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  • 1995-1999  (1)
  • 1970-1974  (3)
  • Isolated Perfused Rat Brain  (3)
  • Key wordsMDM2 amplification  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 243-254 
    ISSN: 1432-1912
    Keywords: Neuroleptics ; Antidepressants ; Isolated Perfused Rat Brain ; High Energy Phosphates ; Glycolytic Pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isolated perfused rat brain was used for a comparative study of the effects of promazine, imipramine, monodesmethyl promazine and desipramine on cerebral energy metabolism. After perfusion for 30 min or 1 h the brain levels of the following substrates and metabolites were estimated: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, pyruvate, lactate, α-ketoglutarate, and ammonia. Drug concentrations of 5·10−6 M and 10−5 M in the perfusion medium caused a significant decrease of glucose-6-P alone. When the drug concentration was raised to a toxic range (10−4 M), reflected in the EEG by the pattern of secondary discharges, an accumulation of P-creatine and glucose and a decrease of glycogen, glucose-6-P and ammonia occurred; the lactate/pyruvate ratios remained unchanged. As there were no qualitative differences between the effects of the investigated neuroleptics and antidepressants on cerebral metabolism, these effects might be unspecific and not correlated with the pharmacological action of the drugs.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 323-332 
    ISSN: 1432-1912
    Keywords: Chloral Hydrate ; Trichloroethanol ; Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isolated perfused rat brain was used for a comparative study of the effects of chloral hydrate and trichloroethanol on cerebral energy metabolism. After a perfusion period of 30 min the brain levels of the following substrates and metabolites were measured spectrophotometrically: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, α-glycero-P, dihydroxyacetone-P, pyruvate, lactate, glutamate, α-ketoglutarate and ammonia. Furthermore, the concentration of chloral hydrate and trichloroethanol in the isolated brain and in the perfusion medium was measured colorimetrically. Little more than 10% of chloral hydrate in the isolated brain and in the perfusion medium were reduced to trichloroethanol. In intact animals there were about 70% of chloral hydrate transformed. Chloral hydrate and trichloroethanol caused an accumulation of P-creatine, no change in the lactate/pyruvate ratio, an increase of the glucose concentration and a decrease of glucose-6-P level in the isolated brain. The rise of brain glucose level was more pronounced after trichloroethanol than after chloral hydrate. The effects of chloral hydrate and trichloroethanol on brain glucose and glucose-6-P levels suggest an inhibition of brain hexokinase activity by these drugs.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1335
    Keywords: Key wordsMDM2 amplification ; Rb LOH ; p53 LOH ; p53 mutation ; Liposarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The present study aimed to investigate the status of alterations of the MDM2, Rb and p53 genes in a series of 45 liposarcomas. Furthermore, the possible correlation with histological and clinical parameters was studied. Methods: MDM2 amplification was examined by non-radioactive Southern blot hybridization with a human MDM2 cDNA probe. Mutations in the p53 gene were screened by polymerase chain reaction/single-strand conformation polymorphism analysis and direct sequencing. To study loss of heterozygosity (LOH) at the tumor-suppressor genes Rb and p53, we used four polymorphic intragenic Rb markers (introns 1, 17, 20, and 25) and two p53 markers (intron 1 and exon 4). Results: MDM2 amplification was found in 19 of 45 liposarcomas (42.2%). The frequency of LOH in Rb and p53 was nearly identical (22%). In 4 of 9 tumors (44.4%) with LOH, allelic loss was a concurrent event in both genes. Of 45 liposarcomas, 6 (13.3%) showed p53 mutations. Overall, alterations of the p53/MDM2/Rb pathway occurred in 30 of 45 liposarcomas (66.6%). In contrast to myxoid and pleomorphic variants, well-differentiated liposarcomas were characterized by a high frequency of MDM2 amplification, a lack of LOH of Rb and p53, and p53 mutations. Conclusions: Obviously MDM2 amplification and LOH at the Rb and p53 genes do not occur simultaneously in the oncogenesis of liposarcomas, as is the case for MDM2 amplification and p53 gene mutations (with one exception). We suggest that well-differentiated, myxoid and pleomorphic liposarcomas are characterized by a different pattern of molecular alterations.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 124-134 
    ISSN: 1432-1912
    Keywords: Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway ; Phenobarbital ; Ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The concentrations of P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, α-glycero-P, lactate and pyruvate were measured in the isolated perfused rat brain as well as in rat brain in vivo. Similar levels were observed in the isolated brain and in intact animals, and the values measured were in good accordance with those described in the literature. Only the pyruvate and lactate content were significantly higher in the isolated brain but the lactate/pyruvate ratio remained unchanged. An anesthetic or ischemia caused just the same effects on energy metabolism of the isolated rat brain as described for intact animals. Thus, 1.5 mM phenobarbital in the perfusion medium produced a statistically significant increase in P-creatine and glucose levels as well as a decrease of pyruvate, lactate and α-glycero-P levels. After ischemia of the isolated brain the concentrations of high-energy phosphates, glycogen, glucose, and pyruvate fell considerably concomitantly with significant accumulations of creatine, AMP, α-glycero-P and lactate. The results indicate that the isolated perfused rat brain may be a useful tool for studying cerebral metabolism.
    Type of Medium: Electronic Resource
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