗
Reduced lethality from ethanol or ethanol plus pentobarbital in mice exposed to 1 or 12 atmospheres absolute helium-oxygen.
The present experiments investigated the effects of 1 and 12 atmospheres absolute (ATA) helium-oxygen on potentially lethal doses of ethanol given alone or in combination with pentobarbital. Drug-naive, male C57BL/6J mice were injected IP with 5.4-6.5 g/kg ethanol, 4.5-6.9 g/kg ethanol plus 20 mg/kg pentobarbital, or 50-110 mg/kg pentobarbital plus 2.5 g/kg ethanol. Following injection, the mice were placed into chambers and exposed to environments of 1 ATA air, 1 ATA helium-oxygen, or 12 ATA helium-oxygen. Exposure to 1 or 12 ATA helium-oxygen significantly reduced the lethal effect (percent mortality at given doses and LD50) of ethanol given alone or with 20 mg/kg pentobarbital when compared to animals exposed to 1 ATA air. The pattern and degree of reduction in lethality for the 1 and 12 ATA helium-oxygen treatments were similar, suggesting that the antagonism resulted from increased helium or decreased nitrogen and not from increased atmospheric pressure. Exposure to these environments did not reduce lethality in mice given 2.5 g/kg ethanol in combination with relatively high doses (50-110 mg/kg) of pentobarbital. These findings suggest that helium-oxygen breathing mixtures may be useful in the treatment of some overdose patients.
Animals↗
The importance of experience in the development of tolerance to ethanol hypothermia.
Studies were conducted to determine if an animal has to experience a reduction in body temperature during the acquisition period in order to develop tolerance to the hypothermic effect of ethanol. Adult, drug-naive C57BL/6J mice were injected with 2.6 or 3.6 g/kg ethanol or normal saline once daily for 6 days. During the tolerance acquisition period, days 1-5, mice were placed into warmed chambers (36 +/- 2(0)C) which offset ethanol hypothermia or into chambers at room temperature (24 +/- 1(0)C). On day 6, all mice were injected with ethanol and placed into chambers at room temperature. Tolerance to ethanol's hypothermic effect did not develop in the ethanol-warm acquisition group. These mice had a significantly greater degree of hypothermia on test day than the ethanol-room temperature acquisition group, which showed tolerance, and their degree of hypothermic response was similar to that of mice injected with saline during acquisition. The differences between groups cannot be attributed to pharmacokinetic alterations or to conditioned responses since there were no differences between groups in blood or brain ethanol concentrations on test day and all groups were exposed to the same acquisition and test situations. These results extend previous work to suggest that the development of tolerance to the physiological, as well as behavioral, aspects of ethanol intoxication requires more than simple exposure to ethanol.
Animals↗
Temperature dependence of ethanol lethality in mice.
The present study provides systematic evidence indicating a direct relationship between environmental temperature, rectal temperature and ethanol lethality. Male, C57 BL/6J mice, previously housed at room temperature (23 +/- 1 degree C), were injected intraperitoneally with 4.8 to 9.2 g kg-1 ethanol and then exposed for 24 h to ambient temperatures that did not appreciably exceed the thermally neutral range for sober mice (20 to 35 degrees C). There was a direct relationship between temperature and ethanol lethality at 8 and 24 h after injection. The 8 h LD50 increased by 64%, from 5.3 to 8.7 g kg-1, as environmental temperature decreased from 35 to 20 degrees C. The 24 h LD50 increased by 51%, from 5.3 to 8.0 g kg-1, across this temperature range. Each 5 degrees C reduction in ambient temperature induced a significant decrease in the rectal temperature of ethanol-injected mice. Mean rectal temperature ranged from 2.2 degrees C above baseline at an ambient temperature of 35 to 15 degrees C below baseline in the 20 degrees C environment. Ethanol induced a significant dose-related hypothermia in mice exposed to the 20, 25 and 30 degrees C environments but did not produce hypothermia in animals kept in the 35 degrees C environment. These findings indicate that the potency of potentially lethal ethanol doses varies with body temperature in accordance with partition and membrane expansion-fluidization theories of anaesthesia.
Animals↗
An in vivo function of glucagon-induced phenylalanine: pyruvate transaminase in p-chlorophenylalanine-treated rats.
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Enzyme Induction↗
Hyperbaric ethanol antagonism in mice: studies on oxygen, nitrogen, strain and sex.
Male and female C57BL/6J and male BALBc/J mice were injected with 3.6 g/kg ethanol or saline and exposed to 1-10 atmospheres absolute (ATA) air, to 1 ATA 80% helium-20% oxygen, or to 12 ATA helium-oxygen having oxygen partial pressures between 0.5 and 18 times normal. Hyperbaric helium-oxygen significantly reduced sleep-time and increased wake-up brain ethanol concentrations in all mice tested. The degree of antagonism was not enhanced by increasing the oxygen partial pressure. Hyperbaric air increased sleep-time and decreased wake-up brain ethanol concentration in C57 mice. Hyperbaric air induced a pressure-related lethal effect beginning at 6 ATA in intoxicated BALBs. These findings demonstrate that hyperbaric ethanol antagonism extends across strains and sexes, that the degree of antagonism cannot be enhanced by increasing the oxygen partial pressure, and that air is not suitable as an antagonistic hyperbaric gas. The findings are consistent with membrane theories of anesthesia.
Air Pressure↗
Hyperbaric ethanol antagonism: role of temperature, blood and brain ethanol concentrations.
Three studies investigated the mechanism of hyperbaric ethanol antagonism. C57 Bl/6j mice were injected intraperitoneally with 3.6 g/kg ethanol and were exposed to 1-12 atmospheres absolute (ATA) helium-oxygen or to 1 ATA air at temperatures that offset the cooling effects of helium or helium and ethanol. Hyperbaric treatment significantly reduced sleep-time and increased wake-up brain ethanol concentrations compared to temperature matched controls. Treatment with 12 ATA helium-oxygen increased the brain ethanol concentration and the brain-blood ethanol ratio at 150 minutes after ethanol administration. These results exclude helium or pressure-induced changes in body temperature, rate of blood ethanol decline or distribution to the brain as mechanisms mediating the antagonism. The data support a membrane site of antagonism.
Animals↗
Interaction of apomorphine and amantadine with ethanol in men.
Male moderate drinkers (n = 12) drank ethanol (0.8 g/kg) and then ingested one of the following: apomorphine (5 mg), amantadine (200 mg), or placebo. Subjects were tested on a battery of physiological and behavioral measures using a double-blind, within-subjects, crossover design. Postethanol ingestion of apomorphine significantly increased ethanol's effect on 3 out of the 8 measures employed (divided attention, objective and subjective inebriation ratings) without significantly altering blood ethanol concentrations or the rate of blood ethanol decline. There was no indication that apomorphine antagonized ethanol's effects. In contrast to reports indicating that amantadine antagonized ethanol depression in rodents, amantadine did not significantly alter the degree of ethanol intoxication in humans. The increase in intoxication induced by apomorphine supports suggestions that dopaminergic systems may be involved in mediating ethanol intoxication and that the sobering effect of catecholamine-augmenting drugs results from noradrenergic, rather than combined noradrenergic and dopaminergic, stimulation. Further studies are necessary to elucidate the role of pre- and postsynaptic dopaminergic receptors in mediating these effects.
Adult↗
Hyperbaric ethanol antagonism in mice: time course.
C57BL/6J mice were injected intraperitoneally with 3.6 g/kg ethanol and exposed to 1 ATA air or to 1 or 12 ATA helium-oxygen immediately, 5, 10 or 20 minutes after injection. Immediate and delayed hyperbaric exposure produced similar significant reductions in sleep-times and increases in wake-up brain ethanol concentrations. These findings demonstrate the effectiveness of delayed hyperbaric treatment in reducing ethanol sleep-time and eliminate decreased absorption and altered distribution as critical factors mediating the antagonism. The results are consistent with current theories of anesthesia and support a direct mechanism involving brain cellular membranes.
Animals↗
Low-level hyperbaric ethanol antagonism in mice. Dose and pressure response.
Dose- and pressure-related interactions between ethanol anesthesia and low-level hyperbaric helium-oxygen environments were studied in mice using conditions which eliminated the possibility of hypoxia during compression and hyperbaric helium-induced hypothermia. Hyperbaric helium-oxygen (1-12 atmospheres absolute) reduced sleep time in a pressure-related manner. The degree of maximum ethanol antagonism decreased as the ethanol dose increased (3.2, 3.6, and 4.0g/kg). The results are consistent with membrane theories of general anesthesia and suggest a possible common mechanism between ethanol antagonism at low hyperbaric pressure and high-pressure reversal of anesthesia.
Anesthesia↗
Temperature dependence of ethanol depression in mice.
The relationship between environmental temperature, body temperature and ethanol depression was investigated in male C57BL/6J mice. Animals were injected with ethanol (3.6 g/kg) or saline and placed in an experimental or normal room temperature (control) environment. Environmental temperatures from 12-37 degrees C significantly influenced rectal temperature, sleep-time and wake-up brain ethanol concentrations. The rectal temperatures of ethanol-treated animals ranged from 1.5 degrees C greater to 11.3 degrees C lower than their matched saline controls, supporting indications that ethanol impairs normal thermoregulation. Sleep-time decreased up to 43% and wake-up brain ethanol concentrations increased as rectal temperature decreased from approximately 38-32 degrees C. More severe hypothermia after ethanol (rectal temperature less than 29 degrees C) increased sleep-time and decreased wake-up brain ethanol concentrations. These results indicate that sleep-time and brain sensitivity to ethanol vary with rectal temperature in accordance with predictions based on membrane expansion and partition theories of anesthesia and the anticipated anesthetic-like actions of severe hypothermia.
Animals↗
The effects of low level hyperbaric treatment on acute ethanol intoxication.
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Alcoholic Intoxication↗
Antagonism of ethanol narcosis in mice by hyperbaric pressures of 4-8 atmospheres.
Hyperbaric treatment with 100% oxygen or oxygen-helium mixtures at 4-8 atmospheres absolute significantly reduced ethanol sleep-time and increased wake-up blood ethanol concentrations in C57 mice. The results indicate that the antagonism does not result from direct effects of oxygen nor from enhanced ethanol elimination, but appears to involve a direct effect of hyper-baric treatment.
Animals↗
Gas-liquid chromatographic profile of neutral and acidic metabolites in cerebrospinal fluid from newborns and infants.
A profile (chromatographic pattern) of the neutral and acidic metabolites present in cerebrospinal fluid from newborns and infants was obtained by gas-liquid chromatography. The metabolites are those extracted with ethyl acetate and diethyl ether. They are converted to trimethylsilyl ether derivatives, and chromatographed on a column containing 5% silicone OV-101 (methyl) packed on Chromosorb W. Several substances were tentatively identified from their methylene unit values. We established a control profile for infants, and compared profiles for infants and adults. Noteworthy qualitative and quantitative differences from the control were seen for cerebrospinal fluid from subjects with neurological disorders of infections. The technique may be of use in neurological diagnosis.
Carboxylic Acids↗