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Biomedical subjects

M T Silva

Publications and source records attributed to M T Silva.

At least 37 records · Page 2Linked to original sources

L-arginine produces NO-independent increases in dopamine efflux in rat striatum.

The effect of L-arginine (L-ARG; 10-100 mM) on dopamine efflux from rat striatum was investigated using in vivo microdialysis. L-ARG (50 mM-100 mM), but not D-arginine (100 mM) nor L-citrulline (100 mM), produced a biphasic effect on dopamine efflux with an initial small reduction, followed by a large sustained increase. The effect of L-ARG was not prevented by nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester or 7-nitroindazole monosodium salt. Efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by L-ARG (10-100 mM), D-arginine (100 mM) and L-citrulline (100 mM). These data suggest that changes in dopamine, DOPAC and HVA efflux produced by high concentrations of L-ARG occur independently of NO, and that the use of high L-ARG concentrations are inappropriate when investigating the role of NO in striatum.

3,4-Dihydroxyphenylacetic Acid↗

Squamous cell carcinoma of the renal pelvis with metastasis in a dog.

The gross and microscopical features of a squamous cell carcinoma of the renal pelvis in an 18-year-old dog are described. This is a rare tumour originating from transitional cells of the pelvis. The tumour, which invaded the renal parenchyma and capsule and the small intestinal wall, metastasized to the lungs. Tumour cells expressed cytokeratin 8 and were arranged in a pattern similar to that of a squamous cell carcinoma found elsewhere, with prickle cells and horny pearls. The tumour was not diagnosed clinically but was found at necropsy. The presence of pelvic calculi in this dog is suggested as a cause of transitional cell squamous metaplasia and malignant transformation.

Animals↗

Deinococcus geothermalis sp. nov. and Deinococcus murrayi sp. nov., two extremely radiation-resistant and slightly thermophilic species from hot springs.

Strains of Deinococcus geothermalis sp. nov. were isolated from the hot spring and runoff at Agnano, Naples, Italy, and from the hot spring at São Pedro do Sul in central Portugal, while strains of Deinococcus murrayi sp. nov. were isolated from the hot springs at São Pedro do Sul, São Gemil, and Alcafache in central Portugal. The strains of D. geothermalis and D. murrayi produce orange-pigmented colonies and have an optimum growth temperature of about 45 to 50 degrees C. The type strains of the two new species are extremely gamma radiation resistant. The fatty acids of these new species are primarily branched-chain fatty acids. The two new species can be distinguished from each other by the lower pH range of D. geothermalis than of D. murrayi, by their fatty acid compositions, and by several biochemical parameters, including the ability of D. geothermalis to grow in minimal medium without yeast extract. 16S rRNA gene sequencing also showed that the isolates constitute two species and that these species are distinct from the other species of the genus Deinococcus. The type strain of D. geothermalis is AG-3a (= DSM 11300), and the type strain of D. murrayi is ALT-1b (= DSM 11303).

Base Composition↗

Neutrophils are involved in the non-specific resistance to listeriosis induced by mycobacterial infections.

A major role has been recently ascribed to the neutrophil in the resistance to infection by Listeria monocytogenes (L. monocytogenes). Here we evaluated whether such neutrophils played a role in the non-specific resistance to listeriosis that develops in hosts infected by mycobacteria. We found that the depletion of neutrophils completely abrogated the resistance conferred by the activated macrophages induced during the mycobacterial infection. The lack of killing by activated Kupffer cells and the visualization of bacteria proliferating inside peritoneal macrophages in neutrophil-depleted mice allowed us to postulate a role for the cooperation between neutrophils and macrophages in the killing of L. monocytogenes. We also found listerial proliferation in hepatocytes of neutrophil-depleted, mycobacteria-infected mice showing that the neutrophils may be involved in the control of listeria infection of parenchymal cells.

Animals↗

Neuroborreliosis as a cause of respiratory failure.

We report three cases of neuroborreliosis presenting with acute respiratory impairment. All the patients had encephalopathy and focal neurological signs with brain stem abnormalities in two. All three patients had respiratory arrest associated with progressive nocturnal hypoventilation or prolonged central apnoea. Tracheostomy and prolonged periods of ventilatory support were necessary in all cases and weaning was complicated by residual central respiratory disturbances. These cases emphasise that Borrelia infection should be considered in the differential diagnosis of unexplained respiratory failure.

Acute Disease↗

Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7-nitro indazole.

The role of nitric oxide (NO) in striatal dopamine release has been controversial. Most NO synthase inhibitors affect more than one isoform of the enzyme and exert vasoconstrictor effects which may also affect striatal dopamine function. We now report on the effect of a soluble monosodium salt of the selective brain NO synthase inhibitor 7-nitro indazole (7-NINA). Using 7-NINA the first study of selective inhibition of the brain isoform of NO synthase on dopamine efflux in rat striatum was undertaken by use of in vivo microdialysis. Perfusion with 7-NINA (1 mM) increased striatal dopamine efflux. The effect of 7-NINA was partially antagonized (67%) by co-perfusion with L-arginine (1 mM), the precursor of NO formation in vivo. This suggests that 7-NINA induces a competitive inhibition of NO synthase activity. These data show that endogenous NO has an inhibitory effect on striatal dopamine efflux in vivo.

Amino Acid Oxidoreductases↗

Susceptibility of beige mice to Mycobacterium avium: role of neutrophils.

The beige mutation in C57BL/6 mice has been shown to increase the susceptibility to infection by Mycobacterium avium. In this study, we confirmed those results and showed that the effect of the beige mutation was most obvious after infection with a strain of lower virulence than with a highly virulent isolate of M. avium. The dissemination of M. avium from the gut was observed with both C57BL/6 and beige mice but was faster in the latter. The expression of gamma interferon (IFN-gamma) and the priming for tumor necrosis factor production during an in vivo infection were similar between beige and immunocompetent C57BL/6 mice. IFN-gamma produced during the infection of beige mice was protective in the spleen, and the administration of recombinant IFN-gamma restored the resistance in the spleen to levels similar to those found in control mice. There were no histological differences between wild-type and beige mice with respect to granuloma formation in the liver. The increased susceptibility of beige mice to M. avium as manifested in the liver was reduced by transfusing neutrophils from wild-type C57BL/6 mice. Likewise, depletion of neutrophils from C57BL/6 mice rendered them as susceptible to M. avium infection of the liver as beige mice. Our results point to the participation of neutrophils in the defect of beige mice in addition to other defects. Furthermore, these results show that neutrophils play a significant role in the defense mechanisms against mycobacterial infections and that beige animals may be a useful model for study of the role of neutrophils in mycobacteriosis.

Animals↗

Characterization of the virulence of Mycobacterium avium complex (MAC) isolates in mice.

The virulence of different isolates of MAC was studied in naturally susceptible BALB/c mice. In preliminary experiments, MAC bacteria forming smooth transparent colonies on solid media (SmT variants) were found to be virulent for BALB/c mice, causing progressive infection; smooth opaque (SmOp) were generally avirulent, being slowly eliminated from the infected organs; and rough (Rg) variants were either avirulent or as virulent as SmT variants. We chose to compare the virulence of different isolates of MAC of different origins, studying only the SmT morphotype. Strains of MAC isolated from naturally infected animals were those that most consistently caused progressive infections. AIDS patients-derived isolates were of intermediate virulence or devoid of virulence in mice. The environmental strains were eliminated from mice or did not proliferate. Strains of MAC isolated from individuals who were not infected by HIV varied in virulence from completely avirulent to highly virulent. There was no close correlation between virulence and restriction fragment length polymorphism (RFLP) type, although all highly virulent strains were of the A/I type. There was also no correlation between virulence analysed in vivo and the ability to grow in cultured macrophages.

Animals↗

Use of marijuana and other drugs by college students of São Paulo, Brazil.

Drug usage in a sample of 1,069 college students of São Paulo, Brazil, was investigated. The highest lifetime prevalence was reported for alcohol (82%) and tobacco (39%) followed by inhalants (28%), marijuana (26%), over-the-counter tranquilizers and stimulants (17%), and cocaine (10%). Current use is considerably smaller. Marijuana users were classified as having a "Stable," "Descending," and "Once" pattern of consumption frequency. These patterns were orderly related to sex, socioeconomic status, use of drugs, drug approval, and peer group. Drug usage appeared as predominantly social-recreational in this population, although the risk of misuse for "Stable" students should be evaluated.

Adolescent↗

Neutrophils as effector cells of T-cell-mediated, acquired immunity in murine listeriosis.

The control of the infections caused by Listeria monocytogenes, considered an example of an intracellular parasite, is thought to involve co-operation between antigen-specific T cells and activated macrophages. Here we investigated the participation of polymorphonuclear leucocytes in the mechanisms of resistance during the immune phase of the antimicrobial response to L. monocytogenes infection. We found that BALB/c mice were unable to express T-cell-mediated (acquired) immunity to this pathogen in the absence of granulocytes. We propose that neutrophils should be included in the concept of cell-mediated immunity and that their antimicrobial role is not exclusively expressed during the early phases of a primary infection.

Animals↗

Adjuvant treatment increases the resistance to Mycobacterium avium infection of mycobacteria-susceptible BALB/c mice.

We have investigated the effect of inflammation on host resistance against infection by Mycobacterium avium, an atypical mycobacteria species that is responsible for life-threatening opportunistic infections in AIDS patients. Inflammation was induced in BALB/c mice by two intraperitoneal injections of mineral oil (Freund's incomplete adjuvant, FIA). The BALB/c strain was chosen because it is naturally susceptible to Myco. avium infection. One week after the second FIA injection, the BALB/c mice were infected intravenously with 2.6 x 10(6) Myco. avium bacilli; at this time, the mice showed systemic granulocytosis because of the FIA injections. The kinetics of the murine infection was determined during 3 months by quantification of Myco. avium loads in the major target organs (liver and spleen) of the mycobacteria. The FIA treatment resulted in a significant decrease in the growth of Myco. avium in the infected BALB/c mice. This enhancement in host resistance to Myco. avium infection lasted for 2-3 months. In contrast with BALB/c animals, C3H mice (naturally resistant to Myco. avium infection) did not show an increased anti-Myco. avium action in association with the FIA treatment. The antimycobacterial effect of the FIA injections in BALB/c mice was compared with that produced by the injection of mycobacterial antigens (heat-killed Myco. tuberculosis) added to the mineral oil (i.e. Freund's complete adjuvant, FCA). The FCA treatment resulted in strong and sustained enhancements in the microbicidal capacities of BALB/c, and also of C3H mice. Data obtained with mutant athymic BALB/c mice revealed that the anti-Myco. avium effect of the FCA treatment was T cell-dependent. Our results indicate that: (i) non-immune inflammatory stimulation (FIA) of Myco. avium-susceptible hosts is able to cause a significant, albeit transient, increase in the resistance to Myco. avium infection; (ii) this protective effect is enhanced if heat-killed mycobacteria are added to the phlogistic agent (FCA), i.e. if a T cell-dependent response is induced; and (iii) systemic increase in the number of circulating granulocytes may help host defence against Myco. avium infection.

Animals↗

In vitro effects of interleukin-4 on interferon-gamma-induced macrophage activation.

Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) have been shown to be secreted by distinct T-helper cell subsets which have different roles in the determination of host resistance to infection. We studied the activity of these two cytokines on effector mechanisms of mouse macrophages. In vitro cultured bone marrow-derived macrophages from C57BL/6 mice were treated with IFN-gamma, IL-4, or a combination of both cytokines and the ability to secrete superoxide or nitrite or to restrict growth of Mycobacterium avium and Toxoplasma gondii was then evaluated. We found that IL-4 could inhibit the priming of macrophages for enhanced superoxide production induced by IFN-gamma although IL-4 when used alone did have some enhancing effect of its own. This effect of IL-4 on IFN-gamma-primed superoxide production was dose dependent and could be observed even if the treatment by IL-4 was done 24 hr after treatment by IFN-gamma. IL-4 did not, however, influence the enhanced production of nitrogen reactive intermediates, the induction of bacteriostatic activity against M. avium, or the restriction of T. gondii by IFN-gamma-treated macrophages, and did not have any effect of its own regarding these latter functions.

Animals↗