Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Intrapreoptic (IPO) microinjections of various agents cause unavoidable brain tissue injury, often resulting in prostaglandin (PG)-mediated core temperature (Tc) rises. However, IPO microinjection of the alpha 2-adrenoreceptor agonist clonidine (Clo) generally evokes a Tc fall, seemingly avoiding the influence of injury due to the microinjection procedure per se. To clarify this, we microinjected bilaterally into the preoptic/anterior hypothalamus of conscious guinea pigs various doses of Clo dissolved in pyrogen-free saline (PFS, 1 microliter/side). Clo caused biphasic hypo-/hyperthermic responses. The initial hypothermia was dose dependent: no decrease in Tc for 0.1 microgram of Clo, -0.4 +/- 0.1 degree C for 0.5 microgram, -0.9 +/- 0.1 degree C for 1.5 microgram, and -1.2 +/- 0.1 degree C for 5.0 micrograms. During the hyperthermic phase, Tc increased to a dose-independent level (1.0-1.5 degrees C), remaining there up to 5 h postinjection. PFS microinjected IPO also induced hyperthermia, but without any initial Tc decrease. This Tc rise was delayed by 100 min when the cyclooxygenase inhibitor indomethacin (Indo, 50 micrograms/microliters) was injected. Nontreated animals (time controls) maintained Tc at baseline levels during the whole experiment. The alpha 2-antagonist rauwolscine (2 micrograms/side), microinjected IPO 10 min before Clo (0.5 microgram/side), abolished the hypothermic without affecting the hyperthermic response phase; Indo (10 mg/kg), injected intramuscularly 20 min after the IPO microinjection of Clo (0.5 microgram), significantly attenuated the hyperthermic phase. These results confirm that an artifactitious, PG-mediated Tc rise consequent to nonspecific brain tissue injury contaminates the thermal response to agents (hyper- or hypothermizing) microinjected IPO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genesis of biphasic thermal response to intrapreoptically microinjected clonidine. 849 75

Lipopolysaccharide (LPS), an endotoxin, produces pain behavior, inflammation, and changes in immune function. Many of these effects are secondary to the production of cytokines. In the present study, we investigated the effect of LPS on the releasing function of afferent terminals as measured by calcitonin gene-related peptide (CGRP) release in ex vivo perfused rat trachea, and examined the possible role of the cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as intermediaries in this effect. Systemic injection of LPS (0.75 mg/kg, i.p.) in adult rats induced an increase in body temperature followed by hypothermia, indicating ongoing infection. We observed that capsaicin-induced (0.1 microM) tracheal CGRP release was significantly enhanced in the LPS-treated animals after 5 hr. This enhancement of the peptide release by LPS was blocked by IL-1beta tripeptide antagonist Lys-D-Pro-Thr (10 microM) and mimicked by IL-1beta and TNF-alpha (10-100 pg/ml), suggesting that the potentiating effect of LPS on CGRP release is mediated by generation of IL-1beta and TNF-alpha. IL-1beta-induced augmentation of CGRP release was blocked by Lys-D-Pro-Thr. Additionally, the cyclooxygenase inhibitor ketorolac (10 microM) significantly attenuated the facilitatory effects of LPS and IL-1b, indicating involvement of prostanoids. These findings suggest that endotoxin treatment generated cytokines such as IL-1b and TNF-alpha that regulated the peripheral releasing function of primary sensory afferents by sensitizing the terminals and facilitating peptide release. This effect is prostanoid dependent.
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PMID:Involvement of cytokines in lipopolysaccharide-induced facilitation of CGRP release from capsaicin-sensitive nerves in the trachea: studies with interleukin-1beta and tumor necrosis factor-alpha. 876 61

The influence of cyclooxygenase inhibitors on functional stability of hippocampal slices, determined by electrophysiological criteria of recovery after slicing and long-term maintainence of population activity, was studied. Transient (3 min) treatment of slices during slicing with indomethacin (45 microM) or aspirin (0.5 mM) allowed registration of the population responses from the second minute. The activity reached 100% after 15 min incubation and could be registrated for 3 days under conditions of overnight hypothermia. The presence of the same drugs for the entire incubation period had the same effect. The present findings suggest that slicing is a crucial point for triggering of pathological events mediated by cyclooxygenase products and that blockade of cyclooxygenase provides for the further high longterm functional stability of brain slices.
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PMID:Functional stability of hippocampal slices after treatment with cyclooxygenase inhibitors. 918 27

Lipopolysaccharide (LPS) and homologous cytokines were tested for their effect on core temperature in mice using battery-operated telemetric devices placed in the peritoneal cavity. One microgram LPS injected intraperitoneally (i.p.) induced a biphasic effect on core body temperature (Tc), a rapid decrease in Tc with a peak around 30-45 min followed by a prolonged rise around 150-300 min. When a higher dose of LPS (5 microg) was used, the hypothermia was increased in magnitude and lasted much longer, and no fever was observed. Both the decrease and the increase in Tc caused by LPS were prevented by pretreating the mice with indomethacin, a cyclooxygenase inhibitor, but not by a nitric oxide synthase inhibitor. Mouse interleukin-1beta (mIL-1beta, 100 ng, i.p.) induced changes resembling those to LPS, a short-lived decrease in Tc, followed by a small increase. When 1 microg mIL-1beta was injected a profound hypothermia lasting more than 3 h was observed. Mouse IL-6 (1 microg) failed to alter core temperature after either intravenous (i.v.) or i.p. administration. Human IL-6 was also ineffective. Recombinant mouse tumor necrosis factor-alpha (mTNFalpha) also failed to alter the core temperature of mice when injected at a dose of 1 microg (i.p. or i.v.). However, a higher dose of mTNFalpha (5 microg i.p.) caused a short-lived decrease in Tc, followed by a small increase. Similar results were obtained with LPS and the cytokines in C57Bl/6J mice, except that mIL-1beta was ineffective in this strain. These results indicate that the endocrine, neurochemical and behavioral responses to IL-1, IL-6 and TNFalpha administration cannot be explained by changes in Tc, although they may contribute to them. They also suggest that IL-1beta may account for the fever observed following LPS, but that these cytokines are probably not the only factors involved in LPS-induced changes in Tc.
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PMID:Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice. 965 Aug 15

Hippocampal slices treated with cyclooxygenase inhibitor indomethacin for three min during the sectioning (45 min) or aspirin (0.5 min) in long term (up to 5 days) preservation in periodic nocturnal hypothermia were studied morphofunctionally using light microscopy and electrophysiological registration of induced population responses of area CAI to stimulation of Schaffers collaterals. Structural disorders were revealed in control slices as early as the third hour of incubation and they were destroyed following the first hypothermal challenge (24 hrs following preparation). The structure in slices treated with blockers remained more stable as compared to control ones and the activity was registered until d 3 (aspirin) and 5 (indomethacin). Morphological changes were not immediately, followed by electric activity decline. On the whole it may be suggested that essential viability increase occurred due to destructive processes inhibition mediated by short living cyclooxygenase metabolites.
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PMID:[Long-term morphofunctional preservation of guinea pig hippocampal slices following short-term treatment with cyclooxygenase inhibitors]. 991 87

Intraoperative mild hypothermia is common. We have investigated the effects of mild hypothermia (34 vs 38 degrees C) on phenylephrine--(10(-8) to 10(-5) mol litre-1) induced contractions of rat aortic rings mounted for isometric tension recordings. A marked decrease in Emax (maximal tension) (P < 0.05) and significant increase in EC50 (phenylephrine concentration producing 50% of maximal tension) were observed at the lower temperature in endothelium intact rings, but there was no effect of temperature when the endothelium had been removed. The decreased contraction with hypothermia in the endothelium intact vessels was restored to 84% by administration of the nitric oxide synthase inhibitor L-NNA and a small additional amount of tone was restored in the presence of the cyclooxygenase inhibitor, indomethacin. We conclude that mild hypothermia markedly decreased phenylephrine-induced rat aortic contraction in vitro by endothelium dependent mechanisms, largely related to increased nitric oxide production or action.
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PMID:Effect of mild hypothermia on the vascular actions of phenylephrine in rat aortic rings. 1056 95

We have previously shown that Escherichia coli O111:B4 serotype lipopolysaccharide (LPS) produced a dual change in rectal temperature (Tb), in which hypothermia preceded fever at subthermoneutral ambient temperature (Tamb; 24-26 degrees C) in rats. In this study, the characteristics of the initial hypothermic response were evaluated. Hypothermia was significant when LPS (50 microg/kg, i.p.) was injected at thermoneutral Tamb (30 degrees C). There was no heat loss through tail skin during hypothermia. The open field activity of the rats did not change during this period. However, serum levels of tumor necrosis factor-alpha (TNF-alpha) elevated at the beginning of the hypothermia, whereas serum levels of interleukin (IL)-1beta and interferon (IFN)-gamma remained unchanged. A nonselective cyclooxygenase inhibitor (indomethacin, 5 mg/kg, s.c.) inhibited hypothermia and serum TNF-alpha elevation, which resulted in an acceleration of the subsequent pyrogenic response. Moreover, a nonselective inhibitor of nitric oxide synthase (nitro L-arginine methyl ester (L-NAME), 10 mg/kg, s.c.) not only abolished fever but also prolonged the initial hypothermic response. These data suggest that the hypothermic component of low dose LPS-induced dual response is a regulated decrease in Tb. The data also suggest that hypothermia and fever may occur independently as two different thermoregulatory strategies against immune challenge in rats.
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PMID:Characterization of the hypothermic component of LPS-induced dual thermoregulatory response in rats. 1190 Jul 81

In BALB/c mice infected with Trichinella spiralis, changes in body temperature (Tb) were observed over 35 days after the infection. T. spiralis infection induced hypothermia two times at 7 and 28 days after infection. The initial decrease persisted for about one week with a peak (37.1 +/- 0.62 degrees C) around 10 days after the infection, while the later phase persisted for at least one week. Both 10 and 35 days after the infection, there were remarkable decreases in Tb. The serum glucose level of infected mice at 10 days was significantly (p < 0.01) decreased compared with that of control mice at the same number of days, while the level in infected mice at 35 days was not decreased. Moreover, the later phase of hypothermia was prevented by the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.), while the initial phase was not. We conclude that hypothermia was caused by two different mechanisms, involving the effects of hypoglycemia and prostaglandins.
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PMID:Biphasic hypothermia in mice infected with a parasitic nematode, Trichinella spiralis. 1201 35

The effects of nimesulide and diclofenac on lipopolysaccharide (LPS)-induced rectal temperature changes and serum tumour necrosis factor (TNF)-alpha elevation were investigated in rats. LPS (Escherichia coli O111:B4; 50 microg/kg, intraperitoneally) produces a dual body temperature response, in which initial hypothermia precedes fever. Serum TNF-alpha levels rise during the initial phase of the induced hypothermia. Nimesulide, a preferential inhibitor of cyclooxygenase-2 (0.05, 0.5 or 1 mg/kg, subcutaneously) completely abolished the hypothermia, resulting in an acceleration of the fever phase. However, the peak and plateau phases of fever were not changed by nimesulide treatment. Nimesulide (0.5 mg/kg) partially prevented serum TNF-alpha elevation. The non-selective cyclooxygenase inhibitor diclofenac inhibited hypothermia at all doses tested (0.03, 0.3 or 3 mg/kg, subcutaneously) although fever was completely abolished at the 3 mg/kg dose only. Diclofenac also partially abolished the elevation in serum TNF-alpha levels, but at the highest dose only (3 mg/kg). These data suggest that nimesulide and diclofenac can preferentially inhibit LPS-induced hypothermia at doses that do not abolish fever in rats. Both these drugs also reduced elevated TNF-alpha levels, a fact which may, at least partly, explain the antihypothermic effect of nimesulide.
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PMID:Nimesulide and diclofenac inhibit lipopolysaccharide-induced hypothermia and tumour necrosis factor-alpha elevation in rats. 1257 19

Fever is a coordinated autonomic, endocrine, and behavioral response mediated by the brain in reaction to inflammatory stimuli. An essential step in transmitting the immune signal to the brain is the formation of prostaglandin E2. Cyclooxygenase (COX) is the critical enzyme in the synthesis of prostaglandins and COX-2, the inducible form of the enzyme, is markedly induced in cells associated with the cerebral blood vessels and the leptomeninges by immune stimuli such as intravenous administration of lipopolysaccharide (LPS). However, the specific roles of COX-1, the constitutive form of cyclooxygenase, and COX-2 in LPS-induced fever are not well understood. We injected LPS i.v. in combination with either a highly selective COX-1 (SC-560) or COX-2 (SC-236) inhibitor to determine the effects of each drug on the subsequent fever response and on the pattern of expression of Fos protein in the brain. The COX-2 inhibitor blocked LPS-induced fever and Fos expression in sites such as the ventromedial preoptic nucleus (VMPO) and the hypothalamic paraventricular nucleus (PVH), although Fos-immunoreactivity in the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and parabrachial nucleus (PB) remained. In contrast, the COX-1 inhibitor resulted in a profound hypothermic response to LPS and blocked LPS-induced Fos-immunoreactivity in the PVH, PB, NTS, and VLM, although it had no effect on the VMPO. Although COX-2 plays a dominant role in mediating fever responses to i.v. LPS, at least some components of the response, including avoiding hypothermia and the induction of Fos in the NTS, VLM, PB, and PVH, appear to depend on COX-1. J.
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PMID:Specific roles of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide-induced fever and Fos expression in rat brain. 1281 98


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