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1.
Virchows Arch ; 475(3): 279-301, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297595

RESUMO

Myocarditis is an inflammatory disease of the myocardium, which may occur in isolation or as part of systemic infectious/immune/autoimmune conditions, characterized by vast aetiologic, clinical and histopathologic heterogeneity. The broad spectrum of myocarditis can be categorized according to the prevalent histopathologic pattern including lymphocytic, lympho-histiocytic, eosinophilic and neutrophilic forms, giant cell myocarditis and myocarditis with granulomata. Diverse histopathologic substrates generally reflect different aetiologies and pathogenetic mechanisms and may be critical to clinical decision-making. Active vasculitis, when present, completes the inflammatory spectrum. Unfortunately, the correlation of histopathologic patterns, clinical presentation and disease course in myocarditis is still largely unresolved, due to limited availability of bioptic samples at specific stages of disease and impracticality of serial sampling. We here review the elements supporting an aetiology-driven diagnostic work-up in myocarditis, emphasizing the importance of integrating pathologic studies with clinical features and information derived from multimodality imaging. Furthermore, we explore myocardial inflammation in genetic cardiomyopathies, its role in driving clinical variability and the potential of transcriptomic and proteomic analysis in our understanding of these complex interrelations.


Assuntos
Miocardite/etiologia , Miocardite/metabolismo , Miocardite/patologia , Biópsia , Eosinófilos/patologia , Humanos , Miocárdio/patologia , Proteômica
2.
Phytomedicine ; 58: 152768, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31005721

RESUMO

BACKGROUND: Cigarette smoking is the leading cause for the initiation and development of cardiovascular disease (CVD). Oxidative stress and inflammatory responses play important roles in the pathophysiological processes of smoking-induced cardiac injury. (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, which is made from Camellia sinensis leaves, has been reported to possess potent anti-oxidant property. PURPOSE: This study aims to investigate whether the antioxidant EGCG could alleviate cigarette smoke medium (CSM)-induced inflammation in human AC16 cardiomyocytes in vitro. METHODS: Human AC16 cardiomyocytes were pre-treated with EGCG, N-acetyl-L-cysteine (NAC), or specific inhibitors for 30 min before 4% CSM was added. Supernatant was collected for determination of interleukin (IL)-8 by ELISA and cells were collected for flow cytometry, biochemical assays and Western blot analysis. RESULTS: EGCG treatment significantly attenuated CSM-induced oxidative stress as evidenced by reducing intracellular and mitochondrial reactive oxygen species (ROS) generations and preventing antioxidant depletion. EGCG treatment reduced CSM-induced inflammatory chemokine interleukin (IL)-8 productions in the supernatant via the inhibition of ERK1/2, p38 MAPK and NF-κB pathways. EGCG treatment further inhibited CSM-induced cell apoptosis. CONCLUSION: Taken together, EGCG protected against CSM-induced inflammation and cell apoptosis by attenuating oxidative stress via inhibiting ERK1/2, p38 MAPK, and NF-κB activation in AC16 cardiomyocytes. These findings suggest that EGCG with its antioxidant, anti-inflammatory and anti-apoptotic properties may act as a promising cardioprotective agent against ROS-mediated cardiac injury.


Assuntos
Catequina/análogos & derivados , Miocardite/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , NF-kappa B/metabolismo , Fumar/efeitos adversos , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Catequina/farmacologia , Linhagem Celular , Humanos , Interleucina-8/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miocardite/induzido quimicamente , Miocardite/patologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Int. j. cardiovasc. sci. (Impr.) ; 32(2): 177-189, mar.-abr. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-988239

RESUMO

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


Assuntos
Humanos , Masculino , Feminino , Imagem por Ressonância Magnética/métodos , Amiloidose/diagnóstico , Amiloidose/terapia , Prognóstico , Diagnóstico por Imagem/métodos , Ecocardiografia/métodos , Biomarcadores , Cadeias Leves de Imunoglobulina , Meios de Contraste , Placa Amiloide/diagnóstico por imagem , Eletrocardiografia/métodos , Gadolínio , Ventrículos do Coração , Miocardite/patologia
4.
Int J Mol Sci ; 20(2)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669615

RESUMO

Theiler's murine encephalomyelitis virus (TMEV), a naturally occurring, enteric pathogen of mice is a Cardiovirus of the Picornaviridae family. Low neurovirulent TMEV strains such as BeAn cause a severe demyelinating disease in susceptible SJL mice following intracerebral infection. Furthermore, TMEV infections of C57BL/6 mice cause acute polioencephalitis initiating a process of epileptogenesis that results in spontaneous recurrent epileptic seizures in approximately 50% of affected mice. Moreover, C3H mice develop cardiac lesions after an intraperitoneal high-dose application of TMEV. Consequently, TMEV-induced diseases are widely used as animal models for multiple sclerosis, epilepsy, and myocarditis. The present review summarizes morphological lesions and pathogenic mechanisms triggered by TMEV with a special focus on the development of hippocampal degeneration and seizures in C57BL/6 mice as well as demyelination in the spinal cord in SJL mice. Furthermore, a detailed description of innate and adaptive immune responses is given. TMEV studies provide novel insights into the complexity of organ- and mouse strain-specific immunopathology and help to identify factors critical for virus persistence.


Assuntos
Doenças dos Animais/virologia , Infecções por Cardiovirus/veterinária , Theilovirus/fisiologia , Imunidade Adaptativa , Doenças dos Animais/imunologia , Doenças dos Animais/patologia , Doenças dos Animais/transmissão , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Humanos , Imunidade Inata , Camundongos , Esclerose Múltipla/etiologia , Esclerose Múltipla/patologia , Miocardite/etiologia , Miocardite/patologia , Miocardite/fisiopatologia , Convulsões/etiologia , Convulsões/patologia , Convulsões/fisiopatologia , Tropismo Viral
5.
Basic Res Cardiol ; 114(2): 11, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30673858

RESUMO

Coxsackieviruses of group B (CVB) are well-known causes of acute and chronic myocarditis. Chronic myocarditis can evolve into dilated cardiomyopathy (DCM) characterized by fibrosis and cardiac remodeling. Interleukin-1ß (IL-1ß) plays a decisive role in the induction of the inflammatory response as a consequence of viral replication. In this study, we analyzed the effects of IL-1ß neutralization on the transition of acute to chronic myocarditis in a mouse model of CVB3 myocarditis. Mice were treated with an anti-murine IL-1ß antibody as a surrogate for Canakinumab at different time points post CVB3 infection. Treatment was performed in the early phase (day 1-14 pi, day 3-14 pi) or at a later stage of myocarditis (day 14-28 pi). Subsequently, the hearts were examined histologically, immunohistochemically and by molecular biology. A significant reduction of viral replication, cardiac damage and inflammation was found after administration of the antibody in the early phase and in the later phase of infection. Furthermore, less collagen I deposition and a considerable reduction of fibrosis were found in antibody-treated mice. Using microarray analysis, a significant upregulation of various extracellular matrix and fibrosis-associated molecules was found in CVB3-infected mice, including TGF-ß, TIMP-1 and MMP12, as well as diverse matricellular proteins, whereas, these molecules were significantly downregulated in all IL-1ß antibody-treated infected mice. Neutralization of IL-1ß at different stages of enteroviral infection prevents the development of chronic viral myocarditis by reducing inflammation, interstitial fibrosis and adverse cardiac remodeling. These findings are relevant for the treatment of patients with acute and chronic myocarditis.


Assuntos
Interleucina-1beta/antagonistas & inibidores , Miocardite/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Anticorpos Monoclonais/farmacologia , Doença Crônica , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/patologia , Enterovirus Humano B , Camundongos , Miocardite/metabolismo , Miocardite/virologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
6.
Intern Med ; 58(9): 1283-1286, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30568151

RESUMO

The natural course of myocardial calcification is unclear. We herein report a case of massive biventricular myocardial calcification associated with fulminant myocarditis and present its natural course. The patient was a 15-year-old boy. Massive calcification was detected in both ventricles on computed tomography several months after left ventricular assist device placement. Although the calcification gradually regressed, the patient's cardiac function did not recover, and he underwent heart transplantation after a waiting period of 3 years. A histological examination revealed severe fibrosis in both ventricles of the original heart. Myocardial calcification might suggest severe myocardial inflammation and injury in cases of fulminant myocarditis.


Assuntos
Coração Auxiliar , Miocardite/complicações , Calcificação Vascular/complicações , Adolescente , Transplante de Coração , Ventrículos do Coração/patologia , Humanos , Masculino , Miocardite/patologia , Miocardite/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Calcificação Vascular/patologia
7.
Intern Med ; 58(8): 1111-1118, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30568130

RESUMO

A 47-year-old man with ulcerative colitis was transferred to our hospital due to progressive dyspnea. Electrocardiography on admission showed ST elevation in leads II, III, aVF, and V5-V6. Coronary angiography revealed no remarkable coronary stenosis, and left ventriculography showed a depressed left ventricular ejection fraction (EF) of 23%. Although the patient received percutaneous cardiopulmonary support, his EF progressively decreased (7-15%), and both ventricular tachycardia (VT) and high-degree atrial-ventricular block occurred. An endomyocardial biopsy showed eosinophilic infiltration in the myocardium. Steroid therapy improved the patient's EF. However, his severe inferior wall hypokinesis and non-sustained VT remained after the abovementioned treatment.


Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Miocardite/tratamento farmacológico , Intervenção Coronária Percutânea/métodos , Esteroides/uso terapêutico , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/etiologia , Eosinofilia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
8.
Int J Cardiol ; 275: 114-119, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30384979

RESUMO

BACKGROUND: Myocarditis may be self-limited but has been identified as an important contributor to downstream cardiomyopathy. Aldosterone mediates myocardial damage in various conditions, but has not been considered specifically as a therapeutic target for inflammatory damage in acute myocarditis. We sought to demonstrate local aldosterone synthesis in human myocardium affected by acute myocarditis. METHODS: We evaluated myocardial samples obtained via endomyocardial biopsy (EMB) for expression of CYP11B2, the final and key enzyme for aldosterone synthesis, from patients with acute myocarditis and from stable heart transplant recipients with no evidence of rejection as negative controls. Excised adrenal glands from patients with aldosterone-secreting adenomas were used as positive controls. An experienced cardiovascular pathologist blinded to clinical information rated CYP11B2 stains as negative, positive, or borderline, also recording location of any CYP11B2-positivity. RESULTS: Sixteen patients' EMB samples showing definite acute myocarditis were identified (50% female). CYP11B2 was positive in 13/16 cases (81%), typically showing diffuse intracardiomyocyte cytoplasmic staining, vs. 2/16 borderline stains in transplant controls (p < 0.001 myocarditis vs. negative controls). All 3 adrenalectomy samples stained positive for CYP11B2 (diffuse intracellular staining). Importantly, no myocarditis or transplant patients were on aldosterone antagonist therapy at the time of biopsy. CONCLUSIONS: In this proof-of-concept study, myocardium from patients with acute myocarditis demonstrates evidence and high prevalence of local aldosterone synthesis by immunohistochemistry that showed high accuracy, specificity, and sensitivity. Aldosterone warrants consideration as a specific target for therapy in patients with myocardial damage due to inflammation towards strategies that reduce downstream complications.


Assuntos
Aldosterona/biossíntese , Miocardite/metabolismo , Miocárdio/metabolismo , Doença Aguda , Adulto , Biomarcadores/metabolismo , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Miocárdio/patologia
9.
Int J Biol Macromol ; 126: 179-186, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30586589

RESUMO

Inflammation plays a crucial role in regulating cardiomyopathy and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that Astragalus polysaccharide (AP) from Astragalus Melittin could inhabit inflammatory gene expression under a variety of pathological conditions. However, the functional roles of AP in CVB3-induced VM still remain unknown. Here, we found that AP significantly enhanced survival for CVB3-induced mice. AP protected the mice against CVB3-induced myocardial injuries characterized by the increased body weight and depressed serum level of creatine kinase-MB (CK-MB), aspartate transaminases (AST) and lactate dehydrogenase (LDH), enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). At the pathological level, AP ameliorated the mice against CVB3-induced myocardial damage, dilated cardiomyopathy and chronic myocardial fibrosis. We subsequently found that AP significantly suppressed CVB3-induced expression of inflammation marker (IL-1ß, IL-6, TNF-α, INF-γ and MCP-1) in heart. Furthermore, we confirmed that AP suppressed the CVB3-induced expression of TLR-4 and phosphorylated NF-κB p65 in heart. Taken together, the data suggest that AP protects against CVB3-induced myocardial damage and inflammation, which may partly attribute to the regulation of TLR-4/NF-κB p65 signal pathway, moreover, suppressive effect of AP on CVB3-induced activation of TLR-4/NF-κB p65 signal was TNF-α-independent.


Assuntos
Astrágalo (Planta)/química , Enterovirus/fisiologia , Inflamação/metabolismo , Inflamação/patologia , Miocardite/virologia , Polissacarídeos/farmacologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Cardiomiopatia Dilatada/patologia , Enterovirus/efeitos dos fármacos , Fibrose , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos C57BL , Miocardite/patologia , Miocárdio/patologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
10.
BMC Infect Dis ; 18(1): 705, 2018 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-30594148

RESUMO

BACKGROUND: Spotted fever group of rickettsial infections are emerging in Sri Lanka. We describe a patient with rapidly progressing ARDS and myocarditis secondary to spotted fever caused by Rickettsia conorii. ARDS and myocarditis are rare complications of Rickettsia conorii infections and only a few cases are reported to date. CASE PRESENTATION: A 53 years old manual worker presented with fever for 5 days and a skin rash. He was in circulatory failure on admission and developed severe hypoxaemia with gross changes in chest radiograph by next day requiring assisted ventilation. He had myocarditis causing left ventricular failure and acute respiratory distress syndrome. He was confirmed to have spotted fever rickettsial infection with rising titre of indirect immunofluorescence antibodies to Ricketssia conorii and made a complete recovery with appropriate antibiotic therapy and supportive care. CONCLUSION: Rickettsial infections can present with diverse manifestations. Even the patients with severe organ involvements such as myocarditis and ARDS can be completely cured if timely identified and treated.


Assuntos
Febre Botonosa/complicações , Miocardite/microbiologia , Síndrome do Desconforto Respiratório do Adulto/microbiologia , Febre Botonosa/diagnóstico , Febre Botonosa/patologia , Febre/complicações , Febre/diagnóstico , Febre/microbiologia , Febre/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Miocardite/patologia , Radiografia Torácica , Síndrome do Desconforto Respiratório do Adulto/diagnóstico , Síndrome do Desconforto Respiratório do Adulto/patologia , Rickettsia conorii/isolamento & purificação , Sri Lanka
11.
Oxid Med Cell Longev ; 2018: 7385639, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30364017

RESUMO

Suramin (Sur) acts as an ecto-NTPDase inhibitor in Trypanosoma cruzi and a P2-purinoceptor antagonist in mammalian cells. Although the potent antitrypanosomal effect of Sur has been shown in vitro, limited evidence in vivo suggests that this drug can be dangerous to T. cruzi-infected hosts. Therefore, we investigated the dose-dependent effect of Sur-based chemotherapy in a murine model of Chagas disease. Seventy uninfected and T. cruzi-infected male C57BL/6 mice were randomized into five groups: SAL = uninfected; INF = infected; SR5, SR10, and SR20 = infected treated with 5, 10, or 20 mg/kg Sur. In addition to its effect on blood and heart parasitism, the impact of Sur-based chemotherapy on leucocytes myocardial infiltration, cytokine levels, antioxidant defenses, reactive tissue damage, and mortality was analyzed. Our results indicated that animals treated with 10 and 20 mg/kg Sur were disproportionally susceptible to T. cruzi, exhibiting increased parasitemia and cardiac parasitism (amastigote nests and parasite load (T. cruzi DNA)), intense protein, lipid and DNA oxidation, marked myocarditis, and mortality. Animals treated with Sur also exhibited reduced levels of nonprotein antioxidants. However, the upregulation of catalase, superoxide dismutase, and glutathione-S-transferase was insufficient to counteract reactive tissue damage and pathological myocardial remodeling. It is still poorly understood whether Sur exerts a negative impact on the purinergic signaling of T. cruzi-infected host cells. However, our findings clearly demonstrated that through enhanced parasitism, inflammation, and reactive tissue damage, Sur-based chemotherapy contributes to aggravating myocarditis and increasing mortality rates in T. cruzi-infected mice, contradicting the supposed relevance attributed to this drug for the treatment of Chagas disease.


Assuntos
Doença de Chagas/patologia , Doença de Chagas/parasitologia , Inflamação/patologia , Miocardite/induzido quimicamente , Miocardite/parasitologia , Antagonistas Purinérgicos/efeitos adversos , Suramina/efeitos adversos , Trypanosoma cruzi/fisiologia , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Doença de Chagas/complicações , Inflamação/complicações , Masculino , Camundongos Endogâmicos C57BL , Miocardite/complicações , Miocardite/patologia , Miocárdio/patologia , Óxido Nítrico/metabolismo , Estresse Oxidativo
12.
J Infect Public Health ; 11(5): 698-701, 2018 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29853266

RESUMO

BACKGROUND: Myocarditis is an inflammatory condition located mainly in the myocardium. It is caused by a variety of bacterial and viral infections. Influenza is one of the most common relevant viruses that cause myocarditis. OBJECTIVES: We attempted to share our experiences about clinical and laboratory findings, cardiac evaluation, and treatment of children with influenza myocarditis. METHODS: This retrospective study was performed by the Department of Pediatric Infectious Diseases at the Faculty of Medicine, Hacettepe University in Turkey. The medical records of patients diagnosed with myocarditis associated with an influenza infection between January 2014 and January 2017 were systematically reviewed. RESULTS: Vaccination seems likely to be an important protection strategy for both influenza infections and complications.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/complicações , Influenza Humana/prevenção & controle , Miocardite/diagnóstico , Miocardite/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Hospitais Universitários , Humanos , Lactente , Vacinas contra Influenza/imunologia , Masculino , Miocardite/epidemiologia , Miocardite/prevenção & controle , Estudos Retrospectivos , Turquia/epidemiologia
13.
BMJ Case Rep ; 20182018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735489

RESUMO

A 65-year-old lady and a 69-year-old gentleman, both with a background history of adult-onset asthma, presented with clinical features of heart failure (HF). High-sensitivity cardiac troponin T and eosinophils were significantly raised, along with poor left ventricular (LV) systolic function on cardiac imaging. Endocardial and skin biopsy (in cases 1 and 2, respectively) showed eosinophilic infiltration. This in combination with the clinical features confirmed the diagnosis of eosinophilic myocarditis (EM) secondary to eosinophilic granulomatosis with polyangiitis in case 1. Both cases were managed with high-dose intravenous corticosteroids and conventional HF medication. Case 1 successfully responded clinically with improvement in LV systolic function. Case 2 required further immunosuppressive therapy (rituximab) and cardiac resynchronisation therapy, but eventually died of septic shock secondary to immunosuppressives. Our cases highlight the importance of early diagnosis and treatment of EM and ongoing monitoring of patients on immunosuppressive therapy.


Assuntos
Cardiomiopatias/complicações , Síndrome de Churg-Strauss/complicações , Eosinófilos/citologia , Insuficiência Cardíaca/complicações , Miocardite/patologia , Administração Intravenosa , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Síndrome de Churg-Strauss/diagnóstico por imagem , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/fisiopatologia , Diagnóstico Diferencial , Eosinófilos/patologia , Evolução Fatal , Feminino , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/patologia , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Miocardite/tratamento farmacológico , Miocardite/etiologia , Miocardite/imunologia , Doenças Raras , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Resultado do Tratamento
14.
Biochim Biophys Acta Mol Basis Dis ; 1864(8): 2579-2589, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29730342

RESUMO

Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac metabolic rewiring and if this process is driven by local inflammation. Transcriptomic analysis of cardiac biopsies from myocarditis patients and a mouse model of VM revealed prominent reductions in the expression of a multitude of genes involved in mitochondrial oxidative energy metabolism. In mice, this coincided with reductions in high-energy phosphate and NAD levels, as determined by Imaging Mass Spectrometry, as well as marked decreases in the activity, protein abundance and mRNA levels of various enzymes and key regulators of cardiac oxidative metabolism. Indicative of fulminant cardiac inflammation, NF-κB signalling and inflammatory cytokine expression were potently induced in the heart during human and mouse VM. In cultured cardiomyocytes, cytokine-mediated NF-κB activation impaired cardiomyocyte oxidative gene expression, likely by interfering with the PGC-1 (peroxisome proliferator-activated receptor (PPAR)-γ co-activator) signalling network, the key regulatory pathway controlling cardiomyocyte oxidative metabolism. In conclusion, we provide evidence that acute VM is associated with extensive cardiac metabolic remodelling and our data support a mechanism whereby cytokines secreted primarily from infiltrating leukocytes activate NF-κB signalling in cardiomyocytes thereby inhibiting the transcriptional activity of the PGC-1 network and consequently modulating myocardial energy metabolism.


Assuntos
Infecções por Coxsackievirus/metabolismo , Enterovirus Humano B , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Proteínas Musculares/metabolismo , Miocardite/metabolismo , NF-kappa B/metabolismo , Doença Aguda , Animais , Infecções por Coxsackievirus/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Miocardite/patologia , Miocardite/virologia , PPAR gama/metabolismo , Fatores de Transcrição/metabolismo
15.
Intern Med ; 57(18): 2675-2679, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29709930

RESUMO

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare type of systemic vasculitis. Cardiac involvement is the main cause of death in patients with this disease. We herein report a case of congestive heart failure in a patient with EGPA. Neither 67Ga scintigraphy nor cardiac magnetic resonance imaging detected inflammation of the myocardium; however, myocardial biopsy revealed numerous infiltrating inflammatory cells, thereby fulfilling the criteria of inflammatory dilated cardiomyopathy. We improved the left ventricular systolic function by increasing the patient's prednisolone dosage. This case shows that in some cases the detection myocardial inflammation - which allows for appropriate therapy - may only be achieved by myocardial biopsy.


Assuntos
Cardiomiopatia Dilatada/etiologia , Granulomatose com Poliangiite/complicações , Miocardite/etiologia , Idoso , Biópsia , Cateterismo Cardíaco , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/patologia , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Miocardite/diagnóstico , Miocardite/tratamento farmacológico , Miocardite/patologia , Miocárdio/patologia , Prednisolona/uso terapêutico , Função Ventricular Esquerda/fisiologia
16.
Eur J Radiol ; 102: 9-14, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29685551

RESUMO

OBJECTIVES: The aim of this study was to investigate whether a flip angle adaptation, which is known to improve SNR and CNR in post contrast SSFP imaging, improves the precision and reproducibility of Feature Tracking (FT) derived strain assessments in post contrast bSSFP imaging. METHODS AND RESULTS: At 1.5T balanced SSFP midventricular short axis cine images were acquired with various flip angles (FA) before (FA = 50°) and 5 min after (FAs = 50°, 80°, 90°, 100°) injection of double dose Gadobutrol. FT derived systolic circumferential strain was then calculated for all pre- and post-contrast images, the intra- and inter-observer variability of strain measurements was assessed. FT derived midventricular peak systolic circumferential strain (PSCS) derived from unadapted (FA: 50°) contrast enhanced bSSFP images was significantly lower than strain derived from unenhanced bSSFP images (-16.45 ±â€¯5.1% vs -20.57 ±â€¯6.2%; p < 0.001) and showed low agreement (mean difference of -4.13 ±â€¯2.4, 95% CI:-5.3 to -3) in all 20 subjects. After adaption of the flip angle (FA: 100°), agreement between strain derived from unenhanced and adapted contrast enhanced bSSFP images (-20.57 ±â€¯6%) was strong (0.01 ±â€¯0.9, CI:-0.43 to 0.41). In comparison to intra- and interobserver variability of strain derived from unenhanced images (intra 2.9%; inter: 3.9%), strain measurements derived from adapted contrast enhanced images (FA: 100°) showed a slightly lower variability (intra: 2.5%; inter: 2.3%). CONCLUSION: If flip angle adaptation is performed, FT based strain analysis may be performed on contrast enhanced bSSFP cine images without loss of precision and accuracy.


Assuntos
Angiografia por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Adulto , Cardiomiopatias/patologia , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Angiografia por Ressonância Magnética/normas , Imagem Cinética por Ressonância Magnética/normas , Masculino , Miocardite/patologia , Variações Dependentes do Observador , Compostos Organometálicos , Estudos Prospectivos , Reprodutibilidade dos Testes , Volume Sistólico/fisiologia , Sístole , Função Ventricular Esquerda/fisiologia , Adulto Jovem
18.
Forensic Sci Med Pathol ; 14(2): 229-235, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29556967

RESUMO

"Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.


Assuntos
Analgésicos Opioides/efeitos adversos , Valva Aórtica/patologia , Codeína/análogos & derivados , Endocardite/induzido quimicamente , Miocardite/induzido quimicamente , Drogas Ilícitas/efeitos adversos , Adulto , Cardiomiopatia Hipertrófica/induzido quimicamente , Cardiomiopatia Hipertrófica/patologia , Codeína/efeitos adversos , Morte Súbita/etiologia , Endocardite/patologia , Insuficiência Cardíaca/induzido quimicamente , Humanos , Masculino , Miocardite/patologia , Transtornos Relacionados ao Uso de Opioides/complicações , Úlcera Cutânea/induzido quimicamente , Úlcera Cutânea/patologia
19.
Zool Res ; 39(1): 52-57, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29511145

RESUMO

Globally, coxsackievirus B4 (CV-B4) has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system (CNS) complications, which remain poorly studied and understood. In the present study, we established an Institute for Cancer Research (ICR) mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. In addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-γ and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.


Assuntos
Edema Encefálico/virologia , Infecções por Coxsackievirus/complicações , Modelos Animais de Doenças , Enterovirus Humano B , Miocardite/virologia , Animais , Edema Encefálico/etiologia , Edema Encefálico/patologia , Infecções por Coxsackievirus/patologia , Citocinas/sangue , Camundongos , Camundongos Endogâmicos ICR , Miocardite/etiologia , Miocardite/patologia , Neurônios/patologia , Carga Viral
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