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)

Histochemical analysis of some lysosomal and sarcoplasmic proteolytic enzymes was assayed in human myocardial biopsies taken from 26 cardiopathic patients subjected to open heart operations, under extracorporeal circulation and protection with cardioplegic solution and hypothermia. The investigated myocardial proteases were: cathepsin B, cysteine aminopeptidase, acid gelatinases, trypsin-like endopeptidase, chymotrypsin-like endopeptidase and neutral gelatinases. The effects of surgical interventions appreciated by comparing the myocardium fragments harvested before, and at various intervals after aorta clamping (6-90 minutes) revealed disorders in the activity and compartmentalization of all the investigated proteases, whose histochemical reactions increased between 10 and 20 minutes after aorta clamping and manifested a lowering tendency with sarcoplasmic diffusion and extracellular release at longer periods than 20 minutes. The early activation of the neutral proteases and their sarcolemmal expression even before 10 minutes after aorta clamping, suggested the involvement of the nonlysosomal proteases in the first proteolytic events implied in the molecular membrane damage of the myocardial fibre. Sequential proteolytic cascades of abnormal neutral and acid proteases were emphasized as possible mediators and effectors of molecular and subcellular damages suffered by the myocardial fibers during the open heart operations, even under cardioplegic and hypothermic protection.
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PMID:Histochemical reactions of myocardial proteases during open heart surgery. 252 27

A 1-year-old child with severe acetaminophen (APAP) poisoning after ingestion of 10 gm APAP demonstrated central nervous system depression, shock, hypothermia, and metabolic acidosis. There was dramatic improvement during treatment with intravenously administered N-acetylcysteine (NAC) and hemodialysis, and the patient recovered without sequelae. A detailed study of APAP metabolism was carried out during the initial 72 hours after ingestion. APAP-sulfate and APAP-glucuronide accounted for 29% and 33%, respectively, of total drug in urine, whereas cysteine and NAC conjugates accounted for only 12%. The low incidence of severe toxicity in children after overdoses of APAP may be related to greater capacity to metabolize APAP via a nontoxic pathway.
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PMID:Metabolism and pharmacokinetics of acetaminophen in a severely poisoned young child. 673 27

The hepatobiliary transport of glutathione (GSH) and methylmercury (MM) was investigated in male and female rats anesthetized with pentobarbital sodium. When bile flow was altered with either sodium dehydrocholate (DHC), hypertonic sucrose infusion, or by hypothermia, the absolute rates of GSH and MM secretion into bile were not affected, resulting in parallel concentration changes in the bile fluid for both GSH and MM. Indocyanine green and sulfobromophthalein (BSP), but not BSP-glutathione complex, inhibited the biliary secretion of free GSH. This inhibition was accompanied by a parallel inhibition of MM secretion into bile and occurred without any changes in liver GSH or MM levels. On the other hand, the intravenous administration of cysteine, GSH, and penicillamine was associated with an increase in the secretion rate of reduced sulfhydryl groups into bile and an increase in the biliary secretion rate of MM. The increased biliary secretion rate of MM after phenobarbital pretreatment was also associated with an increased rate of secretion of GSH into bile. In addition, sex differences and individual variability in the biliary secretion of MM were correlated with differing abilities to secrete GSH into bile. The results suggest the presence of a biliary transport system for GSH that determines the biliary secretion of MM.
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PMID:Biliary transport of glutathione and methylmercury. 683 49

Hydrogen sulphide (H2S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. The production of H2S from L-cysteine is catalysed primarily by two enzymes, cystathionine gamma-lyase and cystathionine beta-synthase. Evidence is accumulating to demonstrate that inhibitors of H2S production or therapeutic H2S donor compounds exert significant effects in various animal models of inflammation, reperfusion injury and circulatory shock. H2S can also induce a reversible state of hypothermia and suspended-animation-like state in rodents. This article overviews the physiology and biochemistry of H2S, summarizes the effects of H2S inhibitors or H2S donors in animal models of disease and outlines the potential options for the therapeutic exploitation of H2S.
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PMID:Hydrogen sulphide and its therapeutic potential. 1794 22

Hypothermic preservation of bioartificial liver (BAL) has long been appreciated in BAL storage and transportation. However, the deterioration of cell activity during hypothermia/rewarming limits its clinical use and the complete prevention of hypothermia-induced hepatocyte injury has not been achieved. In this article, a miniaturized BAL that underwent three preservation stages (i.e. pre-incubation, hypothermia and rewarming) was applied as a hypothermic preservation model to locate the protection of several protective agents against hypothermia-induced cell injury. The agents, including vitamin E, schisandrin B, glycyrrhizic acid, N-acetyl-cysteine, ruthenium red, trehalose, anisodamine, fructose-1, 6-diphosphate, cyclosporin A and matrine (Mat), were found to exert their functions at different preservation stages, which were speculated to associate with the specific protection of each agent as well as the corresponding cell injuries at each stage. Such hypothesis was further strengthened by focusing on Mat, which only suppressed the hypothermia-induced injury through the inhibition of Ca(2+) overload at the rewarming stage, whereas its presence at the hypothermic stage excessively down-regulated the cytosolic free Ca(2+) and then aggravated cell death. The results indicate that the specific cell injury at each preservation stage requires a corresponding protective agent. However, the untimely misuse of the agents may inversely aggravate cell injury.
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PMID:Differential function of protective agents at each stage of the hypothermic preservation of hepatocytes. 2139 67

A compromised intrauterine environment that delivers low levels of oxygen and/or nutrients, or is infected or inflammatory, can result in fetal brain injury, abnormal brain development and in cases of chronic compromise, intrauterine growth restriction. Preterm birth can also be associated with injury to the developing brain and affect the normal trajectory of brain growth. This review will focus on the effects that episodes of perinatal hypoxia (acute, chronic, associated with inflammation or as an antecedent of preterm birth) can have on the developing brain. In animal models of these conditions we have found that relatively brief (acute) periods of fetal hypoxemia can have significant effects on the fetal brain, for example death of susceptible neuronal populations (cerebellum, hippocampus, cortex) and cerebral white matter damage. Chronic placental insufficiency which includes fetal hypoxemia, nutrient restriction and altered endocrine status can result in fetal growth restriction and long-term deficits in neural connectivity in addition to altered postnatal function, for example in the auditory and visual systems. Maternal/fetal inflammation can result in fetal brain damage, particularly but not exclusively in the white matter; injury is more pronounced when associated with fetal hypoxemia. In the baboon, in which the normal trajectory of growth is affected by preterm birth, there is a direct correlation between a higher flux in oxygen saturation and a greater extent of neuropathological damage. Currently, the only established therapy for neonatal encephalopathy in full term neonates is moderate hypothermia although this only offers some protection to moderately but not severely affected brains. There is no accepted therapy for injured preterm brains. Consequently the search for more efficacious treatments continues; we discuss neuroprotective agents (erythropoietin, N-acetyl cysteine, melatonin, creatine, neurosteroids) which we have trialed in appropriate animal models. The possibility of combining hypothermia with such agents or growth factors is now being considered. A deeper understanding of causal pathways in brain injury is essential for the development of efficacious strategies for neuroprotection.
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PMID:The biological basis of injury and neuroprotection in the fetal and neonatal brain. 2152 38

A robust neuroinflammatory response characterized by microglial activation and increased brain production of pro-inflammatory cytokines is common in acute liver failure (ALF). Mechanisms proposed to explain the neuroinflammatory response in ALF include direct effects of systemically-derived proinflammatory cytokines and the effects of brain lactate accumulation on pro-inflammatory cytokine release from activated microglia. Cell culture studies reveal a positive synergistic effect of ammonia and pro-inflammatory cytokines on the expression of proteins involved in glutamate homeostasis and in oxidative/nitrosative stress. Proinflammatory cytokines have the capacity to alter blood-brain barrier (BBB) integrity and preliminary studies suggest that the presence of infection in ALF results in rupture of the BBB and vasogenic brain edema. Treatments currently under investigation that are effective in prevention of encephalopathy and brain edema in ALF which are aimed at reduction of neuroinflammation in ALF include mild hypothermia, albumin dialysis systems, N-acetyl cysteine and the antibiotic minocycline with potent anti-inflammatory actions that are distinct from its anti-microbial properties.
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PMID:Liver-brain proinflammatory signalling in acute liver failure: role in the pathogenesis of hepatic encephalopathy and brain edema. 2321 79

Staphylococcal enterotoxin B (SEB) causes lethal shock by potently stimulating the host immune response. Dexamethasone and N-acetyl cysteine (NAC) are anti-inflammatory and antioxidative drugs, respectively, which can independently modulate immune function. Dexamethasone was previously shown to be effective in preventing SEB-induced shock models only if administered early and in multiple doses for a long duration. In this study, dexamethasone and NAC were used in tandem and protected mice (75%) against SEB-induced lethal shock. Hypothermia and weight loss elicited by SEB were also diminished by this novel combination treatment. The levels of monocyte chemoattractant protein-1, interleukin-2, interleukin-6, and mouse gamma interferon in lung tissue after intranasal exposure to SEB were also significantly reduced in mice given a combination of dexamethasone and NAC versus controls.
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PMID:Efficacy of two FDA-approved drug combination in a mouse model of staphylococcal enterotoxin B-induced shock. 2400 53

Neuropathologic investigations in acute liver failure (ALF) reveal significant alterations to neuroglia consisting of swelling of astrocytes leading to cytotoxic brain edema and intracranial hypertension as well as activation of microglia indicative of a central neuroinflammatory response. Increased arterial ammonia concentrations in patients with ALF are predictors of patients at risk for the development of brain herniation. Molecular and spectroscopic techniques in ALF reveal alterations in expression of an array of genes coding for neuroglial proteins involved in cell volume regulation and mitochondrial function as well as in the transport of neurotransmitter amino acids and in the synthesis of pro-inflammatory cytokines. Liver-brain pro-inflammatory signaling mechanisms involving transduction of systemically-derived cytokines, ammonia neurotoxicity and exposure to increased brain lactate have been proposed. Mild hypothermia and N-Acetyl cysteine have both hepato-protective and neuro-protective properties in ALF. Potentially effective anti-inflammatory agents aimed at control of encephalopathy and brain edema in ALF include etanercept and the antibiotic minocycline, a potent inhibitor of microglial activation. Translation of these potentially-interesting findings to the clinic is anxiously awaited.
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PMID:Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. 2604 66

Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation of peripheral thermogenic sites such as the Brown Adipose Tissue (BAT). In a previous study we found that the anti-oxidant N-acetyl cysteine (NAC) can prevent the high increase in temperature in a mouse model of Meth-hyperthermia. Here, we have further explored the ability of NAC to modulate Meth-induced hyperthermia in correlation with changes in BAT. We found that NAC treatment in controls causes hypothermia, and, when administered prior or upon the onset of Meth-induced hyperthermia, can ameliorate the temperature increase and preserve mitochondrial numbers and integrity, without affecting locomotor activity. This was different from Dantrolene, which decreased motor activity without affecting temperature. The effects of NAC were seen in spite of its inability to recover the decrease of mitochondrial superoxide induced in BAT by Meth. In addition, NAC did not prevent the Meth-induced decrease of BAT glutathione. Treatment with S-adenosyl-L-methionine, which improves glutathione activity, had an effect in ameliorating Meth-induced hyperthermia, but also modulated motor activity. This suggests a role for the remaining glutathione for controlling temperature. However, the mechanism by which NAC operates is independent of glutathione levels in BAT and specific to temperature. Our results show that, in spite of the absence of a clear mechanism of action, NAC is a pharmacological tool to examine the dissociation between Meth-induced hyperthermia and motor activity, and a drug of potential utility in treating the hyperthermia associated with Meth-abuse.
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PMID:Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice. 2634 36


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