Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was undertaken to ascertain the protective effect of topical hypothermia on the anoxic heart. The presence or absence of myocardial damage was judged by myocardial contractility. The papillary muscle of an excised rabbit heart was detached from the mitral annulus and interposed between a fixed point and a force/displacement transducer. The maximal net developed tension (TNmax) of the papillary muscle with normothermic coronary perfusion was used as an index of myocardial contractility. With each temperature drop of 10 degrees C, the anoxia time that resulted in the same recovery level of TNmax was prolonged by a factor of 2.8. A nomogram was constructed correlating percent of myocardial recovery seen with different degrees of myocardial hypothermia during various anoxic periods. Optimum protection was noted at a myocardial temperature of 18 degrees C.
 ...
PMID:Effect of hypothermic anoxic cardioplegia on myocardial contractility. 99 66

The effects of trimethyltin chloride (TMT) on protein synthesis, measured as the incorporation of [3H]valine into trichloroacetic acid-precipitable material, were investigated in mice. One hour after intraperitoneal administration of a 3.0 mg/kg dose, TMT decreased brain protein synthesis by 47% and also caused a significant decrease (4.2 degrees C) in body temperature. When hypothermia was prevented by maintaining the animals at 35 degrees C, TMT decreased protein synthesis by 20%. Twenty-four hours following administration of TMT, protein synthesis was decreased in brain and liver; however, only a reduction of brain protein synthesis was observed at 48 hr. No hypothermia was present at either time point. A regional study in brain showed that at 24 and 48 hr after TMT administration, protein synthesis was decreased by 18-23% in cerebral cortex and hippocampus but not in cerebellum. TMT also inhibited protein synthesis in vitro in mouse brain homogenates with an IC50 of about 100 microM. Neither SnCl2, nor dimethyltin or monomethyltin had any effect on protein synthesis in vitro. These results suggest that, as for other neurotoxicants such as methyl mercury or acrylamide, inhibition of protein synthesis might be involved in TMT neurotoxicity.
 ...
PMID:Inhibition of protein synthesis by trimethyltin. 378 19

The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biological evaluation of a series of conformationally constrained analogues of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74, were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, respectively) and human TRPV1 (IC50 = 7.4 and 3.7 nM, respectively). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund's adjuvant in rats.
 ...
PMID:Novel vanilloid receptor-1 antagonists: 1. Conformationally restricted analogues of trans-cinnamides. 1758 49

We have analysed the published literature on eptacog alfa (recombinant factor VIIa; rFVIIa) for nonhaemophiliac conditions with the aim of determining its current place in therapy. Initial surgical and/or medical management is required for any patient with life-threatening bleeding. In those with continued life-threatening bleeding (i.e. despite maximal surgical and/or medical therapy), eptacog alfa may be considered as additional therapy, in exceptional circumstances. There is good evidence from systematic reviews and randomized controlled trials (RCTs) that eptacog alfa stops bleeding in adults with intracerebral haemorrhage (ICH) if it is given within 4 hours of symptom onset. However, a recent phase III RCT suggests that it does not improve clinically relevant long-term outcomes (death and disability). There is also good evidence against prophylactic use of eptacog alfa during orthotopic liver transplantation or liver resection, and in treating variceal and nonvariceal haemorrhage in patients with cirrhosis. The evidence for the use of eptacog alfa for unexpected life-threatening bleeding in liver, cardiac or other surgery, or in blunt trauma, is not robust. In these circumstances, it should only be given as part of a clinical trial or in exceptional cases when other therapies have failed. The evidence for use of eptacog alfa in penetrating trauma is lacking. Conflicting RCT results exist for the prophylactic use of eptacog alfa in elective surgery; therefore, it cannot be recommended in this situation. There is insufficient evidence for a primary role of eptacog alfa in reversal of anticoagulation with heparin-like molecules and novel anticoagulant agents. There are effective therapies that correct all warfarin-induced factor deficiencies; thus, off-label use of eptacog alfa for reversal of warfarin should only be considered in the context of ICH. The evidence for eptacog alfa use in children is limited. The only RCT is in cardiac surgery for congenital heart disease, where eptacog alfa prophylaxis was actually associated with increased time to chest closure. It may be of potential benefit in some children with life-threatening bleeding in the context of trauma, surgery or liver disease (as additional therapy when surgical and/or medical control of bleeding has failed), but the overall benefit-risk ratio may be unfavourable if there is an underlying risk of thromboembolism (e.g. trauma, congenital heart disease, other hyperviscous or hypercoagulable states, presence of arterial or central venous catheters). Thromboembolism may be associated with eptacog alfa use. Although the magnitude of this risk and possible predisposing factors are not clearly delineated, some data suggest increased risk at higher doses. Variable effects of eptacog alfa use on mortality have been shown in a pooled analysis of RCTs. Data from some observational studies and postmarketing surveillance suggest an increased risk of thromboembolism associated with off-label uses. Further well designed studies are required to more definitively assess the risk of thromboembolism with eptacog alfa and to better determine its effects on mortality. Optimum dosages for nonhaemophiliac conditions are not defined and nor is the optimum timing of administration. Moreover, it is not clear which patients will be most likely to benefit in terms of haemostatic efficacy and mortality. In addition to conventional measures to stop bleeding (i.e. surgery and blood transfusion), correction of hypothermia and acidosis, and reversal of anticoagulation are all recommended. The outcomes (effectiveness and safety) of all off-label uses should be systematically evaluated and reported. Adequate data to assess cost effectiveness for eptacog alfa does not exist for most off-label indications.
 ...
PMID:An evaluation of eptacog alfa in nonhaemophiliac conditions. 1868 90

Scald first-aid needs to reduce the local temperature as well as the bacterial colonization. Bacteria resistant problem has become a major challenge that global public health workers face. Long-term and high dosage use of antibacterial agents is the main reason. In this study, temperature-regulated release antibacterial nanoparticles were applied to poly(n-isopropyl acrylamide) and sodium polyacrylate. This hypothermia coverage could be used as an ideal scald first-aid wound dressing with spontaneous Temperature & Antibacterial regulation properties.
 ...
PMID:Dual layered wound dressing with simultaneous temperature & antibacterial regulation properties. 3042 88

Optimum care of sick neonates often involves transporting them across different levels of care. Since their condition may deteriorate over time, attention needs to be paid to travel distances and how they are transferred. We examined the mode of transport, distances travelled, condition on arrival and outcome of outborn neonates admitted to a district and a regional hospital in Ghana using a cross-sectional study involving caregivers of neonates admitted to these hospitals. Information on referral characteristics and outcome were obtained from questionnaires and the child's case notes. Overall, 153 caregivers and babies were studied. Twelve deaths, 7.8%, occurred. Neonates who died spent a median duration of 120 min at the first health facility they visited compared with 30 min spent by survivors; they travelled mostly by public buses, (41.7%), compared with 36.0% of survivors who used taxis. Majority of survivors, 70.2%, had normal heart rates on arrival compared with only 41.7% of neonates who died; hypothermia was present in 66.7% compared with 47.6% of survivors. These findings indicate that the logistics for neonatal transport were inadequate to keep the neonates stable during the transfer process, thus many of them were compromised especially those who died. Further studies are warranted.
 ...
PMID:The Transport and Outcome of Sick Outborn Neonates Admitted to a Regional and District Hospital in the Upper West Region of Ghana: A Cross-Sectional Study. 3224 43