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)

Butorphanol, a synthetic agonist/antagonist, has been shown to act on mu-, delta- and kappa-opioid receptors. However, the relative involvement of opioid receptor subtypes in mediating butorphanol dependence is not known. In the present study, naltrindole, a delta-selective non-peptide antagonist, was administered intracerebroventricularly (i.c.v.) to mask supraspinal delta-opioid receptors before and during the induction of butorphanol dependence. Treatment with naltrindole (0.1, 1, or 10 nmol/5 microliters per rat) significantly blocked naloxone-, a nonspecific antagonist, precipitated butorphanol withdrawal behaviors (escape behavior, teeth-chattering, wet shakes, forepaw tremors, ptosis, diarrhea, body weight loss, and hypothermia) at all doses tested, and decreased ejaculation at 0.1 nmol in butorphanol-infused rats. In contrast, naltrindole treatment had no effect on yawning, nor urination. These results indicate that central delta-opioid receptors are involved in mediating butorphanol dependence in rats.
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PMID:Involvement of delta-opioid receptors in physical dependence on butorphanol. 840 23

Leaf and bark extracts of Byrsonima crassifolia displayed concentration-dependent, spasmogenic effects on rat fundus in vitro and biphasic effects on rat jejunum and ileum in vitro. Dose-related in vivo effects in intact rats using hippocratic screening were: decrease in motor activity, mild analgesia, back tonus, enophthalmos, reversible palpebral ptosis, ear blanching, Robichaud positive, catalepsy (awake) and strong hypothermia. Rat fundus in vitro was used as the bioassay to carry out an activity-directed separation. Bioactive material was concentrated in a 2% acetic acid leaf extract (HOAcE). Potency of HOAcE was increased by the presence of pargyline in the bathing solution. HOAcE was antagonized noncompetively by 1(1-naphthyl) piperazine (1-NP) and cyproheptadine and antagonized competitively by atropine (ATR). Cumulative concentration-response curves of HOAcE and serotonin (5-HT) did not show significant departure from parallelism (P > 0.1) and 5-HT potency was 6040 times that of HOAcE (95% confidence limits: 4620-7850). Solvent extraction of HOAcE split the spasmogenic activity of HOAcE into two types: (i) high-efficacy, low-potency, n-butanol-extracted, pargyline- and 1-NP-sensitive, ATR-insensitive activity, and (ii) low-efficacy, high-potency, ethyl acetate-extracted, pargyline-insensitive, ATR- and 1-NP-sensitive activity. HOAcE lacked muscarinic and nicotinic effects on rat jejunum and frog rectus abdominis. Results suggest the presence of more than one spasmogenic compound in the plant.
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PMID:Pharmacological and chemical screening of Byrsonima crassifolia, a medicinal tree from Mexico. Part I. 841 47

A combination of increased perioperative morbidity, together with the technical difficulty of an R 0 (curative) resection, is responsible for the poor prognostic factors of supradiaphragmatically extending renal tumors. Six patients aged 53-70 years with vena cava thrombosis extending into the right atrium or ventricle underwent en bloc resection of the primary tumor and tumor thrombus removal. If the atrial tumor mass was large or extended into the ventricle, resection was performed during cardiopulmonary arrest using a cardiopulmonary bypass method with the patient in deep hypothermia (< 18 degrees C). Alternatively if the cardiac tumor infiltration was minimal, resection was performed during an optionally short cardiopulmonary arrest period using a cardiopulmonary bypass method with the patient in hypothermia (23 degrees C). The operative procedure was determined by intracardiac tumor extension, tumor wall adhesions and tumor wall infiltrations, all of which were assessed intraoperatively by vena cava sonography. Six patients were strongly symptomatic preoperatively. Three developed sudden life-threatening cardiopulmonary insufficiency, possibly due to longer-lasting tricuspital valve prolapse with a consecutive right-to-left shunt through a newly reopened foramen ovale. One patient died 14 months postoperatively because of multiple metastases (hepatic, pulmonary and bone). One patient is still alive and has had a local recurrence for 2 months, which was diagnosed 65 months postoperatively. The remaining four patients are alive and well. They have been tumor-free for extended periods of time (29, 34, 62 and 84 months, respectively).
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PMID:[Interdisciplinary surgical therapy of renal tumors with intracardiac tumor thrombi]. 865 Aug 44

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.
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PMID:Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models. 866 90

Emotional disturbances, such as lack of motivation or depression, are common after stroke. The drugs mainly used to treat these syndromes in Japan are the cerebral metabolic enhancers whose biochemical and pharmacological profiles are similar to those of antidepressant drugs. In order to examine the possible therapeutic effect of T-794 [(5R)-3-(6-(cyclopropylmethoxy) 2-naphthalenyl)-5-(methoxymethyl) 2-oxazolidone], a new reversible inhibitor of monoamine oxidase (MAO) type A, on those emotional disturbances, its antidepressant activity was compared with those of major cerebral metabolic enhancers in rodents with or without treatment of cerebral ischemia. Oral administration of T-794 potently prevented reserpine-induced ptosis (ED50 = 4.41 mg/kg), akinesia (ED50 = 3.29 mg/kg), and hypothermia (minimum effective dose = 3 mg/kg) in mice. It was at least 3.7, 13.0, and 3.3 times more potent than cerebral metabolic enhancers tested (indeloxazine, bifemelane, amantadine and idebenone) in antagonism of the ptosis, the akinesia, and the hypothermia, respectively. Effect of T-794 was also examined in the behavioral despair test in rats subjected to forebrain ischemia. The ischemia was induced by a combination of bilateral common carotid artery occlusion (15 min) and systemic hypotension (sodium nitroprusside 5 mg/kg, s.c). From 13 d after the surgery, drugs were orally administered twice daily 7 times, and following the last administration rats were assessed for their behavior. T-794 reduced the duration of immobility in the behavioral despair test at 30 mg/kg without affecting spontaneous motor activity, whereas indeloxazine showed no significant effect. Antidepressant-like activity of T-794 was suggested in rodents with as well as those without cerebral ischemia. The results suggest that T-794 may make an important contribution to the treatment of emotional disturbances following stroke.
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PMID:Possible therapeutic effect of T-794, a novel reversible inhibitor of monoamine oxidase-A, on post-stroke emotional disturbances, assessed in animal models of depression. 914 8

Postnatal day-14 (P14) infant rats remained naive or were implanted with osmotic minipumps infusing saline or fentanyl (50 microg kg(-1) h(-1)). Fentanyl was administered 72 h later for measurement of antinociception in the tail-flick test. The potency of fentanyl was 3.0-fold lower in fentanyl-infused compared to saline-infused P17 rats. Fentanyl-infused P17 rats injected with naloxone underwent withdrawal characterized by increases in spontaneous activity, wall climbing, diarrhea, abdominal stretching, forepaw treading/tremors, wet-dog shakes, jumping, ptosis, rhinorrhea and hypothermia. Other naive, saline-infused and fentanyl-infused P17 rats not challenged with fentanyl or naloxone were housed until maturing into P42 juveniles. Fentanyl's potency was equal among each treatment group. However, morphine's potency was reduced in juveniles tolerant to fentanyl as infants. Morphine was also less potent in P90 adults tolerant to fentanyl as infants. Thus, chronic opiate exposure during infancy may affect the developing central nervous system, and desensitize animals and humans to opiate analgesia throughout life.
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PMID:Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence. 988 76

Tolerance and dependence induced by chronic delta-9-tetrahydrocannabinol (THC) administration were investigated in mice. The effects on body weight, analgesia and hypothermia were measured during 6 days of treatment (10 or 20 mg kg(-1) THC twice daily). A rapid tolerance to the acute effects was observed from the second THC administration. The selective CB-1 receptor antagonist SR 141716A (10 mg kg(-1)) was administered at the end of the treatment, and somatic and vegetative manifestations of abstinence were evaluated. SR 141716A administration precipitated several somatic signs that included wet dog shakes, frontpaw tremor, ataxia, hunched posture, tremor, ptosis, piloerection, decreased locomotor activity and mastication, which can be interpreted as being part of a withdrawal syndrome. Brains were removed immediately after the behavioural measures and assayed for adenylyl cyclase activity. An increase in basal, forskolin and calcium/calmodulin stimulated adenylyl cyclase activities was specifically observed in the cerebellum of these mice. The motivational effects of THC administration and withdrawal were evaluated by using the place conditioning paradigm. No conditioned change in preference to withdrawal associated environment was observed. In contrast, a conditioned place aversion was produced by the repeated pairing of THC (20 mg kg(-1)), without observing place preference at any of the doses used. This study constitutes a clear behavioural and biochemical model of physical THC withdrawal with no motivational aversive consequences. This model permits an easy quantification of THC abstinence in mice and can be useful for the elucidation of the molecular mechanisms involved in cannabinoid dependence.
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PMID:Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with delta-9-tetrahydrocannabinol. 988 86

The interaction with monoamine oxidase A (MAO-A) and B has been shown to be sensitive to the absolute configuration of molecules. Therefore, the aim of this study was to compare the effects of the racemic pirlindole (a selective and reversible MAO-A inhibitor) and its two enantiomers using biochemical techniques (in vitro and ex vivo determination of rat brain MAO-A and MAO-B activity) and behavioural models (forced swimming test and reserpine-induced hypothermia and palpebral ptosis test). In vitro, the MAO-A IC50 of (+/-)-pirlindole, R-(-)-pirlindole and S-(+)-pirlindole were 0.24, 0.43 and 0.18 microM, respectively. Ex vivo, their ID50 were 24.4, 37.8 and 18.7 mg/kg i.p. The differences between the three compounds were not significant, with a ratio between the two enantiomers [R-(-)/S-(+)] of 2.2 in vitro and 2.0 ex vivo. MAO-B was only slightly inhibited. In the forced swimming test and the reserpine-induced hypothermia and ptosis model, the three compounds had an antidepressant profile. In the forced swimming test, the minimal effective dose ratio between the R-(-) and the S-(+) was again around 2.0. The behavioural observations were thus clearly in accordance with the biochemical data.
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PMID:Comparative study of pirlindole, a selective RIMA, and its two enantiomers using biochemical and behavioural techniques. 989 Feb 62

Glutapyrone, a disodium salt of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)- glutaric acid, is a representative of a novel 'class' of amino acid-containing 1,4-dihydropyridine (DHP) compounds developed at the Latvian Institute of Organic Synthesis, Riga, Latvia. Conceptually, the glutapyrone molecule can be regarded as a dipeptide-mimicking structure formed by the "free" amino acid (glutamate) moiety and "crypto" (built into the DHP cycle) amino acid ("GABA") elements. Both of these amino acids are joined by the peptide bond. This compound unlike classical DHPs lacks calcium antagonistic or agonistic properties. Our previous studies revealed a profound and long-term anticonvulsant, stress-protective and neurodeficit-preventive activities of glutapyrone. In view of structural properties the role of glutamatergic mechanisms in the mediation of central effects of glutapyrone was considered. In the present study glutapyrone at the concentration range of 1 microM(-1) mM failed to effect both NMDA ([3H]TCP) and non-NMDA ([3H]KA and [3H]AMPA) receptor ligand binding in the rat cortical membranes in vitro. The compound markedly enhanced motor hyperactivity induced by the NMDA antagonist PCP and the dopamine releasing compound D-amphetamine in the rats. Glutapyrone displayed activity in a variety of animal models relevant for affective/depressive disorders in humans i.e. reserpine-induced ptosis and hypothermia, forced swimming test and open field test. These data indicate that the unusually "broad" pharmacological spectrum of glutapyrone might involve concomitant actions on multiple neurotransmitter systems, particularly, GABA-ergic and the catecholamines. It is discussed whether these functional properties are secondary to action on intracellular events, predominantly, G protein-related since glutapyrone appears to lack direct interactions with a number of receptors including ionotropic glutamate and GABA(A)/Bzd receptors.
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PMID:"Atypical" neuromodulatory profile of glutapyrone, a representative of a novel 'class' of amino acid-containing dipeptide-mimicking 1,4-dihydropyridine (DHP) compounds: in vitro and in vivo studies. 992 26

Preparturient hypocalcemia was identified in 4 cats in a specific pathogen-free colony between 1995 and 1996. All cats had an acute onset of clinical signs, 3 to 17 days prior to parturition. Signs of depression, weakness, tachypnea, and mild muscle tremors were the most common clinical signs, following by vomiting and anorexia. Additional abnormalities included hypothermia, third eyelid prolapse, dehydration, pallor, lethargy, flaccid paralysis, and hyperexcitability. Hematologic abnormalities included leukocytosis with neutrophilia and lymphopenia. Hypocalcemia was documented in each queen. Common serum biochemical abnormalities included high aspartate aminotransferase and creatine kinase activities. All cats responded to IV or SC administration of 10% calcium gluconate. Queens were then given calcium orally prior to and following parturition. The queens did not have additional complications for the duration of the gestational or lactational periods.
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PMID:Preparturient hypocalcemia in four cats. 1053 Mar 27


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