Viral myocarditis serum exosome-derived miR-320 promotes the apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway and targeting phosphatidylinositol 3-kinase regulatory subunit 1 (Pik3r1) / 细胞与分子免疫学杂志

Objective To investigate the effect of viral myocarditis serum exosomal miR-320 on apoptosis of cardiomyocytes and its mechanism. Methods The model of viral myocarditis mice was established by intraperitoneal injection of Coxsackie virus B3. Serum exosomes were extracted by serum exosome extraction kit and co-cultured with cardiomyocytes. The uptake of exosomes by cardiomyocytes was detected by laser confocal microscopy. Cardiomyocytes were transfected with miR-320 inhibitor or mimic, and the expression level of miR-320 was detected by real-time quantitative PCR. Flow cytometry was used to detect cardiomyocyte apoptosis rate, and the expression levels of B cell lymphoma 2 (Bcl2) and Bcl2-related X protein (BAX) were tested by Western blot analysis. The prediction of miR-320 target genes and GO and KEGG enrichment analysis were tested by online database. The relationship between miR-320 and its target gene phosphoinositide-3-kinase regulatory subunit 1(Pik3r1) was examined by luciferase reporter gene. The effect of miR-320 on AKT/mTOR pathway protein was detected by Western blot analysis. Results Viral myocarditis serum exosomes promoted cardiomyocyte apoptosis, and increased the level of BAX while the level of Bcl2 was decreased. miR-320 was significantly up-regulated in myocardial tissue of viral myocarditis mice, and both pri-miR-320 and mature of miR-320 were up-regulated greatly in cardiomyocytes. The level of miR-320 in cardiomyocytes treated with viral myocarditis serum exosomes was significantly up-regulated, while transfection of miR-320 inhibitor counteracted miR-320 overexpression and reduced apoptosis rate caused by exosomes. Pik3r1 is the target gene of miR-320, and its overexpression reversed cardiomyocyte apoptosis induced by miR-320 up-regulation. The overexpression of miR-320 inhibited AKT/mTOR pathway activation. Conclusion Viral myocarditis serum exosome-derived miR-320 promotes apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway by targeting Pik3r1.

Muerte súbita por miocarditis aguda asociada al virus influenza tipo B. Reporte de un caso / Sudden death due to acute myocarditis associated with influenza type B virus. Case report

Resumen La miocarditis es una inflamación del miocardio causada principalmente por infecciones virales, dentro de las cuales se encuentra el virus Influenza tipo B. Su presentación clínica varía desde individuos asintomáticos o con síntomas leves e inespecíficos a una miocarditis fulminante e incluso muerte súbita. La principal consecuencia a largo plazo es una miocardiopatía dilatada con insuficiencia cardiaca. Se presenta el caso de una femenina de 17 años, sin patologías crónicas conocidas, la cual presentó un cuadro viral de dos días de evolución y luego falleció de manera súbita; en la autopsia médico legal se documentó mediante estudios histopatológicos una miocarditis linfocítica aguda y por medio de la técnica de reacción en cadena de la polimerasa (PCR) de un frotis traqueal se evidenció la presencia del virus influenza tipo B. Se realizó una revisión de la literatura sobre miocarditis principalmente miocarditis viral causada por el virus Influenza B.

Abstract Myocarditis is an inflammatory disease of the heart muscle. Viral infections are the most frequent cause of myocarditis, incluided Influenza B virus. The clinical presentation of acute miocarditis is highly variable, ranging from subclinical disease to fulminant heart failure and sometimes with sudden death. The major long term consequence is dilated cardiomyopathy with chronic heart failure. We present a case of a 17 years old woman who presented with viral symptoms for two days and then died suddenly; in the medico-legal autopsy, an acute lymphocytic myocarditis was documented through histopathological studies and the presence of influenza type B virus was evidenced by means of the polymerase chain reaction (PCR) technique of a tracheal smear. A review of the literature on myocarditis, mainly viral miocarditis caused by the Influenza B virus, was made.

Cardiac magnetic resonance and amyloidosis: review / Ressonância magnética cardíaca e amiloidose: revisão

Amyloidosis is a disease caused by extracellular deposition of insoluble protein fibrils, that results in changes in tissue architecture and consequently modification of the organ structure. Cardiac involvement is common in amyloidosis. Two major types of systemic amyloidosis affect the myocardium ­ immunoglobulin light chain and transthyretin amyloidosis ­ each leading to different prognosis. Early detection and diagnosis of cardiac amyloidosis are the main objectives in the assessment of the disease. New techniques of magnetic resonance imaging have minimized the need for biopsies for the diagnosis. Late gadolinium enhancement technique, and more recently T1 mapping, have allowed a simplified evaluation of amyloid deposits and extracellular volume. The aim of this review was to describe basic concepts and updates of the use of magnetic resonance imaging for the diagnosis amyloidosis and evaluation of its severity

Left atrial giant cell myocarditis presenting as a tumor: first-in-man case report

Abstract Giant cell myocarditis is a rare and highly lethal disorder with resultant cardiac insufficiency. It necessitates aggressive immune suppression therapy, although the results are often fatal. When it affects only the atria, the characteristics of the disease changes completely. In this case report, we present atypical presentation of atrial giant cell myocarditis with mass lesion, which completely resolved after successful surgical resection without immuno suppression therapy.

Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition.

Infant acute myocarditis mimicking acute myocardial infarction

Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis.

Clinical and histopathological features of myocarditis in dogs with visceral leishmaniasis / Aspectos clínicos e histopatológicos da miocardite em cães com leishmaniose visceral

Visceral leishmaniasis (VL) is a cosmopolitan parasitic zoonosis that can promote myocarditis and heart rate changes in canine and human hosts. Thus, histopathological aspects of the myocardium and clinical, hematological, biochemical, radiological and electrocardiographic data were evaluated in a group of 36 dogs naturally infected with VL (VLG) and compared to data from 15 non-infected dogs (CG=Control Group). A prevalence of asymptomatic dogs was present in the CG (100%) and polysymptomatic dogs in the VLG (66%). In addition, two dogs in the VLG demonstrated systolic murmurs in the mitral valve region: one with a II/VI intensity and the other with a III/VI intensity. The mean values of RBC, hemoglobin and hematocrit were lower in dogs in VLG and were associated with higher values of total protein, total leukocytes, neutrophils, creatine kinase overall (CK) and the CK-MB fraction (CK-MB). The absence of radiographic changes was accompanied by a predominance of respiratory sinus arrhythmia associated with episodes of migratory pacemaker and sinus arrest in dogs in VLG (75%), sinus rhythm in dogs in CG (60%) and decreased P wave amplitude in VLG electrocardiography. Mononuclear cell infiltration was detected in the myocardium of 77,8% of dogs in GVL and classified primarily as mild multifocal lymphohistioplasmacytic. Amastigotes were detected in only one dog, which did not allow the association between myocarditis and parasitism, although the myocardial lesions that were found constitute irrefutable evidence of myocarditis in the VLG dogs, accompanied by lenient electrocardiographic changes compared to CG.

A leishmaniose visceral (LV) é uma zoonose parasitária cosmopolita capaz de promover miocardite e alterações no ritmo cardíaco em cães e seres humanos. Dessa forma, os aspectos clínicos, hematimétricos, bioquímicos, radiográficos, eletrocardiográficos e histopatológicos do miocárdio foram avaliados em 36 cães naturalmente infectados com LV (GLV) e comparados a 15 cães não infectados (GC). Houve predomínio de cães assintomáticos no GC (100%) e polissintomáticos no GLV (66%). Dois cães do GLV apresentaram sopro sistólico de intensidade II/VI e III/VI, em região de foco mitral. Os valores médios de hemácia, hemoglobina e hematócrito foram inferiores nos cães do GLV, associados a maiores valores de proteína total, leucócitos totais, neutrófilos, creatinina quinase total (CK) e fração MB (CK-MB). Ausência de alterações radiográficas foi acompanhada de predomínio de arritmia sinusal respiratória associada a episódios de marcapasso migratório e sinus arrest nos cães do GLV (75%), ritmo sinusal nos cães do GC (60%) e diminuição da amplitude da onda P no GLV à eletrocardiografia. Infiltrado inflamatório mononuclear foi detectado no miocárdio de 77,8% dos cães do GLV, classificados, em sua maioria, como linfoistioplasmocitário multifocal leve. A forma amastigota foi detectada em apenas um cão, não permitindo a associação entre a miocardite e a parasitose, ainda que as lesões miocárdicas encontradas constituam prova irrefutável da miocardite nos cães do GLV, acompanhadas por alterações eletrocardiográficas brandas em comparação ao GC.

Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice

Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain.

Miocardite crônica em um cão naturalmente infectado com Leishmania (Leishmania) infantum chagasi: aspectos clínicos e patológicos / Chronic myocarditis in a dog naturally infected by Leishmania (Leishmania) infantum chagasi: clinical and pathological aspects

A leishmaniose visceral (LV) é uma doença infecciosa crônica frequentemente fatal causada pela Leishmania infantum chagasi nas Américas. A enfermidade pode acometer vários órgãos, determinando diferentes manifestações clínicas. Contudo o envolvimento do coração raramente tem sido reportado em cães infectados por Leishmania sp. Dessa forma, descreve-se um caso de miocardite crônica com repercussões clínicas e patológicas em um cão naturalmente infectado por Leishmania infantum chagasi. A positividade para Leishmaniose Visceral foi determinada pela presença de anticorpos antiLeishmania sp. nos testes sorológicos (RIFI, ELISA e DPP) e confirmada por visualização de formas amastigotas de Leishmania sp. em punção aspirativa do linfonodo poplíteo. O exame cardiovascular revelou alterações radiográficas, eletrocardiográficas, na pressão arterial e nos biomarcardores cardíacos. Após eutanásia, amostras de tecido cardíaco foram avaliadas histologicamente e submetidas à imunomarcação, onde foi observado infiltrado mononuclear (plasmo-histiolinfocitário), com presença de estruturas arredondadas de coloracão marrom-amareladas (imunomarcadas), indicando formas amastigotas de Leishmania infantum chagasi no miocárdio. Os aspectos etiopatogênicos da leishmaniose visceral sobre o miocárdio neste caso podem estar relacionados tanto à presença do parasita quanto à resposta "reacional inespecífica" do tecido à agressão do parasita no organismo. Todavia ainda não se sabem se as cepas de Leishmania infantum chagasi da região semiárida paraibana apresentam algum tropismo por tecido cardíaco ou se induzem a reação imunológica cruzada, com implicações clínicas.

Visceral leishmaniasis (VL) is a chronic, often fatal infectious disease caused by Leishmania infantum chagasi in the Americas. The disease can affect many organs and may express different clinical forms. However, the involvement of the heart has rarely been reported in dogs infected by Leishmania sp. Thus, we describe a case of chronic myocarditis with clinical and pathological effects in a dog naturally infected by Leishmania infantum chagasi. Positivity for Visceral Leishmaniasis was determined by the presence of anti-Leishmania sp. in serological tests (IFAT, ELISA and DPP) and confirmed by visualization of amastigote forms of the parasite in the popliteal lymph node aspiration samples. The cardiovascular clinical examination showed changes in the radiographic, ECG, blood pressure and heart biomarkers. After euthanasia, heart tissue samples were histologically examined and underwent our immunohistochemistry assessment, where mononuclear infiltrate was observed (plasma cells, lymphocytes and macrophages) with the presence of rounded brownish-yellow (immunomarked) cells, indicating amastigotes of Leishmania infantum chagasi within the myocardium. The etiopathogenic aspects of visceral leishmaniasis in the myocardium in this case may be related either to the presence of the parasite or the "nonspecific reactive" response of the tissue attributable to the aggression of the parasite in the body. However, it is not known if the strains of Leishmania infantum chagasi found in the semi-arid of Paraíba have some tropism for cardiac tissue or if they induce immunological cross-reaction with clinical implications.

Analysis of distribution and pathological characteristics of 9 fatal trichinosis cases in Yunnan / 法医学杂志

OBJECTIVE@#To explore forensic pathology features of the fatal trichinosis cases and to summarize the population distribution characteristics of trichinosis in Yunnan.@*METHODS@#Nine recent fatal trichinosis cases were collected from the Forensic Science Identification Center of Kunming Forensic Hospital. Pathological and epidemiological characteristics of trichinosis were analyzed.@*RESULTS@#The nine cases were all died in heart failure due to myocarditis. Among them, 1 case was complicated by encephalitis and 3 cases were complicated by pneumonia. The population mainly involved Bai and Dai nationalities. The geographic distribution was concentrated in Dali, Dehong, Lincang, Xishuangbanna, etc. The cases commonly appeared in winter and spring.@*CONCLUSION@#The cause of trichinosis is closely due to the habit of eating raw pork. It can be diagnosis through the pathological changes of the muscle system in the death cases.

Perfusão da artéria pulmonar não melhora os índices de fator natriurético cerebral (BNP) em estudo experimental em suínos / Pulmonary artery perfusion does not improve brain natriuretic peptide (BNP) levels in suine experimental research

OBJETIVO: Avaliar se perfusão controlada do tronco pulmonar durante circulação extracorpórea (CEC) modifica os níveis de BNP expressos pelo miocárdio ventricular. MÉTODOS: Estudo experimental com 32 porcos, divididos em dois grupos de acordo com estratégia de CEC - grupo I (cardioplegia) e grupo II (coração batendo). Ambos os grupos foram alocados em três subgrupos, de acordo com a estratégia de perfusão pulmonar - subgrupo A (controle: sem perfusão pulmonar), subgrupo B (perfusão pulmonar com sangue arterial) e subgrupo C (perfusão com sangue venoso). Nos subgrupos B e C, pulmões foram perfundidos por 30 minutos, utilizando pressão arterial média pulmonar (PAPM) préoperatória como pressão de perfusão, a qual foi controlada com manômetro. PAPM e resistência vascular pulmonar (RVP) foram medidas após saída de CEC com cateter de Swan-Ganz. No período pré-operatório e após 30 minutos de perfusão pulmonar, fragmentos de miocárdio ventricular direito foram coletados para avaliar expressão de peptídeo natriurético cerebral (BNP) e padrão histológico tecidual. Técnicas de imunohistoquímica e hematoxilina-eosina foram utilizadas para determinar, respectivamente, expressão de BNP e lesões inflamatórias miocárdicas. RESULTADOS: Nos animais submetidos à perfusão controlada do tronco pulmonar, houve redução pós-operatória da PAPM (P=0,03) e da RVP (P=0,005). Não houve diferenças entre os subgrupos do grupo I (P=0,228) e subgrupos do grupo II (P=0,325) quanto à expressão pós-operatória de BNP. Não houve diferenças entre subgrupos com e sem perfusão pulmonar quanto à intensidade das lesões inflamatórias miocárdicas identificadas no pós-operatório (P>0,05). CONCLUSÃO: Perfusão controlada do tronco pulmonar por 30 minutos não foi suficiente para promover alterações substanciais na expressão de BNP e no padrão histológico miocárdico do ventrículo direito.

OBJECTIVE: Assess if the main pulmonary artery controlled perfusion over cardiopulmonary bypass (CPB) modifies BNP levels expressed by the ventricular myocardium. METHODS: Experimental research involving 32 pigs, divided into two groups according to CPB strategy - group I (cardioplegia) and group II (beating heart). Both groups were allocated into three subgroups according to lung perfusion strategy - subgroup A (control: no lung perfusion), subgroup B (lung perfusion with arterial blood) and subgroup C (lung perfusion with venous blood). In subgroups B and C, lung was perfused for 30 minutes, using preoperative mean pulmonary artery pressure (MPAP) as perfusion pressure, which was monitored through manometer. MPAP and pulmonary vascular resistance (PVR) were measured after coming off CPB using Swan-Ganz catheter. At preoperative time and 30 minutes after lung perfusion, specimens were taken from the right ventricular myocardium aiming to assess brain natriuretic peptide (BNP) and histologic pattern. Immunohistochemical and hematoxylin-eosin techniques were used to determine, respectively, BNP expression and inflammatory myocardial lesions. RESULTS: In animals submitted to controlled lung perfusion, there was a postoperative reduction of MPAP (P=0.03) and PVR (P=0.005).There was no differences among subgroups within the group, I (P=0.228) and subgroups within group II (P=0.325) as to postoperative BNP expression. There were no differences among subgroups with and without lung perfusion as to postoperative inflammatory lesions (P>0.05). CONCLUSION: Main pulmonary artery controlled perfusion for 30 minutes did not yield substantial modifications in BNP expression and histologic pattern of the right ventricular myocardium.

Paciente psiquiátrico em uso de clozapina com febre e taquicardia / Patient on clozapine with fever and tachycardia

A clozapina é uma droga de suma importância para o manejo de pacientes com sintomas psicóticos. Entretanto, efeitos adversos graves como agranulocitose e miocardite podem limitar o seu uso. Apresentamos o caso de um homem de 20 anos de idade que desenvolveu febre e taquicardia alguns dias após o início de uso de clozapina para um provável quadro de esquizofrenia. Após tentativas frustradas de tratamento com antipsicóticos atípicos e lítio, o tratamento com clozapina foi iniciado para controlar sintomas psicóticos. Alguns dias depois, surgiram febre e taquicardia sinusal persistente no eletrocardiograma (ECG). O hemograma revelou leucocitose e eosinofilia. Um ecocardiograma foi realizado e evidenciou aumento do ventrículo esquerdo, hipocinesia difusa e uma fração de ejeção diminuída. Um diagnóstico clínico de miocardite foi feito, e a clozapina foi suspensa, com melhora dos padrões ecocardiográficos e clínicos. A miocardite é um dos muitos potenciais efeitos adversos da clozapina e tem características semelhantes às produzidas pelo ajuste de dose normal da medicação, tornando-se um diagnóstico importante e perigosamente ignorado. Apesar de raros, os efeitos miocárdicos da clozapina podem ser bastante graves, levando ao óbito em alguns casos. Dessa forma, recomenda-se a realização de ECG pré e pós-tratamento e a suspensão da droga caso haja suspeita de acometimento cardíaco.

Clozapine is a useful drug in the treatment of patients with psychotic symptoms. However, severe adverse effects, such as myocarditis and agranulocytosis, can restrict its indications. We present the case of a 20-year-old male who developed fever and tachycardia a few days after initiating treatment with clozapine for a diagnosis of schizophrenia. After unsuccessful treatment attempts with atypical anti-psychotics and lithium, clozapine was initiated to control psychotic symptoms. A few days later, he presented with fever and persistent sinus tachycardia on electrocardiogram (ECG). Blood cell count revealed leukocytosis and eosinophilia. An echocardiogram was performed, which showed left ventricular enlargement, diffuse hypokinesis, and a decreased ejection fraction. A clinical diagnosis of myocarditis was made and clozapine was discontinued, with improvement of both echocardiographic and clinical features. Myocarditis is one of the many potential adverse effects of clozapine and has similar features with its normal dose titration, making it an important and dangerously overlooked diagnosis. Although rare, clozapine’s myocardial effects may be extremely severe, leading to death in some patients. Therefore, it is advisable to obtain an ECG before and after initiating treatment and to immediately discontinue the drug in suspected cases.

Trypanosoma cruzi: parasite antigens sequestered in heart interstitial dendritic cells are related to persisting myocarditis in benznidazole-treated mice

We investigated whether sequestered Trypanosoma cruzi antigens found in heart interstitial dendritic cells (IDCs) contribute to the residual myocarditis found in mice following treatment with benznidazole, a specific chemotherapeutic drug. IDCs are antigen-presenting cells that are MHC-II-receptor dependent. Swiss mice were divided into two experimental groups: the 1st group was infected with the Colombian strain of T. cruzi, which is resistant to treatment with benznidazole, and the 2nd group was infected with clone 21SF-C 3, which has a medium susceptibility to the drug. Treatment of the Colombian strain group started on the 120th day post-infection and for the 21SF-C3 strain group treatment was started on the 90th day. In both groups, treatment lasted for 90 days. The animals were sacrificed either 150 or 200 days post-treatment. The myocardium was analysed by immunohistochemistry using anti-MAC3, 33D1, CD11b and CD11c monoclonal antibodies for IDCs or anti-T. cruzi purified antibodies. Parasite antigens were expressed on the IDC membranes in both treated and untreated mice. Myocarditis subsided following treatment, evidenced by both histological and morphometrical evaluation. A reduction in the number of IDCs carrying T. cruzi antigens in the treated group indicates that the elimination of parasites influences antigen presentation with concomitant decreases in inflammation. There is a correlation between the presence of T. cruzi antigens in these cells and the chronic focal, residual myocarditis seen in treated mice.

Papel do óxido nítrico no desenvolvimento de lesões cardíacas na fase aguda da infecção experimental pelo Trypanosoma cruzi / Role of nitric oxide in the development of cardiac lesions during the acute phase of experimental infection by Trypanosoma cruzi

A doença de Chagas é causada pelo Trypanosoma cruzi e o coração é o órgão mais acometido. O óxido nítrico apresenta importante ação anti-Trypanosoma, porém, com pouca evidência de seu papel no mecanismo de lesão tecidual. O objetivo deste estudo foi analisar a contribuição do óxido nítrico no desenvolvimento da inflamação e da fibrose cardíaca na fase aguda da infecção experimental por cepas Y e Colombiana do Trypanosoma cruzi. A inflamação foi significativamente maior nos animais infectados pela cepa Colombiana, comparada com os infectados com a cepa Y, tanto nos animais C57BL/6 (3,98x1,87 por cento; p=0,004) quanto nos animais C57BL/6 deficientes na sintase do óxido nítrico induzível (3,99x2,4 por cento; p=0,013). O parasitismo cardíaco dos animais C57BL/6 deficientes na sintase do óxido nítrico induzível infectados pela cepa Colombiana foi significativamente maior que o destes mesmos animais infectados com a cepa Y (2,78x0,17 ninhos/mm²; p=0,004) assim como, os animais C57BL/6 infectados com a cepa Colombiana (2,78x1,33 ninhos/mm²; p=0,006) ou cepa Y (2,78x0,53 ninhos/mm²; p=0,005). Os dados reforçam o papel do óxido nítrico no controle do parasitismo e sugerem seu papel na proteção tecidual, controlando a inflamação e potencialmente diminuindo lesões cardíacas durante a fase aguda na doença de Chagas experimental.

Chagas disease is caused by Trypanosoma cruzi and the heart is the organ most affected. Nitric oxide has notable anti-Trypanosoma action, but with little evidence regarding its role in the mechanism for tissue injury. The objective of this study was to analyze the contribution of nitric oxide towards the development of inflammation and cardiac fibrosis during the acute phase of experimental infection by Y and Colombian strains of Trypanosoma cruzi. The inflammation was significantly more intense in animals infected with the Colombian strain, compared with those infected with the Y strain, both in C57BL/6 animals (3.98 vs 1.87 percent; p = 0.004) and in C57BL/6 animals deficient in inducible nitric oxide synthase (3.99 vs 2.4 percent; p = 0.013). The cardiac parasite load in inducible nitric oxide synthase-deficient C57BL/6 animals infected with the Colombian strain was significantly greater than in those infected with the Y strain (2.78 vs. 0.17 nests/mm²; p = 0.004), and also significantly greater than in the C57BL/6 infected with both the Colombian strain (2.78 vs 1.33 nests/mm²; p = 0.006) and Y strains (2.78 vs 0.53 nests/mm²; p = 0.005). The data confirm that nitric oxide has a role in parasite load control and suggest that it has a role in tissue protection, through controlling inflammation and potentially reducing cardiac lesions during the acute phase of Chagas disease.

Sudden death due to cardiac toxoplasmosis.

The recognition of cardiac toxoplasmosis has increased in patients with acquired immunodeficiency syndrome. The functional consequences of toxoplasmosis of heart vary considerably depending on the intensity of inflammatory reaction, the extent of involvement of myocardial muscle fibers by necrosis and intramyocytic presence of tachyzoites of Toxoplasma gondii. This report describes a case of toxoplasma myocarditis that lead to fatal cardiac arrest. To the best of our knowledge, this is the first reported case of cardiac toxoplasmosis in the Indian literature, which has manifested as sudden death.

Reinfections with strains of Trypanosoma cruzi, of different biodemes as a factor of aggravation of myocarditis and myositis in mice

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.

Estudo comparativo das avaliações clínica e ecocardiográfica Doppler na evolução das lesões valvares em crianças e adolescentes portadores de febre reumática / Comparative study of clinical and Doppler echocardiographic evaluations of the progression of valve diseases in children and adolescents with rheumatic fever

OBJETIVO: Comparar os exames clínico e ecocardiográfico Doppler na avaliação das lesões valvares em crianças e adolescentes com febre reumática, bem como investigar a evolução da doença segundo essas avaliações. MÉTODOS: Trata-se de estudo observacional longitudinal que englobou 258 crianças e adolescentes com diagnóstico de febre reumática, baseado nos critérios de Jones. Os pacientes foram acompanhados durante o período de 2 a 15 anos. A presença e a quantificação das lesões valvares nas fases aguda e crônica foram determinadas pelas avaliações clínica e ecocardiográfica Doppler. Utilizou-se a estatística de Kappa para estimar a concordância entre as avaliações, e as evoluções clínica e ecocardiográfica Doppler da cardite e valvite, respectivamente, foram comparadas pelo teste do qui-quadrado ou de Fisher, p < 0,05. RESULTADOS: Dos 109 pacientes submetidos à avaliação ecocardiográfica Doppler na fase aguda, 31 não apresentavam clínica de cardite, mas 17 (54,8 por cento) deles mostravam lesão valvar ao ecocardiograma Doppler (valvite subclínica). Na fase crônica, 153 dos 258 tinham exame cardiovascular normal, mas 85 (55,5 por cento) desses mostravam lesão valvar ao ecocardiograma Doppler (valvopatia crônica subclínica). A involução das lesões valvares segundo a avaliação ecocardiográfica Doppler foi menos freqüente, ocorrendo em 10 (25,0 por cento) dos pacientes com valvite leve e em apenas 1 (2,5 por cento) daqueles com valvite moderada, e em nenhum com valvite grave. CONCLUSAO: A identificação de lesões valvares na febre reumática é maior se a avaliação clínica for acrescida do exame ecocardiográfico Doppler, que também mostra menor índice de regressão das lesões valvares. O diagnóstico de valvite e valvopatia subclínicas tem implicação quanto às profilaxias secundária da febre reumática e da endocardite.