[The first National Conference on University and Family Medicine].
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Congresses as Topic↗
Biomedical subjects
J Saura
Publications and source records attributed to J Saura.
[Clinical protocols: an urgent and necessary evaluation].
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Clinical Protocols↗
Age-related changes on MAO in Bl/C57 mouse tissues: a quantitative radioautographic study.
The distribution of MAO-A and -B in brain and peripheral tissues of Bl/C57 mice and their changes during ageing were studied by quantitative enzyme radioautography with [3H]Ro41-1049 and [3H]Ro19-6327. In the brain, MAO-A decreased between weeks 4 and 8 and then remained unchanged until 25 months, whereas MAO-B increased for the whole period studied. Heart also showed a continuous increase in MAO-B, but not MAO-A, with ageing, and liver showed a decrease in MAO-B in the older animals. These results show marked species differences in the distribution and age-related changes of MAO and might help to elucidate the high sensitivity of Bl/C57 mouse of MPTP, which increases with age.
Aging↗
Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography.
The aetiology and pathogenesis of Alzheimer's disease are currently poorly understood, but symptomatic disease is associated with amyloid plaques, neurofibrillary tangles, neuronal loss and numerous alterations of neurotransmitter systems in the CNS. Monoamine oxidase type B is known to be increased in Alzheimer diseased brains. The distribution and abundance of catalytic sites for monoamine oxidases A and B in post mortem human brains of 11 Alzheimer disease cases and five age-matched controls were investigated by quantitative enzyme radioautography. Using tritiated monoamine oxidase inhibitors (Ro41-1049 and lazabemide)--as high affinity substrates selective for monoamine oxidases A and B, respectively--it was found that monoamine oxidase B activity increased up to three-fold exclusively in temporal, parietal and frontal cortices of Alzheimer disease cases compared with controls. This increase was restricted to discrete patches (approximately 185 microns in diameter) which occupied approximately 12% of the cortical areas examined. In other brain regions (hippocampal formation >> caudate-putamen > cerebellum), patches of [3H]lazabemide-enriched binding were less abundant. [3H]Ro41-1049 binding (i.e. monoamine oxidase A) was unchanged in all tissues of diseased versus control brains. The monoamine oxidase B-enriched patches in all cortical regions correlated, in their distribution and frequency, with glial fibrillary acidic protein-immunoreactive clusters of astrocytes. Diffuse and mature beta-amyloid-immunoreactive senile plaques as well as patches of high density binding of [3H]PK-11195--a high-affinity ligand for peripheral-type (mitochondrial) benzodiazepine binding sites in microglia/macrophages--were found throughout Alzheimer diseased cortices. The up-regulation of monoamine oxidase B in plaque-associated astrocytes in Alzheimer's disease--in analogy to its proposed role in neurodegenerative disorders such as Parkinson's disease--might, indirectly, be a potential source of cytotoxic free radicals. Lazabemide, a selective reversible monoamine oxidase B inhibitor, is currently under clinical evaluation for the treatment of Parkinson's and Alzheimer's diseases. We conclude that enzyme radioautography with [3H]lazabemide is a reliable high resolution assay for plaque-associated astroglioses in Alzheimer's disease. Its clinical diagnostic utility for positron emission tomography or single photon emission computer tomography studies is being investigated.
Aged↗
Molecular neuroanatomy of monoamine oxidases in human brainstem.
Specific, high-resolution techniques (quantitative enzyme radioautography and in situ hybridisation histochemistry) have revealed distribution, abundance and cellular localization of the isoenzymes MAO-A and MAO-B and their mRNAs in human post-mortem brainstem. Whereas MAO-A protein and mRNA are expressed by noradrenergic neurons of the locus coeruleus, MAO-B protein and mRNA are expressed by serotoninergic neurons of the raphé nuclei. In the substantia nigra, MAO-B was more abundant than MAO-A; the former was localized in the reticular zone and the latter in the compact zone (where melanin-containing dopaminergic neurons are found). To date, it has not been possible to detect mRNA for either MAO-A or MAO-B in the substantia nigra or in glial cells of the brain regions investigated, suggesting either that the technique has limited sensitivity, or the possible existence of MAO-A and MAO-B subtypes.
Aged↗
Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain.
Monoamine oxidases A and B (MAO-A and MAO-B) oxidatively deaminate neurotransmitter and xenobiotic amines. Since the cellular localization of the isoenzymes in the CNS and peripheral organs determines to a large extent which substrate has access to which isoenzyme, knowledge of their tissue distribution and cellular localization is essential. Here we describe how reversible and selective inhibitors of MAO-A and MAO-B [Ro 41-1049 and Ro 19-6327 (lazabemide), respectively] can be used, as tritiated radioligands, to map the distribution and abundance of the enzymes in microscopic regions of the rat CNS and peripheral organs, and human brain by quantitative enzyme radioautography. The in vitro binding characteristics of both radiolabeled inhibitors revealed them to be selective, high-affinity ligands for the respective enzymes. KD and Bmax values for 3H-Ro 41-1049 in rat cerebral cortex were 10.7 nM and 7.38 pmol/mg protein, respectively, and for 3H-Ro 19-6327 were 18.4 nM and 3.45 pmol/mg protein, respectively. In accordance with their potencies as enzyme inhibitors, binding to MAO-A and MAO-B was competitively inhibited by clorgyline (IC50 = 1.4 nM) and L-deprenyl (selegiline; IC50 = 8.0 nM), respectively. The capacities of various rat and human tissues to bind the radioligands correlated extremely well with their corresponding enzyme activities. As revealed by the respective binding assays, the distribution and abundance of MAO-A and MAO-B in the tissues investigated differed markedly. MAO-A was most abundant in the locus coeruleus, paraventricular thalamus, bed nucleus of the stria terminalis, median habenular nucleus, ventromedial hypothalamus, raphe nuclei, solitary tract nucleus, inferior olives, interpeduncular nucleus, claustrum, and numerous peripheral tissues, including liver, vas deferens, heart, superior cervical ganglion, and exocrine and endocrine pancreas. In contrast, MAO-B was most abundant in the ependyma, circumventricular organs, olfactory nerve layer, periventricular hypothalamus, cingulum, hippocampal formation, raphe nuclei, paraventricular thalamus, mammillary nuclei, cerebellar Bergmann glia cells, liver, posterior pituitary, renal tubules, and endocrine pancreas. The cellular localization of the isoenzymes in both rat and human brain differs markedly and does not reflect the distribution of the presumed natural substrates, for example, absence of MAO-A in serotoninergic neurons. Indeed, the present evidence suggests that, whereas MAO-A is found in noradrenergic and adrenergic neurons, MAO-B occurs in astrocytes, serotoninergic neurons, as well as ventricular cells, including most circumventricular organs. The physiological roles of the enzymes are discussed in the light of these findings, some of which were unexpected.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
[Pleural effusion and constrictive pericarditis secondary to bromocriptine treatment].
The case of a 60 year old patient with Parkinson's disease is reported, who, following 2 years of treatment with bromocriptine, presented a left pleural effusion in which chronic constrictive pericarditis was demonstrated. Studies aimed at establishing the etiology were negative. Upon withdrawal of bromocriptine, the pleural effusion disappeared and the patient remained asymptomatic, with only pleural thickening persisting in the thoracic radiography. The appearance of polyserositis as an undesirable effect of the use of bromocriptine is discussed. The first case associated to chronic pericarditis is reported.
Bromocriptine↗
Differential age-related changes of MAO-A and MAO-B in mouse brain and peripheral organs.
Distribution and age-related changes of MAO in BL/C57 mouse were studied by quantitative enzyme radioautography with [3H]Ro41-1049 and [3H]Ro19-6327. In the brain, MAO-A was highest in locus coeruleus and interpeduncular nucleus, and MAO-B in raphe nuclei, paraventricular thalamic nucleus, and ependyma of ventricles. Extremely high MAO-B levels were also measured in the choroid plexus in contrast to the very low MAO-B levels in rat choroid plexus. With aging, brain MAO-A showed a clear decrease between 4 and 9 weeks, followed by no change between 9 weeks and 19 months, and a slight increase between 19 and 25 months. On the other hand, all brain structures showed age-related increases in MAO-B. Peripheral organs showed different patterns of MAO age-related changes. Particularly interesting was the marked MAO-B increase in heart, parallel to the MAO-A increase in rat heart. Also of interest is the decrease of liver MAO-B in old animals, which, together with the increase of MAO-B in the brain, might underlie the high sensitivity of old BL/C57 mice to MPTP.
Aging↗
Biphasic and region-specific MAO-B response to aging in normal human brain.
Variations of monoamine oxidases (MAO) A and B were studied during aging in 27 human subjects (age range 17-93 years) in 18 brain structures of temporal cortex, frontal gyrus, hippocampal formation, striatum, cerebellum, and brainstem. [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. Postmortem delay or time of tissue storage did not affect MAO-A or MAO-B levels. There was, moreover, no evidence of sexual dimorphism. A marked age-related increase in MAO-B was observed in most structures. This increase started at the age of 50-60 years. Before this age, MAO-B levels were constant in all structures studied. MAO-B-rich senile plaques were observed in some cortical areas but they did not significantly influence the age-related MAO-B increase. Surprisingly, no age-related MAO-B changes were observed in the substantia nigra. In contrast to MAO-B, no clear age-related changes in MAO-A were observed, indicating an independent regulation of the two isoenzymes, also suggested by the cross-correlation analysis of these data.
Adolescent↗