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)

1. Hypothermia was investigated as a parameter indicating the severity of the acute effects of lipopolysaccharides (LPS) in BALB/c mice, and was compared with the induction of serum levels of IL1 beta, TNF alpha and IL6. 2. Hypothermia induced by low doses of LPS (10-50 micrograms/mouse IP LPS E. coli 0111:B4) peaked at 2 hr after LPS and then either plateaued (50 micrograms) or declined. LPS, 100 and 300 mu, induced greater degrees of hypothermia that plateaued or continued to increase with time for 8 hr. Higher doses of LPS induced similar levels of hypothermia until 4 hr but then continued to increase markedly until 8 hr. 3. TNF alpha levels peaked early (1-2 hr) and declined rapidly, IL6 levels peaked at 3 hr and then declined slowly, and IL1 beta levels peaked at 4 hr, declined at lower doses of LPS, plateaued at higher doses and continued to slowly increase at highest doses. 4. The peak levels of the cytokines (IL1 beta up to 4 hr) and hypothermia (4 hr) increased in relation to the dose of LPS and maximum responses were apparently achieved in all cases at 300-1000 micrograms LPS. 5. A similar parallel between hypothermia and induction of cytokines was observed in C57BL6 and OF1 mice, which were good and poor responders to LPS, respectively, and with the more potent Shigella dysenteria LPS in BALB/c mice. 6. In conclusion, hypothermia is a useful parameter for indicating the strength of the acute effects of LPS. Further studies are necessary to determine whether or not the cytokines studied here play a causative role in hypothermia.
Gen Pharmacol 1996 Sep
PMID:Hypothermia as an indicator of the acute effects of lipopolysaccharides: comparison with serum levels of IL1 beta, IL6 and TNF alpha. 890 77

The effects of neonatal treatment with clomipramine on the sensitivity of cholinergic receptor and passive avoidance behavior were studied to examine the activity of the central cholinergic system. Rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.) and at 3 months of age the thermic responses to three different doses of oxotremorine were measured. One day following oxotremorine challenge study, the animals were subjected to passive avoidance training and retention was measured 24-hr later. Clomipramine treated animals showed an enhanced cholinomimetic-induced hypothermia and an increased latency in passive avoidance test. These findings may reflect an altered sensitivity of central cholinergic system in rats given clomipramine as neonates. The results were compared to other animal models of depression.
J Neural Transm Gen Sect 1995
PMID:Effects of neonatal clomipramine on cholinergic receptor sensitivity and passive avoidance behavior in adult rats. 896 88

The relationship between thyroid status and resistance to water deprivation in a desert rodent, Meriones libycus, has been studied in normal, radiothyroidectomized (Tx), and thyroidectomized T4-supplemented (1.5 microg T4/day) (Tx + T4) animals. In animals given free access to water, 1 month after thyroidectomy water influx and efflux decreased 3-fold. This decrease was partially corrected after 5 days of T4 administration. Thyroidectomy did not modify urinary osmolality nor affect survival. In dehydrated animals, the body weight decreased (about 15%) over 2 weeks in all groups and then stabilized. Water flux decreased sharply in normal or Tx + T4 animals during the 1st week and then stabilized. A further decrease of water flux occurred in hypothyroid animals, which continued over 4 weeks, when fluxes were half those of normal or Tx + T4 animals. The urinary osmolality increased equally sharply in the three groups, at least during the first 5 days of dehydration when sampling was possible. Whereas dehydrated normal and Tx + T4 animals survived at least 7 weeks, 70% of Tx animals had died after 4 weeks and none survived more than 7 weeks. The daily metabolic energy intake was estimated from water flux and metabolic water of the dietary barley. After 4 weeks, when water influx represented only metabolic water from food, metabolic energy intake decreased 2.5-fold in hypothyroid compared with normal or Tx + T4 animals. This low metabolic energy intake led to a trend of body dehydration, hypothermia, and death. Thus, although an effect of thyroidectomy on survival of hydrated animals beyond 4 weeks cannot be excluded, we infer that thyroid hormones play a significant role in the survival of desert rodents under conditions of hydric stress.
Gen Comp Endocrinol 1997 Jan
PMID:Influence of thyroid status on water metabolism and survival of normal and dehydrated desert rodents Meriones libycus. 900 Apr 62

1. The effect of tryptophan on body temperature was studied in rats pretreated with pargyline, an irreversible monoamine oxidase inhibitor (MAOI), and harmaline, a reversible MAOI. 2. Tryptophan (100 mg/kg IP) produced hypothermia followed by hyperthermia in pargyline-pretreated rats, and hypothermia in harmaline-pretreated rats, but tryptophan did not cause body temperature changes by itself. 3. The tryptophan-induced hypo- and hyperthermic effects, which peaked at about 1 and 6 hr after tryptophan administration, respectively, were accompanied by a significant increase in serotonin (5-HT) levels in the pargyline-pretreated rat brain (75%-138.7% and 207%-240.9% increase, respectively), and the 5-HT levels in the hyperthermic state were significantly higher than those in the hypothermic state. 4. In harmaline-pretreated rats, tryptophan also increased the central 5-HT levels (80.5%-95.5% increase) in the hypothermic state, and the effect peaked at about 1 hr after tryptophan administration. The central 5-HT levels in harmaline-pretreated rats slightly decreased at 6 hr after tryptophan administration and were significantly lower than those in the hyperthermic state in the pargyline-pretreated rats. 5. Tryptophan (100 mg/kg IP) administration decreased 5-hydroxy indole acetic acid (5-HIAA) levels, 5-HT turnover, and dopamine (DA) turnover in the brain of pargyline-pretreated rats, but these parameters were not significantly different between the hypothermic and hyperthermic states (i.e., at 1 and 6 hr after tryptophan administration, respectively). 6. These results suggest that the tryptophan-induced body temperature change depends on the different 5-HT levels in the brain and that the 5-HT level needed to induce hyperthermia is higher than that needed to induce hypothermia.
Gen Pharmacol 1997 Mar
PMID:Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats. 906 81

1. We have investigated the ability of several compounds to diminish both infarct area and volume induced by middle cerebral artery occlusion in the mouse. 2. Lifarizine, ipsapirone and N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE) all reduced both infarct area and volume. Ifenprodil diminished the infarct area, but the effect on total infarct volume was much less pronounced. 3. In addition, we tested the protective effects of some other drugs on infarct area only. Nimodipine, verapamil, diltiazem, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine (R56865) and sabeluzole had no effect on infarct area. (S)-Emopamil significantly diminished infarct area. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) also diminished infarct area significantly. 4. In some brain ischemia models hypothermia protects against ischemic damage. Mild hypothermia had no effect on infarct area in the present mouse model of focal ischemia.
Gen Pharmacol 1998 Feb
PMID:Focal cerebral ischemia in the mouse: hypothermia and rapid screening of drugs. 950 74

1. Both L-dopa and low doses of apomorphine potentiated withdrawal symptoms such as jumping, "wet dog" shakes and burrows. L-dopa reduced hypothermia and potentiated body weight loss, whereas apomorphine produced opposite effects. 2. Higher doses of apomorphine attenuated jumping and burrows but had no effect on "wet dog" shakes. On the other hand, and with the exception of sulpiride, all other dopamine (DA) antagonists produced effects opposite those of the agonists with regard to jumping, "wet dog" shakes and burrows. 3. In addition, DA antagonists reduced hypothermia and body weight loss. The effects of DA agonists and antagonists were investigated in mice injected with 6-hydroxydopamine (6-OHDA) intracerebrally to examine whether DA-mediated effects are somehow linked to noradrenergic pathways. 4. Mice pretreated with 6-OHDA developed a higher degree of naloxone-induced withdrawal jumping than did untreated mice. 6-OHDA reversed the effects of apomorphine on "wet dog" shakes and burrows while abolishing those of L-dopa on all withdrawal symptoms, the only exception being jumping, which remained unchanged. 5. 6-OHDA also reversed the effects of sulpiride on all withdrawal symptoms while reversing the effects of pimozide on jumping, and it abolished its effect on hypothermia. 6. These findings provide evidence suggesting that the effects of DA agonists and antagonists are dependent at least partly on intact noradrenergic pathways.
Gen Pharmacol 1998 Apr
PMID:The role of dopamine in the expression of morphine withdrawal. 952 66

1. ATP-sensitive potassium (KATP) channel openers shorten cardiac ventricular muscle action potential duration (APD), reduce resting and developed contractile force, and have been shown to provide cardioprotection when given before, during, and after either short-term ischemia or long-term hypothermia. The authors' aim was to determine the concentration-dependent effect of the potent KATP channel opener bimakalim on transmembrane action potential changes induced by mild (27 degrees C) and moderate (20 degrees C) hypothermia in isolated guinea pig ventricular muscle. 2. Conventional microelectrode techniques were used to record action potentials (APs) in single myocytes during normothermia (37 degrees C) and hypothermia in the presence and absence of 0.1 to 30 mumol.l-1 bimakalim. 3. Hypothermia alone increased APD and depolarized the diastolic membrane potential (DMP): APD90 = 141.7 +/- 7.0 msec and DMP -86.2 +/- 1.4 mV (n = 6) at 37 degrees C versus 235.7 +/- 7.8 msec and -75.6 +/- 1.0 mV at 20 degrees C (n = 7). At 37 degrees C, bimakalim (0.1-10 mumol.l-1) shortened APD in a concentration-dependent fashion. 4. APD90 was markedly reduced from 141.7 +/- 7.0 msec without bimakalim to 9.5 +/- 2.6 msec with 10 mumol.l-1 bimakalim (n = 6); this effect was blocked by glibenclamide. DMP was hyperpolarized by bimakalim. More bimakalim was required to shorten APs during mild and moderate hypothermia. The 50% effective concentration (EC50) of bimakalim required to maximally shorten APD90 was 0.96 +/- 0.10 mumol.l-1 at 37 degrees C; this increased to 3.96 +/- 0.24 mumol.l-1 at 27 degrees C, and to 12.34 +/- 0.72 mumol.l-1 at 20 degrees C. Relative to hypothermia-induced depolarization, bimakalim hyperpolarized DMP toward drug-free values obtained at 37 degrees C. 5. These results indicate that hypothermia shifts the bimakalim concentration APD90 response curve to the right such that 13 times more bimakalim is required at 20 degrees C shorten APD by the same amount as at 37 degrees C. Bimakalim also reverses hypothermia-induced AP lengthening and tends to reverse the hypothermia-induced decrease in DMP. 6. These findings aid in our understanding of the cardioprotective effects of KATP channel openers during hypothermia.
Gen Pharmacol 1998 Jul
PMID:Reversal of hypothermia-induced action potential lengthening by the KATP channel agonist bimakalim in isolated guinea pig ventricular muscle. 959 90

1. Bacterial lipopolysaccharide (LPS)-induced increases in serum cytokines (TNF-alpha, IL-1 and IL-6) and hypothermia were studied in mice sensitized by carrageenan pretreatment and compared with mice sensitized with heat-killed P. acnes or IFN-gamma, all given IP at appropriate intervals (24 hr, 7 days and 12-18 hr, respectively) before LPS. 2. In mice with localized peritoneal inflammation induced by carrageenan, peak TNF-alpha levels (1.5-2 h after LPS) were markedly enhanced after both doses of LPS tested (50 and 200 microg/mouse IP). However, IL-1beta levels were not changed and IL-6 levels were decreased only after the higher dose of LPS. Hypothermia showed weak and inconsistent changes in carrageenan-sensitized mice. 3. IL-1beta levels in spleen lysates were higher but paralleled those in the serum, being increased in IFN-gamma-sensitized but not in carrageenan-sensitized mice. The levels of both TNF-alpha and IL-1beta were high in the peritoneum of carrageenan-sensitized mice, suggesting that the increased serum TNF-alpha did not emanate from the peritoneum. 4. In mice sensitized with the other two agents, as expected, the levels of all three cytokines increased, but peak levels were attained at the same times post-LPS (TNF-alpha: 1-1.5 hr; IL-1: 3-4 hr; IL-6: 3-4 hr). In addition, hypothermia was increased with both of these methods of sensitization. 5. The lack of consistent correlation of the levels of cytokines studied, particularly TNF-alpha, with the degree of hypothermia, raises questions as to their causative role in its induction in these models. 6. The mechanisms underlying these models of sensitization are clearly different, and further understanding of these mechanisms would aid in the interpretation of the effects of drugs in the models.
Gen Pharmacol 1998 Aug
PMID:Selective enhancement of LPS-induced serum TNF-alpha production by carrageenan pretreatment in mice. 968 77

IFNgamma potentiates the production of serum cytokines and mortality induced by LPS, but these responses do not change in parallel, and the underlying mechanisms are not clear. Pretreatment of mice with 15 microg rrIFNgamma intraperitoneally (IP) resulted in potentiation of LPS-induced serum cytokine production and hypothermia, but these changes depended on the pretreatment time and did not occur in parallel. TNFalpha and IL1beta levels showed peak potentiation after 8-h-IFNgamma pretreatment which may result from a process of sensitization of mechanisms involved in LPS responses. IL6 levels were most markedly potentiated after 3- and 6-h-IFNgamma-pretreatment and hypothermia was markedly potentiated after 0-8 h pretreatments. These effects may result from an additional synergistic action of IFNgamma with other mediators when it is present at significant levels earlier after its injection, given that IFNgamma had little (hypothermia) or no effect (cytokines) alone. The degree of potentiation induced by 18-h-IFNgamma pretreatment was related to the dose of LPS, the maximum response having been increased. Two injections of IFNgamma at 42 and 18 h prior to LPS induced greater increases in TNFalpha and IL1beta production than 18-h pretreatment alone, but not in IL6 production or hypothermia. There may be a maximum level of IL6 production which was surpassed under these conditions. These findings suggest that a balance of sensitizing and synergistic actions of IFNgamma with other mediators such as IL1 and TNFalpha, are the major mechanisms underlying its potentiation of LPS responses in mice.
Gen Pharmacol 1999 Apr
PMID:Dual mechanisms of action of interferon-gamma in potentiating responses to LPS in mice: IL1, TNFalpha and IL6 production in serum and hypothermia. 1032 86

Ginsenoside Rc, Rd, and Re induced antinociception in writhing and formalin tests among five representative ginsenosides: Rb1, Rc, Rd, Re, and Rg1. However, these ginsenosides had no effect in the tail-flick test. The antinociceptive effects induced by three ginsenosides were dose dependent. ED50 was 20.5 (7.3-57.4 mg/kg) for Rc, 17 (11.0-27.6 mg/kg) for Rd, and 3.5 (1-12 mg/ kg) for Re in the writhing test and 62 (42-90 mg/kg) for Rc, 45 (20.5-99.0 mg/kg) for Rd, and 82 (48-139 mg/kg) for Re in the second phase of the formalin test. The antinociceptive effects were not blocked by the opioid receptor antagonist naloxone in the writhing and formalin tests. These three ginsenosides did not affect motor function. Ginsenoside Rc and Rd induced hypothermia for 30 to 60 min, and ginsenoside Rc induced hyperthemia after 150 min of treatment at doses of 100 mg/kg. These results suggest that ginsenosides such as Rc, Rd, or Re inhibit mainly chemogenic pain rather than thermal pain by the nonopioid system in mice.
Gen Pharmacol 1999 Jun
PMID:Ginsenosides that produce differential antinociception in mice. 1040 90


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