RESUMO
Although renin-angiotensin system (RAS) imbalance is manifested in cardiomyopathies with different etiologies, the impact of RAS effectors on Chagas cardiomyopathy and skeletal myositis is poorly understood. Given that diminazene aceturate (DMZ) shares trypanocidal, angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) stimulatory effects, we investigated the impact of DMZ on cardiomyocytes infection in vitro, renin-angiotensin system, Chagas cardiomyopathy and skeletal myositis in vivo. Cardiomyocytes and T. cruzi were used to evaluate DMZ toxicity in vitro. The impact of 20-days DMZ treatment (1 mg/kg) was also investigated in uninfected and T. cruzi-infected mice as follows: control uninfected and untreated, uninfected treated with DMZ, infected untreated and infected treated with DMZ. DMZ had low toxicity on cardiomyocytes, induced dose-dependent antiparasitic activity on T. cruzi trypomastigotes, and reduced parasite load but not infection rates in cardiomyocytes. DMZ increased ACE2 activity and angiotensin-(1-7) plasma levels but exerted no interference on angiotensin-converting enzyme (ACE) activity, ACE, ACE2 and angiotensin II levels in uninfected and infected mice. DMZ treatment also reduced IFN-γ and IL-2 circulating levels but was ineffective in attenuating parasitemia, MCP-1, IL-10, anti-T. cruzi IgG, nitrite/nitrate and malondialdehyde production, myocarditis and skeletal myositis compared to infected untreated animals. As the antiparasitic effect of DMZ in vitro did not manifest in vivo, this drug exhibited limited relevance to the treatment of Chagas disease. Although DMZ is effective in upregulating angiotensin-(1-7) levels, this molecule does not act as a potent modulator of T. cruzi infection, which can establish heart and skeletal muscle parasitism, lipid oxidation and inflammatory damage, even in the presence of high concentrations of this RAS effector.
Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Doença de Chagas/tratamento farmacológico , Diminazena/análogos & derivados , Miócitos Cardíacos/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina I/metabolismo , Animais , Linhagem Celular , Cardiomiopatia Chagásica/parasitologia , Doença de Chagas/parasitologia , Diminazena/administração & dosagem , Diminazena/farmacologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/tratamento farmacológico , Miocardite/parasitologia , Miócitos Cardíacos/parasitologia , Miosite/tratamento farmacológico , Miosite/parasitologia , Fragmentos de Peptídeos/metabolismo , Ratos , Tripanossomicidas/administração & dosagem , Tripanossomicidas/farmacologiaRESUMO
Amphibians are hosts for a wide variety of micro- and macro-parasites. Chigger mites from the Hannemania genus are known to infect a wide variety of amphibian species across the Americas. In Chile, three species (H. pattoni, H. gonzaleacunae and H. ortizi) have been described infecting native anurans; however, neither impacts nor the microscopic lesions associated with these parasites have been described. Here, we document 70% prevalence of chigger mite infection in Eupsophus roseus and absence of infection in Rhinoderma darwinii in the Nahuelbuta Range, Chile. Additionally, we describe the macroscopic and microscopic lesions produced by H. ortizi in one of these species, documenting previously undescribed lesions (granulomatous myositis) within the host's musculature. These findings highlight that further research to better understand the impacts of chigger mite infection on amphibians is urgently required in Chile and elsewhere.
Assuntos
Anuros/parasitologia , Infestações por Ácaros/epidemiologia , Miosite/veterinária , Trombiculíase/epidemiologia , Trombiculidae/classificação , Animais , Chile/epidemiologia , Florestas , Infestações por Ácaros/parasitologia , Miosite/parasitologia , Doenças Parasitárias , Prevalência , Trombiculíase/veterináriaRESUMO
Comparative histopathological study and analysis of parasite load in different muscle groups were carried out in BALB/c mice during the acute phase of Chagas disease. Activities of C104 clone of T. cruzi strain TPAP/MX/2002/Albarrada and the parental strain were compared. Panoramic 2D-microscopy imaging of sample surface was used and quantitative analysis of parasitism and pathologic damage was performed. The infection rates in various muscle groups were as follows: myocardium=abdominal muscles=lumbar muscles=femoral muscles<--diaphragm for the clone and myocardium¬abdominal muscles=lumbar muscles=femoral muscles-->diaphragm for the parental strain.
Assuntos
Doença de Chagas/parasitologia , Trypanosoma cruzi/patogenicidade , Músculos Abdominais/parasitologia , Animais , Diafragma/parasitologia , Coração/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Miosite/parasitologia , Especificidade de Órgãos , Carga Parasitária , Trypanosoma cruzi/genéticaRESUMO
INTRODUCTION: Murine infection with Trypanosoma cruzi (Tc) has been used to study the role of T-cells in the pathogenesis of human inflammatory idiopathic myositis. Absence of decay-accelerating factor 1 (Daf1) has been shown to enhance murine T-cell responses and autoimmunity. METHODS: To determine whether Daf1 deficiency can exacerbate Tc-induced myositis, C57BL/6 DAF(+/+) and DAF(-/-) mice were inoculated with 5 × 10(4) trypomastigotes, and their morbidity, parasitemia, parasite burden, histopathology, and T-cell expansion were studied in the acute and chronic stages. RESULTS: DAF(-/-) mice had lower parasitemia and parasite burden but higher morbidity, muscle histopathology, and increased number of CD44(+) (activated/memory phenotype) splenic CD4(+) and CD8(+) T-cells. CONCLUSIONS: An enhanced CD8(+) T-cell immune-specific response may explain the lower parasitemia and parasite burden levels and the increase in histopathological lesions. We propose that Tc-inoculated DAF(-/-) mice are a useful model to study T-cell mediated immunity in skeletal muscle tissues.
Assuntos
Antígenos CD55/genética , Doença de Chagas/imunologia , Miosite/imunologia , Miosite/parasitologia , Trypanosoma cruzi/imunologia , Animais , Antígenos CD55/metabolismo , Doença de Chagas/genética , Doença de Chagas/parasitologia , Doença Crônica , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miosite/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Trypanosoma cruzi/crescimento & desenvolvimentoRESUMO
Recent studies have provided some insights into Leishsmania (Leishmania) amazonensis muscular infection in dogs, although, muscular disease due to leishmaniasis has been poorly documented. The aim of our study was to evaluate involvement of Leishmania in muscular infection of two distinct mouse strains (BALB/c and C3H.He), with different genetic backgrounds. BALB/c mice, susceptible to Leishmania infection, showed, at the beginning of infection, a great number of infected macrophages among muscle fibers; however, in C3H.He resistant mice, muscle fibers were less damaged than in BALB/c mice, but some parasitized macrophages could be seen among them. A follow up of the infection showed an intense inflammatory infiltrate mainly composed of infected macrophages in BALB/c muscles and the presence of amastigotes within muscle fibers; while C3H.He mice exhibited a moderate inflammatory infiltrate among skeletal muscle fibers and an absence of amastigotes. Total destruction of muscles was observed in BALB/c mice in the late phase of infection (day 90) while C3H.He mice showed a process of muscle repair. We concluded that: (1) the muscles of BALB/c mice were more affected by leishmaniasis than those of C3/H.He mice; (2) Leishmania amastigotes are capable of infecting muscular fibers, as observed in BALB/c mice; (3) as inflammatory infiltrate is less intense in C3H.He mice these animals are capable of restoring muscular fibers.
Assuntos
Leishmania mexicana/fisiologia , Leishmaniose Tegumentar Difusa/parasitologia , Músculo Esquelético/parasitologia , Miosite/parasitologia , Animais , DNA de Protozoário/análise , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Pé , Humanos , Leishmania mexicana/genética , Leishmania mexicana/imunologia , Leishmaniose Tegumentar Difusa/imunologia , Leishmaniose Tegumentar Difusa/patologia , Macrófagos/parasitologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Fibras Musculares Esqueléticas/parasitologia , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Miosite/imunologia , Miosite/patologia , Reação em Cadeia da PolimeraseRESUMO
Reinfections with Trypanosoma cruzi in patients from endemic areas have been claimed to be an aggravation factor of cardiac manifestations in Chagas' disease. In the present study, the influence of triple infections with strains of different biodemes, on cardiac and skeletal muscle lesions was experimentally tested. Fifty eight mice chronically infected with the Colombian strain (Biodeme Type III) were successively reinfected as follows: 1st group--reinfected with 21 SF strain (Type II) followed by Y strain (Type I ); 2nd--group reinfections with Y strain followed by 21SF strain. Isoenzyme analysis of parasites from hemocultures obtained from triple infected mice, revealed the patterns of three distinct zymodemes in the same animal. Each Trypanosoma cruzi strain was reisolated after four passages in mice on either the 7th, 14th or 30th day after inoculation with the blood of triple infected mice. Histopathology results demonstrated a significant exacerbation of cardiac and skeletal muscle inflammatory lesions, confirmed by morphometric evaluation, in mice with triple infection. No aggravation of parasitism was detected. The possibility of an enhancement of cellular response in the triple infected mice is suggested.
Assuntos
Doença de Chagas/patologia , Miocardite/parasitologia , Miosite/parasitologia , Trypanosoma cruzi/classificação , Animais , Doença de Chagas/parasitologia , Isoenzimas/análise , Camundongos , Miocardite/patologia , Miosite/patologia , Parasitemia/patologia , Especificidade da Espécie , Fatores de Tempo , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/patogenicidadeRESUMO
Reinfeccões pelo Trypanosoma cruzi em pacientes de áreas endêmicas têm sido mencionadas como fator agravante das manifestacões cardíacas na doenca de Chagas. No presente estudo, a influência da tríplice infeccão com cepas de diferentes biodemas, sobre as lesões do miocárdio e de músculo esquelético foi investigada experimentalmente. Cinqüenta e oito camundongos cronicamente infectados com a cepa Colombiana do Trypanosoma cruzi (Biodema Tipo III) foram sucessivamente reinoculadas como a seguir: 1º grupo - reinfectados com a cepa 21 SF (Tipo II) seguido pela cepa Y (Tipo I); 2º grupo - reinfeccão com a cepa Y seguida pela cepa 21SF. A análise isoenzimática dos parasitas das hemoculturas obtidas dos animais com tríplice infeccão, revelou os padrões dos diferentes zimodemas no mesmo animal. Cada cepa do Trypanosoma cruzi foi re-isolada após quatro passagens em camundongos no 7º, no 14º, ou no 30º dia após a inoculacão com o sangue de camundongos com tríplice infeccão. Resultados da histopatologia demonstraram uma significante exacerbacão das lesões inflamatórias de miocárdio e músculo esquelético, confirmadas pela avaliacão morfométrica. Não foi detectada acentuacão do parasitismo. A possibilidade de aumento da resposta celular nos animais com tríplice infeccão é sugerida.
Assuntos
Camundongos , Animais , Doença de Chagas/patologia , Isoenzimas/análise , Miocardite/parasitologia , Miosite/parasitologia , Trypanosoma cruzi/classificação , Doença de Chagas/parasitologia , Miocardite/patologia , Miosite/patologia , Parasitemia/patologia , Fatores de Tempo , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/patogenicidadeRESUMO
Although Chagas' disease is known to provoke severe acute myositis, information on muscle regeneration is missing. The current paper shows that during T. cruzi infection in rats, skeletal muscle parasitism and the consequent inflammatory process are higher in muscle with a high proportion of type-I myofibres (soleus and diaphragm). Immunohistochemistry showed an acute inflammatory process characterized by ED1+ and ED2+ macrophages, CD8+ lymphocytes, and NK cells. Parasite-nest rupture provoked segmental degeneration of myofibres followed by regeneration. These phenomena were observed at both light and transmission electron microscopy levels. Myofibre regeneration involved activation of satellite cells assessed by the expression of MyoD, a muscle-specific transcription factor. Ultrastructural evidence of fusion of myoblast-like cells with the intact segment of degenerating fibres has been provided. At the chronic phase no signs of fibrosis were found, but sparse and small inflammatory foci were found. Our results argue against the relevant participation of autoimmunity phenomena in both acute and chronic phases and furnish a new view for explaining histopathological findings in human patient muscles.
Assuntos
Músculo Esquelético/patologia , Músculo Esquelético/parasitologia , Miosite/patologia , Miosite/parasitologia , Regeneração , Trypanosoma cruzi/patogenicidade , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/parasitologia , Linfócitos T CD8-Positivos/ultraestrutura , Diafragma/parasitologia , Diafragma/patologia , Diafragma/ultraestrutura , Imuno-Histoquímica , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/parasitologia , Células Matadoras Naturais/ultraestrutura , Macrófagos/imunologia , Macrófagos/parasitologia , Macrófagos/ultraestrutura , Músculo Esquelético/ultraestrutura , Proteína MyoD/genética , Proteína MyoD/metabolismo , Mioblastos/parasitologia , Mioblastos/patologia , Mioblastos/ultraestrutura , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Weanling C3H/HeN mice were fed either a torula yeast-based diet deficient in selenium (Se) or the same diet supplemented with 0.2 ppm Se as sodium selenite. After 4 wk of feeding, the mice were inoculated intraperitoneally with the CA-I strain (clone K98) of Trypanosoma cruzi (TC). Before inoculation, mean serum Se levels were 430 versus 61 ng/ml in adequate and deficient mice, respectively. During the ascending phase of parasitemia, the Se-deficient mice exhibited significantly higher levels of parasites at 22-34 days postinfection (PI). However, no difference was found in the subsequent descending phase. As judged by visual examination at 2-mo-PI, some Se-deficient infected mice presented clinical signs of motor dysfunction. At 3-mo-PI, the end of the observation period, this chronic disease developed into a hind limb flaccid paralysis affecting 5 of 8 infected deficient mice. No signs of paralysis were seen in noninfected mice fed either diet or in infected mice fed the Se-adequate diet. At the histological level, both Se-adequate and Se-deficient infected mice showed mild myocarditis and moderate to severe myositis, with increasing intensity from 1- to 3-mo-PI in both groups. However, the severity of myositis was always more intense in the Se-deficient mice so that prominent areas of skeletal muscle replaced by fibrotic tissue were frequently observed. Thus, it can be concluded that Se deficiency in the murine host increases the severity of TC-induced myositis.