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Biomedical subjects

F Monaco

Publications and source records attributed to F Monaco.

At least 109 records · Page 6Linked to original sources

The free fraction of valproic acid in tears, saliva, and cerebrospinal fluid.

Valproic acid (VPA) was determined by EMIT assay in plasma, tears, saliva, and cerebrospinal fluid (CSF) of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios. The VPA CSF/serum ratio was in good agreement with data in the literature. Salivary levels were extremely erratic, while those for tears were much more reliable. Determination of VPA in tears is therefore the best method of studying the VPA free fraction in those cases in which investigations of protein binding of the drug are necessary.

Adult↗

Normal brain distribution of carbamazepine in cat penicillin focal epilepsy.

Carbamazepine (CBZ) brain distribution was studied in cats rendered epileptic by penicillin topically applied on neocortex. CBZ penetration into the focus did not differ significantly from penetration into the other areas of the brain, with the drug rapidly entering the cerebral tissue (peak at 30 min). As no difference was found between CBZ brain concentrations at 15 and 90 min, substantial early binding of the drug was confirmed in this experimental model of epilepsy. As CBZ was able to decrease rapidly the spike frequency of the penicillin focus, it may be speculated that it was also able to prevent the metabolic alterations associated with severe epileptogenesis that would have caused an impaired CBZ brain distribution.

Animals↗

Cerebellar impairment following acute nontoxic administration of phenytoin in rat.

In awake paralyzed Wistar rats, the following effects of an acute nontoxic dose of phenytoin (PHT) on different parameters of cerebellar electrical activity were evaluated: spontaneous discharge rate of single Purkinje cells (P-cells), field potentials, and responses of P-cells generated by electrical stimulation of a forelimb nerve. Variations of the response of single neurons located in the inferior olive were also studied, in order to assess the effects of PHT on this precerebellar relay station. The drug was administered orally and plasma and cerebellar levels regularly estimated. The results indicate that an acute, nontoxic dose of PHT is associated with an increase of P-cell firing rate. This finding is supported by the analysis of the frequency distribution of interspike intervals, and by the field potentials, P-cell, and olivary responses induced by stimulation of a radial nerve. In addition, it was observed that the increase in P-cell firing was mainly depending upon a higher activity of the climbing fibers. The increase in the response of P-cells and olivary cells was correlated with plasma and cerebellar drug levels. The conclusion was reached that PHT increases the cerebellar cortical activity through two mechanisms: (a) by acting directly on the cerebellar P-cell; and (b) indirectly by acting on the origin of climbing fibers at the inferior olive nucleus.

Animals↗

[Inhibition of the biosynthesis of thyroglobulin with propranolol in the rat].

Thyroglobulin biosynthesis was studied in thyroid glands of rats treated during 30 days with a daily dose of propranolol, a non-selective beta-adrenergic blocking drug. Studies were carried out by extraction of soluble proteins from homogenates after incubation of the glands in presence of [3H]-4,5-L-leucine and [3H]-D-1-galactose. Thyroglobulin 19S, 12S and 4-8S soluble proteins were separated and identified by ultracentrifugation in a saccharose gradient. The glands of rats treated with propranolol showed a decreased amount of soluble proteins as well as a decreased incorporation of [3H] labeled markers. 19S thyroglobulin is poorly represented, but very large amounts of the 12S monomer are present; this suggests an impairment in the dimerization of the 12S subunit, absent in normal controls. This impairment could be due to a structure modification. Propranolol reduces the biosynthesis of thyroglobulin in thyroid gland as well as the formation of T3 from T4 in peripheral tissues; its therapeutical use against thyrotoxicosis is thus justified. The study of its action on the dimerisation of the 12S subunit could be of interest to clear the mechanism of thyroglobulin biosynthesis.

Animals↗

[Inhibition of the biosynthesis of thyroglobulin in the thyroid gland of rats by isoniazid].

Groups of rats have been treated for one month with a daily dose of 50 mg/kg of body weight/day of isoniazide a product used therapeutically in man against tuberculosis. The animals submitted to this experiment showed an increase of thyroid weight (39%) and a decrease of its content in water soluble proteins, including thyroglobulin and precursors. These proteins have been labeled in vitro by [3H]-4,5-L-leucine and by [3H]-galactose, by incubation of isolated glands during 4 h in a medium containing this labeled marker. The decrease of thyroglobulin-like proteins was of 20-37% for [3H]-D-1-galactose, labeled fraction and of 46-53% for the [3H]-leucine labeled fraction. Two thirds of the radioactive protein sedimented by ultracentrifugation in a sucrose gradient were present in a 12S monomer of thyroglobulin. This suggests an impairment of biosynthesis of 19S thyroglobulin, in which two of the subunit are associated. Under experimental conditions adopted this 19S protein was labeled by [3H]-leucine, but not by [3H]-galactose. Two other antituberculous agents studied, ethambutol and rifamizine, exerted not the same effects on thyroid gland in rats. Therefore a control of thyroid function appear to be necessarily only in man treated by isoniazine.

Animals↗

Transcutaneous measurements of carbon dioxide partial pressure in sick neonates.

The authors measured the partial pressure of carbon dioxide transcutaneously (PtcCO2) in 15 sick newborns and compared the PtcCO2 to simultaneously measured partial pressure of arterial carbon dioxide (PaCO2). The PtcCO2 values reflected changes in the PaCO2 values. A linear regression on 106 paired PtcCO2 and PaCO2 values produced a correlation coefficient of 4 = 0.91 with a slope of 1.89 and a y-intercept of --9.4. The authors found the measurement of PtcCO2 to be a clinically useful method of continuously following the trend of PaCO2.

Arteries↗

Ethosuximide in tears, saliva, and cerebrospinal fluid.

Ethosuximide (ESM) was determined by the EMIT technique in tears, saliva, cerebrospinal fluid (CSF), and plasma of epileptic subjects. CSF/plasma, saliva/plasma and saliva/CSF ratios were in good agreement with gas-liquid chromatography (GLC). The tears/plasma ratio was not significantly different from the saliva/plasma ratio, although the standard deviation was higher in the latter. These data indicate that ESM can be determined in a quantitatively similar manner in both saliva and tears by EMIT.

Adult↗

Diphenylhydantoin and primidone in tears.

Diphenylhydantoin (PHT) and primidone (PRM) were determined by the EMIT technique in the plasma, tears, saliva, and CSF of epileptic patients. Results indicate for PHT that tear values are more strictly correlated than are the saliva values to plasma and CSF concentrations. As for PRM, the data obtained show great interindividual variability of concentration in the different body fluids--in agreement with the wide range of both protein binding and half-life of this drug.

Adult↗

[In vivo effects of conjugated estrogens on the insulin receptor and on glucose binding in isolated adipocytes of male rats].

Studies have been carried out with labeled substrates on isolated adipocytes of male rats injected with sulpho-conjugated estrogens. Three days treatment did not affect insulin receptor concentration or affinity in the cells. Conversely glucose uptake is reduced in the absence of insulin, or by reduced responsiveness in the presence of it. After ten days treatment, insulin binding impaired on account of reduced receptor concentration, whereas glucose uptake was normal in the absence of insulin, increased at low and decreased at high insulin concentration, on account of both decreased responsiveness and increased sensibility to insulin. Thus it is suggested that estrogens acts on glucose uptake prior to act on the insulin receptor in the adipocytes.

Adipose Tissue↗

[Tunicamycin inhibition of carbohydrate incorporation into thyroglobulin].

Carbohydrate chains formation into thyroglobulin (Tg) is a prerequisite for thyroid hormones formation and completeness of carbohydrates chains is necessary for secretion of Tg into the follicles. Tg biosynthesis has been investigated by in vitro experiments, incubating rat thyroid glands with labeled amino-acid and carbohydrate in the presence of tunicamycin, a specific inhibitor of protein glycosylation. Tunicamycin inhibit Tg biosynthesis which is impaired in carbohydrate chains addition but slightly in the polypeptide synthesis, as shown by inhibition of 3H-glucosamine incorporation. Thus tunicamycin inhibits carbohydrate incorporation into Tg without affecting the polypeptide chain growth and decreases its secretion into the follicles.

Animals↗

[Effect of change of habitat (sea and fresh water) on in vivo thyroglobulin synthesis in Atlantic glassed eels (Anguilla anguilla L.)].

Thyroid biosynthesis in glassed eels (Anguilla anguilla L.) was studied to establish whether salinity changes could affect it, when they live in sea water or in fresh water containing 125I. Aqueous extrait of homogenized cephalic heads of glassed eels contains an iodinated protein 17-19 S having thyroglobulin-like properties and including iodotyrosins (MIT and DIT) and thyroid hormones (3 and T4). Biosynthesis of this proteins is roughly twice more important in fresh water than in sea water at 19-21 degrees C and its specific radioactivity (125I) is practically double in fresh water.

Acclimatization↗

Psychotic onset of multiple sclerosis.

A case is reported of a woman in whom acute manic attacks were followed later in life by neurological signs of multiple sclerosis, thus suggesting a possible correlation between the two clinical entities.

Adult↗

Acquired ocular-motor apraxia and right-sided cortical angioma.

A case of acquired ocular-motor apraxia featured by failure in voluntary initiation of lid closure, horizontal and vertical eye movements is reported. Electrographic and neuropsychological assessment pointed out several signs referable to bilateral frontal and right parietal lobe involvement, confirmed by neuroradiological finding.

Apraxias↗

Carbamazepine-10,11-epoxide determined by EMIT carbamazepine reagent.

Carbamazepine-10,11-epoxide (CBZ-OX) was determined in physiological solutions by means of EMIT carbamazepine reagent. It was recognized as 12 to 20% of the total amount, the cross-reaction being higher at lower CBZ-OX concentrations. A correction for CBZ-OX is necessary when one wants to correlate EMIT carbamazepine values with gas-liquid chromatography values. However, this correction is relevant only for body fluids other than plasma, since the unbound fraction of CBZ-OX would greatly influence the ultrafiltrate serum ratios.

Biotransformation↗

Effects of propylthiouracil and methylmercaptoimidazole on thyroglobulin synthesis.

The effect of 6-propyl-2-thiouracil (PTU), and 1-methyl-2-mercaptoimidazole (MMI) on thyroglobulin (Tg) biosynthesis has been studied in vivo and in vitro. In vivo experiments were performed in rats treated for 20 days with PTU or MMI, analyzing soluble and particulate, cold and 125I-labelled, Tg. Thyroglobulin biosynthesis was also investigated by in vitro experiments, incubating thyroid tissue with labelled amino acid and carbohydrate in the presence of antithyroid compounds. It has been found that in vivo antithyroid agents decrease the amount of soluble Tg and increase the proportion of particulate Tg. Tg from treated animals is poorly iodinated being mainly represented by its 12S subunit. In vitro studies demonstrate that PTU and MMI inhibit Tg biosynthesis which is impaired in the polypeptide synthesis as well as in carbohydrate chains addition. Thus the inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.

Amino Acids↗

Tears as the best practical indicator of the unbound fraction of an anticonvulsant drug.

Phenobarbital and carbamazepine concentrations were determined by the EMIT technique in tears, saliva, cerebrospinal fluid (CSF), and plasma of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios for the two agents. The phenobarbital CSF/serum ratio was in good agreement with data in the literature, and the higher ratio found for carbamazepine may be caused by an EMIT assay cross-reaction for the free fraction of carbamazepine-10,11-epoxide. In our hands, tears seem to represent the best practical indicator of the unbound fraction of an anticonvulsant drug, and the noninvasiveness of the method makes it specifically useful in pediatric neurology.

Adult↗