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)

Systemic photochemical pretreatment of a rat kidney donor with the photosensitizer 8-methoxypsoralen (8-MOP; 0.06 mg/kg intravenously, 10 min before graft removal) plus ex vivo longwave ultraviolet (UVA) irradiation of the kidney graft during simple hypothermic storage significantly prolonged survival time in allogeneic recipients. In contrast to these results, the present use of UVA irradiation during hypothermic pulsatile kidney perfusion using Euro-Collins solution containing 8-MOP (0.06 mg/ml) did not prolong graft survival compared with untreated controls. Systemic application of 8-MOP to the kidney donor may be necessary for effective action of the combined photochemical treatment as a method of immunoalteration. The extended UVA irradiation time and the local use of 8-MOP in the preservation fluid had no effect on graft survival possibly because of inadequate tissue distribution of 8-MOP during both hypothermia and perfusion.
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PMID:Failure to prolong rat renal allograft survival time by photochemical donor kidney pretreatment during hypothermic pulsatile kidney preservation. 327 79

Studies were undertaken to examine whether methoxsalen (9-methoxyfuro[3,2-g][1]benzopyran-7-one), a specific and relatively selective inhibitor of human CYP2A6, inhibited CYP2A5-mediated nicotine metabolism in vitro. Furthermore, studies were performed in vivo to determine whether methoxsalen would modulate acute nicotine pharmacokinetics and pharmacological effects (antinociception and hypothermia) in the ICR mouse. Our results demonstrated that methoxsalen competitively inhibits in vitro nicotine metabolism in mice. The inhibition was potent, as seen in human inhibition studies, with a Ki of 0.32 microM. In addition, we found that administration of methoxsalen significantly increased the plasma half-life of nicotine (approximately doubled) and increased its area under the curve compared with saline treatment. There was a dose-dependent enhancement in the pharmacological effects of nicotine (body temperature and analgesia) after methoxsalen treatment. Methoxsalen prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg) for periods up to 180 min postnicotine administration. Furthermore, this prolongation in nicotine's effects after methoxsalen was associated with a parallel prolongation of nicotine plasma levels in mice. These data strongly suggest that variation in the rates of nicotine metabolic inactivation substantially alter nicotine's pharmacological effects. In conclusion, these results confirmed that methoxsalen did indeed inhibit the conversion of nicotine to cotinine both in vitro and in vivo. They also suggest that mice may represent a suitable model for studying variation in nicotine metabolism and its impact on mechanisms of nicotine dependence, including the use of inhibitors to reduce nicotine metabolism.
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PMID:Inhibition of nicotine metabolism by methoxysalen: Pharmacokinetic and pharmacological studies in mice. 1702 Dec 60