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Biomedical subjects

E Tolosa

Publications and source records attributed to E Tolosa.

At least 199 records · Page 11Linked to original sources
PubMed1985

Progressive cauda equina syndrome and extensive calification/ossification of the lumbosacral meninges.

A patient with longstanding ankylosing spondylitis (AS) developed a cauda equina syndrome. The myelogram showed a block at the L2 level. Vertebral computerised tomography showed calcification in the centre of the spinal canal. The patient also had features suggestive of a diffuse idiopathic skeletal hyperostosis (DISH). Meningeal calcification has never been reported in AS, so we suggest that this is related to an associated DISH. Cauda equina syndrome has not been described in DISH, and calcification of meninges has not been reported in AS, so we suggest that the meningeal calcifications and associated cauda equina syndrome are related to DISH.

Calcinosis↗
PubMed1975

Cholinergic effects of molecular segments of apomorphine and dopaminergic effects of N,N-dialkylated dopamines.

The hydrochlorides of molecular segments of apomorphine [2-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline, 2-(3'4'-dihydroxybenzyl)piperidine, and 1,2,3,4-tetrahydroisoquinoline with their respective N-methyl and N-n-propyl homologs] and N,N-dialkylated dopamine compounds were synthesized and studied for (1) LD50 in intact mice; (2) stereotypy in intact mice; (3) curving of the body in unilaterally caudectomized mice; (4) rotation in 6-hydroxydopamine-lesioned rats, and (5) activation of adenylate cyclase in homogenates of mouse caudate nuclei. Instead of dopaminergic effects 1-(3',4'-dihydroxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydroisoquinoline showed cholinergic ones. These effects were blocked in atropine-pretreated animals. Of the N,N-dialkylated dopamine compounds synthesized, the N-n-propyl-N-n-butyldopamine ranked in all tests as the strongest dopamine-receptor agonist and N-methyl-N-n-propyldopamine as the weakest. In contrast, N,N-dimethyldopamine and 1-(3,4-dihydroxyphenylethyl)piperidine showed no dopaminergic effects. The effectiveness of the dopaminergic agonists depended on the length of the N-alkyl substituents suggesting interactions with hydrophobic regions of the receptor site.

Adenylyl Cyclases↗
PubMedDate not supplied

Plasticity of the nigrostriatal system in MPTP-treated mice. A biochemical and morphological correlation.

In order to compare the recovery capacity of the nigrostriatal system between adult and old mice, MPTP hydrochloride was administered to 48 BL/C57 male mice, which were sacrificed 24 h or 10 d after the second dose. The animals were divided into four groups, based on age (adult or old) and moment of sacrifice (24 h or 10 d). The detailed morphology of the neurons and the cellular processes of the substantia nigra pars compacta and the striatum were studied using the Golgi method. Immunostaining with a polyclonal glial fibrillary acidic protein antiserum using the peroxidase-antiperoxidase technique was performed to study the glial response. Striatal catecholamines were determined to correlate the biochemical data with the morphological changes. Significant neuronal changes of cellular processes were observed in substantia nigra pars compacta from all MPTP-treated mice, consisting of swelling and distortion of cellular bodies, discontinuous thickness, and nodulations of dendrites with baded aspect. Axons showing focal swelling and nodulations were also found in the neuropil of silver impregnated striata. Marked gliosis with reactive astrocytes in substantia nigra and striatum from all the old treated mice was found. Recovery was only observed in adult mice sacrificed 10 d after withdrawal. At this time, all the old MPTP-treated mice showed marked neuronal changes and a persistent marked gliosis. As expected, 24 h after the MPTP treatment, a marked depletion of dopamine and its metabolites was found in all the animals; at 10 d, the depletion was partially reversed in the adult group. These data correlate well with the observed morphological changes. Our results suggest that, in mice, deterioration of dendritic and axonal neuropil constitutes a significant causal factor of the MPTP neurotoxicity. These features are related to the age of the animals and the integrity of the plasticity phenomena, which appear to be altered in old mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.

BACKGROUND: Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. METHODS: In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. FINDINGS: 88 (13%) patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (-1.18 h rasagiline and -1.2 h entacapone vs placebo -0.4 h; p=0.0001, p<0.0001, respectively) and increased daily on-time without troublesome dyskinesia (0.85 h vs placebo 0.03 h; p=0.0005 for both). We recorded significant mean improvements in CGI scores (-0.86 rasagiline and -0.72 entacapone vs -0.37 placebo; p<0.0001, p=0.0002, respectively). Changes in UPDRS scores also significantly improved for activities of daily living during off-time (-1.71 and -1.38 vs placebo; p<0.0001, p=0.0006, respectively) and motor function during on-time (-2.94 and -2.73 vs placebo; both p<0.0001). Frequency of adverse events was similar for all treatments. INTERPRETATION: Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

Administration, Oral↗
PubMedDate not supplied

Thymus-derived glucocorticoids and the regulation of antigen-specific T-cell development.

Bidirectional interactions of both a stimulatory and inhibitory nature occur between the neuroendocrine and the immune systems, and these interactions play an important modulatory role during T-cell ontogeny. Specifically, glucocorticoids potently induce apoptosis in thymocytes and activated T cells, but can also rescue these cells from activation-induced cell death. The objective of this review is to discuss current data on the interactions of the immune system with steroid hormones in the thymus and to describe a model that includes glucocorticoids in the shaping of the peripheral T-cell antigen-specific repertoire and deals with their potential role in the generation of autoimmune disease.

Animals↗