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)

Mice with a disruption of the IFN-gamma receptor alpha-chain gene (IFN-gamma R alpha o/o mice) were found to be significantly more sensitive than their wild-type counterparts to induction of the anti-CD3-induced disease syndrome. Specifically, when given a selected dose of anti-CD3 Ab, IFN-gamma R alpha o/o mice developed severe hypothermia and hypoglycemia, leading to 100% mortality within 72 h. In contrast, wild-type mice failed to develop overt pathologic manifestations and survived. Histologic examination revealed apoptosis in thymuses and spleens, which were significantly more pronounced in the mutant than in the wild-type mice, as confirmed by flow cytometric and DNA electrophoretic analysis. Apoptosis affected mainly CD4+CD8+ and CD4+CD8- thymocytes. Other histologic alterations were steatosis in livers, and erythrocyte extravasation and infiltration of apoptotic cells in lungs, all of which were exclusively observed in IFN-gamma R alpha o/o mice. Blood levels of TNF, IL-2, IL-6, and IL-10 were slightly more elevated in IFN-gamma R alpha o/o mice, but insufficiently so to explain increased disease severity. Thus, even more elevated cytokine levels in wild-type mice receiving high doses of anti-CD3 Ab were not associated with morbidity or apoptosis. Blood levels of IFN-gamma were barely detectable in anti-CD3-challenged wild-type mice, but were relatively high in the mutant mice. Increased susceptibility of IFN-gamma R alpha o/o mice was associated with impaired nitric oxide (NO) production, as indicated by significantly lower plasma nitrite levels and by more transient expression of spleen inducible NO synthase mRNA. Moreover, treatment of wild-type mice with the NO synthase inhibitor N-nitro-L-arginine methylester resulted in increased anti-CD3-induced morbidity and mortality. The data indicate that IFN-gamma R alpha o/o mice produce less NO and are therefore more sensitive than wild-type mice to the deleterious effect of anti-CD3 Ab.
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PMID:IFN-gamma receptor-deficient mice are hypersensitive to the anti-CD3-induced cytokine release syndrome and thymocyte apoptosis. Protective role of endogenous nitric oxide. 756 Oct 88

To examine the role of neurotensin in opioid-induced thermo-regulation, Tyr-Pro-N-MePhe-D-Pro-NH2 (PL-017, 1.86 nmol i.c.v.), neurotensin (NT, 0.0747-2.98 nmol i.c.v.), ([trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide+ ++]) (U50,488H; U50, 10-40 mg/kg s.c.), dynorphin A1-17 (DY, 4.65 nmol i.c.v.) and DPDPE (4.65 nmol i.c.v.) were injected alone or in combination with NT into unrestrained, male S-D rats. At 20 +/- 2 degrees C ambient, body temperature (Tb) was measured for 3 hr after injection. PL-017 induced dose-dependent hyperthermia; NT, DY and U50 produced dose-related hypothermia. NT (0.0747 nmol) had no effect on PL-017-induced hyperthermia; higher doses of PL-017/NT antagonized the hyperthermia and increased the peak and duration of the hypothermia. Pretreatment with cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 0.74 nmol i.c.v.) blocked the enhanced PL-017/NT-induced hypothermia but had no effect on NT-induced hypothermia. DY/NT reduced Tb dose dependently but the effect did not differ significantly from NT alone. U50 (20 or 40 mg/kg)/NT increased the peak and duration of the hypothermic response. Naloxone pretreatment (10 mg/kg s.c.) blocked the effect of U50 alone and in combination with NT, as did the peripheral opioid antagonist, naloxone methiodide (100 mg/kg s.c.). Nor-binaltorphimine (25 nmol i.c.v.) partially blocked the effect of U50 on Tb and had no effect on NT or U50/NT. DPDPE did not alter Tb alone or in combination with NT. The data presented provide information on the role of NT in opioid-induced thermoregulation.
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PMID:Interaction between opioid agonists and neurotensin on thermoregulation in the rat. I. Body temperature. 761 10

Hypothermia is the major factor influencing autoregulatory properties of the cerebral circulation in human infants undergoing hypothermic cardiopulmonary bypass. The present investigation evaluated the effect of decreased temperature on the contractility of isolated middle cerebral arteries obtained from newborn lambs. Reducing bath temperature from 37 to 21 degrees C caused a temperature-dependent increase in contractile tension, achieving 1.32 +/- 0.09 g above resting tension (0.75 g). Pretreatment with nonselective (alpha 1 and alpha 2) alpha-adrenoceptor antagonist, phentolamine (10(-5) M), with an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), and with a cyclooxygenase inhibitor, indomethacin (10(-5) M), did not affect the contractile response to a decrease in bath temperature from 37 to 21 degrees C. Furthermore, cerebral arteries were responsive to both norepinephrine (constriction) and sodium nitroprusside (relaxation) and the sensitivity of cerebral arteries to the sympathetic neurotransmitter norepinephrine appears to be enhanced at low temperatures. We postulate that direct cerebral vasoconstriction and enhanced adrenergic contractility may be responsible for increased cerebrovascular resistance during and after hypothermic cardiopulmonary bypass with possible ischemic cerebral injury and neurological sequelae.
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PMID:Hypothermia enhances contractility in cerebral arteries of newborn lambs. 804 Nov 54

Tyr-Pro-N-MePhe-D-Pro-NH2 (1.86 nmol), dynorphin A1-17 (4.65 nmol) and DPDPE (4.64 nmol), which are selective for mu-, kappa- and delta- opioid receptors, respectively, were injected into the right lateral ventricle of unrestrained male Sprague-Dawley rats. At ambient temperatures of 30 degrees C and 5 degrees C, brain surface temperature (Tb), oxygen consumption (VO2) and heat exchange (Q) were measured for 3 hr after injection in a gradient-layer calorimeter. Tyr-Pro-N-MePhe-D-Pro-NH2 at 30 degrees C caused significant hyperthermia (1.39 +/- 0.48 degree C) with onset occurring 15 to 30 min after injection and lasting 60 min after injection. Increased Tb was due to a significant decrease in Q (-1.31 +/- 0.31 cal/g/hr) and to a 60 to 75% increase in VO2 compared with saline controls. Thirty-min pretreatment with cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (0.74 nmol), a mu-selective antagonist, blocked the changes. At 30 degrees C, neither dynorphin A1-17 nor DPDPE significantly altered Tb, Q or VO2. At 5 degrees C ambient, Tyr-Pro-N-MePhe-D-Pro-NH2 decreased VO2, resulting in hypothermia (-1.01 degree +/- 0.46 degree C). Q was significantly reduced during the same period. Postinjection thermoregulatory responses to i.c.v. injection of dynorphin A1-17 at 5 degrees C varied widely from animal to animal, and lethality (33%, within 60 min after injection) became a significant factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ambient temperature on the ability of mu-, kappa- and delta-selective opioid agonists to modulate thermoregulatory mechanisms in the rat. 811 97

The labile gas nitric oxide (NO) mediates a wide variety of thermoregulatory processes including vasomotor control, brown fat thermogenesis, and neuroendocrine regulation. Additionally, during endotoxemia, NO modulates the release of cytokines and hypothalamic peptides. To determine the role of NO in thermoregulation and fever, we intravenously injected the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and measured its effects on body temperature during normal thermoregulation and endotoxemia in awake, unrestrained rats. L-NAME produced a stereoselective, dose-dependent hypothermia that lasted up to 4 h after bolus intravenous injection. Intravenous lipopolysaccharide (LPS) produced fever in a dose-dependent manner, which was preceded by hypothermia at higher doses alpha-LPS. NOS inhibition reduced the febrile response to LPS and produced marked hypothermia with a low dose of LPS. These findings indicate that NO may play an important role in thermoregulation and suggest that NO is required for the production of fever.
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PMID:Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever. 877 Jan 31

Two potent inhibitors of nitric oxide synthase (NOS), namely, NG-nitro-L-arginine (NNA) and NG-monomethyl-L-arginine (NMMA) were administered intracerebroventricularly (i.c.v.) in morphine-dependent mice to investigate their effects on abrupt withdrawal and naltrexone-precipitated abstinence signs. Male Swiss-Webster mice were rendered dependent on morphine by subcutaneous implantation of a morphine pellet containing 75 mg of morphine base. Mice implanted with placebo pellets served as controls. NMMA or NNA administered i.c.v. had minimal effects on body weight loss and hypothermia that occur during abrupt withdrawal of morphine. When administered i.c.v., both NNA or NMMA (0.1, 1 and 10 micrograms/mouse) dose-dependently inhibited naltrexone-induced stereotyped jumping behavior in mice. I.c.v. administration of NMMA also attenuated withdrawal induced fecal pellet formation. This effect, however, was not dose-dependent. In conclusion, these results suggest that brain NO plays an important role in the expression of behavioral signs of morphine withdrawal syndrome. In addition, these results support the idea that NOS inhibitors may be potentially useful in the treatment of opioid withdrawal syndrome.
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PMID:Evidence for a role of nitric oxide of the central nervous system in morphine abstinence syndrome. 885 29

This study was undertaken to examine the possible role of nitric oxide (NO) on brown adipose tissue (BAT) thermogenesis in rats. The chronic administration of N omega-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) in drinking water given to rats decreased interscapular BAT (IBAT) weight as well as DNA content in a warm environment (25 +/- 1 degrees C; 2 and 4 weeks), and inhibited the cold-stimulated (5 +/- 1 degrees C; 2 weeks) increase in IBAT weight and DNA content. L-Arginine administration (4 weeks in a warm environment) increased the DNA content of IBAT. Chronic L-NAME administration (2 weeks in a warm environment) eliminated the NE-stimulated increase in in vivo oxygen consumption (VO2), caused hypothermia in acute cold exposure (0 degree C), and suppressed the NE-stimulated increase in in vitro IBAT VO2. In vitro incubation of native IBAT with L-NAME suppressed the basal and NE-stimulated increase in in vitro VO2. In vitro incubation of IBAT with methylene blue (soluble guanylate cyclase inhibitor and a scavenger of free NO) eliminated the NE-stimulated increase in in vitro IBAT VO2. These results suggest that the nitric oxide and NO-cGMP signaling systems are involved in the regulation of BAT cellularity and thermogenesis in rats.
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PMID:Effects of acute and chronic inhibition of nitric oxide synthase on brown adipose tissue thermogenesis. 904 15

We evaluated in rats, the effect of moderate hypothermia (30-31 degrees C) on extracellular levels of amino acids, with special emphasis on the excitatory amino acids (EAAs) glutamate and aspartate, lactate and pyruvate, after severe spinal cord compression. A laminectomy of Th7 and Th8 was made. A probe was inserted in a dorsal horn and microdialysis was performed for 1.5 h before and 4 h after applying severe compression for 5 min. Dialysate samples were collected at intervals of 10 min and analyzed by high-performance liquid chromatography. In normothermic (37.5 degrees C) animals there was a several-fold rise of glutamate that peaked in the first 10 min fraction after trauma. Hypothermic animals showed a similar increase after trauma, which was statistically significant until 20 min after injury. The level of glutamate was significantly higher in hypothermic animals from 20 to 70 min after injury, compared with normothermic animals. Aspartate also showed a marked increase following injury. The peak concentration was similar for both groups, whereas recovery was delayed in hypothermic animals. There was no significant difference between the normothermic and hypothermic animals for arginine, taurine, alanine, glutamine, histadine, glycine, threonine, tyrosine, and asparagine. No significant effect of hypothermia on lactate or lactate/pyruvate was noted. However, the mean level of lactate tended to be lower and recovery was quicker in hypothermic animals. The results of the present study suggest that moderate hypothermia does not attenuate extracellular accumulation of EAAs or markedly improve energy metabolism in our model. Instead, our findings raise the possibility that moderate hypothermia prolongs the duration of glutamate receptor overactivation. Since hypothermia effectively attenuates glutamate release in CNS and spinal cord ischemia models our results suggest different mechanisms of extracellular accumulation of EAAs in ischemia and trauma.
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PMID:Effects of moderate hypothermia on extracellular lactic acid and amino acids after severe compression injury of rat spinal cord. 904 12

Opioids administered by i.c.v. injection produce body temperature (Tb) changes and analgesic responses in rats. The present study was undertaken to investigate the effects on Tb and analgesia of highly selective mu and kappa opioid receptor agonists and antagonists delivered directly into the preoptic anterior hypothalamus (POAH) and periaqueductal gray (PAG) by the intracerebral microdialysis method. Microdialyzed into the POAH, the mu receptor agonist Tyr-Pro-N-MePhe-D-Pro-NH2 induced dose-related hyperthermia that could be prevented or antagonized by the mu receptor antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 or by naloxone, but not by the kappa receptor antagonist nor-binaltorphimine. The kappa receptor agonist dynorphin A(1-17), microdialyzed into the POAH, induced dose-related hypothermia that was prevented or antagonized by nor-binaltorphimine but not cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2. Neither Tyr-Pro-N-MePhe-D-Pro-NH2 nor dynorphin A(1-17) microdialyzed into the PAG produced significant changes in Tb. However, these agonists microdialyzed into the PAG produced analgesic responses that did not occur after administration into the POAH. These results support the hypothesis that the hyperthermic response to opioids is mediated by the mu receptor and the hypothermic response is mediated by the kappa receptor in rats. The POAH is a primary functional area in Tb, but not in analgesic, responses to opioids, whereas the PAG is a sensitive area for analgesic, but not for Tb, responses to opioids.
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PMID:Body temperature and analgesic effects of selective mu and kappa opioid receptor agonists microdialyzed into rat brain. 910 37

After long-standing malnutrition a 15-month-old boy with signs of kwashiorkor was admitted in a moribund state with serious hyponatraemic dehydration, hypothermia, somnolence, and signs of a pontine disconnection syndrome. Folic acid levels were below the detection level in the presence of normal cobalamin levels. MRI of the brain showed global volume loss and signal abnormalities on the T2-weighted images suggestive for central pontine myelinolysis (CPM). Brainstem acoustic evoked responses have remained normal. The serious metabolic and nutritional derangements required substitution of folic acid, vitamins and trace elements as well as slow correction of hyponatraemic dehydration with return of the sodium level over a period of four days. This therapeutic regimen resulted in complete neurological recovery. Follow-up MRI documented normalisation of the initial pathologic findings. The hypothesis was put forward linking the pathogenesis of CPM with the combination of folate depletion and superimposed hyponatraemic dehydration. The previously acquired folate depletion could affect normal appositional function of myelin basic protein molecules due to insufficient methylation of arginine in position 107. The subsequent development of intramyelinic edema and CPM will then be triggered by the superimposed hyponatraemic dehydration. The verification of this hypothesis requires further investigations.
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PMID:Central pontine myelinolysis associated with acquired folate depletion. 920 15


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