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Biomedical subjects

A Machado

Publications and source records attributed to A Machado.

At least 127 records · Page 7Linked to original sources
PubMed1993

Changes in neurotransmitters in superior colliculus after neonatal enucleation: biochemical and immunocytochemical studies.

The turnover rate of dopamine and serotonin and the level of glutamate in superior colliculus are increased in adult, neonatally enucleated rats compared with normal control adult animals. Moreover, immunocytochemical data showed that the stratum zonale and the stratum griseum superficiale of the superior colliculus, specifically of bienucleated rats, display a dense network of serotonin-immunoreactive fibres, suggesting an increase in serotoninergic innervation. At the electron microscope level, serotonin-immunoreactive fibres and large postsynaptic serotonin-immunoreactive profiles exhibiting microtubules could be observed in the stratum zonale and the stratum griseum superficiale of the bienucleated rat. These results suggest that neonatal enucleation produces reorganization of serotoninergic and glutamatergic inputs. It is possible that serotonin may exert a profound influence upon collicular function.

5-Hydroxytryptophan↗
PubMed1993

The process of recurrent choice.

Recurrent choice has been studied for many years. A static law, matching, has been established, but there is no consensus on the underlying dynamic process. The authors distinguish between dynamic models in which the model state is identified with directly measurable behavioral properties (performance models) and models in which the relation between behavior and state is indirect (state models). Most popular dynamic choice models are local, performance models. The authors show that behavior in different types of discrimination-reversal experiments and in extinction is not explained by 2 versions of a popular local model and that the nonlocal cumulative-effects model is consistent with matching and that it can duplicate the major properties of recurrent choice in a set of discrimination-reversal experiments. The model can also duplicate results from several other experiments on extinction after complex discrimination training.

Animals↗
PubMed1993

Low selenium diet affects monoamine turnover differentially in substantia nigra and striatum.

Turnover of dopamine, noradrenaline, serotonin, and their metabolites has been measured in striatum and substantia nigra of adult female rats that were fed control or selenium-deficient diets for 15 days. In addition, the glutathione peroxidase activity has been studied. The most striking result was the increase of dopamine turnover (63%) and 3-methoxytyramine turnover (55%) in substantia nigra between control and experimental animals. On the other hand, no changes were found in the turnover rate of dopamine and its metabolites in the striatum. Likewise, no changes were found in noradrenaline turnover in substantia nigra. In the striatum, there was a significant increase of serotonin turnover versus no change for 5-hydroxy-3-indoleacetic acid. However, in the substantia nigra, serotonin turnover did not show significant changes, whereas 5-hydroxy-3-indoleacetic acid turnover decreased. At the same time, glutathione peroxidase activity significantly decreased in both structures after selenium-deficient diets. These results suggest that a selenium-deficient diet for a short period of time decreases brain protection, principally in the substantia nigra, against oxidative damage.

Animals↗
PubMed1993

In vivo release of dopamine from rat striatum, substantia nigra and prefrontal cortex: differential modulation by baclofen.

1. The effect of baclofen, a GABAB receptor agonist, on the release of dopamine from the striatum (ST), substantia nigra (SN) and prefrontal cortex (PFC) of the rat was examined by intracerebral microdialysis. 2. Perfusion of baclofen 50 microM did not affect the striatal release of dopamine. However, dopamine release was markedly reduced in the SN and PFC. 3. 3,4-Dihydroxyphenylacetic acid and homovanillic acid output increased in the ST and decreased in the SN and PFC when baclofen was perfused through the microdialysis probe. 5-Hydroxyindoleacetic acid levels were not affected in any experimental condition by baclofen perfusion. 4. The results suggest that GABAB receptors modulate the release of dopamine in the SN and PFC, but do not affect the striatal release of dopamine, which indicates that the role of GABA receptor activation is different in the dopaminergic terminals of the ST and PFC.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

[Bone marrow transplantation with major ABO incompatibility. Experience at the bone marrow transplantation unit of the Center of Lisbon at the IPOFG].

Thirteen patients submitted to major ABO incompatible, HLA A and B identical, mixed lymphocyte culture negative bone marrow transplantation (BMT) were retrospectively evaluated. Gravity sedimentation by hydroxyethyl starch was used in almost all cases to deplete erythrocytes from bone marrow (12/13): a removal rate or 90%--corresponding to an erythrocyte residual volume of 27.4 rate ml--and a nucleated cell recovery of 76% (mean values) were obtained. All patients underwent a hyperhydration regimen and received corticosteroid prophylaxis before bone marrow infusion. Considering the most important immunohematological problems associated to this type of transplant we verified that seven patients developed minor complications, and among them only one had long term consequences. In comparison with the control group, ABO identical and with minor incompatibility, the study group had delayed onset of erythropoiesis and needed greater erythrocyte transfusion support. We concluded that major ABO incompatibility does not constitute a drawback to BMT success in most patients.

ABO Blood-Group System↗
PubMed1992

Fast sodium channel dependency of the somatodendritic release of dopamine in the rat's brain.

Somatodendritic release of dopamine (DA) was studied by microdialysis. The basal release of endogenous extracellular DA in the rat's substantia nigra was 1.0 +/- 0.14 fmol/min (mean +/- S.E.M.; n = 6). Compared with the basal extracellular level of DA found in the striatum (12.9 +/- 0.94; n = 12), the former value was about 13 times smaller than the latter value. The addition to the Ringer solution of the fast sodium channel inhibitor, tetrodotoxin (TTX), at a concentration of 1 microM, produced the total disappearance of DA in the substantia nigra. When TTX was removed from the Ringer solution, the DA extracellular level came back slowly to the control value. This result suggests that the somatodendritic basal endogenous DA release measured by microdialysis is dependent on the sodium channel conductance.

Animals↗
PubMed1992

In vivo protection of striatum from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists.

The present study was designed to assess by microdialysis whether N-methyl-D-aspartate (NMDA) non-competitive receptor antagonist, MK-801, is able to protect dopaminergic neurons against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity. An intraperitoneal injection of MK-801, 10 mumol/kg, half an hour before striatal MPP+, 10 mM, perfusion did not protect against its neurotoxicity. Afterwards, rats received an intraperitoneal injection of MK-801 every 4 h, during 24 h. Under these conditions, one day after MPP+ perfusion, DA basal extracellular levels were close to the detection limit of our HPLC equipment in both control and MK-801 treated rats. 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) basal output were lower in the former than in the latter rats. A second MPP+ perfusion statistically increased extracellular levels of DA and decreased DOPAC and HVA output in both groups of rats. However, the increase in extracellular DA overflow was higher in MK-801 treated rats than in the control group, indicating a higher number of surviving dopaminergic terminals. These results suggest that MK-801 is not able to protect against the primary direct neurotoxic action of MPP+, but a second MPP+ neurotoxic action mediated by excitatory amino acids could be partially prevented by MK-801.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Effects of neonatal enucleation on catecholamine and serotonin turnover and amino acid levels in lateral geniculate nucleus and visual cortex of the adult rat.

Changes in turnover of dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine (5-HT)) and their metabolites, together with amino acid content, have been studied in dorsal lateral geniculate nucleus (LGNd) and visual cortex (VC) of neonatal enucleated rats. Enucleation increases the 5-HT turnover in LGNd and catecholamine turnover in VC. In contrast, enucleation decreases glutamate (and/or aspartate) content in LGNd and gamma-aminobutyric acid (GABA) in VC. These changes suggest an increase of the inhibitory action of the biogenic amines in LGNd after neonatal enucleation. The decrease of GABA in VC may reflect the importance of GABA in intracortical circuitry.

Amino Acids↗
PubMed1992

Changes in neurotransmitter levels associated with the deficiency of some essential amino acids in the diet.

The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were measured in rat substantia nigra and corpus striatum following dietary changes, including restriction of protein content (low-protein diet; LPD) and the contents of several large neutral amino acids (isoleucine, leucine, methionine, phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in the concentration of tyrosine (TYR) in the two regions of the brain studied. This effect was also observed with all amino acid deficiencies studied except for valine in the substantia nigra, tryptophan in the striatum and phenylalanine in both regions. Likewise, the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, increased in the substantia nigra but not in the striatum after LPD, as well as with all the amino acid deficiencies studied, with the exception of tryptophan deficiency. In this case there was a dramatic effect on all components of the serotoninergic system, with decreases in the concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour clearly shows an interrelationship between precursor (TRP) availability and 5-HT synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic systems demonstrated opposite effects in the substantia nigra and the corpus striatum, and the behaviour of the two monoamines was also opposite within each structure. The significance of these changes is discussed.

Amino Acids, Essential↗
PubMed1992

Heterogeneity in the allosteric interaction between the gamma-aminobutyric acid (GABA) binding site and three different benzodiazepine binding sites of the GABAA/benzodiazepine receptor complex in the rat nervous system.

In the present communication we have investigated the allosteric coupling between the gamma-aminobutyric acidA (GABAA) receptor and the pharmacologically different benzodiazepine (BZD) receptor subtypes in membranes from various rat nervous system regions. Two types of BZD receptors (type I and type II) have been classically defined using CL 218.872. However, using zolpidem, three different BZD receptors have been identified by binding displacement experiments in membranes. These BZD receptor subtypes displayed high, low, and very low affinity for zolpidem. The distribution of the high- and low-affinity binding sites for zolpidem was similar to that of type I and type II subtypes in cerebellum, prefrontal cortex, and adult cerebral cortex. On the other hand, the very-low-affinity binding site was localized in relative high proportion in spinal cord, hippocampus, and newborn cerebral cortex and, to a minor extent, in superior colliculus. The allosteric coupling between the GABAA receptor and the BZD receptor subtypes was different. The high- and low-affinity binding sites for zolpidem seemed to have a similar high degree of coupling, except in spinal cord. On the other hand, the very-low-affinity binding site for zolpidem displayed a low degree of coupling with the GABAA receptor. These results seem to indicate that the different efficacy of GABA in enhancing the [3H]flunitrazepam binding could be due to the different BZD receptor subtypes present in the GABAA/BZD receptor complex and, moreover, led us to speculate that the low GABA efficacy found in membranes from spinal cord, hippocampus, and newborn cerebral cortex might be due to the presence in relatively high proportion of the very-low-affinity binding site for zolpidem.

Allosteric Site↗
PubMed1992

Changes in the turnover of monoamines in prefrontal cortex of rats fed on vitamin E-deficient diet.

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult rat prefrontal cortex. Turnover rates of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxy-3-indoleacetic acid have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase. NA, DA, and 5-HT turnover rates have been measured as accumulation rates of NA, DA, and 5-HT after pargyline inhibition of monoamine oxidase. No change was found in the turnover rate of NA between control and experimental animals. In contrast, turnover rates of DA and homovanillic acid significantly increased in the animals fed on a low-vitamin E diet. However, the most striking results were found on the serotoninergic system. Levels of 5-HT and its main metabolite, 5-hydroxy-3-indoleacetic acid, and their respective turnover rates were lower in the vitamin E-deficient diet. These results could indicate that vitamin E is necessary for the normal functioning of the serotoninergic neurons in the rat prefrontal cortex. The involvement of vitamin E in preventing the formation of free radicals is well known. Therefore, this lack of protective effect after a 15-day vitamin E-deficient diet could be responsible for the neuronal damage to the serotoninergic system. The opposing results found in DA (increase) and 5-HT (decrease) turnover could provide further evidence for an inhibitory control of the serotoninergic ascending pathways to the dopaminergic system in the prefrontal cortex.

Animals↗
PubMed1992

Behavioral variability and frequency-dependent selection.

In Experiment 1, two conditions were compared: (a) a variability schedule in which food reinforcement was delivered for the fourth peck in a sequence that differed from the preceding N four-peck sequences, with the value of N continuously adjusted to maintain reinforcement probability approximately constant; and (b) a control condition in which the variability constraint was dropped but reinforcement probability remained constant. Pigeons responded approximately randomly under the variability schedule but showed strong stereotyped behavior under the control condition. Experiments 2 and 3 tested the idea that variability is the outcome of a type of frequency-dependent selection, namely differential reinforcement of infrequent behavior patterns. The results showed that pigeons alternate when frequency-dependent selection is applied to single pecks because alternation is an easy-to-learn stable pattern that satisfies the frequency-dependent condition. Nevertheless, 2 of 4 pigeons showed random behavior when frequency-dependent selection was applied to two pecks, even though double alternation is a permissible and stable stereotype under these conditions. It appears that random behavior results when pigeons are unable to acquire the stable stereotyped behavior under a given frequency-dependent schedule.

Animals↗
PubMed1992

[Peranal ulcers caused by ergotamine-containing suppositories].

Perianal ulcerations caused by suppositories application is an exceptional situation. We describe a 64 years old female with recurrent painless perianal ulcerations evoluting from 14 months. She medicates herself daily, since 8 to 10 years, with ergotamine tartarate suppositories, for the treatment of migraine. The diagnosis of ulcerated cutaneous drug reaction induced by ergotamine tartarate was confirmed by the complete healing of the lesions after stopping this medication and by their recurrence after the reintroduction of the treatment. These ulcerations are probably due to vasospasm of regional arterioles.

Anus Diseases↗
PubMed1991

Age effects on monoamine turnover of the rat substantia nigra.

Measurement of turnover of dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine (5-HT), and their metabolites has been performed in 6- and 24-month-old rats. Dopamine synthesis in 24-month-old rats did not show any change with respect to 6-month-old rats. However, our results seem to indicate decreased DA release in 24-month-old rats. This hypothesis could be supported by the changes found in the 3-methoxytyramine (3-MT) accumulation rate after monoamine oxidase inhibition with pargyline. The turnover of NA and its main metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) decreased in 24-month-old rats compared with 6-month-old rats. Serotonin synthesis did not change in 24-month-old rats with respect to 6-month-old rats. However, the metabolism of 5-HT quantified as turnover of 5-hydroxy-3-indoleacetic acid (5-HIAA) increased in 24-month-old rats with respect to 6-month-old rats. The monoamine oxidase B:monoamine oxidase-A ratio increased in 24-month-old rats. The significance of these changes is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Implication of lysine residues in the loss of 6-phosphogluconate dehydrogenase activity in aging human erythrocytes.

The activity of 6-phosphogluconate dehydrogenase (6-PGDH) decreases in aged human erythrocyte populations. The aged enzyme has 11 lysine residues less than the young enzyme, when they are measured with 2,4,6-trinitro-benzenesulfonic acid (TNBS). Treatment of young enzyme with ascorbate for 15 min produces the loss of 8 lysine residues and the diminution of enzymatic activity. These results suggest that there is a modification of lysine residue in human erythrocytes during senescence, probably caused by oxidation. This modification of lysine residue could imply the loss of enzymatic activity. This result is similar to that found in rat liver 6-PGDH during aging, described previously (Gordillo et al., J. Biol. Chem. 264 (1989) 17014-17019).

Adult↗
PubMed1991

The role of NADPH in the regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rat adipose tissue.

Previous studies examining the regulation of the synthesis of G6PDH and 6PGDH in rat liver and adipose tissue have focused on the induction of these enzymes by different diets and some hormones. In rat liver these enzymatic activities seem to be regulated by a mechanism involving changes in the NADPH requirements. In this paper we have studied the effect of changes in the flux through different NADPH-consuming pathways on G6PDH and 6PGDH levels in adipose tissue and on the NADPH/NADP ratio. The results show that: I) an increase in the consumption of NADPH, caused by the activation of either fatty acid synthesis or detoxification systems which consume NADPH, is paralleled by an increase in the levels of these enzymes; II) when the increase in consumption of NADPH is prevented, the G6PDH and 6PGDH levels do not change.

Adipose Tissue↗