Effect of testosterone on compensatory hypertrophy of rat skeletal muscles.
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Biomedical subjects
Publications and source records attributed to M Marchetti.
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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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The new pyridazine derivative 3-hydrazino-6-[N,N-bis(2-hydroxyethyl)-amino]-pyridazine-dihydrochloride (DL 150 IT) was administered to five hypertensive patients at the dose of 50 mug/kg by i.v. bolus injection. A parallel group of five patiens received 250 mug/kg of hydralazine. Hemodynamic measurements were obtained before treatment, and then after 30--60 and 80-120 min. Cardiac output was evaluated by radiocardiography and myocardial perfusion by clearance of 86Rb. The antihypertensive effect of DL 150 IT was most pronounced 2 h after the injection, whereas by this time the increased heart rate and cardiac output tended to revert to the baseline values. On the contrary, the magnitude of these effects did not change during the observation period after hydralazine treatment. Both drugs increased myocardial perfusion. The new compound appears at least five times more potent than hydralazine and, possibly, has a longer duration of action.
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1. Folate metabolism was studied during the early phases of liver regeneration after partial hepatectomy in rats accustomed to eating during the first 8h of a daily 12h dark period. 2. The content of 5-CH(3)-H(4)folate was drastically decreased during the first hours of regeneration. 3. The total HCO-H(4)folate coenzymes showed a constant decrease during the first 3 days of regeneration, and a continuous interconversion between 5-HCO-H(4)folate and 10-HCO-H(4)folate. 4. 10-HCO-H(4)folate synthetase, serine hydroxymethyl-transferase and 5,10-CH(2)-H(4)folate dehydrogenase activities were relatively low during the first hours after the operation, and increased only several hours later. 5. The increase in enzyme activities showed a stepwise pattern, apparently due to an interaction between the regeneration process and the controlled feeding schedules.
The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation.
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