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)

The objective of this study was to investigate energy metabolism of the gut and liver as well as serum inflammatory cytokines following exploratory laparotomy at moderate hypothermia. Two groups of rats were studied, (n=6-8/group); laparotomy at normothermia for 120 min and laparotomy at hypothermia (32-33 degrees C) for 120 min. Study 1: Intestinal glucose, succinate, lactate, phosphocreatine, and ATP as well as hepatic glucose, succinate, lactate, and ATP were measured in terms of micromole per gram using magnetic resonance spectroscopy. Study 2: Serum levels of TNF-alpha, IL-1beta, LPS-inducible chemokine (LIX), and sICAM-1 were measured by ELISA. Histology of the gut and liver were interpreted. Data are expressed as mean and SEM. In Study 1, laparotomy at hypothermia caused an increase in intestinal glucose levels (0.78+/-0.03 vs. 1.29+/-0.11, P=0.0012) with a decrease in hepatic lactate levels (0.82+/-0.04 vs. 0.44+/-0.06, P<0.001). There were no differences in the other metabolites between the two groups. In Study 2, there were no differences in serum TNF-alpha, IL-1beta, LIX, or sICAM-1 between the two groups. Histological features of the gut and liver among groups were comparable. In conclusion, the intestine and liver react to hypothermia differently. However, levels of high-energy phosphates in both organs are not affected by hypothermia suggesting adequate energy for the organs. It is unlikely that hypothermia induces either systemic inflammatory response or hypoxic damage to the intestine and liver in this model.
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PMID:The effects of moderate hypothermia on energy metabolism and serum inflammatory markers during laparotomy. 1632 33

Bacterial endotoxin produces sepsis associated with alterations in body temperature (fever or hypothermia). The intraperitoneal administration of bacterial endotoxin, lipopolysaccharide (LPS; 50 microg/mouse) led to a decrease in colonic temperature starting 1 hr after the injection. The hypothermic effect was accompanied by a significant increase in hypothalamic leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) levels. 5-lipoxygenase inhibitor, zileuton (200 and 400 mg/kg, po) administered 30 min before LPS challenge significantly prevented hypothermia. However, non-selective cyclooxygenase inhibitor, indomethacin (10, 20 mg/kg, po) did not reverse the hypothermic response. Further, pretreatment of mice with zileuton prevented LPS-stimulated increase in hypothalamic LTB4 levels and caused a relatively small increase in PGE2 levels. Indomethacin had no effect on LTB4 levels but it reduced PGE2 levels. These results suggest a possible involvement of leukotrienes in LPS-induced hypothermia and the potential protective role of 5-lipoxygenase inhibitors in endotoxemia.
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PMID:Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice. 1635 26

Microglial cells play a major role in the pathogenesis of many neurological diseases by exacerbating neuronal and non-neuronal cell death, but the mechanisms involved are unclear. To investigate the microglial-neuronal interactions, we used the murine BV-2 microglial cell line and the human neuronal-like SK-N-SH neuroblastoma cell line in a co-culture system that enabled proximity-dependent interaction and communication, a trans-well system that allowed proximity-independent communication through diffusible molecules only, and a conditioned media system through which no proximity-dependent interactions or cell-to-cell communication is possible. Activation of BV-2 cells with lipopolysaccharide and interferon-gamma (LPS/IFN-gamma) decreased viability of the BV-2 cells alone and in co-cultures with SK-N-SH cells, but not SK-N-SH cells grown alone. In contrast, activation of BV-2 cells in the trans-well and conditioned media system did not have any effect on the viability of SK-N-SH cells, suggesting that microglia must be in close proximity to the neural cells to elicit cytotoxicity. To determine the molecules involved in proximity-dependent cell death, inhibitors of microglial activation were investigated. Only the specific inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea, and hypothermia, which is known to suppress microglial iNOS expression, prevented cell death after LPS/IFN-gamma activation. These results suggest that activated microglia release nitric oxide that is, at least partially, responsible for proximity-dependent microglial-mediated neural toxicity.
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PMID:Microglia induce neural cell death via a proximity-dependent mechanism involving nitric oxide. 1656 33

Polymyxin B, a cyclic cationic polypeptide antibiotic, binds to the lipid A of bacterial endotoxin (lipopolysaccharide; LPS) to inhibit LPS-induced fever. On the basis of a casual observation, we hypothesised that in rats (unlike in rabbits and goats), intravenous (i.v.) polymyxin B would decrease resting body temperature. A single i.v. injection of polymyxin B (10, 100 or 1000 microg/kg) induced a rapid, marked drop in body temperature in a dose-related manner, with no change in physical activity. However, the highest dose (1000 microg/kg) seemed to impair heat-loss mechanisms and/or functions controlling the animal's day-night cycle [because the day-time body temperature remained elevated for two days after the injection (versus the pre-injection level)]. By contrast, rats given 100 or 10 microg/kg of the drug showed a normal day-night cycle after recovery from the initial hypothermic effect of the drug. Therefore, we used the middle dose of polymyxin B (100 microg/kg) in the subsequent experiments. In these experiments, significant decreases in metabolic rate and heat-loss responses were observed immediately after an i.v. injection of polymyxin B (100 microg/kg). By contrast, intracerebroventricular injection of polymyxin B (3 microg) had no effect on resting body temperature. These results suggest that the observed decrease in metabolic rate is responsible for the polymyxin-B-induced hypothermia. Further, rats may react with a reduction in heat-loss responses so as to prevent the body temperature decreasing too far in response to polymyxin B. Thus, polymyxin B modulates or interferes with the peripheral mechanisms underlying body temperature regulation in rats.
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PMID:Systemic administration of polymyxin B induces hypothermia in rats via an inhibitory effect on metabolic rate. 1675 41

The roles of gender and sex hormones in lung function and disease are complex and not completely understood. The present study examined the influence of gender on lung function and respiratory mechanics in naive mice and on acute airway inflammation and hyperresponsiveness induced by intratracheal LPS administration. Basal lung function characteristics did not differ between naive males and females, but males demonstrated significantly greater airway responsiveness than females following aerosolized methacholine challenge as evidenced by increased respiratory system resistance and elastance (p < 0.05). Following LPS administration, males developed more severe hypothermia and greater airway hyperresponsiveness than females (p < 0.05). Inflammatory indices including bronchoalveolar lavage fluid total cells, neutrophils, and TNF-alpha content were greater in males than in females 6 h following LPS administration (p < 0.05), whereas whole-lung TLR-4 protein levels did not differ among treatment groups, suggesting that differential expression of TLR-4 before or after LPS exposure did not underlie the observed inflammatory outcomes. Gonadectomy decreased airway inflammation in males but did not alter inflammation in females, whereas administration of exogenous testosterone to intact females increased their inflammatory responses to levels observed in intact males. LPS-induced airway hyperresponsiveness was also decreased in castrated males and was increased in females administered exogenous testosterone. Collectively, these data indicate that airway responsiveness in naive mice is influenced by gender, and that male mice have exaggerated airway inflammatory and functional responses to LPS compared with females. These gender differences are mediated, at least in part, by effects of androgens.
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PMID:Gender differences in murine airway responsiveness and lipopolysaccharide-induced inflammation. 1678 60

Consumption of nutrients rich in hydroxystilbenes has been promoted because of their health benefits, including dampening of inflammatory responses. However, few studies have examined their effects in vivo. Here, we show that the hydroxystilbene oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene: o-RES) blocked hypothermia but caused no significant effect on the febrile response to the immune stimulus, bacterial LPS in rats. This was associated with a reduction in the LPS-induced plasma cytokine, tumor necrosis factor (TNF)-alpha, but not IL-6. Both IL-6-stimulated STAT-3 and LPS-induced cycoloxygenase-2 expression in the hypothalamus were not affected by o-RES. These data strongly suggest that the o-RES-induced dampening of neuroimmune responses is largely due to its inhibitory effect on TNF-alpha production. In contrast to in vitro experiments, o-RES has no direct effect on NF-kappaB signaling pathway in vivo. The specific inhibitory effect of o-RES on TNF-alpha opens new avenues for the clinical use of o-RES in pathological conditions where excessive production of TNF-alpha is deleterious.
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PMID:Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF-alpha. 1680 85

Intraperitoneal administration of E. coli LPS in doses that elicit half-maximal (EC50 - 20 ug/kg) and maximal (EC100 - 160 ug/kg) febrile responses in nonpregnant rats produce hypothermia in near-term pregnant rats. The present experiments have been carried out to determine if the hypothermia results from a "regulated" or "forced" thermoregulatory response. Chronically-instrumented pregnant rats were allocated to one of two experimental groups depending upon whether they were studied in an experimental apparatus configured as a metabolic chamber with a uniform ambient temperature of 25 degrees C or configured as a thermocline with a linear temperature gradient ranging from 10 degrees C to 40 degrees C. The pregnant rats developed hypothermia following intraperitoneal administration of 160 ug/kg of E. coli LPS when they were studied in the thermal gradient as well as when they were studied in the uniform thermoneutral environment. They did not attempt to prevent the hypothermia following administration of bacterial pyrogen by moving to a warmer region of the thermocline. Thus, our data provide evidence that the hypothermia which occurs following intraperitoneal administration of an EC100 dose of E. coli LPS results from a regulated rather than a forced thermoregulatory response. The mechanism and consequences of this pregnancy-induced thermoregulatory response to bacterial pyrogen are unknown.
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PMID:LPS induced hypothermia in pregnant rats: a regulated thermoregulatory response. 1684 52

Systemic inflammation is a leading cause of hospital death. Mild systemic inflammation is accompanied by warmth-seeking behavior (and fever), whereas severe inflammation is associated with cold-seeking behavior (and hypothermia). Both behaviors are adaptive. Which brain structures mediate which behavior is unknown. The involvement of hypothalamic structures, namely, the preoptic area (POA), paraventricular nucleus (PVH), or dorsomedial nucleus (DMH), in thermoregulatory behaviors associated with endotoxin (lipopolysaccharide [LPS])-induced systemic inflammation was studied in rats. The rats were allowed to select their thermal environment by freely moving in a thermogradient apparatus. A low intravenous dose of Escherichia coli LPS (10 microg/kg) caused warmth-seeking behavior, whereas a high, shock-inducing dose (5,000 microg/kg) caused cold-seeking behavior. Bilateral electrocoagulation of the PVH or DMH, but not of the POA, prevented this cold-seeking response. Lesioning the DMH with ibotenic acid, an excitotoxin that destroys neuronal bodies but spares fibers of passage, also prevented LPS-induced cold-seeking behavior; lesioning the PVH with ibotenate did not affect it. Lesion of no structure affected cold-seeking behavior induced by heat exposure or by pharmacological stimulation of the transient receptor potential (TRP) vanilloid-1 channel ("warmth receptor"). Nor did any lesion affect warmth-seeking behavior induced by a low dose of LPS, cold exposure, or pharmacological stimulation of the TRP melastatin-8 ("cold receptor"). We conclude that LPS-induced cold-seeking response is mediated by neuronal bodies located in the DMH and neural fibers passing through the PVH. These are the first two landmarks on the map of the circuitry of cold-seeking behavior associated with endotoxin shock.
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PMID:Neural substrate of cold-seeking behavior in endotoxin shock. 1718 31

We investigated whether LPS-induced hypothermia develops in a serotype-specific manner in biotelemetered conscious rats. Two different Escherichia coli serotypes of LPSs were injected at a dose of 250 mug/kg ip. E. coli O55:B5 LPS elicited an initial hypothermia and subsequent fever, but E. coli O111:B4 LPS caused more potent monophasic hypothermia. Serum tumor necrosis factor (TNF)-alpha levels were dramatically elevated at the initial phase of the hypothermia induced by both LPSs. This elevation tended to subside at the nadir of E. coli O55:B5 LPS-induced response but progressively increased at the nadir of E. coli O111:B4 LPS hypothermia. Serum IL-10 levels were moderately elevated at the initial phase of the hypothermia and persisted at the same level at the nadir of each LPS-induced response. No change was observed at the serum IL-18 levels. A selective cyclooxygenase (COX)-1 enzyme inhibitor, valeryl salicylate (20 mg/kg sc), abolished the hypothermia without any effect on the elevated cytokine levels. Another COX-1-selective inhibitor, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560; 1 mg/kg sc) inhibited hypothermic responses as well. Meanwhile, cytokine levels were also reduced by SC-560 treatment. These findings suggest that LPS-induced hypothermia may have serotype-specific characteristics in rats. E. coli O111:B4 LPS has more potent hypothermic activity than E. coli O55:B5 LPS; that may presumably be related to its higher or sustained capability to release antipyretic cytokines, such as TNF-alpha. COX-1 enzyme may be involved in the generation of the hypothermia, regardless of the type of LPS administered.
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PMID:Escherichia coli lipopolysaccharides produce serotype-specific hypothermic response in biotelemetered rats. 1727 60

Sepsis, the leading cause of death in intensive care units, reflects a detrimental host response to infection in which bacteria or LPS act as potent activators of immune cells, including monocytes and macrophages. In this report, we show that LPS raises the level of the transcriptional regulator hypoxia-inducible factor-1alpha (HIF-1alpha) in macrophages, increasing HIF-1alpha and decreasing prolyl hydroxylase mRNA production in a TLR4-dependent fashion. Using murine conditional gene targeting of HIF-1alpha in the myeloid lineage, we demonstrate that HIF-1alpha is a critical determinant of the sepsis phenotype. HIF-1alpha promotes the production of inflammatory cytokines, including TNF-alpha, IL-1, IL-4, IL-6, and IL-12, that reach harmful levels in the host during early sepsis. HIF-1alpha deletion in macrophages is protective against LPS-induced mortality and blocks the development of clinical markers including hypotension and hypothermia. Inhibition of HIF-1alpha activity may thus represent a novel therapeutic target for LPS-induced sepsis.
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PMID:Cutting edge: Essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. 1754 84


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