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)

The tremorogenic properties of a series of benzylimidoylurea derivatives are described. The most potent member, N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), produces a reproducible, dose-dependent rest tremor in the mouse with oral doses of 5-100 mg/kg which is also seen in other species (rat, cat, dog, rabbit). The tremor is of constant frequency, rapid onset and short duration. It is not accompanied by akinesia, muscle ridigity, antinociceptive activity, parasympathomimetic effects or marked hypothermia and in these respects differs from tremor produced by oxotremorine. Pretreatment with a microsomal enzyme inhibitor had no effect on the tremor. An LD50 of 165 mg/kg p.o. was calculated in the mouse. After repeated administration both acute and chronic tolerance developed to the tremorogenic effects of LON-954. Evidence for a central site of action is presented, since the tremor could be reproduced following injection of small quantities (50-100 microgram) into the cerebral ventricles of the mouse. Furthermore, the use of spinal, decorticate and and decerebrate rats indicated that although tremor is not of cortical origin, it arises in an area rostral to the inferior colliculi. The mechanism underlying the tremor appears to involve dopaminergic pathways, since the action of LON-954 was antagonised by L-dopa and apomorphine and potentiated by pimozide. Atropine and carbachol were without effect. It is suggested that LON-954 could be used as an alternative to oxotremorine for the detection of anti-Parkinson drugs, particularly those exerting their effects through dopaminergic mechanisms.
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PMID:The pharmacology of N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride (LON-954) a new tremorogenic agent. 58 44

In order to assess the long-term effects of cardiopulmonary bypass (CPB) in combination with pupular methods of myocardial protection, 37 dogs were placed on CPB for 100 minutes with the use of a bubble oxygenator without hemodilution. A separate group (I) of eight normal dogs served as a control for assessment of hemodynamic changes. The operative groups were as follows: II, continuous coronary perfusion with an empty, beating heart for 60 minutes at 35 degrees C.; III, hypothermic anoxic arrest (aortic occlusion) for 60 minutes with topical cold saline lavage (4 degrees C.); IV, anoxic arrest for 60 minutes at 35 degrees C. Subgroups of Groups III and IV received intracoronary perfusion with Ringer's lactate or Sacks' solution during aortic occlusion and were compared with those animals receiving no perfusion. Survival in Groups II and III was significantly better than in Group IV (82 and 92 per cent vs. 45 per cent). Coronary perfusion with Ringer's lactate or Sack's solution did not influence survival. The 23 survivors from all groups underwent left heart catheterization and LV cineangiography 5 months after operation. All three operative groups had significant elevation of LVEDP and depression of maximum developed dp/dt when compared with normal dogs. Ejection fraction was significantly depressed in Groups III and IV, and there was evidence of left ventricular hypokinesia and/or akinesia in all three operative groups. Differences in function between Groups II, III, and IV were not significant. The use of intracoronary solutions during anoxic arrest did not significantly influence these functional alterations. Evidence of subendocardial fibrosis was found in each of the operative groups, with the most marked changes found in the normothermic arrest group. Moderate fibrosis was present, however, in some survivors in both the continuous coronary perfusion and topical hypothermic arrest groups. These data indicate that although survival is greatly enhanced when coronary artery perfusion or topical hypothermia is used, neither method prevents chronic deterioration in ventricular function nor the development of subendocardial fibrosis.
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PMID:Long-term morphologic and hemodynamic evaluation of the left ventricle after cardiopulmonary bypass. A comparison of normothermic anoxic arrest, coronary artery perfusion, and profound topical cardiac hypothermia. 118 84

Inhibition of ethanol tolerance by oxytocin has been demonstrated previously using the hypothermic effect only. The purpose of the present experiment was to investigate the effect of oxytocin on the development of tolerance to ethanol-induced hypothermia, myorelaxation and akinesia in mice. Four groups of mice received daily intraperitoneal injections of saline or oxytocin (0.005 mg) plus saline or ethanol (2 g/kg). The peptide was administered 2 hours before ethanol. For five consecutive days, temperature measurements were performed 20 minutes before and after ethanol injection. Myorelaxation and akinesia were evaluated following the second temperature measure. Oxytocin pretreatment, which had no intrinsic effects, resulted in a robust selective attenuation of tolerance to ethanol-induced hypothermia, myorelaxation and akinesia. These results suggest that the mechanisms for peptide modulation are common to these three typical effects of ethanol.
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PMID:Oxytocin attenuates tolerance not only to the hypothermic but also to the myorelaxant and akinesic effects of ethanol in mice. 180 28

GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)-ethyl] 4-(3-phenyl propenyl)-piperazine and dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the "despair test". Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.
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PMID:Comparison of the effects of three indirect dopamine agonists, GK 13, GBR 12783 and dexamphetamine on behavioural tests involving central catecholaminergic transmissions. 197 95

Behavioural tests for predicting antidepressant activity in the animal provide a closer approximation than other tests of states of depression in man but are often long and costly to perform (except the behavioural despair test). The tests proposed here presuppose a pharmacological interaction (except the Porsolt test) but are simple enough to allow screening: included are antagonism of reserpine hypothermia, ptosis and akinesia; antagonism of effects induced by oxotremorine; antagonism of high-dose apomorphine; and potentiation of yohimbine toxicity. In combination with the study of motor activity in the mouse, these tests allow assessment of the specificity of antidepressant activity by establishing a ratio between the "antidepressant" dose and the "stimulant" or "sedative" dose. It can be predicted that a substance will be antidepressant and sedative or stimulant at the same dose if the ratio is close to 1; if the ratio is less than 1, at antidepressant doses the substance will be very sedative or stimulant according to the case. The specificity of the tests discussed can be debatable. Antagonism of reserpine-induced hypothermia indicates substances with direct or indirect beta-mimetic activity, ptosis antagonism, substances with alpha-adrenergic (not antidepressants) or serotoninergic (possibly antidepressants) activity; and akinesia antagonism, a direct or indirect dopaminergic activity (sometimes found in antidepressants) with psychostimulant activity. The oxotremorine test is related to the anticholinergic activity of substances, except in the case of hypothermia antagonism. The high-dose apomorphine test seems to be specific for substances inhibiting norepinephrine reuptake. The yohimbine test is simple to carry out, relatively inexpensive and does not fail to screen any molecule known to be effective to-date. The behavioural despair test is a good complement for screening except for drugs having a beta-agonist activity, it appears that this test is dependent on functional relationships between alpha 2 and serotonergic systems.
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PMID:Is it possible to predict the activity of a new antidepressant in animals with simple psychopharmacological tests? 218 84

The hypothesis of this study was that inadequate right ventricular hypothermia contributes to the right ventricular dysfunction occasionally observed after cardiac operations. Dogs were placed on cardiopulmonary bypass, and 60 minute periods of hypothermic myocardial ischemia were imposed. Left ventricular temperature was always maintained at 15 degrees C and right ventricular temperatures were maintained at 15 degrees C (Group I, n = 8), 25 degrees C (Group II, n = 8), and 35 degrees C (Group III, n = 8). These temperatures were produced by infusion of hypothermic crystalloid cardioplegic solution and appropriate topical cooling and heating of the left and right ventricles, respectively. Multiple indices of ventricular function were obtained 15, 30, 45, and 60 minutes after bypass and compared to prebypass control values. In all Group I animals (left ventricular temperature = 15 degrees C, right ventricular temperature = 15 degrees C), postischemic indices of right ventricular function were not different from control values (p = NS). In Group II (left ventricular temperature = 15 degrees C, right ventricular temperature = 25 degrees C), two animals died 30 and 45 minutes after bypass, respectively, of right ventricular failure. In the other six animals in Group II, all indices of right ventricular function were significantly reduced (p less than 0.05) except for right ventricular systolic pressure. In Group III (left ventricular temperature = 15 degrees C, right ventricular temperature = 35 degrees C), two animals could not be weaned from cardiopulmonary bypass because of right ventricular akinesia. Six animals were weaned from bypass, but two died 15 minutes, one died 30 minutes, and one 45 minutes after bypass. Two animals lived 60 minutes, but all indices of right ventricular function were decreased. Failure to maintain right ventricular temperatures below 25 degrees C during 1 hour of cardiac ischemia in the dog can result in fatal right ventricular failure.
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PMID:Acute right ventricular failure is caused by inadequate right ventricular hypothermia. 397 74

An unusual case of Whipple's disease is reported. The diagnosis was difficult as the characteristic digestive sign and symptoms (malabsorption, diarrhea, mucosal infiltration by PAS-positive macrophages) were absent. After a ten-year history of seronegative arthritis, myocardiopathy, with aortic insufficiency, basilar pulmonary infiltrates, enlarged lymph nodes, the patient, a 56 years old man, was referred to us for a severe vegetative and neurological dysfunction: stupor, dysarthria, akinesia, hypertonia, hypothermia and abnormal thirst. A CT-scan showed a low-density area of the right hypothalamus, and PAS-positive macrophages were found in a lymph node, in the CSF and in a cerebral biopsy. The patient then received a classical antibiotic treatment, yet the neurologic dysfunction remained severe. Finally, a trial with rifampicin brought a striking improvement of the patient's condition, which has now lasted for three years.
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PMID:[Hypothalamic form of Whipple's disease. Favorable effect of rifampicin]. 619 50

The behavioural and histological effects of unilateral or bilateral lesions induced by kainic acid injections into the globus pallidus were investigated in rats. Both lesions provoked a behavioural syndrome similar to those seen in animals treated systemically with neuroleptics or opiates. Animals displayed akinesia, ptosis, catalepsy, hypothermia and muscular rigidity. Also a marked hypersensitivity to touch, and a sensory neglect to touch and pain limited to hindlegs, adipsia, aphagia and high mortality of lesioned rats were observed. These symptoms were much stronger and lasted longer (catalepsy lasted over 15 days) in bilaterally lesioned animals. Subcutaneous injections of apomorphine in bilaterally lesioned rats abolished akinesia and catalepsy while rigidity and ptosis were unaffected. In unilaterally lesioned rats in which the lesion-induced spontaneous catalepsy already disappeared the spiperone-induced catalepsy was suppressed while in bilaterally lesioned animals which showed still pronounced lesion-induced catalepsy the spiperone-induced catalepsy was unchanged when compared to the sham-operated rats. Our results and the literature data suggest that the lesions of the globus pallidus produce biphasic effects: spontaneous catalepsy and unchanged neuroleptic catalepsy in the first phase and suppression of the neuroleptic catalepsy in the second phase. The role of the globus pallidus as a distal link (for neostriatum and n. accumbens) in neuronal chain forming a matrix of central patterns of catalepsy, akinesia and rigidity is discussed.
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PMID:A biphasic influence of globus pallidus lesions: spontaneous catalepsy followed by anticataleptic effect. 635 69

Numerous tests have been proposed to search for a possible antidepressive action. Many of these tests are based on a reversal of different reserpine effects, an approach justified mainly by the use of most the classic or new antidepressants. Three effects of reserpine were examined in mice: hypothermia, ptosis and akinesia. All tests were performed with reserpine 2.5 mg/kg, and the drugs were injected 4 h after reserpine administration. In these three models, we studied the relatively specific effects of 21 drugs known for their influence on the metabolism or action of norepinephrine (noradrenaline), serotonin and dopamine. Our results suggest that hypothermia antagonism is only obtained with drugs stimulating beta-adrenergic receptors directly or indirectly, ptosis antagonism with those stimulating alpha-adrenergic or serotonergic receptors, and akinesia antagonism with those stimulating dopaminergic receptors.
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PMID:The value of the reserpine test in psychopharmacology. 668 96

Ventricular aneurysm is a frequent complication of myocardial infarction, but its diagnostic and prognostic implications are not fully defined. A surgical series of 66 ventricular resections for symptomatic left ventricular aneurysm is analyzed. Pts. age varied between 26-29 years; the interval between the episode of infarction and operation from 2 mos. to 12 years. Indication for surgery was angina in 53% of the cases, heart failure in 23%, arrhythmias in 15%, angina and failure in 9%. In 55 cases surgical findings were consistent with true aneurysm in the anatomical sense, in 11 cases with a wide area of wall akinesia. In 24 cases endocavitary thrombosis was present. In 23 cases aneurysmectomy was the only surgical procedure, with closure of acquired VSD in 1 case and mitral valve prosthesis in 2 cases. In 43 cases aorto-coronary bypass grafting was associated (single bypass in 18, double in 23, triple in 2). Operative technique underwent modifications in time, in relation to the use of local and general hypothermia, of cardioplegia, of early aortic cross-clamping. Surgical mortality was of 7.5% (5 cases); the actuarial courve, including operative mortality, showed survival of 88% at 1 year and of 78% at 5 years interval. Correlation between mortality and clinical symptomatology, hemodynamic data and surgical findings was not statistically significant; a statistically highly significant correlation was found between mortality and operative technique. The results are interpreted and discussed in relation to the diagnostic definition of the problem, to the criteria of indication to surgery and to the operative technique.
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PMID:[Surgical treatment of postinfarctual left ventricular aneurysm (author's transl)]. 746 54


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