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Biomedical subjects

C L Silva

Publications and source records attributed to C L Silva.

At least 91 records · Page 5Linked to original sources
PubMed1989

Participation of tumor necrosis factor in the antitumor activity of mycobacterial trehalose dimycolate (cord factor).

Trehalose dimycolate, a mycobacterial glycolipid also known as cord factor, retains some of the antitumor properties of the intact BCG. Murine macrophages incubated in vitro in the presence of trehalose dimycolate for 20 h at 37 degrees C released a factor which was cytotoxic for the L929 tumor cell line. Anti-tumor necrosis factor (TNF) blocked the cytotoxicity of trehalose dimycolate macrophage supernatant. Therefore the antitumor activity of trehalose dimycolate can be attributed to TNF released in the in vitro assay.

Animals↗
PubMed1988

Mouse cachexia induced by trehalose dimycolate from Nocardia asteroides.

Trehalose dimycolate (TDM) isolated from Nocardia asteroides induced in mice a severely wasted condition known as cachexia. Intraperitoneal injection of mice with five 10 micrograms doses of TDM in mineral oil at intervals of 2 d killed 90% of the animals within 26 d. Death followed a precipitous weight loss and an inflammatory process in the peritoneal cavity. When mice were injected intraperitoneally with a single 10 micrograms dose of TDM, 48 h later, they had begun to lose weight and exhibited extreme hypertriglyceridaemia and hypoglycaemia. Tumour necrosis factor (or cachectin) was detected in the plasma from animals injected with TDM. This cytokine released by mononuclear phagocytes may be involved in the induction of cachexia by TDM.

Animals↗
PubMed1988

Tumor necrosis factor (cachectin) mediates induction of cachexia by cord factor from mycobacteria.

The mechanism by which cord factor (CF), a toxic glycolipid from mycobacteria, induces cachexia was studied in BALB/c mice. Body weight was markedly reduced 48 h after CF administration; the animals became severely wasted and exhibited hypertriglyceridemia, hypoglycemia, and high levels of tumor necrosis factor (TNF) in plasma. After CF administration, a transferable factor which caused cachexia and hypertriglyceridemia in recipient mice was detected in the blood. Dexamethasone partially inhibited the cachexia-inducing action of CF. Conditioned medium from adherent peritoneal cell cultures incubated with CF produced the same wasting symptoms when inoculated intravenously into mice. These studies also demonstrated that adherent peritoneal cells produced a humoral factor in response to CF which was related to CF-induced cachexia. Antiserum to recombinant TNF-alpha prevented the cachectin action in passive-transfer experiments. Our findings indicate that cachectin (TNF) plays a role as a central mediator of the wasting induced by CF.

Animals↗
PubMed1988

The role of cachectin/TNF in the pathogenesis of tuberculosis.

The presence of cachectin or tumor necrosis factor (TNF) associated with hypertriglyceridemia was demonstrated in the serum of patients with pulmonary tuberculosis. The hyperlipidemia that accompanies this infection may be mediated by the TNF inhibition of lipoprotein lipase activity. This sequence of events may be sufficient to explain, in part, the complex metabolic changes and emaciation observed in tuberculosis patients.

Adolescent↗
PubMed1987

The role of fractions from Paracoccidioides brasiliensis in the genesis of inflammatory response.

The influx of inflammatory cells towards the peritoneal cavity in rats inoculated intraperitoneally with subcellular preparations of the fungus Paracoccidioides brasiliensis was studied. In addition to the dead fungus, also fractions F1 of the cell wall, which mainly consisted of polysaccharides and the lipid extract, induced intense cell migration 4 hr after inoculation, with a greatly increased number of polymorphonuclear leucocytes (PMN). Study of the kinetics of cell influx showed that both fraction F1 and the lipid extract initially induced intense PMN migration between the 4th and 24th hr after inoculation of these agents, followed by migration of mononuclear cells (MN) around the 48th hr. We also observed that migration of these cells increased gradually after inoculation of growing doses of fraction F1. The present data suggest that polysaccharides and lipids isolated from P. brasiliensis may participate in the initial phase of the inflammatory response in paracoccidioidomycosis.

Animals↗
PubMed1987

Studies on the pathogenesis of actinomycotic mycetoma in animals injected with fractions isolated from Nocardia brasiliensis.

In the present study the participation was evaluated of isolated fractions of Nocardia brasiliensis in the genesis of the inflammatory response observed in actinomycotic mycetoma. Subcutaneous injection in mice of a suspension containing a polysaccharide fraction F1 obtained by treating cell walls with sodium hydroxide induced an inflammatory response at the inoculation site which was characterized by a large influx of polymorphonuclear (PMN) and mononuclear (MN) leucocytes between the 2nd and 4th days. On the 8th day, a typical granulomatous reaction was observed involving large numbers of epithelioid cells. Intravenous injection of the lipid extract adsorbed to charcoal particles into mice induced an inflammatory reaction around the particles embolized in the pulmonary microcirculation which was similar to that described above. The kinetics of the inflammatory cell migration was studied by total and differential counts of leukocytes that migrated to the peritoneal cavity of rats inoculated intraperitoneally with the F1 and lipid fractions. Both fractions initially induced intense PMN migration, which was later reduced, with a simultaneous increase in mononuclear cells. The present results demonstrate that a polysaccharide fraction (F1) and the lipid fraction reproduce the fundamental lesion of actinomycotic mycetoma.

Animals↗
PubMed1986

Cord factor is associated with the maintenance of the chronic inflammatory reaction caused by mycobacteria.

The distribution of an aqueous suspension of cord factor (CF) from Mycobacterium bovis BCG in several mouse organs was examined after intravenous injection, and the correlation between evolution of the inflammatory granulomatous reaction and the presence of CF in these organs was determined. CF was preferentially deposited in the lungs and liver, and the kinetics of the pulmonary and hepatic inflammatory reaction, evaluated by determining the indices for these organs, showed a gradual increase on day 2 after injection, reached a peak around the fifth day, and declined thereafter. Histological analysis showed that on day 5 both the lungs and the liver were diffusely damaged by a mononuclear inflammatory infiltrate arranged in a granulomatous manner and consisting predominantly of histiocytes. CF elimination was more marked in the liver than in the lungs: 2 d after injection 76% of the material deposited in the liver had been eliminated. Little or no CF was detected in the liver and lungs by day 16, when the inflammatory reaction was also substantially decreased. A second CF dose administered 8 d after the first exacerbated the inflammatory process in both the lungs and the liver, indicating that the intensity of this process depends on CF concentration in the lesion site.

Animals↗
PubMed1986

Mouse toxicity induced by lipids and cell walls isolated from actinomycetes.

The possibility was examined that the toxicity induced in mice by Actinomadura madurae, 'Streptomyces pelletieri' and Nocardia brasiliensis was due to lipid and cell-wall constituents. Mice were inoculated intraperitoneally with heat-killed bacteria, lipid extracts and cell-wall preparations emulsified in mineral oil: toxicity was evaluated by recording weight loss and deaths. Killed cells and cell-wall preparations of all three actinomycetes produced a pronounced loss of body weight, tissue necrosis, splenomegaly, a granulomatous inflammation and sometimes death. Mice inoculated with lipid extracts from A. madurae and 'S. pelletieri' neither died nor showed toxic effects, but mice injected with lipids isolated from N. brasiliensis did suffer toxic effects. They showed more marked wasting symptoms than observed after inoculation of heat-killed bacteria or of the cell-wall preparation.

Actinomycetales↗
PubMed1985

Granulomatous reaction induced by lipids isolated from Paracoccidioides brasiliensis.

The possibility that the histological responses produced in paracoccidioidomycosis might be attributed to lipid constituents of cells of Paracoccidioides brasiliensis was investigated. Charcoal particles coated with the lipid extract were prepared and the suspension inoculated intravenously into mice. The lung inflammation was characterized by an intense mononuclear and polymorphonuclear cell infiltrate surrounding the particles from two to eight days after inoculation. Fractionation of lipid extract by preparative thin-layer chromatography allowed the separation of several fractions and it was observed that fractions containing free fatty acids and triglycerides were the most active. The participation of an uncommon fatty acid eliciting an inflammatory reaction is discussed.

Animals↗
PubMed1985

Granulomatous reactions induced by lipids extracted from Fonsecaea pedrosoi, Fonsecaea compactum, Cladosporium carrionii and Phialophora verrucosum.

Granulomatous reactions induced by lipid extracts from the dermatophyte fungi Fonsecaea pedrosoi, Fonsecaea compactum, Cladosporium carrionii and Phialophora verrucosum, the causal organisms of chromoblastomycosis, were studied. Charcoal particles coated with the lipid extracts were prepared and injected intravenously into mice. Inflammation was characterized by an intense mononuclear cell infiltrate that lodged in the lung from 4 to 8 d after inoculation.

Animals↗
PubMed1985

A Paracoccidioides brasiliensis polysaccharide having granuloma-inducing, toxic and macrophage-stimulating activity.

The occurrence of a polysaccharide fraction of Paracoccidioides brasiliensis cell wall with toxic, granuloma-inducing and macrophage-stimulating activities was demonstrated. After fractionation of the lipid-extracted wall with 1 M-NaOH, three fractions were obtained: (1) an alkali-insoluble fraction; (2) an alkali-soluble, acid-insoluble fraction and (3) an alkali-soluble, acid-soluble fraction. When the three fractions were injected into mice only fraction (1) was able to induce chronic lung inflammation, causing a marked loss in body weight and death at a dose of 6 mg per animal. Analysis of the stimulation of peritoneal macrophages of mice (measured by cell spreading on glass) after intraperitoneal injection of fraction 1 showed that 75% of the cells were able to spread even 20 d after inoculation.

Animals↗
PubMed1985

Role of the fungal cell wall in the granulomatous response of mice to the agents of chromomycosis.

Mice were given, intraperitoneally, inocula of a cell-wall preparation and fractions thereof from Fonsecaea pedrosoi, F. compactum, Cladosporium carrioni and Phialophora verrucosum. Large doses of cell-wall preparation, with or without trypsin treatment, produced a pronounced loss of body weight, a granulomatous reaction and, sometimes, death. After extraction of the cell wall preparation with 1N NaOH, three fractions were obtained: an alkali-insoluble fraction 1; an alkali-soluble acid-insoluble fraction 2; and an alkali- and acid-soluble fraction 3. Intravenous administration showed that only fraction 1 induced a granulomatous reaction and death in mice.

Animals↗
PubMed1985

Role of cord factor in the modulation of infection caused by mycobacteria.

The subcutaneous, intradermal, and pulmonary inflammatory lesions induced in mice by viable Mycobacterium bovis (BCG) with no glycolipid cord factor (CF) on the outer cell wall (delipidated BCG, dBCG) was drastically different from that induced by inoculation with intact bacteria. The reaction caused by dBCG was of an acute nature: the cells making up the inflammatory infiltrate exhibited polymorphonuclear-like (PMNs) morphologic characteristics, there was a decrease on delayed hypersensitivity response, and the lesion was resolved around the 16th day after inoculation. Complete disappearance of viable organisms from the lungs, liver, and spleen of these animals occurred in parallel with the dissipation of the dBCG-induced inflammatory infiltrate, showing that CF plays an important role in the host-parasite relationship that takes place in infections caused by mycobacteria. In addition, when deprived of this glycolipid component, bacilli lose their immunostimulant ability.

Acid Phosphatase↗
PubMed1985

Inflammation induced by mycolic acid-containing glycolipids of Mycobacterium bovis (BCG).

Mycobacterium bovis (BCG) was submitted to lipid extraction involving gentle and drastic procedures. Neutral lipids, glycolipids as well as phospholipids were detected in the diethyl ether extract, whereas the chloroform and chloroform-methanol extracts contained mainly phospholipids. Arabinose mycolates, which represent firmly bound cell wall lipids, were detected in the acidified ether extract. The lipid extracts were adsorbed to charcoal particles and inoculated intravenously into mice. Histological analysis showed that the particles were trapped in the lung microcirculation and strong inflammatory reactions were induced around the charcoal particle coated lipids present in the diethyl ether, chloroform and acidified diethyl ether extracts. Fractionation of these inflammation-inducing extracts by column and preparative thin-layer chromatography led to the isolation of five active mycolic acid-containing glycolipids, identified as glycerol monomycolate, glucose monomycolate, arabinose monomycolate, trehalose monomycolate and trehalose dimycolate on the basis of physical, chemical and spectroscopic analyses. Inflammatory reactions similar to that observed after inoculation of live BCG were induced in the lungs by trehalose monomycolate, trehalose dimycolate or glucose monomycolate. However, the toxic reactions caused by glycerol monomycolate and arabinose monomycolate were characterized by an acute inflammatory process mainly due to the constant and massive presence of polymorphonuclear leukocytes.

Animals↗
PubMed1978

Enzymes of the carbohydrate metabolism in salivary glands from rats submitted to excess of vitamin A.

Male albino rats of the Wistar strain were submitted to daily doses of 15 000 I.U. of vitamin A. Enzymes of the carbohydrate metabolism were assayed in the salivary glands after 1,2, 3 and 4 doses. Phosphofructokinase showed decreased activity in the submandibular gland while it was not affected in the parotid. Glucose-6-phosphate dehydrogenase activity was higher in the submandibular glands of all experimental groups and only in the group of 1 dose for the parotid gland. Hexokinase activity did not alter in the submandibular gland while for parotid it showed higher activity only in the group of 1 dose. Pyruvate kinase activity was different only in the group of 3 doses for both glands.

Animals↗