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1.
Trop Med Int Health ; 18(1): 75-84, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23107306

RESUMO

OBJECTIVES: The cardiac form of Chagas disease is evidenced by a progressive cardiac inflammation that leads to myocarditis, fibrosis and electrocardiographic (ECG) conduction abnormalities. Considering these characteristics, the aim of this study was to prospectively evaluate the early ECG changes in dogs that were experimentally inoculated with Benznidazole (Bz)-susceptibly (Berenice-78) and Bz-resistant (VL-10, and AAS) Trypanosoma cruzi strains and, later, evaluate the efficacy of Bz treatment for preventing these ECG alterations. METHODS: Electrocardiographic changes of treated and untreated animals were prospectively evaluated for up to 270 days after infection, at which point collagen (right atrium) quantification was performed. RESULTS: All infected dogs had a high intensity of heart fibrosis (4616.00 ± 1715.82 collagen/74931 µm(2) in dogs infected with Berenice-78 strain, 5839.2 ± 1423.49 collagen/74931 µm(2) in infected by AAS and 6294.40 ± 896.04 collagen/74931 µm(2) in animals infected with VL-10 strain), while 78.57% of all infected dogs showed ECG alterations. Bz Therapy reduced or prevented fibrosis in Bz-susceptible Berenice-78 (2813.00 ± 607.13 collagen/74931 µm(2) ) and Bz-resistant AAS strains (4024 ± 1272.44 collagen/74931 µm(2) ), coincident with only 10% de ECG alterations at 270 days. However, in those animals infected with a Bz-resistant VL-10 strain, specific treatment did not alter collagen deposition (6749.5 ± 1596.35 collagen/74931 µm(2) ) and there was first atrioventricular block and chamber overload at 120 and 270 days after infection, with 75% abnormal ECG exams. CONCLUSIONS: These findings indicate that an effective antiparasitic treatment in the early stage of Chagas disease can lead to a significant reduction in the frequency and severity of the parasite-induced cardiac disease, even if parasites are not completely eliminated.


Assuntos
Doença de Chagas/tratamento farmacológico , Cicatriz/prevenção & controle , Colágeno/metabolismo , Átrios do Coração/efeitos dos fármacos , Miocárdio/patologia , Nitroimidazóis/uso terapêutico , Trypanosoma cruzi , Animais , Bloqueio Atrioventricular , Doença de Chagas/patologia , Doença de Chagas/fisiopatologia , Doença de Chagas/veterinária , Doença Crônica , Cães , Resistência a Medicamentos/efeitos dos fármacos , Eletrocardiografia , Fibrose/prevenção & controle , Átrios do Coração/fisiopatologia , Nitroimidazóis/farmacologia , Estudos Prospectivos , Resultado do Tratamento , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico
2.
PLoS Negl Trop Dis ; 15(7): e0009613, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34314435

RESUMO

Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qß-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.


Assuntos
Cardiomiopatia Chagásica/prevenção & controle , Coração/parasitologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi , Animais , Anticorpos Antiprotozoários/sangue , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/imunologia , Imunoglobulina G/sangue , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Parasitemia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
3.
ACS Infect Dis ; 6(7): 1807-1815, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32374586

RESUMO

The leading animal model of experimental Chagas disease, the mouse, plays a significant role in studies for vaccine development, diagnosis, and human therapies. Humans, along with Old World primates, alone among mammals, cannot make the terminal carbohydrate linkage of the α-Gal trisaccharide. It has been established that the anti-α-Gal immune response is likely to be a critical factor for protection against Trypanosoma cruzi (T. cruzi) infection in humans. However, the mice customarily employed for the study of T. cruzi infection naturally express the α-Gal epitope and therefore do not produce anti-α-Gal antibodies. Here, we used the C57BL/6 α-1,3-galactosyltransferase knockout (α-GalT-KO) mouse, which does not express the α-Gal epitope as a model for experimental Chagas disease. We found the anti-α-Gal IgG antibody response to an increase in α-GalT-KO mice infected with Arequipa and Colombiana strains of T. cruzi, leading to fewer parasite nests, lower parasitemia, and an increase of INF-γ, TNF-α, and IL-12 cytokines in the heart of α-GalT-KO mice compared with α-GalT-WT mice on days 60 and 120 postinfection. We therefore agree that the C57BL/6 α-GalT-KO mouse represents a useful model for initial testing of therapeutic and immunological approaches against different strains of T. cruzi.


Assuntos
Doença de Chagas , Trypanosoma cruzi , Animais , Galactosiltransferases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
4.
Int J Parasitol ; 46(3): 213-220, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26812026

RESUMO

The anaphylaxis response is frequently associated with food allergies, representing a significant public health hazard. Recently, exposure to tick bites and production of specific IgE against α-galactosyl (α-Gal)-containing epitopes has been correlated to red meat allergy. However, this association and the source of terminal, non-reducing α-Gal-containing epitopes have not previously been established in Brazil. Here, we employed the α-1,3-galactosyltransferase knockout mouse (α1,3-GalT-KO) model and bacteriophage Qß-virus like particles (Qß-VLPs) displaying Galα1,3Galß1,4GlcNAc (Galα3LN) epitopes to investigate the presence of α-Gal-containing epitopes in the saliva of Amblyomma sculptum, a species of the Amblyomma cajennense complex, which represents the main tick that infests humans in Brazil. We confirmed that the α-1,3-galactosyltransferase knockout animals produce significant levels of anti-α-Gal antibodies against the Galα1,3Galß1,4GlcNAc epitopes displayed on Qß-virus like particles. The injection of A. sculptum saliva or exposure to feeding ticks was also found to induce both IgG and IgE anti-α-Gal antibodies in α-1,3-galactosyltransferase knockout mice, thus indicating the presence of α-Gal-containing epitopes in the tick saliva. The presence of α-Gal-containing epitopes was confirmed by ELISA and immunoblotting following removal of terminal α-Gal epitopes by α-galactosidase treatment. These results suggest for the first known time that bites from the A. sculptum tick may be associated with the unknown etiology of allergic reactions to red meat in Brazil.


Assuntos
Hipersensibilidade Alimentar/imunologia , Carne Vermelha/efeitos adversos , Saliva/imunologia , Carrapatos/imunologia , Animais , Brasil , Mapeamento de Epitopos , Epitopos/química , Epitopos/imunologia , Feminino , Hipersensibilidade Alimentar/etiologia , Galactosiltransferases/genética , Galactosiltransferases/imunologia , Humanos , Imunoglobulina E/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Carne Vermelha/análise , Saliva/química , Carrapatos/química
5.
ACS Infect Dis ; 2(12): 917-922, 2016 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-27696820

RESUMO

The α-Gal antigen [Galα(1,3)Galß(1,4)GlcNAcα] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of α-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Chagas disease and the assessment of treatment effectiveness. A panel of sera from patients chronically infected with T. cruzi, both untreated and benznidazole-treated, was compared with sera from patients with leishmaniasis and from healthy donors. The nanoparticle-α-Gal construct allowed for perfect discrimination between Chagas patients and the others, avoiding false negative and false positive results obtained with current state-of-the-art reagents. As previously reported with purified α-Gal-containing glycosylphosphatidylinositol-anchored mucins, the current study also showed concentrations of anti-α-Gal IgG to decrease substantially in patients receiving treatment with benznidazole, suggesting that the semiquantitative assessment of serum levels of this highly abundant type of antibody can report on disease status in individual patients.


Assuntos
Doença de Chagas/diagnóstico , Trissacarídeos/análise , Trypanosoma cruzi/isolamento & purificação , Anticorpos Antiprotozoários/análise , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/análise , Antígenos de Protozoários/imunologia , Doença de Chagas/parasitologia , Ensaio de Imunoadsorção Enzimática , Humanos , Trissacarídeos/imunologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologia , Vírus/genética , Vírus/metabolismo
6.
Am J Trop Med Hyg ; 84(2): 325-31, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21292909

RESUMO

Chagas cardiomyopathy remodeling is based on the presence of Trypanosoma cruzi in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of T. cruzi. Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with T. cruzi-induced ventricular dysfunctions.


Assuntos
Cardiomiopatia Chagásica/veterinária , Doenças do Cão/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Sinvastatina/uso terapêutico , Animais , Cardiomiopatia Chagásica/tratamento farmacológico , Doenças do Cão/parasitologia , Cães , Feminino , Coração/efeitos dos fármacos , Coração/parasitologia , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Interferon gama/sangue , Interleucina-10/sangue , Masculino , Miocárdio/metabolismo , Reação em Cadeia da Polimerase/veterinária , Sinvastatina/administração & dosagem , Volume Sistólico/efeitos dos fármacos , Trypanosoma cruzi , Fator de Necrose Tumoral alfa/sangue
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