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1.
Braz. j. med. biol. res ; 40(3): 391-399, Mar. 2007. graf, ilus
Article in English | LILACS | ID: lil-441761

ABSTRACT

Chagas' disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ET A and ET B receptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas' disease. We investigated the effects of treatment with bosentan, an ET A/ET B receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg-1 day-1) was given per os starting day 0 after infection until sacrifice. Bosentan significantly increased myocardial inflammation, with no effects on parasitemia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-g and TNF-a and the chemokines CCL2/MCP-1, CCL3/MIP-1a and CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 æM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre-treated with bosentan (1 æM) 15 min before incubation with ET-1. However, ET-1 did not alter killing of intracellular parasites after 48 h of in vitro infection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. Infection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protection against acute murine T. cruzi infection.


Subject(s)
Animals , Male , Mice , Chagas Cardiomyopathy/metabolism , Endothelin-1/physiology , Parasitemia/metabolism , Receptors, Endothelin/antagonists & inhibitors , Sulfonamides/pharmacology , Trypanosoma cruzi/physiology , Acute Disease , Chagas Cardiomyopathy/parasitology , Chagas Cardiomyopathy/pathology , Cytokines/analysis , Disease Models, Animal , Parasitemia/immunology , Trypanosoma cruzi/isolation & purification
2.
Braz. j. med. biol. res ; 39(4): 441-445, Apr. 2006. ilus
Article in English | LILACS | ID: lil-425080

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Chemokines, CC/cerebrospinal fluid , Chemokines, CXC/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Adjuvants, Immunologic/therapeutic use , Biomarkers/cerebrospinal fluid , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy
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