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Biomedical subjects

A L Moreira

Publications and source records attributed to A L Moreira.

30 records · Page 2Linked to original sources
PubMed1993

Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation.

We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production and found that the drug enhances the degradation of TNF-alpha mRNA. Thus, the half-life of the molecule was reduced from approximately 30 to approximately 17 min in the presence of 50 micrograms/ml of thalidomide. Inhibition of TNF-alpha production was selective, as other LPS-induced monocyte cytokines were unaffected. Pentoxifylline and dexamethasone, two other inhibitors of TNF-alpha production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-alpha synthesis at distinct points of the cytokine biosynthetic pathway. These observations provide an explanation for the synergistic effects of these drugs. The selective inhibition of TNF-alpha production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-alpha-induced toxicities are observed and where immunity must remain intact.

Animals↗
PubMed1993

Development of giant reaction in response to PPD skin test in lepromatous leprosy patients.

The present study analyzes some clinical and immunological aspects of the giant reaction (GR) in lepromatous leprosy. Sixteen out of a total of 147 (10.9%) lepromatous patients developed the clinical features of GR upon the intradermal administration of PPD; most (14 of 16) GRs occurred in bacteriologically positive cases. GR precipitated an episode of erythema nodosum leprosum (ENL) in three patients. In addition, patients with GR showed enhanced in vitro response to PPD, by the lymphoproliferation test and interferon-gamma assay, as compared to either PPD-negative individuals or PPD-positive patients without GR. Therefore, cell-mediated-immune response to mycobacterial antigens is present in lepromatous patients with GR. It is suggested that the exacerbated in vivo response to PPD in lepromatous leprosy is the result of an increased immunoreactivity to the antigen, which well may be associated with the local and/or systemic release of cytokines [tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma)] by the inflammatory cells. These episodes may, in fact, play an important role in determining the development of disabilities and reactional states, thereby interfering with the prognosis of leprosy disease.

Adolescent↗
PubMed1992

Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.

Erythema Nodosum↗
PubMed1991

Mycobacterium leprae-induced interferon-gamma production by household contacts of leprosy patients: association with the development of active disease.

Identification of individuals at risk for developing leprosy and their early diagnosis are central to effective disease control. Lack of immunologic response to Mycobacterium leprae among persons exposed to the infectious agent may be predictive of susceptibility. M. leprae-induced interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells was used as a measure of immune responsiveness. Household contacts of multibacillary patients likely to be at risk of developing active disease were identified, and a preliminary analysis after 2 years of follow-up is presented. A persistent in vitro negative response to M. leprae was present in 34.6% of the contacts, and a decrease in IFN-gamma production was noted in 52.5%. Five contacts (6.41%) developed leprosy during follow-up and, as predicted, belonged to the group of individuals who were negative or showed reduced levels of IFN-gamma in response to the antigen.

Adolescent↗
PubMed1990

Effect of treatment on immune responsiveness in lepromatous leprosy patients.

This study was performed in order to analyse whether the immune unresponsiveness to Mycobacterium leprae, largely seen in lepromatous patients, persisted after discharge from treatment. Lymphoproliferation and skin tests were performed using two mycobacterial antigens (M. leprae and BCG) in three groups of lepromatous patients grouped by treatment status. Forty-seven per cent of the lepromatous patients tested acquired reactivity to M. leprae after long-term treatment.

Dapsone↗
PubMed1987

Trypanosoma cruzi: phagolysosomal fusion after invasion into non professional phagocytic cells.

Parasite-containing endocytic vacuoles are formed during the process of in vitro interiorization of the trypomastigote forms of Trypanosoma cruzi by primary culture of mouse fibroblasts, heart and skeletal muscle cells. Fusion of these vacuoles with host cell lysosomes takes place. The process of T. cruzi-muscle cell interaction was analysed by ultrastructural cytochemistry. Two lysosomal enzymes, acid phosphatase and aryl sulphatase and the fusion of peroxidase-labeled secondary lysosomes with the parasitophorus vacuoles were studied. These finding indicate that the basic mechanism of interaction of T. cruzi with the so called non phagocytic cells is similar to that which occurs with phagocytic cells.

Acid Phosphatase↗
PubMed1986

The interaction of myotropic and macrophagotropic strains of Trypanosoma cruzi with myoblasts and fibers of skeletal muscle.

The process of interaction of bloodstream trypomastigotes from the myotropic CL and Colombiana strains and the macrophagotropic Y strain of Trypanosoma cruzi with mouse myoblasts and myotubes was analysed. After 24 h of parasite-host cell interaction, parasites from the CL and Colombiana strains appeared to be more infective to myoblasts than those from the Y strain. Parasites from the Colombiana strain were more infective for myotubes than those from the Y strain, while those from the CL strain showed very a low ability to infect the cells. For all strains the infectivity was low for short periods of interaction, increasing with time. Myoblasts infected with parasites from the Y strain fused with other infected and uninfected cells to form myotubes. However, the process of fusion was blocked when the myoblasts were infected with parasites from the CL and Colombiana strains. These data indicate a different behavior of muscle cells when in contact with myotropic or non-myotropic strains of T. cruzi.

Animals↗
PubMedDate not supplied

[Morphological and functional characterization of adherent splenic cells of mice].

The separation, characterization and functional assay of the inflammatory infiltrate present in the site of the lesion has been useful in the study of many diseases. Histochemical techniques for esterase and acid phosphatase, as well as the Phagocytose test and the Giemsa staining were applied to the study of the spleen-cell population of ten mice. A good characterization of the components of the Phagocytic Mononuclear System and the identification and quantification of the total cell population were obtained.

Acid Phosphatase↗