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)

Winter is energetically demanding. Physiological and behavioral adaptations have evolved among nontropical animals to cope with winter because thermoregulatory demands increase when food availability decreases. Seasonal breeding is central within the suite of winter adaptations among small animals. Presumably, reproductive inhibition during winter conserves energy at a time when the adds of producing viable young are low. In addition to the well-studied seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many populations of mammals and birds in the field. Challenging winter conditions, such as low ambient temperatures and decreased food availability, can directly induce death via hypothermia, starvation or shock. In some cases, survival in demanding winter conditions puts individuals under great physiological stress, defined here as an adaptive process that results in elevated blood levels of glucocorticoids. The stress of coping with energetically demanding conditions can also indirectly cause illness and death by compromising immune function. Presumably, the increased blood concentrations of adrenocortical steroids in response to winter stressors compromise immune function and accelerate catabolic mechanisms in the field, although the physiological effects of elevated glucocorticoids induced by artificial stressors have been investigated primarily in the laboratory. However, recurrent environmental stressors could reduce survival if they evoke persistent glucocorticoid secretion. The working hypothesis of this article is that mechanisms have evolved in some animals to combat seasonal stress-induced immunocompromise as a temporal adaptation to promote survival. Furthermore, we hypothesize that mechanisms have evolved that allow individuals to anticipate periods of immunologically challenging conditions, and to cope with these seasonal health-threatening conditions. The primary environmental cue that permits physiological anticipation of season is the daily photoperiod; however, other environmental factors may interact with photoperiod to affect immune function and disease processes. The evidence for seasonal fluctuations in lymphatic organ size, structure, immune function, and disease processes, and their possible interactions with recurrent environmental stressors, is reviewed. Seasonal peaks of lymphatic organ size and structure generally occur in late autumn or early winter and seasonal minima are observed prior to the onset of breeding. Although many of the field data suggest that immune function and disease processes are also enhanced during the winter, the opposite seasonal pattern is also observed in some studies. We propose that compromised immune function may be observed in some populations during particularly harsh winters when stressors override the enhancement of immune function evoked by short day lengths. Because so many factors covary in field studies, assessment of our proposal that photoperiod mediates seasonal changes in immune function requires laboratory studies in which only photoperiod is varied. A review of the effects of photoperiod on immune function in laboratory studies reveals that exposure to short day lengths enhances immune function in every species examined. Short day exposure in small mammals causes reproductive inhibition and concomitant reduction in plasma levels of prolactin and steroid hormones, as well as alterations in the temporal pattern of pineal melatonin secretion. These hormones affect immune function, and influence the development of opportunistic diseases, including cancer: however, it appears that either prolactin or melatonin secretion is responsible for mediating the effects of photoperiod on immune function. Taken together, day length appears to affect immune function in many species, including animals that typically do not exhibit reproductive responsiveness to day length.
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PMID:Seasonal changes in immune function. 898 73

Patients with multiple sclerosis sometimes show subthalamic lesions presenting syndrome of inappropriate secretion of ADH (SIADH), hypothermia, hyperprolactinemia, weight loss, and cachexia. Hyperprolactinemia also has been found in the patients with active systemic lupus erythematosus, because prolactin can be produced from human activated lymphocytes. We described a case of multiple sclerosis showing galactorrhea-amenorrhea syndrome with hyperprolactinemia. A 31-year-old woman showed a high level of prolactin in the serum (79.6 ng/ml) during remission stage 5 months after the onset of multiple sclerosis. She showed galactorrhea-amenorrhea syndrome 3 years later. She showed dysesthesia in her limbs, relapsing monoparesis, visual disturbance and Gd-enhanced plaques in Brain MRI for 6 years. She was admitted to our hospital on November 24, 1995. A neurological examination showed hyporeflexia of the upper extremities, hyperreflexia of the lower extremities, bilateral ankle clonus, truncal ataxia, and neurogenic bladder. Laboratory tests revealed increased level of serum prolactin, exaggerated secretion of serum prolactin after intravenous injection of 500 micrograms TRH, and marked suppression after oral administration of 2.5 mg bromocriptine. Brain MRI showed demyelinating lesions near the lateral ventricle, and cervical MRI (T2 image) showed high signal intensity lesions in the spinal cord from C2 to C5. In the previous case, galactorrhea-amenorrhea syndrome was found during the exacerbation stage of multiple sclerosis. Hyperprolactinemia may be caused from subthalamic lesions or by activated lymphocytes in multiple sclerosis. We considered that hyperprolactinemia and galactorrhea-amenorrhea syndrome in our patient might be caused from subthalamic lesions because lymphocytes were not activated during the remission stage of multiple sclerosis.
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PMID:[A case of multiple sclerosis with galactorrhea-amenorrhea syndrome]. 936 74

The benzofurane (+)-S 14297, the benzamide nafadotride, the aminoindane U 99194 and the arylpiperazine GR 103,691 have been proposed as "selective" antagonists at dopamine D3 vs. D2 receptors. Herein, we compared their in vitro affinities and in vivo actions to those of the aminotetralin D3 antagonists (+)-AJ 76 and (+)-UH 232. Affinities at recombinant, human (h)D3 and/or hD2 sites were determined by employing the mixed D2/D3 antagonist [125I]-iodosulpride and the preferential D3 ligands [3H]-(+)-PD 128, 907 and [3H]-(+)-S 14297. [3H]-(+)-PD 128,907, [3H]-(+)-S 14297 and [125I]-iodosulpride yielded an essentially identical pattern of displacement at D3 sites, which suggests that they recognize the same population of receptors. The rank order of potency (Ki values in nM vs. [3H]-(+)-PD 128,907) was GR 103,691 (0.4) approximately nafadotride (0.5) > haloperidol (2) approximately (+)-UH 232 (3) approximately (+)-S 14297 (5) > (+)-AJ 76 (26) > U 99194 (160). The rank order of preference (Ki ratio, D2:D3) for D3 receptors (labeled by [3H]-PD 128,907) vs. D2 sites (labeled by [125I]-iodosulpride) was (+)-S 14297 (61) approximately GR 103,691 (60) > U 99194 (14) > nafadotride (9) approximately (+)-UH 232 (8) approximately (+)-AJ 76 (6) > haloperidol (0.2). (+)-S 14297 and GR 103,691 also showed greater than 100-fold selectivity at dopamine hD3 vs. hD4 and hD1 sites. However, GR 103,691 showed marked affinity for serotonin1A receptors (5.8 nM) and alpha-1 adrenoceptors (12.6 nM). In vivo, all antagonists except GR 103,691 prevented the induction of hypothermia by (+)-PD 128,907 (0.63 mg/kg s.c.) and a further preferential D3 agonist, (+)-7-OH-DPAT (0.16 mg/kg s.c.). On the other hand, haloperidol, (+)-AJ 76, (+)-UH 232 and nafadotride all induced catalepsy in rats, whereas (+)-S 14297, U 99194 and GR 103,691 were inactive. Haloperidol, (+)-AJ 76, (+)-UH 232, nafadotride and (weakly) U 99194 also enhanced prolactin secretion and striatal dopamine synthesis, whereas (+)-S 14297 and GR 103,691 were inactive. However, despite its high affinity at 5-HT1A receptors and alpha-1 adrenoceptors, both of which are present on raphe-localized serotonergic neurons, GR 103,691 (0.5 mg/kg i.v.) failed to influence their basal firing rate or the inhibition of their electrical activity by the 5-HT1A agonist (+/-)-8-OH-DPAT (0.005 mg/kg i.v.), a result that casts doubt on its activity in vivo. In conclusion, both (+)-S 14297 and GR 103,691 are markedly selective ligands that permit the characterization of actions at hD3 vs. hD2 receptors in vitro, but (+)-S 14297 appears to be of greater utility for the evaluation of their functional significance in vivo. Nevertheless, to develop a better understanding of the respective roles of dopamine D3 and D2 receptors, we need additional, chemically diverse antagonists of improved potency and selectivity.
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PMID:A comparative in vitro and in vivo pharmacological characterization of the novel dopamine D3 receptor antagonists (+)-S 14297, nafadotride, GR 103,691 and U 99194. 976 37

In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic application of ergotamine and 5-HT suppressed the firing activity of CA3 pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A receptor antagonists. Co-application of ergotamine prevented the inhibitory action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine decreased, in a concentration-dependent manner, the electrically evoked release of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was prevented by the nonselective 5-HT receptor antagonist methiothepin but not by the selective 5-HT1B/1D receptor antagonist GR 127935 or the alpha 2-adrenoceptor antagonist idazoxan. Although body temperature in humans remained unchanged following inhaled ergotamine, in the rat, subcutaneously injected ergotamine produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B receptor/beta-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did not alter prolactin or adrenocorticotropic hormone levels, but increased growth hormone level, which was prevented by pindolol. Cortisol level was increased in humans by ergotamine, but this enhancement was unaltered by pindolol. In conclusion, the present results suggest that ergotamine acted in the rat brain as a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor activity but, probably because of lack of receptor selectivity, it did not present the same profile as other 5-HT1A receptor agonists.
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PMID:Effect of ergotamine on serotonin-mediated responses in the rodent and human brain. 977 59

Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. To study the effects of exercise on central serotonergic receptor sensitivity, we performed neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP, 0.4 mg/kg), ipsapirone (0.3 mg/kg) and placebo in 12 marathon runners and 12 healthy controls not practicing regular exercise. After administration of the nonselective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly by means of its action on 5-HT2C receptors, marathon runners showed a significantly reduced cortisol response in comparison to the control group. There was also a statistical trend toward a blunted prolactin response after m-CPP in the athlete group. In contrast, the increase of cortisol and the hypothermia observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude in both groups. The behavioral response to m-CPP or ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not differ between the marathon and the control group. In conclusion, exercise-induced downregulation of 5-HT2C receptors could play an important role in mediating the anxiolytic and antidepressive effects of exercise.
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PMID:Decreased neuroendocrine responses to meta-chlorophenylpiperazine (m-CPP) but normal responses to ipsapirone in marathon runners. 988 95

The selective dopamine D(3)-receptor antagonist S33084 dose dependently attenuated induction of hypothermia by 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT) and PD128,907. S33084 also dose dependently reduced 7-OH-DPAT-induced penile erections (PEs) but had little effect on 7-OH-DPAT-induced yawning and hypophagia, and it did not block contralateral rotation elicited by the preferential D(3) agonist quinpirole in unilateral substantia nigra-lesioned rats. In models of potential antipsychotic activity, S33084 had little effect on conditioned avoidance behavior and the locomotor response to amphetamine and cocaine in rats, and weakly inhibited apomorphine-induced climbing in mice. Moreover, S33084 was inactive in models of potential extrapyramidal activity in rats: induction of catalepsy and prolactin secretion and inhibition of methylphenidate-induced gnawing. Another selective D(3) antagonist, GR218,231, mimicked S33084 in inhibiting 7-OH-DPAT-induced PEs and hypothermia but neither hypophagia nor yawning behavior. Similarly, it was inactive in models of potential antipsychotic and extrapyramidal activity. In distinction to S33084 and GR218,231, the preferential D(2) antagonist L741,626 inhibited all responses elicited by 7-OH-DPAT. Furthermore, it displayed robust activity in models of antipsychotic and, at slightly higher doses, extrapyramidal activity. In summary, S33084 was inactive in models of potential antipsychotic and extrapyramidal activity and failed to modify spontaneous locomotor behavior. Furthermore, it did not affect hypophagia or yawns, but attenuated hypothermia and PEs, elicited by 7-OH-DPAT. This profile was shared by GR218,231, whereas L741,626 was effective in all models. Thus, D(2)-receptors are principally involved in these paradigms, although D(3)-receptors may contribute to induction of hypothermia and PEs. S33084 should comprise a useful tool for further exploration of the pathophysiological significance of D(3)- versus D(2)-receptors.
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PMID:S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: II. Functional and behavioral profile compared with GR218,231 and L741,626. 1086 11

Reproductive experience (RE), i.e., mating, pregnancy, parturition and lactation, has long-term physiological effects. It reduces the basal levels of circulating prolactin in parous women, decreases the intensity of nocturnal and diurnal prolactin surges in multigravid rats during early pregnancy, as well as the hormonal and neurochemical responses to the dopamine receptor antagonists metoclopramide and haloperidol. In the present study, we evaluated the possible influences of RE on some dopaminergic-related behaviors: (1) acute responses to a new environment represented by an open-field arena plus injection stress; (2) modulation of behavior after a short-term withdrawal subsequent to 7 days amphetamine (AMPH) pretreatment; (3) stereotypy elicited by AMPH and apomorphine (APO); and (4) APO-induced hypothermia. In the 3-min open-field test, there was a decrease in locomotor activity as a function of RE. Behavioral depression was mild and AMPH pretreatment revealed RE alterations. APO-induced stereotyped behavior was slightly more intense in primiparous animals, although no significant differences were found in AMPH-induced stereotyped behavior. No differences were observed between intact and ovariectomized primiparous and nulliparous animals in APO-induced hypothermia. Our data suggest that RE modifies some DA-related behavioral responses. The physiological relevance of the phenomenon is discussed.
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PMID:Reproductive experience modulates dopamine-related behavioral responses. 1132 14

The hypothalamus plays an important role in the regulation of several visceral processes, including food intake, thermoregulation and control of anterior pituitary secretion. Endogenous cannabinoids and CB(1) cannabinoid receptors have been found in the hypothalamus. In the present review, we would like to clarify the role of the endocannabinoid system in the regulation of the above-mentioned visceral functions. There is historical support for the role of marihuana (i.e. exogenous cannabinoids) in the regulation of appetite. Endocannabinoids also stimulate food intake. Furthermore, the specific CB(1) receptor antagonist SR141716 reduces food intake. Leptin treatment decreases endocannabinoid levels in normal rats and ob/ob mice. These findings provide evidence for the role of the hypothalamic endocannabinoid system in food intake and appetite regulation. Cannabinoids can change body temperature in a dose-dependent manner. High doses cause hypothermia while low doses cause hyperthermia. Cannabinoid administration decreases heat production. It seems that the effects of can- nabinoids on thermoregulation is exerted by altering some neurochemical mediator effects at both the presynaptic and postsynaptic level.THC and endocannabinoids have mainly inhibitory effects on the regulation of reproduction. Administration of anandamide (AEA) decreases serum luteinizing hormone (LH) and prolactin (PRL) levels. AEA causes a prolongation of pregnancy in rats and temporarily inhibits the postnatal development of the hypothalamo-pituitary axis in offspring. The action of AEA on the reproductory parameters occurs at both the hypothalamic and pituitary level. CB(1) receptors have also been found in the anterior pituitary. Further, LH levels in CB(1) receptor-inactivated mice were decreased compared with wild-type mice. Taken together, all these observations suggest that the endocannabinoid system is playing an important part in the regulation of the mentioned visceral functions and it provides the bases for further applications of cannabinoid receptor agonists and/or antagonists in visceral diseases regulated by the hypothalamus.
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PMID:The role of endocannabinoids in the hypothalamic regulation of visceral function. 1205 44

The hypothermia produced by 5-HT1A agonists had initially been claimed to be caused by the activation of cell body 5-HT1A autoreceptors resulting in decreased 5-HT transmission in laboratory animals. In order to address this issue in humans, 12 healthy volunteers underwent a dietary tryptophan depletion paradigm to decrease 5-HT availability, under double-blind conditions, during which body temperature was monitored following oral administration of the 5-HT1A agonist buspirone (30 mg). In addition, plasma prolactin and growth hormone evaluations, two responses that are mediated via the direct activation of postsynaptic 5-HT1A receptors, were determined. The hypothesis was that if responses are mediated by decreased transmission at postsynaptic 5-HT1A receptors, resulting from dampened 5-HT release as a consequence of 5-HT1A autoreceptors activation, then responses to the exogenous 5-HT1A agonist should be attenuated when 5-HT availability has been markedly decreased beforehand. Buspirone produced the same significant increase in prolactin and growth hormone in the tryptophan-depleted state as in the control condition. Similarly, the degree of hypothermia produced by buspirone was not significantly different in the two experimental conditions. In conclusion, these results strongly suggest that the hypothermia and the increases in prolactin and growth hormone produced by buspirone are attributable to the enhanced activation of postsynaptic 5-HT1A receptors, and not to a decrease in 5-HT transmission resulting from the activation of the 5-HT1A cell body autoreceptors on 5-HT neurons.
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PMID:Serotonin 1A receptor activation and hypothermia in humans: lack of evidence for a presynaptic mediation. 1209 4

1-(2-ethoxy-phenyl)-4-[3-(3-thiophen-2-yl-isoxazolin-5-yl)-propyl]-piperazine (KCH-1110), has a high affinity for human dopamine D3 (hD3) receptor (Ki=1.28 nM) with about 90-fold selectivity over the human dopamine D2L (hD2L) receptor. Antipsychotic or antidopaminergic activity of KCH-1110 was investigated in the models for the positive symptoms of schizophrenia, apomorphine-induced climbing and cocaine-induced hyperlocomotion, in mice. Intraperitoneal (i.p.) or oral (p.o.) administration of KCH-1110 potently inhibited the apomorphine-induced cage climbing without any rotarod ataxia in mice. Cocaine-induced hyperactivity was also antagonised by KCH-1110. In addition, KCH-1110 attenuated the hypothermia induced by a selective dopamine D3 agonist, 7-OH-DPAT in mice. KCH-1110 did not induce catalepsy in mice, but at much higher doses only a slight catalepsy response was shown. Although high doses of KCH-1110 significantly enhanced serum prolactin secretion in rats, low dose of KCH-1110 did not increase prolactin levels in rats. The present studies, therefore, suggest that KCH-1110 is a potent and relatively selective dopamine D3 receptor antagonist with antipsychotic actions.
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PMID:Pharmacological actions of a novel and selective dopamine D3 receptor antagonist, KCH-1110. 1452 27


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