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

The synthesis and biological properties of a series of nicotinamide ethers are described. These compounds, structurally novel calcium-independent phosphodiesterase inhibitors, also inhibit the binding of [3H]rolipram to rat brain membranes and reverse reserpine-induced hypothermia in the mouse. Several compounds exhibited potent in vivo activity comparable to the standard agent, rolipram.
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PMID:Nicotinamide ethers: novel inhibitors of calcium-independent phosphodiesterase and [3H]rolipram binding. 182 16

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

The effects of different levels of arterial blood oxygen content (CaO2) on brain tissue adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) were studied during cerebral hypoxia in normothermic and hypothermic male Wistar rats with unilateral carotid ligation. Animals were exposed to hypoxia (PaO2 19--26 torr) for 25 min, and brain tissue metabolite values measured microfluorometrically were compared with those of normothermic normoxic controls. CaO2 was 4.0 +/- 0.2 ml/dl (mean +/- SEM) at PaO2 26 torr in normothermic animals. CaO2 was increased to 8.2 +/- 0.3 ml/dl at PaO2 26 torr by means of bicarbonate infusion producing a leftward shift of the oxyhemoglobin-dissociation curve in one normothermic hypoxic group. In all normothermic hypoxic groups ATP and PCr decreased and lactate and NADH increased significantly compared with control values. There was no significant difference in brain tissue metabolite values among these groups despite an increase in CaO2 by twofold in one group. Hypothermia (32 C) resulted in CaO2 8.4 +/- 0.2 ml/dl at PaO2 26 torr. This was decreased to 4.0 +/- 0.2 ml/dl by decreasing PaO2 to 19 torr in another group at the same temperature. ATP and PCr were well preserved in both groups despite the difference in CaO2s. Although the lactate and NADH levels were increased in the hypothermic group with CaO2 4.0 +/- 0.2 ml/dl, they were significantly lower than those values in normothermic hypoxic groups. These results indicate that the increase in CaO2 produced by hypothermia is not a major determinant in hypothermic protection during cerebral hypoxia.
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PMID:Effect of high vs. low arterial blood oxygen content on cerebral energy metabolite levels during hypoxia with normothermia and hypothermia in the rat. 676 65

The effect of arterial hypotension on cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PGr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) was studied in male Wistar rats with unilateral carotid ligation exposed to arterial by hypoxia (PaO2 25 torr) for 20 min. while the body temperature was maintained at 32 degrees C and 27 degrees C. Brain metabolite levels were normal in normotensive hypothermic animals exposed to hypoxia, but reduction in arterial pressure to 75 torr caused a significant (p less than 0.05) decrease in ATP and PCr values and a significant increase in lactate and NADH levels. These changes were comparable to those of normothermic normotensive, hypoxic animals. Furthermore, there was no significant differences in the brain metabolite levels between the two hypotensive hypoxic groups. These results indicate that arterial hypotension severely alters the cerebral protective effect of hypothermia against injury caused by hypoxia, and that further reduction in body temperature (from 32 degrees C to 27 degrees C) will not prevent the harmful effect of hypoxia upon the brain in hypotensive rats.
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PMID:Reduction of the cerebral protective effect of hypothermia by oligemic hypotension during hypoxia in the rat. 680 24

Amino acid enrichment of cardioplegic solutions has been shown to improve both the metabolic and functional recovery of ischemic myocardium. However, because of the marked systemic vasodilatation involved, use of amino acid enrichment is limited to the periods of induction and reperfusion. Fumarate is a Krebs' cycle intermediate whose conversion to succinate is responsible for the generation of adenosone triphosphate and the oxidation of the reduced form of nicotinamide-adenine nucleotide which is the pathway by which aspartate exerts its effect. Fumarate may also function as a free-radical scavenger and is involved in calcium transport. To determine if fumarate-enriched blood cardioplegia would improve the functional recovery of the neonatal heart, 14 neonatal piglet hearts were isolated and placed on a blood-perfused working heart circuit. After the baseline functional and metabolic assessment was done, cold ischemic arrest was initiated with either standard blood cardioplegic solution (group I; N = 7) or fumarate-enriched (13 mmol/L) blood cardioplegic solution (group II; N = 7). Cardioplegic solution was given at a pressure of 40 mm Hg every 20 minutes for 2 hours, and topical hypothermia was used. Sixty minutes after warm whole blood reperfusion, the functional recovery at left atrial pressures of 3, 6, 9, and 12 mm Hg was 70%, 66%, 66%, and 65%, respectively, in group I, versus 102%, 106%, 105%, and 109%, respectively, in group II (p < 0.05). The tissue creatinine phosphate levels after reperfusion were significantly higher in group II hearts (15.0 +/- 1.2 mumol/g dry heart tissue) than in group I hearts (9.2 +/- 1.9 mumol/g dry heart tissue), although the adenosine triphosphate levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fumarate-enriched blood cardioplegia results in complete functional recovery of immature myocardium. 801 Aug 14

Neuropathological mechanisms triggered by excitatory aminoacids are known to involve nitric oxide (NO). Neurons containing NO are histochemically reactive to nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), which labels NO synthase in CNS. Sprague-Dawley male rats subjected to perinatal asphyxia (PA) at 37 degrees C, and PA plus 15 degrees C hypothermia were evaluated when 6 months old by NADPH-d histochemical reaction. Computarized image analysis was used for quantification of stained sections. NADPH-d neurons in striatum from subsevere and severe PA showed a significant increment in soma size and dendritic process length versus control and hypothermic treated rats. Post-ischemic damage neurons are therefore involved in NO changes induced by PA that may be prevented by hypothermia treatment.
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PMID:Striatal cytomegalic neurons containing nitric oxide are associated with experimental perinatal asphyxia: implication of cold treatment. 893 70

Nitric oxide (NO) is known to be involved in the neuropathological mechanisms triggered by excitatory aminoacids. NO(+) neurons in the brain may be detected histochemically by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical technique, as the latter readily labels NO synthase in the central nervous system (CNS). NADPH-d stained striatal and cortical sections were studied in 6-month-old male Sprague-Dawley rats exposed to perinatal asphyxia (PA) at 37 degrees C, as well as in animals subjected to PA plus hypothermia treatment at 15 degrees C. Quantitative image analysis was performed to compare the staining pattern in the various groups. NADPH-d(+) neurons in striatum and cortex from subsevere and severe asphyctic animals showed a significant increase in soma size and in dendritic processes versus controls and hypothermia-treated rats. These findings indicate that chronic NO changes are involved in postischemic striatal and cortical alterations induced by PA that may be prevented by hypothermia.
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PMID:Long term changes in NADPH-diaphorase reactivity in striatal and cortical neurons following experimental perinatal asphyxia: neuroprotective effects of hypothermia. 913 44

Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis of bioactive fatty acid amides and esters such as the endogenous cannabinoid receptor ligands, anandamide (N-arachidonoyl-ethanolamine) and 2-arachidonoylglycerol, and the putative sleep inducing factor cis-9-octadecenoamide (oleamide). Most FAAH blockers developed to date also inhibit cytosolic phospholipase A2 (cPLA2) and/or bind to the CB1 cannabinoid receptor subtype. Here we report the finding of four novel FAAH inhibitors, two of which, malhamensilipin A and grenadadiene, were screened out of a series of thirty-two different algal natural products, and two others, arachidonoylethylene glycol (AEG) and arachidonoyl-serotonin (AA-5-HT) were selected out of five artificially functionalized polyunsaturated fatty acids. When using FAAH preparations from mouse neuroblastoma N18TG2 cells and [14C]anandamide as a substrate, the IC50s for these compounds ranged from 12.0 to 26 microM, the most active compound being AA-5-HT. This substance was also active on FAAH from rat basophilic leukaemia (RBL-2H3) cells (IC50 = 5.6 microM), and inhibited [14C]anandamide hydrolysis by both N18TG2 and RBL-2H3 intact cells without affecting [14C]anandamide uptake. While AEG behaved as a competitive inhibitor and was hydrolyzed to arachidonic acid (AA) by FAAH preparations, AA-5-HT was resistant to FAAH-catalyzed hydrolysis and behaved as a tight-binding, albeit non-covalent, mixed inhibitor. AA-5-HT did not interfere with cPLA2-mediated, ionomycin or antigen-induced release of [3H]AA from RBL-2H3 cells, nor with cPLA2 activity in cell-free experiments. Finally, AA-5-HT did not activate CB1 cannabinoid receptors since it acted as a very weak ligand in in vitro binding assays, and, at 10-15 mg/kg body weight, it was not active in the 'open field', 'hot plate' and rectal hypothermia tests carried out in mice. Conversely AEG behaved as a cannabimimetic substance in these tests as well as in the 'ring' immobility test where AA-5-HT was also active. AA-5-HT is the first FAAH inhibitor reported to date which is inactive both against cPLA2 and at CB1 receptors, whereas AEG represents a new type of cannabinoid receptor agonist.
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PMID:Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase. 970 57

Neurotoxicity induced by different substituted amphetamines has been associated with the exhaustion of intracellular energy stores. Accordingly, we examined the influence of 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glucose uptake and metabolism, and nicotinamide, an agent that improves energy metabolism, on 3, 4-methylenedioxymethamphetamine (MDMA)-induced 5-hydroxytryptamine (5-HT; serotonin) deficits. Administration of MDMA (15 mg/kg i.p.) produced a significant hyperthermia, whereas 2-DG caused a profound hypothermia that lasted throughout the experiment. When MDMA was given to 2-DG-treated rats, an immediate but transient hyperthermia occurred and was followed by a return to hypothermia. 2-DG had no effect on 5-HT concentrations in the frontal cortex, hippocampus, and striatum but prevented the neurotoxicity induced by MDMA. When rats were injected with 2-DG/MDMA and were warmed to prevent hypothermia, the protection afforded by 2-DG was abolished. Nicotinamide had no effect on body temperature of the rats, and the hyperthermia induced by the nicotinamide/MDMA treatment was similar to that of the saline/MDMA-treated rats. However, the long-term 5-HT deficits induced by MDMA were potentiated by nicotinamide in all the brain regions examined. Finally, no change on ATP concentrations in the frontal cortex, hippocampus, and striatum was observed up to 3 h after a single dose of MDMA. These results suggest that an altered energy metabolism is not the main cause of the neurotoxic effects induced by MDMA.
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PMID:2-Deoxy-D-glucose prevents and nicotinamide potentiates 3, 4-methylenedioxymethamphetamine-induced serotonin neurotoxicity. 1093 79

While the endogenous fatty acid amide oleamide has hypnotic properties, neither the breadth of its behavioral actions nor the mechanism(s) by which these behaviors may be mediated has been elucidated. Therefore, the effects of oleamide on the performance of rats in tests of motor function, analgesia, and anxiety were investigated. Oleamide reduced the distance traveled in the open field (ED50 = 14, 10-19 mg/kg, mean, 95% confidence interval), induced analgesia and hypothermia, but did not cause catalepsy. Moreover, a dose of oleamide without effect on motor function was anxiolytic in the social interaction test and elevated plus-maze. These actions of a single dose of oleamide lasted for 30 to 60 min. While rats became tolerant to oleamide following 8 days of repeated administration, oleamide is a poor inducer of physical dependence. Pretreatment with antagonists of the serotonin (5HT)1A, 5HT2C, and vanilloid receptors did not modify oleamide's effects. However, the cannabinoid receptor antagonist SR 141716A inhibited oleamide-induced analgesia in the tail-flick assay, the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline reversed the analgesia and hypothermia, and the dopamine D2 receptor antagonist L 741626 blocked oleamide's locomotor and analgesic actions. Interestingly, oleamide analogs resistant to hydrolysis by fatty acid amide hydrolase (FAAH) maintained but did not show increased behavioral potency or duration of action, whereas two FAAH inhibitors produced analogous behavioral effects. Thus, oleamide induces behaviors reminiscent of the actions of endogenous cannabinoids, but the involvement of GABAergic and dopaminergic systems, either directly or indirectly, in the actions of oleamide cannot be ruled out.
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PMID:Behavioral evidence for the interaction of oleamide with multiple neurotransmitter systems. 1156 Oct 96


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