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1.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1118-1119: 148-156, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31039544

RESUMO

A simple, rapid and sensitive HPLC-MS/MS method for simultaneous determination of 4 of amino acids, guanidinoacetic acid, S-adenosylmethionine and S-adenosylhomocysteine in human plasma was developed and validated. The method requires no tedious sample preparation, derivatization reagents or ion-pairing reagents. Samples were prepared by combining plasma with a chilled mixture of acetonitrile (ACN) and water, followed by centrifugation and diluting the supernatant with 2 volumes of water. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization (ESI). In the assay, all the analytes showed good linearity over the investigated concentration range (r > 0.99). The accuracy expressed in relative error (RE) was between -5.0% and 13.2%, and the precision expressed in coefficient of variation (CV) ranged from 0.6% to 14.7%. In the two spiked levels (low and high), the averaged recoveries of analytes were between 45.0% and 110.9% and the recovery of internal standard was 92.0%. This method was successfully applied to studying the concentration changes of endogenous creatine (Cr) synthesis precursors in the plasma of children with viral myocarditis after intravenous administration of phosphocreatine (PCr).


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Creatina/sangue , Miocardite/sangue , Espectrometria de Massas em Tandem/métodos , Viroses/sangue , Aminoácidos/sangue , Aminoácidos/química , Aminoácidos/metabolismo , Criança , Creatina/química , Creatina/metabolismo , Humanos , Modelos Lineares , Miocardite/diagnóstico , Miocardite/virologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Viroses/diagnóstico , Viroses/virologia
2.
PLoS Pathog ; 15(4): e1007674, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30958867

RESUMO

Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. Using IFIT locus knockout (IFITKO) cardiomyocytes we show that, in the absence of the IFIT locus, viral replication is dramatically increased, indicating that constitutive IFIT expression suppresses CVB replication in this cell type. IFNß pre-treatment strongly suppresses CVB3 replication in wild type (wt) cardiomyocytes, but not in IFITKO cardiomyocytes, indicating that other interferon-stimulated genes (ISGs) cannot compensate for the loss of IFITs in this cell type. Thus, in isolated wt cardiomyocytes, the anti-CVB3 activity of IFITs is biphasic, being required for protection both before and after T1IFN signaling. These in vitro findings are replicated in vivo. Using novel IFITKO mice we demonstrate accelerated CVB3 replication in pancreas, liver and heart in the hours following infection. This early increase in virus load in IFITKO animals accelerates the induction of other ISGs in several tissues, enhancing virus clearance from some tissues, indicating that-in contrast to cardiomyocytes-other ISGs can offset the loss of IFITs from those cell types. In contrast, CVB3 persists in IFITKO hearts, and myocarditis occurs. Thus, cardiomyocytes have a specific, biphasic, and near-absolute requirement for IFITs to control CVB infection.


Assuntos
Proteínas de Transporte/fisiologia , Infecções por Coxsackievirus/prevenção & controle , Enterovirus Humano B/patogenicidade , Miocardite/prevenção & controle , Miócitos Cardíacos/enzimologia , Animais , Células Cultivadas , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocardite/metabolismo , Miocardite/virologia , Replicação Viral
3.
Microb Cell Fact ; 18(1): 66, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947747

RESUMO

BACKGROUND: Oral vaccine is highly desired for infectious disease which is caused by pathogens infection through the mucosal surface. The design of suitable vaccine delivery system is ongoing for the antigen protection from the harsh gastric environment and target to the Peyer's patches to induce sufficient mucosal immune responses. Among various potential delivery systems, bacterial inclusion bodies have been widely used as delivery systems in the field of nanobiomedicine. However, a large number of heterologous complex proteins could be difficult to propagate in E. coli and fusion partners are often used to enhance target protein expression. As a safety concern the fusion protein need to be removed from the target protein to get tag-free protein, especially for the production of protein antigen in vaccinology. Until now, there is no report on how to remove fusion tag from inclusion body particles in vitro and in vivo. Coxsackievirus B3 (CVB3) is a leading causative agent of viral myocarditis and orally protein vaccine is high desired for CVB3-induced myocarditis. In this context, we explored a tag-free VP1 inclusion body nanoparticles production protocol though a truncated Ssp DnaX mini-intein spontaneous C-cleavage in vivo and also exploited the VP1 inclusion bodies as an oral protein nanoparticle vaccine to protect mice against CVB3-induced myocarditis. RESULTS: We successfully produced the tag-free VP1 inclusion body nanoparticle antigen of CVB3 and orally administrated to mice. The results showed that the tag-free VP1 inclusion body nanoparticles as an effective antigen delivery system targeting to the Peyer's patches had the capacity to induce mucosal immunity as well as to efficiently protect mice from CVB3 induce myocarditis without any adjuvant. Then, we proposed the use of VP1 inclusion body nanoparticles as good candidate for oral vaccine to against CVB3-induced myocarditis. CONCLUSIONS: Our tag-free inclusion body nanoparticles production procedure is easy and low cost and may have universal applicability to produce a variety of tag-free inclusion body nanoparticles for oral vaccine.


Assuntos
Proteínas do Capsídeo/imunologia , Enterovirus Humano B/imunologia , Miocardite/prevenção & controle , Vacinas Virais/imunologia , Administração Oral , Animais , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/administração & dosagem , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Enterovirus Humano B/química , Enterovirus Humano B/genética , Humanos , Imunidade nas Mucosas , Inteínas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/imunologia , Miocardite/virologia , Nanopartículas/química , Vacinas Virais/administração & dosagem , Vacinas Virais/química , Vacinas Virais/genética
4.
J Fish Dis ; 42(6): 825-833, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919979

RESUMO

Losses due to cardiomyopathy syndrome (CMS) keep increasing in salmon-producing countries in the North-Atlantic. Recently, Piscine myocarditis virus (PMCV) has been detected in post-smolts shortly after sea-transfer, indicating a possible carry-over from the hatcheries. In addition, there are reports of prevalences of PMCV as high as 70%-90% in certain groups of broodfish, and a recent outbreak of CMS in the Faroe Islands has been linked to the importation of eggs from a CMS-endemic area. Thus, there is a need to investigate whether PMCV can be transmitted vertically from infected broodstock to their progeny. In the present study, samples from eggs, larvae, fingerlings and presmolt originating from PMCV-positive broodstock from two commercial Atlantic salmon producers were tested for PMCV. The prevalence of PMCV in the broodstock was 98% in the hearts, 69% in the roe and 59% in the milt. Piscine myocarditis virus was detected in all stages of the progeny until and including the 40 g stage. Piscine myocarditis virus was also detected in presmolt sampled for tissue tropism. This provides farmers with several options for minimizing the risk of transfer of PMCV from broodstock to progeny, including screening of broodstock and aiming to use only those that are negative for PMCV or have low levels of virus.


Assuntos
Doenças dos Peixes/transmissão , Transmissão Vertical de Doença Infecciosa/veterinária , Miocardite/veterinária , Infecções por Vírus de RNA/veterinária , Salmo salar/virologia , Animais , Aquicultura , Estudos de Coortes , Dinamarca , Doenças dos Peixes/virologia , Larva/virologia , Estágios do Ciclo de Vida , Miocardite/virologia , Óvulo/virologia , Infecções por Vírus de RNA/transmissão , Salmo salar/crescimento & desenvolvimento , Totiviridae/fisiologia , Carga Viral
5.
Pharmacology ; 103(3-4): 136-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30602153

RESUMO

To investigate the effect of Tanshinone IIA (TSA) on viral myocarditis (VMC). VMC animal model was established using BALB/c mice by intraperitoneally injecting Coxsackie virus B3 (CVB3). The mice were randomly divided into control group, model group, and TSA group. We detected the survival rate, the heart weight to body weight (HW/BW) ratio and hemodynamic and cardiac function parameters. The pathological features of VMC were measured through H&E staining. The expression of serum enzyme, inflammatory cytokines, and T helper (Th)1/Th2 markers was also investigated. TSA remarkably alleviated CVB3-caused myocardial injury, decreased the HW/BW ratio, and improved survival rate. TSA obviously improved hemodynamic parameters and reversed the damage to the heart pump function. Furthermore, the serum levels of lactate dehydrogenase, creatine kinase, and Th1 cytokines in the TSA group were significantly lower than those in the VMC group, and TSA treatment significantly improved the pathological condition. The interferon-gamma (IFN-γ) and interleukin-2 (IL-2) levels in VMC model group was higher than control group, and lower levels of IL-4 and IL-10 were identified. However, TSA treatment elevated IL-4 and IL-10 levels and decreased IFN-γ and IL-2 levels. TSA could effectively protect the myocardium against CVB3-induced myocarditis by the inhibition of inflammation and modulation Th1/Th2 balance in mice.


Assuntos
Anti-Inflamatórios/farmacologia , Infecções por Coxsackievirus/prevenção & controle , Diterpenos de Abietano/farmacologia , Enterovirus/patogenicidade , Miocardite/prevenção & controle , Miocárdio , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Infecções por Coxsackievirus/sangue , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Citocinas/sangue , Modelos Animais de Doenças , Enterovirus/imunologia , Mediadores da Inflamação/sangue , Masculino , Camundongos Endogâmicos BALB C , Miocardite/sangue , Miocardite/imunologia , Miocardite/virologia , Miocárdio/imunologia , Miocárdio/metabolismo , Miocárdio/patologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/virologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/virologia
6.
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
7.
BMC Infect Dis ; 19(1): 15, 2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30612548

RESUMO

BACKGROUND: We report a case of hantavirus-induced myocarditis in a young adult. Hantavirus showed a rapid increase of infections in the year 2017. Only scarce data is available about potential myocardial involvement in hantavirus infections. With ECG and echocardiography providing often inconclusive results, a multiparametric cardiac magnetic resonance protocol with distinct myocardial tissue characterization seems to be the adequate tool for detecting even slight myocardial alterations. CASE PRESENTATION: This case started with the presentation of young adult suffering from headache and abdominal pain. Thrombocytes were decreased, creatinine was elevated, and there was massive proteinuria. Puumala virus IgG ELISA turned out to be positive, and specific antibodies (IgG and IgM) could be detected in the serum, and confirmed by immunoassay. The patient was admitted to the nephrology department for supportive therapy. Few days later, the patient reported chest pain and dyspnea. High sensitivity troponin I rose up to 0.32 µg/l (normal range below 0.04 µg/l) with an increase of the creatinkinase to 319 U/l (normal max. 190 U/l), no dynamic ECG changes could be observed. Echocardiography revealed a normal left ventricular function without regional wall motion abnormalities, no pericardial effusion or valve abnormalities, coronary artery disease could be excluded by computed tomography. A multiparametric cardiac magnetic resonance protocol including recent mapping techniques confirmed myocardial involvement induced by acute hantavirus infection. In the next few weeks, the patient's state of health rapidly improved and symptoms of chest pain and dyspnea disappeared. Follow up multiparametric CMR exam showed substantial decrease of the previously observed myocardial alterations during acute hantavirus infection suggesting myocardial healing. CONCLUSIONS: This case demonstrates that a CMR protocol including recent mapping techniques and established late gadolinium enhancement technique is an adequate non-invasive tool for both 1) initial detection, and 2) follow up of patients with hantavirus-induced myocarditis, which might be more common than previously known.


Assuntos
Infecções por Hantavirus/complicações , Imagem por Ressonância Magnética/métodos , Miocardite/diagnóstico por imagem , Miocardite/virologia , Adulto , Dor no Peito/diagnóstico por imagem , Dor no Peito/etiologia , Dor no Peito/virologia , Ecocardiografia , Eletrocardiografia , Infecções por Hantavirus/diagnóstico por imagem , Humanos , Masculino , Miocárdio/patologia , Função Ventricular Esquerda
8.
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
9.
BMJ Case Rep ; 11(1)2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30567124

RESUMO

A 2-month-old girl with normal development and no previous physical illnesses was resuscitated having been found lifeless on her back at home. On admission to Paediatric Intensive Care, she had severe metabolic disturbance, associated with an extremely troubling neurological signs. She died 2 hours later. A full body CT scan did not reveal injury and her parents declined an autopsy. Peripheral blood and cerebrospinal fluid samples were sterile. However, a broad-range PCR coupled with electrospray-ionisation mass spectrometry onto the PLEX-ID automat of peripheral blood revealed the presence of varicella zoster virus. There was a specific viral load in whole blood of 20 542 copies/ml. It is presumed that Varicella myocarditis was the likely cause of death. Our case illustrates the potential usefulness of a broad range PCR strategy in determining infectious causes of death in sudden infant death. Varicella is a potential cause of sudden infant death.


Assuntos
Herpesvirus Humano 3/genética , Miocardite/complicações , Reação em Cadeia da Polimerase/instrumentação , Morte Súbita do Lactente/genética , Causas de Morte , Varicela/complicações , Evolução Fatal , Feminino , Herpesvirus Humano 3/isolamento & purificação , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Miocardite/virologia , Morte Súbita do Lactente/diagnóstico , Morte Súbita do Lactente/etiologia , Carga Viral
10.
BMC Infect Dis ; 18(1): 681, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567553

RESUMO

BACKGROUND: Dengue is a global problem mainly in the tropics. Meticulous clinical management of cases has reduced the death rate significantly, but large numbers of people still succumb to severe complications of the infection. Presence of myocarditis is often overlooked leading to a poor outcome. Clinical management guidelines of dengue do not stress the importance of myocarditis as a manifestation in dengue infection. Severe hepatic dysfunction also needs emphasis. CASE PRESENTATION: We present three patients who had come to hospital on the 3rd day of fever. Two of them (case 1 and 3) were in shock on admission and case 2, who was stable on the3rd day, went into the critical phase and developed shock while in the hospital on the 4thday. All three had tachycardia on admission that got worse with time. The clinical course was unstable with fluctuations in urine output and deterioration of organ function. Despite frequent monitoring and life support they survived only 2-3 days in hospital. All three patients had myocarditis during the critical phase. In the first case, myocarditis was confirmed by troponin estimation and echocardiogram. In the second and third cases, histopathology confirmed myocarditis. Haemorrhagic necrosis of the liver was found in case 2 and 3 with exponential rise of transaminases. In all three cases, viral RNA was detected in both heart and liver tissues by PCR amplification. CONCLUSIONS: We stress that detection of myocarditis and liver involvement in any dengue patient is important from the onset of the illness where treatment should be tailored to prevent development of hypotension. Our findings are novel as PCR and histology are rarely done on tissues of deceased dengue patients in the world. Studies are needed to find therapeutic interventions to reverse cardiac and hepatic dysfunction in dengue infection.


Assuntos
Dengue/virologia , Coração/virologia , Fígado/virologia , Adulto , Dengue/diagnóstico , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Ecocardiografia , Evolução Fatal , Feminino , Febre/complicações , Febre/diagnóstico , Febre/virologia , Coração/diagnóstico por imagem , Hemorragia/diagnóstico , Hemorragia/virologia , Humanos , Falência Hepática/diagnóstico , Falência Hepática/virologia , Masculino , Miocardite/diagnóstico , Miocardite/virologia , Reação em Cadeia da Polimerase , RNA Viral/análise
11.
Phytomedicine ; 46: 32-38, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30097120

RESUMO

BACKGROUND: Viral myocarditis is defined as viral infection of myocardial tissue leading to impaired heart function and heart failure. Accumulating evidences have shown that arrhythmia is one of important complicating diseases of viral myocarditis causing increased mortality and morbidity. There are no effective treatment for the viral infection and complicating arrhythmia. PURPOSE: This study investigated the effect and mechanism of Astragalus Root dry extract (ARDE) on arrhythmia induced by CVB3 in mice. METHODS: The mice and HL-1 cells were treated with CVB3 and ARDE. Reciprocal regulation of Cx43 and miR-1 were observed in the CVB3 infected mouse myocardium and culture HL-1 cells. RESULTS: CVB3 IP injection increased immune cell infiltration in mouse left ventricle and caused irregular arrhythmia. ARDE treatment prevented the increase of immune cell infiltration and arrhythmia. Overexpression of miR-1 significantly inhibited both endogenous Cx43 expression and Cx43 3'UTR luciferase activity in HL-1 cells. Mutation of census binding site of +1586-1593 bp not +465-472 bp in Cx43 3'UTR luciferase resulted in abolishment of miR-1 inhibitory effects in HL-1 cells. Loss-of- function of miR-1 restored CVB3-induced Cx43 expression reduction in cultured HL-1 cells. The presence of ARDE attenuated the augmented miR-1 induced by CVB3 infection in vivo and in vitro. CONCLUSION: This study identified that CVB3 infection reduced Cx43 expression by elevating miR-1 level in mouse viral myocarditis. For the first time, ARDE was shown to prevent arrhythmia, and rescue CVB3-induced endogenous Cx43 expression by regulating miR-1 level.


Assuntos
Astrágalo (Planta)/química , Conexina 43/metabolismo , MicroRNAs/metabolismo , Miocardite/tratamento farmacológico , Miocardite/virologia , Extratos Vegetais/farmacologia , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/virologia , Linhagem Celular , Enterovirus Humano B , Coração/efeitos dos fármacos , Luciferases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Raízes de Plantas/química
12.
Am J Case Rep ; 19: 678-684, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29891833

RESUMO

BACKGROUND Rhabdomyolysis and primary dilated cardiomyopathies without skeletal muscle weakness are rare features of X-linked dystrophinopathies. We report a rare case of an X-linked dilated cardiomyopathy (XLDCM) presenting with acute rhabdomyolysis and myocarditis. We illustrate the confounding diagnostic influence of a reactivated, persistent EBV myocarditis as the presumed cause for this patient's XLDCM. CASE REPORT A 23-year-old Australian man presented with acute rhabdomyolysis and elevated creatine kinase (CK) levels. He was managed conservatively with intravenous hydration and developed acute pulmonary edema. Cardiac MRI and transthoracic echocardiogram revealed a dilated cardiomyopathy and viral myocarditis. Extensive sero-logical investigations identified reactivation of EBV, which was presumed to account for his viral myocarditis. The patient recovered and was discharged with down-trending CK levels. Follow-up transthoracic echocardiograms and cardiac MRI showed a persisting dilated cardiomyopathy. His CK continued to remain elevated and his EBV IgM serology remained positive. An inflammatory polymyositis with either a primary autoimmune pathophysiology or secondary to a chronic EBV infection was considered. Oral corticosteroids were trialed and reduced his CK significantly until therapy was ceased. Massively parallel sequencing eventually identified a two-exon deletion targeting Xp21 consistent with the diagnosis of a rare XLDCM. CONCLUSIONS Rhabdomyolysis and co-existing primary dilated cardiomyopathies are rare diagnostic manifestations in a minority of X-linked dystrophinopathies. Chronic viral infections and their reactivation may complicate the diagnostic process and incorrectly attribute an inherited cardiomyopathy to an acquired infective etiology. EBV reactivation rarely induces myocarditis. Therefore, primary and unresolving dilated cardiomyopathy with persistently elevated CK must prompt consideration of an underlying dystrophinopathy.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Miocardite/virologia , Rabdomiólise/virologia , Adulto , Animais , Cardiomiopatia Dilatada/virologia , Bovinos , Infecções por Vírus Epstein-Barr/virologia , Humanos , Masculino , Miocardite/diagnóstico , Rabdomiólise/diagnóstico , Ativação Viral , Latência Viral , Adulto Jovem
13.
Am J Case Rep ; 19: 540-544, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29735962

RESUMO

BACKGROUND Influenza viruses induce uncomplicated infections in most cases in individuals with no known predisposing factors. Acute febrile illness is generally limited to upper respiratory symptoms and several constitutional symptoms, including headache, lethargy, and myalgia. However, influenza A virus is a cause of severe morbidity and mortality worldwide. Some patients are at risk for serious and fatal complications. Cardiac involvement is a well-known condition, but, clinically apparent influenza myocarditis is not common. Few reports exist regarding recurrent fulminant influenza myocarditis. CASE REPORT We report here a fatal case of heart failure following myocarditis in a 14-year-old female who had seasonal flu symptoms but was otherwise healthy. H3N2 influenza virus infection was detected by molecular analyses of throat and nasal swabs, suggesting damage to myocardial cells caused directly by the virus. CONCLUSIONS Pericardial effusion myopericarditis may occur during influenza virus infection in young individuals, even those with no known predisposing factors. Physicians need to be aware that acute myopericarditis can be a fatal complication of recent influenza virus infection in all patients with instable hemodynamics. Early diagnosis and treatment could reduce, in some cases, the risk of severe cardiac events. However, this sudden and fatal outcome was difficult to predict in a healthy young female with no known risk factors.


Assuntos
Vírus da Influenza A Subtipo H3N2 , Influenza Humana/diagnóstico , Miocardite/virologia , Adolescente , Evolução Fatal , Feminino , Parada Cardíaca/virologia , Humanos , Derrame Pericárdico/virologia
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.
BMJ Case Rep ; 20182018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29776940

RESUMO

Neonatal cardiogenic shock most commonly occurs due to critical congenital heart disease, sepsis, metabolic disorder or arrhythmias. In particular, enterovirus infections are common in the neonatal period, and patients can present with fulminant myocarditis. Early recognition is imperative due to its high morbidity and mortality without prompt and aggressive treatment. We present the successful treatment of fulminant neonatal enteroviral myocarditis in a pair of monochorionic diamniotic twins with cardiopulmonary support, intravenous immunoglobulin and pocapavir, an enteroviral capsid inhibitor. The twins took an almost exact parallel hospital course, including day of extracorporeal membrane oxygenation (ECMO) cannulation, day of ECMO decannulation, improvement of cardiac function, discharge and status at follow-up. While it was difficult to assess the relative contribution of each intervention, our case shows promise in the use of pocapavir for treatment of severe enteroviral infections. Remarkably, both twins demonstrated remarkable recovery within 2 weeks, underscoring that early aggressive cardiopulmonary support, and potentially pocapavir, contributed to their recovery.


Assuntos
Antivirais/uso terapêutico , Doenças em Gêmeos/terapia , Infecções por Enterovirus/terapia , Oxigenação por Membrana Extracorpórea/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Miocardite/terapia , Éteres Fenílicos/uso terapêutico , Choque Cardiogênico/terapia , Terapia Combinada , Doenças em Gêmeos/virologia , Infecções por Enterovirus/complicações , Coração/virologia , Humanos , Recém-Nascido , Masculino , Miocardite/virologia , Choque Cardiogênico/virologia , Resultado do Tratamento , Gêmeos Monozigóticos
16.
Exp Mol Pathol ; 104(2): 140-145, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29530464

RESUMO

Interleukin-17A (IL-17A) has been implicated in the pathogenesis of viral myocarditis (VMC). However, the role of IL-17A polymorphisms in susceptibility to VMC has not been reported to date. The aim of this study was to explore the association between IL-17A variants as well as serum IL-17 levels with VMC. Three single-nucleotide polymorphisms (SNPs) (rs2275913, rs3819025, and rs3748067) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in 236 VMC patients and 259 controls from China. Serum IL-17A levels were measured by enzyme-linked immunosorbent assay kits. Multivariable logistic regression analysis that the rs2275913 AA genotype and the haplotype -197A/+45G/+1249G (AGG) were associated with an increased risk of VMC (all P < 0.05). Consistent with these findings, the rs2275913 AA genotype was linked to higher serum IL-17A compared to GG/AG genotype (all P < 0.001). We observed no associations between the other two SNPs and risk of VMC. Serum IL-17A levels were significantly higher in the VMC group than controls (P < 0.001) and gradually increased with the increase of New York Heart Association grade in VMC patients (P < 0.05). Spearman correlation test revealed that the serum IL-17A level was correlated with the cardiac damage and left ventricular systolic functions among VMC patients (all P < 0.05). Our study reveals that IL-17A expression may contribute to the development and severity of VMC. The SNP rs2275913 in the IL-17A gene might exert influence on susceptibility to VMC via linking with the serum IL-17A level.


Assuntos
Interleucina-17/sangue , Interleucina-17/genética , Miocardite/genética , Miocardite/virologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Criança , Eletrocardiografia , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
17.
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
18.
BMC Pediatr ; 18(1): 51, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29433478

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infection is common and may be severe among patients with preexisting cardiac anomalies, but direct involvement of myocardial damage is not common in those patients. Additionally, myocardial involvement has been rarely described among immune compromised children. CASE PRESENTATION: A 4-year-old girl with acute lymphoblastic leukemia who received maintenance chemotherapy in an outpatient clinic developed systemic inflammatory response syndrome. RSV infection was confirmed by a positive rapid antigen test and serological assay. Subsequently, she was diagnosed with severe myocarditis caused by RSV infection, which was diagnosed by abnormal findings of cardiac echography and ECG and elevated biomarkers for myocardial damage. Then, she was treated in the intensive care unit for 13 days. High amounts of RSV type B RNA was detected in tracheal aspirates and serum sample. CONCLUSION: This case report emphasizes that RSV infection may be associated with myocarditis in immunocompromised children receiving maintenance chemotherapy.


Assuntos
Hospedeiro Imunocomprometido , Miocardite/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Pré-Escolar , Feminino , Humanos , Quimioterapia de Manutenção , Miocardite/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
19.
Diagn Microbiol Infect Dis ; 91(2): 153-155, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29459054

RESUMO

We describe a male patient who presents 2 years posttransplant with cough and dyspnea. A negative pulmonary workup led to an endomyocardial biopsy and the diagnosis of cytomegalovirus (CMV) myocarditis. The patient was treated with ganciclovir and intravenous immunoglobulin. This illustrates a very late presentation of posttransplant CMV myocarditis and the usefulness of myocardial biopsy in diagnosis of CMV carditis.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transplante de Coração , Miocardite , Idoso , Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Ganciclovir/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Masculino , Miocardite/diagnóstico , Miocardite/tratamento farmacológico , Miocardite/virologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/virologia , Fatores de Tempo
20.
Can J Cardiol ; 34(4): 492-501, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29455951

RESUMO

BACKGROUND: Viral myocarditis is a widespread cardiac disease associated with inflammation and myocardial injury and is predominantly caused by coxsackievirus B3 (CVB3) infection in humans as well as in mice. CVB3-induced myocarditis shows sexually dimorphic sensitivity and is more prevalent in male mice. Our previous studies showed that natural killer (NK) cells played an indispensable role in CVB3-induced myocarditis, and female mice exhibited less pathological cardiac interferon gamma (IFN-γ)+ NK cell infiltration than did male mice. However, the precise mechanisms were not well elucidated. METHODS: We investigated the influence of estrogen on cardiac IFN-γ+ NK cell enrichment in CVB3-induced myocarditis and explored the underlying molecular mechanism. RESULTS: In this study, we found that CVB3 stimulation could clearly induce IFN-γ expression by NK cells; however, this trend could be blunted by estrogen treatment. Consistently, ovariectomized female mice with decreased estrogen levels exhibited substantially increased enrichment of cardiac IFN-γ+ NK cells and displayed significantly aggravated myocarditis. Similarly, estrogen-treated male mice showed less cardiac IFN-γ+ NK cell infiltration, accompanied by significantly alleviated viral myocarditis. In sharp contrast, sexually immature female and male mice (with similar estrogen levels) showed comparable levels of cardiac IFN-γ+ NK cell infiltration and similar levels of myocarditis severity. Upon further exploration of the underlying mechanisms, we found that estrogen could downregulate expression of Th1-specific T box transcription factor (T-bet), the key transcription factor associated with IFN-γ production, in CVB3-stimulated NK cells. CONCLUSIONS: Overall, this study might help us understand the mechanism of increased cardiac infiltration by IFN-γ+ NK cells in CVB3-infected male mice compared with that in female mice and might provide new clues for the sex bias in CVB3-induced myocarditis.


Assuntos
Infecções por Coxsackievirus , Enterovirus Humano B/patogenicidade , Estrogênios/análise , Interferon gama , Células Matadoras Naturais/imunologia , Miocardite , Animais , Infecções por Coxsackievirus/complicações , Infecções por Coxsackievirus/imunologia , Regulação para Baixo , Feminino , Interferon gama/análise , Interferon gama/imunologia , Masculino , Camundongos , Miocardite/imunologia , Miocardite/metabolismo , Miocardite/virologia , Estatística como Assunto , Proteínas com Domínio T/metabolismo
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