Radical pelvic surgical experience in combined treatment of advanced uterine cervico-carcinomas.
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Biomedical subjects
Publications and source records attributed to M Marchetti.
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1. Liver pteroylpolyglutamate distribution was studied during regeneration after partial hepatectomy in rats maintained under controlled feeding conditions. 2. Pteroylhexaglutamate, pteroylpentaglutamate and pteroyltetraglutamate concentrations decrease from 12 to 72 h after operation, then increase and reach normal values at 180 h. Pteroyltriglutamate concentration, already high at 12 h, remains so in the subsequent periods. Pteroyldiglutamate concentration was unchanged. Monoglutamate concentrations at first decrease, and at 180 h exceed normal values. 3. The decrease in polyglutamate derivatives with a high number of glutamate residues, at present considered to be the coenzyme forms of folate, could be related not to a decreased synthesis, but to a greater requirement for these compounds during the early periods of regeneration, when biosynthetic processes are markedly increased. It is indeed probable that the increased availability of the preferred substrate of pteroylpolyglutamate synthetase, i.e. tetrahydrofolate, enhances conversion of folate into coenzyme forms.
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The liver content of higher polyglutamate forms of folic acid, which in partially hepatectomized rats is markedly lower as compared with sham operated animals, is normalized by the vitamin administration. The greater availability of folic acid and consequently of the tetrahydrofolates, promotes the synthesis of actual coenzymic forms; so their content, in regenerating liver, is maintained at normal values in spite of a higher requirement caused by the exaltation of biosynthetic processes.
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In view of role played by pteroylpolyglutamates as actual folate coenzymes in single-carbon unit metabolism, the effect of folic acid deficiency on the distribution of these compounds in rat liver has been studied. In deficient rats the liver levels of pteroylpolyglutamates and in particular of those containing a higher number of glutamyl residues are more decreased as compared with monoglutamates. In fact penta- and other higher polyglutamates: mono-, di- and tri-glutamates ratio is lower in deficient rats than that in control rats. The decreased amount of these coenzymic forms observed in this condition may be considered as the consequence of the severe alterations of process which adds glutamate moieties to monoglutamate forms.
The distribution in liver of pteroylpolyglutamates and urinary excretion of folate metabolites was studied in folic acid deficient rats after injection of the vitamin, in order to evaluate the effect of folic acid deficiency on the conversion of the vitamin into actual coenzymic forms. Any significant difference neither in total activity nor in pteroylpolyglutamates of liver does not appear between deficient supplemented and unsupplemented animals. Also the urinary amounts of reduced metabolites in deficient rats do not increase after injection of folic acid. Therefore the inability of deficient rat liver to synthesize polyglutamates may be ascribed to the lower availability of tetrahydrofolates as they are the preferred substrates of pteroylpolyglutamate synthetase.
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The distribution of a solubilizate between micelles and the aqueous phase does not obey a simple partition law when a second solubilizate species is present. Alterations of the apparent partition coefficient cannot be explained in terms of a simple displacement mechanism, following the interaction of both solubilizates with the same site of the micelle. A non linear increase in solubilizate association to micelles following an increase in surfactant concentration is observed in the presence of a second solubilizate. A depression in the cloud point temperature follows the addition of a second species and is such that cannot be interpreted as a simple additive effect. Alteration of the apparent partition coefficient in a miscellar solution has an effect on the permeation rate of the solubilizate across an artificial membrane. Biopharmaceutical implications are discussed.
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The urinary elimination of calcium, other electrolytes, and hydroxyproline and the oral absorption of 47Ca have been evaluated in three groups of 8 patients before and during a 15-day treatment with prednisone at daily doses of 25 and 50 mg and with oxazacort, a new glucocorticoid, at a daily dose of 50 mg. The results obtained demonstrate that oxazacort in short-term teatment with a high dose has no significant effect on the urinary elimination of calcium and hydroxypyroline in experimental conditions in which prednisone produces statistically significant and clinically relevant increase, both when given at the same dose and when given at half that dose. On the other hand, the oral absorption of 47Ca is decreased by oxazacort, but less than by prednisone at the same dose. As the antirheumatic activity of oxazacort appears to be only slightly lower than that of prednisone (activity ratio of about 0.84: 1), these findings may have interesting therapeutic implications.
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