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)

Maple syrup urine disease results in accumulation of leucine and its metabolites, which may lead in the long term to neurological dysfunction. In acute neonatal crises, large amounts of leucine may be removed by continuous venovenous haemofiltration. This extracorporeal technique has its risks and hazards, which increase with duration of treatment. We report three neonates in life-threatening conditions due to maple syrup urine disease, treated for not more than 12 h with various continuous venovenous techniques: continuous haemofiltration, haemodiafiltration and haemodialysis. The efficiency of and tolerance to these techniques was evaluated. For all three patients, plasma leucine levels decreased dramatically from 2186, 3818 and 2536 mumol/L to 1131, 1275 and 488 mumol/L, respectively. Leucine clearance obtained was 4.28 ml/min in haemodiafiltration. Their patients' neurological status improved rapidly and they have a normal developmental quotient at 22 months, 13 months, and 11 months of age, respectively. Tolerance was good except for hypothermia and drop in haematocrit in all cases. Haemodiafiltration management was more cumbersome and time consuming because it required continual adjustment of the substitution fluid flow rate to precisely balance inflow and outflow rates. We recommend continuous venovenous haemodialysis as the therapy of choice. It might be anticipated that improvement of this technique, by increasing dialysate flow rate and blood flow rate, will allow leucine concentration to be decreased below 1000 mumol/L within 6-8 h, whatever the initial level.
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PMID:Continuous venovenous haemodiafiltration in the acute phase of neonatal maple syrup urine disease. 926 82

The effects of neuropeptide FF (NPFF) and its analogues on mouse body temperature were examined. In a thermoneutral environment, administration of NPFF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2), 1DMe ([D.Tyr1, (N.Me)Phe3] NPFF), and 3D ([D.Tyr1, D.Leu2, D.Phe3] NPFF) in the third ventricle produced marked hypothermia. The effect of 1DMe was dose-dependent, and 45 nmol decreased body temperature by 5.6 degrees C. This effect was more pronounced when mice were placed at 4 degrees C. Hypothermia was not reversed by naloxone, an opioid antagonist, and was not modified by morphine. After 5 days of chronic treatment with 1DMe, mice did not became tolerant to the hypothermic effect. These results indicate that central NPFF receptors may control body temperature independently from opioid functions.
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PMID:Hypothermic effects of neuropeptide FF analogues in mice. 930 Jun 19

Several effects of bacterial endotoxins involve an opioid pathway and neuropeptide FF is an endogenous peptide known to modulate opioid activity, mainly in the central nervous system. The aim of this study was to investigate in rats the role of central neuropeptide FF receptors in intestinal motor disturbances and body temperature changes induced by endotoxins and platelet-activating factor (PAF), a major endotoxin mediator. Rats were fitted with intestinal electrodes, an intraperitoneal thermistor probe and an intracerebroventricular (i.c.v.) cannula for long-term use. E. coli endotoxin (100 microg/kg, i.v.) disrupted the cyclic pattern of intestinal migrating myoelectric complexes and induced a biphasic increase in body temperature while PAF (25 microg/kg, i.p.) disrupted the migrating myoelectric complexes and induced hypothermia for about 2 h. The neuropeptide FF analog, (1 DME)Y8Fa (D-Tyr-D-Leu[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2) administered i.c.v. 40 and 100 microg/kg reduced the duration of migrating myoelectric complex disruption induced by endotoxin and PAF and abolished the PAF-induced hypothermia. Only at the dose of 100 microg/kg did (1 DME)Y8Fa change the biphasic endotoxin-induced hyperthermia into a monophasic increase. Naloxone (1 mg/kg, s.c.) reduced only the duration of migrating myoelectric complex disruption induced by endotoxin. These results indicate that central neuropeptide FF modulates the intestinal motor disturbances and changes in body temperature induced by endotoxin and PAF. Its action against endotoxin may involve an anti-opioid pathway whereas its action against PAF does not.
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PMID:Effects of neuropeptide FF on intestinal motility and temperature changes induced by endotoxin and platelet-activating factor. 934 30

Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.
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PMID:Ampullosporin, a new peptaibol-type antibiotic from Sepedonium ampullosporum HKI-0053 with neuroleptic activity in mice. 936 Jun 15

We report on the biochemical, cellular and pharmacological activities of SQA-neuropeptide FF (Ser-Gln-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2), a peptide sequence contained in the human neuropeptide FF (neuropeptide FF, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) precursor. Quantitative autoradiography revealed that, in the superficial layers of the rat spinal cord, SQA-neuropeptide FF displayed the same high affinity for [125I]1DMe ([125I]D-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2) binding sites (Ki = 0.33 nM) as did neuropeptide FF (Ki = 0.38 nM). In acutely dissociated mouse dorsal root ganglion neurones, SQA-neuropeptide FF reduced by 40% the depolarisation-induced rise in intracellular Ca2+ as measured with the Ca2+ indicator, Fluo-3. In mice, 1DMe and SQA-neuropeptide FF dose-dependently inhibited the antinociceptive effect of intracerebroventricular (i.c.v.) injections of morphine, but SQA-neuropeptide FF was less potent than 1DMe. Furthermore, SQA-neuropeptide FF, as well as 1DMe, produced marked hypothermia following third ventricle injections in mice. These data demonstrate that the human peptide, SQA-neuropeptide FF, exhibits biochemical and pharmacological properties similar to those of neuropeptide FF or neuropeptide FF analogues, and belongs to the neuropeptide FF family.
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PMID:Biochemical, cellular and pharmacological activities of a human neuropeptide FF-related peptide. 975 17

In neuronal cultures from the forebrain of 14-d-old rat embryos, transient hypoxia (95% N2/5% CO2, 37 degrees C) for 6 h has been shown to trigger delayed apoptotic death through sequential changes in protein synthesis, whereas preconditioning by a brief episode of hypoxia can rescue neurons. Because hypothermia has been reported to be neuroprotective, the present study was designed to test the influence of reduced temperature on the consequences of lethal hypoxia in our culture model, and cellular mechanisms involved were compared with those underlying preconditioning effects. After 6 d in vitro, cultures were subjected to hypoxia for 6 h. They were either placed at 32 degrees C concomitantly with hypoxia for 6 h or preconditioned the day before by a 1-h episode of hypoxia. The hypoxic insult decreased cell viability by 38% at 96 h after reoxygenation, and 23% of the neurons showed morphologic features of apoptosis. Both hypothermia and preconditioning prevented neuronal death and reduced apoptosis. Preconditioning led to time-dependent changes in leucine incorporation, with persistent overexpression of the survival proteins Bcl-2 and heat-shock protein 70. It also increased thymidine incorporation, in line with induction of the cofactor for DNA polymerase, proliferating cell nuclear antigen. Hypothermia reduced basal apoptosis and necrosis, but did not affect thymidine incorporation, and abolished hypoxia-associated protein synthesis. Therefore, both treatments were protective against neuronal injury consecutive to hypoxia in developing brain neurons in vitro. Whereas preconditioning activated a program that stimulated the expression of anti-apoptotic gene products and regulatory components of the cell cycle, hypothermia did not trigger active processes, but depressed cell activity, which in turn may impair the apoptotic phenomenon.
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PMID:Effects of hypothermia on hypoxia-induced apoptosis in cultured neurons from developing rat forebrain: comparison with preconditioning. 1070 40

This study examined the ability of the anti-opioid Neuropeptide FF (NPFF) to modify the endogenous activity of nitric oxide (NO). Antinociceptive and hypothermic effects of 1DMe (D.Tyr-Leu-(n.Me)Phe-Gln-Pro-Gln-Arg-Phe-NH(2)), an NPFF agonist, and of L-NAME (N(omega)nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase, were investigated in mice. Intraperitoneal (i.p.) injection of L-NAME induced, in the hot plate test, a dose-dependent antinociception not reversed by naloxone, an opioid antagonist, but inhibited by L-Arg, the NO synthesis precursor. Intracerebroventricular (i.c.v.) injections of 1DMe inhibit the antinociceptive activity of L-NAME in a dose-dependent manner. On the contrary, L-NAME markedly potentiated hypothermia induced by 1DMe injected in the third ventricle. These data show that Neuropeptide FF receptors exert a dual effect on endogenous NO functions and could modulate pain transmission independently of opioids.
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PMID:Opposing interplay between Neuropeptide FF and nitric oxide in antinociception and hypothermia. 1103 7

Although several studies have indicated that neurotensin administered acutely has several pharmacological properties common with those of antipsychotic drugs, the effects of repeated exposure to neurotensin receptor agonism have been less well characterised. Here, we investigated the effect of the novel neurotensin-(8-13) analogue NT69L [(N-methyl-Arg), Lys, Pro, L-neo-Trp, tert-Leu, Leu] in animal models sensitive to central neurotensin receptor stimulation as well as in predictive models for antipsychotic activity and motor side-effect liability. Acute injection of NT69L (0.19-6.1 micromol/kg, s.c./i.p.) caused hypothermia (>2.5 degrees C) and reduction in spontaneous locomotor activity but failed to induce catalepsy. Furthermore, NT69L (0.10 micromol/kg, s.c.) counteracted the hyperlocomotion elicited by amphetamine (0.5 mg/kg, s.c.). However, repeated injections of NT69L (0.19 micromol/kg, s.c. for 6 days, twice daily) significantly reduced its effect on spontaneous locomotor activity and completely abolished its effect on amphetamine-elicited hyperactivity. Our data obtained after single injections of NT69L indicate that this drug stimulates central neurotensin receptors after peripheral administration and collectively support the notion that neurotensin receptor agonism is associated with an attractive pre-clinical profile as regards both antipsychotic activity and motor side-effect liability. However, the present results also indicate that repeated neurotensin receptor stimulation may cause a desensitisation of neurotensin receptor mediated effects.
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PMID:Induction of tolerance to the suppressant effect of the neurotensin analogue NT69L on amphetamine-induced hyperactivity. 1143 Sep 16

A series of analogues of the fungal peptaibol type metabolite ampullosporin A containing modifications in the C and N terminus as well as alpha-aminoisobutyric acid (Aib) substitutions in different positions of the peptide were synthesized by solid phase synthesis using the 9-fluorenylmethyloxycarbonyl strategy. Depending on the sequence position, couplings were performed with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/1-hydroxybenzotriazole and tetramethylfluoroformamidinium hexafluorophosphate, respectively. The structures of the target peptides were analyzed by electrospray ionization mass spectrometry and chromatographic methods (high-performance liquid chromatography, thin-layer chromatography). The biological activities of these compounds have been evaluated by assaying their potencies for the induction of pigment formation on the fungus Phoma destructiva as well as for the induction of hypothermia and inhibition of locomotoric activity in mice and were compared to the naturally occurring ampullosporins. Native ampullosporin A and analogues with C-terminal Leu or Leu-NH(2) showed comparable activity in the pigmentation assay. Similarly, the ampullosporin A analogues with N-terminal aromatic amino acid residues, such as D-Trp and Tic, also have high potency for pigment formation. The peptides containing structural modifications of ampullosporin A by systematic replacement of Aib by Ala (Ala scan) displayed moderate or high activity in the pigmentation assay, whereas simultaneous substitution of all Aib residues by Ala and Ile, respectively, or by insertion of nonaromatic residues into position 1 resulted in a loss of the effect on P. destructiva. Most of the compounds with no or weak activity in the microbial assay were not active in the hypothermic test, too, except the compound with 1-amino-1-cyclohexane carboxylic acid in position 4 instead of Aib. However, only a few compounds with high potency for pigmentation induction were found to produce strong hypothermia in mice. Thus, in contrast to the native ampullosporins, we succeeded to a certain degree in differentiation of the bioactivities with our synthetic analogues.
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PMID:Synthesis and biological evaluation of analogues of the peptaibol ampullosporin A. 1206 80

The neuroprotective effect of the neurotensin analogue H-Lys-psi(CH2NH)Lys-Pro-Tyr-Ile-Leu-OH (JMV-449) was assessed in a mouse model of permanent distal middle cerebral artery occlusion. Mice were injected with 0.6 nmol JMV-449 or vehicle i.c.v. immediately after ischaemia. The core temperature declined by 6-7 degrees C after 30 min and the hypothermia persisted for 4-5 h. JMV-449 treatment was able to reduce the infarct volume significantly both at 24 h and 14 days after onset of ischaemia. No neuroprotective effect could be seen if the mice were kept normothermic after the JMV-449 treatment suggesting that the neuroprotective effect is mediated via the hypothermia.
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PMID:Neuroprotective effect of the neurotensin analogue JMV-449 in a mouse model of permanent middle cerebral ischaemia. 1462 34


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