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)

Induction of hypothermia is used routinely in neurosurgical and cardiovascular operations to protect the brain from ischemic insult. However, despite a plethora of experimental evidence supporting the use of hypothermia to protect the brain from ischemia, clinical experience using deliberate hypothermia in humans has not shown a convincing benefit. The authors tested the hypothesis that hypothermia and rewarming alter tone in human cerebral vessels and may interfere with cerebral perfusion in the setting of deliberate hypothermia. They examined human cerebral arteries during hypothermia (32 degrees C and 17 degrees C) and during rewarming to delineate the direct effects of cooling and rewarming on cerebrovascular tone. Artery segments obtained from autopsy material and from specimens excised at elective temporal lobectomies were tested in tissue baths using isometric tension measurements. Temperature-induced changes in vascular tone were measured and quantified with respect to contractile responses to serotonin (5-HT; 10(-6) M). Cooling induced mild relaxation in cerebral vessels (-38 +/- 12% 5-HT response in 50 vessels from autopsy specimens, -69 +/- 10% 5-HT response in 51 vessels from lobectomy specimens). On rewarming, vessels contracted significantly beyond their baseline tone (108 +/- 18% 5-HT response in 50 vessels from autopsy specimens, 42 +/- 12% 5-HT response in 51 vessels from lobectomy specimens). Rewarming-induced hypercontractility was inhibited by the tyrosine kinase inhibitor genistein (-5 +/- 7% vs. 70 +/- 23% 5-HT response, genistein vs. control, 14 segments, p < 0.05) and enhanced by the tyrosine phosphatase inhibitor sodium orthovanadate (339 +/- 54% vs. 104 +/- 20% 5-HT response, sodium orthovanadate vs. control, five segments, p < 0.05), indicating a possible role for tyrosine kinase activation in the rewarming-induced contraction.
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PMID:Induction of hypercontractility in human cerebral arteries by rewarming following hypothermia: a possible role for tyrosine kinase. 928 10

Bombesin (BN) and structurally related peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), injected into the lateral ventricle produce multiple effects such as hypothermia, anorexia and hormone release. In this study, the pharmacological characteristics of BN receptors mediating hypothermia in the central nervous system (CNS) were investigated using free-moving male Wistar rats. Intracerebroventricular injections of BN, GRP and NMB produced hypothermia in a dose-dependent manner. The BN (0.3 microg)-induced effect showed a short latency and a 4-h duration with a potency increased by more than 100 times compared to the NMB-induced effect. Pretreatment with [D-Tyr(6)]BN(6-13)methylester, a GRP receptor antagonist, inhibited the BN (0.3 microg)- and NMB (7 microg)-induced hypothermia. On the other hand, BIM23127, an NMB receptor antagonist, did not influence the hypothermia. Of the protein kinase C (PKC) inhibitors, chelerythrine, Go6983, staurosporine and GF109203X, the first two partially blocked the BN-induced hypothermia. A PKC activator, phorbol-12,13-dibutyrate, decreased the rectal temperature. Genistein (a tyrosine kinase inhibitor), Y-27632 (a Rho kinase inhibitor) and PD98059 (a MAPK inhibitor) tended to suppress the BN-induced hypothermia, however, these were not significant. The inhibitory effect of a mixture of the three inhibitors, chelerythrine, genistein and Y-27632, on the BN-induced hypothermia was of a similar degree to that of chelerythrine alone. The BN receptor mediating the hypothermia seem to be the GRP subtype, and the effect involves activation of PKC.
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PMID:Pharmacological characteristics of bombesin receptor mediating hypothermia in the central nervous system of rats. 1267 68

Effective therapies for malignant gliomas are still elusive and limited survival improvements are provided only by Temozolomide or fluorescence guided resection. The efficacy of photodynamic therapy (PDT) in this indication is limited by the higher sensitivity of normal brain structures compared to glioma necessitating a modulation of its sensitivity. We evaluate the influence of hypothermia and the tyrosine kinase inhibitor Erlotinib on cell's ability to synthesize PPIX following the administration of ALA which was not previously investigated. We demonstrate that both hypothermia and Erlotinib are favorable in PPIX selectivity as only glioma cell lines demonstrate an increased PPIX synthesis, whereas the neuronal and astrocytic synthesis is remaining unaffected. The results are encouraging to consider hypothermia and Erlotinib as adjuvant therapies to increase the PDT therapeutic index between GBM and normal intracranial tissues, as well as to improve contrast in fluorescence guided resection.
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PMID:Modulation of PPIX synthesis and accumulation in various normal and glioma cell lines by modification of the cellular signaling and temperature. 2403 24