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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of infra-red spectra of cardiac microsomal fraction revealed the changes in the membrane structure, induced by acute hypoxia and hypothermia in one's lifetime. These changes affect alpha- and beta-conformations of protein, phospholipid part of sarcoplasmic reticulum and are accompanied by the change in the activity of membrane-bound ATPases.
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PMID:[Infra-red spectra and ATPase activity of cardiac sarcoplasmatic reticulum under extreme conditions]. 12 88

The tremorogenic properties of a series of benzylimidoylurea derivatives are described. The most potent member, N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), produces a reproducible, dose-dependent rest tremor in the mouse with oral doses of 5-100 mg/kg which is also seen in other species (rat, cat, dog, rabbit). The tremor is of constant frequency, rapid onset and short duration. It is not accompanied by akinesia, muscle ridigity, antinociceptive activity, parasympathomimetic effects or marked hypothermia and in these respects differs from tremor produced by oxotremorine. Pretreatment with a microsomal enzyme inhibitor had no effect on the tremor. An LD50 of 165 mg/kg p.o. was calculated in the mouse. After repeated administration both acute and chronic tolerance developed to the tremorogenic effects of LON-954. Evidence for a central site of action is presented, since the tremor could be reproduced following injection of small quantities (50-100 microgram) into the cerebral ventricles of the mouse. Furthermore, the use of spinal, decorticate and and decerebrate rats indicated that although tremor is not of cortical origin, it arises in an area rostral to the inferior colliculi. The mechanism underlying the tremor appears to involve dopaminergic pathways, since the action of LON-954 was antagonised by L-dopa and apomorphine and potentiated by pimozide. Atropine and carbachol were without effect. It is suggested that LON-954 could be used as an alternative to oxotremorine for the detection of anti-Parkinson drugs, particularly those exerting their effects through dopaminergic mechanisms.
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PMID:The pharmacology of N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride (LON-954) a new tremorogenic agent. 58 44

delta 9-Tetrahydrocannabinol (delta 9-THC) has been reported to attenuate both reserpine-induced serotonin depletion and reserpine-induced hypothermia. We have observed that delta 9-THC preincubation led to a dose-responsive increase in the amount of 3H-reserpine bound to a crude mitochondrial fraction of rat forebrain. The experiments reported here further characterize this phenomenon. Preincubation with delta 9-THC produced a shift in the localization of 3H-reserpine from the incubation medium and the microsomal supernatant (decrease of 66%) to the crude mitochondrial (CM) pellet (increase of 154%). The CM pellet was subfractionated both by differential centrifugation after osmotic shock and by layering on a five-step discontinuous sucrose gradient and centrifuging at 80,000 x g. Osmotic shock with 0.032 M sucrose and centrifugation revealed that the delta 9-THC-induced increase in 3H-reserpine was contained in both the synaptic vesicle fraction (247%) and the fraction containing myelin, ruptured synaptosomes and mitochondria (324%). Separating the CM fraction into five component parts showed that delta 9-THC increased the 3H-reserpine bound by about 275% in the three fractions containing myelin, membrane fragments or mitochondria. Even more dramatic increases (greater than 1000%) were observed in the two fractions containing cholinergic and non-cholinergic nerve endings. In addition, we have determined that many other drugs which are believed to have membrane mediated mechanisms have no effect on the amount of 3H-reserpine bound to the crude mitochondrial fraction. Although other possibilities exist, these data support the hypothesis that delta 9-THC retards the action of reserpine by altering the normal distribution of reserpine in various membrane components of the rat brain.
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PMID:In vitro alteration of the subcellular distribution of 3H-reserpine in the rat forebrain by delta 9-tetrahydrocannabinol. 100 13

We found a statistically significant increase in duration of pentobarbital-induced narcosis in doxapram-treated mice. The influence of doxapram (a respiratory stimulant) pretreatment on pentobarbital metabolism in mice was assessed by measurements of sleeping times, hypothermia, LD50 values, hepatic microsomal metabolism and relative plasma and brain levels of pentobarbital. When doxapram was given intraperitoneally 60 min. prior to administration of pentobarbital, doxapram potentiated pentobarbital-induced narcosis in a dose- and time-dependent manner, but had no effect on onset time. Doxapram potentiated hypothermia, increased acute toxicity, and prolonged the pentobarbital half-life in brain and plasma, but measurement of the concentration of pentobarbital in the brain and plasma immediately upon recovery from narcosis showed that there were no differences in any of the groups examined. Also, brain-to-plasma ratios of pentobarbital did not differ between the control and doxapram-treated groups. Doxapram competitively inhibited the hepatic metabolism of pentobarbital in 9000 x g supernatant incubation mixtures. The results obtained from these experiments indicate that inhibition of drug-metabolizing enzymes by doxapram may account for its enhancement of the duration of pentobarbital-induced narcosis.
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PMID:Interaction of doxapram and pentobarbital in mice. 195 80

An increased sensitivity of adrenalectomized (Adex) rats to intravenous (IV) injection of recombinant human tumor necrosis factor (rHuTNF) was manifested by a marked increase in the rate of mortality. The rats that died exhibited severe hypoglycemia and hypothermia. Administration of 2.5 or 10 micrograms/100 g body weight (3% or 12%) of the lethal dose in sham-operated rats (90 micrograms/100 g body weight) rHuTNF caused a mortality rate of 50% or 100%, respectively, within 4 hours of its injection. Pre-administration of dexamethasone or intermittent glucose infusion protected the animals from the lethal effect of rHuTNF. Indomethacin did not change the mortality rate in rHuTNF-treated Adex rats, but prevented it in sham-operated rats. The rats that died exhibited a marked decrease in body temperature, but only Adex rats developed hypoglycemia after low doses of TNF. Pretreatment with dexamethasone prevented the hypothermia in both Adex and sham-operated rats, while indomethacin was effective only in sham-operated rats and did not prevent the hypothermia or the hypoglycemia in Adex rats. In the surviving rHuTNF-treated Adex rats, a rapid increase in body temperature occurred, blood glucose decreased to 30 mg/dL, serum insulin concentration decreased to 6 microU/mL, liver glycogen content was reduced by 98%, and a significant reduction in liver phosphoeonolpyruvate carboxykinase (PEPCK) and liver microsomal glucose-6-phosphatase activities was observed. Repeated administration of glucose IV to rHuTNF-treated Adex rats caused an increase in blood glucose and insulin concentrations, and some repletion in liver glycogen content. Injection of rHuTNF, 2.5 to 10 micrograms/100 g body weight, to sham-operated rats caused a significant but slower increase in body temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lethal hypoglycemia and hypothermia induced by administration of low doses of tumor necrosis factor to adrenalectomized rats. 215 69

We investigated the response of mitochondrial function and microsomal adenosine triphosphatase (ATPase) activity in rat liver tissue subjected to in vitro ischemia at either 0 degree C to 4 degrees C or 37 degrees C for 30 to 60 minutes. Mitochondrial coupling, expressed as respiratory control index, was preserved at up to 60 minutes' cold ischemia. However, respiratory control index was decreased significantly from control by 30 minutes of warm ischemia. Both microsomal magnesium-activated ATPase and sodium-potassium ATPase activity were significantly increased by 60 minutes of warm ischemia yet were unaltered by 60 minutes of ischemia at 0 degree C to 4 degrees C. Warm ischemia produces deleterious effects on energy-generating (mitochondria) and energy-utilizing (ATPase) activity. Hypothermia provides a significant prolongation of cellular viability in ischemic tissue in terms of bioenergetic status. In addition to organ procurement and transplantation, hypothermic cytoprotection may prove valuable in areas such as shock, ischemia, and other clinical conditions of compromised visceral perfusion.
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PMID:Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia. 295 19

The desulfuration of thiopental to pentobarbital has previously been shown to be a relatively minor pathway of thiopental metabolism. In two cases, we observed significant conversion, resulting in blood pentobarbital concentrations up to 50 percent of total blood barbiturate (thiopental and pentobarbital) concentrations. Both patients received continuous infusions of thiopental and had present a condition (hypothermia) or drug (cimetidine) known to inhibit hepatic microsomal enzyme activity. It is suggested that inhibition of hepatic microsomal enzyme activity may prevent thiopental's metabolism to its major metabolite, a carboxylic acid analogue, and increase the amount of thiopental desulfurated to pentobarbital. Inhibition of hepatic microsomal metabolism also decreases the metabolism of pentobarbital. Until further elucidation of the causes of altered thiopental metabolism is available to identify patients more likely to have elevated concentrations of pentobarbital, monitoring of blood drug concentrations in patients receiving thiopental should include determination of both thiopental and pentobarbital concentrations.
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PMID:Blood pentobarbital concentrations during thiopental therapy. 369 25

1. Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30-32 degrees C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4-fold at 500 mg/kg.2. Under these conditions, ether sleeping time was not prolonged.3. Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome-rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation.4. Delta(1)-Tetrahydrocannabinol (Delta(1)-THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water-soluble fractions of the extract were inactive on pentobarbitone sleep.5. Cannabidiol was strongly active by both tests; in vivo 39.8 muM/kg (12.5 mg/kg) prolonged sleep by 190%, and in vitro 12.7 muM inhibited phenazone metabolism 20%. These actions were dose related, and could account for the effect of the extract.6. The prolongation of pentobarbitone sleep by cannabis extract in a dose of 200 mg/kg, intraperitoneally, was maximal when given 30 min before the pentobarbitone, still present at 3 h, but undetectable at 24 hours. No phase of enhanced metabolism at 24 or 48 h after single cannabis injection was detected.7. It is concluded that cannabis extract inhibits microsomal activity of mouse liver, chiefly by virtue of its cannabidiol content. It is probable that cannabis consumption by man could lead to altered disposal of many other drugs, used in medicine or otherwise.
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PMID:Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism. 466 92

In male mice of ddY strain, a single dose of 1,1-dichloroethylene (1,1-DCE, 0.1 ml/kg, ip) produced severe renal damage at 24 hr, as evidenced by elevations in plasma urea nitrogen concentration and kidney calcium content and by massive renal tubular necrosis, while hepatic damage was less severe. A precipitous decrease in body temperature started as early as 30 min after administration of 1,1-DCE and lasted for 24 hr. Glutathione concentrations decreased in the liver and kidney, with a rebound increase seen in the former but not in the latter tissue. In carbon tetrachloride-poisoned mice, the renal toxicity of 1,1-DCE was markedly potentiated. Pretreatment with either diethyldithiocarbamate (DTC) or carbon disulfide (CS2) blocked all of these 1,1-DCE-induced toxic manifestations in normal and carbon tetrachloride-poisoned mice. Both agents, however, did not prevent the hypothermia induced by monochloroacetic acid or chloroacetyl chloride, proposed active metabolites of 1,1-DCE. Since DTC and CS2 inhibited hepatic and renal microsomal drug metabolizing enzyme activities (Masuda and Nakayama, 1982, 1983), it is probable that the protective action of DTC and CS2 against renal and hepatic injury induced by 1,1-DCE may be due to an inhibition of the metabolic activation of 1,1-DCE to its proposed epoxide in each organ. The action of DTC given po may be mediated by CS2 produced in the stomach. The hypothermia induced by 1,1-DCE may not result from a direct action of 1,1-DCE per se, but by its metabolites.
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PMID:Protective action of diethyldithiocarbamate and carbon disulfide against acute toxicities induced by 1,1-dichloroethylene in mice. 631 3

Oral administration of diethyldithiocarbamate (DTC) and carbon disulfide (CS2) protected mice against CHCl3-induced kidney injury, as evidenced by normalization of delayed plasma phenolsulfonphthalein clearance, suppression of increased kidney calcium content and prevention of renal tubular necrosis. In CCl4-treated mice, in which liver microsomal monooxygenase activities were decreased markedly, and kidney microsomal aniline hydroxylase and p-nitroanisole demethylase activities were increased to about twice those of the untreated mice, renal toxicity of CHCl3 was greatly potentiated, and the latter effect was also blocked by both agents. DTC and CS2 per se markedly decreased kidney microsomal aniline hydroxylase and p-nitroanisole demethylase activities at 1 hr after oral administration, accompanying a moderate loss of cytochrome P-450 content, in both normal and CCl4-treated mice. The protection was not due to hypothermia, because pretreatment with DTC or CS2 (p.o.) also prevented the hypothermia induced by CHCl3. The mechanism of the protection may have involved inhibition of metabolic activation of CHCl3 in the kidney rather than in the liver.
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PMID:Protective action of diethyldithiocarbamate and carbon disulfide against renal injury induced by chloroform in mice. 631 19


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