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)

Necrotizing enterocolitis (NEC) is responsible for substantial infant morbidity and mortality. NEC has been hypothesized to result from hypoxemia and mucosal injury, aggravated by feeding and bacterial proliferation. A study conducted at Kasturba Hospital Manipal in Karnataka, India, during 1990-94 attempted to further define risk factors for NEC. The 34 infants with NEC represented 1.38% of total admissions to the hospital's Neonatal Intensive Care Unit during the study period. The mean birth weight of NEC infants was 1584.56 g, with a mean gestational age of 33.53 weeks. 28 infants (82.35%) were preterm and 33 (97.05%) weighed under 2500 g. The most frequent clinic signs in infants with NEC were abdominal distension (79.4%), hyperbilirubinemia (67.6%), hypoglycemia (58.8%), and umbilical erythema (55.9%). When the 23 infants with NEC born within the hospital were compared with 46 weight-matched controls, there were no significant differences in birth weight, gestational age, or feeding patterns. However, NEC cases had a higher frequency of pregnancy-induced hypertension, low mean Apgar scores, polycythemia, hypothermia, and septicemia than controls. These findings suggest that poor gut blood flow may be another important etiologic factor in NEC.
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PMID:Neonatal necrotizing enterocolitis. 925 Dec 79

2-Arachidonoyl-glycerol (2-Ara-GI) has been isolated from various tissues and identified as an endogenous ligand for both cannabinoid receptors, CB1 and CB2. Here we report that in spleen, as in brain and gut, 2-Ara-GI is accompanied by several 2-acyl-glycerol esters, two major ones being 2-linoleoyl-glycerol (2-Lino-Gl) and 2-palmitoyl-glycerol (2-Palm-Gl). These two esters do not bind to the cannabinoid receptors, nor do they inhibit adenylyl cyclase via either CB1 or CB2; however, they significantly potentiate the apparent binding of 2-Ara-Gl and its apparent capacity to inhibit adenylyl cyclase. Together these esters also significantly potentiate 2-Ara-Gl inhibition of motor behavior, immobility on a ring, analgesia on a hot plate and hypothermia caused by 2-Ara-Gl in mice. 2-Lino-Gl, but not 2-Palm-GI, significantly inhibits the inactivation of 2-Ara-Gl by neuronal and basophilic cells. These data indicate that the biological activity of 2-Ara-Gl can be increased by related, endogenous 2-acyl-glycerols, which alone show no significant activity in any of the tests employed. This effect ('entourage effect') may represent a novel route for molecular regulation of endogenous cannabinoid activity.
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PMID:An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. 972 Oct 36

Rewarming victims of hypothermia such as divers or immersion victims, participants in winter sports and military operations, and surgical patients on cardiopulmonary bypass (CPB) may lead to vascular instability, multiorgan failure, shock, and even death. While the causes of these rewarming symptoms are unknown, they may be related to bacterial lipopolysaccharide (LPS) translocated from the intestines into the circulation due to splanchnic ischemia. We have determined LPS during the cooling (to 31.5 degrees-34.0 degrees C) and rewarming phases of hypothermic surgery in 11 patients at the Stanford University Medical Center. During rewarming, there was an LPS spike in 6/11, in one more patient there was an LPS spike during surgery but not during rewarming, and in 4/11 there was no rise in LPS, i.e., a temporary endotoxemia occurred in 7/11 (63.6%) patients, usually at the commencement of rewarming. All four patients with no LPS spike received dexamethasone for at least 7 days before surgery. We propose that hypothermia reduced splanchnic blood flow (BF), causing ischemic damage to the gut wall and translocation of LPS from the gut into the vascular space. Upon rewarming, splanchnic BF is restored, the translocated LPS transits from the splanchnic to the systemic circulations as a bolus, and the gut wall is healed. No sequelae occurred in these patients because of their adequately functioning immune systems. However, had they been immunocompromised, symptoms might have occurred. Rewarming of accident victims probably also incurs a similar risk of endotoxemia, and dexamethasone may have protected the gut wall. Further studies are indicated.
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PMID:Rewarming from hypothermia leads to elevated plasma lipopolysaccharide concentrations. 1081 33

The in situ rat gut technique was used to explore the effects of hypothermia on the intestinal absorption of L-dopa and uracil. A hypothermic state was induced when male Sprague-Dawley rats, weighing between 300 and 370 g, were exposed to an atmosphere of helox (helium:oxygen, 80:20) at 0-4 degrees C. After 4 to 5 h, the rectal temperatures were decreased from 37 to 20 degrees C. The rewarming process for hypothermic animals undergoing anesthesia appears to be prolonged. The animals were prepared for surgery using ether as anesthetic after a rectal temperature of 20 degrees C was attained. Hypothermia showed a significant influence on decreasing L-dopa and uracil disappearances from the intestinal lumen. About 40 percent reduction of the rates of disappearance was observed with a 10 degrees C reduction of the rectal temperature. Additionally, a rapid drop of the rate of drug disappearance was observed in the beginning stage of rectal temperature decrease (31-36 degrees C) as well as in the hypothermic state with rectal temperatures < 26 degrees C. There appears to be a thermal stable region for absorption between 26 and 30 degrees C. Water efflux was studied in both normothermic and hypothermic animals. Normothermic rats showed greater average cumulative water efflux over a period of 30 min (71 and 61% for L-dopa and uracil, respectively) in comparison with that of hypothermic rats (34 and 41% for L-dopa and uracil, respectively). The cold-treated animals showed decreased rates of disappearance associated with the decreased water efflux. Therefore, the reduction of the rates of drug disappearance from the intestinal lumen caused by hypothermia may be partially related to the decrease of water efflux during hypothermia.
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PMID:Effect of hypothermia on the intestinal absorption of uracil and L-dopa in the rat. 1100 2

The vagus nerve may indirectly influence thermoregulation by modulation of energy balance: its afferent fibers convey signals that represent information on feeding state, resulting in either depression or stimulation of metabolic processes. A regulated metabolic depression can be detected in the background of fasting-induced hypometabolism and hypothermia. In its development (besides humoral signals) vagally transmitted neural signals of gastrointestinal and hepatoportal origin are important. These signals are related to hunger, to decrease of mechanical/chemical stimuli from the gut, to decline of blood glucose; they alter discharge rates of vagal afferents and activity of the nucleus of the solitary tract, eliciting inhibition of metabolic rate and enhancement of food intake. In this hunger-related metabolic inhibition the nucleus of the solitary tract is in interaction with hypothalamic nuclei, that contribute to neuropeptide changes characterized by high neuropeptide Y activity (with energy-conserving type of regulation) and depressed cholecystokinin and corticotropin releasing hormone activities (with depressed energy-expenditure). In postalimentary states the hypermetabolism and hyperthermia are due to opposite changes in metabolic regulation. Satiety-related stimulatory signals of abdominal origin, transmitted via hepatic vagal afferents to the nucleus of the solitary tract, contribute to enhancement of sympathetic activity and stress-responsiveness, leading to hypermetabolism and hyperthermia. Depressed neuropeptide Y release and enhanced cholecystokinin and corticotropin releasing hormone activities participate in the central regulatory changes, and in the high energy-expenditure. The biological role of these vagal functions is not directly the regulation of body temperature, rather the regulation of energy balance and energy content in the body.
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PMID:The vagus nerve in thermoregulation and energy metabolism. 1118 24

Protein synthesis is severely depressed in hibernating mammals. In the absence of significant protein synthesis, the continued turnover of proteins as a function of normal cellular activity would result in the net depletion of protein pools. We measured levels of ubiquitylated proteins in the gut of thirteen-lined ground squirrels ( Spermophilus tridecemlineatus) and liver of golden-mantled ground squirrels ( Spermophilus lateralis). In both tissues, ubiquitin conjugate concentrations increased during entrance into torpor and were elevated 2-3 fold by late torpor compared with levels in active animals. The data are consistent with a depression of proteolysis with a resultant high level of ubiquitylated proteins during the natural hypothermia of torpor. The periodic returns to euthermy during the hibernation season allow for degradation of these conjugated proteins and may serve to restore protein pools.
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PMID:Ubiquitin conjugate dynamics in the gut and liver of hibernating ground squirrels. 1191 8

Results of neuropathologic, spectroscopic, and neurochemical studies continue to confirm a major role for ammonia in the pathogenesis of the central nervous system complications of both acute and chronic liver failure. Damage to astrocytes characterized by cell swelling (acute liver failure) or Alzheimer Type II astrocytosis (chronic liver failure) can be readily reproduced by acute or chronic exposure of these cells in vitro to pathophysiologically relevant concentrations of ammonia. Furthermore, exposure of the brain or cultured astrocytes to ammonia results in similar alterations in expression of genes coding for key astrocytic proteins. Such proteins include the structural glial fibrillary acidic protein, glutamate transporters, and peripheral-type (mitochondrial) benzodiazepine receptors. Brain-blood ammonia concentration ratios (normally of the order of 2) are increased up to fourfold in liver failure and arterial blood ammonia concentrations are good predictors of cerebral herniation in patients with acute liver failure. Studies using 1H magnetic resonance spectroscopy in patients with chronic liver failure reveal a positive correlation between the severity of neuropsychiatric symptoms and brain concentrations of the brain ammonia-detoxification product glutamine. Increased intracellular glutamine may be a contributory cause of brain edema in hyperammonemia. Positron emission tomography studies using 13HN3 provide evidence of increased blood-brain ammonia transfer and brain ammonia utilization rates in patients with chronic liver failure. In addition to the use of nonabsorbable disaccharides and antibiotics to reduce gut ammonia production, new approaches to the treatment of hepatic encephalopathy by lowering of brain ammonia include the use of L-ornithine-L-aspartate and mild hypothermia.
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PMID:Pathophysiology of hepatic encephalopathy: a new look at ammonia. 1260 99

Brain edema and consequent increase in intracranial pressure is a major complication of acute liver failure (ALF) and is a major cause of death in this condition. Rapid accumulation of ammonia in brain has been implicated in the pathogenesis of brain edema in ALF. Increased brain ammonia may cause brain swelling via the osmotic effects of an increase in astrocytic glutamine concentration or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in the brain, some of which code for proteins involved in central nervous system function such as the glutamate transporter GLT-1, the astrocytic structural protein, glial fibrillary acidic protein, and the water channel protein, aquaporin IV. Loss of expression of GLT-1 results in increased extracellular brain glutamate. Therapeutic measures currently used to prevent and treat brain edema in acute liver failure include mannitol; strategies aimed at lowering of gut ammonia production are generally ineffective. Studies in experimental animals suggest that mild hypothermia or the use of L-ornithine-L-aspartate may be useful in the prevention of brain edema in these patients.
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PMID:Brain edema in acute liver failure. 1502 58

Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothermia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 +/- 1.1 kg) were anesthetized by IV fentanyl (15 microg . kg(-1) . h(-1)) and midazolam (1.0 mg . kg(-1) . h(-1)). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6 degrees +/- 0.2 degrees C for 6 h and were then rewarmed and kept normothermic at 37.7 degrees +/- 0.3 degrees C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% +/- 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% +/- 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.
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PMID:The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs. 1578 13

Multisystem organ failure represents a major cause of mortality in intestinal ischemia and reperfusion (I/R), and oxidative stress plays a key role in its pathogenesis. Hypothermia is beneficial in I/R injury, but its effects on systemic oxidative stress have not been elucidated. The aim of this study was to evaluate the effects of moderate hypothermia on systemic oxidative stress after intestinal I/R injury. Anaesthetized adult rats (n = 10 per group) underwent 60 min of intestinal ischemia followed by 120 min of reperfusion or sham operation at normothermia (36 degrees C-38 degrees C) or moderate hypothermia (30 degrees C-32 degrees C). At sacrifice, ileum, liver, lungs, and kidneys were removed to determine the concentration of malondialdehyde (a marker of lipid peroxidation), reduced and oxidized glutathione (a major endogenous antioxidant), and glutathione redox state. Plasma malondialdehyde and nitrate plus nitrite (reflecting nitric oxide production) were also analyzed. A marked elevation of malondialdehyde was observed after I/R at normothermia in plasma, ileum, and lungs; however, hypothermia during I/R prevented this increase. I/R at normothermia caused a profound decrease in reduced glutathione and glutathione redox state in the ileum, but this was not observed in I/R at hypothermia. Interestingly, hypothermia increased glutathione content of control intestine. Nitric oxide production was increased only in normothermic I/R animals. Moderate hypothermia attenuates systemic oxidative stress associated with experimental intestinal I/R in an animal model by decreasing lipid peroxidation in plasma, ileum, lungs, and kidneys, by preventing the depletion of gut glutathione, and by reducing systemic nitric oxide production. However, whether these effects persist after rewarming is unknown.
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PMID:Moderate hypothermia protects against systemic oxidative stress in a rat model of intestinal ischemia and reperfusion injury. 1604 87


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