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Sample records for regulating parasite-induced myocarditis

  1. Genetic complexity of autoimmune myocarditis

    PubMed Central

    Li, Haiyan S.; Ligons, Davinna L.; Rose, Noel R.

    2008-01-01

    Autoimmune myocarditis, a chronic stage of myocardial inflammation, occurs in a small subset of patients after acute cardiotropic viral infection and can lead to dilated cardiomyopathy (DCM). This disease can be recapitulated in susceptible mouse strains by infection with coxsackievirus B3, or by immunization with cardiac myosin or cardiac troponin I. The etiologies of myocarditis are multifactorial and genetically complex. Genetic linkage between susceptibility to myocarditis/DCM and the major histocompatibility complex (MHC) genes have been reported in both humans and experimentally induced mouse models. However, unlike other autoimmune diseases, the non-MHC genes seem to have greater impact than MHC genes on disease susceptibility. Several myocarditis-related non-MHC loci have been identified by our laboratory and others in different models. Most of these loci overlap with other autoimmune disease susceptibility loci, suggesting common or shared genetic traits influencing general autoimmunity. For example, we have demonstrated that Eam1 and Eam 2 may influence disease susceptibility via regulating T cell apoptosis at different developmental stages. Blockade of signaling through specific genes, such as CTLA4, ICOS and PD-1, can either enhance or prevent the development of experimental autoimmune myocarditis, but it remains unclear whether functional polymorphisms in these genes are involved in predisposition to disease. In humans, mutations/deletions in immunologically important genes such as CD45, and genes encoding cardiac proteins, have been reported in patients with recurrent myocarditis or DCM. Identification of genetic polymorphisms controlling autoimmune myocarditis will help us understand the mechanisms underlying autoimmune diseases in general, thereby improving potential therapies in patients. PMID:18190873

  2. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation

    PubMed Central

    Gui, Jun; Chen, Ruizhen; Xu, Wei; Xiong, Sidong

    2015-01-01

    Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41H68O14, MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-κB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-κB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC. PMID:25728713

  3. Coagulation, Protease Activated Receptors and Viral Myocarditis

    PubMed Central

    Antoniak, Silvio; Mackman, Nigel

    2013-01-01

    The coagulation protease cascade plays an essential role in hemostasis. In addition, a clot contributes to host defense by limiting the spread of pathogens. Coagulation proteases induce intracellular signaling by cleavage of cell surface receptors called protease-activated receptors (PARs). These receptors allow cells to sense changes in the extracellular environment, such as infection. Viruses activate the coagulation cascade by inducing tissue factor expression and by disrupting the endothelium. Virus infection of the heart can cause myocarditis, cardiac remodeling and heart failure. Recent studies using a mouse model have shown that tissue factor, thrombin and PAR-1 signaling all positively regulate the innate immune during viral myocarditis. In contrast, PAR-2 signaling was found to inhibit interferon-β expression and the innate immune response. These observations suggest that anticoagulants may impair the innate immune response to viral infection and that inhibition of PAR-2 may be a new target to reduce viral myocarditis.. PMID:24203054

  4. Forensic grading of myocarditis: an experimental contribution to the distinction between lethal myocarditis and incidental myocarditis.

    PubMed

    Casali, Michelangelo Bruno; Lazzaro, Antonella; Gentile, Guendalina; Blandino, Alberto; Ronchi, Enzo; Zoja, Riccardo

    2012-11-30

    Myocarditis can be either the cause of the death of a person or just an incidental finding during the autopsy and the following histological examinations. To establish whether a single myocarditis is a lethal or just an incidental pathology a very careful grading is always mandatory. The aim of the present work is thus to test the hypothesis about the reliability of an evidence-based distinction between the lethal myocarditis and the incidental myocarditis. The present work compares clinical and histological features from two different groups of myocarditis. Group A is composed of patients having myocarditis at the time of death, who certainly died from other reasons (i.e.: death by head gunshot with no survival time). Group B is composed of patients who died having a myocarditis as the only pathological evidence at the autopsy and the following histological and toxicological examinations and then who died because of the myocarditis. The lethal myocarditis and the incidental myocarditis differ statistically about last days' anamnesis, acute findings in the macroscopic analysis of the heart, neutrophilic infiltration, myocite necrosis, multiple sites interstitial oedema and perivascular cuffs. Such variables can be summarized in a scoring system able to quantitatively separate the lethal myocarditis from the incidental myocarditis. Such a reliable scoring system develops far behind the isolated grading of the myocite necrosis, even though the myocite necrosis should always be considered as a pivot variable for distinguishing lethal myocarditis from incidental myocarditis. The proposed scoring system is very easy to use and it is also appreciably money-sparing with its foundations in the simple combination of clinical anamnesis, autopsy and basic histology. Its routinary application could implement the objectivity in the forensic grading of myocarditis.

  5. Myocarditis in Clinical Practice.

    PubMed

    Sinagra, Gianfranco; Anzini, Marco; Pereira, Naveen L; Bussani, Rossana; Finocchiaro, Gherardo; Bartunek, Jozef; Merlo, Marco

    2016-09-01

    Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class.

  6. Myocarditis in Clinical Practice.

    PubMed

    Sinagra, Gianfranco; Anzini, Marco; Pereira, Naveen L; Bussani, Rossana; Finocchiaro, Gherardo; Bartunek, Jozef; Merlo, Marco

    2016-09-01

    Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class. PMID:27489051

  7. The management of myocarditis.

    PubMed

    Schultheiss, Heinz-Peter; Kühl, Uwe; Cooper, Leslie T

    2011-11-01

    Despite considerable advances in our understanding of myocarditis pathogenesis, the clinical management of myocarditis has changed relatively little in the last few years. This review aims to help bridge the widening gap between recent mechanistic insights, which are largely derived from animal models, and their potential impact on disease burden. We illustrate the pathogenetic mechanisms that are prime targets for novel therapeutic interventions. Pathway and pathogen-specific molecular diagnostic tests have expanded the role for endomyocardial biopsy. State of the art cardiac magnetic resonance imaging can now provide non-invasive tissue characterization and localize inflammatory infiltrates but imaging techniques are misleading if infectious agents are involved. We emphasize the gaps in our current clinical knowledge, particularly with respect to aetiology-based therapy, and suggest opportunities for high impact, translational investigations.

  8. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  9. Erysipelas and acute myocarditis: an unusual combination.

    PubMed

    Domínguez, Fernando; Cobo-Marcos, Marta; Guzzo, Gonzalo; Cavero, Miguel A; Mirelis, Jesús G; Alonso-Pulpon, Luis; Garcia-Pavia, Pablo

    2013-09-01

    Myocarditis is a rare disease with variable clinical presentation and diverse electrocardiographic and echocardiographic features. Viral infection is the most common cause, but myocarditis can also be caused by bacterial infection. The most frequently involved bacterial agent is group A Streptococcus, which is also an etiologic agent of erysipelas. We present the case of a man aged 46 years with left-leg erysipelas who developed myocarditis. Cardiac magnetic resonance played an essential role in diagnosis. This case is, to our knowledge, the first description of an association between erysipelas and myocarditis.

  10. Myocarditis and the military patient.

    PubMed

    Cox, Andrew T; White, S; Ayalew, Y; Boos, C; Haworth, K; McKenna, W J

    2015-09-01

    Myocarditis, simply defined as inflammation of the heart muscle, is a commonly encountered cardiac disease in primary and secondary care, both in the UK and on Operational deployments. In the UK Armed Forces, myocarditis results in deaths as well as the premature termination of military careers on medical grounds. The aetiology is usually the result of a number of infectious aetiologies with viruses being the most common pathogens in the vast majority of cases. However, it may also be the result of autoimmune activation, chemical or pharmacological toxins, environmental insult or hypersensitivity reactions. Particular aetiologies that are more likely to be seen in a military population are discussed and include certain infections, smallpox vaccine, and hyperthermia and hypothermia. The clinical features can be highly variable ranging from an asymptomatic infection to fulminant heart failure. Features pertinent to the military doctor, including the natural history, investigative modalities and management strategies, with a particular emphasis on the occupational impact of myocarditis in the UK Armed Forces are reviewed.

  11. Myocarditis

    MedlinePlus

    Inflammation - heart muscle ... by these cells can also damage the heart muscle. As a result, the heart can become thick, ... Fever and other signs of infection including headache, muscle aches, sore throat, diarrhea, or rashes Joint pain ...

  12. Eosinophilic myocarditis: characteristics, diagnostics and outcomes of a rare condition.

    PubMed

    Wang, T K M; Watson, T; Pemberton, J; Pemberton, L; Lowe, B; Ellis, C; Kingston, N; Ruygrok, P

    2016-09-01

    Eosinophilic myocarditis is a rare and potentially fatal condition characterised by eosinophilic inflammatory infiltration of myocardium. We report seven consecutive cases of eosinophilic myocarditis at our centre and discuss the important characteristics, investigation and management of this disease. PMID:27633471

  13. Gene expression patterns underlying parasite-induced alterations in host behaviour and life history.

    PubMed

    Feldmeyer, Barbara; Mazur, Johanna; Beros, Sara; Lerp, Hannes; Binder, Harald; Foitzik, Susanne

    2016-01-01

    Many parasites manipulate their hosts' phenotype. In particular, parasites with complex life cycles take control of their intermediate hosts' behaviour and life history to increase transmission to their definitive host. The proximate mechanisms underlying these parasite-induced alterations are poorly understood. The cestode Anomotaenia brevis affects the behaviour, life history and morphology of parasitized Temnothorax nylanderi ants and indirectly of their unparasitized nestmates. To gain insights on how parasites alter host phenotypes, we contrast brain gene expression patterns of T. nylanderi workers parasitized with the cestode, their unparasitized nestmates and unparasitized workers from unparasitized colonies. Over 400 differentially expressed genes between the three groups were identified, with most uniquely expressed genes detected in parasitized workers. Among these are genes that can be linked to the increased lifespan of parasitized workers. Furthermore, many muscle (functionality) genes are downregulated in these workers, potentially causing the observed muscular deformations and their inactive behaviour. Alterations in lifespan and activity could be adaptive for the parasite by increasing the likelihood that infected workers residing in acorns are eaten by their definitive host, a woodpecker. Our transcriptome analysis reveals numerous gene expression changes in parasitized workers and their uninfected nestmates and indicates possible routes of parasite manipulation. Although causality still needs to be established, parasite-induced alterations in lifespan and host behaviour appear to be partly explained by morphological muscle atrophy instead of central nervous system interference, which is often the core of behavioural regulation. Results of this study will shed light upon the molecular basis of antagonistic species interactions.

  14. Gene expression patterns underlying parasite-induced alterations in host behaviour and life history.

    PubMed

    Feldmeyer, Barbara; Mazur, Johanna; Beros, Sara; Lerp, Hannes; Binder, Harald; Foitzik, Susanne

    2016-01-01

    Many parasites manipulate their hosts' phenotype. In particular, parasites with complex life cycles take control of their intermediate hosts' behaviour and life history to increase transmission to their definitive host. The proximate mechanisms underlying these parasite-induced alterations are poorly understood. The cestode Anomotaenia brevis affects the behaviour, life history and morphology of parasitized Temnothorax nylanderi ants and indirectly of their unparasitized nestmates. To gain insights on how parasites alter host phenotypes, we contrast brain gene expression patterns of T. nylanderi workers parasitized with the cestode, their unparasitized nestmates and unparasitized workers from unparasitized colonies. Over 400 differentially expressed genes between the three groups were identified, with most uniquely expressed genes detected in parasitized workers. Among these are genes that can be linked to the increased lifespan of parasitized workers. Furthermore, many muscle (functionality) genes are downregulated in these workers, potentially causing the observed muscular deformations and their inactive behaviour. Alterations in lifespan and activity could be adaptive for the parasite by increasing the likelihood that infected workers residing in acorns are eaten by their definitive host, a woodpecker. Our transcriptome analysis reveals numerous gene expression changes in parasitized workers and their uninfected nestmates and indicates possible routes of parasite manipulation. Although causality still needs to be established, parasite-induced alterations in lifespan and host behaviour appear to be partly explained by morphological muscle atrophy instead of central nervous system interference, which is often the core of behavioural regulation. Results of this study will shed light upon the molecular basis of antagonistic species interactions. PMID:26615010

  15. Fulminant Myocarditis with Combination Immune Checkpoint Blockade.

    PubMed

    Johnson, Douglas B; Balko, Justin M; Compton, Margaret L; Chalkias, Spyridon; Gorham, Joshua; Xu, Yaomin; Hicks, Mellissa; Puzanov, Igor; Alexander, Matthew R; Bloomer, Tyler L; Becker, Jason R; Slosky, David A; Phillips, Elizabeth J; Pilkinton, Mark A; Craig-Owens, Laura; Kola, Nina; Plautz, Gregory; Reshef, Daniel S; Deutsch, Jonathan S; Deering, Raquel P; Olenchock, Benjamin A; Lichtman, Andrew H; Roden, Dan M; Seidman, Christine E; Koralnik, Igor J; Seidman, Jonathan G; Hoffman, Robert D; Taube, Janis M; Diaz, Luis A; Anders, Robert A; Sosman, Jeffrey A; Moslehi, Javid J

    2016-11-01

    Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).

  16. α-Galactosylceramide protects mice from lethal Coxsackievirus B3 infection and subsequent myocarditis

    PubMed Central

    Wu, C Y; Feng, Y; Qian, G C; Wu, J H; Luo, J; Wang, Y; Chen, G J; Guo, X K; Wang, Z J

    2010-01-01

    Myocarditis is an inflammation of the myocardium which often follows virus infections. Coxsackievirus B3 (CVB3), as a marker of the enterovirus group, is one of the most important infectious agents of virus-induced myocarditis. Using a CVB3-induced myocarditis model, we show that injection α-galactosylceramide (α-GalCer), a ligand for invariant natural killer (NK) T (iNK T) cells, can protect the mice from viral myocarditis. After the systemic administration of α-GalCer in CVB3 infected mice, viral transcription and titres in mouse heart, sera and spleen were reduced, and the damage to the heart was ameliorated. This is accompanied by a better disease course with an improved weight loss profile. Compared with untreated mice, α-GalCer-treated mice showed high levels of interferon (IFN)-γ and interleukin (IL)-4, and reduced proinflammatory cytokines and chemokines in their cardiac tissue. Anti-viral immune response was up-regulated by α-GalCer. Three days after CVB3 infection, α-GalCer-administered mice had larger spleens. Besides NK T cells, more macrophages and CD8+ T cells were found in these spleens. Upon stimulation with phorbol myristate acetate plus ionomycin, splenocytes from α-GalCer-treated mice produced significantly more cytokines [including IFN-γ, tumour necrosis factor-α, IL-4 and IL-10] than those from untreated mice. These data suggest that administration of α-GalCer during acute CVB3 infection is able to protect the mice from lethal myocarditis by local changes in inflammatory cytokine patterns and enhancement of anti-viral immune response at the early stage. α-GalCer is a potential candidate for viral myocarditis treatment. Our work supports the use of anti-viral treatment early to reduce the incidence of virus-mediated heart damage. PMID:20726989

  17. Myocarditis associated with reovirus in turkey poults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis associated with reovirus was diagnosed in 17 day-old male turkey poults based on virus isolation, reverse transcript – polymerase chain reaction (RT-PCR), demonstration of reovirus antigen in the cytoplasm of mononuclear inflammatory cells and myocytes in the heart by immunohistochemistr...

  18. Gallium-positive Lyme disease myocarditis

    SciTech Connect

    Alpert, L.I.; Welch, P.; Fisher, N.

    1985-09-01

    In the course of a work-up for fever of unknown origin associated with intermittent arrhythmias, a gallium scan was performed which revealed diffuse myocardial uptake. The diagnosis of Lyme disease myocarditis subsequently was confirmed by serologic titers. One month following recovery from the acute illness, the abnormal myocardial uptake completely resolved.

  19. Predictors of Mortality in Paediatric Myocarditis

    PubMed Central

    Ansari, Mohammed Junaid; Mittal, Mahima; Kushwaha, K.P.

    2016-01-01

    Introduction Paediatric myocarditis can present as mild flu like symptoms to fulminent form. Early identification of the severity of illness and prioritization of intensive care is helpful especially in developing countries with limited resources. Aim To know the factors at admission that can predict mortality in paediatric myocarditis. Materials and Methods This was an observational study which enrolled children who presented with fever of acute onset (less than 15 days in duration), and were diagnosed as suspected myocarditis on the basis of clinical features, Troponin I and echocardiography, according to Expanded criteria for myocarditis in Paediatric ward at our institute over a period from August 2014 to December 2015. Their clinical features, cardiac biomarkers and echocardiography findings were compared between survivors and non-survivors. Statistical Analysis All statistical analysis was done using graphpad Prism 5 and SPSS statistical software. A Fisher exact p-value <0.05 was regarded as significant. Multivariate Logistic Regression was carried out to quantify the relationship between cardiac death and other predictor variables. The logistic coefficients for the predictor variables and their exponents, that is, log odds were calculated. Statistical significance of these predictor variables was interpreted by p-values. Results A 17.7% (n=11/62) patients of paediatric myocarditis died in this study. New York Heart Association (NYHA) class IV dyspnea (p=0.0115) and hypotension (p=0.0174) were more in patients who did not survive. The mean value of Troponin I was more in the non-survivor group (0.958 ± 1.13ng/ml); (p=0.0074). More number of patients who died had Brain Natriuretic Peptide (BNP) levels increased in their plasma (p=0.0087) with higher mean value (p=0.0175). LV ejection fraction was decreased markedly in non survivor group with mean value of 37±8.09 % as compared to survivor group with mean value of 46.6±10.5%, (p=0.0115). On multivariate

  20. Fulminant myocarditis caused by Legionella pneumophila: case report.

    PubMed

    Damásio, Ana Filipa; Rodrigues, Luís; Miranda, Luís; Coelho, Pedro; Banazol, Nuno; Colaço, João; Fragata, José

    2014-03-01

    Myocarditis is defined as inflammation of the myocardium. The clinical manifestations of myocarditis vary from flu-like symptoms to fatal fulminant forms. We report the case of a 39-year-old woman with a diagnosis of cardiogenic shock caused by fulminant myocarditis. Extracorporeal membrane oxygenation was used as a bridge to recovery. Etiological study revealed Legionella pneumophila serogroup 1 infection. Recovery of biventricular function was seen after treatment with azithromycin.

  1. Pediatric myocarditis: A sentinel of non-cardiac chronic diseases?

    PubMed Central

    Felszeghy, Enikő; Kovács, Tamás; Berkes, Andrea; Tóth, László; Balla, György; Korponay-Szabó, Ilma

    2014-01-01

    Introduction Although long-term outcome studies in large pediatric myocarditis/cardiomyopathy populations have been reported in literature, none of them focused on comorbidities. Methods All children and adolescents (age <18 years) treated with myocarditis at the Department of Pediatrics, University of Debrecen, Hungary were followed. Patients suffering from myocarditis during the period 1996–2011 were enrolled. Results Over the 16-year period, a diagnosis of myocarditis was established in nine children. Their median age was 1.11 (0.03–8.71) years. Three of the nine patients died. Left ventricular dilatation and ejection fraction normalized within 1–21 months in the survivors. None of the cases progressed to dilated cardiomyopathy. Regarding non-cardiac comorbidities, myocarditis or recurrent peri-myocarditis preceded the manifestation of celiac disease in two patients, while cystic fibrosis was diagnosed after the improvement of cardiac function in another, and Alström syndrome was diagnosed several years after complete recovery from myocarditis in yet another patient. Conclusion These results suggest that manifestations of other chronic pediatric diseases may be more frequent among survivors of pediatric myocarditis. Prolonged follow-up of patients who survive myocarditis is therefore recommended not only to detect possible progression to cardiomyopathy but also to identify non-cardiac comorbidities. PMID:25598988

  2. Cardiac Sarcoidosis or Giant Cell Myocarditis? On Treatment Improvement of Fulminant Myocarditis as Demonstrated by Cardiovascular Magnetic Resonance Imaging

    PubMed Central

    Bogabathina, Hari; Olson, Peter; Rathi, Vikas K.; Biederman, Robert W. W.

    2012-01-01

    Giant cell myocarditis, but not cardiac sarcoidosis, is known to cause fulminant myocarditis resulting in severe heart failure. However, giant cell myocarditis and cardiac sarcoidosis are pathologically similar, and attempts at pathological differentiation between the two remain difficult. We are presenting a case of fulminant myocarditis that has pathological features suggestive of cardiac sarcoidosis, but clinically mimicking giant cell myocarditis. This patient was treated with cyclosporine and prednisone and recovered well. This case we believe challenges our current understanding of these intertwined conditions. By obtaining a sense of severity of cardiac involvement via delayed hyperenhancement of cardiac magnetic resonance imaging, we were more inclined to treat this patient as giant cell myocarditis with cyclosporine. This resulted in excellent improvement of patient's cardiac function as shown by delayed hyperenhancement images, early perfusion images, and SSFP videos. PMID:24826266

  3. Dengue myocarditis in Singapore: two case reports.

    PubMed

    Marques, N; Gan, V C; Leo, Y-S

    2013-06-01

    The authors report two cases of complicated dengue viral infection with acute myocarditis involving young male adults, of which one was fatal. The first case presented with typical signs of myocardial disease: chest pain and diaphoresis with myocardial depression in the electrocardiograph. The second case deteriorated rapidly and demised within the first day of admission. Histology of the heart muscles showed multiple small foci of myocyte necrosis surrounded by lymphocytes, in keeping with viral myocarditis. Both cases fulfilled the World Health Organization (WHO) diagnosis of probable dengue: the first case had positive dengue serology, both IgM and IgG at day six of illness, and the second case was polymerase chain reaction (PCR) positive for dengue and identified as serotype 2. Despite the severe outcome, both cases did not completely fulfil the criteria for dengue haemorrhagic fever (DHF). Although severe cardiac impairment is not commonly reported in dengue infection, it can be life threatening.

  4. Clinical outcomes of acute myocarditis in childhood

    PubMed Central

    Lee, K; McCrindle, B; Bohn, D; Wilson, G; Taylor, G; Freedom, R; Smallhorn, J; Benson, L

    1999-01-01

    OBJECTIVE—To describe clinical outcomes of a paediatric population with histologically confirmed lymphocytic myocarditis.
DESIGN—A retrospective review between November 1984 and February 1998.
SETTING—A major paediatric tertiary care hospital.
PATIENTS—36 patients with histologically confirmed lymphocytic myocarditis.
MAIN OUTCOME MEASURES—Survival, cardiac transplantation, recovery of ventricular function, and persistence of dysrhythmias.
RESULTS—Freedom from death or cardiac transplantation was 86% at one month and 79% after two years. Five deaths occurred within 72 hours of admission, and one late death at 1.9 years. Extracorporeal membrane oxygenation support was used in four patients, and three patients underwent heart replacement. 34 patients were treated with intravenous corticosteroids. In the survivor/non-cardiac transplantation group (n = 29), the median follow up was 19 months (range 1.2-131.6 months), and the median period for recovery of a left ventricular ejection fraction to > 55% was 2.8 months (range 0-28 months). The mean (SD) final left ventricular ejection and shortening fractions were 66 (9)% and 34 (8)%, respectively. Two patients had residual ventricular dysfunction. No patient required antiarrhythmic treatment. All survivors reported no cardiac symptoms or restrictions in physical activity.
CONCLUSIONS—Our experience documents good outcomes in paediatric patients presenting with acute heart failure secondary to acute lymphocytic myocarditis treated with immunosuppression. Excellent survival and recovery of ventricular function, with the absence of significant arrhythmias, continued cardiac medications, or restrictions in physical activity were the normal outcomes.


Keywords: myocarditis; paediatric cardiology; immunosuppression PMID:10409542

  5. Clinical and experimental aspects of viral myocarditis.

    PubMed Central

    Leslie, K; Blay, R; Haisch, C; Lodge, A; Weller, A; Huber, S

    1989-01-01

    Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated. PMID:2650861

  6. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    PubMed

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress. PMID:26657007

  7. Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells

    PubMed Central

    Raetz, Megan; Hwang, Sun-hee; Wilhelm, Cara; Kirkland, Donna; Benson, Alicia; Sturge, Carolyn; Mirpuri, Julie; Vaishnava, Shipra; Hou, Baidong; DeFranco, Anthony L.; Gilpin, Christopher J; Hooper, Lora V.; Yarovinsky, Felix

    2012-01-01

    Activation of Toll-like receptors (TLRs) by pathogens triggers cytokine production and T cell activation, immune defense mechanisms that are linked to immunopathology. Here we show that IFN-γ production by CD4+ TH1 cells during mucosal responses to the protozoan parasite Toxoplasma gondii results in dysbiosis and the elimination of Paneth cells. Paneth cell death led to loss of antimicrobial peptides and occurred in conjunction with uncontrolled expansion of the Enterobacteriaceae family of Gram-negative bacteria. The expanded intestinal bacteria were required for the parasite-induced intestinal pathology. The investigation of cell type-specific factors regulating TH1 polarization during T. gondii infection identified the T cell intrinsic TLR pathway as a major regulator of IFN-γ production in CD4+ T cells responsible for Paneth cell death, dysbiosis and intestinal immunopathology. PMID:23263554

  8. Myocarditis confirmed by biopsy presenting as acute myocardial infarction.

    PubMed Central

    Costanzo-Nordin, M R; O'Connell, J B; Subramanian, R; Robinson, J A; Scanlon, P J

    1985-01-01

    Two cases of acute myocardial infarction occurred in association with myocarditis, which was confirmed by biopsy. The first patient suffered an anteroseptal and the second patient an inferior wall myocardial infarction shortly after an acute viral illness. In both patients, coronary angiography showed normal coronary arteries, and right ventricular endomyocardial biopsy confirmed myocarditis. Histological abnormalities attributable to ischaemic heart disease were absent. The first patient's condition became stable after immunosuppressive treatment. Myocarditis resolved spontaneously within three months in the second patient. Coronary artery spasm and myocardial involvement with a systemic disease were unlikely. Endomyocardial biopsy in patients with acute myocardial infarction and normal coronary arteries may be useful in identifying myocarditis associated with myocardial necrosis. Myocarditis in acute myocardial infarction in the absence of coronary artery obstruction has not previously been documented during life. Images PMID:3966948

  9. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance

    PubMed Central

    Rao, Krishnasree; Matulevicius, Susan

    2016-01-01

    Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis. PMID:27303242

  10. Effects of carvedilol treatment on cardiac cAMP response element binding protein expression and phosphorylation in acute coxsackievirus B3-induced myocarditis

    PubMed Central

    2013-01-01

    Background The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of β-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective β-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis. Methods This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied. Results The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-α in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-α were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-α with amelioration of acute viral myocarditis. Conclusion These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation. PMID:24225056

  11. The role of sex differences in autophagy in the heart during coxsackievirus B3 induced myocarditis

    PubMed Central

    Koenig, Andreas; Sateriale, Adam; Budd, Ralph C.; Huber, Sally A.; Buskiewicz, Iwona A.

    2014-01-01

    Under normal conditions, autophagy maintains cardiomyocyte health and integrity through turnover of organelles. During stress, oxygen and nutrient deprivation or microbial infection, autophagy prolongs cardiomyocyte survival. Sex differences in induction of cell death may to some extent explain the disparity between the sexes in many human diseases. However, sex differences in gene expression, which regulate cell death and autophagy were so far not taken in consideration to explain the sex bias of viral myocarditis. Coxsackievirus B3 (CVB3) induced myocarditis is a sex-biased disease, with females being substantially less susceptible than males and sex hormones largely determine this bias. CVB3 was shown to induce and subvert the autophagosome for its optimal viral RNA replication. Gene expression analysis on mouse and human, healthy and CVB3 infected, cardiac samples of both sexes, suggests sex differences in autophagy related gene expression. This review discusses the aspects of sex bias in autophagy induction in cardiomyocytes. PMID:24323874

  12. Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause

    PubMed Central

    Shibazaki, Shunichi; Eguchi, Shunsuke; Endo, Takashi; Wakabayashi, Tadamasa; Araki, Makoto; Gu, Yoshiaki; Imai, Taku; Asano, Kouji; Taniuchi, Norihide

    2016-01-01

    Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case  1, whereas a corticosteroid and albendazole were used in Case  2 as induction therapy. Both patients recovered. Albendazole was also used in Case  1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole. PMID:27123346

  13. Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause.

    PubMed

    Shibazaki, Shunichi; Eguchi, Shunsuke; Endo, Takashi; Wakabayashi, Tadamasa; Araki, Makoto; Gu, Yoshiaki; Imai, Taku; Asano, Kouji; Taniuchi, Norihide

    2016-01-01

    Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case  1, whereas a corticosteroid and albendazole were used in Case  2 as induction therapy. Both patients recovered. Albendazole was also used in Case  1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole. PMID:27123346

  14. Characterization of the parasite-induced lesions in the posterior segment of the eye

    PubMed Central

    El-Sayed, Nagwa Mostafa; Safar, Elmeya Hassan

    2015-01-01

    Ocular lesions are frequently associated with different parasitic infections. The classes of infection include protozoa, nematodes, cestodes, and ectoparasites. Ocular parasitic infections can manifest in any part of the eye; the disease manifestations are frequently characterized as either posterior or anterior eye disease. Parasite-induced lesions may be due to damage directly caused by the parasite, indirect pathology caused by toxic products or the immune response initiated by infectious parasitism. This review characterized the parasite-induced lesions in the posterior segment of the eye. Prompt diagnosis and early treatment of these lesions can reduce ocular morbidity. The method of the literature search was conducted on PubMed, Elsevier Scopus database, and Google Scholar with no limitation on the year of publication databases. It was limited to English articles published for ocular lesions in clinical studies and was focused on parasitic infections of the eye. PMID:26862090

  15. Expression of inducible nitric oxide synthase in experimental viral myocarditis.

    PubMed

    Glück, B; Merkle, I; Dornberger, G; Stelzner, A

    2000-05-01

    Nitric oxide (NO) is an important bioactive molecule with regulatory, cytotoxic or cytoprotective properties. In virus-induced myocarditis, NO mediates host defense mechanisms against the infection or causes cardiac dysfunctions. NO is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). The expression of the inducible form of the nitric oxide synthase (iNOS) is regulated by cytokines, involved in the complex myocardial immune response to enterovirus infections. The present study was undertaken to characterize the role of iNOS and NO in the murine model of viral myocarditis induced by coxsackievirus B3 (CVB3). In response to CVB3 infection we investigated the time course of iNOS induction in correlation with cytokine mRNA expression (TNF-alpha, IL-1 alpha, IFN-gamma, TGF-beta) in the heart of NMRI mice by RT-PCR. Positive PCR signals for viral RNA were found in the acute and chronic stage of disease by seminested PCR, indicating the persistence of viral genome. We found distinct expression of iNOS at all time points (1, 2, 3, 4, 7, 14, 28, 56, 98 days post infection [p.i.]). Higher iNOS mRNA levels were identified between days 4 until 28 p.i. in comparison to day 56 and 98 p.i. using densitometric values. The mRNA of the inflammatory cytokines TNF-alpha, IL-1 alpha, IFN-gamma appeared at days 1, 4, and 7 p.i., peaked at day 7 p.i. and persisted until day 98 p.i. Similar like the iNOS mRNA pattern was the expression profile of TGF-beta. Using in situ hybridization and immunohistochemistry iNOS was localized in infiltrates, vascular endothelial cells, smooth muscle cells, myocytes and throughout the interstitial spaces between myocardial fibers in the heart sections of NMRI mice. Increased levels of NO were measured as total nitrate/nitrite concentration in the sera of mice from day 7 until day 28 p.i.

  16. The Prognostic Role of QTc Interval in Acute Myocarditis

    PubMed Central

    Hung, Yuan; Lin, Wei-Hsiang; Lin, Chin-Sheng; Cheng, Shu-Meng; Tsai, Tsung-Neng; Yang, Shih-Ping; Lin, Wen-Yu

    2016-01-01

    Background Acute myocarditis is an inflammatory disease of the myocardium. Although a fulminant course of the disease is difficult to predict, it may lead to acute heart failure and death. Previous studies have demonstrated that reduced left ventricular systolic function and prolonged QRS duration can predict the fulminant course of acute myocarditis. This study aimed to identify whether prolonged QTc interval could also be predictive of fulminant disease in this population. Methods We retrospectively included 40 patients diagnosed with acute myocarditis who were admitted to our hospital between 2002 and 2013. They were divided into the fulminant group (n = 9) and the non-fulminant group (n = 31). Clinical symptoms, laboratory findings, electrocardiographic, and echocardiographic parameters were analyzed. Multivariate logistic regression analysis was used to identify the independent factors predictive of fulminant disease. Results Patients with fulminant myocarditis had a higher mortality rate than those with non-fulminant disease (55.6% vs. 0%, p < 0.001). Multivariate analysis revealed that wider QRS durations (133.22 ± 45.85 ms vs. 92.81 ± 15.56 ms, p = 0.030) and longer QTc intervals (482.78 ± 69.76 ms vs. 412.00 ± 33.31 ms, p = 0.016) were significant predictors associated with a fulminant course of myocarditis. Conclusions Prolonged QRS duration and QTc interval, upon patient admission, may be associated with an increased risk of fulminant disease and increased in-hospital mortality. Therefore, early recognition of fulminant myocarditis and early mechanical support could provide improved patient outcomes. PMID:27122953

  17. Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes.

    PubMed

    Dieval, Céline; Deligny, Christophe; Meyer, Alain; Cluzel, Philippe; Champtiaux, Nicolas; Lefevre, Guillaume; Saadoun, David; Sibilia, Jean; Pellegrin, Jean-Luc; Hachulla, Eric; Benveniste, Olivier; Hervier, Baptiste

    2015-07-01

    Antisynthetase syndrome (aSS) corresponds to an overlapping inflammatory myopathy identified by various myositis-specific autoantibodies (directed against tRNA-synthetases). Myocardial involvement in this condition is poorly described.From a registry of 352 aSS patients, 12 cases of myocarditis were retrospectively identified on the basis of an unexplained increase in troponin T/I levels associated with either suggestive cardiac magnetic resonance imaging (MRI) findings, nonsignificant coronary artery abnormalities or positive endomyocardial biopsy.The prevalence of myocarditis in aSS is 3.4% and was not linked to any autoantibody specificity: anti-Jo1 (n = 8), anti-PL7 (n = 3), and anti-PL12 (n = 1). Myocarditis was a part of the first aSS manifestations in 42% of the cases and was asymptomatic (n = 2) or revealed by an acute (n = 4) or a subacute (n = 6) cardiac failure. It should be noted that myocarditis was always associated with an active myositis. When performed (n = 11), cardiac MRI revealed a late hypersignal in the T1-images in 73% of the cases (n = 8). Half of the patients required intensive care. Ten patients (83%) received dedicated cardiotropic drugs. Steroids and at least 1 immunosuppressive drug were given in all cases. After a median follow-up of 11 months (range 0-84) 9 (75%) patients recovered whereas 3 (25%) developed a chronic cardiac insufficiency. No patient died.The prevalence of myocarditis in aSS is similar to that of other inflammatory myopathies. Although the prognosis is relatively good, myocarditis is a severe condition and should be carefully considered as a possible manifestation in active aSS patients.

  18. The distribution of Echinococcus granulosus in moose: evidence for parasite-induced vulnerability to predation by wolves?

    PubMed

    Joly, Damien O; Messier, François

    2004-08-01

    The role of parasites in influencing the trophic dynamics of hosts is becoming increasingly recognized in the ecological literature. Echinococcus granulosus is a tapeworm that relies on the predator-prey relationship between the definitive host (wolf, Canis lupus) and the intermediate host, (moose, Alces alces) to complete its life cycle. Heavy infection by E. granulosus may predispose moose to increased risk of predation by wolves. Theory predicts that parasite-induced vulnerability to predation will reduce the degree of aggregation of parasites in a host population. We tested for different levels of aggregation of E. granulosus in moose in areas of low, moderate, and high levels of wolf predation using Green's coefficient of dispersion. Parasite aggregation was lower in an area with high predation rate, thus we hypothesize that heavy infection by E. granulosus predisposes moose to predation by wolves. This increase in predation rate due to parasite infection may influence the role of wolves in regulating moose populations. We discuss alternative explanations for the negative correlation between predation rate and parasite aggregation.

  19. Thoratec left ventricular assist device removal after toxic myocarditis.

    PubMed

    Leontiadis, Evangelos; Morshuis, Michiel; Arusoglu, Latif; Cobaugh, Dagmar; Koerfer, Reiner; El-Banayosy, Aly

    2008-12-01

    The clinical manifestation and natural history of myocarditis range is variable from asymptomatic stages to intractable circulatory compromise and death. Supportive therapy is paramount in the treatment of this condition. The use of mechanical circulatory support as bridge-to-recovery or bridge-to-transplantation in cases of cardiovascular collapse is often the only therapeutic option for these patients. We report the case of an adolescent boy with toxic myocarditis, due to cannabis abuse, who was supported with a Thoratec left ventricular assist device (Thoratec Laboratories Corp, Pleasanton, CA) for 96 days before device removal. PMID:19022028

  20. Silencing MicroRNA-155 Attenuates Cardiac Injury and Dysfunction in Viral Myocarditis via Promotion of M2 Phenotype Polarization of Macrophages

    PubMed Central

    Zhang, Yingying; Zhang, Mengying; Li, Xueqin; Tang, Zongsheng; Wang, Xiangmin; Zhong, Min; Suo, Qifeng; Zhang, Yao; Lv, Kun

    2016-01-01

    Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4+ T lymphocytes during acute myocarditis. In contrast with wildtype (WT) mice, microRNA-155−/− mice developed attenuated viral myocarditis, which was characterized by decreased cardiac inflammation and decreased intracardiac CD45+ leukocytes. Hearts of microRNA-155−/− mice expressed decreased levels of the IFN-γ and increased levels of the cytokines IL-4 and IL-13. Although total CD4+ and regulatory T cells were unchanged in miR-155−/− spleen proportionally, the activation of T cells and CD4+ T cell proliferation in miR-155−/− mice were significantly decreased. Beyond the acute phase, microRNA-155−/− mice had reduced mortality and improved cardiac function during 5 weeks of follow-up. Moreover, silencing microRNA-155 led to increased levels of alternatively-activated macrophages (M2) and decreased levels of classically-activated macrophages (M1) in the heart. Combined, our studies suggest that microRNA-155 confers susceptibility to viral myocarditis by affecting macrophage polarization, and thus may be a potential therapeutic target for viral myocarditis. PMID:26931072

  1. Potential for parasite-induced biases in aquatic invertebrate population studies

    USGS Publications Warehouse

    Fisher, Justin D.L.; Mushet, David M.; Stockwell, Craig A.

    2014-01-01

    Recent studies highlight the need to include estimates of detection/capture probability in population studies. This need is particularly important in studies where detection and/or capture probability is influenced by parasite-induced behavioral alterations. We assessed potential biases associated with sampling a population of the amphipod Gammarus lacustris in the presence of Polymorphus spp. acanthocephalan parasites shown to increase positive phototaxis in their amphipod hosts. We trapped G. lacustris at two water depths (benthic and surface) and compared number of captures and number of parasitized individuals at each depth. While we captured the greatest number of G. lacustris individuals in benthic traps, parasitized individuals were captured most often in surface traps. These results reflect the phototaxic movement of infected individuals from benthic locations to sunlit surface waters. We then explored the influence of varying infection rates on a simulated population held at a constant level of abundance. Simulations resulted in increasingly biased abundance estimates as infection rates increased. Our results highlight the need to consider parasite-induced biases when quantifying detection and/or capture probability in studies of aquatic invertebrate populations.

  2. Cranberry Resistance to Dodder Parasitism: Induced Chemical Defenses and Behavior of a Parasitic Plant.

    PubMed

    Tjiurutue, Muvari Connie; Sandler, Hilary A; Kersch-Becker, Monica F; Theis, Nina; Adler, Lynn A

    2016-02-01

    Parasitic plants are common in many ecosystems, where they can structure community interactions and cause major economic damage. For example, parasitic dodder (Cuscuta spp.) can cause up to 80-100 % yield loss in heavily infested cranberry (Vaccinium macrocarpon) patches. Despite their ecological and economic importance, remarkably little is known about how parasitic plants affect, or are affected by, host chemistry. To examine chemically-mediated interactions between dodder and its cranberry host, we conducted a greenhouse experiment asking whether: (1) dodder performance varies with cranberry cultivar; (2) cultivars differ in levels of phytohormones, volatiles, or phenolics, and whether such variation correlates with dodder parasitism; (3) dodder parasitism induced changes in phytohormones, volatiles, or phenolics, and whether the level of inducible response varied among cultivars. We used five cranberry cultivars to assess host attractiveness to dodder and dodder performance. Dodder performance did not differ across cultivars, but there were marginally significant differences in host attractiveness to dodder, with fewer dodder attaching to Early Black than to any other cultivar. Dodder parasitism induced higher levels of salicylic acid (SA) across cultivars. Cultivars differed in overall levels of flavonols and volatile profiles, but not phenolic acids or proanthocyanidins, and dodder attachment induced changes in several flavonols and volatiles. While cultivars differed slightly in resistance to dodder attachment, we did not find evidence of chemical defenses that mediate these interactions. However, induction of several defenses indicates that parasitism alters traits that could influence subsequent interactions with other species, thus shaping community dynamics. PMID:26905738

  3. Characterization of the Myocarditis during the worst outbreak of dengue infection in China.

    PubMed

    Li, Yingying; Hu, Zhongwei; Huang, Yuli; Li, Jianping; Hong, Wenxin; Qin, Zhihui; Tong, Yuwei; Li, Jinglong; Lv, Mingfang; Li, Meiyu; Zheng, Xiaoke; Hu, Jun; Hua, Jinghai; Zhang, Fuchun; Xu, Ding-Li

    2016-07-01

    Myocarditis is a common complication of severe dengue infection. However, data about prevalence and characterization of myocarditis in dengue are still lacking. In 2014, the worst outbreak of dengue in the last two decades in China occurred. In this study, we described the clinical and laboratory diagnostic features of dengue with myocarditis. Totally, 1782 diagnosed dengue patients were admitted from August to October, 2014, all of whom were subjected to electrocardiogram, ultrasound cardiogram, and cardiac enzyme test. About 201 cases of dengue patients were diagnosed with myocarditis and the prevalence of myocarditis in hospitalized dengue was 11.28%. The prevalence of myocarditis in nonsevere dengue with warning signs and severe dengue [NSD(WS+)/SD] and nonsevere dengue without warning signs [NSD(WS-)] was 46.66% and 9.72%, respectively. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac symptoms, supraventricular tachycardia (14.29% vs. 0%, P < 0.001), atrial fibrillation (25.71% vs. 10.24%, P = 0.019) and heart failure compared with NSD (WS-) patients with myocarditis. About 150 cases of dengue patients without myocarditis in the same period of time in department of Cardiology were recruited as control group. The proportion of NSD(WS+)/SD in dengue patients with and without myocarditis was 17.41% and 2.53%, respectively. Dengue patients with myocarditis experienced longer hospital stay than those without myocarditis (7.17 ± 4.64 vs. 5.98 ± 2.69, P = 0.008). There was no difference between patients with and without myocarditis in the proportion of symptoms, auxiliary methods abnormality, arrhythmia, and heart failure on the discharge day. Our study demonstrates the prevalence of myocarditis in worst outbreak of dengue in China was 11.28% and the incidence of myocarditis increased with the severity of dengue. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac complication compared

  4. West Nile Virus Encephalitis and Myocarditis in Wolf and Dog

    PubMed Central

    Heinz-Taheny, Kathleen; Osborne, Tanasa S.; Novak, Robert J.; Lewis, Beth A.; Firth, Margaret L.

    2003-01-01

    In the third season (2002) of the West Nile virus epidemic in the United States, two canids (wolf and dog) were diagnosed with West Nile virus encephalitis and myocarditis with similarities to known affected species (humans, horses, and birds). The West Nile virus infections were confirmed by immunohistochemistry and polymerase chain reaction. PMID:14609468

  5. Parasite-induced aposematism” protects entomopathogenic nematode parasites against invertebrate enemies

    PubMed Central

    Fenton, Andy; Speed, Michael P.

    2016-01-01

    Aposematism is a well-known strategy in which prey defend themselves from predation by pairing defenses such as toxins, with warning signals that are often visually conspicuous color patterns. Here, we examine the possibility that aposematism can be induced in a host by colonies of infectious parasites in order to protect the parasites from the consequences of attacks on the host. Earlier studies show that avian predators are reluctant to feed on carcasses of host prey that are infected with the entomopathogenic nematode, Heterorhabditis bacteriophora. As the age of infection increases, the parasites kill and preserve the host and subsequently cause its color to change, becoming bright pink then red. Nematode colonies in dead hosts may also be vulnerable, however, to nocturnally active foragers that do not use vision in prey detection. Here, then we test a novel hypothesis that the nematode parasites also produce a warning odor, which functions to repel nocturnally active predators (in this case, the beetle Pterostichus madidus). We show that beetles decrease their feeding on infected insect prey as the age of infection increases and that olfactory cues associated with the infections are effective mechanisms for deterring beetle predation, even at very early stages of infection. We propose that “parasite-induced aposematism” from the nematodes serves to replace the antipredator defenses of the recently killed host. Because sessile carcasses are exposed to a greater range of predators than the live hosts, several alternative defense mechanisms are required to protect the colony, hence aposematic signals are likely diverse in such “parasite-induced aposematism.” PMID:27004015

  6. Veno-arterial extracorporeal membrane oxygenation for cardiogenic shock due to myocarditis in adult patients.

    PubMed

    Pozzi, Matteo; Banfi, Carlo; Grinberg, Daniel; Koffel, Catherine; Bendjelid, Karim; Robin, Jacques; Giraud, Raphaël; Obadia, Jean François

    2016-07-01

    Myocarditis is an inflammatory disease of the heart muscle with established histological, immunological and immunohistochemical diagnostic criteria. Different triggers could be advocated as possible etiologies of myocarditis such as viral and non-viral infections, medications, systemic autoimmune diseases and toxic reactions. The spectrum of clinical presentations of myocarditis is broad and varies from subclinical asymptomatic courses to refractory cardiogenic shock. The prognosis of patients with myocarditis depends mainly on the severity of clinical presentation. In particular, myocarditis patients developing cardiogenic shock refractory to optimal maximal medical treatment may benefit from the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a temporary mechanical circulatory support (MCS). The aim of the present report is to offer a review of the most important articles of the literature showing the results of VA-ECMO in the specific setting of cardiogenic shock due to myocarditis in adult patients. PMID:27499982

  7. Torsade de pointes tachycardia as a rare manifestation of acute enteroviral myocarditis

    PubMed Central

    Badorff, C; Zeiher, A; Hohnloser, S

    2001-01-01

    A patient with cardiac arrest and documented torsade de pointes ventricular tachycardia is presented in whom acute coxsackievirus B2 myocarditis was identified as the most likely underlying cardiac condition. This case shows that torsade de pointes may occur as a rare manifestation of viral myocarditis. Serial serological tests and endomyocardial biopsies may be helpful in establishing a diagnosis in such patients.


Keywords: torsade de pointes; ventricular tachycardia; viral myocarditis PMID:11602535

  8. Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis.

    PubMed

    Shaughnessy, Kerry K; Bouchard, Susan M; Mohr, Melinda R; Herre, John M; Salkey, Kimberly S

    2010-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare serious adverse effect associated with a variety of medications. We present a case of minocycline-induced DRESS syndrome, which resulted in acute renal failure, transient thyroiditis, and transaminitis, and a persistent lymphocytic myocarditis resulting in congestive heart failure. To our knowledge, this is the third reported case of minocycline-induced myocarditis. Additionally, we report successful plasmapheresis and rituximab treatment for minocycline-induced myocarditis associated with the DRESS syndrome.

  9. Salmonella enteritidis induced myocarditis in a 16-year-old girl.

    PubMed

    Childs, Lucy; Gupta, Sandy

    2012-11-27

    Myocarditis typically presents with non-specific clinical symptoms, and can easily be missed in the absence of a high index of clinical suspicion. Myocarditis caused by bacterial pathogens is rare in immunocompetent individuals, more commonly seen following viral infection. Although more classically associated with typhoid fever and gastroenteritis, Salmonella species are a rare cause of myocarditis. We report a case of Salmonella enteritidis-induced myocarditis after gastrointestinal infection in a 16 year-old girl, and discuss the diagnostic tools currently utilised to ascertain the diagnosis.

  10. [Prognostic significance of bicycle ergometry test in patients with myocarditis].

    PubMed

    Gavalova, R F; Borodina, V I

    1992-04-01

    A total of 42 patients with rheumatic carditis were examined in the acute-subacute period and following 3-5 years. Seventeen patients were diagnosed as having primary rheumatic carditis, 9 presented with tonsillogenic rheumatic carditis, and 16 had viral rheumatic carditis. The diagnosis of myocarditis was established on the basis of clinical, immunological, and virological findings. The study involved ECG, PhCG, PCG, and bicycle ergometer testing recordings. Groups of patients with good and poor prognosis were identified. Low threshold exercise, exercise-inadequate tachycardia, complex cardiac arrhythmias, phasic myocardial hypodynamic syndrome and volume exercise syndrome that are formed during performance are prognostically poor indicators. More profound electric and mechanic dysfunctions were observed in patients with tonsillogenic or viral myocarditis.

  11. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection.

    PubMed

    Costagliola, Alessandro; Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. PMID:27413751

  12. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection

    PubMed Central

    Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. PMID:27413751

  13. Mononuclear cell secretome protects from experimental autoimmune myocarditis

    PubMed Central

    Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

    2015-01-01

    Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. PMID:23321350

  14. Low rate of cardiovascular events in patients with acute myocarditis diagnosed by cardiovascular magnetic resonance

    PubMed Central

    De Stefano, Luciano; Yeyati, Ezequiel Levy; Pietrani, Marcelo; Kohan, Andres; Falconi, Mariano; Benger, Juan; Dragonetti, Laura; Garcia-Monaco, Ricardo; Cagide, Arturo

    2014-01-01

    Background Myocarditis is a relatively common inflammatory disease that affects the myocardium. Infectious disease accounts for most of the cases either because of a direct viral infection or post-viral immune-mediated reaction. Cardiovascular magnetic resonance (CMR) has become an established non-invasive diagnosis tool for acute myocarditis. A recent large single centre study with patients with biopsy-proven viral myocarditis undergoing CMR scans found a high rate of mortality. The aim of this study was to assess the rate of clinical events in our population of patients with diagnosed myocarditis by CMR scan. Methods Patients who consulted to the emergency department with diagnosis of myocarditis by CMR were retrospectively included in the study from January 2008 to May 2012. A CMR protocol was used in all patients, and were followed up to assess the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or implantable cardiac defibrillator (ICD). A descriptive statistical analysis was performed. Results Thirty-two patients with myocarditis were included in the study. The mean age was 42.6±21.2 years and 81.2% were male. In a mean follow up of 30.4±17.8 months, the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or ICD was 15.6% (n=5). Two patients had heart failure (one of them underwent heart transplant), one patient needed ICD because of ventricular tachycardia and two other patients were re-hospitalized, for recurrent chest pain and for recurrent myocarditis respectively. Conclusions In our series of acute myocarditis diagnosed by CMR we found a low rate of cardiovascular events without mortality. These findings might oppose data from recently published myocarditis trials. PMID

  15. Parasite-induced aggression and impaired contest ability in a fish host

    PubMed Central

    2010-01-01

    Background Success of trophically transmitted parasites depends to a great extent on their ability to manipulate their intermediate hosts in a way that makes them easier prey for target hosts. Parasite-induced behavioural changes are the most spectacular and diverse examples of manipulation. Most of the studies have been focused on individual behaviour of hosts including fish. We suggest that agonistic interactions and territoriality in fish hosts may affect their vulnerability to predators and thus the transmission efficiency of trophically transmitted parasites. The parasite Diplostomum spathaceum (Trematoda) and juvenile rainbow trout, Oncorhynchus mykiss, were used to study whether infection can alter aggression rates and territorial behaviour of intermediate fish hosts. Results The changes in behaviour of rainbow trout, Oncorhynchus mykiss, infected with an eye fluke Diplostomum spathaceum (Trematoda), was monitored over the course of an experimental infection for 1.5 months. At the beginning of their development, not yet infective D. spathaceum metacercariae decreased the aggressiveness of rainbow trout. By the time that metacercariae were fully infective to their definitive hosts, the aggressiveness increased and exceeded that of control fish. Despite the increased aggressiveness, the experimentally infected fish lost contests for a territory (dark parts of the bottom) against the control fish. Conclusions The results obtained indicate that the parasitized fish pay the cost of aggressiveness without the benefit of acquiring a territory that would provide them with better protection against predators. This behaviour should increase transmission of the parasite as expected by the parasite manipulation hypothesis. PMID:20226098

  16. A fatal case of acute HHV-6 myocarditis following allogeneic haemopoietic stem cell transplantation.

    PubMed

    Brennan, Yvonne; Gottlieb, David J; Baewer, David; Blyth, Emily

    2015-11-01

    Human herpesvirus 6 (HHV-6) is an ubiquitous virus that can reactivate in immunocompromised hosts, resulting in diverse clinical sequelae. We describe a case of fatal acute HHV-6 myocarditis in a patient who underwent allogeneic haemopoietic stem cell transplantation (HSCT). To our knowledge, this is the first reported case of biopsy proven HHV-6 myocarditis post-HSCT.

  17. ORI2 inhibits coxsackievirus replication and myocardial inflammation in experimental murine myocarditis.

    PubMed

    Lim, Byung-Kwan; Kim, Jin Hee

    2014-01-01

    We purified ORI2 [3-(3,4-dihydroxyphenyl)acrylic acid 1-(3,4-dihydroxyphenyl)-2-methoxycarbonylethyl ester] from an extract of the plant Isodon excisus. We tested the antiviral effect of ORI2 in a coxsackievirus-induced myocarditis model. Coxsackievirus B3 (CVB3) is a common cause of myocarditis and dilated cardiomyopathy. Activation of extracellular signal-regulated kinase (ERK) and Akt signaling in virus-infected cells is essential for CVB3 replication. Antiviral compounds were screened by HeLa cell survival assay. Several purified natural compounds were added to HeLa cells cultured in 96-well plates for 30 min after 1 multiplicity of infection (m.o.i) CVB3 infection. ORI2 significantly improved HeLa cell survival in a dose-dependent manner. For in vivo studies, BALB/c mice (n=20) were infected with CVB3, then 10 of the mice were treated by daily intraperitoneal injections of ORI2 (100 mM) for 3 consecutive days. ORI2 treatment significantly improved early survival in the treated mice compared to untreated mice (85% vs. 50%, respectively). Organ virus titers and myocardial damage were significantly lower in the ORI2-treated mice than in untreated mice. These results demonstrate that ORI2, delivered by intraperitoneal injection after CVB3 infection, has a significant antiviral effect by markedly inhibiting virus replication, resulting in a decrease in organ virus titer and myocardial damage. ORI2 may be developed as a potential therapeutic agent for the treatment of CVB3 infections. PMID:25273388

  18. Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis

    PubMed Central

    Weissleder, Ralph; Lichtman, Andrew H.; McCarthy, Jason R.; Libby, Peter

    2015-01-01

    Rationale The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditides. Objective This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8+ T lymphocytes. Methods and Results We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8+ T lymphocyte-mediated myocarditis using fluorescence reflectance imaging (FRI), validated by histologic examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with co-registered computed tomography imaging (FMT-CT). A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle vs. dexamethasone: 504±263 vs. 194±77 fluorescence intensities in hearts, P=0.002). Conclusions Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention. PMID:26199323

  19. Acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis.

    PubMed

    Kitulwatte, Indira D; Kim, Patrick J H; Pollanen, Michael S

    2015-09-01

    We report a case of acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis. A 48-year-old previously healthy male was found dead in his locked apartment. At autopsy he was found to be malnourished, and his lungs showed gross evidence of bilateral pneumonia with abscess formation and bullous emphysema. Multiple petechial hemorrhages were observed in the brain and mainly involved white matter in the cerebral hemispheres including the corpus callosum and internal capsule, as well as the cerebellum, brainstem, and spinal cord. Microscopy of the brain and spinal cord revealed perivenular hemorrhages, central microthrombi in venules with fibrin exudation into the subcortical white matter, and early perivenular demyelination associated with scanty mixed cellular infiltrates. Other microscopic features included widespread diffuse viral myocarditis, extensive suppurative bronchopneumonia, and chronic bronchitis. This case illustrates the death of a man with a rare fatal disease associated with two other potentially lethal diseases. The case also illustrates the importance of a holistic approach when determining the cause of death, especially when there are competing causes of death. PMID:26148811

  20. Quantitative MRI myocarditis analysis by a PCA-based object recognition algorithm

    NASA Astrophysics Data System (ADS)

    Romano, Rocco; Acernese, Fausto; Giordano, Gerardo; De Giorgi, Igino; Orientale, Antonio; Babino, Giovanni; Barone, Fabrizio

    2016-03-01

    Magnetic Resonance Imaging (MRI) has shown promising results in diagnosing myocarditis that can be qualitatively observed as enhanced pixels on the cardiac muscles images. In this paper, a quantitative MRI Myocarditis Analysis is proposed. Analysis consists in introducing a myocarditis index, defined as the ratio between enhanced pixels, representing an inflammation, and the total pixels of myocardial muscle. In order to recognize and quantify enhanced pixels, a PCA-based recognition algorithm is used. The algorithm, implemented in Matlab, was tested by examining a group of 12 patients, referred to MRI with presumptive, clinical diagnosis of myocarditis. To assess intra- and interobserver variability, two observers blindly analyzed data related to the 12 patients by delimiting myocardial region and selecting enhanced pixels. After 10 days the same observers redid the analysis. The obtained myocarditis indexes were compared to an ordinal variable (values in the 1 - 5 range) that represented the blind assessment of myocarditis seriousness given by two radiologists on the base of the patient case histories. Results show that there is a significant correlation (P < 0:001; r = 0:96) between myocarditis indexes and the radiologists' clinical judgments. Furthermore, a good intraobserver and interobserver reproducibility was obtained.

  1. Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

    PubMed Central

    Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Ianni, Barbara Maria; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Frade, Amanda; Donadi, Eduardo; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

    2012-01-01

    Background Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that

  2. Protective Role of the Cholinergic Anti-Inflammatory Pathway in a Mouse Model of Viral Myocarditis

    PubMed Central

    Jing-Lin, Zhao; Wen-Wu, Zhang; Xue-Si, Chen; Xing-Xing, Chen; Yue-Chun, Li

    2014-01-01

    Background Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis. Methodology/Principal Findings In a coxsackievirus B3 murine myocarditis model (Balb/c), nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group. Conclusions/Significance These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases

  3. Acute nonrheumatic streptococcal myocarditis resembling ST-elevation acute myocardial infarction in a young patient

    PubMed Central

    Jurado, Margarita; Porres-Aguilar, Mateo; Olivas-Chacon, Cristina; Porres-Muñoz, Mateo; Mukherjee, Debabrata; Taveras, Juan

    2015-01-01

    Acute myocarditis can be induced by various concomitant disease processes including infections. Most of these cases are viral in origin; however, bacterial infections are also implicated to a lesser degree. Group A streptococcus is a frequent culprit in bacterial-induced myocarditis. Its diagnosis is suspected by the presence of signs and symptoms of rheumatic fever as established by the Jones criteria. The development and refinement of current diagnostic tools has improved our ability to identify specific pathogens. It has been found that group A streptococcus may be responsible for more cases of infection-induced acute myocarditis than previously thought, and often without the clinical features of rheumatic fever. We present the case of a 43-year-old man hospitalized with chest pain that was initially diagnosed as an acute ST-elevation myocardial infarction. Further evaluation confirmed that his chief complaint was due to acute nonrheumatic streptococcal myocarditis. PMID:25829649

  4. High-Degree Atrioventricular Block in a Child with Acute Myocarditis

    PubMed Central

    Caughey, Robert W.; Humphrey, John M.; Thomas, Patricia E.

    2014-01-01

    Background Viral myocarditis is a common cause of transient electrocardiogram (EKG) abnormalities in children. The clinical presentation of acute myocarditis ranges from asymptomatic infection to fulminant heart failure and sudden death. Many children present with nonspecific symptoms such as dyspnea or vomiting, frequently leading to misdiagnosis. EKG abnormalities are a sensitive indicator of acute myocarditis and are present in more than 90% of cases. Case Report A 13-year-old female suffered a syncopal episode and was found to have high-grade atrioventricular (AV) block caused by acute presumed viral myocarditis. With close monitoring, the EKG abnormalities resolved over the following 48 hours. In this case report, we discuss the incidence, pathogenesis, and outcomes of conduction disturbances in acute myocarditis. Conclusion High-degree AV block can occur in patients with acute myocarditis, and higher-degree AV block is correlated with greater myocardial injury. Additionally, severity of pathological changes may reflect the reversibility of AV block. In the majority of cases, however, this rhythm disturbance is transient and does not require permanent pacemaker placement. PMID:24940135

  5. Successful early diagnosis and treatment in a case of Toxocara canis-induced eosinophilic myocarditis with eosinophil-rich pericardial effusion.

    PubMed

    Sangen, Hideto; Tanabe, Jun; Takano, Hitoshi; Shimizu, Wataru

    2015-01-01

    Fulminant myocarditis can become fatal if left untreated. Treatments for most types of myocarditis, including mechanical support, are limited. However, immediate systemic corticosteroids are known to be effective against eosinophilic myocarditis; therefore, prompt diagnosis of this disease is crucial. Unfortunately, the standard diagnostic tool for myocarditis, endomyocardial biopsy, does not provide immediate histopathological findings. Thus, a rapid diagnostic tool for identifying types of myocarditis is urgently required. We report here the first case of Toxocara canis-induced eosinophilic fulminant myocarditis which was diagnosed based on eosinophil-rich pericardial effusion where the patient recovered with early corticosteroid therapy. PMID:26338242

  6. Acute eosinophilic myocarditis with dramatic response to steroid therapy: the central role of echocardiography in diagnosis and follow-up.

    PubMed

    Eppenberger, Manuela; Hack, Dietrich; Ammann, Peter; Rickli, Hans; Maeder, Micha T

    2013-01-01

    Acute eosinophilic myocarditis is a rare cause of acute heart failure. We present the case of a 32-year-old woman who had presumptive eosinophilic myocarditis as part of a generalized hypersensitivity reaction (Drug Rash with Eosinophilia and Systemic Symptoms [DRESS] syndrome) that exhibited a dramatic response to steroid therapy. We highlight the central role of 2-dimensional and tissue-Doppler echocardiography in the diagnosis of myocarditis and the serial evaluation of left ventricular systolic and diastolic function in this setting.

  7. The endoparasitoid, Cotesia vestalis, regulates host physiology by reprogramming the neuropeptide transcriptional network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endoparasitoids develop inside another insect; success depends on regulating host immunity and development by maternal factors injected into hosts during oviposition, including venom, polydnaviruses and teratocytes. Although prior results provide insights into parasitism-induced immunosuppression, l...

  8. Increased Echogenicity and Radiodense Foci on Echocardiogram and MicroCT in Murine Myocarditis

    PubMed Central

    Dalton, Nancy D.; Gu, Yusu; Chao, Chieh-Ju; Peterson, Kirk L.; Knowlton, Kirk U.

    2016-01-01

    Objectives To address the question as to whether echocardiographic and/or microcomputed tomography (microCT) analysis can be utilized to assess the extent of Coxsackie B virus (CVB) induced myocarditis in the absence of left ventricular dysfunction in the mouse. Background Viral myocarditis is a significant clinical problem with associated inflammation of the myocardium and myocardial injury. Murine models of myocarditis are commonly used to study the pathophysiology of the disease, but methods for imaging the mouse myocardium have been limited to echocardiographic assessment of ventricular dysfunction and, to a lesser extent, MRI imaging. Methods Using a murine model of myocarditis, we used both echocardiography and microCT to assess the extent of myocardial involvement in murine myocarditis using both wild-type mice and CVB cleavage-resistant dystrophin knock-in mice. Results Areas of increased echogenicity were only observed in the myocardium of Coxsackie B virus infected mice. These echocardiographic abnormalities correlated with the extent of von Kossa staining (a marker of membrane permeability), inflammation, and fibrosis. Given that calcium phosphate uptake as imaged by von Kossa staining might also be visualized using microCT, we utilized microCT imaging which allowed for high-resolution, 3-dimensional images of radiodensities that likely represent calcium phosphate uptake. As with echocardiography, only mice infected with Coxsackie B virus displayed abnormal accumulation of calcium within individual myocytes indicating increased membrane permeability only upon exposure to virus. Conclusions These studies demonstrate new, quantitative, and semi-quantitative imaging approaches for the assessment of myocardial involvement in the setting of viral myocarditis in the commonly utilized mouse model of viral myocarditis. PMID:27486657

  9. Characterization of Benign Myocarditis Using Quantitative Delayed-Enhancement Imaging Based on Molli T1 Mapping

    PubMed Central

    Toussaint, Marcel; Gilles, Raymond J.; Azzabou, Noura; Marty, Benjamin; Vignaud, Alexandre; Greiser, Andreas; Carlier, Pierre G.

    2015-01-01

    Abstract Delayed contrast enhancement after injection of a gadolinium-chelate (Gd-chelate) is a reference imaging method to detect myocardial tissue changes. Its localization within the thickness of the myocardial wall allows differentiating various pathological processes such as myocardial infarction (MI), inflammatory myocarditis, and cardiomyopathies. The aim of the study was first to characterize benign myocarditis using quantitative delayed-enhancement imaging and then to investigate whether the measure of the extracellular volume fraction (ECV) can be used to discriminate between MI and myocarditis. In 6 patients with acute benign myocarditis (32.2 ± 13.8 year-old, subepicardial late gadolinium enhancement [LGE]) and 18 patients with MI (52.3 ± 10.9 year-old, subendocardial/transmural LGE), myocardial T1 was determined using the Modified Look-Locker Imaging (MOLLI) sequence at 3 Tesla before and after Gd-chelate injection. T1 values were compared in LGE and normal regions of the myocardium. The myocardial T1 values were normalized to the T1 of blood, and the ECV was calculated from T1 values of myocardium and blood pre- and post-Gd injection. In both myocarditis and MI, the T1 was lower in LGE regions than in normal regions of the left ventricle. T1 of LGE areas was significantly higher in myocarditis than in MI (446.8 ± 45.8 vs 360.5 ± 66.9 ms, P = 0.003) and ECV was lower in myocarditis than in MI (34.5 ± 3.3 vs 53.8 ± 13.0 %, P = 0.004). Both inflammatory process and chronic fibrosis induce LGE (subepicardial in myocarditis and subendocardial in MI). The present study demonstrates that the determination of T1 and ECV is able to differentiate the 2 histological patterns. Further investigation will indicate whether the severity of ECV changes might help refine the predictive risk of LGE in myocarditis. PMID:26512599

  10. A Rare Case of Toxic Myocarditis Caused by Bacterial Liver Abscess Mimicking Acute Myocardial Infarction

    PubMed Central

    Zou, Yuhai; Lin, Lin; Xiao, Hua; Xiang, Dingcheng

    2016-01-01

    Patient: Male, 66 Final Diagnosis: Toxic myocarditis Symptoms: — Medication: — Clinical Procedure: Emergency Specialty: Cardiology Objective: Rare disease Background: Chills, high fever, right upper abdomen pain, and increased white blood cell count are the main and common clinical features of bacterial liver abscess. It is rare to see bacterial liver abscess present symptoms of myocardial injury first, and this can lead to misdiagnosis. Case Report: We report a case of toxic myocarditis caused by bacterial liver abscess. The patient first presented with chest pain, ST segment elevation, and elevated TNI, which misled us to diagnose myocardial infarction, but the coronary artery had no stenosis or obstructive lesions after emergency coronary angiography. Then we modified the diagnosis to toxic myocarditis. Bacterial liver abscess was the proposed etiology after a series of auxiliary examinations. Finally, antibiotics and percutaneous liver puncture catheter drainage were used to improve the clinical outcome. Conclusions: It is rare that patients with bacterial liver abscess first present symptoms of myocardial injury. Differential diagnosis between myocarditis and myocardial infarction should be careful, as myocarditis is a diagnosis of exclusion, and coronary angiography is necessary to confirm coronary disease. Percutaneous liver puncture catheter drainage can effectively cure bacterial liver abscess. PMID:26726772

  11. Cardiac myosin-Th17 responses promote heart failure in human myocarditis

    PubMed Central

    Myers, Jennifer M.; Cooper, Leslie T.; Kem, David C.; Stavrakis, Stavros; Kosanke, Stanley D.; Shevach, Ethan M.; Fairweather, DeLisa; Stoner, Julie A.; Cox, Carol J.; Cunningham, Madeleine W.

    2016-01-01

    In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-β, and IL-23 as well as GM-CSF–secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17–producing T cells and IL-17–promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-β, IL-6, and IL-23 from myocarditic CD14+ monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option. PMID:27366791

  12. Acute mechanical circulatory support for fulminant myocarditis complicated by cardiogenic shock.

    PubMed

    Mody, Kanika P; Takayama, Hiroo; Landes, Elissa; Yuzefpolskaya, Melana; Colombo, Paolo C; Naka, Yoshifumi; Jorde, Ulrich P; Uriel, Nir

    2014-03-01

    In fulminant myocarditis complicated by cardiogenic shock, early mechanical circulatory support (MCS) may prevent cardiomyopathy and death. We sought to examine the outcomes of patients with fulminant myocarditis supported with MCS. A retrospective review of patients with acute cardiogenic shock treated with MCS from 2007 to 2013 was conducted, and patients with a diagnosis of fulminant myocarditis were included in this series. At our center, 260 patients received MCS for acute cardiogenic shock, and 11 were implanted for fulminant myocarditis. Eight received the Centrimag biventricular assist device (BIVAD), and three received veno-arterial extracorporeal membrane oxygenator (VA ECMO), though 1 VA ECMO-supported patient was transitioned to BIVAD due to refractory shock. The mean acute support time was 14.7 ± 4.4 days. Two patients required long-term left ventricular assist devices and were further supported for 55 and 112 days. Eight patients recovered with a mean ejection fraction of 54 ± 7 %, and one was successfully transplanted. Eight patients survived to discharge (73 %) with mean follow-up: 292.6 ± 306.8 days. All three deaths were due to neurologic complications. MCS should be considered in patients with fulminant myocarditis complicated by shock. With aggressive medical therapy, early utilization of MCS carries promising outcomes.

  13. Learning from myocarditis: mimicry, chaos and black holes.

    PubMed

    Rose, Noel R

    2014-01-01

    Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens.

  14. Learning from myocarditis: mimicry, chaos and black holes.

    PubMed

    Rose, Noel R

    2014-01-01

    Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens. PMID:24904749

  15. Detection of trichodysplasia spinulosa-associated polyomavirus in a fatal case of myocarditis in a seven-month-old girl.

    PubMed

    Tsuzuki, Shinya; Fukumoto, Hitomi; Mine, Sohtaro; Sato, Noriko; Mochizuki, Makoto; Hasegawa, Hideki; Sekizuka, Tsuyoshi; Kuroda, Makoto; Matsushita, Takeji; Katano, Harutaka

    2014-01-01

    Trichodysplasia spinulosa-associated polyomavirus (TSV) was identified in a seven-month-old girl with myocarditis. The number of TSV genomes detected was higher in the heart than in the other organs. The full-length TSV genome was cloned from the heart. This suggests a possible role of TSV infection in the pathogenesis of myocarditis in infants. PMID:25197415

  16. Lessons Learned and Questions Raised by an Atypical Case of Clozapine-Induced Myocarditis.

    PubMed

    Earnshaw, Charles H; Powell, Lucy; Haeney, Owen

    2016-01-01

    A Caucasian male in his early twenties suffering from treatment resistant schizophrenia was started on clozapine. After three days he developed tachycardia, a common side effect of clozapine induction. He had one temperature spike (38.9°C) on day ten after induction but remained clinically well. An ECG and blood tests were normal. Due to persistent tachycardia and an episode of collapse whilst seated on day 12, he was admitted to hospital for further investigation. A diagnosis of myocarditis was confirmed as a result of elevated cardiac enzyme levels and an echocardiogram. Following withdrawal of clozapine, supportive management, and initiation of cardiac medication, the patient made a successful recovery. He will be followed up with the cardiology team to ensure that his heart function returns to normal. Given the incidence of clozapine-induced myocarditis, the associated mortality risk, and diagnostic difficulties, this case raises questions about whether a formal system for identifying myocarditis should be adopted. PMID:27478671

  17. Necropsy diagnosis of myocarditis: a retrospective study using CD45RO immunohistochemistry

    PubMed Central

    Feeley, K; Harris, J; Suvarna, S

    2000-01-01

    Aim—To use CD45RO immunohistochemistry to investigate the numbers of T lymphocytes found in sections of myocardium from a routine necropsy series, and to determine the incidence of myocarditis in this series. Methods—Myocardial sections from 163 routine hospital necropsies were stained with CD45RO and the numbers of positive lymphocytes/mm2 were counted. The results were correlated with the H/E opinion and the clinical context of the necropsy. Results—Most (143) cases showed low numbers (0–3) of CD45RO positive lymphocytes/mm2. Fifteen cases showed 7–13 positive lymphocytes/mm2, comprising a wide variety of clinical conditions, generally with no specific cardiac pathology. Five cases showed 14 or more positive lymphocytes/mm2, comprising one case of active myocarditis, three cases of cardiac transplant rejection, and one post-transplant lymphoproliferative disorder, all conditions in which large numbers of lymphocytes would be expected. Conclusions—The incidence of myocarditis in our series was 0.6%. In most cases the normal myocardium has a low T lymphocyte count (0–3/mm2). In some cases immunohistochemistry shows more positive cells than would have been expected on light microscopy. Immunohistochemistry is a useful and reliable means of confirming a diagnosis of myocarditis. The results support the conclusion of the 1997 ISFC task force that 14 or more lymphocytes or macrophages/mm2 of myocardium in the appropriate clinical context is a reliable threshold for the diagnosis of chronic myocarditis. Key Words: myocarditis • immunohistochemistry • T lymphocytes • necropsy PMID:10767832

  18. Immunohistochemical diagnosis of myocarditis on (infantile) autopsy material: Does it improve the diagnosis?

    PubMed

    Grasmeyer, Sarah; Madea, Burkhard

    2015-06-01

    The standard for the histopathologic diagnosis of myocarditis has been the Dallas criteria. Recently, immunohistochemical studies that include the specification and quantification of interstitial inflammatory cells have been proposed as the diagnostic approach for myocarditis. Cut-off limits regarding inflammatory cell numbers for the positive diagnosis of myocarditis have been recommended. However, it is unclear whether these can be applied to postmortem tissues or to infants, as they were established from endomyocardial biopsies and for adults. Nevertheless, cut-off limits for the postmortem diagnosis of myocarditis in the first year of life have been proposed. Studies using these cut-off limits identified myocarditis in a high percentage of presumed sudden infant death syndrome (SIDS) cases. These results were re-evaluated by the present study, which examined heart specimens from infants less than 1 year of age. The study had a test group of 92 SIDS cases and a control group of 15. Myocardial tissue was examined from eight standardized locations, stained with hematoxylin-eosin and for three different immunohistochemical reagents (LCA for leukocytes, CD68 for macrophages, CD45-RO for T-lymphocytes). Histopathological assessment of the number of inflammatory cells was carried out on an aggregate of 80 mm(2) of myocardial tissue per case. Myocarditis, based on the Dallas criteria, was histologically diagnosed in only two cases. Immunohistochemical quantification revealed elevated cell counts in the SIDS group for LCA and CD45-RO. However, those differences were neither statistically significant nor clinically relevant as the mean cell counts per mm(2) were low. The density of inflammatory cells differed considerably from section to section and even within single sections. Therefore the commonly used arithmetic mean value was not diagnostically relevant, suggesting cut-off values based on the arithmetic mean value as recommended in the literature, cannot be regarded

  19. Exercise-Triggered Chest Pain as an Isolated Symptom of Myocarditis in Children

    PubMed Central

    Tshimanga, Prisca; Daron, Benoît; Farhat, Nesrine; Desprechins, Brigitte; Gewillig, Marc

    2016-01-01

    In childhood, chest pain occurring at exercise is a common complaint. A cardiac etiology for it is exceptionally found, explaining that most children do not undergo systematic cardiological investigation. However, chest pain at exercise may manifest as the unique symptom of a viral myocarditis. Recognizing this form of myocardial injury, however, might help to avoid clinical deterioration by providing adequate care. In this paper, we report on two children presenting with the unique clinical symptom of chest pain related to physical activity and in whom laboratory and cardiac investigations suggested transient myocardial damage related to myocarditis. PMID:27478581

  20. Pyogranulomatous myocarditis due to Staphylococcus aureus septicaemia in two harbour porpoises (Phocoena phocoena).

    PubMed

    Siebert, U; Müller, G; Desportes, G; Weiss, R; Hansen, K; Baumgärtner, W

    2002-03-01

    Staphylococcus aureus septicaemia was diagnosed in a dead, stranded harbour porpoise from the German Baltic Sea and in a live harbour porpoise by-caught in inner Danish waters and taken into captivity. Lesions included pyogranulomatous myocarditis, necrotising suppurative bronchopneumonia, pyelonephritis, osteomyelitis and leptomeningitis, and abscesses in lymph nodes and skeletal muscles. The captive animal had fibrinous suppurative epicarditis and pyogranulomatous myocarditis with abscesses. In both animals the organism was suspected to have entered through skin lesions or via the respiratory tract. PMID:11918049

  1. Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice

    NASA Astrophysics Data System (ADS)

    Hong, Fashui; Wang, Ling; Yu, Xiaohong; Zhou, Yingjun; Hong, Jie; Sheng, Lei

    2015-08-01

    Currently, impacts of exposure to TiO2 nanoparticles (NPs) on the cardiovascular system are not well understood. The aim of this study was to investigate whether TiO2 NPs induce myocarditis and its underlying molecular mechanism in the cardiac inflammation in mice. Mice were exposed to TiO2 NPs for 6 months; biochemical parameters of serum and expression of Th1-related and Th2-related cytokines in the heart were investigated. The results showed that TiO2 NP exposure resulted in cardiac lesions coupling with pulmonary inflammation; increases of aspartate aminotransferase (AST), creatine kinase (CK), C-reaction protein (CRP), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels; and a reduction of nitric oxide (NOx) level in the serum. These were associated with increases of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, transforming growth factor-β (TGF-β), creatine kinase, CRP, adhesion molecule-1, and monocyte chemoattractant protein-1, interferon-γ (IFN-γ), signal transducers and activators of transcription (STAT)1, STAT3, or STAT6, GATA-binding domain-3, GATA-binding domain-4, endothelin-1 expression levels, and T-box expressed in T cells expression level that is the master regulator of pro-inflammatory cytokines and transcription factors in the heart. These findings imply that TiO2 NP exposure may increase the occurrence and development of cardiovascular diseases.

  2. NADPH oxidase inhibition ameliorates Trypanosoma cruzi-induced myocarditis during Chagas disease

    PubMed Central

    Dhiman, Monisha; Garg, Nisha Jain

    2015-01-01

    Trypanosoma cruzi, the aetiological agent of Chagas disease, invades nucleated mammalian cells including macrophages. In this study, we investigated the crosstalk between T. cruzi-induced immune activation of reactive oxygen species (ROS) and pro-inflammatory responses, and their role in myocardial pathology. Splenocytes of infected mice (C3H/HeN) responded to Tc-antigenic stimulus by more than a two-fold increase in NADPH oxidase (NOX) activity, ROS generation, cytokine production (IFN-γ > IL-4 > TNFα > IL1-β ≈ IL6), and predominant expansion of CD4+ and CD8+ T cells. Inhibition of NOX, but not of myeloperoxidase and xanthine oxidase, controlled the ROS (>98%) and cytokine (70–89%) release by Tc-stimulated splenocytes of infected mice. Treatment of infected mice with apocynin (NOX inhibitor) in drinking water resulted in a 50–90% decline in endogenous NOX/ROS and cytokine levels, and splenic phagocytes’ proliferation. The splenic percentage of T cells was maintained, though more than a 40% decline in splenic index (spleen weight/body weight) indicated decreased T-cell proliferation in apocynin-treated/infected mice. The blood and tissue parasite burden were significantly increased in apocynin-treated/infected mice, yet acute myocarditis, ie inflammatory infiltrate consisting of macrophages, neutrophils, and CD8+ T cells, and tissue oxidative adducts (eg 8-isoprostanes, 3-nitrotyrosine, and 4-hydroxynonenal) were diminished in apocynin-treated/infected mice. Consequently, hypertrophy (increased cardiomyocytes’ size and β-MHC, BNP, and ANP mRNA levels) and fibrosis (increased collagen, glycosaminoglycans, and lipid contents) of the heart during the chronic phase were controlled in apocynin-treated mice. We conclude that NOX/ROS is a critical regulator of the splenic response (phagocytes, T cells, and cytokines) to T. cruzi infection, and bystander effects of heart-infiltrating phagocytes and CD8+ T cells resulting in cardiac remodelling in chagasic

  3. The parasite's long arm: a tapeworm parasite induces behavioural changes in uninfected group members of its social host.

    PubMed

    Beros, Sara; Jongepier, Evelien; Hagemeier, Felizitas; Foitzik, Susanne

    2015-11-22

    Parasites can induce alterations in host phenotypes in order to enhance their own survival and transmission. Parasites of social insects might not only benefit from altering their individual hosts, but also from inducing changes in uninfected group members. Temnothorax nylanderi ant workers infected with the tapeworm Anomotaenia brevis are known to be chemically distinct from nest-mates and do not contribute to colony fitness, but are tolerated in their colonies and well cared for. Here, we investigated how tapeworm- infected workers affect colony aggression by manipulating their presence in ant colonies and analysing whether their absence or presence resulted in behavioural alterations in their nest-mates. We report a parasite-induced shift in colony aggression, shown by lower aggression of uninfected nest-mates from parasitized colonies towards conspecifics, potentially explaining the tolerance towards infected ants. We also demonstrate that tapeworm-infected workers showed a reduced flight response and higher survival, while their presence caused a decrease in survival of uninfected nest-mates. This anomalous behaviour of infected ants, coupled with their increased survival, could facilitate the parasites' transmission to its definitive hosts, woodpeckers. We conclude that parasites exploiting individuals that are part of a society not only induce phenotypic changes within their individual hosts, but in uninfected group members as well. PMID:26582019

  4. Case of a healthy infant born following antenatal enterovirus myocarditis and hydrops.

    PubMed

    Bonnin, Aurore; Tassin, Mikael; Vauloup-Fellous, Christelle; Letamendia, Emmanuelle; Stos, Bertrand; Bonnet, Damien; Gajdos, Vincent; Mabille, Mylène; Benachi, Alexandra

    2014-11-01

    Fetal hydrops and myocarditis were diagnosed in a woman at 32 weeks of gestation (WG). Transplacental enterovirus infection was suspected because all other causes of myocarditis and hydrops were excluded, it was during an endemic period, and there was a setting of maternal infection (fever a few days before). We opted for in utero treatment because of the risk of resuscitating a neonate with myocarditis and hydrops. We administered dexamethasone 12mg twice for pulmonary maturation and presumed it would partially improve the myocarditis. Fetal arrhythmia was noted at 35 WG and we decided to deliver the infant as postnatal treatment of the heart disorder would be more effective. RT-PCR (ARGENE(®)) showed that the neonate's throat and anal tissues and cord blood sampled on the day of birth contained enterovirus ribonucleic acid and coxsackievirus B5, as did the mother's anal sample. Laboratory tests, heart MRI and probably brain MRI indicated neonatal enterovirus infection. Findings were normal at two-year follow-up. PMID:25242311

  5. Anévrysme ventriculaire gauche et communication interventriculaire compliquant un infarctus du myocarde

    PubMed Central

    Belkhadir, Mohammed; MoutakiAllah, Younes; Raissouni, Zainab; Abdou, Abdessamad; Bamous, Mehdi; Nya, Fouad; Atmani, Noureddine; Houssa, Mahdi Ait; El Bekkali, Youssef; Boulahya, Abdellatif

    2014-01-01

    L'association d'une communication interventriculaire post infarctus du myocarde et d'un anévrysme du ventricule gauche chez un même patient est extrêmement rare et survient habituellement durant la première semaine qui suit un infarctus du myocarde. Nous rapportons le cas insolite d'un patient âgé de 63 ans, admis pour choc cardiogénique en rapport avec une communication inter ventriculaire apicale et un anévrysme ventriculaire gauche causés par un infarctus du myocarde antérieur. La correction chirurgicale a consisté en une fermeture du défect septal par un patch en dacron via une ventriculotomie gauche associée à une anévrysectomie et un mono pontage coronaire. Cette observation illustre d'une part la rareté de l'association communication inter ventriculaire-anévrysme ventriculaire gauche post infarctus du myocarde, et d'autre part l'efficacité du traitement chirurgical qui reste la seule option salvatrice pour cette pathologie. PMID:25328617

  6. Myocardial uptake of antimyosin monoclonal antibody in a murine model of viral myocarditis

    SciTech Connect

    Matsumori, A.; Ohkusa, T.; Matoba, Y.; Okada, I.; Yamada, T.; Kawai, C.; Tamaki, N.; Watanabe, Y.; Yonekura, Y.; Endo, K.

    1989-02-01

    The myocardial uptake of 125I- and 131I-antimyosin monoclonal antibody Fab in experimental myocarditis in BALB/c mice induced by encephalomyocarditis virus was studied. The biodistribution of 125I-antimyosin demonstrated that the highest ratio of radioactivity appears in the heart of infected mice on day 14 (the ratio of percent dose per gram for the organ to percent dose per milliliter for blood; 9.75 +/- 2.79 vs. 1.27 +/- 0.78 at 24 hours in inoculated mice vs. control mice). There was no statistically significant difference between the mean activity ratios of tissues other than the heart in control and inoculated mice. The uptake ratio for the heart increased significantly 3 days after virus inoculation and reached a maximum on day 14 when myocardial lesions were most extensive and prominent. The uptake ratio decreased significantly, but it still remained high compared with controls on day 28 when cellular infiltration had decreased and fibrosis was evident. The scintigraphic images obtained with 131I-antimyosin monoclonal antibody clearly demonstrated that visualization of the heart in experimental myocarditis was possible 24 hours after administration of radiotracer, and localized activity was still observed in the 48-hour image. We conclude that antimyosin monoclonal antibodies localize selectively in the heart from the acute to subacute stage of viral myocarditis. These findings indicate that antimyosin scintigraphy is a reliable noninvasive method for the evaluation of patients suspected of having myocarditis.

  7. Postural hypotension as the initial presentation of fulminant right ventricular myocarditis.

    PubMed

    Ho, Cheng-Hsuan; Wu, Ya-Chieh; Lin, Yen-Yue; Hsu, Chin-Wang; Tsai, Shih-Hung

    2010-07-01

    Myocarditis can be totally asymptomatic or can manifest with chest pain syndromes, ranging from mild persistent chest pain of acute myopericarditis to severe symptoms that mimic acute myocardial infarction. About 60% of patients may have antecedent arthralgias, malaise, fevers, sweats, or chills consistent with viral infections 1 to 2 weeks before onset. Here, we report a postpartum young woman who developed postural hypotension as the first manifestation of fulminant myocarditis with initially acute "cold and dry" right-sided heart failure and cardiogenic shock. Common causes of postural hypotension include volume depletion, medications, diabetes, alcohol, infection, and varicose veins as well as dysautonomic syndromes. Fulminant myocarditis can cause cardiogenic shock. Myocardial inflammation more frequently affects localized areas of the left ventricle free wall, rarely right ventricle (RV). However, predominant RV involvement with acute right-sided heart failure and low cardiac output syndrome can be easily overlooked due to lack of typical heart failure signs. On reviewing medical literatures, we had found no report regarding the RV involvement with acute right-sided heart failure as the initial presentation of fulminant myocarditis. PMID:20637387

  8. Case of a healthy infant born following antenatal enterovirus myocarditis and hydrops.

    PubMed

    Bonnin, Aurore; Tassin, Mikael; Vauloup-Fellous, Christelle; Letamendia, Emmanuelle; Stos, Bertrand; Bonnet, Damien; Gajdos, Vincent; Mabille, Mylène; Benachi, Alexandra

    2014-11-01

    Fetal hydrops and myocarditis were diagnosed in a woman at 32 weeks of gestation (WG). Transplacental enterovirus infection was suspected because all other causes of myocarditis and hydrops were excluded, it was during an endemic period, and there was a setting of maternal infection (fever a few days before). We opted for in utero treatment because of the risk of resuscitating a neonate with myocarditis and hydrops. We administered dexamethasone 12mg twice for pulmonary maturation and presumed it would partially improve the myocarditis. Fetal arrhythmia was noted at 35 WG and we decided to deliver the infant as postnatal treatment of the heart disorder would be more effective. RT-PCR (ARGENE(®)) showed that the neonate's throat and anal tissues and cord blood sampled on the day of birth contained enterovirus ribonucleic acid and coxsackievirus B5, as did the mother's anal sample. Laboratory tests, heart MRI and probably brain MRI indicated neonatal enterovirus infection. Findings were normal at two-year follow-up.

  9. Fatal Subacute Myocarditis Associated with Human Bocavirus 2 in a 13-Month-Old Child

    PubMed Central

    Vanlieferinghen, Philippe; Déchelotte, Pierre; Boutry, Morgane; Peigue-Lafeuille, Hélène; Henquell, Cécile

    2014-01-01

    Human bocavirus has rarely been incriminated in fatal or life-threatening respiratory infections. We report a case of fatal disseminated infection with subacute lymphocytic myocarditis in a 13-month-old child. The human bocavirus 2 genome was detected by PCR analysis in nasal swab, plasma, urine, ascitic fluid, and mesenteric node, skeletal muscle, and lung tissue specimens. PMID:24371238

  10. A Case of Clozapine-Induced Myocarditis in a Young Patient with Bipolar Disorder

    PubMed Central

    Cohen, Ronny; Lysenko, Alla; Mallet, Thierry; Mirrer, Brooks; Gale, Michael; Loarte, Pablo; McCue, Robert

    2015-01-01

    We present a case of drug-induced myocarditis manifesting as acute heart failure in a young patient with bipolar disorder being treated for depression. The case describes a 20-year-old man being treated in the psychiatry ward for worsening depression when he started complaining of chest pain and shortness of breath. His list of medications included clozapine, lithium, lorazepam, and haloperidol. The main findings on physical examination were tachycardia, low-grade fever, crackles in both lung bases on auscultation, and the absence of any notable edema. Abnormal labs included a troponin of 0.9, with a CK of 245 and CK-MB of 3.1. An ECG revealed sinus tachycardia and left anterior fascicular block (LAFB). An echocardiogram revealed global hypokinesis, severe left ventricular dysfunction with an ejection fraction estimated at 20%. The patient had an admitting diagnosis of acute left ventricular systolic dysfunction likely secondary to drug-induced myocarditis (suspect clozapine) versus acute coronary syndrome. He was managed conservatively and transferred to another facility for endomyocardial biopsy confirming myocarditis. This case is an example of one of the most typical presentations of suspected drug-induced acute myocarditis and will hopefully prompt the reader to think of this underdiagnosed entity in the right clinical setting. PMID:26413355

  11. New-Onset Myocarditis in an Immunocompetent Adult with Acute Metapneumovirus Infection

    PubMed Central

    Weinreich, Mark A.; Jabbar, Ahmad Y.; Malguria, Nagina; Haley, Robert W.

    2015-01-01

    Introduction. A number of viruses have been implicated in viral myocarditis; however, there has been no previous report of human metapneumovirus (hMPV) causing this condition. Discovered in 2001, hMPV is typically associated with upper respiratory illness, mainly affecting children. Case Presentation. We report the case of a 25-year-old man with acute systolic heart failure from viral myocarditis secondary to the hMPV. The patient was initially admitted to the general medical ward but developed increasing oxygen requirements resulting in transfer to the cardiac intensive care unit. Cardiac magnetic resonance imaging was used to help confirm the diagnosis. He was treated with intravenous diuretics, and afterload and preload agents, and he was subsequently discharged home after seven days of hospitalization. Discussion. hMPV is typically a respiratory pathogen; however, it was associated with in myocarditis in our patient. Due to the recent ability to detect this virus, we may see more cases of this, particularly during peak months of infection. Conclusion. This is the first case description of myocarditis associated with hMPV infection. PMID:26421018

  12. New-Onset Myocarditis in an Immunocompetent Adult with Acute Metapneumovirus Infection.

    PubMed

    Weinreich, Mark A; Jabbar, Ahmad Y; Malguria, Nagina; Haley, Robert W

    2015-01-01

    Introduction. A number of viruses have been implicated in viral myocarditis; however, there has been no previous report of human metapneumovirus (hMPV) causing this condition. Discovered in 2001, hMPV is typically associated with upper respiratory illness, mainly affecting children. Case Presentation. We report the case of a 25-year-old man with acute systolic heart failure from viral myocarditis secondary to the hMPV. The patient was initially admitted to the general medical ward but developed increasing oxygen requirements resulting in transfer to the cardiac intensive care unit. Cardiac magnetic resonance imaging was used to help confirm the diagnosis. He was treated with intravenous diuretics, and afterload and preload agents, and he was subsequently discharged home after seven days of hospitalization. Discussion. hMPV is typically a respiratory pathogen; however, it was associated with in myocarditis in our patient. Due to the recent ability to detect this virus, we may see more cases of this, particularly during peak months of infection. Conclusion. This is the first case description of myocarditis associated with hMPV infection.

  13. Rapid Extracorporeal Membrane Oxygenation Overcomes Fulminant Myocarditis Induced by 5‑Fluorouracil

    PubMed Central

    Pachika, Ajay; Grubb, Kendra J.; DeFilippis, Andrew P.

    2016-01-01

    Fulminant myocarditis is a rare but potentially life-threatening illness caused by 5-fluorouracil cardiotoxicity. Data supporting the use of extracorporeal membrane oxygenation for the treatment of fulminant myocarditis are limited. A 49-year-old, previously healthy white man, recently diagnosed with anal squamous cell carcinoma, developed severe chest pain hours after completing his first 96-hour intravenous 5-fluorouracil treatment. Over a period of 3 days from onset of symptoms, the patient developed cardiogenic shock secondary to fulminant myocarditis induced by 5-fluorouracil cardiotoxicity. This required emergency initiation of extracorporeal membrane oxygenation. The patient's systolic function recovered by day 5, and on the 17th day he was discharged in hemodynamically stable condition, without symptoms of heart failure. This case shows the importance of prompt recognition of cardiogenic shock secondary to 5-fluorouracil–induced myocarditis and how the immediate initiation of extracorporeal membrane oxygenation can restore adequate tissue perfusion, leading to myocardial recovery and ultimately the survival of the patient. PMID:27127440

  14. Genetic and antigenic characterisation of Bungowannah virus, a novel pestivirus causing myocarditis in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In June 2003 a syndrome of sudden death in sucker pigs, an elevation in the proportion of stillborn foetuses, increased preweaning losses and to a lesser extent increased mummification rates was recognised on a property in NSW, Australia [1]. This disease has been described as the porcine myocarditi...

  15. Ultra-low dose comprehensive cardiac CT imaging in a patient with acute myocarditis.

    PubMed

    Tröbs, Monique; Brand, Michael; Achenbach, Stephan; Marwan, Mohamed

    2014-01-01

    The ability of contrast-enhanced CT to detect "late enhancement" in a fashion similar to magnetic resonance imaging has been previously reported. We report a case of acute myocarditis with coronary CT angiography as well as "late enhancement" imaging with ultra-low effective radiation dose. PMID:25439792

  16. An infant with out-of-hospital cardiac arrest secondary to enteroviral myocarditis surviving up to cardiac transplantation.

    PubMed

    McGovern, Eimear; Ryan, Ethel; McMahon, Colin J

    2016-01-01

    We report the case of a 13-day-old infant with enteroviral myocarditis surviving an out-of-hospital cardiac arrest. She underwent orthotopic cardiac transplantation three months later. A year after the transplantation, she is alive and well. Enteroviral infection is common in neonates with high mortality in cases of enteroviral myocarditis. Cardiac transplantation is a treatment option for infants who fail to recover and remain dependent on inotropic support. This is the first report of an infant with out-of-hospital cardiac arrest secondary to enteroviral myocarditis surviving up to cardiac transplantation.

  17. Enhanced expression and production of monocyte chemoattractant protein-1 in myocarditis

    PubMed Central

    Fuse, K; Kodama, M; Hanawa, H; Okura, Y; Ito, M; Shiono, T; Maruyama, S; Hirono, S; Kato, K; Watanabe, K; Aizawa, Y

    2001-01-01

    Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family that has been shown to play a major role in the migration of monocytes and T cells to an inflammatory focus. To clarify the role of MCP-1 in the pathogenesis of myocarditis, we have examined the expression of MCP-1 in rat hearts with experimental autoimmune myocarditis (EAM), and have also measured serum levels of MCP-1 in patients with histology-proven acute myocarditis. Lewis rats were immunized with cardiac myosin and were killed 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42 and 56 days after immunization. Large mononuclear cells in the myocardial interstitium were stained with an anti-MCP-1 antibody. mRNA of MCP-1 increased in the hearts of EAM rats from days 15–27 as shown by quantitative reverse transcription-polymerase chain reaction. Serum MCP-1 levels of the rats with EAM were significantly elevated from days 15–24. In the clinical study, serum levels of MCP-1 in 24 patients with acute myocarditis at the time of admission (165·2 ± 55·8 pg/ml) were significantly (P = 0·0301) elevated compared with those of 20 healthy volunteers (61·8 ± 10·7 pg/ml). Serum MCP-1 levels of 8 fatal cases (371·8 ± 145·2 pg/ml) were significantly (P = 0·0058) higher than those of 16 cases who survived (65·5 ± 12·8 pg/ml). In conclusions, MCP-1 may play an important role in the pathogenesis of human acute myocarditis as well as in the progression of rat EAM. PMID:11472393

  18. Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

    PubMed Central

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-01

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

  19. The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected] [published erratum appears in J Exp Med 1994 Jan 1;179(1):371

    PubMed Central

    1993-01-01

    Experimental induction of most autoimmune diseases appears to depend on the activation of CD4+ T helper cells, while CD8+ lymphocytes may have a role in disease progression. To study the role of CD4+ and CD8+ T cell subsets in T cell-dependent autoimmunity, mice lacking CD4 or CD8 molecules after gene targeting were injected with cardiac myosin to induce organ specific autoimmune myocarditis. Mice homozygous for the CD8 mutation (CD8-/-) developed significantly more severe disease as compared to CD4+/-CD8+/- controls. Surprisingly, CD4-/- mice developed autoimmune myocarditis with infiltration of TCR alpha beta +CD4-CD8- T cells in the heart tissue and appearance of autoantibodies. These data demonstrate that the lack of CD4+ or CD8+ T cells has no significant influence on the initiation of autoimmune myocarditis. CD4+ and CD8+ cells regulate disease severity and these results may explain the occurrence of autoimmunity in CD4 immunodeficiencies. PMID:8228830

  20. Granulomatous myocarditis and coelomic effusion due to Salmonella enterica arizonae in a Madagascar Dumerili's boa (Acrantophis dumerili, Jan. 1860).

    PubMed

    Schilliger, Lionel; Vanderstylen, David; Piétrain, Jérôme; Chetboul, Valérie

    2003-05-01

    A granulomatous myocarditis due to Salmonella enterica arizonae was diagnosed in an 8-year-old Madagascar Dumerili's boa (Acrantophis dumerili) based on positive coelomic effusion culture, ultrasound visualization of abnormal ventricular myocardium, necropsy and cardiac histological examination.

  1. Acute myocardial infarction or acute myocarditis? Discharge registry-based study of likelihood and associated features in hospitalised patients

    PubMed Central

    Kytö, Ville; Sipilä, Jussi; Rautava, Päivi

    2015-01-01

    Objective To evaluate the likelihood of and patient features associated with acute myocardial infarction (AMI) versus acute myocarditis in different population segments. Design Nationwide, multihospital observational retrospective registry study of 9.6 years in Finland. Participants All consecutive patients aged ≥18 years hospitalised with a primary diagnosis of AMI (n=89 399) or acute myocarditis (n=2131) in 22 hospitals with a coronary catheterisation laboratory. Primary outcome measures Likelihood of AMI versus acute myocarditis and associated patient features. Results Men were over-represented in patients with AMI (59.8%) and in patients with acute myocarditis (76.1%). Age distributions of AMI and acute myocarditis were opposite as a majority of patients with myocarditis were aged 18–29 years, while the number of patients with AMI increased gradually up to 80 years of age. Patients aged 18–29 years were more likely to have acute myocarditis as the cause of hospitalisation (relative risk (RR)=11.4; 95% CI 7.6 to 16.1 for myocarditis, p<0.0001), but after 30 years of age the likelihood of infarction was higher with exponentially increasing RR for AMI. In youngest patients (18–29 years), the likelihood of AMI was higher in women, but men had higher odds for AMI after 40 years of age. Overall, men had OR of 1.97 (95% CI 1.74 to 2.23, p<0.0001) for AMI versus myocarditis when compared with women. Hypercholesterolaemia, chronic coronary artery disease, diabetes and hypertension predicted AMI in multivariate analysis. Odds for myocarditis were significantly higher if the patient had an otolaryngeal infection (OR 18.13; 95% CI 8.96 to 36.67, p<0.0001). Conclusions Acute myocarditis is more common than AMI in hospitalised patients aged 18–29 years, but the risk of AMI increases exponentially thereafter. Hypercholesterolaemia, diabetes and hypertension predict AMI regardless of age and gender. PMID:26009575

  2. Increased Expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis

    PubMed Central

    2012-01-01

    Background Recently, a new subset of T helper (Th) cell that predominantly secret cytokine interleukin-22 (IL-22) is identified, termed Th22 cells. The Th22 subset has been demonstrated to be involved in immunity and tissue inflammation. However, the existence of Th22 cells and role of IL-22 in acute viral myocarditis (AVMC) remain unknown. Methods BALB/c mice were intraperitoneally (i.p) infected with CVB3 for establishing AVMC models. Control mice were treated with phosphate-buffered saline (PBS) i.p. On day 14 post injection, frequencies of splenic Th22 cells were determined, productions of IL-22 and expressions of IL-22R (IL-22 receptor) were measured. To further investigate the effects of IL-22, AVMC mice treated with Anti-IL-22 neutralizing antibody were explored. The severity of AVMC were monitored; the frequencies of Th22 cells, the expressions of IL-22 and IL-22R were investigated; in addition to IFN-γ, inflammatory cytokines IL-17, TNF-α, IL-6 as well as IL-1β, were evaluated. Cardiac viral replication were detected. Results Compared with control group, significant elevations of circulating Th22 cells and IL-22, cardiac protein and mRNA of IL-22, and IL-22R1 were demonstrated in AVMC group. Treatment of AVMC mice with Anti-IL-22 Ab exacerbated the severity of viral myocarditis, verified by lower survival rate, higher HW/BW ratios and cardiac pathological scores. Anti-IL-22 Ab decreased the frequencies of Th22 cells and the levels of IL-22, and increased the expressions of cardiac IL-22R1. Up-regulations of IL-17, IL-6 and TNF-α, down-regulations of IFN-γ proteins and gene expressions in the plasma and myocardium, were observed in Anti-IL-22 Ab group. Furthermore, neutralization of IL-22 significantly promoted cardiac viral replication. Conclusions Our data indicate that the increased frequencies of IL-22-producing Th22 cells may play an important role in the pathogenesis of CVB3-induced mice AVMC, IL-22 may act as an myocardium-protective cytokine

  3. [Fetal myocarditis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block with good outcome].

    PubMed

    De La Villeon, C-G; Dulac, Y; Ohanessian, G; Ziani, A; Paranon, S; Acar, P

    2010-10-01

    We report a case of fetal myocarditis without conductive abnormality in a pregnant woman with anti-Ro/La antibodies. Fetal echocardiography showed myocarditis with ventricular and valvular hyperechogenicity, which was confirmed by postnatal transthoracic echography. Treatment with dexamethasone (4 mg/day) was started in the 22nd week of gestation. The outcome was good, with the child remaining asymptomatic 2 years later. This observation describes one of the rare forms of fetal myocarditis with favorable outcome.

  4. CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis.

    PubMed

    Marino, A P M P; Silva, A A; Santos, P V A; Pinto, L M O; Gazinelli, R T; Teixeira, M M; Lannes-Vieira, J

    2005-03-01

    The comprehension of the pathogenesis of Trypanosoma cruzi-elicited myocarditis is crucial to delineate new therapeutic strategies aiming to ameliorate the inflammation that leads to heart dysfunction, without hampering parasite control. The augmented expression of CCL5/RANTES and CCL3/MIP-1alpha, and their receptor CCR5, in the heart of T. cruzi-infected mice suggests a role for CC-chemokines and their receptors in the pathogenesis of T. cruzi-elicited myocarditis. Herein, we discuss our recent results using a CC-chemokine receptor inhibitor (Met-RANTES), showing the participation of CC-chemokines in T. cruzi infection and unraveling CC-chemokine receptors as an attractive therapeutic target for further evaluation in Chagas disease.

  5. Successive circulatory support stages: a triple bridge to recovery from fulminant myocarditis.

    PubMed

    Jaroszewski, Dawn E; Marranca, Michael C; Pierce, Christopher N; Wong, Raymond K; Steidley, Eric D; Scott, Robert L; Devaleria, Patrick A; Arabia, Francisco

    2009-09-01

    Fulminant myocarditis with rapid onset of symptoms and hemodynamic compromise is a rare indication for mechanical support. Because of the potentially reversible nature of this illness, advanced mechanical circulatory support is warranted to achieve recovery or as a bridge to transplantation. Circulatory device options currently available allow for a phased implementation of support modalities in a manner that reduces costs and patient risk. We present a patient with fulminant myocarditis where extracorporeal membrane oxygenation (ECMO) support escalated to short-term Levitronix CentriMag (Levitronix, Waltham, MA) biventricular assist devices (BiVADs). These in turn were exchanged, without major surgery, to long-term paracorporeal VADs (Thoratec, Pleasanton, CA). After rehabilitation and nearly total recovery, the patient was weaned from mechanical circulatory support after 104 cumulative days.

  6. Clozapine-induced myocarditis may be associated with rapid titration: A case report verified with autopsy.

    PubMed

    Chopra, Nitin; de Leon, Jose

    2016-01-01

    Clozapine-induced myocarditis is a poorly understood, rare, potentially fatal adverse drug reaction with absolute risks ranging from 7 to 34 per 1000 in Australia and 0.07-0.6 per 1000 in other countries. Hypersensitivity reactions have been postulated including some cases probably associated with rapid titrations. This case describes a 50-year-old African-American man with schizoaffective disorder, naïve to clozapine, who probably died from clozapine-induced myocarditis. He was started on 25 mg/day of clozapine and received 1625 mg over 14 days, prior to his death on day 15. The autopsy found predominantly lymphocytic infiltrate of the perivascular soft tissue and myocardium of the ventricles, with occasional eosinophils. Using the Liverpool ADR Causality Assessment Tool, it was deemed probable that the patient's death was secondary to myocarditis. The patient had fulminant death with no obvious changes in vital signs. Neither C-reactive protein nor troponin was measured, but it is unlikely that the results would have arrived in time to prevent the patient's death. Age, rapid titration, and concomitant use of valproate contributed to this case, which was probably an idiosyncratic adverse drug reaction associated with rapid titration. Lamotrigine-induced Stevens-Johnson syndrome also appears to be an idiosyncratic adverse drug reaction associated with rapid titration, but its incidence has been remarkably reduced since the recommended starting lamotrigine dose was reduced and corrected by the effect of inhibitors such as valproate. Similarly, clozapine-induced myocarditis incidence probably can be reduced with the use of slow titrations, including even slower titrations for patients with lower ability to metabolize clozapine, such as those taking valproate.

  7. Antimyosin antibody cardiac imaging: Its role in the diagnosis of myocarditis

    SciTech Connect

    Dec, G.W.; Palacios, I.; Yasuda, T.; Fallon, J.T.; Khaw, B.A.; Strauss, H.W.; Haber, E. )

    1990-07-01

    Right ventricular endomyocardial biopsy currently remains the procedure of choice for identifying patients with symptomatic heart failure due to myocarditis from the larger population with idiopathic dilated cardiomyopathy. Despite its specificity, the sensitivity of right ventricular biopsy remains uncertain because of the focal or multifocal nature of the disease. Because myocyte necrosis is an obligate component of myocarditis, the use of indium-111 antimyosin imaging was evaluated in 82 patients with suspected myocarditis. Seventy-four patients had dilated cardiomyopathy of less than 1 year's duration (mean left ventricular ejection fraction 0.30 +/- 0.02); eight patients had normal left ventricular function (mean ejection fraction 0.59 +/- 0.03). Symptoms at presentation included congestive heart failure (92%), chest pain mimicking myocardial infarction (6%) and life-threatening ventricular tachyarrhythmias (2%). All patients underwent planar and single photon emission computed tomographic (SPECT) cardiac imaging after injection of indium-111-labeled antimyosin antibody fragments and right ventricular biopsy within 48 h of imaging. Antimyosin images were interpreted as either abnormal or normal and correlated with biopsy results. On the basis of the right ventricular histologic examination, the sensitivity of antimyosin imaging was 83%, specificity 53% and predictive value of a normal scan 92%. Improvement in left ventricular function occurred within 6 months of treatment in 54% of patients with an abnormal antimyosin scan compared with 18% of those with a normal scan (p less than 0.01). Antimyosin cardiac imaging may be useful for the initial evaluation of patients with dilated and nondilated cardiomyopathy and clinically suspected myocarditis.

  8. Acute Eosinophilic Myocarditis and Hyper IgE in HIV Infection: A Case Report

    PubMed Central

    Thawabi, Mohammad; Habib, Mirette; Shaaban, Hamid; Shamoon, Fayez

    2014-01-01

    Context: Eosinophilic myocarditis is a rare cause of myocarditis. It is manifested histopathologically by diffuse or focal myocardial inflammation with eosinophilic infiltration, often in association with peripheral blood eosinophilia. Patients infected with Human Immunodeficiency Virus (HIV), especially those with lower CD4 counts, can occasionally have hyperimmunoglobulinemia E (Hyper IgE) and eosinophilia. Case Report: We report a case of a 29-year-old patient with Acquired Immunodeficiency Syndrome (AIDS) who had a persistent elevation of eosinophil counts and elevated IgE levels for a year prior to admission. He was presented to our emergency department with chest pain and laboratory tests revealed peripheral blood eosinophilia and elevated troponins. Coronary angiogram showed nonobstructive coronary artery disease. He then underwent cardiac magnetic resonance imaging which was consistent with an infiltrative myocarditis. After being put on steroid therapy, his peripheral eosinophilia resolved and his cardiac symptoms improved. Conclusion: Our case highlights that eosinophilia and Hyper IgE in HIV patients has the potential to contribute to end-organ damage. PMID:25077083

  9. Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis

    SciTech Connect

    Yamada, T.; Matsumori, A.; Watanabe, Y.; Tamaki, N.; Yonekura, Y.; Endo, K.; Konishi, J.; Kawai, C. )

    1990-11-01

    The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis.

  10. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection

    SciTech Connect

    Carrio, I.; Berna, L.; Ballester, M.; Estorch, M.; Obrador, D.; Cladellas, M.; Abadal, L.; Ginjaume, M.

    1988-12-01

    Indium-111 antimyosin scans were used to assess myocardial damage in patients with suspected myocarditis and cardiac transplant rejection. The calculation of a myocardium to lung ratio (AM index) to quantify antimyosin uptake was performed. AM index in normal subjects (n = 8) at 48 hr postinjection was 1.46 +/- 0.04. In patients with suspected myocarditis (16 studies in 13 patients), AM index was 2.0 +/- 0.5 (p less than 0.001); suggesting a considerable incidence of ongoing cell damage in this group, despite the small proportion of positive right ventricular endomyocardial biopsy (RVbx) (4/13). In patients studied after cardiac transplantation (37 studies in 17 patients), AM indexes correlated with RVbx. In patients with RVbx proven rejection (n = 14), AM index was 1.87 +/- 0.19 (p less than 0.001). In patients with RVbx showing infiltrates but not myocyte damage (n = 13), AM index was 1.80 +/- 0.27 (p = 0.02). In patients with normal RVbx (n = 10), AM index was 1.56 +/- 0.17 (p = NS versus controls; p = 0.001 versus those with positive RVbx). Calculated AM indexes correlated with graded visual analysis of the scans (r = 0.823; p = 0.001). Antimyosin scans are an appropriate method to assess myocardial damage in patients with suspected myocarditis and cardiac rejection.

  11. Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: a rare case report.

    PubMed

    Singh, Harpal; Kundal, Ramesh

    2015-01-01

    Idiopathic granulomatous myocarditis is extremely rare, particularly since the introduction of drugs effective against tuberculosis (TB), viruses, fungi and the effective treatment of sarcoidosis. Here is a case of a 65-year-old female prisoner having history of sudden collapse and ultimately death. Autopsy findings of various viscera on histopathological examination show granulomatous pathology, that is, in spleen, liver and in the left ventricular wall of heart. Ziehl-Neelsen staining of the sections show the absence of acid fast bacilli, negative for fungal staining as most of the granulomas are noncaseating type with presence of giant cells having no asteroid body and Schuamann body, real-time polymerase chain reaction for TB is negative. Idiopathic giant cell myocarditis is a disease of relatively young adults, that is, between 3 rd and 4 th decade of life. So, this case is strongly considered to be a case of sudden death due to myocarditis as a result of idiopathic systemic granulomatous pathology, a rare case in in literature. PMID:25673606

  12. Fulminant Peripartum myocarditis associated with sudden cardiac death: a case report.

    PubMed

    Ciccone, Marco Matteo; Dentamaro, Ilaria; Carbonara, Santa; Ricci, Gabriella; Vestito, Domenico; Marzullo, Andrea; Tunzi, Francesco; Solarino, Biagio

    2016-01-01

    Myocarditis is an inflammatory disease of myocardium, associated with nonischemic necrosis and degeneration of myocytes. Although the clinical course is rapid, myocarditis can lead to dilated cardiomyopathy with chambers dilatation and ventricular dysfunction. The pathophysiology of myocarditis in humans is not completely understood. There are several etiological agents implicated, mainly viral agents. The clinical presentation is extremely various, with nonspecific systemic symptoms until sudden death. The great variability of symptoms makes the diagnosis, therefore, extremely difficult. We report the case of a 40-year-old woman who developed, after childbirth, hyperthermia associated with neck and left arm pain; initially treated with acetaminophen, without any benefit, the young woman, after few days, died suddenly. The autopsy documented the presence of edematous lungs and enlarged and congested liver. The microbiological tests performed 4 days after death were negative. The heart was normal in shape and volume; a section of the left ventricle wall showed subendocardial discromic areas histologically characterized by multifocal perivascular and interstitial inflammatory infiltrates. These infiltrates consisted mainly of neutrophils with eosinophil component associated with myocyte necrosis and hemorrhagic interstitial infiltration.

  13. Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.

    PubMed

    Muench, Frédéric; Retel, Joren; Jeuthe, Sarah; O h-Ici, Darach; van Rossum, Barth; Wassilew, Katharina; Schmerler, Patrick; Kuehne, Titus; Berger, Felix; Oschkinat, Hartmut; Messroghli, Daniel R

    2015-12-01

    Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS ((1)H-MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals. Myocardial function of male young Lewis rats with EAM was quantified by performing left ventricular ejection fraction (LVEF) analysis in short-axis cine images throughout the whole heart. Inflammatory cellular infiltrate was assessed by immunohistochemistry. Myocardial tissue was analyzed using ex vivo proton magic angle spinning MRS ((1)H-MAS-MRS). Myocarditis was confirmed histologically by the presence of an inflammatory cellular infiltrate and CD68 positive staining. A significant increase in the metabolic ratio of Tau/tCr (taurine/total creatine) obtained by (1)H-MAS-MRS was observed in myocarditis compared with healthy controls (21 d acute EAM, 4.38 (±0.23); 21 d control, 2.84 (±0.08); 35 d chronic EAM, 4.47 (±0.83); 35 d control, 2.59 (±0.38); P < 0.001). LVEF was reduced in diseased animals (EAM, 55.2% (±11.3%); control, 72.6% (±3.8%); P < 0.01) and correlated with Tau/tCr ratio (R = 0.937, P < 0.001). Metabolic alterations occur acutely with the development of myocarditis. Myocardial Tau/tCr ratio as detected by (1)H-MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM.

  14. Olmesartan, an AT1 Antagonist, Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Cardiac Inflammatory Mediators in Rats with Heart Failure Induced by Experimental Autoimmune Myocarditis

    PubMed Central

    Sukumaran, Vijayakumar; Watanabe, Kenichi; Veeraveedu, Punniyakoti T.; Gurusamy, Narasimman; Ma, Meilei; Thandavarayan, Rajarajan A.; Lakshmanan, Arun Prasath; Yamaguchi, Ken'ichi; Suzuki, Kenji; Kodama, Makoto

    2011-01-01

    Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM) by suppression of oxidative stress, endoplasmic reticulum (ER) stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day) or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL)-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ)] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox) and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), and the cardiac apoptosis were also significantly decreased by the treatment with olmesartan compared with those of vehicle-treated rats. Furthermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mitogen-activated protein kinase (MAPK) and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and inflammatory cytokines. PMID:21383952

  15. Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis.

    PubMed

    Jaquenod De Giusti, Carolina; Ure, Agustín E; Rivadeneyra, Leonardo; Schattner, Mirta; Gomez, Ricardo M

    2015-08-01

    Macrophage influx and galectin 3 production have been suggested as major players driving acute inflammation and chronic fibrosis in many diseases. However, their involvement in the pathogenesis of viral myocarditis and subsequent cardiomyopathy are unknown. Our aim was to characterise the role of macrophages and galectin 3 on survival, clinical course, viral burden, acute pathology, and chronic fibrosis in coxsackievirus B3 (CVB3)-induced myocarditis. Our results showed that C3H/HeJ mice infected with CVB3 and depleted of macrophages by liposome-encapsulated clodronate treatment compared with infected untreated mice presented higher viral titres but reduced acute myocarditis and chronic fibrosis, compared with untreated infected mice. Increased galectin 3 transcriptional and translational expression levels correlated with CVB3 infection in macrophages and in non-depleted mice. Disruption of the galectin 3 gene did not affect viral titres but reduced acute myocarditis and chronic fibrosis compared with C57BL/6J wild-type mice. Similar results were observed after pharmacological inhibition of galectin 3 with N-acetyl-d-lactosamine in C3H/HeJ mice. Our results showed a critical role of macrophages and their galectin 3 in controlling acute viral-induced cardiac injury and the subsequent fibrosis. Moreover, the fact that pharmacological inhibition of galectin 3 induced similar results to macrophage depletion regarding the degree of acute cardiac inflammation and chronic fibrosis opens up the possibility of new pharmacological strategies for viral myocarditis.

  16. The global burden of myocarditis: part 1: a systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study.

    PubMed

    Cooper, Leslie T; Keren, Andre; Sliwa, Karen; Matsumori, Akira; Mensah, George A

    2014-03-01

    Myocarditis contributes to the global burden of cardiovascular disease primarily through sudden death and dilated cardiomyopathy. A systematic approach to identify the cardiovascular mortality and major morbidity attributable to myocarditis has not been performed. A writing group convened by the GBD 2010 (Global Burden of Diseases, Injuries and Risk Factors) Study systematically reviewed the world's literature by a manual review of all titles since 1966 on myocarditis identified using Ovid Medline, development of a disease model, and provision of estimates when possible of the incidence, prevalence, risk of death, and major morbidity for the world regions. Accurate population-based estimates of myocarditis incidence and prevalence are not directly available in any world region. However, a model that quantitates the risk of acute death and chronic heart failure following myocarditis was derived from the published data. Using hospital dismissal data, the burden of myocarditis as a percentage of prevalent heart failure varied by age and region from approximately 0.5% to 4.0%. The novel combination of multiple data sources may provide an estimate of the years of life lost and years of life disabled from myocarditis. Pending the integration of these data sources, the burden of dilated cardiomyopathy and myocarditis were reported together in the 2010 GBD report. The 2013 GBD project may refine these estimates with the inclusion of more comprehensive payor databases and more precise case definitions. PMID:25432122

  17. Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis

    PubMed Central

    Ratzlaff, Robert A.; Menke, David M.; Olave, Maria C.; Maleszewski, Joseph J.

    2016-01-01

    Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis.

  18. Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis

    PubMed Central

    Ratzlaff, Robert A.; Menke, David M.; Olave, Maria C.; Maleszewski, Joseph J.

    2016-01-01

    Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis. PMID:27648312

  19. Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis.

    PubMed

    Ripoll, Juan G; Ratzlaff, Robert A; Menke, David M; Olave, Maria C; Maleszewski, Joseph J; Díaz-Gómez, José L

    2016-01-01

    Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis. PMID:27648312

  20. Effects of Zileuton on the Development of Autoimmune Myocarditis in an Experimental Rat Model

    PubMed Central

    Odemis, Ender; Turkay, Sadi; Koca, Cemile; Kiyici, Halil; Karadag, Ahmet; Bayrak, Reyhan; Mete, Emin; Catal, Ferhat; Yigitoglu, Ramazan

    2007-01-01

    Background: Myocarditis is associated with high morbidity and mortality in childhood, but the pathogenesis of this disease is still unclear. Current knowledge indicates that complex immunopathogenic mechanisms are involved. It is understood that leukotrienes play an important role in the inflammation associated with asthma, and recent reports indicate that leukotrienes participate in immune processes and in autoimmunity. Objective: The aim of this study was to assess the role of leukotriene synthesis in the development of myocardial inflammation and necrosis during myocarditis. Methods: The effect of zileuton, a leukotriene synthesis inhibitor, was assessed in an experimental model of autoimmune myocarditis in rats. Healthy adult (10-week-old) male Wistar albino rats were randomly divided into 3 groups. Groups A and B received injections of 1.0 mg porcine cardiac myosin to induce autoimmune myocarditis and group C (the control group) received phosphate-buffered saline. Group B also received zileuton by oral gavage at 100 mg/kg · d−1. Myocardial inflammation was assessed biochemically via serum concentrations of creatine kinase MB subunit (CK-MB) and troponin T. Cardiac tissue was assessed macroscopically (0 = no inflammation; 1 = a small discolored focus; 2 = diffuse discolored areas covering less than half of the cardiac surface; 3 = diffuse discolored areas covering more than half of the cardiac surface) and microscopically (0 = no inflammation; 1 = ⪯5% infiltration; 2 = 5% to <10% infiltration; 3 = 10% to < 20% infiltration; 4 = >20% infiltration). Results: Twenty-four rats were divided equally into 3 groups. All rats survived the duration of the study. After 21 days, all rats were euthanized. No significant differences were found between groups A and B in terms of serum concentrations of CK-MB or troponin T. The microscopic pathology score was significantly lower in group B (myosin + zileuton) than in group A (myosin only) (0.12 [0.35] vs 1.25 [1.03]; P

  1. Use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant

    PubMed Central

    Durães, André Rodrigues; Figueira, Fernando Augusto Marinho dos Santos; Lafayette, André Rabelo; Martins, Juliana de Castro Solano; Juliano Cavalcante de, Sá

    2015-01-01

    A 17-year-old Brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. Echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). After 48 hours with no clinical or hemodynamic improvement, an extracorporeal membrane oxygenation was implanted. The patient presented with hemodynamic, systemic perfusion and renal and liver function improvements; however, his cardiac function did not recover after 72 hours, and he was transfer to another hospital. Air transport was conducted from Salvador to Recife in Brazil. A heart transplant was performed with rapid recovery of both liver and kidney functions, as well as good graft function. Histopathology of the explanted heart showed chronic active myocarditis and amastigotes of Trypanosoma cruzi. The estimated global prevalence of T. cruzi infections declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Myocarditis is an inflammatory disease due to infectious or non-infectious conditions. Clinical manifestation is variable, ranging from subclinical presentation to refractory heart failure and cardiogenic shock. Several reports suggest that the use of extracorporeal membrane oxygenation in patients presenting with severe refractory myocarditis is a potential bridging therapy to heart transplant when there is no spontaneous recovery of ventricular function. In a 6-month follow-up outpatient consult, the patient presented well and was asymptomatic. PMID:26761479

  2. Therapeutic effect of recombinant lentiviral vector containing succinate dehydrogenase iron-sulfur protein on the treatment of experimental autoimmunity myocarditis.

    PubMed

    Han, Lina; Wang, Chunxi; Guo, Shuli; Liu, Siyu; Yang, Liming

    2016-08-01

    Cardiac autoimmune reaction takes part in myocarditis, dilated cardiomyopathy and heart failure. Existing literature has confirmed that the occurrence of cardiomyopathy belongs to mitochondrial diseases and is related to the oxidative respiratory chain subunit. The special structure of iron-sulfur protein (ISP) is responsible for the oxidative stress in oxidative phosphorylation, which is also a target that is easily attacked by various damage factors. Using gene therapy technology to restore succinate dehydrogenase iron-sulfur protein (SDISP) function- and thus resume myocardial mitochondria function and myocardial function is hypothesized to alleviate the experimental autoimmunity myocarditis (EAM).

  3. Cytomegalovirus Myocarditis Required Extracorporeal Membrane Oxygenation Support Followed by Ganciclovir Treatment in Infant

    PubMed Central

    Kim, Bong Jun; Jung, Jo Won; Shin, Yu Rim; Park, Han Ki; Park, Young Hwan; Shin, Hong Ju

    2016-01-01

    A 7-month-old girl with no medical history was treated with mechanical circulatory support due to myocarditis. Her cardiac contractility did not improve despite more than one week of extracorporeal membrane oxygenation treatment. Thus, we planned a heart transplant. However, a high level of cytomegalovirus was found in blood laboratory results by quantitative polymerase chain reaction. The patient’s heart contractility recovered to normal range four days after ganciclovir treatment. She was discharged with slightly decreased cardiac contractility with a left ventricular ejection fraction of 45%. PMID:27298799

  4. Does the Influenza Vaccine Prevent Sequelae Such as Myocarditis from Developing?

    PubMed Central

    Whitney, Ryan; Dazley, Jason; Gilbert, Ryan; Slim, Jihad

    2015-01-01

    Vaccination continues to be a valuable and simple procedure to guard patients from an illness that may prevent them from completing their normal everyday tasks, missing days of work, and even lead to unnecessary sequelae. The following case describes one of the many complications that are seen on a regular basis in any community hospital in different regions of the world. The objective of this publication is to remind the public and practitioner of the urgency to vaccinate each season; thereby, curbing the virus's ability to mutate and preventing unwanted consequences such as bacterial super infection or myocarditis. PMID:26392720

  5. Advances in the Traditional Chinese Medicine-Based Management of Viral Myocarditis.

    PubMed

    Cao, Yong; Xu, Xia; Zhang, Peiying

    2015-09-01

    Viral myocarditis (VMC) is a common clinical condition; however, no specific treatment has been available from the perspective of modern western medicine, and typically only symptomatic treatment is provided in clinical settings. The traditional Chinese medicine (TCM) has shown certain advantages in treating VMC. Last few years have witnessed certain advances in the TCM-based research on the etiology and pathogenesis of VMC and its clinical management. This article reviews the clinical advances made in the TCM-based management of VMC in the last 5 years.

  6. Ga-67 citrate myocardial uptake in a patient with AIDS, toxoplasmosis, and myocarditis.

    PubMed

    Memel, D S; DeRogatis, A J; William, D C

    1991-05-01

    A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis. PMID:2054984

  7. Fatal cardiac arrhythmia in a patient with interstitial myocarditis related to chronic arsenic poisoning.

    PubMed

    Hall, J C; Harruff, R

    1989-12-01

    We have reported the case of a 42-year-old man exposed to arsenic at least three times over a ten-month period from an agricultural source. He showed classical symptoms and signs of arsenic poisoning. During chelation therapy and apparent recovery from the poisoning, he suddenly and unexpectedly died; postmortem examination revealed a myocarditis similar to that reported previously. The case demonstrates the need for electrocardiographic monitoring of all patients with arsenic poisoning, during both the initial phase of the illness and convalescence.

  8. Fatal recurrence of fulminant giant cell myocarditis and recovery after initialisation of an alternative immunosuppressive regime

    PubMed Central

    Fluschnik, Nina; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2014-01-01

    We report on a challenging case of a 34-year-old male patient with giant cell myocarditis (GCM) and fulminant relapse after discontinuing immunomodulatory therapy 2 years after the initial event. Specific combined immunosuppressive therapy with antithymocyte globulin (ATG), cyclosporine and high-dose glucocorticoids combined with guideline-based heart failure medication led to the recovery of GCM, improvement of systolic left ventricular function and clinical remission. This case report emphasises the importance of an immunosuppressive therapy for the prognosis and outcome and the risk of discontinuation. Most importantly, ATG seems to be one new possible potential treatment option for patients with acute GCM. PMID:25246472

  9. Lethal enterovirus-induced myocarditis and pancreatitis in a 4-month-old boy.

    PubMed

    Dettmeyer, R B; Padosch, S A; Madea, B

    2006-01-01

    After inconspicuous pregnancy and birth, a 16-year-old mother presented her male baby 5 days later with severe diarrhoea and vomiting. During the following weeks, the child temporarily showed hypotension, hypothermia and increased body temperature, bradyarrythmia with apnoea, continuing diarrhoea, sometimes vomiting and developed signs of pancreatic insufficiency. Due to increasing loss of weight and obviously severe dystrophia, parenteral nutrition had to be initiated. All clinical investigations revealed no underlying disease. Numerous biopsies, mainly from the gastrointestinal tract were taken, but no relevant pathological findings were disclosed. The baby was found lifeless by his mother, 4 months after birth. According to the death certificate, the physicians regarded the lethal outcome as a case of sudden infant death syndrome (SIDS). Histological and immunohistochemical investigations of organ samples revealed signs of myocarditis, pancreatitis and focal pneumonia. Molecularpathological techniques were used to detect enterovirus RNA from tissue samples from the myocardium, liver and pancreas. Enteroviral myocarditis with concomitant pancreatitis was determined as cause of death. PMID:16410153

  10. Myocarditis caused by Feline Immunodeficiency Virus in Five Cats with Hypertrophic Cardiomyopathy.

    PubMed

    Rolim, V Machado; Casagrande, R Assis; Wouters, A Terezinha Barth; Driemeier, D; Pavarini, S Petinatti

    2016-01-01

    Viral infections have been implicated as the cause of cardiomyopathy in several mammalian species. This study describes hypertrophic cardiomyopathy (HCM) and myocarditis associated with feline immunodeficiency virus (FIV) infection in five cats aged between 1 and 4 years. Clinical manifestations included dyspnoea in four animals, one of which also exhibited restlessness. One animal showed only lethargy, anorexia and vomiting. Necropsy examination revealed marked cardiomegaly, marked left ventricular hypertrophy and pallor of the myocardium and epicardium in all animals. Microscopical and immunohistochemical examination showed multifocal infiltration of the myocardium with T lymphocytes and fewer macrophages, neutrophils and plasma cells. An intense immunoreaction for FIV antigen in the cytoplasm and nucleus of lymphocytes and the cytoplasm of some macrophages was observed via immunohistochemistry (IHC). IHC did not reveal the presence of antigen from feline calicivirus, coronavirus, feline leukaemia virus, feline parvovirus, Chlamydia spp. or Toxoplasma gondii. The results demonstrate the occurrence of FIV infection in inflammatory cells in the myocardium of five cats with myocarditis and HCM. PMID:26797583

  11. Churg-Strauss syndrome presenting with acute myocarditis and cardiogenic shock.

    PubMed

    Courand, Pierre-Yves; Croisille, Pierre; Khouatra, Chahéra; Cottin, Vincent; Kirkorian, Gilbert; Bonnefoy, Eric

    2012-03-01

    Churg-Strauss syndrome (CSS) is a multisystem disorder characterised by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. We report the case of a 22 year-old man admitted to the intensive care unit for acute myocarditis complicated with cardiogenic shock. Eosinophilia, history of asthma, lung infiltrates, paranasal sinusitis, glomerulonephritis, and abdominal pain suggested the diagnosis of CSS. Cardiac MRI confirmed cardiac involvement with a diffuse subendocardial delayed enhancement of the left ventricular wall, and a left ventricular ejection fraction (LVEF) of 30%. Acute myocarditis was confirmed with myocardial biopsy. The patient was successfully treated with systemic corticosteroids, intravenous cyclophosphamide, vasopressor inotropes, intra-aortic balloon pump and mechanical ventilation, and was discharged 21 days later. One year after diagnosis, the patient was asymptomatic. The eosinophilic cell count was normal. Follow-up MRI at one year showed LVEF of 40% with persistent delayed enhancement. Cardiac involvement by CSS requires immediate therapy with corticosteroids and cyclophosphamide, which may allow recovery of the cardiac function. PMID:21963398

  12. What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and Animal Studies.

    PubMed

    Tse, Gary; Yeo, Jie M; Chan, Yin Wah; Lai, Eric T H Lai; Yan, Bryan P

    2016-01-01

    Sudden cardiac death (SCD) remains an unsolved problem in the twenty-first century. It is often due to rapid onset, ventricular arrhythmias caused by a number of different clinical conditions. A proportion of SCD patients have identifiable diseases such as cardiomyopathies, but for others, the causes are unknown. Viral myocarditis is becoming increasingly recognized as a contributor to unexplained mortality, and is thought to be a major cause of SCD in the first two decades of life. Myocardial inflammation, ion channel dysfunction, electrophysiological, and structural remodeling may play important roles in generating life-threatening arrhythmias. The aim of this review article is to examine the electrophysiology of action potential conduction and repolarization and the mechanisms by which their derangements lead to triggered and reentrant arrhythmogenesis. By synthesizing experimental evidence from pre-clinical and clinical studies, a framework of how host (inflammation), and viral (altered cellular signaling) factors can induce ion electrophysiological and structural remodeling is illustrated. Current pharmacological options are mainly supportive, which may be accompanied by mechanical circulatory support. Heart transplantation is the only curative option in the worst case scenario. Future strategies for the management of viral myocarditis are discussed. PMID:27493633

  13. What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and Animal Studies

    PubMed Central

    Tse, Gary; Yeo, Jie M.; Chan, Yin Wah; Lai, Eric T. H. Lai; Yan, Bryan P.

    2016-01-01

    Sudden cardiac death (SCD) remains an unsolved problem in the twenty-first century. It is often due to rapid onset, ventricular arrhythmias caused by a number of different clinical conditions. A proportion of SCD patients have identifiable diseases such as cardiomyopathies, but for others, the causes are unknown. Viral myocarditis is becoming increasingly recognized as a contributor to unexplained mortality, and is thought to be a major cause of SCD in the first two decades of life. Myocardial inflammation, ion channel dysfunction, electrophysiological, and structural remodeling may play important roles in generating life-threatening arrhythmias. The aim of this review article is to examine the electrophysiology of action potential conduction and repolarization and the mechanisms by which their derangements lead to triggered and reentrant arrhythmogenesis. By synthesizing experimental evidence from pre-clinical and clinical studies, a framework of how host (inflammation), and viral (altered cellular signaling) factors can induce ion electrophysiological and structural remodeling is illustrated. Current pharmacological options are mainly supportive, which may be accompanied by mechanical circulatory support. Heart transplantation is the only curative option in the worst case scenario. Future strategies for the management of viral myocarditis are discussed. PMID:27493633

  14. Eosinophilic myocarditis associated with eosinophilic pneumonia and eosinophilia following antibiotic and narcotic analgesic treatment.

    PubMed

    Çelik, Aziz İnan; Deniz, Ali; Tangalay, Mustafa; Karaaslan, Muhammet Buğra; Bağır Kılıç, Emine

    2016-09-01

    Eosinophilic myocarditis (EM) is a rare form of myocarditis that usually presents with heart failure due to eosinophilic infiltration. EM is often a component of hypereosinophilic syndrome (HES). HES is a rare disorder characterized by persistent, marked eosinophilia combined with organ system dysfunction. A 38-year-old man was admitted to emergency services with left inguinal pain and fever, and was hospitalized with diagnosis of nephrolithiasis and urinary tract infection. Intravenous antibiotic therapy of 3 grams meropenem per day and analgesic of 50 mg pethidine per day were administered. Typical angina pectoris and dyspnea developed approximately 24 hours after treatment. Rash on the chest, and diminished bilateral lung sounds and rales were observed. Nonspecific changes were present on electrocardiogram. Laboratory analysis showed progressively increasing levels of cardiac biomarkers and eosinophilia. Peripheral blood smear, bone marrow aspiration, and biopsy demonstrated eosinophilia. Chest x-ray revealed diffuse, bilateral interstitial and reticulonodular infiltrates. Transthoracic echocardiography showed thickened left ventricle. Coronary angiography revealed normal coronary arteries. EM was suspected, endomyocardial biopsy was performed, and pathologic specimen confirmed the diagnosis. Corticosteroid treatment was initiated, and within 1 day, angina pectoris and dyspnea had dramatically reduced, and cardiac biomarkers and eosinophil count had decreased. Normal chest x-ray was observed after 72 hours. The patient was discharged with steroid treatment. PMID:27665334

  15. Drug-induced hypersensitivity syndrome due to minocycline complicated by severe myocarditis.

    PubMed

    Kanno, Kyoko; Sakai, Hiroyuki; Yamada, Yutaka; Iizuka, Hajime

    2014-02-01

    A 60-year-old woman presented with a 13-day history of a generalized erythematous rash accompanied by fever, periorbital edema and axillary lymphadenopathy. Prior to the appearance of the rash, the patient had been treated with intermittent courses of oral minocycline for cystitis. The patient was diagnosed with drug-induced hypersensitivity syndrome (DIHS) due to minocycline. During the admission, infectious endocarditis was suspected and the patient was treated with i.v. gammaglobulin (0.4 g/kg per day). The following day, the patient suffered from systemic deterioration and symptomatic low blood pressure that prompted repeat echocardiography which revealed an ejection fraction of 10%. DIHS-associated myocarditis was suspected and management with circulation assistance devices and steroid pulse therapy were started, resulting in satisfactory resolution. A rise in titer of human herpesvirus-6, cytomegalovirus and Herpes simplex virus-1 antibodies was detected. Although minocycline-induced myocarditis is rare, this severe drug reaction should be considered with DIHS.

  16. Reversible Myocarditis and Pericarditis after Black Widow Spider Bite or Kounis Syndrome?

    PubMed Central

    Yaman, Mehmet; Mete, Turkan; Ozer, Ismail; Yaman, Elif; Beton, Osman

    2015-01-01

    Clinical manifestation of black widow spider bite is variable and occasionally leads to death in rural areas. Cases of myocarditis and pericarditis after black widow spider bite are rare and the associated prognostic significance is unknown. Kounis syndrome has been defined as an acute coronary syndrome in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults that manifests as vasospastic angina or acute myocardial infarction or stent thrombosis. Allergic myocarditis is caused by myocardial inflammation triggered by infectious pathogens, toxic, ischemic, or mechanical injuries, such as drug-related inflammation and other immune reactions. A 15-year-old child was admitted to the emergency department with pulmonary edema after spider bite. ST segment depression on ECG, elevated cardiac enzymes and global left ventricular hypokinesia (with ejection fraction of 22%), and local pericardial effusion findings confirmed the diagnosis of myopericarditis. After heart failure and pulmonary edema oriented medical therapy, clinical status improved. Patient showed a progressive improvement and LV functions returned to normal on the sixth day. Myopericarditis complicating spider bite is rare and sometimes fatal. The mechanism is not clearly known. Alpha-latrotoxin of the black widow spider is mostly convicted in these cases. But allergy or hypersensitivity may play a role in myocardial damage. PMID:26509087

  17. NK-derived IFN-γ/IL-4 triggers the sexually disparate polarization of macrophages in CVB3-induced myocarditis.

    PubMed

    Liu, Li; Yue, Yan; Xiong, Sidong

    2014-11-01

    Coxsackievirus B3 (CVB3) is a common etiology of myocarditis with an increased morbidity and mortality in males. We previously reported that differential polarization of macrophages contributed to sexually dimorphic susceptibility of mice to CVB3-induced myocarditis. However, the underlying kinetics, impetus as well as the molecular mechanism remain unclear. Here, we demonstrated that myocardial macrophages started to polarize at as early as day 5 post CVB3 infection in both genders of BALB/c mice, with M1 phenotype detected in males and M2a phenotype in females, and this trend was further amplified at day 7 when myocarditis reached peak. In addition, we identified that prevailed IFN-γ in males and dominant IL-4 in females were critical myocardial cytokines for the disparate macrophage polarization, which respectively activated JAK1-STAT1 and JAK3-STAT6 pathways. Strikingly, we found that the main source of IFN-γ and IL-4 cytokines in both genders were myocardial infiltrating NK cells, which differentially secreted cytokines in various microenvironments manifested synergistically by sex hormones and CVB3 infection. Consistently, depletion of NK cells significantly impeded the myocardial macrophage polarization in both genders of CVB3-infected mice. Collectively, these data indicated that myocardial NK-derived IFN-γ/IL-4 was critical for the differential polarization of macrophages in CVB3-induced myocarditis via activating JAK1-STAT1 and JAK3-STAT6 pathways respectively. Our study may help understand the mechanism of sexually differential polarization of macrophages and provide clues for the gender bias in CVB3-induced myocarditis.

  18. Adult-onset Still's disease with myocarditis and hemophagocytic lymphohistiocytosis: Rare manifestation with fatal outcome.

    PubMed

    Gupta, Devika; Jagani, Rajat; Mendonca, Satish; Rathi, Khushi Ram

    2016-01-01

    Adult-onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology characterized by fever, evanescent pink salmon rash, arthritis, and multiorgan involvement. Here, we report an unusual manifestation of AOSD in a 40-year-old male who presented to our hospital with pyrexia of unknown origin and rash of 3 weeks duration. All his serological investigations and imaging studies were unremarkable. He was fulfilling clinical and laboratory criteria as per Yamaguchi for AOSD and was managed for the same. Our patient did not respond well to the treatment, had a downhill course, and succumbed to his illness. Autopsy confirmed myocarditis and florid bone marrow reactive hemophagocytosis as the cause of his death. PMID:26960645

  19. Inflammatory response to clozapine in the absence of myocarditis: case report

    PubMed Central

    Gee, Siobhan; Shergill, Sukhi S.

    2016-01-01

    Summary A case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent. Clozapine was started and then stopped twice following extensive investigation and with specialist cardiology consultation. Physical symptoms and CRP elevation resolved shortly after clozapine cessation. We believe this constituted an idiosyncratic systemic inflammatory response to clozapine treatment. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703781

  20. Autoimmunity in Coxsackievirus B3 induced myocarditis: role of estrogen in suppressing autoimmunity

    PubMed Central

    2010-01-01

    SUMMARY Picornaviruses are small, non-enveloped, single stranded, positive sense RNA viruses which cause multiple diseases including myocarditis/dilated cardiomyopathy, type 1 diabetes, encephalitis, myositis, orchitis and hepatitis. Although picornaviruses directly kill cells, tissue injury primarily results from autoimmunity to self antigens. Viruses induce autoimmunity by: aborting deletion of self-reactive T cells during T cell ontogeny; reversing anergy of peripheral autoimmune T cells; eliminating T regulatory cells; stimulating self-reactive T cells through antigenic mimicry or cryptic epitopes; and acting as an adjuvant for self molecules released during virus infection. Most autoimmune diseases (SLE, rheumatoid arthritis, Grave’s disease) predominate in females, but diseases associated with picornavirus infections predominate in males. T regulatory cells are activated in infected females because of the combined effects of estrogen and innate immunity. PMID:20963181

  1. Acute myocarditis mimicking acute myocardial infarction: a clinical nightmare with forensic implications.

    PubMed

    Pomara, Cristoforo; Villani, Angelo; D'Errico, Stefano; Riezzo, Irene; Turillazzi, Emanuela; Fineschi, Vittorio

    2006-09-10

    Authors present the case of the sudden death of a 30-year-old man, 3 h since his hospitalization by the onset of aspecific chest pain. ECG findings revealed the presence of localized ST segment elevation in precordial leads (V1-V4) and DII-DII, and aVF mimicking acute antero-inferior myocardial infarction. A diagnosis of acute antero-inferior myocardial infarction was advanced and the patient introduced to thrombolytic therapy. Suddenly, on ECG monitor, conduction abnormalities were early recorded (ventricular extrasystole) followed by ventricular tachycardia degenerating in fatal ventricular fibrillation. An alleged medical malpractice was sued against the cardiologist. A complete immunohistochemical study was performed. Histologically, the heart presented massive interstitial lymphocytic infiltrate and focal myocytes necrosis. The diagnosis of acute lymphocytic myocarditis was established as the cause of death.

  2. Systemic Coxiella-like infection with myocarditis and hepatitis in an eclectus parrot (Eclectus roratus).

    PubMed

    Vapniarsky, N; Barr, B C; Murphy, B

    2012-07-01

    A multiorgan infection with a Coxiella-like organism was determined to be the cause of death of a female eclectus parrot (Eclectus roratus). The diagnosis was based on gross lesions, histopathology, Gimenez and Gram special stains, immunohistochemistry, electron microscopy, and polymerase chain reaction amplification and sequencing of a bacterial 16s rRNA gene fragment isolated from hepatic and cardiac tissue. Gross postmortem examination revealed multifocal to coalescing foci of hepatic necrosis. The most significant histologic lesions included multifocal lymphohistiocytic necrotizing hepatitis, locally extensive lymphoplasmacytic myocarditis, and myocardial degeneration and necrosis. Intralesional cytoplasmic organisms were identified in cardiomyocytes, biliary epithelium, and pancreatic exocrine cells. This is the first description of a Coxiella-like organism with wide-ranging cellular tropisms in a psittacine bird. In addition, lymphoplasmacytic neuritis, myositis, splenitis, airsacculitis, and enteritis were detected. It is also the first report of a Coxiella-like infection in an eclectus parrot.

  3. Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

    PubMed

    Del-Pozo, J; Girling, S; Pizzi, R; Mancinelli, E; Else, R W

    2011-05-01

    This report provides the first account of the pathological changes associated with infection by Serratia marcescens in an adult male axolotl. The infection resulted in septicaemia with severe multifocal necrotizing myocarditis. The latter lesion evolved to cardiac rupture, haemopericardium and death resulting from cardiac tamponade. This animal was exposed to higher than usual temperatures (24-25 °C) 2 weeks before the onset of disease and this may have resulted in immunocompromise and opportunistic bacterial infection. S. marcescens was isolated from the coelomic and pericardial cavity. Both isolates were identical and were resistant to β-lactam antibiotics, but not to aminoglycosides or fluoroquinolones. The production of red prodigiosin pigment by the bacterium suggested an environmental origin. Overall, the clinical and histopathological presentation suggests that S. marcescens should be included in the list of aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of amphibians.

  4. Giant cell myocarditis: a life-threatening disorder heralded by orbital myositis.

    PubMed

    Ali, Muhammad Sajawal; Mba, Benjamin I; Husain, Aliya Noor; Ciftci, Farah Diba

    2016-01-01

    A 40-year-old man with a history of orbital myositis (OM) presented to the emergency department with ventricular tachycardia requiring electrical cardioversion. Postcardioversion ECG showed right bundle branch block, while an echocardiogram revealed an ejection fraction of 20% and a dilated right ventricle. Cardiac MRI produced suboptimal images because the patient was having frequent arrhythmias. The rest of the work up, including coronary angiography, was unremarkable. Given the dilated right ventricle, we suspected arrhythmogenic right ventricular cardiomyopathy and discharged the patient with an implantable cardioverter-defibrillator. 1 week later, he was readmitted with cardiogenic shock; endomyocardial biopsy revealed giant cell myocarditis (GCM). To the best of our knowledge, this is the seventh case report of GCM described in a patient with OM. We recommend that clinicians maintain a high degree of suspicion for GCM in patients with OM presenting with cardiac problems. PMID:27009192

  5. Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats

    PubMed Central

    Matsuzaki, Takashi; Araki, Ryo; Tsuchida, Shota; Thanikachalam, Punniyakoti V.; Fukuta, Tatsuya; Asai, Tomohiro; Yamato, Masaki; Sanada, Shoji; Asanuma, Hiroshi; Asano, Yoshihiro; Asakura, Masanori; Hanawa, Haruo; Hao, Hiroyuki; Oku, Naoto; Takashima, Seiji; Kitakaze, Masafumi; Sakata, Yasushi; Minamino, Tetsuo

    2016-01-01

    Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug’s effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents. PMID:27501378

  6. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma.

    PubMed

    Läubli, Heinz; Balmelli, Cathrin; Bossard, Matthias; Pfister, Otmar; Glatz, Kathrin; Zippelius, Alfred

    2015-01-01

    Antibodies that stimulate the immune system by targeting inhibitory T cell receptors were successfully introduced into oncological practice and are capable to overcome tumor-induced immune evasion. In particular, targeting of the inhibitory receptors CTLA-4 and PD-1 or its ligand PD-L1 have been shown to be beneficial for patients with melanoma, renal cell cancer, non-small cell lung cancer and a growing list of other cancers with impressive response rates. Here, we report a severe, potentially life-threatening side effect of anti-PD-1 immunotherapy with pembrolizumab, which has not been previously described in the literature. A 73-year-old woman with metastatic uveal melanoma treated with pembrolizumab in third line developed severe heart failure due to pembrolizumab-mediated autoimmune myocarditis. Echocardiographic studies revealed a severely impaired left ventricular function with dyssynchrony. All tests for cardiotropic viruses were negative and histological analysis of a myocardial biopsy showed lymphocytic infiltration with a predominance of CD8 positive cells and a reduction of FOXP3 positive regulatory T cells. After initiation of corticosteroids and guideline-conform heart failure therapy, the symptoms rapidly improved and the left ventricular function recovered. While autoimmune myocarditis is a documented side effect of other checkpoint inhibitors, as for example ipilimumab and in one case with anti-PD-L1 antibody, it is not described for anti-PD-1-antibodies like pembrolizumab or nivolumab. As the FDA recently approved both pembrolizumab and nivolumab for melanoma progressing after anti-CTLA-4 treatment with ipilimumab, more patients will soon receive anti-PD-1 therapy. Thus, it is important to be aware of such rare, but severe immune-related adverse events.

  7. A Case of Influenza Associated Fulminant Myocarditis Successfully Treated with Intravenous Peramivir

    PubMed Central

    Jeong, Han Saem; Kim, Sun Jin; Yoon, Young Kyung; Sohn, Jang Wook

    2015-01-01

    We report the case of a patient with fulminant myocarditis caused by influenza A virus, who presented with acute-onset heart failure and cardiogenic shock and was treated successfully with single dose of intravenous peramivir and with pharmacologic hemodynamic support. A 45-year-old Korean woman presented to our emergency department (ED) with shortness of breath and an episode of seizure that developed abruptly 5 hours before she arrived in the ED. She had a history of recurrent epileptic seizure 25 years ago, but denied other specific medical illnesses. In the ED, she was hypoxemic (arterial partial pressure of oxygen, 59.8 mmHg on room air) and chest radiography revealed bilateral alveolar infiltrates. A rapid antigen test for influenza A virus was positive, and she was administered a single dose of peramivir (300 mg) intravenously. Five hours later, the patient's dyspnea had worsened and she was hypotensive (blood pressure, 86/53 mmHg), requiring norepinephrine infusion. Further evaluation disclosed an increased cardiac troponin I level of 1.36 ng/mL and a depressed left ventricular ejection fraction of 30%. Under the diagnosis of influenza A-associated myocarditis and cardiogenic shock, she was managed with continuous critical care in the intensive care unit. On day 3, the patient's dyspnea began to resolve and her ventricular function returned to normal. Real-time polymerase chain reaction assays for influenza viruses in serial nasopharyngeal aspirates were positive for influenza A (hH3N2) with a threshold cycle value of 27.39 on day 2, but these became negative by day 4. The patient recovered and was discharged on day 9 after admission. In conclusion, this case indicates that intravenous peramivir might be an effective antiviral agent for the treatment of severe influenza A virus infection. PMID:26788413

  8. Myocarditis - pediatric

    MedlinePlus

    ... can also damage the heart muscle (called the myocardium) in the process of fighting the infection. This ... 19. Spicer RL, Ware SM. Diseases of the myocardium. In: Kliegman RM, Stanton BF, St Geme JW, ...

  9. Do highly ornamented and less parasitized males have high quality sperm? - an experimental test for parasite-induced reproductive trade-offs in European minnow (Phoxinus phoxinus).

    PubMed

    Kekäläinen, Jukka; Pirhonen, Juhani; Taskinen, Jouni

    2014-11-01

    Parasites take their resources from hosts and thus directly reduce available resources for hosts' own body functions, such as growth and reproduction. Furthermore, parasite infections cause significant indirect costs to their hosts in terms of increased investments on immune defense. In this study, we investigated the impact of parasite infection on the sperm quality and expression of secondary sexual ornamentation (saturation of the red abdominal colouration and number of breeding tubercles) in the Eurasian minnow (Phoxinus phoxinus). We exposed minnows to a high and low dose of common nonspecific fish ectoparasite, the glochidia larvae of duck mussel (Anodonta anatina) and tested whether parasite infection leads to trade-off in sperm quality and/or ornamental expression. We found that glochidia infection reduces the curvature of the sperm swimming trajectory, number of breeding tubercles, and possibly male competitive ability, but does not affect expression of male color ornamentation. Furthermore, glochidia infection was found to reduce sperm motility, but only when all the noninfected individuals were excluded from the model. Supporting one of the predictions by phenotype-linked fertility hypothesis both in high-infection and low-infection group male breeding colouration was positively associated with sperm quality. Our results suggest that although glochidia infection may have negative impact on male reproductive success, parasite-induced costs may not create strong trade-off between breeding colouration and sperm quality or that such trade-off become detectable only in resource-limited conditions. PMID:25540686

  10. Do highly ornamented and less parasitized males have high quality sperm? – an experimental test for parasite-induced reproductive trade-offs in European minnow (Phoxinus phoxinus)

    PubMed Central

    Kekäläinen, Jukka; Pirhonen, Juhani; Taskinen, Jouni

    2014-01-01

    Parasites take their resources from hosts and thus directly reduce available resources for hosts’ own body functions, such as growth and reproduction. Furthermore, parasite infections cause significant indirect costs to their hosts in terms of increased investments on immune defense. In this study, we investigated the impact of parasite infection on the sperm quality and expression of secondary sexual ornamentation (saturation of the red abdominal colouration and number of breeding tubercles) in the Eurasian minnow (Phoxinus phoxinus). We exposed minnows to a high and low dose of common nonspecific fish ectoparasite, the glochidia larvae of duck mussel (Anodonta anatina) and tested whether parasite infection leads to trade-off in sperm quality and/or ornamental expression. We found that glochidia infection reduces the curvature of the sperm swimming trajectory, number of breeding tubercles, and possibly male competitive ability, but does not affect expression of male color ornamentation. Furthermore, glochidia infection was found to reduce sperm motility, but only when all the noninfected individuals were excluded from the model. Supporting one of the predictions by phenotype-linked fertility hypothesis both in high-infection and low-infection group male breeding colouration was positively associated with sperm quality. Our results suggest that although glochidia infection may have negative impact on male reproductive success, parasite-induced costs may not create strong trade-off between breeding colouration and sperm quality or that such trade-off become detectable only in resource-limited conditions. PMID:25540686

  11. Correlation between Presence of Trypanosoma cruzi DNA in Heart Tissue of Baboons and Cynomolgus Monkeys, and Lymphocytic Myocarditis

    PubMed Central

    Mubiru, James N.; Yang, Alice; Dick, Edward J.; Owston, Michael; Sharp, R. Mark; VandeBerg, Jane F.; Shade, Robert E.; VandeBerg, John L.

    2014-01-01

    Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and cynomolgus monkeys (Macaca fascicularis) have been reported to be infected naturally with T. cruzi. In this study, we retrospectively reviewed cases of animals that were diagnosed with lymphocytic myocarditis and used a polymerase chain reaction (PCR)-based method (S36/S35 primer set) to amplify T. cruzi DNA from archived frozen and formalin-fixed paraffin-embedded (FFPE) cardiac tissues. We show that the PCR method is applicable in archived frozen and FFPE tissues and the sensitivity is in the femtogram range. A positive correlation between PCR positivity and lymphocytic myocarditis in both baboons and cynomolgus monkeys is shown. We also show epicarditis as a common finding in animals infected with T. cruzi. PMID:24567317

  12. Salmonella myocarditis in a young adult patient presenting with acute pulmonary edema, rhabdomyolysis, and multi-organ failure.

    PubMed

    Al-aqeedi, Rafid Fayadh; Kamha, Ahmed; Al-aani, Fuad K; Al-ani, Ahmed A

    2009-12-01

    The mortality and morbidity of salmonella infections is seriously underestimated. Salmonella myocarditis is an unusual complication of salmonella sepsis in adults. Cases that do occur may be associated with high morbidity and mortality. We present a rare case of salmonella myocarditis with multi-organ failure in a previously healthy young adult man who was brought to the emergency room with fever, diarrhea, shortness of breath, and altered sensorium, discovered to have acute pulmonary edema and respiratory compromise for which he was assisted with mechanical ventilation for 8 days. Blood culture grew Salmonella typhi. Biochemically he exhibited myocardial, hepatic, and muscular enzymatic surge with renal failure, features of rhabdomyolysis, and disseminated intravascular coagulation. The patient showed a progressive improvement on treatment with ceftriaxone for 2 weeks in addition to decongestive therapy. He was discharged in good condition afterward. PMID:19944325

  13. Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients.

    PubMed

    Lee, Ing-Kit; Lee, Wen-Huei; Liu, Jien-Wei; Yang, Kuender D

    2010-10-01

    We report a case of dengue hemorrhagic fever (DHF) complicated by acute myocarditis and review the literature. A 65-year-old woman experienced DHF due to dengue virus serotype 3, complicated with acute myocarditis and acute pulmonary edema. Clinically this masqueraded as acute myocardial infarction, with an electrocardiographically depressed ST segment in precordial leads and elevated serum cardiac-specific troponin I level. Under supportive management, the patient recovered 3 days later. A total of 18 pertinent articles involving 339 dengue-affected patients with cardiac complications were found by PubMed search. Clinical manifestations of cardiac complications varied considerably, from self-limiting tachy-brady arrhythmia to severe myocardial damage, leading to hypotension and pulmonary edema. Although rare, a fatal outcome was reported in some cases of dengue with cardiac complications. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for cardiac complications in patients with dengue illness and should manage this accordingly.

  14. A premature low-birth-weight infant with congenital complete atrioventricular block and myocarditis successfully treated by staged pacemaker implantation.

    PubMed

    Fujioka, Tao; Nii, Masaki; Tanaka, Yasuhiko

    2016-06-01

    Congenital complete atrioventricular block is a known lethal condition. Although antenatal diagnosis and the technical advances of pacemaker treatment have reduced its mortality, treatment of premature babies with significant myocardial damage remains a challenge. In this paper, we report the case of a premature low-birth-weight infant with congenital complete atrioventricular block and extremely low ventricular rate, fetal hydrops, and myocarditis who was successfully treated with staged permanent pacemaker implantation. PMID:27071550

  15. Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

    PubMed Central

    Li-Sha, Ge; Jing-Lin, Zhao; Guang-Yi, Chen; Li, Liu; De-Pu, Zhou; Yue-Chun, Li

    2015-01-01

    The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis. PMID:26507386

  16. Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3.

    PubMed

    Li-Sha, Ge; Jing-Lin, Zhao; Guang-Yi, Chen; Li, Liu; De-Pu, Zhou; Yue-Chun, Li

    2015-10-28

    The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.

  17. The effect of alpha 1-blocker, bunazosin on a murine model of congestive heart failure induced by viral myocarditis.

    PubMed

    Yamada, T; Matsumori, A; Okada, I; Tominaga, M; Kawai, C

    1992-11-01

    The purpose of this study was to investigate the therapeutic effect of an alpha 1-blocker, bunazosin, using an experimental murine model of congestive heart failure induced by viral myocarditis. This model is characterized by a high incidence of severe myocarditis and subsequent congestive heart failure, and is suitable for the evaluation of the effect of drugs. To estimate myocardial damage objectively and quantitatively, we used antimyosin monoclonal antibody in addition to histopathological grading. Four-week-old BALB/c mice were inoculated with encephalomyocarditis virus. The mice were injected daily with bunazosin or saline as a placebo from the day of viral inoculation until day 7 (protocol-I) or day 14 (protocol-II), or from day 4 to day 14 (protocol-III). They were then injected with 1.5 microCi of indium-111 labeled antimyosin antibody and were killed 24 h later. The antimyosin cardiac uptake was counted and histopathological grading was performed. The heart-weight to body-weight ratio, left ventricular dimension, histopathological grades and antimyosin cardiac uptake were significantly lower in the bunazosin group than in the placebo group in protocol-II, but not in protocol-I or protocol-III. Bunazosin showed a protective effect against viral myocarditis only when it was started early after infection and continued until the stage of congestive heart failure.

  18. MicroRNA-19b Downregulates Gap Junction Protein Alpha1 and Synergizes with MicroRNA-1 in Viral Myocarditis

    PubMed Central

    Lin, Junyi; Xue, Aimin; Li, Liliang; Li, Beixu; Li, Yuhua; Shen, Yiwen; Sun, Ning; Chen, Ruizhen; Xu, Hongfei; Zhao, Ziqin

    2016-01-01

    Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction protein α1 (GJA1) in VMC. In this study, miR-19b was found to be significantly upregulated using the microarray analysis in a mouse model of VMC, and overexpression of miR-19b led to irregular beating pattern in human cardiomyocytes derived from the induced pluripotent stem cells (hiPSCs-CMs). The upregulation of miR-19b was associated with decreased GJA1 in vivo. Furthermore, a miR-19b inhibitor increased, while its mimics suppressed the expression of GJA1 in HL-1 cells. When GJA1 was overexpressed, the miR-19b mimics-mediated irregular beating was reversed in hiPSCs-CMs. In addition, the effect of miR-19b on GJA1 was enhanced by miR-1 in a dose-dependent manner. These data suggest miR-19b contributes to irregular beating through regulation of GJA1 by cooperating with miR-1. Based on the present and our previous studies, it could be indicated that miR-19b and miR-1 might be critically involved in cardiac arrhythmia associated with VMC. PMID:27213338

  19. Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection.

    PubMed

    Guerrero, Néstor A; Camacho, Mercedes; Vila, Luis; Íñiguez, Miguel A; Chillón-Marinas, Carlos; Cuervo, Henar; Poveda, Cristina; Fresno, Manuel; Gironès, Núria

    2015-01-01

    Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2-dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.

  20. The interferon inducer ampligen [poly(I)-poly(C12U)] markedly protects mice against coxsackie B3 virus-induced myocarditis.

    PubMed

    Padalko, Elizaveta; Nuyens, Dieter; De Palma, Armando; Verbeken, Erik; Aerts, Joeri L; De Clercq, Erik; Carmeliet, Peter; Neyts, Johan

    2004-01-01

    Viral replication, as well as an immunopathological component, is assumed to be involved in coxsackie B virus-induced myocarditis. We evaluated the efficacy of the interferon inducer Ampligen on coxsackie B3 virus-induced myocarditis in C3H/HeNHsd mice. The efficacy of Ampligen was compared with that of the interferon inducer poly(inosinic acid)-poly(cytidylic acid) [poly(IC)], alpha interferon 2b (INTRON A), and pegylated alpha interferon 2b (PEG-INTRON-alpha-2b). Ampligen at 20 mg/kg of body weight/day was able to reduce the severity of virus-induced myocarditis, as assessed by morphometric analysis, by 98% (P = 3.0 x 10(-8)). When poly(IC) was administered at 15 mg/kg/day, it reduced the severity of virus-induced myocarditis by 93% (P = 5.6 x 10(-5)). Alpha interferon 2b (1 x 10(5) U/day) and pegylated alpha interferon 2b (5 x 10(5) U/day) were less effective and reduced the severity of virus-induced myocarditis by 66% (P = 0.0009) and 78% (P = 0.0002), respectively. The observed efficacies of Ampligen and poly(IC) were corroborated by the observation that the drugs also markedly reduced the virus titers in the heart, as detected by (i) quantitative real-time reverse transcription-PCR and (ii) titration for infectious virus content. Whereas the electrocardiograms for untreated mice with myocarditis were severely disturbed, the electrocardiographic parameters were normalized in Ampligen- and poly(IC)-treated mice. Even when start of treatment with Ampligen was delayed until day 2 postinfection, a time at which lesions had already appeared in untreated control animals, a marked protective effect on the development of viral myocarditis (as assessed at day 6 postinfection) was still noted.

  1. Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels.

    PubMed

    Cunha, Burke A; Pherez, Francisco M; Alexiadis, Varvara; Gagos, Marios; Strollo, Stephanie

    2010-01-01

    erythema. We present a case of adult Kawasaki's disease with myocarditis and splenomegaly. The patient's myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasaki's disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL; (normal<189 ng/mL). To the best of our knowledge, this is the first report of adult Kawasaki's disease with highly elevated serum ferritin levels. This is also the first report of splenomegaly in adult Kawasaki's disease. We conclude that Kawasaki's disease should be considered in the differential diagnosis in adult patients with rash/fever for> or =5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels.

  2. Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

    PubMed

    Root-Bernstein, Robert; Fairweather, DeLisa

    2015-06-21

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related.

  3. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    PubMed Central

    Soares, Milena B. P.; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M.; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ∼30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease causal agent, ie, the T. cruzi, are described herein. Bone marrow cells injected intravenously into chronic chagasic mice migrated to the heart and caused a significant reduction in the inflammatory infiltrates and in the interstitial fibrosis characteristics of chronic chagasic cardiomyopathy. The beneficial effects were observed up to 6 months after bone marrow cell transplantation. A massive apoptosis of myocardial inflammatory cells was observed after the therapy with bone marrow cells. Transplanted bone marrow cells obtained from chagasic mice and from normal mice had similar effects in terms of mediating chagasic heart repair. These results show that bone marrow cell transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy. PMID:14742250

  4. Unresolved issues in theories of autoimmune disease using myocarditis as a framework

    PubMed Central

    Root-Bernstein, Robert; Fairweather, DeLisa

    2014-01-01

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. PMID:25484004

  5. IL-9 Inhibits Viral Replication in Coxsackievirus B3-Induced Myocarditis

    PubMed Central

    Yu, Miao; Long, Qi; Li, Huan-Huan; Liang, Wei; Liao, Yu-Hua; Yuan, Jing; Cheng, Xiang

    2016-01-01

    Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8+ T cells on day 5 and CD4+ T cells on day 7 in the myocardium. Further, IL-9 knockout exacerbated cardiac damage following CVB3 infection, along with a sharp increase in viral replication and IL-17a expression, as well as a decrease in TGF-β. In contrast, the repletion of IL-9 in Balb/c mice with CVB infection induced the opposite effect. Studies in vitro further revealed that IL-9 directly inhibited viral replication in cardiomyocytes by reducing coxsackie and adenovirus receptor expression, which might be associated with upregulation of TGF-β autocrine effect in these cells. However, IL-9 had no direct effect on apoptosis in cardiomyocytes. Our data indicated that IL-9 played a protective role in disease progression by inhibiting CVB3 replication in the early stages of VMC. PMID:27766098

  6. Coxsackievirus B detection in cases of myocarditis, myopericarditis, pericarditis and dilated cardiomyopathy in hospitalized patients

    PubMed Central

    GAALOUL, IMED; RIABI, SAMIRA; HARRATH, RAFIK; HUNTER, TIMOTHY; HAMDA, KHALDOUN B.; GHZALA, ASSIA B.; HUBER, SALLY; AOUNI, MAHJOUB

    2014-01-01

    Coxsackieviruses B (CV-B) are known as the most common viral cause of human heart infections. The aim of the present study was to assess the potential role of CV-B in the etiology of infectious heart disease in hospitalized patients. The present study is based on blood, pericardial fluid and heart biopsies from 102 patients and 100 control subjects. All of the samples were examined for the detection of specific enteroviral genome using the reverse transcription polymerase chain reaction (RT-PCR) and sequence analysis. Immunohistochemical investigations for the detection of the enteroviral capsid protein, VP1, from the biopsies were performed. The samples were cultured on confluent KB monolayer cell line for possible virus isolation. The epidemiological data were also collected. CV-B was detected in 28 of the 102 patients. The sequence analysis demonstrated that 27 strains were identical to CV-B3 and only one strain was identical to CV-B1. Furthermore, VP1 in the heart biopsies was detected in enterovirus-positive cases, as revealed by RT-PCR. Pericarditis infection was more frequent than myocarditis (P<0.05) or myopericarditis (P=0.05). The epidemiological data demonstrate that CV-B heart infections occur mainly during autumn and winter, and young male adults are more susceptible than adolescents or adults (P<0.5). The present findings demonstrate a higher prevalence of viral heart infections, suggesting that CV-B may significantly contribute to heart infections. PMID:25241846

  7. Native T1-mapping detects the location, extent and patterns of acute myocarditis without the need for gadolinium contrast agents

    PubMed Central

    2014-01-01

    Background Acute myocarditis can be diagnosed on cardiovascular magnetic resonance (CMR) using multiple techniques, including late gadolinium enhancement (LGE) imaging, which requires contrast administration. Native T1-mapping is significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging in detecting myocarditis. The aims of this study were to demonstrate how to display the non-ischemic patterns of injury and to quantify myocardial involvement in acute myocarditis without the need for contrast agents, using topographic T1-maps and incremental T1 thresholds. Methods We studied 60 patients with suspected acute myocarditis (median 3 days from presentation) and 50 controls using CMR (1.5 T), including: (1) dark-blood T2W imaging; >(2) native T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3) areas of injury by T2W, T1-mapping and LGE. Results Compared to controls, patients had more edema (global myocardial T2 SI ratio 1.71 ± 0.27 vs.1.56 ± 0.15), higher mean myocardial T1 (1011 ± 64 ms vs. 946 ± 23 ms) and more areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%) and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms (sensitivity 90%, specificity 88%) detected significantly larger areas of involvement than T2W and LGE imaging in patients, and additional areas of injury when T2W and LGE were negative. T1-mapping significantly improved the diagnostic confidence in an additional 30% of cases when at least one of the conventional methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental thresholds, T1-mapping can display the non-ischemic patterns of injury typical of myocarditis. Conclusion Native T1-mapping can display the typical non-ischemic patterns in acute myocarditis, similar to LGE imaging but without the need for contrast agents. In

  8. Coxsackievirus group B type 3 infection upregulates expression of monocyte chemoattractant protein 1 in cardiac myocytes, which leads to enhanced migration of mononuclear cells in viral myocarditis.

    PubMed

    Shen, Yan; Xu, Wei; Chu, Yi-Wei; Wang, Ying; Liu, Quan-Sheng; Xiong, Si-Dong

    2004-11-01

    Coxsackievirus group B type 3 (CVB3) is an important cause of viral myocarditis. The infiltration of mononuclear cells into the myocardial tissue is one of the key events in viral myocarditis. Immediately after CVB3 infects the heart, the expression of chemokine(s) by infected myocardial cells may be the first trigger for inflammatory infiltration and immune response. However, it is unknown whether CVB3 can induce the chemokine expression in cardiac myocytes. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemokine that stimulates the migration of mononuclear cells. The objective of the present study was to investigate the effect of CVB3 infection on MCP-1 expression in murine cardiac myocytes and the role of MCP-1 in migration of mononuclear cells in viral myocarditis. Our results showed that the expression of MCP-1 was significantly increased in cardiac myocytes after wild-type CVB3 infection in a time- and dose-dependent manner, which resulted in enhanced migration of mononuclear cells in mice with viral myocarditis. The migration of mononuclear cells was partially abolished by antibodies specific for MCP-1 in vivo and in vitro. Administration of anti-MCP-1 antibody prevented infiltration of mononuclear cells bearing the MCP-1 receptor CCR2 in mice with viral myocarditis. Infection by UV-irradiated CVB3 induced rapid and transient expression of MCP-1 in cardiac myocytes. In conclusion, our results indicate that CVB3 infection stimulates the expression of MCP-1 in myocardial cells, which subsequently leads to migration of mononuclear cells in viral myocarditis. PMID:15507642

  9. Two-dimensional speckle-tracking-derived segmental peak systolic longitudinal strain identifies regional myocardial involvement in patients with myocarditis and normal global left ventricular systolic function.

    PubMed

    Uppu, Santosh C; Shah, Amee; Weigand, Justin; Nielsen, James C; Ko, H Helen; Parness, Ira A; Srivastava, Shubhika

    2015-06-01

    The presence of myocardial late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging in concert with electrocardiography and elevated biomarkers helps support the diagnosis of acute myocarditis. Two-dimensional echocardiography is limited to global and qualitative regional function assessment and may not contribute to the diagnosis, especially in the presence of normal LV systolic function. Two-dimensional speckle-tracking (2D-STE)-derived segmental peak systolic (pkS) longitudinal strain (LS) may identify segmental myocardial involvement in myocarditis. We sought to identify an association between segmental pkS, LGE, and troponin levels in patients with myocarditis. Retrospective analysis of myocardial segmental function by 2D-STE segmental strain was compared to the presence of LGE and admission peak troponin levels in patients with acute myocarditis and preserved global LV systolic function. American Heart Association 17-segment model was used for comparison between imaging modalities. Global function was assessed by m-mode-derived shortening fraction (SF). Descriptive statistics and regression analysis were utilized. Forty-four CMRs performed to evaluate for myocarditis were identified. Of the 44, 10 patients, median age 17.5 years (14-18.5 years) and median SF 35 % (28-44 %), had paired CMR and 2D-STE data for analysis, and 161/170 segments could be analyzed by both methods for comparison. PkS LS was decreased in 51 % of segments that were positive for LGE with average pkS of -14.7 %. Segmental pkS LS abnormalities were present in all but one patient who had abnormal pkS circumferential strain. Global pkS LS was decreased in patients with myocarditis. There is a moderate correlation between decreased pkS LS and the presence of LGE by CMR, 2D-STE for myocardial involvement in acute myocarditis can serve as an useful noninvasive adjunct to the existing tests used for the diagnosis of acute myocarditis and might have a role in prognostication.

  10. Triple bridge-to-transplant in a case of giant cell myocarditis complicated by human leukocyte antigen sensitization and heparin-induced thrombocytopenia type II.

    PubMed

    Schenk, Soren; Arusoglu, Latif; Morshuis, Michiel; Minami, Kazutomo; Sarnowski, Peter; Koerfer, Reiner; El-Banayosy, Aly

    2006-03-01

    Bridge-to-bridge experience has documented the feasibility of a switch from short-term to long-term mechanical circulatory support until heart transplant. We describe a case of irreversible cardiogenic shock due to giant cell myocarditis treated consecutively with extracorporal membrane oxygenation, bi-ventricular assist device, and total artificial heart. The postoperative course was complicated by human leukocyte antigen sensitization and heparin-induced thrombocytopenia type II. Our patient successfully underwent heart transplant after 10 months of support and was discharged in good condition. This case illustrates suitable device selection for myocarditis and represents two treatable immunological complications.

  11. [Effect of metabolic therapy on the course of heart failure in patients after myocarditis complicated with systemic connecting tissue diseases].

    PubMed

    Kuriata, A V; Karavanskaia, I L; Pavlichenko, N A

    2010-01-01

    In the course of observation over 40 patients after an old myocarditis against general systemic diseases of connective tissue who had been given a pharmacotherapy regarding main disease and a chronic heart failure, additionally Vazonat (campaign of "Olajnfarm", Latvia), preparation of the myocardial cytoprotection was prescribed in a therapeutic dose of 500 mg per day. Vazonat inclusion in basic therapy during 1 month was accompanied by improvement of a clinical condition of the patients, reduction of heart failure signs, and improvement of life quality. PMID:21488376

  12. Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.

    PubMed

    Semper, H; Muehlberg, F; Schulz-Menger, J; Allewelt, M; Grohé, C

    2016-09-01

    Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response. PMID:27565924

  13. Molecular phenotypes of human parvovirus B19 in patients with myocarditis

    PubMed Central

    Bock, C-Thomas; Düchting, Anja; Utta, Friederike; Brunner, Eva; Sy, Bui Tien; Klingel, Karin; Lang, Florian; Gawaz, Meinrad; Felix, Stephan B; Kandolf, Reinhard

    2014-01-01

    AIM: To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM). METHODS: Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software. RESULTS: The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P < 0.0001). The detection of B19V-mRNA replication intermediates proved that replication of B19V was present. RFLP-PCR assays showed that B19V-genotype 1 (57.4%) and B19V-genotype 2 (36.7%) were the most prevalent viral genotypes. B19V-genotype 2 was observed more frequently in EMBs with iCMP (65.0%) compared to DCM (35%) (P = 0.049). Although there was no significant difference in gender-specific B19V

  14. Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A retrospective study.

    PubMed

    Yu, Dan-Qing; Wang, Ying; Ma, Gui-Zhou; Xu, Rong-He; Cai, Zhi-Xiong; Ni, Chu-Min; Chen, Ping; Zhu, Zhi-Dan

    2014-01-01

    Acute fulminant myocarditis (AFM) is a serious heart disease with limited treatment. This observational retrospective study aimed to investigate whether intravenous immunoglobulin (IVIG) was able to improve left ventricular function and reduce the episodes of arrhythmia in adult patients with AFM. The medical records of all patients with AFM who were admitted to the Critical Care Unit of Guangdong General Hospital (Guangzhou, China) between January 2001 and December 2010 were reviewed. A cohort of 58 patients was included in the study. Of these 58, 32 patients were treated with IVIG (400 mg/kg per day) for five days, while the remaining patients did not receive IVIG therapy. The patients who received IVIG therapy had a higher left ventricular ejection fraction (LVEF) and a reduced left ventricular end-diastolic diameter (LVDD) compared with the non-IVIG therapy patients four weeks subsequent to the treatment (PLVEF=0.011 and PLVDD=0.048). The post-treatment incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) and atrioventricular block (AVB) was reduced in the patients who received IVIG therapy compared with the baseline values (PVT/VF=0.025, PAVB=0.003); however, no significant differences were observed in the non-IVIG therapy patients (PVT/VF=0.564, PAVB=0.083) following treatment. There were two mortalities in the IVIG therapy group and seven in the non-IVIG therapy group (P=0.072). This retrospective study suggested that the use of IVIG for the treatment of AFM may be associated with improved left ventricular function and reduced episodes of fulminant arrhythmias. PMID:24348772

  15. Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice.

    PubMed Central

    Blay, R.; Simpson, K.; Leslie, K.; Huber, S.

    1989-01-01

    DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect. Images Figure 1 PMID:2573284

  16. Usefulness of Rabbit Anti-thymocyte Globulin in Patients With Giant Cell Myocarditis.

    PubMed

    Suarez-Barrientos, Aida; Wong, Joyce; Bell, Alexander; Lyster, Haifa; Karagiannis, Georgios; Banner, Nicholas R

    2015-08-01

    Giant cell myocarditis (GCM) is an aggressive inflammatory myocardial disease. Immunosuppression is an effective treatment for some cases. However, the duration of action of agents such as muromonab CD3 is short and others such as the calcineurin inhibitors may lead to renal failure. Here we describe the outcome of a novel approach to treatment using rabbit anti-thymocyte globulin (RATG). A retrospective analysis of 6 patients treated with RATG for GCM was performed. Diagnosis was confirmed by endomyocardial biopsy, and RATG was administered with a high dose of corticosteroids. None of the patients had cytokine release syndrome or leukopenia, and 5 had thrombocytopenia (2 of them severe). Only 1 had a serious bleeding event that occurred after implantation of mechanical circulatory support. None developed impaired renal function after the treatment. Five were successfully discharged home with an increase in global left ventricular ejection fraction of 29%. Four are currently alive without recurrent disease, 1 of them after heart transplantation, with a mean follow-up of 970 days (423 to 1,875 days), left ventricular ejection fraction of 53%, and all in current New York Heart Association Classification class ≤II. Only 1 case had GCM recurrence. There were 2 deaths: one because of intracranial bleeding after mechanical circulatory support implantation and the other caused by primary graft dysfunction. In conclusion, patients with GCM can be successfully immunosuppressed with RATG and corticosteroids, thereby avoiding renal impairment. Early thrombocytopenia is the main adverse event. Larger cohorts of patients are necessary to compare the different immunosuppressant strategies available for GCM in a randomized fashion. PMID:26048854

  17. CCR5 plays a critical role in the development of myocarditis and host protection in mice infected with Trypanosoma cruzi.

    PubMed

    Machado, Fabiana S; Koyama, Natalia S; Carregaro, Vanessa; Ferreira, Beatriz R; Milanezi, Cristiane M; Teixeira, Mauro M; Rossi, Marcos A; Silva, João S

    2005-02-15

    The pathogenesis of myocarditis during Trypanosoma cruzi infection is poorly understood. We investigated the role played by chemokine receptor 5 (CCR5) in the influx of T cells to the cardiac tissue of T. cruzi-infected mice. mRNA and protein for the CCR5 ligands CCL3, CCL4, and CCL5 were detected in the hearts of infected mice in association with CD4+ and CD8+ T cells. There was a high level of CCR5 expression on CD8+ T cells in the hearts of infected mice. Moreover, CCR5 expression on CD8+ T cells was positively modulated by T. cruzi infection. CCR5-deficient mice infected with T. cruzi experienced a dramatically inhibited migration of T cells to the heart and were also more susceptible to infection. These results suggest that CCR5 and its ligands play a central role in the control of T cell influx in T. cruzi-infected mice. Knowledge of the mechanisms that trigger and control the migration of cells to the heart in patients with Chagas disease may help in the design of drugs that prevent myocarditis and protect against the development of severe disease.

  18. Characterisation of a novel pestivirus associated with an outbreak of stillbirths and pre-weaning deaths in pigs due to myocarditis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A syndrome of stillbirths and preweaning losses with myocarditis occurred on 2 Australian pig farms in 2003. While extensive investigations excluded a wide range of know agents, a foetal inoculation study confirmed an infectious agent was present and likely to be viral. This paper describes the iden...

  19. [The clinical practice guidelines of the Sociedad Española de Cardiología on cardiomyopathies and myocarditis].

    PubMed

    Galve Basilio, E; Alfonso Manterola, F; Ballester Rodés, M; Castro Beiras, A; Fernández de Soria Pantoja, R; Penas Lado, M; Sánchez Domínguez, J

    2000-03-01

    Myocardial diseases are a extraordinarily heterogeneous group of processes that only have in common the fact that they involve heart muscle and that they cause a wide spectrum of myocardial dysfunction. The approach of the management and treatment of the cardiomyopathies is a continuous matter of discussion because the vast majority of alternatives in this field have not been based on the best scientific possible evidence and, since except for the case of heart failure associated with dilated cardiomyopathy. The majority of different options have not been studied by means of large (or even small) randomized trials. Nevertheless, this chapter has tried to provide the reader with different approaches on how to deal with important clinical problems in dilated, hypertrophic and restrictive cardiomyopathies, and in myocarditis as well. For this, we have utilized the most relevant information found coupled with our best clinical judgment, although we admit that many of the clinical recommendations can be controversial.

  20. First successful bridge to recovery with the Impella Recover 100 left ventricular assist device for fulminant acute myocarditis.

    PubMed

    Colombo, Tiziano; Garatti, Andrea; Bruschi, Giuseppe; Lanfranconi, Marco; Russo, Claudio; Milazzo, Filippo; Catena, Emanuele; Frigerio, Maria; Vitali, Ettore

    2003-09-01

    A patient with septic and cardiogenic shock secondary to acute fulminant myocarditis was successfully treated by mechanical offloading of the left ventricle using the Impella Recover 100, a new implantable micro-axial blood pump designed for short-term circulatory support (for a maximum of 7 days). The possibility of implanting this device without using cardiopulmonary bypass allowed as to manage the septic shock, to reverse cardiac and hepatorenal failure and to wean the patient off treatment after 18 days of support. At 3 months the left and right ventricular function was satisfactory. The widespread application of this kind of support depends on the availability of an inexpensive "mini-invasive" blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.

  1. [Fulminant myocarditis causing severe left heart failure and massive thrombus formation following cardiac tamponade: a case report].

    PubMed

    Miyamoto, Koji; Yasuda, Satoshi; Noguchi, Teruo; Tanimoto, Takashi; Kakuchi, Hiroyuki; Morii, Isao; Kawamura, Atsushi; Nakatani, Takeshi; Nonogi, Hiroshi; Goto, Yoichi; Miyazaki, Shunichi

    2005-07-01

    A woman aged middle thirties presented with common cold-like symptoms, and was hospitalized due to hypotension and tachycardia. Echocardiography revealed pericardial effusion and preserved left ventricular fractional shortening (28%). Cardiac index, pulmonary capillary wedge and right atrial pressure were 1.8 l/min/m2, 15 and 13 mmHg, respectively. After drainage of pericardial effusion, cardiac index increased to 3.4 l/min/m2. On the fifth hospital day, left ventricular dysfunction developed (fractional shortening: 16%, cardiac index: 1.5 l/min/m2, pulmonary capillary wedge pressure: 18 mmHg, right atrial pressure: 12 mmHg), so percutaneous cardiopulmonary support was introduced. However, the heart failed in asystole and the cavity was occupied by massive thrombus, probably related to heparin-induced thrombocytopenia. This case of fulminant myocarditis passed through various clinical features of heart failure. She died on the 12th hospital day.

  2. A DNA vaccine encoding CCL4/MIP-1beta enhances myocarditis in experimental Trypanosoma cruzi infection in rats.

    PubMed

    Roffê, Ester; Souza, Adriano L S; Caetano, Bráulia C; Machado, Patrícia P; Barcelos, Lucíola S; Russo, Remo C; Santiago, Helton C; Souza, Danielle G; Pinho, Vanessa; Tanowitz, Herbert B; Camargos, Elisabeth R S; Bruña-Romero, Oscar; Teixeira, Mauro M

    2006-10-01

    Chagas' disease, caused by Trypanosoma cruzi, is a major cause of cardiovascular disease in Latin America. Exacerbated inflammation disproportional to parasite load characterizes chronic myocardial lesions in chagasic patients. Chemokines and their receptors are expected to account for the renewed inflammatory processes after the inoculation of the parasite, but their potential unique functions are far from being clear. Herein, we evaluated the effect of a DNA vaccine encoding CCL4/MIP-1beta, a CC-chemokine, in T. cruzi-elicited myocarditis in rats. Holtzman rats were given intramuscularly cardiotoxin and the CCL4/MIP-1beta DNA-containing plasmid (100microg) was delivered in this muscular site four times. Fourteen days after last immunization, animals were inoculated with a myotropical CL-Brener T. cruzi clone. Peak of parasitism was observed at day 15 after infection, preceding the peak of myocardial inflammation at day 20. Myocarditis was still intense at day 30, but the inflammatory infiltrates showed a more focal distribution. The expression of CCL2/MCP-1 and CCL4/MIP-1beta correlated closely with the kinetics of myocardial inflammation. The CCL4/MIP-1beta DNA vaccine induced an increase of the levels of the anti-CCL4/MIP-1beta observed in T. cruzi-infected animals. This was associated with an exacerbation of myocardial inflammation and fibrosis, although alterations in parasitemia and myocardial parasitism were not observed. Our data suggest that CCL4/MIP-1beta plays a role in preventing excessive inflammation and pathology rather than in controlling parasite replication.

  3. Activated nuclear transcription factor {kappa}B in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function

    SciTech Connect

    Alter, Peter . E-mail: palter@med.uni-marburg.de; Rupp, Heinz; Maisch, Bernhard

    2006-01-06

    Objectives and background: Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-{kappa}B (NF{kappa}B). Methods: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NF{kappa}B was performed. Results: NF{kappa}B was increased in patients with myocarditis when compared with controls (11.1 {+-} 7.1% vs. 5.0 {+-} 5.3%, P < 0.005) whereas dilated cardiomyopathy showed no significant increase. Patients with myocarditis and preserved left ventricular function exhibited increased activated NF{kappa}B when compared with reduced function (r {sup 2} = 0.72, P < 0.001). In parallel, inverse correlation of NF{kappa}B and left ventricular enddiasstolic volume was found (r {sup 2} = 0.43, P < 0.02). Increased activated NF{kappa}B was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NF{kappa}B activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NF{kappa}B activation. Conclusions: Increased activation of NF{kappa}B is related to inflammatory processes in myocarditis. Since activated NF{kappa}B correlates with left ventricular function, it could be assumed that NF{kappa}B activation occurs at early stages of inflammation. Potentially, NF{kappa}B could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NF{kappa}B is a crucial key transcription factor of inflammation, its

  4. Neonatal Enterovirus Infection: Case Series of Clinical Sepsis and Positive Cerebrospinal Fluid Polymerase Chain Reaction Test with Myocarditis and Cerebral White Matter Injury Complications

    PubMed Central

    Morriss, Frank H.; Lindower, Julie B.; Bartlett, Heather L.; Atkins, Dianne L.; Kim, Jean O.; Klein, Jonathan M.; Ford, Bradley A.

    2016-01-01

    Objective We describe five neonates with enteroviral (EV) infection to demonstrate central nervous system (CNS) and cardiac complications and report successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in two. Study Design Case series identified during three enteroviral seasons in one neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse transcriptase polymerase chain reaction (PCR) testing for EV in neonates suspected to have sepsis, but with sterile bacterial cultures. Results Cases were identified in each of three sequential years in a NICU with 800 to 900 admissions/year. Two cases were likely acquired perinatally; all were symptomatic with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis and/or meningitis; one progressed to periventricular leukomalacia and encephalomalacia. Two recovered from myocarditis after treatment that included IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR testing. Cases may be underdiagnosed in the early neonatal period if specific testing is not performed. Neonates with EV infection should be investigated for evidence of periventricular leukomalacia, screened for myocarditis, and considered for IVIG treatment. PMID:27695644

  5. Neonatal Enterovirus Infection: Case Series of Clinical Sepsis and Positive Cerebrospinal Fluid Polymerase Chain Reaction Test with Myocarditis and Cerebral White Matter Injury Complications

    PubMed Central

    Morriss, Frank H.; Lindower, Julie B.; Bartlett, Heather L.; Atkins, Dianne L.; Kim, Jean O.; Klein, Jonathan M.; Ford, Bradley A.

    2016-01-01

    Objective We describe five neonates with enteroviral (EV) infection to demonstrate central nervous system (CNS) and cardiac complications and report successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in two. Study Design Case series identified during three enteroviral seasons in one neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse transcriptase polymerase chain reaction (PCR) testing for EV in neonates suspected to have sepsis, but with sterile bacterial cultures. Results Cases were identified in each of three sequential years in a NICU with 800 to 900 admissions/year. Two cases were likely acquired perinatally; all were symptomatic with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis and/or meningitis; one progressed to periventricular leukomalacia and encephalomalacia. Two recovered from myocarditis after treatment that included IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR testing. Cases may be underdiagnosed in the early neonatal period if specific testing is not performed. Neonates with EV infection should be investigated for evidence of periventricular leukomalacia, screened for myocarditis, and considered for IVIG treatment.

  6. TNFR-Fc fusion protein expressed by in vivo electroporation improves survival rates and myocardial injury in coxsackievirus induced murine myocarditis

    SciTech Connect

    Kim, Jong-Mook; Lim, Byung-Kwan; Ho, Seong-Hyun; Yun, Soo-Hyeon; Shin, Jae-Ok; Park, Eun-Min; Kim, Duk-Kyung; Kim, Sunyoung; Jeon, Eun-Seok . E-mail: esjeon@smc.samsung.co.kr

    2006-06-09

    Tumor necrosis factor-{alpha} (TNF-{alpha}) is one of the major cytokines that modulate the immune response in viral myocarditis, but its role has not yet been thoroughly evaluated. We antagonized TNF-{alpha} using the expressed soluble p75 TNF receptor linked to the Fc portion of the human IgG1 gene (sTNFR:Fc) by in vivo electroporation, and evaluated its effects on experimental coxsackieviral B3 (CVB3) myocarditis. A plasmid DNA encoding sTNFR:Fc (15 {mu}g/mouse) was injected into the gastrocnemius muscles of Balb/C male mice followed by electroporation (day -1). Control mice were injected with an empty vector. One day after electroporation, mice were infected with CVB3 (day 0). Serum levels of sTNFR:Fc increased from day 2 and peaked at day 5 following electroporation. The heart virus titers of sTNFR:Fc mice were higher than those of controls at day 3. However, subsequent to day 12, the survival rates of the sTNFR:Fc mice were significantly higher than those of the controls (36% versus 0% at day 27, P < 0.01). Histopathological examination indicated that inflammation and myocardial fibrosis were significantly decreased in sTNFR:Fc mice at day 12. The expressed sTNFR:Fc could modulate the inflammatory process during the post-viremic phase of viral myocarditis.

  7. Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as a Biomarker in the Mouse Model of Experimental Autoimmune Myocarditis (EAM)

    PubMed Central

    Grabmaier, U.; Kania, G.; Kreiner, J.; Grabmeier, J.; Uhl, A.; Huber, B. C.; Lackermair, K.; Herbach, N.; Todica, A.; Eriksson, U.; Weckbach, L. T.; Brunner, S.

    2016-01-01

    Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM. PMID:27501319

  8. Interferon-γ Causes Cardiac Myocyte Atrophy via Selective Degradation of Myosin Heavy Chain in a Model of Chronic Myocarditis

    PubMed Central

    Cosper, Pippa F.; Harvey, Pamela A.; Leinwand, Leslie A.

    2013-01-01

    Interferon-γ (IFN-γ), a proinflammatory cytokine, has been implicated in the pathogenesis of a number of forms of heart disease including myocarditis and congestive heart failure. In fact, overexpression of IFN-γ in mice causes dilated cardiomyopathy. However, the direct effects of IFN-γ on cardiac myocytes and the mechanism by which it causes cardiac dysfunction have not been described. Here, we present the molecular pathology of IFN-γ exposure and its effect on myofibrillar proteins in isolated neonatal rat ventricular myocytes. Treatment with IFN-γ caused cardiac myocyte atrophy attributable to a specific decrease in myosin heavy chain protein. This selective degradation of myosin heavy chain was not accompanied by a decrease in total protein synthesis or by an increase in total protein degradation. IFN-γ increased both proteasome and immunoproteasome activity in cardiac myocytes and their inhibition blocked myosin heavy chain loss and myocyte atrophy, whereas inhibition of the lysosome or autophagosome did not. Collectively, these results provide a mechanism by which IFN-γ causes cardiac pathology in the setting of chronic inflammatory diseases. PMID:23058369

  9. Host defence versus intraspecific competition in the regulation of infrapopulations of the flea Xenopsylla conformis on its rodent host Meriones crassus.

    PubMed

    Hawlena, Hadas; Abramsky, Zvika; Krasnov, Boris R; Saltz, David

    2007-07-01

    Mechanisms that regulate parasite populations may influence the evolution of hosts and parasites, as well as the stability of host-parasite dynamics but are still poorly understood. A manipulation experiment on the grooming ability of rodent hosts (Meriones crassus) and flea (Xenopsylla conformis) densities on these hosts successfully disentangled two possible regulating mechanisms: (i) behavioural defence of the host and (ii) intraspecific competition among parasites, and revealed their importance in suppressing the feeding of fleas. Moreover, the results suggest that flea competition is direct and is not mediated by host grooming, immune response, or parasite-induced damage to the host. These mechanisms, together with interspecific competition and density-dependent parasite-induced host damage, may limit the parasite burden on an individual host and may prevent parasites from overexploiting their host population.

  10. Quantitative trait locus analysis, pathway analysis, and consomic mapping show genetic variants of Tnni3k, Fpgt, or H28 control susceptibility to viral myocarditis.

    PubMed

    Wiltshire, Sean A; Leiva-Torres, Gabriel André; Vidal, Silvia M

    2011-06-01

    Coxsackievirus B3 (CVB3) infection is the most common cause of viral myocarditis. The pathogenesis of viral myocarditis is strongly controlled by host genetic factors. Although certain indispensable components of immunity have been identified, the genes and pathways underlying natural variation between individuals remain unclear. Previously, we isolated the viral myocarditis susceptibility 1 (Vms1) locus on chromosome 3, which influences pathogenesis. We hypothesized that confirmation and further study of Vms1 controlling CVB3-mediated pathology, combined with pathway analysis and consomic mapping approaches, would elucidate both pathological and protective mechanisms accounting for natural variation in response to CVB3 infection. Vms1 was originally mapped to chromosome 3 using a segregating cross between susceptible A/J and resistant B10.A mice. To validate Vms1, C57BL/6J-Chr 3(A)/NaJ (a chromosome substitution strain that carries a diploid A/J chromosome 3) were used to replicate susceptibility compared with resistant C57BL/6J (B6). A second segregating F2 cross was generated between these, confirming both the localization and effects of Vms1. Microarray analysis of the four strains (A/J, B10.A, C57BL/6J, and C57BL/6J-Chr 3(A)/NaJ) illuminated a core program of response to CVB3 in all strains that is comprised mainly of IFN-stimulated genes. Microarray analysis also revealed strain-specific differential expression programs and genes that may be prognostic or diagnostic of susceptibility to CVB3 infection. A combination of analyses revealed very strong evidence for the existence and location of Vms1. Differentially expressed pathways were identified by microarray, and candidate gene analysis revealed Fpgt, H28, and Tnni3k as likely candidates for Vms1.

  11. An unusual case of fulminant myocarditis closely mimicking ST-segment elevation myocardial infarction and presenting as refractory cardiogenic shock complicated by multiple life-threatening arrhythmias.

    PubMed

    Wang, Zhi-quan; Li, Yi-Gang

    2015-12-01

    We report a case of severe fulminant myocarditis that closely mimicked acute inferior ST-segment elevation myocardial infarction (STEMI) and presented with refractory cardiogenic shock, multiple life-threatening arrhythmias and rapidly progressive liver failure. This case was successfully differentiated from STEMI by emergency coronary angiography. Recurrent cardiogenic shock was reversed by intra-aortic balloon pumping (IABP). Life-threatening arrhythmias including ventricular tachycardia, ventricular fibrillation, and high-degree atrioventricular block (AVB) were terminated by immediate cardioversion and temporary pacemaker. High-dose hydrocortisone effectively attenuated the inflammatory injury to the myocardium. The patient recovered and was well at the follow-up visit four months after discharge.

  12. Suitable in vitro culture of Eimeria bovis meront II stages in bovine colonic epithelial cells and parasite-induced upregulation of CXCL10 and GM-CSF gene transcription.

    PubMed

    Hermosilla, Carlos; Stamm, Ivonne; Menge, Christian; Taubert, Anja

    2015-08-01

    We here established a suitable in vitro cell culture system based on bovine colonic epithelial cells (BCEC) for the development of Eimeria bovis merozoites I and the characterization of early parasite-induced innate epithelial host cell reactions as gene transcription of proinflammatory molecules. Both primary and permanent BCEC (BCEC (rim) and BCEC(perm)) were suitable for E. bovis merozoite I invasion and subsequent development of meronts II leading to the release of viable merozoites II. E. bovis merozoite II failed to develop any further neither into gamont nor oocyst stages in BCEC in vitro. E. bovis merozoite I induced innate epithelial host cell reactions at the level of CXC/CCL chemokines (CXCL1, CXCL8, CXCL10, CCL2), IL-6, and GM-CSF gene transcription. Overall, both BCEC types were activated by merozoite I infections since they showed significantly enhanced gene transcript levels of the immunomodulatory molecules CXCL10 and GM-CSF. However, gene transcription profiles of BCEC(prim) and BCEC(perm) revealed different reaction patterns in response to merozoite I infection with regard to quality and kinetics of chemokine/cytokine gene transcription. Although both BCEC types equally showed most prominent responses for CXCL10 and GM-CSF, the induction of CXCL1, CXCL8, CCL2, and IL-6 gene transcripts varied qualitatively and quantitatively. Our results demonstrate that BCEC seem capable to respond to E. bovis merozoite I infection by the upregulation of CXCL10 and GM-CSF gene transcription and therefore probably contribute to host innate effector mechanisms against E. bovis.

  13. Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: Diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials

    PubMed Central

    Howlett, Jonathan G; McKelvie, Robert S; Arnold, J Malcolm O; Costigan, Jeannine; Dorian, Paul; Ducharme, Anique; Estrella-Holder, Estrellita; Ezekowitz, Justin A; Giannetti, Nadia; Haddad, Haissam; Heckman, George A; Herd, Anthony M; Isaac, Debra; Jong, Philip; Kouz, Simon; Liu, Peter; Mann, Elizabeth; Moe, Gordon W; Tsuyuki, Ross T; Ross, Heather J; White, Michel

    2009-01-01

    The Canadian Cardiovascular Society published a comprehensive set of recommendations on the diagnosis and management of heart failure in January 2006. Based on feedback obtained through a national program of heart failure workshops and through active solicitation of stakeholders, several topics were identified because of their importance to the practicing clinician. Topics chosen for the present update include best practices for the diagnosis and management of right-sided heart failure, myocarditis and device therapy, and a review of recent important or landmark clinical trials. These recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. The present update has been written from a clinical perspective to provide a user-friendly and practical approach. Specific clinical questions that are addressed include: What is right-sided heart failure and how should one approach the diagnostic work-up? What other clinical entities may masquerade as this nebulous condition and how can we tell them apart? When should we be concerned about the presence of myocarditis and how quickly should patients with this condition be referred to an experienced centre? Among the myriad of recently published landmark clinical trials, which ones will impact our standards of clinical care? The goals are to aid physicians and other health care providers to optimally treat heart failure patients, resulting in a measurable impact on patient health and clinical outcomes in Canada. PMID:19214293

  14. Assessment of antibody mediated cytolysis of adult cardiocytes isolated by centrifugation in a continuous gradient of Percoll in patients with acute myocarditis.

    PubMed

    Maisch, B; Trostel-Soeder, R; Berg, P A; Kochsiek, K

    1981-01-01

    Principal objections to conventional cytotoxicity assays in cardiac disease with myocytes as target cells are the use of fetal or neonatal myocardium, the cell-membrane of which does not express all antigenic determinants, and the use of trypsin as enzyme for isolation of the cells, since this alters the myolemmal membrane considerably. An improved and rapid procedure for the isolation of intact adult cardiocytes with collaggenase was developed. by means of a performed continuous self-generating silica sol and gradient centrifugation average enrichment of 81% vital myocytes was achieved by a single isopycnic procedure. The yield was improved to 94 +/- 3% vital cells by identical second centrifugation. Cardiocytes isolated by this method were used as target cells in an assay measuring the cytolytic activity of antibodies in the presence of complement: sera of patients suffering from acute viral myocarditis (Coxsackie B- and influenza-virus) with complement fixing antisacrolemmal antibodies (ASA) of the IgG- and IgM-type showed significant cardiocytolysis. ASA are postulated to play a role in the pathogenesis of acute Coxsackie B- and influenza-virus myocarditis. PMID:6268709

  15. Lupus myocarditis: case report

    SciTech Connect

    LaManna, M.M.; Lumia, F.J.; Gordon, C.I.; Sumathisena; Maranhao, V.

    1988-03-01

    Although gallium-67 (/sup 67/Ga) accumulates in both neoplastic and inflammatory tissues, indium-111 (/sup 111/In) labeled leukocytes are seen only in inflammatory cells. Indium-111-labeled leukocytes therefore are a useful agent in the noninvasive differentiation of inflammatory tissue from neoplastic tissue. This case is an interesting example of the use of /sup 111/In-labeled leukocytes to make that differentiation.

  16. Emphysematous gastritis in a patient with coxsackie B3 myocarditis and cardiogenic shock requiring veno-arterial extra-corporeal membrane oxygenation

    PubMed Central

    Ashfaq, Awais; Chapital, Alyssa B.

    2015-01-01

    Introduction Emphysematous gastritis is a rare condition in which gas accumulates in the stomach lining usually due to an infectious source. Case presentation We present a 16 year old female with viral myocarditis and cardiogenic shock transferred to our hospital on extracorporeal membrane oxygenation (ECMO) who developed emphysematous gastritis. After listing the patient for heart transplant, patient underwent Bi-VAD placement requiring veno-venous ECMO support. Subsequently, she developed worsening abdominal distention. CT of abdomen/pelvis showed the stomach to be diffusely edematous, thick-walled, containing intramural gas collections, consistent with emphysematous gastritis. Patient underwent nonoperative management and two weeks later had complete resolution of the gastritis. Unfortunately, her overall condition deteriorated in the subsequent days and support was withdrawn. Discussion Management of emphysematous gastritis usually revolves around supportive care, broad spectrum antibiotics and bowel rest. Our patients’ gastritis resolved with non-operative management, albeit, she succumbed to multiorgan failure due to other causes. Conclusion We believe, this is a unique case of a veno-arterial ECMO causing emphysematous gastritis. PMID:26263451

  17. Short treatment with the tumour necrosis factor-α blocker infliximab diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma cruzi reactivation

    PubMed Central

    Pérez, A R; Fontanella, G H; Nocito, A L; Revelli, S; Bottasso, O A

    2009-01-01

    Tumour necrosis factor (TNF)-α is crucial for resistance to Trypanosoma cruzi acute infection, but there is scant information on its role during the chronic phase. To address this issue, we analysed whether a short treatment with a TNF-α blocker affected the course and characteristics of chronic disease in a rat experimental model of T. cruzi infection. An anti-TNF-α agent (infliximab) was administered during the chronic phase for a period of 4 weeks (3 mg/kg/week), while control infected rats were inoculated with saline physiological solution. Search for parasites yielded non-successful results in all infected groups, irrespective of treatment. Nevertheless, the presence of T. cruzi kDNA in heart tissue was detected in infected and infected plus treated animals. Because infliximab might induce changes in the anti-parasite cytokine response, circulating levels of interleukin (IL)-10, interferon-gamma and nitric oxide were evaluated. An increase in IL-10 levels was observed only in the infected group treated with the anti-TNF-α blocker compared to the remaining groups (P < 0·05). A clear attenuation of histological damage associated with a diminution of cardiac TNF-α mRNA expression was observed in the infected and treated animals compared to the infected and non-treated group. Blocking of TNF-α during a relatively short period in chronically infected rats did not lead to evident parasite reactivation but reduced myocarditis severity significantly, indicating a role of this cytokine in the pathogenesis of chronic myocardial damage. PMID:19604269

  18. Communication interventriculaire post infarctus du myocarde circonférentiel: à propos d'un cas et revue de la literature

    PubMed Central

    M'hamdi, Ilham; Benjelloune, Halima

    2015-01-01

    Malgré la réduction importante de la mortalité des infarctus aigus durant ces dernières décennies grâce a une prise en charge médicale adéquate; monitoring cardiaque, une reperfusion précoce; le taux de mortalité suite à une rupture du septum interventriculaire (communication interventriculaire CIV) reste considérable. Les facteurs de risques de cette complications a fait l'objet de plusieurs études: l'HTA, l’âge avancé, le sexe féminin, l'absence d'angine de poitrine et la localisation antérieure de l'ischémie. Les techniques de réparation chirurgicales ont évolué au fil du temps, mais le pronostic demeure très sombre avec un taux de mortalité inchangé depuis 1990. C'est pourquoi, il est très important d'en connaître les manifestations cliniques de façon à préciser le diagnostic par échocardiographie et permettre une prise en charge médico-chirurgicale urgente. Nous allons illustrer cette complication mortelle de l'infarctus du myocarde et mettre le point sur les différents facteurs prédictifs de son développement à travers un cas clinique et une revue de la littérature. PMID:26161233

  19. Effects of Shenqi Fuzheng injection on Fas/FasL protein expression levels in the cardiomyocytes of a mouse model of viral myocarditis

    PubMed Central

    WU, TIANMIN; CHEN, JINSHUI; FAN, LIUFANG; XIE, WENYAN; XU, CHANGSHENG; WANG, HUAJUN

    2016-01-01

    The aim of the present study was to examine the effects of Shenqi Fuzheng injection (SFI) on Fas and FasL protein expression levels in the cardiomyocytes of mice with viral myocarditis (VMC) and to explore the underlying anti-apoptotic mechanisms. A total of 120 male BALB/c mice were randomly divided into five groups as follows: Blank control group, model group, ribavirin group, low-dose SFI group and high-dose SFI group. The VMC model was established by the injection of coxsackievirus group B type 3 and saline, ribavirin or SFI was administered 30 min later. Cardiac samples were harvested from mice in each group on days 3, 10 and 30. Apoptosis of cardiac cells was examined using terminal deoxynucleotidyl transferase dUTP nick-end labeling, and Fas and FasL protein expression levels were detected using immunohistochemistry. Myocardial apoptosis and Fas/FasL protein expression levels were significantly increased in the model group, as compared with the blank group (P<0.01), whereas the apoptotic index (AI) and Fas/FasL protein expression levels of cardiac cells in the high-dose SFI group were significantly decreased compared with those in the model group on day 10 (acute phase; P<0.01). The AI and Fas/FasL protein expression levels of cardiac cells in the low- and high-dose SFI groups were also significantly decreased on day 30 (chronic phase; P<0.01); however, no differences between the high- and low-dose groups were detected. In conclusion, SFI relieves VMC via the downregulation of Fas and FasL protein expression and the inhibition of cell apoptosis. PMID:27168814

  20. Novel regulators of cardiac inflammation: Matricellular proteins expand their repertoire.

    PubMed

    Rienks, Marieke; Papageorgiou, Anna-Pia

    2016-02-01

    More than 20years ago, Paul Bornstein coined the term matricellular protein to describe a group of secreted extracellular matrix proteins with de-adhesive properties. Though this is still true today, this family of proteins is vastly expanding with new emerging functions pushing the boundaries of this classic definition. In the heart, matricellular proteins have been extensively investigated in models of myocardial infarction, pressure overload, viral myocarditis and age-related cardiomyopathy with clear implications during cardiac fibrosis yet their involvement in regulating cardiac inflammation is less established. In this review, we describe our current understanding of the immune activation by damage- or pathogen-associated molecular pattern molecules during cardiac injury making a distinction between sterile versus non-sterile cardiac inflammation, and explain how matricellular proteins influence this crucial pathophysiological response in the heart.

  1. The Aryl Hydrocarbon Receptor Modulates Production of Cytokines and Reactive Oxygen Species and Development of Myocarditis during Trypanosoma cruzi Infection.

    PubMed

    Barroso, Andréia; Gualdrón-López, Melisa; Esper, Lísia; Brant, Fátima; Araújo, Ronan R S; Carneiro, Matheus B H; Ávila, Thiago V; Souza, Danielle G; Vieira, Leda Q; Rachid, Milene A; Tanowitz, Herbert B; Teixeira, Mauro M; Machado, Fabiana S

    2016-10-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in controlling several aspects of immune responses, including the activation and differentiation of specific T cell subsets and antigen-presenting cells, thought to be relevant in the context of experimental Trypanosoma cruzi infection. The relevance of AhR for the outcome of T. cruzi infection is not known and was investigated here. We infected wild-type (WT) mice and AhR knockout (AhR KO) mice with T. cruzi (Y strain) and determined levels of parasitemia, myocardial inflammation and fibrosis, expression of AhR/cytokines/suppressor of cytokine signaling (SOCS) (spleen/heart), and production of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO(-)) (spleen). AhR expression was increased in the heart of infected WT mice. Infected AhR KO mice displayed significantly reduced parasitemia, inflammation, and fibrosis of the myocardium. This was associated with an anticipated increased immune response characterized by increased levels of inflammatory cytokines and reduced expression of SOCS2 and SOCS3 in the heart. In vitro, AhR deficiency caused impairment in parasite replication and decreased levels of ROS production. In conclusion, AhR influences the development of murine Chagas disease by modulating ROS production and regulating the expression of key physiological regulators of inflammation, SOCS1 to -3, associated with the production of cytokines during experimental T. cruzi infection.

  2. Infarctus du myocarde révélateur d'une thrombocytémie essentielle chez un sujet jeune noir africain: à propos d'une observation

    PubMed Central

    Yaméogo, Nobila Valentin; Kagambèga, Larissa Justine; Yaméogo, Aimé Arsène; Kologo, Koudougou Jonas; Millogo, Georges Rosario Christian; Toguyéni, Boubacar Jean Yves; Samadoulougou, André Koudnoaga; Zabsonré, Patrice

    2014-01-01

    La thrombocytémie essentielle est un syndrome myéloprolifératif qui se complique rarement d'infarctus du myocarde. Nous rapportons l'observation d'un patient de 23 ans, sans facteurs de risque cardio-vasculaire connus, aux antécédents de thrombose veineuse cérébrale à l’âge de 20 ans, admis dans le service de cardiologie pour un syndrome douloureux thoracique. L'examen physique était pauvre. L'ECG, la troponinémie et la coronarographie ont conclu à un infarctus du myocarde par obstruction distale de l'IVA. La numération formule sanguine objectivait une importante thrombocytose isolée à 1.197.000/mm3. La recherche de la mutation V617F de JAK2 était positive. Il n'y avait pas de thrombophilie. L’évolution était favorable sous héparine de bas poids moléculaire, antiagrégant plaquettaire, hydroxyurée et hydratation alcaline abondante. PMID:25574323

  3. Cardioprotective effects of sarcolemmal and mitochondrial K-ATP channel openers in an experimental model of autoimmune myocarditis. Role of the reduction in calcium overload during acute heart failure.

    PubMed

    Niwano, Shinichi; Hirasawa, Shoji; Niwano, Hiroe; Sasaki, Sae; Masuda, Ray; Sato, Kiyotaka; Masuda, Takashi; Izumi, Tohru

    2012-01-01

    It has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase). In the acute phase, the control EAM rats exhibited a reduced left ventricular ejection fraction (LVEF) and prolonged monophasic action potential duration (MAPD). Neither drug had an affect on the LVEF or degree of myocarditis, but Mex 25 mg suppressed the MAPD prolongation. In the chronic phase, EAM+Nic and EAM+Mex 25 mg exhibited a higher LVEF than the control EAM. Although the control EAM exhibited sustained MAPD prolongation, the other groups showed recovery of the MAPD in the chronic phase. The mitochondorial redox state was lower in the control EAM than in the sham, and EAM+Nic exhibited a similar level of the redox state as the sham in the chronic phase. Nicorandil exhibited a cardioprotective effect through the protection of mitochondrial function. Mexiletine exhibited a cardioprotective effect possibly through a reduction in the calcium overload by shortening the MAPD in the acute phase. PMID:22688320

  4. Mechanisms of parasite-induced sex reversal in Gammarus duebeni.

    PubMed

    Rodgers-Gray, Trevor P; Smith, Judith E; Ashcroft, Alison E; Isaac, R Elwyn; Dunn, Alison M

    2004-05-01

    The amphipod Gammarus duebeni is host to the feminising microsporidian parasite Nosema granulosis that converts males into functional females. To test the hypothesis that the parasite acts through endocrine disruption we compared the morphology of the gonad and activity of the androgenic gland, which coordinates male sexual differentiation, in infected and uninfected animals. Male gonad consisted of testis, seminal vesicle and vas deferens that was anchored to the genital papilla on segment 7. The androgenic gland was associated with the distal end of the vas deferens. In female and intersex animals the bi-lobed ovary opened into the oviduct at segment 5, vestigial vas deferens and vestigial androgenic gland were retained. The majority of parasitised individuals (38/39) were either phenotypic females or intersexes with fully developed ovaries and an undifferentiated androgenic gland. Our data suggest that the parasite prevents differentiation of the androgenic gland. In further support of this hypothesis, mass spectrometry of a single androgenic gland from males revealed a dominant molecular ion with a mass/charge ratio of 4818.4+H, corresponding to a peptide of androgenic gland hormone from Armadillidium vulgare. In contrast the vestigial androgenic gland from parasitised and unparasitised females showed only low intensity peaks. Our observations demonstrate that the parasite manipulates host sex by preventing androgenic gland differentiation, androgenic gland hormone production and consequently male differentiation. This is in agreement with observations of A. vulgare with inherited Wolbachia infection, suggesting that phylogenetically distant feminisers manipulate hosts through a common mechanism. The high frequency of infection in intersexes (89.3%) suggests that this phenotype results from incomplete feminisation by the parasite. PMID:15111096

  5. Parasite-induced permeation of nucleosides in Plasmodium falciparum malaria.

    PubMed

    Upston, J M; Gero, A M

    1995-06-14

    A mechanism which mediates the transport of the nonphysiological nucleoside, L-adenosine, was demonstrated in Plasmodium falciparum infected erythrocytes and naturally released merozoites. L-Adenosine was not a substrate for influx in freed intraerythrocytic parasites or in normal human erythrocytes nor was L-adenosine transported in a variety of cell types including other parasitic protozoa such as Crithidia luciliae, Trichomonas vaginalis, Giardia intestinalis, or the mammalian cells, Buffalo Green Monkey and HeLa cells. L-Adenosine transport in P. falciparum infected cells was nonsaturable, with a rate of 0.13 +/- 0.01 pmol/microliter cell water per s per microM L-adenosine, yet the transport was inhibited by furosemide, phloridzin and piperine with IC50 values between 1-13 microM, distinguishing the transport pathway from simple diffusion. The channel-like permeation was selective as disaccharides were not permeable to parasitised cells. In addition, an unusual metabolic property of parasitic adenosine deaminase was found in that L-adenosine was metabolised to L-inosine by both P. falciparum infected erythrocytes and merozoites, an activity which was inhibited by 50 nM deoxycoformycin. No other cell type examined displayed this enzymic activity. The results further substantiate that nucleoside transport in P. falciparum infected cells was significantly altered compared to uninfected erythrocytes and that L-adenosine transport and metabolism was a biochemical property of Plasmodium infected cells and merozoites and not found in normal erythrocytes nor any of the other cell types investigated.

  6. VOLTAGE REGULATOR

    DOEpatents

    Von Eschen, R.L.; Scheele, P.F.

    1962-04-24

    A transistorized voltage regulator which provides very close voitage regulation up to about 180 deg F is described. A diode in the positive line provides a constant voltage drop from the input to a regulating transistor emitter. An amplifier is coupled to the positive line through a resistor and is connected between a difference circuit and the regulating transistor base which is negative due to the difference in voltage drop across thc diode and the resistor so that a change in the regulator output causes the amplifier to increase or decrease the base voltage and current and incrcase or decrease the transistor impedance to return the regulator output to normal. (AEC)

  7. The Endoparasitoid, Cotesia vestalis, Regulates Host Physiology by Reprogramming the Neuropeptide Transcriptional Network

    PubMed Central

    Shi, Min; Dong, Shuai; Li, Ming-tian; Yang, Yan-yan; Stanley, David; Chen, Xue-xin

    2015-01-01

    Endoparasitoids develop inside another insect by regulating host immunity and development via maternal factors injected into hosts during oviposition. Prior results have provided insights into parasitism-induced immunosuppression, including the neuropeptide accumulation in parasitized insects. Nonetheless, our understanding of neuropeptide influence on host development and behavior is not yet complete. We posed the hypothesis that parasitization alters expression of genes encoding pro-neuropeptides and used larvae of Plutella xylostella and its endoparasitoid, Cotesia vestalis to test our hypothesis. We prepared transcriptomes from the larval P. xylostella brain-CC-CA complex and identified transcripts encoding 19 neuropeptides. All corresponding cDNAs were confirmed by RACE. Our results demonstrate that parasitism significantly down-regulated, or delayed, expression of genes encoding pro-neuropeptides within 48 h post-parasitization. Changing expression of these genes may account for the previously reported decreased feeding behavior, reduced growth rates and aborted development in the host larvae. In effect, parasitization may operate at the molecular level within the CNS to create global changes in larval host biology. The significance of our finding is that, in addition to the known effects on immunity, parasitoids influence host pro-neuropeptide gene transcription. This finding reveals a new mechanism operating in host-parasitoid relationships to the advantage of the parasitoid. PMID:25640113

  8. Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection

    PubMed Central

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H.; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Boyle, Glen M.; Price, Ric N.; Anstey, Nicholas M.; Loughland, Jessica R.; Burel, Julie; Doolan, Denise L.; Haque, Ashraful; McCarthy, James S.; Engwerda, Christian R.

    2016-01-01

    Summary The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement. PMID:27705789

  9. NORM regulations

    SciTech Connect

    Gray, P.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  10. Trichomonas vaginalis haemolysis: pH regulates a contact-independent mechanism based on pore-forming proteins.

    PubMed

    Fiori, P L; Rappelli, P; Addis, M F; Sechi, A; Cappuccinelli, P

    1996-02-01

    There is a controversy in literature about involvement of secreted factors in the pathogenetic mechanisms of Trichomonas vaginalis, described mostly as contact-dependent. We found that the protozoan, under triggering conditions, is able to release molecules that lead to lysis without direct contact between parasite and target cells as a prerequisite. In this paper we characterize contact-independent cytotoxicity using the red blood cell as a cellular model. Contact-independent haemolysis is a phenomenon were pH exerts a key role, triggering the secretion of a lytic molecule and regulating its activity. A partial physicochemical characterization of the haemolytic factor suggests that a protein of M(r) > 30 kDa could be the effector responsible for damage. Furthermore, the parasite-induced membrane permeabilization, detected by measuring potassium escape from the target cell, and an effective osmotic protection by carbohydrates allowed us to relate the previously described pore-forming mechanism involved in contact-dependent cytotoxicity with the contact-independent lysis. PMID:8722099

  11. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi

    PubMed Central

    Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N.; Lima, Maria F.; Pratap, Siddharth; Nde, Pius N.

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  12. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

    PubMed

    Udoko, Aniekanabassi N; Johnson, Candice A; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N; Lima, Maria F; Pratap, Siddharth; Nde, Pius N

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  13. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

    PubMed

    Udoko, Aniekanabassi N; Johnson, Candice A; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N; Lima, Maria F; Pratap, Siddharth; Nde, Pius N

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  14. Charge regulation circuit

    DOEpatents

    Ball, Don G.

    1992-01-01

    A charge regulation circuit provides regulation of an unregulated voltage supply in the range of 0.01%. The charge regulation circuit is utilized in a preferred embodiment in providing regulated voltage for controlling the operation of a laser.

  15. When parasites disagree: evidence for parasite-induced sabotage of host manipulation.

    PubMed

    Hafer, Nina; Milinski, Manfred

    2015-03-01

    Host manipulation is a common parasite strategy to alter host behavior in a manner to enhance parasite fitness usually by increasing the parasite's transmission to the next host. In nature, hosts often harbor multiple parasites with agreeing or conflicting interests over host manipulation. Natural selection might drive such parasites to cooperation, compromise, or sabotage. Sabotage would occur if one parasite suppresses the manipulation of another. Experimental studies on the effect of multi-parasite interactions on host manipulation are scarce, clear experimental evidence for sabotage is elusive. We tested the effect of multiple infections on host manipulation using laboratory-bred copepods experimentally infected with the trophically transmitted tapeworm Schistocephalus solidus. This parasite is known to manipulate its host depending on its own developmental stage. Coinfecting parasites with the same aim enhance each other's manipulation but only after reaching infectivity. If the coinfecting parasites disagree over host manipulation, the infective parasite wins this conflict: the noninfective one has no effect. The winning (i.e., infective) parasite suppresses the manipulation of its noninfective competitor. This presents conclusive experimental evidence for both cooperation in and sabotage of host manipulation and hence a proof of principal that one parasite can alter and even neutralize manipulation by another.

  16. Immune antibodies and helminth products promote CXCR2-dependent repair of parasite-induced injury

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Helminth parasites cause massive damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination. We observed that mice lacking antibodies (AID-/-) or activating Fc receptors (FcR'-/-) displayed impaired intestinal repair followi...

  17. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

    PubMed

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-08-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

  18. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection

    PubMed Central

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida TG; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-01-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s—the active form of the UPR mediator XBP1—and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

  19. Parasite-induced alteration of odour responses in an amphipod-acanthocephalan system.

    PubMed

    Stone, Charles F; Moore, Janice

    2014-11-01

    Odour-related behaviours in aquatic invertebrates are important and effective anti-predator behaviours. Parasites often alter invertebrate host behaviours to increase transmission to hosts. This study investigated the responses of the amphipod Hyalella azteca when presented with two predator chemical cues: (i) alarm pheromones produced by conspecifics and (ii) kairomones produced by a predatory Green Sunfish (Lepomis cyanellus). We compared the responses of amphipods uninfected and infected with the acanthocepalan parasite Leptorhynchiodes thecatus. Uninfected amphipods reduced activity and increased refuge use after detecting both the alarm pheromones and predator kairomones. Infected amphipods spent significantly more time being active and less time on the refuge than uninfected amphipods, and behaved as if they had not detected the chemical stimulus. Therefore, L. thecatus infections disrupt the amphipods' anti-predator behaviours and likely make their hosts more susceptible to predation. PMID:25200352

  20. Parasite-induced trophic facilitation exploited by a non-host predator: a manipulator's nightmare.

    PubMed

    Mouritsen, Kim N; Poulin, Robert

    2003-09-15

    Parasites with complex life cycles, relying on trophic transmission to a definitive host, very often induce changes in the behaviour or appearance of their intermediate hosts. Because this usually makes the intermediate host vulnerable to predation by the definitive host, it is generally assumed that the parasite's transmission rate is increased, and that the modification of the host is, therefore, of great adaptive significance to the parasite. However, in the ecological "real world" other predators unsuitable as hosts may just as well take advantage of the facilitation process and significantly erode the benefit of host manipulation. Here we show that the intertidal New Zealand cockle (Austrovenus stutchburyi), manipulated by its echinostome trematode (Curtuteria australis) to rest on the sediment surface fully exposed to predation from the avian definitive host, is also subject to sublethal predation from a benthic feeding fish (Notolabrus celidotus, Labridae). The fish is targeting only the cockle-foot, in which the parasite preferentially encysts, reducing the infection intensity of manipulated cockles to levels comparable with those in non-manipulated, buried cockles. Based on the frequency and intensity of the foot cropping and predation rates on surfaced cockles by avian hosts, it is estimated that 2.5% of the parasite population in manipulated cockles is transmitted successfully whereas 17.1% is lost to fish. We argue that the adaptive significance of manipulation in the present system depends critically on the feeding behaviour of the definitive host. If cockles constitute the majority of prey items, there will be selection against manipulation. If manipulated cockles are taken as an easily accessible supplement to a diet composed mostly of other prey organisms, behavioural manipulation of the cockle host appears a high risk, high profit transmission strategy. Both these feeding behaviours of birds are known to occur in the field.

  1. When parasites disagree: Evidence for parasite-induced sabotage of host manipulation

    PubMed Central

    Hafer, Nina; Milinski, Manfred

    2015-01-01

    Host manipulation is a common parasite strategy to alter host behavior in a manner to enhance parasite fitness usually by increasing the parasite's transmission to the next host. In nature, hosts often harbor multiple parasites with agreeing or conflicting interests over host manipulation. Natural selection might drive such parasites to cooperation, compromise, or sabotage. Sabotage would occur if one parasite suppresses the manipulation of another. Experimental studies on the effect of multi-parasite interactions on host manipulation are scarce, clear experimental evidence for sabotage is elusive. We tested the effect of multiple infections on host manipulation using laboratory-bred copepods experimentally infected with the trophically transmitted tapeworm Schistocephalus solidus. This parasite is known to manipulate its host depending on its own developmental stage. Coinfecting parasites with the same aim enhance each other's manipulation but only after reaching infectivity. If the coinfecting parasites disagree over host manipulation, the infective parasite wins this conflict: the noninfective one has no effect. The winning (i.e., infective) parasite suppresses the manipulation of its noninfective competitor. This presents conclusive experimental evidence for both cooperation in and sabotage of host manipulation and hence a proof of principal that one parasite can alter and even neutralize manipulation by another. PMID:25643621

  2. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

    PubMed

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-08-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection.

  3. Quantitative genetic architecture of parasite-induced cataract in rainbow trout, Oncorhynchus mykiss.

    PubMed

    Kuukka-Anttila, H; Peuhkuri, N; Kolari, I; Paananen, T; Kause, A

    2010-01-01

    Parasites impose costs on their hosts. The capability to fight against them is of great advantage, but may also be traded off with other traits. Although often observed at the phenotypic level, our knowledge of the extent to which such trade-offs are genetically determined is relatively poor. We tested this possibility with a farmed rainbow trout population suffering from natural Diplostomum spp. infections that cause cataracts in fish. We estimated the heritability of cataract severity and examined phenotypic and genetic correlations between cataract and a set of performance traits measured three times during a 3-year rearing period. A cataract score was used as an indicator of the host's capability to resist and/or tolerate the parasite. Our results showed moderate heritability for the cataract. Nevertheless, we found no evidence for a genetic or phenotypic trade-off between parasite resistance/tolerance and the measured performance traits. Initial body weight was not correlated with the cataract score. Phenotypic and genetic correlations of cataract severity with body mass and condition measured in the second and third year were strongly negative, indicating reduced growth and condition in fish with a high cataract score. The reduced body size and condition in cataract-bearing fish were probably reflected in the phenotypic association between a high cataract score and delayed maturity age in females. Put together, our study did not provide evidence of genetic or phenotypic trade-offs between Diplostomum resistance/tolerance and a number of performance traits. Therefore, selection for lessened Diplostomum-caused cataracts is unlikely to have a negative impact on the studied performance traits.

  4. Parasite-induced changes in nitric oxide levels in Drosophila paramelanica.

    PubMed

    Carton, Y; Frey, F; Nappi, A J

    2009-10-01

    In larvae of Drosophila paramelanica, eggs and larvae of the endoparasitic wasp Leptopilina heterotoma succumb to an effective host reaction that does not involve blood cell-mediated melanotic encapsulation, a response that characterizes cellular immunity in various species of Drosophila and in many insects and other arthropods. A significant increase occurs, however, in the number of lamellocytes, a type of blood cell that functions in encapsulation reactions. The appearance of activated lamellocytes in D. paramelanica is viewed as an early response to infection, one most likely initiated by non-self-recognition processes that similarly function in other wasp-infected Drosophila. However, ensuing cytotoxic responses, about which little is presently known, are not accompanied by melanotic encapsulation in D. paramelanica. Concurrent analyses of the cell-signaling molecule nitric oxide (*NO) revealed significant alterations in the levels of this free radical during the early stages of infection, most notably a dramatic increase immediately upon infection, and precipitous decreases occurring at times when parasites were killed. Injections of a specific inhibitor of nitric oxide synthase (NOS) into the host's body cavity prior to infection significantly increased parasite survival. These observations suggest some involvement of *NO in the host immune response, either in recruiting hemocytes to sites of infection or as a component of the insect's cytotoxic arsenal, given the capacity of the radical to generate toxic molecules through interactions with various intermediates of oxygen and nitrogen. PMID:19388790

  5. In silico exploration of the mechanisms that underlie parasite-induced anorexia in sheep.

    PubMed

    Laurenson, Yan C S M; Bishop, Stephen C; Kyriazakis, Ilias

    2011-10-01

    A model was used to investigate two mechanisms describing reductions in food intake (anorexia) observed during gastrointestinal parasitism in lambs, and to explore relationships between anorexia and food composition. The mechanisms were either a reduction in intrinsic growth rate, leading to a consequent reduction in food intake (mechanism 1; M1), or a direct reduction in food intake (mechanism 2; M2). For both mechanisms, lambs growing from 2 to 6 months of age were modelled, with one of three levels of trickle challenge with Teladorsagia circumcincta. Scenarios were simulated for feeds varying in either protein or energy content, or both. Major differences were found between the predictions resulting from M1 and M2 on low-energy foods that constrained the intake of uninfected lambs through bulk. With M1, food intake was governed by the first operating constraint, whereas with M2 an additivity of constraints was observed. On the other foods, the duration of anorexia increased with increasing energy content of feed for M1, whilst the duration of anorexia decreased with increasing protein content of feed for M2.For foods that did not have an impact upon lambs' gastrointestinal tract capacity, published data were consistent with predictions of M2. Due to an absence of experimental data, no conclusions could be drawn for relationships between anorexia and food composition in the presence of other limiting constraints, such as bulk for low-energy foods. In conclusion, available experimental data and model predictions were consistent with anorexia having an impact directly on food intake, and with impacts of anorexia increasing with decreasing protein content.

  6. Parasite-induced and parasite development-dependent alteration of the swimming behavior of fish hosts.

    PubMed

    Santos, E G N; Santos, C Portes

    2013-07-01

    Parasites with complex life cycles have the ability to change the behavior of their intermediate host in a way that increases their transmission rate to the next host. However, the level of behavioral changes can vary considerably, depending on the stage of parasite development and parasite intensity. To investigate the influence of such parameters, we evaluated the locomotory activity of the fish Poecilia vivipara prior to experimental infections, 7 days post-infection (dpi) and 14dpi with cercariae of the digenean Ascocotyle (Phagicola) pindoramensis. The locomotory activity was monitored using an image system, Videomex(®), linked to with a video camera able to record the swimming behavior of the fishes. At the end of the experiments, fishes were dissected and all metacercariae from the gills and mesenteries, the specific sites utilized by A. (P.) pindoramensis, were recovered and counted. There was a significant decrease in the swimming behavior of fishes after 14dpi. Similarly, we found a significant correlation between the swimming behavior of the fishes and parasite intensity in both sites of infection. It is surmised that the decrease in locomotory activity of P. vivipara caused by A. (P.) pindoramensis can disturb its predator-prey relationship in natural environment.

  7. Up-regulated HMGB1 in EAM directly led to collagen deposition by a PKCβ/Erk1/2-dependent pathway: cardiac fibroblast/myofibroblast might be another source of HMGB1

    PubMed Central

    Su, Zhaoliang; Yin, Jingping; Wang, Ting; Sun, Yingkun; Ni, Ping; Ma, Rui; Zhu, Haitao; Zheng, Dong; Shen, Huiling; Xu, Wenlin; Xu, Huaxi

    2014-01-01

    High mobility group box 1 (HMGB1), an important inflammatory mediator, is actively secreted by immune cells and some non-immune cells or passively released by necrotic cells. HMGB1 has been implicated in many inflammatory diseases. Our previous published data demonstrated that HMGB1 was up-regulated in heart tissue or serum in experimental autoimmune myocarditis (EAM); HMGB1 blockade could ameliorate cardiac fibrosis at the last stage of EAM. And yet, until now, no data directly showed that HMGB1 was associated with cardiac fibrosis. Therefore, the aims of the present work were to assess whether (1) up-regulated HMGB1 could directly lead to cardiac fibrosis in EAM; (2) cardiac fibroblast/myofibroblasts could secrete HMGB1 as another source of high-level HMGB1 in EAM; and (3) HMGB1 blockade could effectively prevent cardiac fibrosis at the last stage of EAM. Our results clearly demonstrated that HMGB1 could directly lead to cardiac collagen deposition, which was associated with PKCβ/Erk1/2 signalling pathway; furthermore, cardiac fibroblast/myofibroblasts could actively secrete HMGB1 under external stress; and HMGB1 secreted by cardiac fibroblasts/myofibroblasts led to cardiac fibrosis via PKCβ activation by autocrine means; HMGB1 blockade could efficiently ameliorate cardiac fibrosis in EAM mice. PMID:24912759

  8. Load regulating expansion fixture

    DOEpatents

    Wagner, L.M.; Strum, M.J.

    1998-12-15

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located therebetween. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig.

  9. Load regulating expansion fixture

    DOEpatents

    Wagner, Lawrence M.; Strum, Michael J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located therebetween. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components.

  10. Pressure reducing regulator

    DOEpatents

    Whitehead, J.C.; Dilgard, L.W.

    1995-10-10

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure is disclosed. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes. 10 figs.

  11. Pressure reducing regulator

    DOEpatents

    Whitehead, John C.; Dilgard, Lemoyne W.

    1995-01-01

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes.

  12. TOWARD MORE EFFECTIVE REGULATION

    SciTech Connect

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  13. [Epigenetic regulation in spermatogenesis].

    PubMed

    Xu, Chen; Song, Ning

    2014-05-01

    Spermatogenesis is a process consisting of spermatogonial proliferation, spermatocytic meiosis, and spermiogenesis, and is also considered to be a process in which heterochromatins gradually aggregate and finally reach a highly condensed formation in the sperm head. Recent studies show that epigenetic regulation plays a key role in spermatogenesis. This review discusses the mechanisms of epigenetic regulation in spermatogenesis in three aspects, DNA methylation, histone modification, and noncoding RNAs. These factors are essential for spermatogenesis, fertilization, and embryogenesis by mutual regulation as well as by gene expression regulation, transposon activation, sex chromosome inactivation, and genome imprinting. PMID:24908726

  14. Plant Growth Regulators.

    ERIC Educational Resources Information Center

    Nickell, Louis G.

    1978-01-01

    Describes the effect of "plant growth regulators" on plants, such as controlling the flowering, fruit development, plant size, and increasing crop yields. Provides a list of plant growth regulators which includes their chemical, common, and trade names, as well as their different use(s). (GA)

  15. Regulation of University Teaching

    ERIC Educational Resources Information Center

    Lindblom-Ylanne, Sari; Nevgi, Anne; Trigwell, Keith

    2011-01-01

    The aims of the present study are twofold: firstly, to explore dimensions in the regulation of teaching in a multidisciplinary sample of university teachers, and secondly, to analyse factors related to the regulation of university teaching. Seventy-three university teachers representing several disciplines participated in the study. These teachers…

  16. Extracellular matrix remodelling after coxsackievirus B3-induced murine myocarditis.

    PubMed Central

    Gómez, R. M.; Castagnino, C. G.; Berría, M. I.

    1992-01-01

    Weanling inbred Balb/c mice were intraperitoneally inoculated with a myocarditic variant of coxsackievirus B3. At days 1, 2, 4, 6, 8, 10, 14, 24 and 30 post-infection (p.i.), myocardial tissue was harvested for viral infectivity titrations and histological studies, including routine techniques (haematoxylin-eosin, Masson trichrome and von Kossa) and specialized procedures (silver impregnation for reticulin, picrosirius red stain for collagen and immunoperoxidase labelling for laminin). Virus was isolated as from day 2, reached maximal infectivity at days 6-8 and decreased gradually to become undetectable by day 14. Early histological findings during the 1st week consisted mainly of scattered foci of necrotic myocytes showing calcium deposits; slight mononuclear cell infiltration and fragmentation of both reticulin fibres and pericellular laminin were also present. From the 2nd up to 4th week p.i., inflammatory reaction abated concomitantly with the gradual development of fibrosis, as evidenced by reticulin fibre thickening, irregular laminin distribution and collagen fibre increase. Our results suggest that viral-induced necrosis is able to trigger marked extracellular matrix remodelling even in the case of minimal inflammation. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1329915

  17. Phosphoinositides regulate ion channels

    PubMed Central

    Hille, Bertil; Dickson, Eamonn J.; Kruse, Martin; Vivas, Oscar; Suh, Byung-Chang

    2014-01-01

    Phosphoinositides serve as signature motifs for different cellular membranes and often are required for the function of membrane proteins. Here, we summarize clear evidence supporting the concept that many ion channels are regulated by membrane phosphoinositides. We describe tools used to test their dependence on phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate, and consider mechanisms and biological meanings of phosphoinositide regulation of ion channels. This lipid regulation can underlie changes of channel activity and electrical excitability in response to receptors. Since different intracellular membranes have different lipid compositions, the activity of ion channels still in transit towards their final destination membrane may be suppressed until they reach an optimal lipid environment. PMID:25241941

  18. HIGH PRESSURE GAS REGULATOR

    DOEpatents

    Ramage, R.W.

    1962-05-01

    A gas regulator operating on the piston and feedback principle is described. The device is particularly suitable for the delicate regulation of high pressure, i.e., 10,000 psi and above, gas sources, as well as being perfectly adaptable for use on gas supplies as low as 50 psi. The piston is adjustably connected to a needle valve and the movement of the piston regulates the flow of gas from the needle valve. The gas output is obtained from the needle valve. Output pressure is sampled by a piston feedback means which, in turn, regulates the movement of the main piston. When the output is other than the desired value, the feedback system initiates movement of the main piston to allow the output pressure to be corrected or to remain constant. (AEC)

  19. Stable hydraulic pressure regulator

    NASA Technical Reports Server (NTRS)

    Gold, H.

    1979-01-01

    Neither sensing line restrictors nor frictional dampers are required for stability. Analysis presents method by which stability margin, response, and droop magnitude can be incorporated during design of direct-acting hydraulic pressure regulators.

  20. Proposed EEOC Regulations.

    ERIC Educational Resources Information Center

    Farrell, Michael

    1978-01-01

    This article explains how proposed Equal Employment Opportunity Commission (EEOC) regulations attempt to circumvent the case of Weber vs Kaiser Aluminum Corp. by providing employers with backpay immunity in reverse discrimination suits. (Author)

  1. The Hippo pathway: regulators and regulations

    PubMed Central

    Yu, Fa-Xing; Guan, Kun-Liang

    2013-01-01

    Control of cell number is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation or organ degeneration. The Hippo pathway in both Drosophila and mammals regulates cell number by modulating cell proliferation, cell death, and cell differentiation. Recently, numerous upstream components involved in the Hippo pathway have been identified, such as cell polarity, mechanotransduction, and G-protein-coupled receptor (GPCR) signaling. Actin cytoskeleton or cellular tension appears to be the master mediator that integrates and transmits upstream signals to the core Hippo signaling cascade. Here, we review regulatory mechanisms of the Hippo pathway and discuss potential implications involved in different physiological and pathological conditions. PMID:23431053

  2. Neuroendocrine Regulation of Metabolism.

    PubMed

    Cornejo, M P; Hentges, S T; Maliqueo, M; Coirini, H; Becu-Villalobos, D; Elias, C F

    2016-07-01

    Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei that comprise the hypothalamus, the arcuate nucleus is one of the major mediators in the regulation of food intake. The regulation of energy balance is also a key factor ensuring the maintenance of any species as a result of the dependence of reproduction on energy stores. Adequate levels of energy reserves are necessary for the proper functioning of the hypothalamic-pituitary-gonadal axis. This review discusses valuable data presented in the 2015 edition of the International Workshop of Neuroendocrinology concerning the fundamental nature of the hormonal regulation of the hypothalamus and the impact on energy balance and reproduction.

  3. Worldwide regulations for mycotoxins.

    PubMed

    van Egmond, Hans P

    2002-01-01

    Since the discovery of the aflatoxins in the 1960s, regulations have been established in many countries to protect the consumer from the harmful effects of mycotoxins that may contaminate foodstuffs. Various factors play a role in the decision-making process of setting limits for mycotoxins. These include scientific factors such as the availability of toxicological data, survey data, knowledge about the distribution of mycotoxins in commodities, and analytical methodology. Economical and political factors such as commercial interests and sufficiency of food supply have their impact as well. International enquiry's on existing mycotoxin legislation in foodstuffs and animal feedstuffs have been carried out several times in the 1980s and 1990s and details about tolerances, legal basis, responsible authorities, official protocols of analysis and sampling have been published. Recently a comprehensive update on worldwide regulations was published as FAO Food and Nutrition Paper 64. It appeared that at least 77 countries now have specific regulations for mycotoxins, 13 countries are known to have no specific regulations, whereas no data are available for about 50 countries, many of them in Africa. Over the years, a large diversity in tolerance levels for mycotoxins has remained. Some free trade zones (EU, MERCOSUR) are in the process of harmonizing the limits and regulations for mycotoxins in their respective member states, but it is not likely that worldwide harmonized limits for mycotoxins will soon be within reach.

  4. Androgen receptor genomic regulation

    PubMed Central

    Jin, Hong-Jian; Kim, Jung

    2013-01-01

    The transcriptional activity of the androgen receptor (AR) is not only critical for the normal development and function of the prostate but also pivotal to the onset and progression of prostate cancer (PCa). The studies of AR transcriptional regulation were previously limited to a handful of AR-target genes. Owing to the development of various high-throughput genomic technologies, significant advances have been made in recent years. Here we discuss the discoveries of genome-wide androgen-regulated genes in PCa cell lines, animal models and tissues using expression microarray and sequencing, the mapping of genomic landscapes of AR using Combining Chromatin Immunoprecipitation (ChIP)-on-chip and ChIP-seq assays, the interplay of transcriptional cofactors in defining AR binding profiles, and the genomic regulation and AR reprogramming in advanced PCa. PMID:25237629

  5. Environmentally regulated aerospace coatings

    NASA Technical Reports Server (NTRS)

    Morris, Virginia L.

    1995-01-01

    Aerospace coatings represent a complex technology which must meet stringent performance requirements in the protection of aerospace vehicles. Topcoats and primers are used, primarily, to protect the structural elements of the air vehicle from exposure to and subsequent degradation by environmental elements. There are also many coatings which perform special functions, i.e., chafing resistance, rain erosion resistance, radiation and electric effects, fuel tank coatings, maskants, wire and fastener coatings. The scheduled promulgation of federal environmental regulations for aerospace manufacture and rework materials and processes will regulate the emissions of photochemically reactive precursors to smog and air toxics. Aerospace organizations will be required to identify, qualify and implement less polluting materials. The elimination of ozone depleting chemicals (ODC's) and implementation of pollution prevention requirements are added constraints which must be addressed concurrently. The broad categories of operations affected are the manufacture, operation, maintenance, and repair of military, commercial, general aviation, and space vehicles. The federal aerospace regulations were developed around the precept that technology had to be available to support the reduction of organic and air toxic emissions, i.e., the regulations cannot be technology forcing. In many cases, the regulations which are currently in effect in the South Coast Air Quality Management District (SCAQMD), located in Southern California, were used as the baseline for the federal regulations. This paper addresses strategies used by Southern California aerospace organizations to cope with these regulatory impacts on aerospace productions programs. All of these regulatory changes are scheduled for implementation in 1993 and 1994, with varying compliance dates established.

  6. Nuclear regulation and safety

    SciTech Connect

    Hendrie, J.M.

    1982-01-01

    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed. (DLC)

  7. Other-Regulation in Collaborative Groups: Implications for Regulation Quality

    ERIC Educational Resources Information Center

    Rogat, Toni Kempler; Adams-Wiggins, Karlyn R.

    2014-01-01

    The current study examines variation in other-regulation, conceptualized as efforts by one student to regulate their group's work. This study extends research which has conceptualized other-regulation as temporarily guiding others' conceptual understanding and skill development by broadening the spectrum of other-regulation to include…

  8. The Impact of Regulating Social Science Research with Biomedical Regulations

    ERIC Educational Resources Information Center

    Durosinmi, Brenda Braxton

    2011-01-01

    The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

  9. Focus on PTEN Regulation

    PubMed Central

    Bermúdez Brito, Miriam; Goulielmaki, Evangelia; Papakonstanti, Evangelia A.

    2015-01-01

    The role of phosphatase and tensin homolog on chromosome 10 (PTEN) as a tumor suppressor has been for a long time attributed to its lipid phosphatase activity against PI(3,4,5)P3, the phospholipid product of the class I PI3Ks. Besides its traditional role as a lipid phosphatase at the plasma membrane, a wealth of data has shown that PTEN can function independently of its phosphatase activity and that PTEN also exists and plays a role in the nucleus, in cytoplasmic organelles, and extracellularly. Accumulating evidence has shed light on diverse physiological functions of PTEN, which are accompanied by a complex regulation of its expression and activity. PTEN levels and function are regulated transcriptionally, post-transcriptionally, and post-translationally. PTEN is also sensitive to regulation by its interacting proteins and its localization. Herein, we summarize the current knowledge on mechanisms that regulate the expression and enzymatic activity of PTEN and its role in human diseases. PMID:26284192

  10. REGULATIONS FOR COMMUNITY COLLEGES.

    ERIC Educational Resources Information Center

    Pennsylvania State Board of Education, Harrisburg.

    THE COMMUNITY COLLEGE LAW AND PROCEDURES ESTABLISHED BY THE DEPARTMENT OF PUBLIC INSTRUCTION ARE THE BASIS FOR ADMINISTRATION OF COMMUNITY COLLEGES IN PENNSYLVANIA. REGULATIONS PROVIDE FOR ADMINISTRATIVE ORGANIZATION, CURRICULUM, TUITION, AND STANDARDS FOR GRADING, RECORD KEEPING, FACULTY AND STAFF RATIOS. ALSO DESCRIBED ARE PROCEDURES FOR…

  11. Metabolic regulation of yeast

    NASA Astrophysics Data System (ADS)

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  12. Regulated Gene Therapy.

    PubMed

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  13. Regulating the New Governance

    ERIC Educational Resources Information Center

    Cope, Stephen; Goodship, Jo; Holloway, David

    2003-01-01

    This article arises out of a research project that sought to assess the development of regulation within the public sector. It examines the forms and impact of the regulatory systems that now operate within the public sector focusing on the further education sector. The research project developed out of an awareness that the increase in various…

  14. Mitochondrial regulation of apoptosis.

    PubMed

    Mayer, Bernd; Oberbauer, Rainer

    2003-06-01

    Mitochondria play a central part in cellular survival and apoptotic death. These processes are highly regulated by pro- and antiapoptotic Bcl-2 superfamily members. A key feature within apoptosis cascades is disruption of mitochondrial transmembrane potential and apoptogenic protein release, caused by opening of the permeability transition pore (PT). New data, however, indicate that mitochondrial apoptosis may occur without PT involvement.

  15. Regulation and Markets

    ERIC Educational Resources Information Center

    Gardner, Margaret; Wells, Julie

    2007-01-01

    There has been much critical comment in recent years about the tensions between the regulation imposed on public universities and the flexibility needed to compete effectively in international and national markets for students and funding. In the partisan world of politics each side points the finger at the other as the author of "too much"…

  16. Lightweight Regulated Power Supply

    NASA Technical Reports Server (NTRS)

    Mclyman, C. W.

    1985-01-01

    Power-supply circuit regulates output voltage by adjusting frequency of chopper circuit according to variations. Currently installed in battery charger for electric wheelchair, circuit is well suited to other uses in which light weight is important - for example, in portable computers, radios, and test instruments.

  17. Lysosomal Trafficking Regulator (LYST).

    PubMed

    Ji, Xiaojie; Chang, Bo; Naggert, Jürgen K; Nishina, Patsy M

    2016-01-01

    Regulation of vesicle trafficking to lysosomes and lysosome-related organelles (LROs) as well as regulation of the size of these organelles are critical to maintain their functions. Disruption of the lysosomal trafficking regulator (LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, prolonged bleeding, severe immunodeficiency, recurrent bacterial infection, neurologic dysfunction and hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes, cytolytic granules and platelet dense bodies. The most striking CHS ocular pathology observed is an enlargement of melanosomes in the retinal pigment epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and results in photophobia and decreased visual acuity. Understanding the molecular function of LYST and identification of its interacting partners may provide therapeutic targets for CHS and other diseases associated with the regulation of LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania amazonensis infections. PMID:26427484

  18. Regulation of serum phosphate

    PubMed Central

    Lederer, Eleanor

    2014-01-01

    The regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate have major implications for what is understood as ‘normal’ and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin-like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied. PMID:24973411

  19. TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockade.

    PubMed

    Kroll-Palhares, Karina; Silvério, Jaline Coutinho; Silva, Andrea Alice da; Michailowsky, Vladimir; Marino, Ana Paula; Silva, Neide Maria; Carvalho, Cristiano Marcelo Espinola; Pinto, Luzia Maria de Oliveira; Gazzinelli, Ricardo Tostes; Lannes-Vieira, Joseli

    2008-06-01

    In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-alpha levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-alpha, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-alpha+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-alpha treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-alpha-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-alpha treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.

  20. Chemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection

    PubMed Central

    Raja, Amber I.; Cai, Yeping; Reiman, Jennifer M.; Groves, Penny; Chakravarty, Sumana; McPhun, Virginia; Doolan, Denise L.; Cockburn, Ian; Hoffman, Stephen L.; Stanisic, Danielle I.

    2016-01-01

    The development of a vaccine is essential for the elimination of malaria. However, despite many years of effort, a successful vaccine has not been achieved. Most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scrutiny. Here, we test chemically attenuated Plasmodium yoelii 17X and demonstrate significant protection following homologous and heterologous blood-stage challenge. Protection against blood-stage infection persisted for at least 9 months. Activation of both CD4+ and CD8+ T cells was shown after vaccination; however, in vivo studies demonstrated a pivotal role for both CD4+ T cells and B cells since the absence of either cell type led to loss of vaccine-induced protection. In spite of significant activation of circulating CD8+ T cells, liver-stage immunity was not evident. Neither did vaccine-induced CD8+ T cells contribute to blood-stage protection; rather, these cells contributed to pathogenesis, since all vaccinated mice depleted of both CD4+ and CD8+ T cells survived a challenge infection. This study provides critical insight into whole-parasite vaccine-induced immunity and strong support for testing whole-parasite vaccines in humans. PMID:27245410

  1. Temperature- and parasite-induced changes in toxicity and lethal body burdens of pentachlorophenol in the freshwater clam Pisidium amnicum.

    PubMed

    Heinonen, J; Kukkonen, J V; Holopainen, I J

    2001-12-01

    Seasonal variation in abiotic and biotic environments may modify the toxicity of organic chemicals for aquatic organisms. In present study, survival of the freshwater clam Pisidium amnicum was studied in laboratory exposures to pentachlorophenol (PCP) in April (at 5 degress C) and July (at 19 degress C). Behavioral responses, mean survival times (MSTs), and the lethal body burdens (LBBs) of PCP for uninfected clams and for clams infected by digenean trematodes were determined separately in two PCP concentrations, 100 and 300 microgram/L. Analysis of data revealed reduced behavioral activity of the clams in the PCP exposure compared to that in the control. The time needed for toxic responses was greatly affected by temperature; MSTs were 5 to 15 times longer in winter than at summer temperatures. Unexpectedly, the infected clams in summer were more tolerant to PCP than the uninfected clams. Despite the differences in survival times, the LBBs between the seasons were constant. However, in summer, the infected clams had significantly higher LBBs than the uninfected clams. The differences in survival and LBBs between the infected and uninfected clams are suggested to be caused by the high lipid contents found in parasites, which may change the internal distribution of PCP.

  2. Insights into anti-parasitism induced by a C-type lectin from Bothrops pauloensis venom on Toxoplasma gondii.

    PubMed

    Castanheira, Letícia; Naves de Souza, Dayane Lorena; Silva, Rafaela José; Barbosa, Bellisa; Mineo, José Roberto; Tudini, Kelly Aparecida; Rodrigues, Renata; Ferro, Eloísa Vieira; de Melo Rodrigues, Veridiana

    2015-03-01

    Here we evaluate the effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom, on Toxoplasma gondii parasitism. BpLec (0.195-12.5 μg/mL) did not interfere with HeLa (host cell) viability by MTT assay, whereas higher doses decreased viability and changed HeLa morphology. In addition, the host cell treatment before infection did not influence adhesion and proliferation indexes. BpLec did not alter T. gondii tachyzoite viability, as carried out by trypan blue exclusion, but decreased both adhesion and parasite replication, when tachyzoites were treated before infection. Galactose (0.4 M) inhibited the BpLec effect on adhesion assays, suggesting that BpLec probably recognize some glycoconjugate from T. gondii membrane. Additionally, we performed cytokine measurements from supernatants collected from HeLa cells infected with T. gondii tachyzoites previously treated with RPMI or BpLec. MIF and IL-6 productions by HeLa cells were increased by BpLec treatment. Also, TGF-β1 secretion was diminished post-infection, although this effect was not dependent on BpLec treatment. Taken together, our results show that BpLec is capable of reducing T. gondii parasitism after tachyzoite treatment and may represent an interesting tool in the search for parasite antigens involved in these processes. PMID:25541358

  3. ELECTRON EMISSION REGULATING MEANS

    DOEpatents

    Brenholdt, I.R.

    1957-11-19

    >An electronic regulating system is described for controlling the electron emission of a cathode, for example, the cathode in a mass spectrometer. The system incorporates a transformer having a first secondary winding for the above-mentioned cathode and a second secondary winding for the above-mentioned cathode and a second secondary winding load by grid controlled vacuum tubes. A portion of the electron current emitted by the cathode is passed through a network which develops a feedback signal. The system arrangement is completed by using the feedback signal to control the vacuum tubes in the second secondary winding through a regulator tube. When a change in cathode emission occurs, the feedback signal acts to correct this change by adjusting the load on the transformer.

  4. European Union Regulations.

    PubMed

    Fürst, Peter

    2011-01-01

    The European Union (EU) has been a leader in the development of both guidance and regulations to ensure food safety throughout the member states. Because of the free movement of food commodities among the countries that belong to the European Union, there is a great need to assure high quality monitoring of both imported food and member state products. The procedures and methods required need to be practical, state-of-the art, and harmonised. The European Commission has developed a network of laboratories and scientific studies to meet this goal. This chapter describes the current Regulations, Directives and Decisions of the European Commission that protect the food supply throughout Europe. Because imported food needs to comply with the EU requirements, and the need to have common compliance throughout the member states, the developed system could be a worldwide template for monitoring the food supply. In addition, the integral role of chromatography hyphenated to mass spectrometry is described.

  5. Regulation of Meiotic Recombination

    SciTech Connect

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  6. Redox regulated peroxisome homeostasis.

    PubMed

    Wang, Xiaofeng; Li, Shuo; Liu, Yu; Ma, Changle

    2015-01-01

    Peroxisomes are ubiquitous organelles present in nearly all eukaryotic cells. Conserved functions of peroxisomes encompass beta-oxidation of fatty acids and scavenging of reactive oxygen species generated from diverse peroxisomal metabolic pathways. Peroxisome content, number, and size can change quickly in response to environmental and/or developmental cues. To achieve efficient peroxisome homeostasis, peroxisome biogenesis and degradation must be orchestrated. We review the current knowledge on redox regulated peroxisome biogenesis and degradation with an emphasis on yeasts and plants.

  7. Redox regulated peroxisome homeostasis.

    PubMed

    Wang, Xiaofeng; Li, Shuo; Liu, Yu; Ma, Changle

    2015-01-01

    Peroxisomes are ubiquitous organelles present in nearly all eukaryotic cells. Conserved functions of peroxisomes encompass beta-oxidation of fatty acids and scavenging of reactive oxygen species generated from diverse peroxisomal metabolic pathways. Peroxisome content, number, and size can change quickly in response to environmental and/or developmental cues. To achieve efficient peroxisome homeostasis, peroxisome biogenesis and degradation must be orchestrated. We review the current knowledge on redox regulated peroxisome biogenesis and degradation with an emphasis on yeasts and plants. PMID:25545794

  8. Taiwan Regulation of Biobanks.

    PubMed

    Fan, Chien-Te; Hung, Tzu-Hsun; Yeh, Chan-Kun

    2015-01-01

    This paper introduces legal framework and governance structure in relation to the management and development of biobanks in Taiwan. At first, we briefly describe Taiwan's population, political system and health care system. Secondly, this research introduces biobanking framework of Taiwan including 25 biobanks established with the approval of the Ministry of Health and Welfare. In those biobanks, "Taiwan Biobank" is the first and the largest government-supported biobank which comprises population-based cohort study and disease- oriented study. Since the collection of information, data, and biological specimen of biobanks often involve highly sensitive personal information, in the legal framework of Taiwan, there is a specific regulation, "Human Biobank Management Act" (HBMA), which plays an important role in regulating biobanks in Taiwan. HBMA, the Personal Information Act and other regulations constitute a comprehensive legal and regulatory privacy framework of biobanks. Through the introduction and analysis of the current legal framework applicable to biobanks, we found that there are several challenges that need to be solved appropriately that involve duplicate review systems, the obstacles in the international collaboration, and data sharing between biobanks in Taiwan.

  9. Flow compensating pressure regulator

    NASA Technical Reports Server (NTRS)

    Baehr, E. F. (Inventor)

    1978-01-01

    An apparatus for regulating pressure of treatment fluid during ophthalmic procedures is described. Flow sensing and pressure regulating diaphragms are used to modulate a flow control valve. The pressure regulating diaphragm is connected to the flow control valve to urge the valve to an open position due to pressure being applied to the diaphragm by bias means such as a spring. The flow sensing diaphragm is mechanically connected to the flow control valve and urges it to an opened position because of the differential pressure on the diaphragm generated by a flow of incoming treatment fluid through an orifice in the diaphragm. A bypass connection with a variable restriction is connected in parallel relationship to the orifice to provide for adjusting the sensitivity of the flow sensing diaphragm. A multiple lever linkage system is utilized between the center of the second diaphragm and the flow control valve to multiply the force applied to the valve by the other diaphragm and reverse the direction of the force.

  10. Regulation reform slows down

    SciTech Connect

    1995-03-29

    Regulatory reformers in Congress are easing off the accelerator as they recognize that some of their more far-reaching proposals lack sufficient support to win passage. Last week the proposed one-year moratorium on new regulations was set back in the Senate by it main sponsor, Sen. Non Nickles (R., OK), who now seeks to replace it with a more moderate bill. Nickel`s substitute bill would give Congress 45 days after a regulation is issued to decide whether to reject it. It also retroactively allows for review of 80 regulations issued since last November 9, 1994. Asked how his new proposal is superior to a moratorium, which is sharply opposed by the Clinton Administration, Nickles says he thinks it is better because its permanent. The Chemical Manufacturer`s Association (CMA) has not publicly made a regulatory moratorium a top priority, but has quietly supported it by joining with other industry groups lobbying on the issue. A moratorium would halt EPA expansion of the Toxics Release Inventory (TRI) and alloys the delisting of several TRI chemicals.

  11. Ensembl regulation resources.

    PubMed

    Zerbino, Daniel R; Johnson, Nathan; Juetteman, Thomas; Sheppard, Dan; Wilder, Steven P; Lavidas, Ilias; Nuhn, Michael; Perry, Emily; Raffaillac-Desfosses, Quentin; Sobral, Daniel; Keefe, Damian; Gräf, Stefan; Ahmed, Ikhlak; Kinsella, Rhoda; Pritchard, Bethan; Brent, Simon; Amode, Ridwan; Parker, Anne; Trevanion, Steven; Birney, Ewan; Dunham, Ian; Flicek, Paul

    2016-01-01

    New experimental techniques in epigenomics allow researchers to assay a diversity of highly dynamic features such as histone marks, DNA modifications or chromatin structure. The study of their fluctuations should provide insights into gene expression regulation, cell differentiation and disease. The Ensembl project collects and maintains the Ensembl regulation data resources on epigenetic marks, transcription factor binding and DNA methylation for human and mouse, as well as microarray probe mappings and annotations for a variety of chordate genomes. From this data, we produce a functional annotation of the regulatory elements along the human and mouse genomes with plans to expand to other species as data becomes available. Starting from well-studied cell lines, we will progressively expand our library of measurements to a greater variety of samples. Ensembl's regulation resources provide a central and easy-to-query repository for reference epigenomes. As with all Ensembl data, it is freely available at http://www.ensembl.org, from the Perl and REST APIs and from the public Ensembl MySQL database server at ensembldb.ensembl.org. Database URL: http://www.ensembl.org. PMID:26888907

  12. Taiwan Regulation of Biobanks.

    PubMed

    Fan, Chien-Te; Hung, Tzu-Hsun; Yeh, Chan-Kun

    2015-01-01

    This paper introduces legal framework and governance structure in relation to the management and development of biobanks in Taiwan. At first, we briefly describe Taiwan's population, political system and health care system. Secondly, this research introduces biobanking framework of Taiwan including 25 biobanks established with the approval of the Ministry of Health and Welfare. In those biobanks, "Taiwan Biobank" is the first and the largest government-supported biobank which comprises population-based cohort study and disease- oriented study. Since the collection of information, data, and biological specimen of biobanks often involve highly sensitive personal information, in the legal framework of Taiwan, there is a specific regulation, "Human Biobank Management Act" (HBMA), which plays an important role in regulating biobanks in Taiwan. HBMA, the Personal Information Act and other regulations constitute a comprehensive legal and regulatory privacy framework of biobanks. Through the introduction and analysis of the current legal framework applicable to biobanks, we found that there are several challenges that need to be solved appropriately that involve duplicate review systems, the obstacles in the international collaboration, and data sharing between biobanks in Taiwan. PMID:26711420

  13. Epigenetic regulation in obesity.

    PubMed

    Lavebratt, C; Almgren, M; Ekström, T J

    2012-06-01

    The availability to the DNA strand and the activity of the transcription machinery is crucial for the cell to use the information in the DNA. The epigenetic mechanisms DNA methylation, modification of histone tails, other chromatin-modifying processes and interference by small RNAs regulate the cell-type-specific DNA expression. Epigenetic marks can be more or less plastic perpetuating responses to various molecular signals and environmental stimuli, but in addition apparently stochastic epigenetic marks have been found. There is substantial evidence from animal and man demonstrating that both transient and more long-term epigenetic mechanisms have a role in the regulation of the molecular events governing adipogenesis and glucose homeostasis. Intrauterine exposure such as poor maternal nutrition has consistently been demonstrated to contribute to a particular epigenotype and thereby developmental metabolic priming of the exposed offspring in animal and man. Epigenetic modifications can be passed not only from one cell generation to the next, but metabolic disease-related epigenotypes have been proposed to also be transmitted germ-line. Future more comprehensive knowledge on epigenetic regulation will complement genome sequence data for the understanding of the complex etiology of obesity and related disorder.

  14. Regulation of adipocyte lipolysis.

    PubMed

    Frühbeck, Gema; Méndez-Giménez, Leire; Fernández-Formoso, José-Antonio; Fernández, Secundino; Rodríguez, Amaia

    2014-06-01

    In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under fasting conditions or times of elevated energy demands is tightly regulated by neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among the classic regulators of lipolysis, adrenergic stimulation and the insulin-mediated control of lipid mobilisation are the best known. Initially, hormone-sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for lipolysis initiation. Pivotal, previously unsuspected components have also been identified at the protective interface of the lipid droplet surface and in the signalling pathways that control lipolysis. Perilipin, comparative gene identification-58 (CGI-58) and other proteins of the lipid droplet surface are currently known to be key regulators of the lipolytic machinery, protecting or exposing the TAG core of the droplet to lipases. The neuroendocrine control of lipolysis is prototypically exerted by catecholaminergic stimulation and insulin-induced suppression, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent decades adipose tissue has been shown to secrete a large number of adipokines, which exert direct effects on lipolysis, while adipocytes reportedly express a wide range of receptors for signals involved in lipid mobilisation. Recently recognised mediators of lipolysis include some adipokines, structural membrane proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen-activated protein kinase. Lipolysis needs to be reanalysed from the broader perspective of its specific physiological or pathological context since basal or stimulated lipolytic rates occur under diverse conditions and by different mechanisms.

  15. Regulation of adipocyte lipolysis.

    PubMed

    Frühbeck, Gema; Méndez-Giménez, Leire; Fernández-Formoso, José-Antonio; Fernández, Secundino; Rodríguez, Amaia

    2014-06-01

    In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under fasting conditions or times of elevated energy demands is tightly regulated by neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among the classic regulators of lipolysis, adrenergic stimulation and the insulin-mediated control of lipid mobilisation are the best known. Initially, hormone-sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for lipolysis initiation. Pivotal, previously unsuspected components have also been identified at the protective interface of the lipid droplet surface and in the signalling pathways that control lipolysis. Perilipin, comparative gene identification-58 (CGI-58) and other proteins of the lipid droplet surface are currently known to be key regulators of the lipolytic machinery, protecting or exposing the TAG core of the droplet to lipases. The neuroendocrine control of lipolysis is prototypically exerted by catecholaminergic stimulation and insulin-induced suppression, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent decades adipose tissue has been shown to secrete a large number of adipokines, which exert direct effects on lipolysis, while adipocytes reportedly express a wide range of receptors for signals involved in lipid mobilisation. Recently recognised mediators of lipolysis include some adipokines, structural membrane proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen-activated protein kinase. Lipolysis needs to be reanalysed from the broader perspective of its specific physiological or pathological context since basal or stimulated lipolytic rates occur under diverse conditions and by different mechanisms. PMID:24872083

  16. Bifunctional gas-flow regulator

    NASA Technical Reports Server (NTRS)

    Koch, E. F.

    1979-01-01

    Simple modification converts conventional high-pressure regulator to combination pressure-regulator/shutoff valve. Modification entails adding second diaphragm and pressure compartment. Modified valve is switched between its two functions by external two-position low-pressure valve.

  17. REGULATION OF VASCULOGENESIS AND ANGIOGENESIS

    EPA Science Inventory

    Regulation of vasculogenesis and angiogenesis.
    B.D. Abbott
    Reproductive Toxicology Division, Environmental Protection Agency, Research Triangle Park, North Carolina, USA
    Vasculogenesis and angiogenesis are regulated by a complex, interactive family of receptors and lig...

  18. 77 FR 13155 - Waste Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-05

    ... received under the Antarctic Conservation Act of 1978, Public Law 95-541. SUMMARY: The National Science... regulated under the Antarctic Conservation Act of 1978 (Pub. L. 95-541; Code of Federal Regulations Title...

  19. Genes and gene regulation

    SciTech Connect

    MacLean, N.

    1988-01-01

    Genetics has long been a central topic for biologists, and recent progress has captured the public imagination as well. This book addresses questions that are at the leading edge of this continually advancing discipline. In tune with the increasing emphasis on molecular biology and genetic engineering, this text emphasizes the molecular aspects of gene expression, and the evolution of gene sequence organization and control. It reviews the genetic material of viruses, bacteria, and of higher organisms. Cells and organisms are compared in terms of gene numbers, their arrangements within a cell, and the control mechanisms which regulate the activity of genes.

  20. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1992-01-01

    This report describes accomplishments over the past year on understanding of terpene synthesis in mint plants and sage. Specifically reported are the fractionation of 4-S-limonene synthetase, the enzyme responsible for the first committed step to monoterpene synthesis, along with isolation of the corresponding RNA and DNA cloning of its gene; the localization of the enzyme within the oil glands, regulation of transcription and translation of the synthetase, the pathway to camphor biosynthesis,a nd studies on the early stages and branch points of the isoprenoid pathway.

  1. Self-regulating valve

    DOEpatents

    Humphreys, D.A.

    1982-07-20

    A variable, self-regulating valve having a hydraulic loss coefficient proportional to a positive exponential power of the flow rate. The device includes two objects in a flow channel and structure which assures that the distance between the two objects is an increasing function of the flow rate. The range of spacing between the objects is such that the hydraulic resistance of the valve is an increasing function of the distance between the two objects so that the desired hydraulic loss coefficient as a function of flow rate is obtained without variation in the flow area.

  2. Circadian regulation of chloroplasts.

    PubMed

    Atkins, Kelly A; Dodd, Antony N

    2014-10-01

    Circadian rhythms produce a biological measure of time that increases plant performance. The mechanisms that underlie this increase in productivity require investigation to provide information that will underpin future crop improvement. There is a growing body of evidence that a sophisticated signalling network interconnects the circadian oscillator and chloroplasts. We consider this in the context of circadian signalling to chloroplasts and the relationship between retrograde signalling and circadian regulation. We place circadian signalling to chloroplasts by sigma factors within an evolutionary context. We describe selected recent developments in the integration of light and circadian signals that control chloroplast gene expression.

  3. Variable orifice flow regulator

    NASA Technical Reports Server (NTRS)

    Christianson, Rollin C. (Inventor)

    1991-01-01

    A flow regulator for high-pressure fluids at elevated temperatures includes a body having a flow passage extending between inlet and outlet openings. First and second orifice members are arranged in the flow passage so at least one of the orifice members can be moved transversely in relation to the flow passage between one operating position where the two orifice openings are aligned for establishing a maximum flow rate of fluids flowing through the flow passage and at least one other operating position in which the two openings are moderately misaligned with one another for establishing a predetermined reduced flow rate of fluids flowing through the flow passage.

  4. Growth regulation by macrophages

    SciTech Connect

    Wharton, W.; Walker, E.; Stewart, C.C.

    1982-01-01

    The evidence reviewed here indicates that macrophages, either acting alone or in concert with other cells, influence the proliferation of multiple types of cells. Most of the data indicate that these effects are mediated by soluble macrophage-elaborated products (probably proteins) although the role of direct cell-to-cell contacts cannot be ruled out in all cases. A degree of success has been achieved on the biochemical characterization of these factors, due mainly to their low specific activity in conditioned medium and the lack of rapid, specific assays. Understanding the growth-regulating potential of macrophages is an important and needed area of research.

  5. Industry perspective on regulation issues

    SciTech Connect

    Myrick, C.

    1994-12-31

    Current industry estimates indicate that regulatory compliance costs for retail crop protection chemical and fertilizer dealers will on average increase 300% from 1990 to 1997. Even though recent studies show that most dealers are willing to proactively comply with environmental and worker safety regulations, the impact of over-regulation could be substantial. The agrichemical industry must begin to develop and implement a strategy to increase compliance with needed regulations and prohibit duplicative or unnecessary regulations.

  6. Temperature controlled high voltage regulator

    DOEpatents

    Chiaro, Jr., Peter J.; Schulze, Gerald K.

    2004-04-20

    A temperature controlled high voltage regulator for automatically adjusting the high voltage applied to a radiation detector is described. The regulator is a solid state device that is independent of the attached radiation detector, enabling the regulator to be used by various models of radiation detectors, such as gas flow proportional radiation detectors.

  7. Effective doses, guidelines & regulations.

    PubMed

    Burch, Michael D

    2008-01-01

    A number of countries have developed regulations or guidelines for cyanotoxins and cyanobacteria in drinking water, and in some cases in water used for recreational activity and agriculture. The main focus internationally has been upon microcystin toxins, produced predominantly by Microcystis aeruginosa. This is because microcystins are widely regarded as the most significant potential source of human injury from cyanobacteria on a world-wide scale. Many international guidelines have taken their lead from the World Health Organization's (WHO) provisional guideline of 1 microg L(-1) for microcystin-LR in drinking-water released in 1998 (WHO 2004). The WHO guideline value is stated as being 'provisional', because it covers only microcystin-LR, for reasons that the toxicology is limited and new data for toxicity of cyanobacterial toxins are being generated. The derivation of this guideline is based upon data that there is reported human injury related to consumption of drinking water containing cyanobacteria, or from limited work with experimental animals. It was also recognised that at present the human evidence for microcystin tumor promotion is inadequate and animal evidence is limited. As a result the guideline is based upon the model of deriving a Tolerable Daily intake (TDI) from an animal study No Observed Adverse Effects Level (NOAEL), with the application of appropriate safety or uncertainty factors. The resultant WHO guideline by definition is the concentration of a toxin that does not result in any significant risk to health of the consumer over a lifetime of consumption. Following the release of this WHO provisional guideline many countries have either adopted it directly (e.g., Czech Republic, France, Japan, Korea, New Zealand, Norway, Poland, Brazil and Spain), or have adopted the same animal studies, TDI and derivation convention to arrive at slight variants based upon local requirements (e.g., Australia, Canada). Brazil currently has the most

  8. Environmental regulations on chlorofluorocarbons

    SciTech Connect

    Hoffman, J.S.; Wells, J.B. )

    1989-05-01

    In August 1988, the US Environmental Protection Agency issued final regulations that implement the Montreal Protocol on Substances that Deplete the Ozone Layer. The regulations require a 50% reduction in consumption of fully halogenated chlorofluorocarbons (CFCs) within 10 years and a freeze on consumption of halons within 4 years. The Montreal Protocol provisions were designed in September 1987 based on the results of a 2-year international series of scientific, technical, and economic workshops. As would be expected, scientific investigations continued during this period. While these investigations suggested that significant global depletion had already occurred, these preliminary findings were not taken into account during negotiations or rulemaking. In March 1988, however, the international Ozone Trends Panel confirmed the findings. Depletion greater than that projected under the Montreal Protocol has already occurred. An early reassessment of the Protocol provisions appears to be inevitable. Restrictions on CFCs will affect the refrigeration and air-conditioning industries. Emerging alternatives to CFCs include newly developed refrigerants, innovative designs, and engineering controls. Key issues in evaluating these alternatives include energy efficiency, capital costs, service to consumers, and compatibility with existing designs.

  9. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  10. Regulation of testicular descent.

    PubMed

    Hutson, John M; Li, Ruili; Southwell, Bridget R; Newgreen, Don; Cousinery, Mary

    2015-04-01

    Testicular descent occurs in two morphologically distinct phases, each under different hormonal control from the testis itself. The first phase occurs between 8 and 15 weeks when insulin-like hormone 3 (Insl3) from the Leydig cells stimulates the gubernaculum to swell, thereby anchoring the testis near the future inguinal canal as the foetus grows. Testosterone causes regression of the cranial suspensory ligament to augment the transabdominal phase. The second, or inguinoscrotal phase, occurs between 25 and 35 weeks, when the gubernaculum bulges out of the external ring and migrates to the scrotum, all under control of testosterone. However, androgen acts mostly indirectly via the genitofemoral nerve (GFN), which produces calcitonin gene-related peptide (CGRP) to control the direction of migration. In animal models the androgen receptors are in the inguinoscrotal fat pad, which probably produces a neurotrophin to masculinise the GFN sensory fibres that regulate gubernacular migration. There is little direct evidence that this same process occurs in humans, but CGRP can regulate closure of the processus vaginalis in inguinal hernia, confirming that the GFN probably mediates human testicular descent by a similar mechanism as seen in rodent models. Despite increased understanding about normal testicular descent, the common causes of cryptorchidism remain elusive.

  11. Regulation of brain aquaporins.

    PubMed

    Zelenina, Marina

    2010-11-01

    Three aquaporins are expressed in the brain. AQP4, the predominant brain water channel, is expressed in astrocyte endfeet facing brain capillaries, perisynaptic spaces, and nodes of Ranvier. It is implicated in brain edema formation and resolution. It is also believed to assist clearance of K(+) released during neuronal activity. AQP1 is expressed in epithelial cells of choroid plexus and is implicated in cerebrospinal fluid formation. AQP9, which has been reported to be present in astrocytes and in subpopulations of neurons, is implicated in the brain energy metabolism. All three brain AQPs are strongly upregulated in brain tumors and in injured brain tissue. Water and solute transport via AQPs depends on concentration gradients across the membrane, but the magnitude of the transport is to a large extent determined by the single channel permeability of AQPs and by their abundance in the cell membrane. The future therapies will have to address not only the forces driving the water and solute transport (e.g. as mannitol infusion does in the treatment of brain edema), but also the regulation of AQPs, which provide the means for water entry to the brain, for water exit from the brain, and for redistribution of water and solutes within the brain compartments. This review summarizes the data concerning structure, permeability, role in the brain, short-term and long-term regulation of the three AQPs.

  12. Federal energy regulation

    SciTech Connect

    McKie, J.W.

    1984-01-01

    Federal energy policy since World War II has developed into a vast and multidirectional program of controls, incentives, restraints, and promotions. This development accelerated greatly during the critical decade after 1973, and has become a pervasive and sometimes controlling influence in the energy economy. Its purposes, responding to a multitude of interests and aims in the economy, have frequently been inconsistent, if not obscure, and the results have often been confusing or disappointing. This contribution considers the development and purposes of federal energy regulation during the last twenty years, especially since the ''''energy crisis'' of the early 1970s, and offers an appraisal of the successes and failures of several major federal regulatory programs. Whatever the motives and purposes that have actually guided the federal government in its intervention in the energy economy, economists and other critics may evaluate its programs according to whether or not they promote various ends that are deemed to be in the ''public interest.'' Regulation is often rationalized as an attempt to correct or compensate for a failure of the free, unregulated market to achieve some goal thought to be essential for good economic performance, or to fulfill other necessary public purposes.

  13. Bidirectional Pressure-Regulator System

    NASA Technical Reports Server (NTRS)

    Burke, Kenneth; Miller, John R.

    2008-01-01

    A bidirectional pressure-regulator system has been devised for use in a regenerative fuel cell system. The bidirectional pressure-regulator acts as a back-pressure regulator as gas flows through the bidirectional pressure-regulator in one direction. Later, the flow of gas goes through the regulator in the opposite direction and the bidirectional pressure-regulator operates as a pressure- reducing pressure regulator. In the regenerative fuel cell system, there are two such bidirectional regulators, one for the hydrogen gas and another for the oxygen gas. The flow of gases goes from the regenerative fuel cell system to the gas storage tanks when energy is being stored, and reverses direction, flowing from the storage tanks to the regenerative fuel cell system when the stored energy is being withdrawn from the regenerative fuel cell system. Having a single bidirectional regulator replaces two unidirectional regulators, plumbing, and multiple valves needed to reverse the flow direction. The term "bidirectional" refers to both the bidirectional nature of the gas flows and capability of each pressure regulator to control the pressure on either its upstream or downstream side, regardless of the direction of flow.

  14. Emotion Regulation and Anxiety Disorders

    PubMed Central

    Cisler, Josh M.; Olatunji, Bunmi O.

    2013-01-01

    A growing body of research suggests that the construct of emotion regulation is important for understanding the onset, maintenance, and treatment of anxiety disorders. In this review, we provide a selective overview of this emerging field and highlight the major sources of evidence. First, evidence suggests that the construct of emotion regulation can be differentiated from the construct of emotion. Second, there is a large and consistent body of research demonstrating that emotion regulation strategies can modulate emotional responding, and this finding is observed in both behavioral and neuroimaging studies. Third, measures of emotion regulation explain incremental variance in measures of anxiety disorder symptoms not accounted for by measures of negative affect. Although the research implicating emotion regulation in the anxiety disorders is promising, future research will be necessary to further clarify causal mechanisms explaining how emotion regulation confers vulnerability for anxiety disorders and to improve the clarity and consistency of definitions of emotion regulation. PMID:22392595

  15. Regulation of Potassium Homeostasis.

    PubMed

    Palmer, Biff F

    2015-06-01

    Potassium is the most abundant cation in the intracellular fluid, and maintaining the proper distribution of potassium across the cell membrane is critical for normal cell function. Long-term maintenance of potassium homeostasis is achieved by alterations in renal excretion of potassium in response to variations in intake. Understanding the mechanism and regulatory influences governing the internal distribution and renal clearance of potassium under normal circumstances can provide a framework for approaching disorders of potassium commonly encountered in clinical practice. This paper reviews key aspects of the normal regulation of potassium metabolism and is designed to serve as a readily accessible review for the well informed clinician as well as a resource for teaching trainees and medical students.

  16. Magnetostrictive Pressure Regulating System

    NASA Technical Reports Server (NTRS)

    Richard, James A. (Inventor); Pickens, Herman L. (Inventor)

    2013-01-01

    A magnetostrictive pressure regulating system includes a magnetostrictive valve that incorporates a magnetostrictive actuator with at least one current-carrying coil disposed thereabout. A pressure force sensor, in fluid communication with the fluid exiting the valve, includes (i) a magnetostrictive material, (ii) a magnetic field generator in proximity to the magnetostrictive material for inducing a magnetic field in and surrounding the magnetostrictive material wherein lines of magnetic flux passing through the magnetostrictive material are defined, and (iii) a sensor positioned adjacent to the magnetostrictive material and in the magnetic field for measuring changes in at least one of flux angle and flux density when the magnetostrictive material experiences an applied force that is aligned with the lines of magnetic flux. The pressure of the fluid exiting the valve causes the applied force. A controller coupled to the sensor and to the current-carrying coil adjusts a current supplied to the current-carrying coil based on the changes so-measured.

  17. Regulation of Terpene Metabolism

    SciTech Connect

    Rodney Croteau

    2004-03-14

    OAK-B135 Research over the last four years has progressed fairly closely along the lines initially proposed, with progress-driven expansion of Objectives 1, 2 and 3. Recent advances have developed from three research thrusts: 1. Random sequencing of an enriched peppermint oil gland cDNA library has given access to a large number of potential pathway and regulatory genes for test of function; 2. The availability of new DNA probes and antibodies has permitted investigation of developmental regulation and organization of terpenoid metabolism; and 3. The development of a transformation system for peppermint by colleagues at Purdue University has allowed direct transgenic testing of gene function and added a biotechnological component to the project. The current status of each of the original research objectives is outlined below.

  18. Pubertal development and regulation.

    PubMed

    Abreu, Ana Paula; Kaiser, Ursula B

    2016-03-01

    Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The hypothalamic-pituitary-gonadal axis controls puberty and reproduction and is tightly regulated by a complex network of excitatory and inhibitory factors. This axis is active in the embryonic and early postnatal stages of life and is subsequently restrained during childhood, and its reactivation culminates in puberty initiation. The mechanisms underlying this reactivation are not completely known. The age of puberty onset varies between individuals and the timing of puberty initiation is associated with several health outcomes in adult life. In this Series paper, we discuss pubertal markers, epidemiological trends of puberty initiation over time, and the mechanisms whereby genetic, metabolic, and other factors control secretion of gonadotropin-releasing hormone to determine initiation of puberty.

  19. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  20. Regulation of melanopsin expression.

    PubMed

    Hannibal, Jens

    2006-01-01

    Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light-detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non-imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of melanopsin, an opsin-like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking melanopsin. Furthermore, heterologous expression of melanopsin in non-neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of melanopsin exists, little is known about the regulation of melanopsin gene expression. Studies in albino Wistar rats showed that the expression of melanopsin is diurnal at both the mRNA and protein levels. The diurnal changes in melanopsin expression seem, however, to be overridden by prolonged exposure to light or darkness. Significant increase in melanopsin expression was observed from the first day in constant darkness and the expression continued to increase during prolonged exposure in constant darkness. Prolonged exposure to constant light, on the other hand, decreased melanopsin expression to an almost undetectable level after 5 days of constant light. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 days. These observations show that dual mechanisms regulate melanopsin gene expression and that the intrinsic light-responsive RGCs in the albino Wistar rat adapt their expression of melanopsin to environmental light and darkness.

  1. TFEB regulates lysosomal proteostasis.

    PubMed

    Song, Wensi; Wang, Fan; Savini, Marzia; Ake, Ashley; di Ronza, Alberto; Sardiello, Marco; Segatori, Laura

    2013-05-15

    Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a β-hexosaminidase mutant associated with the development of another LSD, Tay-Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs. PMID:23393155

  2. Endocannabinoids in cerebrovascular regulation.

    PubMed

    Benyó, Zoltán; Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál

    2016-04-01

    The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. PMID:26825517

  3. Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations.

    PubMed

    2014-07-28

    This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register.

  4. Sustainable regulation of construction.

    PubMed

    2000-11-01

    The seminar examined the role building codes and regulations can have in promoting a more sustainable approach to construction, particularly through their application to non-industrial building materials. A range of building materials such as straw, bamboo, rammed earth, adobe, and cob (a mixture of clay and chopped straw) were described and illustrated by slides to show their building potential. The current codes have a prime concern to protect the health and safety of people from the built environment. They have been developed almost exclusively for mainstream industrial materials and methods of construction, which makes them difficult to use with alternative, indigenous, or non-industrial building materials, even though those materials may be considered more sustainable. The argument was put forward that with only one-third of the world population living in modern industrial buildings today, it is not sustainable to re-house the remaining rapidly expanding population in high technology dwellings. Many of the low technology building materials and methods now used by the majority of people in the world need only incremental improvement to be equal or superior to many of their industrial replacements. Since these can be more sustainable methods of building, there needs to be an acceptance of the use of alternative materials, particularly in the developing parts of the world, where they are being rejected for less sustainable industrial methods. However, many codes make it difficult to use non-industrial materials; indeed, many of the industrial materials would not meet the demands that must be now met if they were now being introduced as new materials. Consequently, there is a need to develop codes to facilitate the use of a wider range of materials than in current use, and research is needed to assist this development. Sustainable regulation should take into account the full range of real impacts that materials and systems have in areas such as resource use and

  5. Regulation of sphingomyelin metabolism.

    PubMed

    Bienias, Kamil; Fiedorowicz, Anna; Sadowska, Anna; Prokopiuk, Sławomir; Car, Halina

    2016-06-01

    Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD). PMID:26940196

  6. Redox regulation in cancer

    PubMed Central

    Das, Ila; Chandhok, Des

    2010-01-01

    Oxidative stress, implicated in the etiology of cancer, results from an imbalance in the production of reactive oxygen species (ROS) and cell’s own antioxidant defenses. ROS deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis. Ultraviolet (UV) exposures, γ-radiation and other environmental carcinogens generate ROS in the cells, which can exert apoptosis in the tumors, thereby killing the malignant cells or induce the progression of the cancer growth by blocking cellular defense system. Cancer stem cells take the advantage of the aberrant redox system and spontaneously proliferate. Oxidative stress and gene-environment interactions play a significant role in the development of breast, prostate, pancreatic and colon cancer. Prolonged lifetime exposure to estrogen is associated with several kinds of DNA damage. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. BRCA1, a tumor suppressor against hormone responsive cancers such as breast and prostate cancer, plays a significant role in inhibiting ROS and estrogen mediated DNA damage; thereby regulate the redox homeostasis of the cells. Several transcription factors and tumor suppressors are involved during stress response such as Nrf2, NFκB and BRCA1. A promising strategy for targeting redox status of the cells is to use readily available natural substances from vegetables, fruits, herbs and spices. Many of the phytochemicals have already been identified to have chemopreventive potential, capable of intervening in carcinogenesis. PMID:20716925

  7. Regulation of ovarian hyperluteinization.

    PubMed

    Ivanisevic-Milovanovic, O K; Demajo, M A; Karakasevic, A M; Pantic, V R

    1998-01-01

    Adult female rats with neonatally damaged posterior hypothalamus, made by a transversal cut, were investigated. Plasma levels of prolactin (PRL), gonadotropic hormones (GTH) and female gonadal steroids (GS) were determined by radioimmunoassay. The animals were sacrificed, at the ages of 4 and 6 months and their hypothalamus, pituitary gland, ovary and uterus were examined using light microscopy. The results can be summarized as follows: body mass of animals, with damaged posterior hypothalamus, was significantly reduced. Masses of luteinized ovaries were increased and uterine tissues decreased. Serum levels of PRL were significantly increased and luteinizing hormone (LH) decreased. Ultrastructural changes in the corpora lutea (CL), previously described, showed clear signs of their reduced capacities to produce GS, both estradiol (Oe) and progesterone (Pg) per total ovarian mass. However, prostaglandin 2 alfa (PGF2alpha) known as a luteolytic factor, was also diminished in the evidently retarded endometrium. As a result of decreased plasma values of LH, Pg and PGF2 alpha, luteolysis of CL in hyperluteinized ovaries did not occur, and their new generations were accumulated during subsequent cycles. The character of interruption and recovery of aminergic and peptidergic neurons, involved in regulation of hypothalamic-pituitary gonadal axis and feed-back effects of steroid hormones, require further studies.

  8. Load regulating latch

    NASA Technical Reports Server (NTRS)

    Appleberry, W. T. (Inventor)

    1977-01-01

    A load regulating mechanical latch is described that has a pivotally mounted latch element having a hook-shaped end with a strike roller-engaging laterally open hook for engaging a stationary strike roller. The latch element or hook is pivotally mounted in a clevis end of an elongated latch stem that is adapted for axial movement through an opening in a support plate or bracket mounted to a structural member. A coil spring is disposed over and around the extending latch stem and the lower end of the coil spring engages the support bracket. A thrust washer is removably attached to the other end of the latch stem and engages the other end of the coil spring and compresses the coil spring thereby preloading the spring and the latch element carried by the latch stem. The hook-shaped latch element has a limited degree of axial travel for loading caused by structural distortion which may change the relative positions of the latch element hook and the strike roller. Means are also provided to permit limited tilt of the latch element due to loading of the hook.

  9. Metabolic regulation via enzyme filamentation

    PubMed Central

    Aughey, Gabriel N.; Liu, Ji-Long

    2016-01-01

    Abstract Determining the mechanisms of enzymatic regulation is central to the study of cellular metabolism. Regulation of enzyme activity via polymerization-mediated strategies has been shown to be widespread, and plays a vital role in mediating cellular homeostasis. In this review, we begin with an overview of the filamentation of CTP synthase, which forms filamentous structures termed cytoophidia. We then highlight other important examples of the phenomenon. Moreover, we discuss recent data relating to the regulation of enzyme activity by compartmentalization into cytoophidia. Finally, we hypothesize potential roles for enzyme filament formation in the regulation of metabolism, development and disease. PMID:27098510

  10. Glucocorticoid Regulation of Reproduction.

    PubMed

    Geraghty, Anna C; Kaufer, Daniela

    2015-01-01

    It is well accepted that stress, measured by increased glucocorticoid secretion, leads to profound reproductive dysfunction. In times of stress, glucocorticoids activate many parts of the fight or flight response, mobilizing energy and enhancing survival, while inhibiting metabolic processes that are not necessary for survival in the moment. This includes reproduction, an energetically costly procedure that is very finely regulated. In the short term, this is meant to be beneficial, so that the organism does not waste precious energy needed for survival. However, long-term inhibition can lead to persistent reproductive dysfunction, even if no longer stressed. This response is mediated by the increased levels of circulating glucocorticoids, which orchestrate complex inhibition of the entire reproductive axis. Stress and glucocorticoids exhibits both central and peripheral inhibition of the reproductive hormonal axis. While this has long been recognized as an issue, understanding the complex signaling mechanism behind this inhibition remains somewhat of a mystery. What makes this especially difficult is attempting to differentiate the many parts of both of these hormonal axes, and new neuropeptide discoveries in the last decade in the reproductive field have added even more complexity to an already complicated system. Glucocorticoids (GCs) and other hormones within the hypothalamic-pituitary-adrenal (HPA) axis (as well as contributors in the sympathetic system) can modulate the hypothalamic-pituitary-gonadal (HPG) axis at all levels-GCs can inhibit release of GnRH from the hypothalamus, inhibit gonadotropin synthesis and release in the pituitary, and inhibit testosterone synthesis and release from the gonads, while also influencing gametogenesis and sexual behavior. This chapter is not an exhaustive review of all the known literature, however is aimed at giving a brief look at both the central and peripheral effects of glucocorticoids on the reproductive function.

  11. Team Regulation, Regulation of Social Activities or Co-Regulation: Different Labels for Effective Regulation of Learning in CSCL

    ERIC Educational Resources Information Center

    Saab, Nadira

    2012-01-01

    Computer-supported collaborative learning (CSCL) is an approach to learning in which learners can actively and collaboratively construct knowledge by means of interaction and joint problem solving. Regulation of learning is especially important in the domain of CSCL. Next to the regulation of task performance, the interaction between learners who…

  12. Deceptive Business Practices: Federal Regulations.

    ERIC Educational Resources Information Center

    Rohrer, Daniel Morgan

    Federal regulations to prevent deceptive advertising seek to balance the advertiser's freedom of speech with protection of the consumer. This paper discusses what the Federal Trade Commission (FTC) has done to regulate advertising and evaluates the adequacy of its controls. The commission uses cease-and-desist orders, affirmative disclosure,…

  13. Design for pressure regulating components

    NASA Technical Reports Server (NTRS)

    Wichmann, H.

    1973-01-01

    The design development for Pressure Regulating Components included a regulator component trade-off study with analog computer performance verification to arrive at a final optimized regulator configuration for the Space Storable Propulsion Module, under development for a Jupiter Orbiter mission. This application requires the pressure regulator to be capable of long-term fluorine exposure. In addition, individual but basically identical (for purposes of commonality) units are required for separate oxidizer and fuel pressurization. The need for dual units requires improvement in the regulation accuracy over present designs. An advanced regulator concept was prepared featuring redundant bellows, all metallic/ceramic construction, friction-free guidance of moving parts, gas damping, and the elimination of coil springs normally used for reference forces. The activities included testing of actual size seat/poppet components to determine actual discharge coefficients and flow forces. The resulting data was inserted into the computer model of the regulator. Computer simulation of the propulsion module performance over two mission profiles indicated satisfactory minimization of propellant residual requirements imposed by regulator performance uncertainties.

  14. Gravity and body mass regulation

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Horwitz, B. A.; Fuller, C. A.

    1997-01-01

    The effects of altered gravity on body mass, food intake, energy expenditure, and body composition are examined. Metabolic adjustments are reviewed in maintenance of energy balance, neural regulation, and humoral regulation are discussed. Experiments with rats indicate that genetically obese rats respond differently to hypergravity than lean rats.

  15. Affect and Self-Regulation

    ERIC Educational Resources Information Center

    Malmivuori, Marja-Liisa

    2006-01-01

    This paper presents affect as an essential aspect of students' self-reflection and self-regulation. The introduced concepts of self-system and self-system process stress the importance of self-appraisals of personal competence and agency in affective responses and self-regulation in problem solving. Students are viewed as agents who constantly…

  16. Technological Change in Regulated Industries.

    ERIC Educational Resources Information Center

    Capron, William M., Ed.

    The articles in this volume discuss how well industries operating under government regulation respond to technical innovation: do the effects of regulations vary among industries, and if so, does this result from variations in the regulatory approach, the organization of the firms, or the nature of the technology? Industries considered include…

  17. Regulating Pornography: A Public Dilemma.

    ERIC Educational Resources Information Center

    Thompson, Margaret E.; And Others

    1990-01-01

    Examines attitudes toward sex and pornography by means of a telephone survey of Dane County, Wisconsin, adults. Describes survey questions about sexual attitudes, perceived effects of pornography, and pornography regulation. Concludes that adults who feel more strongly that pornography has negative effects are more opposed to its regulation. (SG)

  18. The Universities and Federal Regulation.

    ERIC Educational Resources Information Center

    Crowley, John C.

    The impact of increasing federal regulation on American universities is discussed based on an informal survey of senior academic and administrative officials in 13 public and private universities. As government regulation is becoming more intensive and compliance more resource- and time-consuming, government is perceived as having little…

  19. Street sweeping and stormwater regulations

    SciTech Connect

    Not Available

    1993-10-01

    This article examines the role of street sweeping in meeting the requirements of the Clean Water Act stormwater regulations. The article identifies those industrial and municipal activities which are covered by the regulations and cites frequent sweeping of site surfaces for industry and street sweeping for municipalities as an integral part of compliance plans.

  20. Regulation of GMOs in China.

    PubMed

    Liu, Yinliang

    2008-12-01

    Genetically modified organisms (GMOs) are created by biotechnology to serve people with much benefit while may impose risks to ecological environment and human health and therefore need careful regulation. During the past two decades, GMOs have been well developed in China and so has their corresponding regulation. This paper reviews and comments the multiple aspects of mainly the agricultural GMOs, including their safety assessment, control measures, trade activities, import, labels, and GM food, which have been prescribed by the corresponding laws, regulations and administrative measures. It is held that till present a framework for regulation of agricultural GMOs and GM food has been established basically in China, while a more comprehensive system for regulation of all kinds of GMOs and all kinds of related activities is still needed at present and in the future.

  1. RNA-guided transcriptional regulation

    DOEpatents

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  2. REGULATION OF AUTOSENSITIZATION

    PubMed Central

    Cohen, Irun R.; Wekerle, Hartmut

    1973-01-01

    lymphocytes to self-antigens can be regulated by serum factors which act on the lymphocytes. The immunospecificity of the inhibitory effect suggests that these factors may be soluble self-antigens in a tolerogenic form. PMID:4539845

  3. Regulating chemicals: law, science, and the unbearable burdens of regulation.

    PubMed

    Silbergeld, Ellen K; Mandrioli, Daniele; Cranor, Carl F

    2015-03-18

    The challenges of regulating industrial chemicals remain unresolved in the United States. The Toxic Substances Control Act (TSCA) of 1976 was the first legislation to extend coverage to the regulation of industrial chemicals, both existing and newly registered. However, decisions related to both law and science that were made in passing this law inevitably rendered it ineffectual. Attempts to fix these shortcomings have not been successful. In light of the European Union's passage of innovative principles and requirements for chemical regulation, it is no longer possible to deny the opportunity and need for reform in US law and practice. PMID:25785889

  4. Regulating chemicals: law, science, and the unbearable burdens of regulation.

    PubMed

    Silbergeld, Ellen K; Mandrioli, Daniele; Cranor, Carl F

    2015-03-18

    The challenges of regulating industrial chemicals remain unresolved in the United States. The Toxic Substances Control Act (TSCA) of 1976 was the first legislation to extend coverage to the regulation of industrial chemicals, both existing and newly registered. However, decisions related to both law and science that were made in passing this law inevitably rendered it ineffectual. Attempts to fix these shortcomings have not been successful. In light of the European Union's passage of innovative principles and requirements for chemical regulation, it is no longer possible to deny the opportunity and need for reform in US law and practice.

  5. Mental fatigue impairs emotion regulation.

    PubMed

    Grillon, Christian; Quispe-Escudero, David; Mathur, Ambika; Ernst, Monique

    2015-06-01

    Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation.

  6. Precipitated silica as flow regulator.

    PubMed

    Müller, Anne-Kathrin; Ruppel, Joanna; Drexel, Claus-Peter; Zimmermann, Ingfried

    2008-08-01

    Flow regulators are added to solid pharmaceutical formulations to improve the flow properties of the powder mixtures. The primary particles of the flow regulators exist in the form of huge agglomerates which are broken down into smaller aggregates during the blending process. These smaller aggregates adsorb at the surface of the solid's grains and thus diminish attractive Van-der-Waals-forces by increasing the roughness of the host's surface. In most cases amorphous silica is used as flow additive but material properties like particle size or bond strength influence the desagglomeration tendency of the agglomerates and thus the flow regulating potency of each silica. For some silica types we will show that the differences in their flow regulating potency are due to the rate and extent by which they are able to cover the surface of the host particles. Binary powder mixtures consisting of a pharmaceutical excipient and an added flow regulator were blended in a Turbula mixer for a defined period of time. As pharmaceutical excipient corn starch was used. The flow regulators were represented by a selection of amorphous silicon dioxide types like a commercial fumed silica and various types of SIPERNAT precipitated silica provided by Evonik-Degussa GmbH, Hanau, Germany. Flowability parameters of the mixtures were characterized by means of a tensile strength tester. The reduction of tensile strength with the blending time can be correlated with an increase in fragmentation of the flow regulator. PMID:18595668

  7. Regulation and selection of patients.

    PubMed

    Leenen, H J

    1985-01-01

    During the past decades health legislation and regulation have been on the increase in most industrialized countries. The growing role of government in the provision and financing of health care, the need to correct given aspects of health care and the mandate to protect the underprivileged have been some of the many reasons for increased regulation. Different regulatory approaches and their respective advantages and disadvantages are reviewed in this paper. Particular attention is given to the crucial issue of how to regulate the access to scarce resources and how to cope within a legislative approach with the resulting patient selection. PMID:10270736

  8. Wolf population regulation revisited: again

    USGS Publications Warehouse

    McRoberts, Ronald E.; Mech, L. David

    2014-01-01

    The long-accepted conclusion that wolf density is regulated by nutrition was recently challenged, and the conclusion was reached that, at greater levels of prey biomass, social factors such as intraspecific strife and territoriality tend to regulate wolf density. We reanalyzed the data used in that study for 2 reasons: 1) we disputed the use of 2 data points, and 2) because of recognized heteroscedasticity, we used weighted-regression analysis instead of the unweighted regressions used in the original study. We concluded that the data do not support the hypothesis that wolf densities are regulated by social factors.

  9. Voltage Regulators for Photovoltaic Systems

    NASA Technical Reports Server (NTRS)

    Delombard, R.

    1986-01-01

    Two simple circuits developed to provide voltage regulation for highvoltage (i.e., is greater than 75 volts) and low-voltage (i.e., is less than 36 volts) photovoltaic/battery power systems. Use of these circuits results in voltage regulator small, low-cost, and reliable, with very low power dissipation. Simple oscillator circuit controls photovoltaic-array current to regulate system voltage and control battery charging. Circuit senses battery (and system) voltage and adjusts array current to keep battery voltage from exceeding maximum voltage.

  10. Flow-compensating pressure regulator

    NASA Technical Reports Server (NTRS)

    Baehr, E. F.

    1979-01-01

    Pressure regulator developed for use with cataract-surgery instrument controls intraocular pressure during substantial variations in flow rate of infusion fluid. Device may be applicable to variety of eye-surgery instruments.

  11. Lipid Regulation of Sodium Channels.

    PubMed

    D'Avanzo, N

    2016-01-01

    The lipid landscapes of cellular membranes are complex and dynamic, are tissue dependent, and can change with the age and the development of a variety of diseases. Researchers are now gaining new appreciation for the regulation of ion channel proteins by the membrane lipids in which they are embedded. Thus, as membrane lipids change, for example, during the development of disease, it is likely that the ionic currents that conduct through the ion channels embedded in these membranes will also be altered. This chapter provides an overview of the complex regulation of prokaryotic and eukaryotic voltage-dependent sodium (Nav) channels by fatty acids, sterols, glycerophospholipids, sphingolipids, and cannabinoids. The impact of lipid regulation on channel gating kinetics, voltage-dependence, trafficking, toxin binding, and structure are explored for Nav channels that have been examined in heterologous expression systems, native tissue, and reconstituted into artificial membranes. Putative mechanisms for Nav regulation by lipids are also discussed. PMID:27586290

  12. State Regulation of Private Education.

    ERIC Educational Resources Information Center

    Lines, Patricia M.

    1982-01-01

    Examines state laws and the actions of various courts on home instruction and unauthorized educational programs. Suggests reforming the regulation of private education through legislative action that requires periodic testing as an alternative to compulsory school attendance. (Author/MLF)

  13. Transistorized converter provides nondissipative regulation

    NASA Technical Reports Server (NTRS)

    1964-01-01

    A transistorized regulator converter efficiently converts fluctuating input voltages to a constant output voltage, avoiding the use of saturable reactors. It is nondissipative in operation and functions in an open loop through variable duty cycles.

  14. Turgor regulation in hyphal organisms.

    PubMed

    Lew, Roger R; Levina, Natalia N; Walker, Sophie K; Garrill, Ashley

    2004-11-01

    Turgor regulation in two saprophytic hyphal organisms was examined directly with the pressure probe technique. The ascomycete Neurospora crassa, a terrestrial fungi, regulates turgor after hyperosmotic treatments when growing in a minimal medium containing K(+), Mg(2+), Ca(2+), Cl(-), and sucrose. Turgor recovery by N. crassa after hyperosmotic treatment is concurrent with changes in ion transport: hyperpolarization of the plasma membrane potential and a decline in transmembrane ion conductance. In contrast the oomycete Achlya bisexualis, a freshwater hyphal organism, does not regulate turgor after hyperosmotic treatment, although small transient increases in turgor were occasionally observed. We also monitored turgor in both organisms during hypoosmotic treatment and did not observe a turgor increase, possibly due to turgor regulation. Both hyphal organisms grow with similar morphologies, cellular expansion rates and turgor (0.4-0.7 MPa), yet respond differently to osmotic stress. The results do not support the assumption of a universal mechanism of tip growth driven by cell turgor.

  15. APPARATUS FOR REGULATING HIGH VOLTAGE

    DOEpatents

    Morrison, K.G.

    1951-03-20

    This patent describes a high-voltage regulator of the r-f type wherein the modulation of the r-f voltage is accomplished at a high level, resulting in good stabilization over a large range of load conditions.

  16. Epigenetic regulation of persistent pain

    PubMed Central

    Bai, Guang; Ren, Ke; Dubner, Ronald

    2014-01-01

    Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

  17. YCRD: Yeast Combinatorial Regulation Database

    PubMed Central

    Wu, Wei-Sheng; Hsieh, Yen-Chen; Lai, Fu-Jou

    2016-01-01

    In eukaryotes, the precise transcriptional control of gene expression is typically achieved through combinatorial regulation using cooperative transcription factors (TFs). Therefore, a database which provides regulatory associations between cooperative TFs and their target genes is helpful for biologists to study the molecular mechanisms of transcriptional regulation of gene expression. Because there is no such kind of databases in the public domain, this prompts us to construct a database, called Yeast Combinatorial Regulation Database (YCRD), which deposits 434,197 regulatory associations between 2535 cooperative TF pairs and 6243 genes. The comprehensive collection of more than 2500 cooperative TF pairs was retrieved from 17 existing algorithms in the literature. The target genes of a cooperative TF pair (e.g. TF1-TF2) are defined as the common target genes of TF1 and TF2, where a TF’s experimentally validated target genes were downloaded from YEASTRACT database. In YCRD, users can (i) search the target genes of a cooperative TF pair of interest, (ii) search the cooperative TF pairs which regulate a gene of interest and (iii) identify important cooperative TF pairs which regulate a given set of genes. We believe that YCRD will be a valuable resource for yeast biologists to study combinatorial regulation of gene expression. YCRD is available at http://cosbi.ee.ncku.edu.tw/YCRD/ or http://cosbi2.ee.ncku.edu.tw/YCRD/. PMID:27392072

  18. YCRD: Yeast Combinatorial Regulation Database.

    PubMed

    Wu, Wei-Sheng; Hsieh, Yen-Chen; Lai, Fu-Jou

    2016-01-01

    In eukaryotes, the precise transcriptional control of gene expression is typically achieved through combinatorial regulation using cooperative transcription factors (TFs). Therefore, a database which provides regulatory associations between cooperative TFs and their target genes is helpful for biologists to study the molecular mechanisms of transcriptional regulation of gene expression. Because there is no such kind of databases in the public domain, this prompts us to construct a database, called Yeast Combinatorial Regulation Database (YCRD), which deposits 434,197 regulatory associations between 2535 cooperative TF pairs and 6243 genes. The comprehensive collection of more than 2500 cooperative TF pairs was retrieved from 17 existing algorithms in the literature. The target genes of a cooperative TF pair (e.g. TF1-TF2) are defined as the common target genes of TF1 and TF2, where a TF's experimentally validated target genes were downloaded from YEASTRACT database. In YCRD, users can (i) search the target genes of a cooperative TF pair of interest, (ii) search the cooperative TF pairs which regulate a gene of interest and (iii) identify important cooperative TF pairs which regulate a given set of genes. We believe that YCRD will be a valuable resource for yeast biologists to study combinatorial regulation of gene expression. YCRD is available at http://cosbi.ee.ncku.edu.tw/YCRD/ or http://cosbi2.ee.ncku.edu.tw/YCRD/. PMID:27392072

  19. 7 CFR 29.29 - Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.29 Regulations. Rules and regulations of the Secretary under the Act....

  20. 7 CFR 987.48 - Container regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Container regulation. 987.48 Section 987.48... IN RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Container Regulation § 987.48 Container regulation. Whenever the Committee deems it advisable to establish a container regulation for any variety...

  1. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Regulations committee. 20.153 Section 20... Regulations § 20.153 Regulations committee. (a) Notice of meetings. Notice of each meeting of the Regulations... meeting of the Regulations Committee for which notice is published pursuant to paragraph (a) of...

  2. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Regulations committee. 20.153 Section 20... Regulations § 20.153 Regulations committee. (a) Notice of meetings. Notice of each meeting of the Regulations... meeting of the Regulations Committee for which notice is published pursuant to paragraph (a) of...

  3. 7 CFR 993.49 - Incoming regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Incoming regulation. 993.49 Section 993.49 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Order Regulating Handling Grade and Size Regulations § 993.49 Incoming regulation. (a) No handler...

  4. 7 CFR 993.50 - Outgoing regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Outgoing regulation. 993.50 Section 993.50 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Order Regulating Handling Grade and Size Regulations § 993.50 Outgoing regulation. (a) Except...

  5. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Regulations committee. 20.153 Section 20... Regulations § 20.153 Regulations committee. (a) Notice of meetings. Notice of each meeting of the Regulations... meeting of the Regulations Committee for which notice is published pursuant to paragraph (a) of...

  6. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Regulations committee. 20.153 Section 20... Regulations § 20.153 Regulations committee. (a) Notice of meetings. Notice of each meeting of the Regulations... meeting of the Regulations Committee for which notice is published pursuant to paragraph (a) of...

  7. Precision Adjustable Liquid Regulator (ALR)

    NASA Astrophysics Data System (ADS)

    Meinhold, R.; Parker, M.

    2004-10-01

    A passive mechanical regulator has been developed for the control of fuel or oxidizer flow to a 450N class bipropellant engine for use on commercial and interplanetary spacecraft. There are several potential benefits to the propulsion system, depending on mission requirements and spacecraft design. This system design enables more precise control of main engine mixture ratio and inlet pressure, and simplifies the pressurization system by transferring the function of main engine flow rate control from the pressurization/propellant tank assemblies, to a single component, the ALR. This design can also reduce the thermal control requirements on the propellant tanks, avoid costly Qualification testing of biprop engines for missions with more stringent requirements, and reduce the overall propulsion system mass and power usage. In order to realize these benefits, the ALR must meet stringent design requirements. The main advantage of this regulator over other units available in the market is that it can regulate about its nominal set point to within +/-0.85%, and change its regulation set point in flight +/-4% about that nominal point. The set point change is handled actively via a stepper motor driven actuator, which converts rotary into linear motion to affect the spring preload acting on the regulator. Once adjusted to a particular set point, the actuator remains in its final position unpowered, and the regulator passively maintains outlet pressure. The very precise outlet regulation pressure is possible due to new technology developed by Moog, Inc. which reduces typical regulator mechanical hysteresis to near zero. The ALR requirements specified an outlet pressure set point range from 225 to 255 psi, and equivalent water flow rates required were in the 0.17 lb/sec range. The regulation output pressure is maintained at +/-2 psi about the set point from a P (delta or differential pressure) of 20 to over 100 psid. Maximum upstream system pressure was specified at 320 psi

  8. Thyroid hormone regulation of metabolism.

    PubMed

    Mullur, Rashmi; Liu, Yan-Yun; Brent, Gregory A

    2014-04-01

    Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.

  9. To Regulate or Not to Regulate? Views on Electronic Cigarette Regulations and Beliefs about the Reasons for and against Regulation

    PubMed Central

    Sanders-Jackson, Ashley; Tan, Andy S. L.; Bigman, Cabral A.; Mello, Susan; Niederdeppe, Jeff

    2016-01-01

    Background Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes) are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition. Methods Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies. Results A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement) versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%). The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support. Discussion This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue. Implications Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices) may be effectively deployed by policy makers or health advocates in communicating with the public. PMID:27517716

  10. Post regulation circuit with energy storage

    DOEpatents

    Ball, Don G.; Birx, Daniel L.; Cook, Edward G.

    1992-01-01

    A charge regulation circuit provides regulation of an unregulated voltage supply and provides energy storage. The charge regulation circuit according to the present invention provides energy storage without unnecessary dissipation of energy through a resistor as in prior art approaches.

  11. Cosmetic Regulations: A Comparative Study.

    PubMed

    Suhag, Jyoti; Dureja, Harish

    2015-01-01

    The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations. PMID:26380505

  12. Neuronal regulation of tendon homoeostasis.

    PubMed

    Ackermann, Paul W

    2013-08-01

    The regulation of tendon homoeostasis, including adaptation to loading, is still not fully understood. Accumulating data, however, demonstrates that in addition to afferent (sensory) functions, the nervous system, via efferent pathways which are associated with through specific neuronal mediators plays an active role in regulating pain, inflammation and tendon homeostasis. This neuronal regulation of intact-, healing- and tendinopathic tendons has been shown to be mediated by three major groups of molecules including opioid, autonomic and excitatory glutamatergic neuroregulators. In intact healthy tendons the neuromediators are found in the surrounding structures: paratenon, endotenon and epitenon, whereas the proper tendon itself is practically devoid of neurovascular supply. This neuroanatomy reflects that normal tendon homoeostasis is regulated from the tendon surroundings. After injury and during tendon repair, however, there is extensive nerve ingrowth into the tendon proper, followed by a time-dependent emergence of sensory, autonomic and glutamatergic mediators, which amplify and fine-tune inflammation and regulate tendon regeneration. In tendinopathic condition, excessive and protracted presence of sensory and glutamatergic neuromediators has been identified, suggesting involvement in inflammatory, nociceptive and hypertrophic (degenerative) tissue responses. Under experimental and clinical conditions of impaired (e.g. diabetes) as well as excessive (e.g. tendinopathy) neuromediator release, dysfunctional tendon homoeostasis develops resulting in chronic pain and gradual degeneration. Thus there is a prospect that in the future pharmacotherapy and tissue engineering approaches targeting neuronal mediators and their receptors may prove to be effective therapies for painful, degenerative and traumatic tendon disorders.

  13. Progress toward risk informed regulation

    SciTech Connect

    Rogers, K.C.

    1997-01-01

    For the last several years, the NRC, with encouragement from the industry, has been moving in the direction of risk informed regulation. This is consistent with the regulatory principle of efficiency, formally adopted by the Nuclear Regulatory Commission in 1991, which requires that regulatory activities be consistent with the degree of risk reduction they achieve. Probabilistic risk analysis has become the tool of choice for selecting the best of several alternatives. Closely related to risk informed regulation is the development of performance based rules. Such rules focus on the end result to be achieved. They do not specify the process, but instead establish the goals to be reached and how the achievement of those goals is to be judged. The inspection and enforcement activity is based on whether or not the goals have been met. The author goes on to offer comments on the history of the development of this process and its probable development in the future. He also addresses some issues which must be resolved or at least acknowledged. The success of risk informed regulation ultimately depends on having sufficiently reliable data to allow quantification of regulatory alternatives in terms of relative risk. Perhaps the area of human reliability and organizational performance has the greatest potential for improvement in reactor safety. The ability to model human performance is significantly less developed that the ability to model mechanical or electrical systems. The move toward risk informed, performance based regulation provides an unusual, perhaps unique, opportunity to establish a more rational, more effective basis for regulation.

  14. How Europe regulates its genes

    SciTech Connect

    Balter, M.

    1991-06-07

    As Europe moves toward unification in 1992, more than two dozen regulations and directives that will affect biotech are working their way through the complex European legislative system. The result could mean tough scrutiny for genetically engineered products. One reason is that the European Community (EC) has chosen to examine genetically engineered products as a special category - an approach the FDA has rejected. Another is that the EC is considering enacting regulations that would mandate consideration of the socioeconomic effects of biotech products in addition to their safety. In addition, some - particularly in industry - fear a nightmare of overlapping and contradictory regulations. It's too soon to tell how well the European system will work, or how stifling the regulations might be. In all likelihood the regulations emerging in Europe won't be demonstrably superior - or inferior - to the American ones, just different, with different strengths and weaknesses. But since many US biotech companies are looking to the huge market that a unified Europe represents, the specifics of those strengths and weaknesses will ultimately be of more than passing interest.

  15. Law and regulation of benzene.

    PubMed Central

    Feitshans, I L

    1989-01-01

    OSHA has created final benzene regulations after extensive rulemakings on two occasions, 1978 and 1987. These standards have been the subject of extensive litigation for nearly 20 years. This article examines in detail the conceptual underpinnings of the Benzene Case, (which was decided by the U.S. Supreme Court in 1980) in light of U.S. administrative law precedents that have set limits upon administrative discretion under the test for "substantial evidence" and the "hard look doctrine." This article also addresses recent developments in the wake of the Benzene Case and their implications for benzene regulations following the "significant risk" doctrine in that case. This article briefly describes other national, regional, and international laws governing the use of benzene. This article concludes that the revisions of the benzene regulation and subsequent rulemaking provide substantial evidence of scientific underpinnings for regulatory action and that laws from other nations reflect an international consensus that occupational exposure to benzene is a proper subject of regulation. Such regulations and policies are therefore likely to withstand scrutiny and remain enforceable as widely accepted norms. PMID:2792048

  16. Cosmetic Regulations: A Comparative Study.

    PubMed

    Suhag, Jyoti; Dureja, Harish

    2015-01-01

    The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

  17. Neuronal regulation of tendon homoeostasis

    PubMed Central

    Ackermann, Paul W

    2013-01-01

    The regulation of tendon homoeostasis, including adaptation to loading, is still not fully understood. Accumulating data, however, demonstrates that in addition to afferent (sensory) functions, the nervous system, via efferent pathways which are associated with through specific neuronal mediators plays an active role in regulating pain, inflammation and tendon homeostasis. This neuronal regulation of intact-, healing- and tendinopathic tendons has been shown to be mediated by three major groups of molecules including opioid, autonomic and excitatory glutamatergic neuroregulators. In intact healthy tendons the neuromediators are found in the surrounding structures: paratenon, endotenon and epitenon, whereas the proper tendon itself is practically devoid of neurovascular supply. This neuroanatomy reflects that normal tendon homoeostasis is regulated from the tendon surroundings. After injury and during tendon repair, however, there is extensive nerve ingrowth into the tendon proper, followed by a time-dependent emergence of sensory, autonomic and glutamatergic mediators, which amplify and fine-tune inflammation and regulate tendon regeneration. In tendinopathic condition, excessive and protracted presence of sensory and glutamatergic neuromediators has been identified, suggesting involvement in inflammatory, nociceptive and hypertrophic (degenerative) tissue responses. Under experimental and clinical conditions of impaired (e.g. diabetes) as well as excessive (e.g. tendinopathy) neuromediator release, dysfunctional tendon homoeostasis develops resulting in chronic pain and gradual degeneration. Thus there is a prospect that in the future pharmacotherapy and tissue engineering approaches targeting neuronal mediators and their receptors may prove to be effective therapies for painful, degenerative and traumatic tendon disorders. PMID:23718724

  18. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  19. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  20. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  1. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  2. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  3. Chloroplast retrograde signal regulates flowering.

    PubMed

    Feng, Peiqiang; Guo, Hailong; Chi, Wei; Chai, Xin; Sun, Xuwu; Xu, Xiumei; Ma, Jinfang; Rochaix, Jean-David; Leister, Dario; Wang, Haiyang; Lu, Congming; Zhang, Lixin

    2016-09-20

    Light is a major environmental factor regulating flowering time, thus ensuring reproductive success of higher plants. In contrast to our detailed understanding of light quality and photoperiod mechanisms involved, the molecular basis underlying high light-promoted flowering remains elusive. Here we show that, in Arabidopsis, a chloroplast-derived signal is critical for high light-regulated flowering mediated by the FLOWERING LOCUS C (FLC). We also demonstrate that PTM, a PHD transcription factor involved in chloroplast retrograde signaling, perceives such a signal and mediates transcriptional repression of FLC through recruitment of FVE, a component of the histone deacetylase complex. Thus, our data suggest that chloroplasts function as essential sensors of high light to regulate flowering and adaptive responses by triggering nuclear transcriptional changes at the chromatin level. PMID:27601637

  4. Developmental regulators in Aspergillus fumigatus.

    PubMed

    Park, Hee-Soo; Yu, Jae-Hyuk

    2016-03-01

    The filamentous fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. This fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. The initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousands of genes associated with formation of the asexual developmental structure conidiophore, and biogenesis of conidia. In this review, we summarize key regulators that directly or indirectly govern conidiation in this important pathogenic fungus. Better understanding these developmental regulators may provide insights into the improvement in controlling both beneficial and detrimental aspects of various Aspergillus species.

  5. Transcriptional Regulation of Hepatic Lipogenesis

    PubMed Central

    Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

    2016-01-01

    Fatty acid and fat synthesis in liver is a highly regulated metabolic pathway critical for energy distribution. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcription level. Transcription factors, such as USF, SREBP-1c, LXR and ChREBP play critical roles in this process. Recently, insights have been gained into how various signaling pathways regulate these transcription factors. After feeding, high blood glucose and insulin induce lipogenic genes through several pathways, including DNA-PK, aPKC and Akt-mTOR. Various transcription factors and coregulators undergo specific modifications, such as phosphorylation, acetylation, or ubiquitination, which affect their function, stability, or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance. PMID:26490400

  6. Neuroendocrine regulation of maternal behavior.

    PubMed

    Bridges, Robert S

    2015-01-01

    The expression of maternal behavior in mammals is regulated by the developmental and experiential events over a female's lifetime. In this review the relationships between the endocrine and neural systems that play key roles in these developmental and experiential processes that affect both the establishment and maintenance of maternal care are presented. The involvement of the hormones estrogen, progesterone, and lactogens are discussed in the context of ligand, receptor, and gene activity in rodents and to a lesser extent in higher mammals. The roles of neuroendocrine factors, including oxytocin, vasopressin, classical neurotransmitters, and other neural gene products that regulate aspects of maternal care are set forth, and the interactions of hormones with central nervous system mediators of maternal behavior are discussed. The impact of prior developmental factors, including epigenetic events, and maternal experience on subsequent maternal care are assessed over the course of the female's lifespan. It is proposed that common neuroendocrine mechanisms underlie the regulation of maternal care in mammals.

  7. Girls, aggression, and emotion regulation.

    PubMed

    Conway, Anne M

    2005-04-01

    Many studies have demonstrated that boys are more aggressive than girls (see J. D. Coie & K. Dodge, 1997, for a review) and that emotion regulation difficulties are associated with problematic behaviors (N. Eisenberg & R. A. Fabes, 1999; M. Gilliom, D. S. Shaw, J. E. Beck, M. A. Schonberg, & J. L. Lukon, 2002). However, recent findings indicate that gender differences in aggressive behaviors disappear when assessments are broadened to include relational aggression--behaviors designed to harm the relationship goals of others by spreading rumors, gossiping, and eliciting peer rejection of others. Moreover, although difficulties regulating emotions have been reported for physically aggressive children, little research has examined these processes in relationally aggressive children. This article argues that investigation into the associations between emotion regulation and relational aggression is a critical direction for future research on the etiology and prevention of mental health problems in girls. PMID:15839769

  8. Developmental regulators in Aspergillus fumigatus.

    PubMed

    Park, Hee-Soo; Yu, Jae-Hyuk

    2016-03-01

    The filamentous fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. This fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. The initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousands of genes associated with formation of the asexual developmental structure conidiophore, and biogenesis of conidia. In this review, we summarize key regulators that directly or indirectly govern conidiation in this important pathogenic fungus. Better understanding these developmental regulators may provide insights into the improvement in controlling both beneficial and detrimental aspects of various Aspergillus species. PMID:26920882

  9. Phosphoinositide regulation of TRP channels

    PubMed Central

    Rohacs, Tibor

    2015-01-01

    Transient Receptor Potential (TRP) channels are activated by stimuli as diverse as heat, cold, noxious chemicals, mechanical forces, hormones, neurotransmitters, spices, and voltage. Besides their presumably similar general architecture, probably the only common factor regulating them is phosphoinositides. The regulation of TRP channels by phosphoinositides is complex. There is a large number of TRP channels where phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2 or PIP2], acts as a positive cofactor, similarly to many other ion channels. In several cases however, PI(4,5)P2 inhibits TRP channel activity, sometimes even concurrently with the activating effect. This review will provide a comprehensive overview of the literature on regulation of TRP channels by membrane phosphoinositides. PMID:24961984

  10. Circadian Regulation of Macronutrient Absorption.

    PubMed

    Hussain, M Mahmood; Pan, Xiaoyue

    2015-12-01

    Various intestinal functions exhibit circadian rhythmicity. Disruptions in these rhythms as in shift workers and transcontinental travelers are associated with intestinal discomfort. Circadian rhythms are controlled at the molecular level by core clock and clock-controlled genes. These clock genes are expressed in intestinal cells, suggesting that they might participate in the circadian regulation of intestinal functions. A major function of the intestine is nutrient absorption. Here, we will review absorption of proteins, carbohydrates, and lipids and circadian regulation of various transporters involved in their absorption. A better understanding of circadian regulation of intestinal absorption might help control several metabolic disorders and attenuate intestinal discomfort associated with disruptions in sleep-wake cycles.

  11. ISOs: The new antitrust regulators?

    SciTech Connect

    Raskin, D.B.

    1998-04-01

    Fear of seller market power in emerging electricity markets has led regulators to sanction use of independent system operators as private market police. A more restrained approach is likely to yield better results without the chilling effects of private regulation. This new industry regulatory paradigm has received little critical attention to date. This is unfortunate because ISO antitrust regulation raises serious legal and policy concerns. The California and New England Power Pool (NEPOOL) plans are quite intrusive. They require the ISO to make difficult distinctions between acceptable and unacceptable market behavior. They create considerable risk that desirable competitive behavior will be chilled and that market participants will incur significant explicit and implicit costs to meet regulatory requirements.

  12. PTEN regulates cilia through Dishevelled

    PubMed Central

    Shnitsar, Iryna; Bashkurov, Mikhail; Masson, Glenn R.; Ogunjimi, Abiodun A.; Mosessian, Sherly; Cabeza, Eduardo Aguiar; Hirsch, Calley L.; Trcka, Daniel; Gish, Gerald; Jiao, Jing; Wu, Hong; Winklbauer, Rudolf; Williams, Roger L.; Pelletier, Laurence; Wrana, Jeffrey L.; Barrios-Rodiles, Miriam

    2015-01-01

    Cilia are hair-like cellular protrusions important in many aspects of eukaryotic biology. For instance, motile cilia enable fluid movement over epithelial surfaces, while primary (sensory) cilia play roles in cellular signalling. The molecular events underlying cilia dynamics, and particularly their disassembly, are not well understood. Phosphatase and tensin homologue (PTEN) is an extensively studied tumour suppressor, thought to primarily act by antagonizing PI3-kinase signalling. Here we demonstrate that PTEN plays an important role in multicilia formation and cilia disassembly by controlling the phosphorylation of Dishevelled (DVL), another ciliogenesis regulator. DVL is a central component of WNT signalling that plays a role during convergent extension movements, which we show here are also regulated by PTEN. Our studies identify a novel protein substrate for PTEN that couples PTEN to regulation of cilia dynamics and WNT signalling, thus advancing our understanding of potential underlying molecular etiologies of PTEN-related pathologies. PMID:26399523

  13. Cellular regulation by protein phosphorylation.

    PubMed

    Fischer, Edmond H

    2013-01-11

    A historical account of the discovery of reversible protein phosphorylation is presented. This process was uncovered in the mid 1950s in a study undertaken with Edwin G. Krebs to elucidate the complex hormonal regulation of skeletal muscle glycogen phosphorylase. Contrary to the known activation of this enzyme by AMP which serves as an allosteric effector, its hormonal regulation results from a phosphorylation of the protein by phosphorylase kinase following the activation of the latter by Ca(2+) and ATP. The study led to the establishment of the first hormonal cascade of successive enzymatic reactions, kinases acting on kinases, initiated by cAMP discovered by Earl Sutherland. It also showed how two different physiological processes, carbohydrate metabolism and muscle contraction, could be regulated in concert.

  14. Updating the International Health Regulations.

    PubMed

    Tucker, Jonathan B

    2005-01-01

    First adopted in 1951, the International Health Regulations (IHR) provide the international legal framework for efforts to prevent and control the cross-border spread of communicable diseases. In 1995, after outbreaks of emerging infections had rendered the IHR increasingly obsolete, the 192 member states of the World Health Organization (WHO) requested a major updating of the regulations to adapt them to the highly mobile, globalized world of the 21st century. After negotiations in 2004 and 2005, the revised IHR text was adopted unanimously by the World Health Assembly, WHO's highest policymaking body. This article reviews the 2005 regulations and discusses their implications for the international response to natural epidemics and to incidents involving the accidental or deliberate release of biological or chemical agents or radiological materials. PMID:16366843

  15. 75 FR 68217 - Acquisition Regulation: Agency Supplementary Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... (65 FR 13735). DOE has examined today's rule and has determined that it does not preempt State law and... Acquisition Regulation (DEAR) on DOE Management and Operating Contracts to make changes to conform to the... does not alter substantive rights or obligations under current law. DATES: Effective Date: December...

  16. 75 FR 32719 - Acquisition Regulation: Agency Supplementary Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-09

    ... ``significant regulatory action'' under Executive Order 12866, ``Regulatory Planning and Review,'' (58 FR 51735... new regulations, section 3(a) of Executive Order 12988, ``Civil Justice Reform,'' 61 FR 4729 (February... 13132 Executive Order 13132, 64 FR 43255 (August 4, 1999), imposes certain requirements on...

  17. Autoimmune regulator, Aire, is a novel regulator of chondrocyte differentiation.

    PubMed

    Si, Yuan; Inoue, Kazuki; Igarashi, Katsuhide; Kanno, Jun; Imai, Yuuki

    2013-08-01

    Chondrocyte differentiation is controlled by various regulators, such as Sox9 and Runx2, but the process is complex. To further understand the precise underlying molecular mechanisms of chondrocyte differentiation, we aimed to identify a novel regulatory factor of chondrocyte differentiation using gene expression profiles of micromass-cultured chondrocytes at different differentiation stages. From the results of microarray analysis, the autoimmune regulator, Aire, was identified as a novel regulator. Aire stable knockdown cells, and primary cultured chondrocytes obtained from Aire(-/-) mice, showed reduced mRNA expression levels of chondrocyte-related genes. Over-expression of Aire induced the early stages of chondrocyte differentiation by facilitating expression of Bmp2. A ChIP assay revealed that Aire was recruited on an Airebinding site (T box) in the Bmp2 promoter region in the early stages of chondrocyte differentiation and histone methylation was modified. These results suggest that Aire can facilitate early chondrocyte differentiation by expression of Bmp2 through altering the histone modification status of the promoter region of Bmp2. Taken together, Aire might play a role as an active regulator of chondrocyte differentiation, which leads to new insights into the regulatory mechanisms of chondrocyte differentiation.

  18. Positively regulated bacterial expression systems

    PubMed Central

    Brautaset, Trygve; Lale, Rahmi; Valla, Svein

    2009-01-01

    Summary Regulated promoters are useful tools for many aspects related to recombinant gene expression in bacteria, including for high‐level expression of heterologous proteins and for expression at physiological levels in metabolic engineering applications. In general, it is common to express the genes of interest from an inducible promoter controlled either by a positive regulator or by a repressor protein. In this review, we discuss established and potentially useful positively regulated bacterial promoter systems, with a particular emphasis on those that are controlled by the AraC‐XylS family of transcriptional activators. The systems function in a wide range of microorganisms, including enterobacteria, soil bacteria, lactic bacteria and streptomycetes. The available systems that have been applied to express heterologous genes are regulated either by sugars (l‐arabinose, l‐rhamnose, xylose and sucrose), substituted benzenes, cyclohexanone‐related compounds, ε‐caprolactam, propionate, thiostrepton, alkanes or peptides. It is of applied interest that some of the inducers require the presence of transport systems, some are more prone than others to become metabolized by the host and some have been applied mainly in one or a limited number of species. Based on bioinformatics analyses, the AraC‐XylS family of regulators contains a large number of different members (currently over 300), but only a small fraction of these, the XylS/Pm, AraC/PBAD, RhaR‐RhaS/rhaBAD, NitR/PnitA and ChnR/Pb regulator/promoter systems, have so far been explored for biotechnological applications. PMID:21261879

  19. Positively regulated bacterial expression systems.

    PubMed

    Brautaset, Trygve; Lale, Rahmi; Valla, Svein

    2009-01-01

    Regulated promoters are useful tools for many aspects related to recombinant gene expression in bacteria, including for high-level expression of heterologous proteins and for expression at physiological levels in metabolic engineering applications. In general, it is common to express the genes of interest from an inducible promoter controlled either by a positive regulator or by a repressor protein. In this review, we discuss established and potentially useful positively regulated bacterial promoter systems, with a particular emphasis on those that are controlled by the AraC-XylS family of transcriptional activators. The systems function in a wide range of microorganisms, including enterobacteria, soil bacteria, lactic bacteria and streptomycetes. The available systems that have been applied to express heterologous genes are regulated either by sugars (L-arabinose, L-rhamnose, xylose and sucrose), substituted benzenes, cyclohexanone-related compounds, ε-caprolactam, propionate, thiostrepton, alkanes or peptides. It is of applied interest that some of the inducers require the presence of transport systems, some are more prone than others to become metabolized by the host and some have been applied mainly in one or a limited number of species. Based on bioinformatics analyses, the AraC-XylS family of regulators contains a large number of different members (currently over 300), but only a small fraction of these, the XylS/Pm, AraC/P(BAD), RhaR-RhaS/rhaBAD, NitR/PnitA and ChnR/Pb regulator/promoter systems, have so far been explored for biotechnological applications.

  20. Medical device regulation for manufacturers.

    PubMed

    McAllister, P; Jeswiet, J

    2003-01-01

    Manufacturers of medical devices are held to a higher standard than manufacturers of many other products due to the potential severity of the consequences of introducing inferior or unsafe products to the market-place. In Canada, the medical device industry is regulated by Health Canada under the Medical Device Regulations of the Food and Drug Act. The Medical Device Regulations define requirements of medical device design, development and manufacture to ensure that products reaching the public are safe and effective. Health Canada also requires that medical device manufacturers maintain distribution records to ensure that devices can be traced to the source and consumers can be contacted successfully in the event that a device is recalled. Medical devices exported from Canada must be compliant with the regulations of the country of import. The Canadian Medical Device Regulations were based on the Medical Device Directives of the European Union thus facilitating approval of Canadian devices for the European market. The United States Food and Drug Administration has separate and distinct requirements for safety and quality of medical devices. While effort has been made to facilitate approval and trade of Canadian medical devices in the United States and the European Union, obtaining approval from multiple regulatory bodies can result in increased device development time and cost. The Global Harmonization Task Force is an organization composed of members from Japanese, Australian, European, Canadian and American medical device regulatory bodies. This organization was formed with the objective of harmonizing medical device regulations in an effort to facilitate international trade and standardize the quality of medical devices available to all countries. This paper discusses the requirements that must be met by manufacturers when designing and manufacturing medical devices.

  1. Regulations against the human nature

    NASA Astrophysics Data System (ADS)

    Elizondo-Garza, Fernando J.

    2001-05-01

    The discussion around the concept of the addiction to noise has evidenced the importance of noise for the human being and explains why in some cases the regulations fail to control the noise in cities. In this presentation the different uses, consciously or unconsciously, of the noise will be analyzed, uses that go from habits to maybe addictions. Also discussed are the implications of establishing regulations against the human nature as well as the importance of education to manage the noise and design acoustically instead of trying to ban the noise in some social circumstances.

  2. The role of food intake regulating peptides in cardiovascular regulation.

    PubMed

    Mikulášková, B; Maletínská, L; Zicha, J; Kuneš, J

    2016-11-15

    Obesity is a risk factor that worsens cardiovascular events leading to higher morbidity and mortality. However, the exact mechanisms of relation between obesity and cardiovascular events are unclear. Nevertheless, it has been demonstrated that pharmacological therapy for obesity has great potential to improve some cardiovascular problems. Therefore, it is important to determine the common mechanisms regulating both food intake and blood pressure. Several hormones produced by peripheral tissues work together with neuropeptides involved in the regulation of both food intake and blood pressure. Anorexigenic (food intake lowering) hormones such as leptin, glucagon-like peptide-1 and cholecystokinin cooperate with α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated peptide as well as prolactin-releasing peptide. Curiously their collective actions result in increased sympathetic activity, especially in the kidney, which could be one of the factors responsible for the blood pressure increases seen in obesity. On the other hand, orexigenic (food intake enhancing) peptides, especially ghrelin released from the stomach and acting in the brain, cooperates with orexins, neuropeptide Y, melanin-concentrating hormone and galanin, which leads to decreased sympathetic activity and blood pressure. This paradox should be intensively studied in the future. Moreover, it is important to know that the hypothalamus together with the brainstem seem to be major structures in the regulation of food intake and blood pressure. Thus, the above mentioned regions might be essential brain components in the transmission of peripheral signals to the central effects. In this short review, we summarize the current information on cardiovascular effects of food intake regulating peptides. PMID:27450151

  3. The role of food intake regulating peptides in cardiovascular regulation.

    PubMed

    Mikulášková, B; Maletínská, L; Zicha, J; Kuneš, J

    2016-11-15

    Obesity is a risk factor that worsens cardiovascular events leading to higher morbidity and mortality. However, the exact mechanisms of relation between obesity and cardiovascular events are unclear. Nevertheless, it has been demonstrated that pharmacological therapy for obesity has great potential to improve some cardiovascular problems. Therefore, it is important to determine the common mechanisms regulating both food intake and blood pressure. Several hormones produced by peripheral tissues work together with neuropeptides involved in the regulation of both food intake and blood pressure. Anorexigenic (food intake lowering) hormones such as leptin, glucagon-like peptide-1 and cholecystokinin cooperate with α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated peptide as well as prolactin-releasing peptide. Curiously their collective actions result in increased sympathetic activity, especially in the kidney, which could be one of the factors responsible for the blood pressure increases seen in obesity. On the other hand, orexigenic (food intake enhancing) peptides, especially ghrelin released from the stomach and acting in the brain, cooperates with orexins, neuropeptide Y, melanin-concentrating hormone and galanin, which leads to decreased sympathetic activity and blood pressure. This paradox should be intensively studied in the future. Moreover, it is important to know that the hypothalamus together with the brainstem seem to be major structures in the regulation of food intake and blood pressure. Thus, the above mentioned regions might be essential brain components in the transmission of peripheral signals to the central effects. In this short review, we summarize the current information on cardiovascular effects of food intake regulating peptides.

  4. Hormonal regulation of female reproduction.

    PubMed

    Christensen, A; Bentley, G E; Cabrera, R; Ortega, H H; Perfito, N; Wu, T J; Micevych, P

    2012-07-01

    Reproduction is an event that requires the coordination of peripheral organs with the nervous system to ensure that the internal and external environments are optimal for successful procreation of the species. This is accomplished by the hypothalamic-pituitary-gonadal axis that coordinates reproductive behavior with ovulation. The primary signal from the central nervous system is gonadotropin-releasing hormone (GnRH), which modulates the activity of anterior pituitary gonadotropes regulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) release. As ovarian follicles develop they release estradiol, which negatively regulates further release of GnRH and FSH. As estradiol concentrations peak they trigger the surge release of GnRH, which leads to LH release inducing ovulation. Release of GnRH within the central nervous system helps modulate reproductive behaviors providing a node at which control of reproduction is regulated. To address these issues, this review focuses on several critical questions. How is the HPG axis regulated in species with different reproductive strategies? What internal and external conditions modulate the synthesis and release of GnRH? How does GnRH modulate reproductive behavior within the hypothalamus? How does disease shift the activity of the HPG axis?

  5. Student Travel: Policies - Regulations - Exhibits.

    ERIC Educational Resources Information Center

    Trujillo, Lorenzo A.; And Others

    The Jefferson County (Colorado) Public Schools' regulations and policies concerning student travel covers these forms of travel: student activity travel, extended student travel, district sponsored student travel, district authorized student travel, student exchange, and bonus learning trips. Issues and items addressed include: (1) authorization…

  6. Deceptive Business Practices: State Regulations.

    ERIC Educational Resources Information Center

    Rohrer, Daniel Morgan

    Although much has been done at the federal level to control deceptive advertising practices, many states have no criminal laws designed to regulate advertising, and several states recently repealed such laws. This paper examines states' efforts to balance the advertiser's freedom of speech with the consumer's need for information about products by…

  7. Regulation of International Information Flows.

    ERIC Educational Resources Information Center

    Maisonrouge, J. G.

    1981-01-01

    Describes the current status of developments concerning the regulation of information flow across national borders. Similarities and trends in various privacy laws from European countries are discussed, as are the business position on data protection and efforts to harmonize national laws. (SW)

  8. The Regulation of Carcinogenic Hazards.

    ERIC Educational Resources Information Center

    Gori, Gio Batta

    1980-01-01

    It is suggested that a system of relative standards be formulated which would compare utility of substances to their relative risk as carcinogens. This would define a range of use restrictions. Substances intended for specific uses would then be regulated according to these standards. (Author/RE)

  9. Endolysosomal proteolysis and its regulation.

    PubMed Central

    Pillay, Ché S; Elliott, Edith; Dennison, Clive

    2002-01-01

    The endolysosomal system comprises a unique environment for proteolysis, which is regulated in a manner that apparently does not involve protease inhibitors. The system comprises a series of membrane-bound intracellular compartments, within which endocytosed material and redundant cellular components are hydrolysed. Endocytosed material tends to flow vectorially through the system, proceeding through the early endosome, the endosome carrier vesicle, the late endosome and the lysosome. Phagocytosis and autophagy provide alternative entry points into the system. Late endosomes, lysosome/late endosome hybrid organelles, phagosomes and autophagosomes are the principal sites for proteolysis. In each case, hydrolytic competence is due to components of the endolysosomal system, i.e. proteases, lysosome-associated membrane proteins, H(+)-ATPases and possibly cysteine transporters. The view is emerging that lysosomes are organelles for the storage of hydrolases, perhaps in an inactivated form. Once a substrate has entered a proteolytically competent environment, the rate-limiting proteolytic steps are probably effected by cysteine endoproteinases. As these are affected by pH and possibly redox potential, they may be regulated by the organelle luminal environment. Regulation is probably also affected, among other factors, by organelle fusion reactions, whereby the meeting of enzyme and substrate may be controlled. Such systems would permit simultaneous regulation of a number of unrelated hydrolases. PMID:11964142

  10. Mechanisms of Hsp90 regulation

    PubMed Central

    Prodromou, Chrisostomos

    2016-01-01

    Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated. PMID:27515256

  11. Temperature: Human Regulating, Ants Conforming

    ERIC Educational Resources Information Center

    Clopton, Joe R.

    2007-01-01

    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  12. Wood stove air flow regulating

    SciTech Connect

    Brefka, P.E.

    1983-10-04

    A wood stove has primary and secondary air regulator doors at the bottom and top, respectively, of the stove door each rotating about the axis of a tightening knob in the center of the door opposite a baffle plate that defines with the door inside an air channel open at the top and bottom.

  13. Adrenocortical Activity and Emotion Regulation.

    ERIC Educational Resources Information Center

    Stansbury, Kathy; Gunnar, Megan R.

    1994-01-01

    This essay argues that the activity of the hypothalamic-pituitary-adrenocortical (HPA) system does not appear to be related to emotion regulation processes in children, although individual differences in emotion processes related to negative emotion temperaments appear to be associated with individual differences in HPA reactivity among normally…

  14. Nutritional regulation of epigenetic changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The "Nutritional Regulation of Epigenetic Changes" Symposium was held in San Diego on April 25 in conjunction with the 2012 Annual Meetings of the American Society of Nutrition. The symposium was co-chaired by Drs. Romagnoo and Ziegler. In his opening remarks, Dr. Zeigler highlighted salient aspec...

  15. 77 FR 14571 - Waste Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... From the Federal Register Online via the Government Publishing Office NATIONAL SCIENCE FOUNDATION Waste Regulation AGENCY: National Science Foundation. ACTION: Correction to notice of permit modification request received under the Antarctic Conservation Act of 1978, Public Law 95-541. SUMMARY:...

  16. Regulating Collaboration in Teacher Education

    ERIC Educational Resources Information Center

    Dobber, Marjolein; Akkerman, Sanne F.; Verloop, Nico; Vermunt, Jan D.

    2014-01-01

    Collaboration in teacher education can be seen as a way to prepare student teachers for future social practices at school. When people collaborate with each other, they have to regulate their collaboration. In the Dutch teacher education programme that was investigated, student teachers were members of different types of groups, each of which had…

  17. Regulated Childhood: Equivalence with Variation

    ERIC Educational Resources Information Center

    Vallberg Roth, Ann-Christine; Mansson, Annika

    2009-01-01

    The overriding aim of this article is to make a contribution to the discussion on individual development plans (IDPs) in Sweden as an expression of a regulated childhood and institutional practice. Individual development plans are seen as a phenomenon linked to the emergence of an auditing society. In sum, children are studied as subjects in…

  18. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR Part 7—Labeling and Advertising of Malt Beverages. 27 CFR Part 28—Exportation of Alcohol. 27 CFR Part 29—Stills and Miscellaneous Regulations. 31 CFR Part 225—Acceptance...

  19. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... OF THE TREASURY ALCOHOL BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR Part 7—Labeling and Advertising of Malt Beverages. 27 CFR Part 28—Exportation of Alcohol. 27 CFR Part 29—Stills and Miscellaneous Regulations. 31 CFR Part 225—Acceptance...

  20. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR Part 7—Labeling and Advertising of Malt Beverages. 27 CFR Part 28—Exportation of Alcohol. 27 CFR Part 29—Stills and Miscellaneous Regulations. 31 CFR Part 225—Acceptance...

  1. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... OF THE TREASURY ALCOHOL BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR Part 7—Labeling and Advertising of Malt Beverages. 27 CFR Part 28—Exportation of Alcohol. 27 CFR Part 29—Stills and Miscellaneous Regulations. 31 CFR Part 225—Acceptance...

  2. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Regulations generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

  3. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR Part 7—Labeling and Advertising of Malt Beverages. 27 CFR Part 28—Exportation of Alcohol. 27 CFR Part 29—Stills and Miscellaneous Regulations. 31 CFR Part 225—Acceptance...

  4. 76 FR 35740 - North Korea Sanctions Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... Office of Foreign Assets Control 31 CFR Part 510 North Korea Sanctions Regulations AGENCY: Office of... Foreign Assets Control (``OFAC'') is amending the North Korea Sanctions Regulations to implement Executive... Control published the North Korea Sanctions Regulations, 31 CFR part 510 (the ``Regulations''),...

  5. 31 CFR 316.3 - Governing regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....3 Governing regulations. (a) The regulations in 31 CFR part 315 apply to definitive Series E bonds that have not been converted to book-entry bonds. (b) The regulations in 31 CFR part 363 apply to... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Governing regulations. 316.3...

  6. 31 CFR 316.3 - Governing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....3 Governing regulations. (a) The regulations in 31 CFR part 315 apply to definitive Series E bonds that have not been converted to book-entry bonds. (b) The regulations in 31 CFR part 363 apply to... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Governing regulations. 316.3...

  7. 31 CFR 316.3 - Governing regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....3 Governing regulations. (a) The regulations in 31 CFR part 315 apply to definitive Series E bonds that have not been converted to book-entry bonds. (b) The regulations in 31 CFR part 363 apply to... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Governing regulations. 316.3...

  8. 31 CFR 316.3 - Governing regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... § 316.3 Governing regulations. (a) The regulations in 31 CFR part 315 apply to definitive Series E bonds that have not been converted to book-entry bonds. (b) The regulations in 31 CFR part 363 apply to... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Governing regulations. 316.3...

  9. 31 CFR 316.3 - Governing regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....3 Governing regulations. (a) The regulations in 31 CFR part 315 apply to definitive Series E bonds that have not been converted to book-entry bonds. (b) The regulations in 31 CFR part 363 apply to... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Governing regulations. 316.3...

  10. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Regulations. 100.5 Section 100.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the Department of Homeland Security, published as chapter I of title 8 of...

  11. 33 CFR 165.13 - General regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false General regulations. 165.13... Areas § 165.13 General regulations. (a) The master of a vessel in a regulated navigation area shall operate the vessel in accordance with the regulations contained in Subpart F. (b) No person may cause...

  12. 50 CFR 216.86 - Local regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Local regulations. 216.86 Section 216.86..., DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Pribilof Islands Administration § 216.86 Local regulations. Local regulations will be published from...

  13. 7 CFR 3.87 - Agency regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Agency regulations. 3.87 Section 3.87 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may issue regulations or policies not inconsistent with OPM regulations (5 CFR part...

  14. 25 CFR 275.4 - Implementing regulations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Implementing regulations. 275.4 Section 275.4 Indians... ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act will be issued by the Civil Service Commission. The regulations will cover the situations described...

  15. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Regulations. 100.5 Section 100.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the Department of Homeland Security, published as chapter I of title 8 of...

  16. 50 CFR 35.3 - General regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false General regulations. 35.3 Section 35.3... regulations. Rules and regulations governing administration of the National Wildlife Refuge System will apply to wilderness units where said rules and regulations do not conflict with provisions of...

  17. 50 CFR 35.14 - Special regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Special regulations. 35.14 Section 35.14... regulations. (a) Special regulations will be issued by the Director for individual wilderness units within the National Wildlife Refuge System as established by Public Law. These special regulations will supplement...

  18. 5 CFR 610.306 - Supplemental regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart....

  19. 7 CFR 993.48 - Regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Regulation. 993.48 Section 993.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Order Regulating Handling Prohibition on Handling § 993.48 Regulation. No handler shall handle...

  20. 7 CFR 3.87 - Agency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Agency regulations. 3.87 Section 3.87 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may issue regulations or policies not inconsistent with OPM regulations (5 CFR part...

  1. 5 CFR 610.306 - Supplemental regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart....

  2. 15 CFR 922.44 - Emergency regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Emergency regulations. 922.44 Section 922.44 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued... MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General Applicability §...

  3. 5 CFR 610.306 - Supplemental regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart....

  4. 28 CFR 42.403 - Agency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Agency regulations. 42.403 Section 42.403... regulations. (a) Any federal agency subject to title VI which has not issued a regulation implementing title... submit a proposed regulation to the Assistant Attorney General pursuant to paragraph (c) of this...

  5. 7 CFR 987.48 - Container regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Container regulation. 987.48 Section 987.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... IN RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Container Regulation § 987.48...

  6. 7 CFR 993.48 - Regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Regulation. 993.48 Section 993.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Prohibition on Handling § 993.48 Regulation. No handler shall handle...

  7. 7 CFR 993.48 - Regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Regulation. 993.48 Section 993.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Prohibition on Handling § 993.48 Regulation. No handler shall handle...

  8. 50 CFR 35.3 - General regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false General regulations. 35.3 Section 35.3... regulations. Rules and regulations governing administration of the National Wildlife Refuge System will apply to wilderness units where said rules and regulations do not conflict with provisions of...

  9. 25 CFR 275.4 - Implementing regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Implementing regulations. 275.4 Section 275.4 Indians... ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act will be issued by the Civil Service Commission. The regulations will cover the situations described...

  10. 25 CFR 275.4 - Implementing regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Implementing regulations. 275.4 Section 275.4 Indians... ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act will be issued by the Civil Service Commission. The regulations will cover the situations described...

  11. 5 CFR 610.306 - Supplemental regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart....

  12. 28 CFR 14.11 - Supplementing regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Supplementing regulations. 14.11 Section... ACT § 14.11 Supplementing regulations. Each agency is authorized to issue regulations and establish procedures consistent with the regulations in this part....

  13. 7 CFR 983.51 - Quality regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Quality regulations. 983.51 Section 983.51 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements..., ARIZONA, AND NEW MEXICO Regulations § 983.51 Quality regulations. For any production year, the...

  14. 28 CFR 14.11 - Supplementing regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Supplementing regulations. 14.11 Section... ACT § 14.11 Supplementing regulations. Each agency is authorized to issue regulations and establish procedures consistent with the regulations in this part....

  15. 36 CFR 34.5 - Applicable regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Applicable regulations. 34.5... PORTAL ADMINISTRATIVE SITE REGULATIONS § 34.5 Applicable regulations. The following sections and... incorporated and made a part of this part except as modified by the regulations in this part: (a)...

  16. 33 CFR 165.13 - General regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false General regulations. 165.13... Areas § 165.13 General regulations. (a) The master of a vessel in a regulated navigation area shall operate the vessel in accordance with the regulations contained in Subpart F. (b) No person may cause...

  17. 7 CFR 993.48 - Regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Regulation. 993.48 Section 993.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Order Regulating Handling Prohibition on Handling § 993.48 Regulation. No handler shall handle...

  18. 50 CFR 35.14 - Special regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Special regulations. 35.14 Section 35.14... regulations. (a) Special regulations will be issued by the Director for individual wilderness units within the National Wildlife Refuge System as established by Public Law. These special regulations will supplement...

  19. 50 CFR 35.3 - General regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false General regulations. 35.3 Section 35.3... regulations. Rules and regulations governing administration of the National Wildlife Refuge System will apply to wilderness units where said rules and regulations do not conflict with provisions of...

  20. 7 CFR 927.316 - Handling regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Handling regulation. 927.316 Section 927.316 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... WASHINGTON Rules and Regulations Assessment Rate § 927.316 Handling regulation. During the period August...

  1. 15 CFR 922.44 - Emergency regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Emergency regulations. 922.44 Section 922.44 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued... MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General Applicability §...

  2. 15 CFR 922.44 - Emergency regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Emergency regulations. 922.44 Section 922.44 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued... MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General Applicability §...

  3. 5 CFR 610.306 - Supplemental regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart....

  4. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Regulations. 100.5 Section 100.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the Department of Homeland Security, published as chapter I of title 8 of...

  5. 50 CFR 35.14 - Special regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Special regulations. 35.14 Section 35.14... regulations. (a) Special regulations will be issued by the Director for individual wilderness units within the National Wildlife Refuge System as established by Public Law. These special regulations will supplement...

  6. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Regulations. 100.5 Section 100.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the Department of Homeland Security, published as chapter I of title 8 of...

  7. 25 CFR 275.4 - Implementing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Implementing regulations. 275.4 Section 275.4 Indians... ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act will be issued by the Civil Service Commission. The regulations will cover the situations described...

  8. 15 CFR 922.44 - Emergency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Emergency regulations. 922.44 Section 922.44 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued... MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General Applicability §...

  9. 7 CFR 983.51 - Quality regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Quality regulations. 983.51 Section 983.51 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., ARIZONA, AND NEW MEXICO Regulations § 983.51 Quality regulations. For any production year, the...

  10. 7 CFR 927.316 - Handling regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Handling regulation. 927.316 Section 927.316 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... WASHINGTON Rules and Regulations Assessment Rate § 927.316 Handling regulation. During the period August...

  11. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Regulations. 100.5 Section 100.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the Department of Homeland Security, published as chapter I of title 8 of...

  12. 28 CFR 14.11 - Supplementing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Supplementing regulations. 14.11 Section... ACT § 14.11 Supplementing regulations. Each agency is authorized to issue regulations and establish procedures consistent with the regulations in this part....

  13. 7 CFR 927.316 - Handling regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Handling regulation. 927.316 Section 927.316 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... WASHINGTON Rules and Regulations Assessment Rate § 927.316 Handling regulation. During the period August...

  14. 28 CFR 14.11 - Supplementing regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Supplementing regulations. 14.11 Section... ACT § 14.11 Supplementing regulations. Each agency is authorized to issue regulations and establish procedures consistent with the regulations in this part....

  15. 28 CFR 42.403 - Agency regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Agency regulations. 42.403 Section 42.403... regulations. (a) Any federal agency subject to title VI which has not issued a regulation implementing title... submit a proposed regulation to the Assistant Attorney General pursuant to paragraph (c) of this...

  16. 7 CFR 993.48 - Regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Regulation. 993.48 Section 993.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Prohibition on Handling § 993.48 Regulation. No handler shall handle...

  17. 7 CFR 987.48 - Container regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Container regulation. 987.48 Section 987.48 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... IN RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Container Regulation § 987.48...

  18. 7 CFR 3.87 - Agency regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Agency regulations. 3.87 Section 3.87 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may issue regulations or policies not inconsistent with OPM regulations (5 CFR part...

  19. 25 CFR 167.2 - General regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true General regulations. 167.2 Section 167.2 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER NAVAJO GRAZING REGULATIONS § 167.2 General regulations. Part 166 of this subchapter authorizes the Commissioner of Indian Affairs to regulate the...

  20. 50 CFR 35.3 - General regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false General regulations. 35.3 Section 35.3... regulations. Rules and regulations governing administration of the National Wildlife Refuge System will apply to wilderness units where said rules and regulations do not conflict with provisions of...

  1. 7 CFR 3.87 - Agency regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Agency regulations. 3.87 Section 3.87 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may issue regulations or policies not inconsistent with OPM regulations (5 CFR part...

  2. 36 CFR 34.5 - Applicable regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Applicable regulations. 34.5... PORTAL ADMINISTRATIVE SITE REGULATIONS § 34.5 Applicable regulations. The following sections and... incorporated and made a part of this part except as modified by the regulations in this part: (a)...

  3. 28 CFR 42.403 - Agency regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Agency regulations. 42.403 Section 42.403... regulations. (a) Any federal agency subject to title VI which has not issued a regulation implementing title... submit a proposed regulation to the Assistant Attorney General pursuant to paragraph (c) of this...

  4. 28 CFR 42.403 - Agency regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Agency regulations. 42.403 Section 42.403... regulations. (a) Any federal agency subject to title VI which has not issued a regulation implementing title... submit a proposed regulation to the Assistant Attorney General pursuant to paragraph (c) of this...

  5. 50 CFR 35.14 - Special regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Special regulations. 35.14 Section 35.14... regulations. (a) Special regulations will be issued by the Director for individual wilderness units within the National Wildlife Refuge System as established by Public Law. These special regulations will supplement...

  6. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Regulations generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

  7. Regulation of the fungal secretome.

    PubMed

    McCotter, Sean W; Horianopoulos, Linda C; Kronstad, James W

    2016-08-01

    The ability of countless representatives of the Kingdom Fungi to adapt to and proliferate in diverse environments is facilitated by regulation of their secretomes to respond to changes in environmental conditions and to mediate interactions with other organisms. Secretome changes often fulfill common functions of nutrient acquisition, facilitation of host/symbiont interactions, cell wall modification, and optimization of the enzyme suite to adapt to new environmental resources. In this review, we expand on our recent work on signaling and the secretome in the pathogenic fungus Cryptococcus neoformans to consider a range of selected examples of regulation of fungal secretomes. These examples include the impact of carbon source and aspects of the response to plant and animal hosts. Additionally, the influence of key protein kinases (e.g., Pka1, Snf1) and transcription factors (e.g., Rim101/PacC) is highlighted to illustrate some underlying regulatory factors influencing the secretome. Although there is a wealth of information about fungal secretomes from both experimentation and genome sequence mining, there are also major gaps in our knowledge about the complete composition of fungal secretomes and mechanisms of dynamic change. For example, a more comprehensive understanding of the composition and regulation of the secretome will require consideration of the emerging roles of unconventional secretion and extracellular vesicles in delivering proteins outside the cell. Overall, changes in the secretome are well documented in diverse fungi and the underlying mechanisms are currently under investigation; however, there remain unknown steps in the regulation of secretory pathways and gaps in understanding the regulation of unconventional secretion, which warrant further research. PMID:26879194

  8. Calcium regulation of mitochondrial carriers.

    PubMed

    Del Arco, Araceli; Contreras, Laura; Pardo, Beatriz; Satrustegui, Jorgina

    2016-10-01

    Mitochondrial function is regulated by calcium. In addition to the long known effects of matrix Ca(2+), regulation of metabolite transport by extramitochondrial Ca(2+) represents an alternative Ca(2+)-dependent mechanism to regulate mitochondrial function. The Ca(2+) regulated mitochondrial transporters (CaMCs) are well suited for that role, as they contain long N-terminal extensions harboring EF-hand Ca(2+) binding domains facing the intermembrane space. They fall in two groups, the aspartate/glutamate exchangers, AGCs, major components of the NADH malate aspartate shuttle (MAS) and urea cycle, and the ATP-Mg(2+)/Pi exchangers or short CaMCs (APCs or SCaMCs). The AGCs are activated by relatively low Ca(2+) levels only slightly higher than resting Ca(2+), whereas all SCaMCs studied so far require strong Ca(2+) signals, above micromolar, for activation. In addition, AGCs are not strictly Ca(2+) dependent, being active even in Ca(2+)-free conditions. Thus, AGCs are well suited to respond to small Ca(2+) signals and that do not reach mitochondria. In contrast, ATP-Mg(2+)/Pi carriers are inactive in Ca(2+) free conditions and activation requires Ca(2+) signals that will also activate the calcium uniporter (MCU). By changing the net content of adenine nucleotides of the matrix upon activation, SCaMCs regulate the activity of the permeability transition pore, and the Ca(2+) retention capacity of mitochondria (CRC), two functions synergizing with those of the MCU. The different Ca(2+) activation properties of the two CaMCs are discussed in relation to their newly obtained structures. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:27033520

  9. Essential infrastructure: national nuclear regulation.

    PubMed

    Paperiello, Carl J

    2011-01-01

    In order for nuclear power to expand to many countries that do not currently have it, it will be essential for these countries to have laws, regulations, guidance and organizations that can license or permit nuclear power plants and support nuclear facilities, ensure compliance by inspection, and enforce nuclear regulations. The viability of nuclear power worldwide depends on an extremely high level of safety everywhere, and compliance with a number of international treaties is required before supplier nations will provide the material, both hardware and software, to build and operate nuclear power plants. While infrastructure support can be obtained from the IAEA and other countries, an essential core of expertise must exist in the country seeking to establish domestic nuclear power generation. While some reliance can be placed on the safety reviews of standard reactor designs by the nuclear regulators in supplier nations, the certification of fuel design, the quality of instruments, and the matching of a new reactor to a proposed site in the importing nation will require site-specific reviews. National arrangements are also needed for emergency preparedness, environmental protection, fuel transportation and the storage, transportation and disposal of radioactive waste. If foreign contractors and consultants are engaged to perform much of the technical work for the regulatory body(s) that has to be performed by the importing nation, that nation must have a core cadre of technically knowledgeable regulators and an organization to provide management and oversight of the contractors and consultants. Consistency in national nuclear regulations, the deployment of standardized nuclear power plant designs and standardized supporting material infrastructure can promote the safe and secure worldwide growth in nuclear power.

  10. Essential infrastructure: national nuclear regulation.

    PubMed

    Paperiello, Carl J

    2011-01-01

    In order for nuclear power to expand to many countries that do not currently have it, it will be essential for these countries to have laws, regulations, guidance and organizations that can license or permit nuclear power plants and support nuclear facilities, ensure compliance by inspection, and enforce nuclear regulations. The viability of nuclear power worldwide depends on an extremely high level of safety everywhere, and compliance with a number of international treaties is required before supplier nations will provide the material, both hardware and software, to build and operate nuclear power plants. While infrastructure support can be obtained from the IAEA and other countries, an essential core of expertise must exist in the country seeking to establish domestic nuclear power generation. While some reliance can be placed on the safety reviews of standard reactor designs by the nuclear regulators in supplier nations, the certification of fuel design, the quality of instruments, and the matching of a new reactor to a proposed site in the importing nation will require site-specific reviews. National arrangements are also needed for emergency preparedness, environmental protection, fuel transportation and the storage, transportation and disposal of radioactive waste. If foreign contractors and consultants are engaged to perform much of the technical work for the regulatory body(s) that has to be performed by the importing nation, that nation must have a core cadre of technically knowledgeable regulators and an organization to provide management and oversight of the contractors and consultants. Consistency in national nuclear regulations, the deployment of standardized nuclear power plant designs and standardized supporting material infrastructure can promote the safe and secure worldwide growth in nuclear power. PMID:21399415

  11. Calcium regulation of mitochondrial carriers.

    PubMed

    Del Arco, Araceli; Contreras, Laura; Pardo, Beatriz; Satrustegui, Jorgina

    2016-10-01

    Mitochondrial function is regulated by calcium. In addition to the long known effects of matrix Ca(2+), regulation of metabolite transport by extramitochondrial Ca(2+) represents an alternative Ca(2+)-dependent mechanism to regulate mitochondrial function. The Ca(2+) regulated mitochondrial transporters (CaMCs) are well suited for that role, as they contain long N-terminal extensions harboring EF-hand Ca(2+) binding domains facing the intermembrane space. They fall in two groups, the aspartate/glutamate exchangers, AGCs, major components of the NADH malate aspartate shuttle (MAS) and urea cycle, and the ATP-Mg(2+)/Pi exchangers or short CaMCs (APCs or SCaMCs). The AGCs are activated by relatively low Ca(2+) levels only slightly higher than resting Ca(2+), whereas all SCaMCs studied so far require strong Ca(2+) signals, above micromolar, for activation. In addition, AGCs are not strictly Ca(2+) dependent, being active even in Ca(2+)-free conditions. Thus, AGCs are well suited to respond to small Ca(2+) signals and that do not reach mitochondria. In contrast, ATP-Mg(2+)/Pi carriers are inactive in Ca(2+) free conditions and activation requires Ca(2+) signals that will also activate the calcium uniporter (MCU). By changing the net content of adenine nucleotides of the matrix upon activation, SCaMCs regulate the activity of the permeability transition pore, and the Ca(2+) retention capacity of mitochondria (CRC), two functions synergizing with those of the MCU. The different Ca(2+) activation properties of the two CaMCs are discussed in relation to their newly obtained structures. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.

  12. Vasopressin and the Regulation of Aquaporin-2

    PubMed Central

    Wilson, Justin L.L.; Miranda, Carlos A.; Knepper, Mark A.

    2013-01-01

    Water excretion is regulated in large part through the regulation of the osmotic water permeability of the renal collecting duct epithelium. The water permeability is controlled by vasopressin through regulation of the water channel, aquaporin-2 (AQP2). Two processes contribute: 1) regulation of AQP2 trafficking to the apical plasma membrane; and 2) regulation of the total amount of the AQP2 protein in the cells. Regulation of AQP2 abundance is defective in several water balance disorders including many polyuric disorders and the syndrome of inappropriate antidiuresis (SIADH). Here we review vasopressin signaling in the renal collecting duct that is relevant to the two modes of water permeability regulation. PMID:23584881

  13. Nongenomic Mechanisms of PTEN Regulation

    PubMed Central

    Fata, Jimmie E.; Debnath, Shawon; Jenkins, Edmund C.; Fournier, Marcia V.

    2012-01-01

    A large amount of data supports the view that PTEN is a bona fide tumor suppressor gene. However, recent evidence suggests that derailment of cellular localization and expression levels of functional nonmutated PTEN is a determining force in inducing abnormal cellular and tissue outcomes. As the cellular mechanisms that regulate normal PTEN enzymatic activity resolve, it is evident that deregulation of these mechanisms can alter cellular processes and tissue architecture and ultimately lead to oncogenic transformation. Here we discuss PTEN ubiquitination, PTEN complex formation with components of the adherens junction, PTEN nuclear localization, and microRNA regulation of PTEN as essential regulatory mechanisms that determine PTEN function independent of gene mutations and epigenetic events. PMID:22536248

  14. Regulation of an Actin Spring

    NASA Astrophysics Data System (ADS)

    Tam, Barney; Shin, Jennifer; Brau, Ricardo; Lang, Matthew; Mahadevan, L.; Matsudaira, Paul

    2006-03-01

    To produce motion, cells rely on the conversion of potential energy into mechanical work. One such example is the dramatic process involving the acrosome reaction of Limulus sperm, whereby a 60 μm-long bundle of actin filaments straightens from a coiled conformation to extend out of the cell in five seconds. This cellular engine and the motion it produces represent a third type of actin-based motility fundamentally different from polymerization or myosin-driven processes. The motive force for this extension originates from stored elastic energy in the overtwisted, pre-formed coil---much like a compressed mechanical spring. When the actin bundle untwists, this energy is converted to mechanical work powering the extension. We report on experiments probing the regulation of this actin spring by extracellular calcium. We find that extracellular calcium needs to be present for the spring to activate, and that calcium regulates the velocity of the extension.

  15. Various Themes of Myosin Regulation.

    PubMed

    Heissler, Sarah M; Sellers, James R

    2016-05-01

    Members of the myosin superfamily are actin-based molecular motors that are indispensable for cellular homeostasis. The vast functional and structural diversity of myosins accounts for the variety and complexity of the underlying allosteric regulatory mechanisms that determine the activation or inhibition of myosin motor activity and enable precise timing and spatial aspects of myosin function at the cellular level. This review focuses on the molecular basis of posttranslational regulation of eukaryotic myosins from different classes across species by allosteric intrinsic and extrinsic effectors. First, we highlight the impact of heavy and light chain phosphorylation. Second, we outline intramolecular regulatory mechanisms such as autoinhibition and subsequent activation. Third, we discuss diverse extramolecular allosteric mechanisms ranging from actin-linked regulatory mechanisms to myosin:cargo interactions. At last, we briefly outline the allosteric regulation of myosins with synthetic compounds.

  16. Cardiac myofilaments: mechanics and regulation

    NASA Technical Reports Server (NTRS)

    de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

    2003-01-01

    The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

  17. Biosimilar regulation in the EU.

    PubMed

    Kurki, Pekka; Ekman, Niklas

    2015-01-01

    In the EU, the EMA has been working with biosimilars since 1998. This experience is crystallized in the extensive set of guidelines, which range from basic principles to details of clinical trials. While the guidance may appear complicated, it has enabled the development of biosimilars, of which 21 have managed to get marketing authorization. Currently marketed biosimilars in the EU have a good track record in safety and traceability. No biosimilars have been withdrawn from the market because of safety concerns. The most controversial issues with biosimilars are immunogenicity and extrapolation of therapeutic indications. The available data for these topics do not raise concerns among EU regulators. Interchangeability and substitution are regulated by individual EU member states. PMID:26294076

  18. Gene regulation by mechanical forces

    NASA Technical Reports Server (NTRS)

    Oluwole, B. O.; Du, W.; Mills, I.; Sumpio, B. E.

    1997-01-01

    Endothelial cells are subjected to various mechanical forces in vivo from the flow of blood across the luminal surface of the blood vessel. The purpose of this review was to examine the data available on how these mechanical forces, in particular cyclic strain, affect the expression and regulation of endothelial cell function. Studies from various investigators using models of cyclic strain in vitro have shown that various vasoactive mediators such as nitric oxide and prostacyclin are induced by the effect of mechanical deformation, and that the expression of these mediators may be regulated at the transcription level by mechanical forces. There also seems to be emerging evidence that endothelial cells may also act as mechanotransducers, whereby the transmission of external forces induces various cytoskeletal changes and second messenger cascades. Furthermore, it seems these forces may act on specific response elements of promoter genes.

  19. Renewable energy and utility regulation

    SciTech Connect

    Not Available

    1991-04-10

    This report summarizes the results of a joint project on renewable energy of the National Association of Regulatory Utility Commissioners (NARUC) and the US DOE. NARUC'S Task Force on Renewable Energy conducted a review of the current state of renewable energy technologies to evaluate their potential and extract key policy lessons from experience already gained in deployment of these technologies in numerous states. The main focus of this effort has been to clarify how utility regulators affect the development of renewable energy resources. The goal of the project was twofold: (1) identify the factors that have led to success or failure or renewable energy technologies in various energy markets, and (2) to develop an agenda on renewable energy and utility regulation for NARUC and the DOE. This report consists of three sections: renewable energy contributions, costs and potential; factors affecting development of renewable energy resources; and a renewable energy agenda for NARUC.

  20. Renewable energy and utility regulation

    SciTech Connect

    Not Available

    1991-04-10

    This report summarizes the results of a joint project on renewable energy of the National Association of Regulatory Utility Commissioners (NARUC) and the US DOE. NARUC`S Task Force on Renewable Energy conducted a review of the current state of renewable energy technologies to evaluate their potential and extract key policy lessons from experience already gained in deployment of these technologies in numerous states. The main focus of this effort has been to clarify how utility regulators affect the development of renewable energy resources. The goal of the project was twofold: (1) identify the factors that have led to success or failure or renewable energy technologies in various energy markets, and (2) to develop an agenda on renewable energy and utility regulation for NARUC and the DOE. This report consists of three sections: renewable energy contributions, costs and potential; factors affecting development of renewable energy resources; and a renewable energy agenda for NARUC.

  1. Astrocytes: Key Regulators of Neuroinflammation.

    PubMed

    Colombo, Emanuela; Farina, Cinthia

    2016-09-01

    Astrocytes are crucial regulators of innate and adaptive immune responses in the injured central nervous system. Depending on timing and context, astrocyte activity may exacerbate inflammatory reactions and tissue damage, or promote immunosuppression and tissue repair. Recent literature has unveiled key factors and intracellular signaling pathways that govern astrocyte behavior during neuroinflammation. Here we have re-visited in vivo studies on astrocyte signaling in neuroinflammatory models focusing on evidences obtained from the analysis of transgenic mice where distinct genes involved in ligand binding, transcriptional regulation and cell communication have been manipulated in astrocytes. The integration of in vivo observations with in vitro data clarifies precise signaling steps, highlights the crosstalk among pathways and identifies shared effector mechanisms in neuroinflammation.

  2. Genetic Regulation of Prostate Development

    PubMed Central

    Meeks, Joshua; Schaeffer, Edward M

    2011-01-01

    Prostatic development is a dynamic process in which basic mechanisms of epithelial outgrowth and epithelial-mesenchymal interaction are initiated by androgens and androgen receptor signaling. Even in adulthood, the prostate's function remains tightly regulated by androgens--without them, pathologic diseases including hyperplastic and malignant growth which together plague nearly 50% of aging males does not occur. Unraveling the etiology of these pathologic processes is a complex and important goal. In fact, many insights into these processes have come from an intimate understanding of the complex signaling networks that regulate physiologic prostatic growth in development. This review aims to highlight important key molecules such as Nkx3.1, sonic hedgehog and Sox9 as well as key signaling pathways including the Fibroblast growth factor and Wnt pathways. These molecules and pathways are critical for prostate development with both know and postulated roles in prostatic pathology. PMID:20930191

  3. Regulation by light in Fusarium.

    PubMed

    Avalos, Javier; Estrada, Alejandro F

    2010-11-01

    The genus Fusarium stands out as research model for pathogenesis and secondary metabolism. Light stimulates the production of some Fusarium metabolites, such as the carotenoids, and in many species it influences the production of asexual spores and sexual fruiting bodies. As found in other fungi with well-known photoresponses, the Fusarium genomes contain several genes for photoreceptors, among them a set of White Collar (WC) proteins, a cryptochrome, a photolyase, a phytochrome and two presumably photoactive opsins. The mutation of the opsin genes produced no apparent phenotypic alterations, but the loss of the only WC-1 orthologous protein eliminated the photoinduced expression of the photolyase and opsin genes. In contrast to other carotenogenic species, lack of the WC photoreceptor did not impede the light-induced accumulation of carotenoids, but produced alterations in conidiation, animal pathogenicity and nitrogen-regulated secondary metabolism. The regulation and functional role of other Fusarium photoreceptors is currently under investigation.

  4. Regulation of inflammasomes by autophagy.

    PubMed

    Saitoh, Tatsuya; Akira, Shizuo

    2016-07-01

    Inflammasomes detect pathogen-associated molecular patterns to induce inflammatory innate immune responses and play a key role in host defense against infectious agents. However, inflammasomes are often wrongly activated by metabolites, amyloids, and environmental irritants. This induces massive inflammation, causing severe tissue damage, and results in the development of inflammatory diseases. Hence cellular machineries regulating both "activation" and "inactivation" of inflammasomes are definitely important. Recent studies have shown that autophagy, an intracellular degradation system associated with maintenance of cellular homeostasis, plays a key role in inflammasome inactivation. Notably, autophagy deficiency caused by gene mutation disrupts organelle elimination and thus induces aberrant activation of inflammasomes, leading to severe tissue damage. Here we review recent findings regarding the involvement of autophagy in the regulation of inflammasome activation and development of inflammatory disorders. PMID:27373323

  5. Lipid Regulation of Acrosome Exocytosis.

    PubMed

    Cohen, Roy; Mukai, Chinatsu; Travis, Alexander J

    2016-01-01

    Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the "DNA--RNA-protein" synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes-cholesterol, phospholipids, and the ganglioside G(M1)--in context of the modern paradigm of acrosome exocytosis. We describe how these various- species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis. PMID:27194352

  6. Frequency regulator for synchronous generators

    DOEpatents

    Karlicek, R.F.

    1982-08-10

    The present invention is directed to a novel frequency regulator which controls a generator output frequency for variations in both the input power to the generator and the power supplied to an uncontrolled external load. The present invention further includes over current and current balance protection devices which are relatively inexpensive to manufacture, which may be encapsulated to provide protection from the operating environment and which respond more quickly than previously known electromechanical devices. 11 figs.

  7. Photomultiplier tube gain regulating system

    DOEpatents

    Johnson, Wayne F.

    1976-01-01

    This invention relates to an improved system for regulating the gain of a photomultiplier tube, and was designed for use with the photomultiplier tubes of a GeMSAEC fast analyzers. It has the following advantages over the prior system: noise is virtually eliminated; sample analysis can begin after 3 to 4 revolutions of the rotor; fluorescent and light scattering solutions can be used as a reference; and the reference solution can be in any cuvette on the rotor.

  8. Frequency regulator for synchronous generators

    DOEpatents

    Karlicek, Robert F.

    1982-01-01

    The present invention is directed to a novel frequency regulator which controls a generator output frequency for variations in both the input power to the generator and the power supplied to an uncontrolled external load. The present invention further includes over current and current balance protection devices which are relatively inexpensive to manufacture, which may be encapsulated to provide protection from the operating environment and which respond more quickly than previously known electromechanical devices.

  9. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  10. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  11. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  12. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  13. Negative regulators of cell proliferation

    NASA Technical Reports Server (NTRS)

    Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Cell proliferation is governed by the influence of both mitogens and inhibitors. Although cell contact has long been thought to play a fundamental role in cell cycling regulation, and negative regulators have long been suspected to exist, their isolation and purification has been complicated by a variety of technical difficulties. Nevertheless, over recent years an ever-expanding list of putative negative regulators have emerged. In many cases, their biological inhibitory activities are consistent with density-dependent growth inhibition. Most likely their interactions with mitogenic agents, at an intracellular level, are responsible for either mitotic arrest or continued cell cycling. A review of naturally occurring cell growth inhibitors is presented with an emphasis on those factors shown to be residents of the cell surface membrane. Particular attention is focused on a cell surface sialoglycopeptide, isolated from intact bovine cerebral cortex cells, which has been shown to inhibit the proliferation of an unusually wide range of target cells. The glycopeptide arrest cells obtained from diverse species, both fibroblasts and epithelial cells, and a broad variety of transformed cells. Signal transduction events and a limited spectrum of cells that are refractory to the sialoglycopeptide have provided insight into the molecular events mediated by this cell surface inhibitor.

  14. Detecting aquaporin function and regulation

    NASA Astrophysics Data System (ADS)

    Madeira, Ana; Moura, Teresa; Soveral, Graça

    2016-02-01

    Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostic and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery.

  15. Epigenetic regulation in Parkinson's disease.

    PubMed

    Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Ross, Owen A

    2016-10-01

    Recent efforts have shed new light on the epigenetic mechanisms driving gene expression alterations associated with Parkinson's disease (PD) pathogenesis. Changes in gene expression are a well-established cause of PD, and epigenetic mechanisms likely play a pivotal role in regulation. Studies in families with PD harboring duplications and triplications of the SNCA gene have demonstrated that gene dosage is associated with increased expression of both SNCA mRNA and protein, and correlates with a fulminant disease course. Furthermore, it is postulated that even subtle changes in SNCA expression caused by common variation is associated with disease risk. Of note, genome-wide association studies have identified over 30 loci associated with PD with most signals located in non-coding regions of the genome, thus likely influencing transcript expression levels. In health, epigenetic mechanisms tightly regulate gene expression, turning genes on and off to balance homeostasis and this, in part, explains why two cells with the same DNA sequence will have different RNA expression profiles. Understanding this phenomenon will be crucial to our interpretation of the selective vulnerability observed in neurodegeneration and specifically dopaminergic neurons in the PD brain. In this review, we discuss epigenetic mechanisms, such as DNA methylation and histone modifications, involved in regulating the expression of genes relevant to PD, RNA-based mechanisms, as well as the effect of toxins and potential epigenetic-based treatments for PD.

  16. Blue light regulated shade avoidance.

    PubMed

    Keuskamp, Diederik H; Keller, Mercedes M; Ballaré, Carlos L; Pierik, Ronald

    2012-04-01

    Most plants grow in dense vegetation with the risk of being out-competed by neighboring plants. These neighbors can be detected not only through the depletion in light quantity that they cause, but also through the change in light quality, which plants perceive using specific photoreceptors. Both the reduction of the red:far-red ratio and the depletion of blue light are signals that induce a set of phenotypic traits, such as shoot elongation and leaf hyponasty, which increase the likelihood of light capture in dense plant stands. This set of phenotypic responses are part of the so called shade avoidance syndrome (SAS). This addendum discusses recent findings on the regulation of the SAS of Arabidopsis thaliana upon blue light depletion. Keller et al. and Keuskamp et al. show that the low blue light attenuation induced shade avoidance response of seedling and rosette-stage A. thaliana plants differ in their hormonal regulation. These studies also show there is a regulatory overlap with the R:FR-regulated SAS.

  17. Detecting Aquaporin Function and Regulation

    PubMed Central

    Madeira, Ana; Moura, Teresa F.; Soveral, Graça

    2016-01-01

    Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery. PMID:26870725

  18. Auricular Acupuncture and Vagal Regulation

    PubMed Central

    He, Wei; Wang, Xiaoyu; Shi, Hong; Shang, Hongyan; Li, Liang; Jing, Xianghong; Zhu, Bing

    2012-01-01

    Auricular acupuncture has been utilized in the treatment of diseases for thousands of years. Dr. Paul Nogier firstly originated the concept of an inverted fetus map on the external ear. In the present study, the relationship between the auricular acupuncture and the vagal regulation has been reviewed. It has been shown that auricular acupuncture plays a role in vagal activity of autonomic functions of cardiovascular, respiratory, and gastrointestinal systems. Mechanism studies suggested that afferent projections from especially the auricular branch of the vagus nerve (ABVN) to the nucleus of the solitary tract (NTS) form the anatomical basis for the vagal regulation of auricular acupuncture. Therefore, we proposed the “auriculovagal afferent pathway” (AVAP): both the autonomic and the central nervous system could be modified by auricular vagal stimulation via projections from the ABVN to the NTS. Auricular acupuncture is also proposed to prevent neurodegenerative diseases via vagal regulation. There is a controversy on the specificity and the efficacy of auricular acupoints for treating diseases. More clinical RCT trials on auricular acupuncture and experimental studies on the mechanism of auricular acupuncture should be further investigated. PMID:23304215

  19. Regulation of the centrosome cycle

    PubMed Central

    Fujita, Hiroki; Yoshino, Yuki; Chiba, Natsuko

    2016-01-01

    ABSTRACT The centrosome, consisting of mother and daughter centrioles surrounded by the pericentriolar matrix (PCM), functions primarily as a microtubule organizing center (MTOC) in most animal cells. In dividing cells the centrosome duplicates once per cell cycle and its number and structure are highly regulated during each cell cycle to organize an effective bipolar spindle in the mitotic phase. Defects in the regulation of centrosome duplication lead to a variety of human diseases, including cancer, through abnormal cell division and inappropriate chromosome segregation. At the end of mitosis the daughter centriole disengages from the mother centriole. This centriole disengagement is an important licensing step for centrosome duplication. In S phase, one new daughter centriole forms perpendicular to each centriole. The centrosome recruits further PCM proteins in the late G2 phase and the two centrosomes separate at mitotic entry to form a bipolar spindle. Here, we summarize research findings in the field of centrosome biology, focusing on the mechanisms of regulation of the centrosome cycle in human cells. PMID:27308597

  20. NRC - regulator of nuclear safety

    SciTech Connect

    1997-05-01

    The U.S. Nuclear Regulatory Commission (NRC) was formed in 1975 to regulate the various commercial and institutional uses of nuclear energy, including nuclear power plants. The agency succeeded the Atomic Energy Commission, which previously had responsibility for both developing and regulating nuclear activities. Federal research and development work for all energy sources, as well as nuclear weapons production, is now conducted by the U.S. Department of Energy. Under its responsibility to protect public health and safety, the NRC has three principal regulatory functions: (1) establish standards and regulations, (2) issue licenses for nuclear facilities and users of nuclear materials, and (3) inspect facilities and users of nuclear materials to ensure compliance with the requirements. These regulatory functions relate to both nuclear power plants and to other uses of nuclear materials - like nuclear medicine programs at hospitals, academic activities at educational institutions, research work, and such industrial applications as gauges and testing equipment. The NRC places a high priority on keeping the public informed of its work. The agency recognizes the interest of citizens in what it does through such activities as maintaining public document rooms across the country and holding public hearings, public meetings in local areas, and discussions with individuals and organizations.