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)

1. Uptake of [3H]uridine into the nucleotide precursor pool after intraventricular injection occurs with the same intensity in the brain of torpid and normothermic awakened ground squirrels. This indicates that the membrane uridine transporters and uridine kinases operate in the hibernator's brain in a hypothermia-tolerant way. 2. Utilization of the [3H]uridine pool for synthesis of the rapidly labelled RNA in the brain of torpid ground squirrels falls more than eight times against RNA labelling in the brain of the active animals between bouts of hibernation. 3. Two hours from the beginning of the artificially provoked awakening, RNA uridine incorporation in the brain of ground squirrels has risen 6.5 times. 4. Drastic changes in [3H]uridine RNA labelling under the stable uridine uptake exclude the precursors and energy supply as the main factors determining changes in intensity of the brain RNA synthesis in the different stages of hibernation.
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PMID:Uridine uptake and RNA synthesis in the brain of torpid and awakened ground squirrels. 137 96

Effects of acute or chronic ethanol administration have been studied on protein, RNA and DNA synthesis in the developing brain in the absence or presence of hypothermia. Acute ethanol was given intraperitoneally (4 g/kg) and for chronic ethanol treatment the pups were allowed to suckle on the ethanol-fed dams. Dams were pair-fed on nutritionally adequate liquid-sustacal diet. Ethanol administration, both acutely and chronically, inhibited the in vivo and in vitro protein synthesis in the absence or presence of hypothermia. This data suggests that ethanol per se is capable of producing the inhibition of protein synthesis in brain without its hypothermic effect. However, the inhibitory effect of ethanol is more pronounced in the presence of ethanol-mediated hypothermia. Hypothermia in itself also causes a decrease in the synthesis of proteins. Maternal ethanol consumption results in a significant decrease in the synthesis of both RNA and DNA in the developing brain of suckling newborn either in the absence or presence of hypothermia. RNA and DNA synthesis was measured by following the incorporation of (5-(3)H) uridine and (14C)thymidine respectively. Decrease in body temperature alone also resulted in decreased RNA and DNA synthesis in the developing brain. Ethanol reaching the suckling newborn from maternal milk resulted in decreased brain weights, total protein, ribosomal protein, total RNA, ribosomal RNA, and total DNA of the brain. Neonatal brain proteolytic and DNA-polymerase activities were inhibited in the ethanol-fed group. An inhibition of proteolytic activity reflects a compensatory mechanism of the developing brain to decrease the breakdown of proteins in response to the inhibitory effect of ethanol on protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nucleic acid and protein synthesis inhibition in developing brain by ethanol in the absence of hypothermia. 258 87

Administration of high-dose uridine or cytidine (3500 mg/kg) resulted in severe hypothermia of 6-10 degrees C in mice. This effect of uridine was observed in three different mouse strains, C57B1/6, Balb/c, and Swiss. A high-dose of uridine also caused hypothermia in Wistar rats. Co-infusion of uridine with benzylacyclouridine, an inhibitor of uridine phosphorylase, partially prevented uridine-mediated hypothermia in mice. A low dose of uridine (100 mg/kg) resulted in a slight increase in temperature. Plasma pharmacokinetics of uridine (at 3500 mg/kg) were studied in two mouse strains, C57B1/6 and Balb/c, and those of cytidine only in C57B1/6 mice. Peak plasma concentrations of uridine in both strains after uridine administration were about 20 mM (at 30-60 min). The peak plasma concentration of cytidine in C57B1/6 mice after cytidine administration was about 12 mM and that of uridine, 1.3 mM. The mean residence time for uridine was about 105 min. The area under the plasma concentration-time curve for uridine was about 50 mmol h/l, and that for cytidine, about 25 mmol h/l. In various tissues of C57B1/6 mice the levels of uridine, uracil and total uracil and cytosine nucleotide pools were determined before and 2 h after uridine administration. Uridine levels increased about 53-fold in liver, about 70-fold in a colon tumor, and only about 7-fold in brain, while the corresponding uracil levels increased about 9-fold, 4-fold and 11-fold, respectively. Total uracil nucleotide pools increased about 8-fold, 3.2-fold and 1.6-fold, respectively. Cytosine nucleotide pools did not increase in the brain. In conclusion, high-dose uridine administration caused severe hypothermia. Plasma levels of uridine and uracil were enhanced to a considerably higher extent than the levels in the tissues. The hypothermia might be related to breakdown products of uridine, since inhibition of uridine breakdown partially prevented hypothermia and since in brain uracil nucleotide levels were only slightly increased after uridine administration, while those of uracil were more markedly increased than in other tissues.
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PMID:Uridine-induced hypothermia in mice and rats in relation to plasma and tissue levels of uridine and its metabolites. 366 29

Hypoxic-ischemic encephalopathy (HIE), is the most common brain disorder in neonates during the perinatal period, which, to date, can only be managed to some extent by hypothermia. Uridine is the principal circulating pyrimidine in humans which is utilized as a precursor for membrane phospholipid biosynthesis. Uridine has recently been shown to provide clinical benefit in treatment of Alzheimer's disease due to its involvement in increasing number of brain synapses along with other phospholipid precursors. We previously showed that uridine treatment ameliorated brain damage by reducing apoptosis in a rat model of neonatal HIE. The aim of the present study was to investigate the effects of uridine administration on cognitive functions during periadolescent period in rats subjected to hypoxic-ischemic (HI) brain damage in neonatal period. Male newborn rats were subjected to HI insult on postnatal day 7 (P7) and were injected intraperitoneally with either saline or uridine (500mg/kg) for three consecutive days. Part of pups in each group were sacrificed on P10 to collect brain samples for active Caspase-3 analyses and the remaining pups were raised through P40 to evaluate early reflexes, sensorimotor coordination and learning and memory functions by Negative Geotaxis (NG), Beam Walking (BW) and Morris Water Maze (MWM) tasks, respectively. Confirming our previous findings, we showed that uridine administration reduced apoptotic cell damage on P10. No significant difference was observed between uridine and saline groups in early reflexes or sensorimotor coordination. On the other hand, rats receiving uridine displayed improved learning and memory in MWM during periadolescent period. We conclude that uridine treatment improves learning and memory in the long term by, probably, reducing apoptotic cell death in early newborn period. This is the first study to show beneficial cognitive effects of uridine in rats with brain damage.
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PMID:Long-term cognitive effects of uridine treatment in a neonatal rat model of hypoxic-ischemic encephalopathy. 2812 2

Adenosine is a constituent of many molecules of life; increased free extracellular adenosine indicates cell damage or metabolic stress. The importance of adenosine signaling in basal physiology, as opposed to adaptive responses to danger/damage situations, is unclear. We generated mice lacking all four adenosine receptors (ARs), Adora1-/-;Adora2a-/-;Adora2b-/-;Adora3-/- (quad knockout [QKO]), to enable investigation of the AR dependence of physiologic processes, focusing on body temperature. The QKO mice demonstrate that ARs are not required for growth, metabolism, breeding, and body temperature regulation (diurnal variation, response to stress, and torpor). However, the mice showed decreased survival starting at about 15 weeks of age. While adenosine agonists cause profound hypothermia via each AR, adenosine did not cause hypothermia (or bradycardia or hypotension) in QKO mice, indicating that AR-independent signals do not contribute to adenosine-induced hypothermia. The hypothermia elicited by adenosine kinase inhibition (with A134974), inosine, or uridine also required ARs, as each was abolished in the QKO mice. The proposed mechanism for uridine-induced hypothermia is inhibition of adenosine transport by uridine, increasing local extracellular adenosine levels. In contrast, adenosine 5'-monophosphate (AMP)-induced hypothermia was attenuated in QKO mice, demonstrating roles for both AR-dependent and AR-independent mechanisms in this process. The physiology of the QKO mice appears to be the sum of the individual knockout mice, without clear evidence for synergy, indicating that the actions of the four ARs are generally complementary. The phenotype of the QKO mice suggests that, while extracellular adenosine is a signal of stress, damage, and/or danger, it is less important for baseline regulation of body temperature.
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PMID:Physiology and effects of nucleosides in mice lacking all four adenosine receptors. 3082 1