Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microwave irradiation of 6 kw at 2450 MHz for 300 msec was sufficient to completely inactivate mouse brain cholinesterase and choline acetyltransferase. After this method of sacrifice, the acetylcholine contents of mouse brain regions, given in nanomoles per gram, were found to be: striatum, 81; medulla-pons, 44; diencephalon-midbrain, 34; hippocampus, 31; cerebral cortex, 26; and cerebellum, 17. Sodium pentobarbital caused a dose-dependent increase in whole brain acetylcholine. A maximal increase of 81% in whole brain was seen at 15 minutes with 80 mg/kg of sodium pentobarbital. The increase in acetylcholine after sodium pentobarbital treatment was not caused by anoxia from respiratory depression or by hypothermia. All brain regions except the cerebellum exhibited an increase in acetylcholine after pentobarbital treatment. Fifteen minutes after treatment, cerebellar acetylcholine was significantly decreased. However, at the time when half of the animals had regained the righting reflex, the unconscious mice showed an increase in cerebellar acetylcholine which was statistically significant as compared to control. The relative accumulation rate of acetylcholine calculated for cerebral cortex and hippocampus was higher than that for striatum although the absolute rate of accumulation of ACh was higher in the striatum. Thus, after sodium pentobarbital treatment, the cerebral cortex and hippocampus exhibit a greater cholinergic response than the striatum.
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PMID:Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions. 0 94

The investigations have been performed on Wistar rats intoxicated with paraoxon in toxic sublethal doses. There have been measured the variations of rectal temperature at various time periods following the anticholinesterase agent. The authors established the pharmacodynamic correlations of paraoxon-induced hypothermia with cholinesterase reactivators (toxogonin, isonitrosine), anticholinergic substances (atropine, butylscopolamine), carbamic anticholinesterase (eserine, neoeserine) and chlorpromazine. The efficiency of atropine and cholinesterase reactivators in antagonization of hypothermia induced by organophosphorics on the one hand, and only of atropine against hypothermia induced by carbamates on the other hand allow the hypothesis of a central cholinergic mechanism, predominantly muscarinic, involved in hypothermia induced by anticholinesterasics and of a direct correlation of this mechanism with phosphorylation or carbamylation processes of cerebral cholinesterases.
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PMID:Some pharmacological correlations of hypothermia induced by anticholinesterasics. 82 47

Experiments set up on mice demonstrated that galanthamine, hydrobromide, physostymine salicilate and iodomethylate produce a fall of the renal temperature, the hypothermal effect being proportional to the suppression of the cerebral cholinesterase. Anticholinergics benactyzine and atropine were largely capable of preventing hypothermia produced by the introduction of galathamine hydrobromide, the latter increasing the resistance of the animals to the action of high temperature.
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PMID:[Mechanism of the hypothermic action of reversible cholinesterase inhibitors]. 122 97

Cholinergic replacement therapy for Alzheimer's disease using existing cholinesterase inhibitors is compromised by short duration, meagre benefits restricted to subgroups of patients, and peripheral toxicity. Heptyl physostigmine is a lipophilic carbamate derivative of physostigmine. In rhesus monkeys, heptyl physostigmine (0.2-0.9 mg/kg i.m.) fully reversed a scopolamine-induced cognitive impairment. Following oral administration in squirrel monkeys, heptyl physostigmine (8 mg/kg) induced long-lasting hypothermia (greater than or equal to 4 h), a centrally-mediated cholinergic effect. Erythrocyte acetylcholinesterase activity was inhibited by 86% at the time of peak hypothermia (180 min). Clinical trials with heptyl physostigmine will enable a more rigorous evaluation of cholinomimetic therapy for dementia.
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PMID:Reversal of cognitive impairment by heptyl physostigmine, a long-lasting cholinesterase inhibitor, in primates. 156 24

This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents.
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PMID:Relationship between cholinesterase inhibition and thermoregulation following exposure to diisopropyl fluorophosphate in the rat. 175 22

This study examined the effects of an oral 30-mg dose of pyridostigmine bromide (PYR) on thermoregulatory and physiological responses of men undergoing cold stress. Six men were immersed in cold water (20 degrees C) for up to 180 min on two occasions, once each 2 h after ingestion of PYR and 2 h after ingestion of a placebo. With PRY, erythrocyte cholinesterase inhibition was 33 +/- 12% (SD) 110 min postingestion (10 min preimmersion) and 30 +/- 7% at termination of exposure (mean 117 min). Percent cholinesterase inhibition was significantly related to lean body mass (r = -0.91, P less than 0.01). Abdominal discomfort caused termination in three of six PYR experiments but in none of the control experiments (mean exposure time 142 min). During immersion, metabolic rate, ventilatory volume, and respiratory rate increased significantly (P less than 0.05) over preimmersion levels and metabolic rate increased with duration of immersion (P less than 0.01) in both treatment but did not differ between conditions. PYR had no significant effect on rectal temperature, mean body temperature, thermal sensations, heart rate, plasma cortisol, or change in plasma volume. It was concluded that a 30-mg dose of PYR does not increase an individual's susceptibility to hypothermia during cold water immersion; however, in combination with cold stress, PYR may result in marked abdominal cramping and limit cold tolerance.
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PMID:Effects of pyridostigmine bromide on human thermoregulation during cold water immersion. 193 14

Experiments were designed to assess the mechanisms of diisopropyl fluorophosphate (DFP)-induced changes in thermoregulation of the rat. In one study, male rats of the Long-Evans strain were injected with DFP (s.c.) at doses ranging from 0 to 2.0 mg/kg while maintained at an ambient temperature (Ta) of 20--24 degrees C. Body (Tb) and tail skin (Tt) temperatures were recorded for 5 h post-injection. DFP doses of greater than or equal to 1.0 mg/kg resulted in significant decreases in Tb lasting up to 5 h and increases in Tt lasting up to 1 h post-injection. In a second study, metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), Tb, and Tt were measured at 2 h post-injection of 0, 0.5, 1.0, and 1.5 mg/kg DFP (s.c.) at Ta values of 10, 20, and 30 degrees C. DFP treatment resulted in hypothermia at all three Ta values, but the effect was attenuated at 30 degrees C. MR was significantly reduced at a Ta of 20 degrees C following 1.5 mg/kg, unaffected by DFP at a Ta of 30 degrees C, and stimulated at 10 degrees C following 0.5 mg/kg DFP. EWL was significantly elevated at 30 degrees C following 1.5 mg/kg DFP. MA was significantly reduced following greater than or equal to 1.0 mg/kg DFP at 20 and 30 degrees C and 1.5 mg/kg at 10 degrees C. Tt was elevated and reduced by DFP at Ta values of 30 and 10 degrees C, respectively. In a third study, rats were injected with DFP and placed in a temperature gradient for 1 to 2 h post-injection while selected Ta and Tb were monitored. While both control and DFP-treated rats remained in the cool end of the gradient, rats administered DFP at doses of 1.0 and 1.5 mg/kg were significantly hypothermic. It was also found that Ta values of 10, 20, and 30 degrees C had no effect on DFP-induced inhibition of cholinesterase activity of plasma and erythrocyte fractions of whole blood. Overall, these data support the hypothesis that acute DFP may lower the set-point for the control of body temperature in the rat and demonstrates that the toxicity of DFP is modified by changes in Ta.
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PMID:Acute effects of diisopropyl fluorophosphate (DFP) on autonomic and behavioral thermoregulatory responses in the Long-Evans rat. 201 60

When rats were administered methyl isocyanate (MIC) by inhalation or subcutaneous route it produced severe hyperglycemia, clinical lactic acidosis, highly elevated plasma urea, and reduced plasma cholinesterase activity with unaltered erythrocyte acetyl cholinesterase activity. Irrespective of the route of administration, MIC also caused severe hypothermia, which was not ameliorated by prior administration of atropine sulphate. Acute toxic effects of MIC are essentially similar by either route except for the intensity of the effects.
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PMID:Acute toxicity of methyl isocyanate in mammals. II. Induction of hyperglycemia, lactic acidosis, uraemia, and hypothermia in rats. 235 32

The effects of the compound SM-10888 (9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate) in a number of pharmacological and biochemical tests were studied and compared to those of tacrine (THA), amiridin, HP-029 and physostigmine. SM-10888 inhibited cholinesterase activity (IC50: 2.3 x 10(-7) M) in rat cortical P2 fraction with almost the same potency as THA, while SM-10888 was 2-4 times more potent than amiridin and HP-029, but about 10 times less potent than physostigmine. When given to mice p.o., SM-10888 induced central (hypothermia) and peripheral (salivation) cholinergic effects. When the ratio of the ED50 value for hypothermia to that for salivation was regarded as the index of the selectivity to the central nervous system (CNS), SM-10888 was shown to be about 3 times more selective to the CNS than the other four drugs in mice. The minimum effective dose of SM-10888 for its increasing effect on acetylcholine (ACh) content in the mouse cerebral cortex was about 10 times higher than that of physostigmine, but 5-10 times lower than those of THA, amiridin and HP-029. These results suggest that SM-10888 is an adequate drug for increasing the brain ACh content with less peripheral cholinergic side effects than THA, amiridin, HP-029 and physostigmine.
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PMID:Pharmacological and biochemical assessment of SM-10888, a novel cholinesterase inhibitor. 238 1

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49


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