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

Previous studies have shown that treatment with free radical scavengers attenuated the D-amphetamine (AMPH) neurotoxicity. But several of these agents also prevent AMPH-induced elevation of body temperature in the rat. Thus, further studies are needed to determine if blockade of the production of free radical or hypothermia are related to the neuroprotective mechanism of the free radical scavengers for AMPH neurotoxicity. In the present study, we examined the effects of the free radical scavengers alpha-phenyl-N-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC) on long-term depletion of striatal dopamine (DA) and lipid peroxidation formation and on hyperthermia induced by AMPH. We also determined their effects on acute hydroxyl radical formation after direct intrastriatal infusion of AMPH. The results showed that both significantly attenuated long-term DA depletion and lipid peroxidation formation in the rat striatum at the dose range that did not block hyperthermia induced by AMPH. These agents also completely inhibited the production of hydroxyl radical after AMPH infusion into the striatum. Our results suggest that free radical scavengers such as PBN and NAC could protect against AMPH-induced oxidative stress and DAergic terminal toxicity via their free radical removing property independent of lowering the core body temperature of rats, and imply that supplement with antioxidants is a potential strategy in the treatment of AMPH neurotoxicity.
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PMID:Effects of alpha-phenyl-N-tert-butyl nitrone and N-acetylcysteine on hydroxyl radical formation and dopamine depletion in the rat striatum produced by d-amphetamine. 1606 57

Hypoxic ischemic (HI) injury in neonates may have devastating, long-term consequences. Recently completed clinical trials in HI neonates indicate that hypothermia within 6 h of birth results in modest improvement in the combined outcome of death or severe disability. The aim of this study was to investigate the effects of combining hypothermia and N-acetylcysteine (NAC) on brain injury, neonatal reflexes and myelination after neonatal HI. Seven-day-old rats were subjected to right common carotid artery ligation and hypoxia (8% oxygen) for 2 h. Systemic hypothermia (30 + 0.5 degrees C) was induced immediately after the period of HI and was maintained for 2 h. NAC (50 mg/kg) was administered by intraperitoneal injection daily until sacrifice. Brain infarct volumes were significantly reduced at 48 h post-HI in the hypothermia plus NAC group (21.5 +/- 3.84 mm3) compared with vehicle (240.85 +/- 4.08 mm3). Neonatal reflexes were also significantly improved by combination therapy at days 1 and 7. There was a significant loss of right hemispheric brain volume in the untreated group at 2 and 4 wk after HI insult. Brain volumes were preserved in hypothermia plus NAC group and were not significantly different when compared with the sham group. Similarly, increased myelin expression was seen in brain sections from hypothermia plus NAC group, when stained for Luxol Fast Blue (LFB), Myelin Basic Protein (MBP) and Proteolipid protein (PLP). These results indicate that hypothermia plus NAC combination therapy improves infarct volume, myelin expression and functional outcomes after focal HI injury.
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PMID:Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats. 1662 82

Severe hepatitis A infection is an infrequent but well-recognized cause of acute liver failure that can now be effectively prevented with vaccination against hepatitis A virus. Bromfenac and troglitazone hepatotoxicity as well as various herbal remedies are some of the newly identified causes of acute liver failure. The recently identified transfusion-transmitted virus has been implicated in some cases of idiopathic acute liver failure whereas hepatitis G virus does not appear to be a causative agent. Recognizing, monitoring, and treating patients with life-threatening cerebral edema remain critically important but difficult aspects of the clinical care of acute liver failure. Hypothermia and N-acetylcysteine are promising experimental approaches to cerebral edema but emergency liver transplantation is the only proven means of improving patient survival. Although recent changes in organ allocation may reduce waiting time to transplantation, more reliable and validated markers of liver regeneration and prognosis are needed to triage patients. The potential application and limitations of novel technologies including bioartificial liver devices and auxiliary liver transplantation continue to evolve from pioneering work in animal models and human subjects.
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PMID:Acute liver failure. 1702 55

Continued elucidation of the mechanisms of brain edema in acute liver failure (ALF) has established ammonia and the astrocyte as major players in its pathogenesis. The metabolism of ammonia to glutamine appears to be a requisite, and is followed by an osmotic disturbance in the brain, mitochondrial dysfunction with oxidative/nitrosative stress, and alterations of brain glucose metabolism. Cerebral blood flow (CBF) is also altered in ALF and strongly influence the development of brain edema and intracranial hypertension. Additional factors such as systemic inflammation, alterations of the brain extracellular concentration of amino acids and neurotransmitters, and others have been identified and may contribute to the cerebral alterations of ALF. Such pathophysiologic insights are reflected in the various clinical trials of novel therapeutic interventions using ammonia-lowering agents, N-acetylcysteine, hypertonic saline, indomethacin, high-volume plasmapheresis, bio-artificial liver assist devices, albumin dialysis and mild hypothermia.
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PMID:Mechanisms of brain edema in acute liver failure and impact of novel therapeutic interventions. 1817 8

Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (approximately 60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research.
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PMID:Acute liver failure: Summary of a workshop. 1831 40

Antioxidants specifically addressed to mitochondria have been studied to determine if they can decelerate senescence of organisms. For this purpose, a project has been established with participation of several research groups from Russia and some other countries. This paper summarizes the first results of the project. A new type of compounds (SkQs) comprising plastoquinone (an antioxidant moiety), a penetrating cation, and a decane or pentane linker has been synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ derivatives with the highest permeability, namely plastoquinonyl-decyl-triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19 (SkQR1), and methylplastoquinonyldecyltriphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in aqueous solution, detergent micelles, liposomes, BLM, isolated mitochondria, and cell cultures. In mitochondria, micromolar cationic quinone derivatives were found to be prooxidants, but at lower (sub-micromolar) concentrations they displayed antioxidant activity that decreases in the series SkQ1=SkQR1>SkQ3>MitoQ. SkQ1 was reduced by mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Nanomolar SkQ1 specifically prevented oxidation of mitochondrial cardiolipin. In cell cultures, SkQR1, a fluorescent SkQ derivative, stained only one type of organelles, namely mitochondria. Extremely low concentrations of SkQ1 or SkQR1 arrested H(2)O(2)-induced apoptosis in human fibroblasts and HeLa cells. Higher concentrations of SkQ are required to block necrosis initiated by reactive oxygen species (ROS). In the fungus Podospora anserina, the crustacean Ceriodaphnia affinis, Drosophila, and mice, SkQ1 prolonged lifespan, being especially effective at early and middle stages of aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of development of such age-related diseases and traits as cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of the thymus, hypothermia, torpor, peroxidation of lipids and proteins, etc. SkQ1 manifested a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision was restored to 67 of 89 animals (dogs, cats, and horses) that became blind because of a retinopathy. Instillation of SkQ1-containing drops prevented the loss of sight in rabbits with experimental uveitis and restored vision to animals that had already become blind. A favorable effect of the same drops was also achieved in experimental glaucoma in rabbits. Moreover, the SkQ1 pretreatment of rats significantly decreased the H(2)O(2) or ischemia-induced arrhythmia of the isolated heart. SkQs strongly reduced the damaged area in myocardial infarction or stroke and prevented the death of animals from kidney ischemia. In p53(-/-) mice, 5 nmol/kgxday SkQ1 decreased the ROS level in the spleen and inhibited appearance of lymphomas to the same degree as million-fold higher concentration of conventional antioxidant NAC. Thus, SkQs look promising as potential tools for treatment of senescence and age-related diseases.
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PMID:An attempt to prevent senescence: a mitochondrial approach. 1915 10

In most cases of neonatal hypoxic-ischemic encephalopathy, the exact timing of the hypoxic-ischemic event is unknown, and we have few reliable biomarkers to precisely identify the phase of injury or recovery in an individual patient. However, it is becoming increasingly clear that for neuroprotection in neonates to succeed, an understanding of the phase of injury is important to ascertain. In addition, in utero antecedents of chronic hypoxia, hypoxic preconditioning, intrauterine infection, and fetal gender may change the expected time course of injury. Neuroprotective interventions, such as hypothermia and N-acetylcysteine, currently have efficacy in human and animal studies only if instituted early in the inflammatory cascade. Although these cascades are currently being investigated, molecular mechanisms of recovery have received little attention and may ultimately reveal a window for therapeutic intervention that is much longer than current paradigms.
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PMID:Neuroprotective interventions: is it too late? 1974 93

Neuroprotection is a major health care priority, given the enormous burden of human suffering and financial cost caused by perinatal brain damage. With the advent of hypothermia as therapy for term hypoxic-ischemic encephalopathy, there is hope for repair and protection of the brain after a profound neonatal insult. However, it is clear from the published clinical trials and animal studies that hypothermia alone will not provide complete protection or stimulate the repair that is necessary for normal neurodevelopmental outcome. This review critically discusses drugs used to treat seizures after hypoxia-ischemia in the neonate with attention to evidence of possible synergies for therapy. In addition, other agents such as xenon, N-acetylcysteine, erythropoietin, melatonin and cannabinoids are discussed as future potential therapeutic agents that might augment protection from hypothermia. Finally, compounds that might damage the developing brain or counteract the neuroprotective effects of hypothermia are discussed.
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PMID:Synergistic neuroprotective therapies with hypothermia. 2020

Septic shock is associated with life-threatening vasodilation and hypotension. To cause vasodilation, vascular endothelium may release nitric oxide (NO), prostacyclin (PGI2), and the elusive endothelium-derived hyperpolarizing factor (EDHF). Although NO is critical in controlling vascular tone, inhibiting NO in septic shock does not improve outcome, on the contrary, precipitating the search for alternative therapeutic targets. Using a hyperacute tumor necrosis factor (TNF)-induced shock model in mice, we found that shock can develop independently of the known vasodilators NO, cGMP, PGI2, or epoxyeicosatrienoic acids. However, the antioxidant tempol efficiently prevented hypotension, bradycardia, hypothermia, and mortality, indicating the decisive involvement of reactive oxygen species (ROS) in these phenomena. Also, in classical TNF or lipopolysaccharide-induced shock models, tempol protected significantly. Experiments with (cell-permeable) superoxide dismutase or catalase, N-acetylcysteine and apocynin suggest that the ROS-dependent shock depends on intracellular (*)OH radicals. Potassium channels activated by ATP (K(ATP)) or calcium (K(Ca)) are important mediators of vascular relaxation. While NO and PGI2-induced vasodilation involves K(ATP) and large-conductance BK(Ca) channels, small-conductance SK(Ca) channels mediate vasodilation induced by EDHF. Interestingly, also SK(Ca) inhibition completely prevented the ROS-dependent shock. Our data thus indicate that intracellular (*)OH and SK(Ca) channels represent interesting new therapeutic targets for inflammatory shock. Moreover, they may also explain why antioxidants other than tempol fail to provide survival benefit during shock.
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PMID:Reactive oxygen species and small-conductance calcium-dependent potassium channels are key mediators of inflammation-induced hypotension and shock. 2049 72

Hypoxic ischaemic encephalopathy continues to be a significant cause of death and disability worldwide. In the last 1-2 years, therapeutic hypothermia has entered clinical practice in industrialized countries and neuroprotection of the newborn has become a reality. The benefits and safety of cooling under intensive care settings have been shown consistently in trials; therapeutic hypothermia reduces death and neurological impairment at 18 months with a number needed to treat of approximately nine. Unfortunately, around half the infants who receive therapeutic hypothermia still have abnormal outcomes. Recent experimental data suggest that the addition of another agent to cooling may enhance overall protection either additively or synergistically. This review discusses agents such as inhaled xenon, N-acetylcysteine, melatonin, erythropoietin and anticonvulsants. The role of biomarkers to speed up clinical translation is discussed, in particular, the use of the cerebral magnetic resonance spectroscopy lactate/N-acetyl aspartate peak area ratios to provide early prognostic information. Finally, potential future therapies such as regeneration/repair and postconditioning are discussed.
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PMID:Experimental treatments for hypoxic ischaemic encephalopathy. 2057 Apr 49


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