Biomedical subjects

W Tavares de Lima

Publications and source records attributed to W Tavares de Lima.

9 recordsLinked to original sources

PubMed2004

Effects of amphetamine on immune-mediated lung inflammatory response in rats.

OBJECTIVE: The present study analyzed the effects of acute amphetamine (AMPH) treatment on immune-mediated lung inflammatory response in rats. METHODS: There were four experiments. In the first and second experiments, rats were treated with AMPH (1 mg/kg) or 0.9% NaCl, and locomotor activity (experiment 1) and serum AMPH concentrations (experiment 2) were measured 1 or 12 h after treatment. In the third experiment, rats which were immunized with ovalbumin (OVA) were treated 14 days later with 0.9% NaCl or AMPH (1 mg/kg). Twelve hours after these treatments, all animals were submitted to challenge by 1% OVA inhalation being analyzed afterwards for bronchoalveolar lavage fluid (BAL), peripheral blood and bone marrow cellularity. In the fourth and final experiment, rats were treated and studied as for experiment 3, except that half of the animals within each group were previously treated with metyrapone prior to the OVA challenge. RESULTS: In the non-immunized rats, AMPH treatment induced an increase in locomotor activity synchronized to high serum AMPH concentrations 1 h after, but not 12 h after treatment. In OVA-challenged rats, AMPH treatment decreased the total number of inflammatory cells, recovered in both BAL and peripheral blood and increased the total number of bone marrow cells. These effects, observed 1 day after OVA challenge, were abrogated by previous metyrapone treatment. CONCLUSION: AMPH treatment changed HPA-axis responsiveness to the stress condition imposed by the OVA challenge decreasing lung and blood leukocytes cellularity most probably via corticosterone actions on bone marrow activity.

Amphetamine↗

PubMed2004

Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin.

Hormones play a modulating role in allergic inflammation. An inverse relationship between atopy and diabetes mellitus was reported. The mechanisms regulating this interaction are not completely understood. This study examined whether insulin influences mast cell activation following antigen challenge in rats. The experimental design included alloxan-induced diabetic rats and matching controls. Experiments were performed 30 days after alloxan injection. The animals were sensitised by s.c. injection of ovalbumin (OA) and aluminium hydroxide. OA-induced airway contraction, morphometric analysis of airway mast cells and tissue histamine quantification were evaluated in the isolated main bronchus and intrapulmonary bronchus upon exposure to antigen in vitro. Relative to controls, a reduced contraction to OA was observed in bronchial segments isolated from diabetic rats. This was accompanied by a 50% reduction in the number of degranulated mast cells and in histamine release. A complete recovery of the impaired responses was observed under the influence of insulin. In conclusion, the data suggested that insulin might modulate the controlling of mast cell degranulation; therefore, the early-phase response to antigen provocation, which represents a new insight into a better understanding of the mechanisms, accounted for the decreased risk of asthma among type-1 diabetic patients.

Animals↗

PubMed2001

Pharmacological modulation of allergic inflammation in the rat airways and association with mast cell heterogeneity.

Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15 min) protein exudation in different airway tissues, as determined by Evans blue staining. This was associated with marked mast cell degranulation determined by histological examination, with there being no difference between mucosal and connective tissue mast cells. A 5-day administration regimen with compound 48/80 selectively depleted connective tissue mast cell (positive to berberine staining) without modifying ovalbumin-induced plasma protein extravasation. Treatment of rats with dexamethasone (1 mg/kg, -12 h) or nor-dihydroguaiaretic acid (30 mg/kg i.p., -30 min) significantly reduced ovalbumin-induced protein extravasation and preserved mucosal mast cell morphology. Indomethacin (4 mg/kg i.v., -30 min) exerted no effect on either parameter. In conclusion, we propose the mucosal mast cell as a target cell responsible at least partly for the inhibitory actions of known anti-inflammatory drugs. We suggest an involvement of endogenous leukotriene(s), but not prostanoid(s), in mucosal mast cell activation/degranulation.

Administration, Inhalation↗

PubMed2001

Melatonin modulates allergic lung inflammation.

Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well-known immunostimulatory effects of melatonin, research has identified some of its anti-inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma.

Animals↗

PubMed1999

Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in proximal rat trachea.

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM) and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.

Animals↗

PubMed1999

Modulation of hypersensitivity reaction by lipids given orally.

The effect of lipids administration by gavage (0.4% body weight) given daily during four weeks on the hypersensitivity reaction in trachea, upper and lower bronchi, liver, kidney, mesentery, and pancreas was investigated in male rats. The plasma exudation was assessed by using Evans blue (EB) dye extravasation method. There was a significant difference in the permeability of the organs in nonimmunized rats. The immunization increased the vascular permeability and the response with the organs varied greatly. The effect of lipids on anaphylactic reaction was compared to those of untreated rats (control group). The EB extravasation was significantly increased in the trachea obtained from rats treated with cocoa butter and soybean oil. In the upper bronchi of rats treated with soybean oil, the EB extravasation was increased. However, in the lower bronchi, none of the treatments with lipids changed the extravasation of EB. The same was observed in the liver and kidney. The animals treated with lipids by gavage did not present differences in EB extravasation in the mesentery. However, in the pancreas and duodenum, the treatment with fish and soybean oils and cocoa butter markedly lowered EB extravasation.

Administration, Oral↗

PubMed1998

Modulation by lipid mediators of immune complex-induced lung inflammation in mice.

The present study characterized a murine model of immune complex-induced pneumonitis and investigated the role of platelet-activating factor (PAF) and eicosanoids as mediators of lung neutrophil infiltration and hemorrhagic lesions. Rabbit antibodies to bovine serum albumin were injected into the airways and bovine serum albumin was injected intravenously into C3H/HePas and BALB/c mice. After 24 h, a significant increase in neutrophil infiltration and hemoglobin concentration in the bronchoalveolar lavage fluid and lung parenchyma was observed in both strains despite the C3H/HePas strain being 10 times more sensitive to PAF. Neutrophil influx and vascular lesions were not affected by pre-treatment of the mice with the PAF receptor antagonist, WEB 2170 (5-(2-chlorphenyl)carbonyl)-3,4-dihydro- 10-methyl-3-((4-morpholinyl)-2H,7H-cyclopenta(4,5)thieno(3,2-f)(1,2,4)-t riazolo-(4,3-a)(1,4)-diazepine). In contrast, neutrophil influx and vascular lesions were increased by the cyclo-oxygenase inhibitor, indomethacin, and reduced by the inhibitor of leukotriene synthesis, MK 886 (3-[1-(4-chlorobenzyl-3-t-butyl-thio-t-isopropyl-indol-2y-1]-2-2-+ ++dimethylpropanoic acid) and by the leukotriene B4 receptor antagonist, RO 0254094 (2-[(5-carboxypentyl)-6-[6-[3,4-dihidro-4-oxo-8-propyl-2H-1-benzop yran-7-yl)hexyl] benzenepropanoic acid). Increased levels of leukotriene B4, leukotriene C4/D4, thromboxane B2 were found in bronchoalveolar lavage fluid 4 h after induction of the reaction. There is also a tendency to increased prostaglandins E2 levels. Neutrophil infiltration and vascular lesions in immune complex-induced pneumonitis in mice are mediated by leukotriene B4.

Animals↗

PubMed1998

Lipid mediators, tumor necrosis factor and nitric oxide and their interactions in immune-complex-induced lung injury.

We investigated the contribution of eicosanoids, platelet-activating factor, tumor necrosis factor and nitric oxide to the neutrophil influx and development of pulmonary haemorrhagic lesions following immune-complex-induced pneumonitis in rats and possible interactions between these mediators. Increased levels of leukotriene B4 and tumor necrosis factor, measured by enzyme immunoassay and L-929 cytotoxicity assay, were found in the bronchoalveolar lavage 1 and 4 h after induction of the reaction, respectively, and their release was dependent on the previous generation of platelet activating factor. Antagonism of leukotriene B4 receptors by RO-0254094 (2-[(5-carboxypentyl])oxy]-6-[6-[3,4-dihydro-4-oxo-8-propyl-2H-1-benzopy ran-7-yl)oxy]hexyl] benzenepropanoic acid), inhibition of nitric oxide synthesis by L-NAME (Nw-nitro-L-arginine methyl ester) and antagonism of PAF-receptors by WEB-2170 (5-(2-chlorphenyl)-3-4-dihydro-10-methyl-3-((4-morpholinyl)carbony l)-2 H,7H-cyclopenta (4,5)thieno(3,2-f)(1,2,4)-triazolo-4,3,a)91,4)diazepine), significantly inhibited the intensity of haemorrhage, evaluated by the increased levels of extravascular hemoglobin in homogenates of lung tissues. Little evidence support the role of tumor necrosis factor in these lesions. The infiltration of neutrophils, evaluated by measuring myeloperoxidase in homogenates of lungs, was reduced by compounds L-663,536 (3-[1-(4 chlorobenzyl)-3-t-butyl thio-5-isopropylindol-2-yl]-2-2-dimethylpropanoic acid), WEB-2170 and L-NAME. These results indicate that neutrophil infiltration and haemorrhagic lesions in immune-complex-induced lung inflammation are mediated by platelet activating factor, leukotriene B4 and nitric oxide and point out to interesting interactions between these mediators.

Animals↗

PubMed1998

Impairment in connective tissue mast cells degranulation in spontaneously hypertensive rats: stimulus dependent resistance.

1. Microvascular permeability in the mesentery and consequent leakage of protein into the peritoneum of spontaneously hypertensive rats (SHR) and normotensive rats (NTR) was measured in vivo by the extravasation of Evans blue dye. 2. In sensitized NTR, challenge with antigen produced extensive increases in dye extravasation in the mesentery and in peritoneal lavage fluid within 10 min. 3. In sensitized SHR there was no increase in the permeability of the mesentery and a very weak increase in dye extravasation in the peritoneal cavity following challenge. 4. The glucocorticoid antagonist RU38486 did not change the permeability response induced by antigen in sensitized NTR and SHR. 5. However, compound 48/80 was equally effective in either NTR or SHR in causing increased vasopermeability. 6. Mesenteric mast cells in the NTR were degranulated after immunological challenge, whereas those in the SHR were resistant, as measured histologically. 7. Similarly, challenge ex vivo of mesentery from sensitized NTR induced contraction of guinea-pig ileum in co-incubation experiments, whereas SHR mesentery was unresponsive. 8. Plasma levels of antigen-specific IgE and IgG2a in sensitized NTR and SHR were identical. 9. Immune serum from SHR was unable to induce a passive cutaneous anaphylaxis (PCA) reaction in the skin of NTR and SHR did not develop a PCA reaction upon passive sensitization with NTR immune serum. 10. We conclude that the mast cells of SHR are resistant to degranulation following immunological challenge, although the relevant antibodies are present.

Animals↗