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

Transient global ischaemia induces the expression of immediate early genes. Using in situ hybridization, the expression of c-fos, fosB, fra-1, fra-2, c-jun and junB was studied after 15 min of normothermic and hypothermic (33 degrees C) transient forebrain ischaemia in the rat, induced by common carotid occlusion combined with systemic hypotension. Two phases of induction of the immediate early genes were observed. The early phase, peaking at 1-2 h of reperfusion, was dominated by marked expression in the dentate gyrus. The second phase, with maximal expression at 12-36 h of reperfusion, was observed particularly in the vulnerable CA1 and CA3 regions. Hypothermia increased the early induction of one of the genes studied, signifying a differential effect of hypothermia upon the signal transduction mechanisms activating these genes. The late induction occurred earlier after hypothermic than after normothermic ischaemia. The early expression of immediate early genes is due to the rapid activation of cytosolic response elements caused by the ischaemic insult. We suggest that the late induction is a stress signal for activation of repair processes, analogous to the cellular response seen after UV light-induced DNA damage. The relatively fast induction of the immediate early genes following hypothermic ischaemia may reflect a faster resumption of normal intracellular signalling, enhancing neuronal recovery.
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PMID:Biphasic expression of the fos and jun families of transcription factors following transient forebrain ischaemia in the rat. Effect of hypothermia. 854 58

Severe traumatic brain injuries are extremely heterogeneous. At least seven of the secondary derangements in the brain that have been identified as occurring after most traumatic brain injuries also occur after cardiac arrest. These secondary derangements include posttraumatic brain ischemia. In addition, traumatic brain injury causes insults not present after cardiac arrest, i.e., mechanical tissue injury (including axonal injury and hemorrhages), followed by inflammation, brain swelling, and brain herniation. Brain herniation, in the absence of a mass lesion, is due to a still-to-be-clarified mix of edema and increased cerebral blood flow and blood volume. Glutamate release immediately after traumatic brain injury is proven. Late excitotoxicity needs exploration. Inflammation is a trigger for repair mechanisms. In the 1950s and 1960s, traumatic brain injury with coma was treated empirically with prolonged moderate hypothermia and intracranial pressure monitoring and control. Moderate hypothermia (30 degrees to 32 degrees C), but not mild hypothermia, can help prevent increases in intracranial pressure. How to achieve optimized hypothermia and rewarming without delayed brain herniation remains a challenge for research. Deoxyribonucleic acid (DNA) damage and triggering of programmed cell death (apoptosis) by trauma deserve exploration. Rodent models of cortical contusion are being used effectively to clarify the molecular and cellular responses of brain tissue to trauma and to study axonal and dendritic injury. However, in order to optimize therapeutic manipulations of posttraumatic intracranial dynamics and solve the problem of brain herniation, it may be necessary to use traumatic brain injury models in large animals (e.g., the dog), with long-term intensive care. Stepwise measures to prevent lethal brain swelling after traumatic brain injury need experimental exploration, based on the multifactorial mechanisms of brain swelling. Novel treatments have so far influenced primarily healthy tissue; future explorations should benefit damaged tissue in the penumbra zones and in remote brain regions. The prehospital arena is unexplored territory for traumatic brain injury research.
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PMID:Resuscitation from severe brain trauma. 860 6

The protective effect of hypothermia on DNA fragmentation following transient forebrain ischemia in mongolian gerbils was investigated. The DNA fragmentation demonstrated in situ in gerbil hippocampal CA1 was compared between intra- and post-ischemic hypothermia. Intra-ischemic hypothermia prevented the DNA fragmentation in hippocampal CA1 completely, while severe DNA damage was observed in post-ischemic hypothermia group. the degree of DNA fragmentation of hippocampal CA1 in the post-ischemic hypothermia group was equal to that in the ischemic control group. The results suggest that hypothermia during a transient forebrain ischemia exerts a protective effect on the post-ischemic hippocampal damage by preventing the DNA fragmentation in CA1 neurons.
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PMID:Hypothermic prevention of nuclear DNA fragmentation in gerbil hippocampus following transient forebrain ischemia. 862 3

The significance of mild hypothermia as a therapeutic measure for ischemic brain damage is presented on the basis of different experimental results. An extracellular glutamate surge, a sustained activation of N-methyl-D-aspartate (NMDA) receptors, and an enhancement of DNA binding activity to transcription factor AP-1, all being key items directly linked to excitotoxic neuronal damage, are deeply affected by slightly lowering temperature (mild hypothermia [MH]). The cellular mechanism of MH seems rather nonspecific but tends to collectively involve these key items rendering neurons resistant to ischemic damage. Clinical application of MH should be a great challenge to relieve deadly effects on central neurons.
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PMID:Ischemic neuronal damage. How does mild hypothermia modulate it? 887 59

Perinatal hypoxia-ischaemia induces a biphasic cerebral injury: the depletion in high energy phosphates during the insult returns to normal soon after resuscitation. However, some 8-15 h later a second phase of impaired energy metabolism begins, which is related to the severity of later neurodevelopmental impairment. Delayed injury differs from acute hypoxia-ischaemia because intracellular acidosis does not occur. Apoptosis may be a mechanism of delayed cellular injury. Apoptotic cells and typical DNA fragmentation have been found after perinatal hypoxia-ischaemia. In newborn piglets, fraction of apoptotic cells was directly related to the degree of high energy phosphate depletion during hypoxia-ischaemia. Apoptosis may be interrupted: in piglets, brain cooling for 12 h following resuscitation reduced the fraction of apoptotic but not necrotic cells. These results have implications for both the understanding of cerebral injury and the use of hypothermia as a neural rescue strategy in the developing brain.
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PMID:Apoptosis in perinatal hypoxic-ischaemic cerebral damage. 900 35

This study was undertaken to examine the possible role of nitric oxide (NO) on brown adipose tissue (BAT) thermogenesis in rats. The chronic administration of N omega-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) in drinking water given to rats decreased interscapular BAT (IBAT) weight as well as DNA content in a warm environment (25 +/- 1 degrees C; 2 and 4 weeks), and inhibited the cold-stimulated (5 +/- 1 degrees C; 2 weeks) increase in IBAT weight and DNA content. L-Arginine administration (4 weeks in a warm environment) increased the DNA content of IBAT. Chronic L-NAME administration (2 weeks in a warm environment) eliminated the NE-stimulated increase in in vivo oxygen consumption (VO2), caused hypothermia in acute cold exposure (0 degree C), and suppressed the NE-stimulated increase in in vitro IBAT VO2. In vitro incubation of native IBAT with L-NAME suppressed the basal and NE-stimulated increase in in vitro VO2. In vitro incubation of IBAT with methylene blue (soluble guanylate cyclase inhibitor and a scavenger of free NO) eliminated the NE-stimulated increase in in vitro IBAT VO2. These results suggest that the nitric oxide and NO-cGMP signaling systems are involved in the regulation of BAT cellularity and thermogenesis in rats.
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PMID:Effects of acute and chronic inhibition of nitric oxide synthase on brown adipose tissue thermogenesis. 904 15

We have previously reported that amifostine potentiates the anti-tumour activity of carboplatin in mice. The present study was carried out in well-established human ovarian cancer xenografts OVCAR-3, A2780 and FMa grown subcutaneously in the nude mouse. It was found that a single dose of amifostine resulted in a higher increase in the anti-tumour activity of carboplatin than three doses of amifostine. A single dose of amifostine increased the AUC (area under the curve) values of total platinum in plasma ultrafiltrate (30.1 vs 18.2 microM x h), liver (307.7 vs 236.4 nmol g(-1) x h), kidney (500.8 vs 368.3 nmol g(-1) x h) and OVCAR-3 tumour tissue (184.0 vs 146.8 nmol g(-1) x h). Despite this increase in total platinum, a decrease in platinum (Pt)-DNA adduct levels was observed in liver, kidney and bone marrow, which was significant in liver. In tumour tissue an insignificant increase in Pt-DNA adduct levels, specifically the Pt-GG adduct, was observed after treatment with a single dose of amifostine, which may explain the increase in anti-tumour activity. The increase in the AUC of total platinum was probably caused by a reduction in body temperature, which was most severe after three doses of amifostine. The extreme hypothermia may be the reason that three doses of amifostine resulted in less potentiation of the efficacy of carboplatin.
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PMID:Influence of single and multiple doses of amifostine on the efficacy and the pharmacokinetics of carboplatin in mice. 916 35

Gel retardation electrophoresis revealed that binding of a radiolabelled double-stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 was markedly potentiated in the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils with transient forebrain ischemia for 5 min, which is known to induce delayed death of pyramidal neurons exclusively in the CA1 subfield. The potentiation was transient in the vulnerable CA1 subfield, but persistent up to 18 h in the resistant CA3 subfield and dentate gyrus. However, no significant alteration was detected in endogenous levels of cyclic AMP response element binding protein phosphorylated at serine133 in these three different hippocampal structures 3 h after the reperfusion. On the other hand, hypothermia during ischemia which is known to protect the CA1 subfield against ischemic damages, led to a prolonged elevation of the activator protein-1 binding up to 9 h after the reperfusion in this vulnerable subfield at least in part through expression of c-Fos protein. Moreover, activator protein-1 binding was significantly elevated in the CA1 subfield up to 12 h after forebrain ischemia for 2 min which is shown not to induce marked damages to the vulnerable subfield. These results suggest that prolonged elevation of DNA binding activity of activator protein-1 may be responsible for molecular mechanisms underlying the unique vulnerability and/or resistance of particular subfields to a transient ischemic insult in the gerbil hippocampus.
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PMID:Positive correlation between prolonged potentiation of binding of double-stranded oligonucleotide probe for the transcription factor AP1 and resistance to transient forebrain ischemia in gerbil hippocampus. 921 65

This study was designed to determine the effects of short episodes of mild hypothermia on cell apoptosis in the testis of the adult rat. Apoptosis was assessed by in situ DNA 3'-end labeling in the testes from rats killed 2 hours after cooling (10 degrees C for 30 minutes), quantitated, and compared with spontaneous apoptosis found in control animals. A significantly increased number of dying germ cells appeared after cold treatment at specific stages (stage XIV, P < 0.0001; stage XII, P < 0.001) of the seminiferous epithelium, mainly due to dying primary metaphasic spermatocytes (P < 0.0001), followed by secondary interphase spermatocytes (P < 0.001), and A2 spermatogonia (P < 0.05). The highly specific effect of mild hypothermia on germ cell apoptosis suggests that the process is tightly regulated.
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PMID:Mild hypothermia induces apoptosis in rat testis at specific stages of the seminiferous epithelium. 934 52

To examine the role of the early changes occurring in the liver within the first hours after a partial hepatectomy and in an attempt to demonstrate the involvement of subsequent regulatory mechanisms, the size of the remnant liver was modified at various times and by different surgical techniques. Male Wistar rats were submitted to a two-thirds "temporary partial hepatectomy" produced by a 3-h occlusion of the pedicle of the anterior lobes protected by local hypothermia. Various indexes of cell proliferation ([3H]thymidine uptake and 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen labeling) were not increased despite a c-myc expression as high as that observed after a two-thirds partial hepatectomy. The temporary partial hepatectomy and a sham operation induced modifications of the hepatocytes, allowing rapid DNA synthesis after a subsequent two-thirds partial hepatectomy. After this initial nonspecific response, the extent of the regenerative response is determined according to the size of the liver mass present approximately from the 10th to the 18th hour after the initial stimulus. For instance, when a one-third partial hepatectomy was converted into a two-thirds partial hepatectomy at the 10th hour, the DNA synthesis at the 24th hour reached the value observed after a straightforward two-thirds partial hepatectomy. Inversely, the regenerative response was significantly reduced when additional liver lobes were connected to neck vessels between the 14th and the 18th hour after a two-thirds partial hepatectomy. In conclusion, the actual liver mass present during the period corresponding to mid- to late G1 appears to control the magnitude of the proliferative response, which is not the simple consequence of the early changes following a partial hepatectomy.
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PMID:Control of rate and extent of the proliferative response after partial hepatectomy. 935 34


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