Science.gov

Sample records for regulating parasite-induced myocarditis

  1. Myocarditis

    MedlinePlus

    ... and diagnosis of myocarditis in adults. http://www.uptodate.com/home. Accessed Sept. 2, 2015. Cooper LT. ... and prognosis of myocarditis in adults. http://www.uptodate.com/home. Accessed Sept. 2, 2015. Cooper LT. ...

  2. Myocarditis.

    PubMed

    Fung, Gabriel; Luo, Honglin; Qiu, Ye; Yang, Decheng; McManus, Bruce

    2016-02-05

    Viral myocarditis remains a prominent infectious-inflammatory disease for patients throughout the lifespan. The condition presents several challenges including varied modes of clinical presentation, a range of timepoints when patients come to attention, a diversity of approaches to diagnosis, a spectrum of clinical courses, and unsettled perspectives on therapeutics in different patient settings and in the face of different viral pathogens. In this review, we examine current knowledge about viral heart disease and especially provide information on evolving understanding of mechanisms of disease and efforts by investigators to identify and evaluate potential therapeutic avenues for intervention.

  3. Myocarditis (image)

    MedlinePlus

    Myocarditis is inflammation and weakness of the heart muscle usually caused by a viral infection that reaches ... the influenza (flu) virus, Coxsackie virus, and adenovirus. Myocarditis can damage the heart muscle causing it to ...

  4. Myocarditis - pediatric

    MedlinePlus

    ... enable JavaScript. Pediatric myocarditis is inflammation of the heart muscle in an infant or young child. Causes Myocarditis is rare in ... the infection. This can lead to symptoms of heart failure. ... to detect. However, in newborns and infants, symptoms may sometimes appear suddenly. Symptoms may include: ...

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

    PubMed

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

    2015-04-01

    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 (C41 H68 O14 , 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.

  6. 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

  7. Oxidative stress and myocarditis.

    PubMed

    Tada, Yuko; Suzuki, Jun-Ichi

    2016-01-01

    Reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide are produced highly in myocarditis. ROS, which not only act as effectors for pathogen killing but also mediate signal transduction in the stress responsive pathways, are closely related with both innate and adaptive immunity. On the other hand, oxidative stress overwhelming the capacity of anti-oxidative system generated in severe inflammation has been suggested to damage tissues and exacerbate inflammation. Oxidative stress worsens the autoimmunological process of myocarditis, and suppression of the anti-oxidative system and long-lasting oxidative stress could be one of the pathological mechanisms of cardiac remodeling leading to inflammatory cardiomyopathy. Oxidative stress is considered to be one of the promising treatment targets of myocarditis. Evidences of anti-oxidative treatments in myocarditis have not been fully established. Basic strategies of anti-oxidative treatments include inhibition of ROS production, activation of anti-oxidative enzymes and elimination of generated free radicals. ROS are produced by mitochondrial respiratory chain reactions and enzymes including NADPH oxidases, cyclooxygenase, and xanthine oxidase. Other systems involved in inflammation and stress response, such as NF-κB, Nrf2/Keap1, and neurohumoral factors also influence oxidative stress in myocarditis. The efficacy of anti-oxidative treatments could also depend on the etiology and the phases of myocarditis. We review in this article the pathological significance of ROS and oxidative stress, and the potential anti-oxidative treatments in myocarditis.

  8. Hormonal Regulation of CD4+ T-Cell Responses in Coxsackievirus B3-Induced Myocarditis in Mice

    PubMed Central

    Huber, S. A.; Kupperman, J.; Newell, M. K.

    1999-01-01

    Coxsackievirus B3 infection causes significant cardiac inflammation in male, but not female, B1.Tg.Eα mice. This gender difference in disease susceptibility correlates with selective induction of CD4+ Th1 (gamma interferon-positive) cell responses in animals with testosterone, whereas estradiol promotes preferential CD4+ Th2 (interleukin-4 positive [IL-4+]) cell responses. Differences in immune deviation of CD4+ T cells cannot be explained by variation in B7-1 or B7-2 expression. Infection significantly upregulated both molecules, but no differences were detected between estradiol- and testosterone-treated groups. Significantly increased numbers of activated (CD69+) T cells expressing the γδ T-cell receptor were found in male and testosterone-treated male and female mice. In vivo depletion of γδ+ cells by using monoclonal antibodies inhibited myocarditis and resulted in a shift from a Th1 to Th2 response phenotype. Taken together, our results indicate that testosterone promotes a CD4+ Th1 cell response and myocarditis by promoting increased γδ+ cell activation. PMID:10233928

  9. Acute viral myocarditis

    PubMed Central

    Dennert, Robert; Crijns, Harry J.; Heymans, Stephane

    2008-01-01

    Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482

  10. 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.

  11. 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.

  12. Reversible myocarditis after spider bite

    PubMed Central

    Kara, Hasan; Ak, Ahmet; Bayir, Aysegul; Avci, Ahmet

    2013-01-01

    Black widow spiders (Latrodectus tredecimguttatus) are poisonous spiders endemic in Turkey. Latrodectus bites may cause myocarditis with increased cardiac enzymes. We treated two men (aged 20 and 33 years) who had myocarditis after black spider bites with leucocytosis and elevated levels of troponin I, creatine kinase and creatine kinase-MB fraction. Both patients had normal results on an ECG, and one patient had abnormal echocardiography with minimal left ventricular wall movement disorder. Both patients were hospitalised in the intensive care unit and treated with intravenous fluids, analgesics, spasmolytic drugs, tetanus prophylaxis and cardiac monitoring. The levels of troponin I, creatine kinase and creatine kinase-MB fraction improved, and the patients were discharged home on the third and fifth hospital day without complications. Myocarditis after a Latrodectus bite is rare, but may be associated with serious complications. Therefore, in regions endemic with Latrodectus spiders, prudent treatment of spider bites may include cardiac evaluation and monitoring. PMID:23572268

  13. Reversible myocarditis after spider bite.

    PubMed

    Kara, Hasan; Ak, Ahmet; Bayir, Aysegul; Avci, Ahmet

    2013-04-08

    Black widow spiders (Latrodectus tredecimguttatus) are poisonous spiders endemic in Turkey. Latrodectus bites may cause myocarditis with increased cardiac enzymes. We treated two men (aged 20 and 33 years) who had myocarditis after black spider bites with leucocytosis and elevated levels of troponin I, creatine kinase and creatine kinase-MB fraction. Both patients had normal results on an ECG, and one patient had abnormal echocardiography with minimal left ventricular wall movement disorder. Both patients were hospitalised in the intensive care unit and treated with intravenous fluids, analgesics, spasmolytic drugs, tetanus prophylaxis and cardiac monitoring. The levels of troponin I, creatine kinase and creatine kinase-MB fraction improved, and the patients were discharged home on the third and fifth hospital day without complications. Myocarditis after a Latrodectus bite is rare, but may be associated with serious complications. Therefore, in regions endemic with Latrodectus spiders, prudent treatment of spider bites may include cardiac evaluation and monitoring.

  14. Inducible nitric oxide synthase in the myocard.

    PubMed

    Buchwalow, I B; Schulze, W; Karczewski, P; Kostic, M M; Wallukat, G; Morwinski, R; Krause, E G; Müller, J; Paul, M; Slezak, J; Luft, F C; Haller, H

    2001-01-01

    Recognition of significance of nitric oxide synthases (NOS) in cardiovascular regulations has led to intensive research and development of therapies focused on NOS as potential therapeutic targets. However, the NOS isoform profile of cardiac tissue and subcellular localization of NOS isoforms remain a matter of debate. The aim of this study was to investigate the localization of an inducible NOS isoform (NOS2) in cardiomyocytes. Employing a novel immunocytochemical technique of a catalyzed reporter deposition system with tyramide and electron microscopical immunocytochemistry complemented with Western blotting and RT-PCR, we detected NOS2 both in rat neonatal and adult cultured cardiomyocytes and in the normal myocard of adult rats as well as in the human myocard of patients with dilative cardiomyopathy. NOS2 was targeted predominantly to a particulate component of the cardiomyocyte--along contractile fibers, in the plasma membrane including T-tubules, as well as in the nuclear envelope, mitochondria and Golgi complex. Our results point to an involvement of NOS2 in maintaining cardiac homeostasis and contradict to the notion that NOS2 is expressed in cardiac tissue only in response to various physiological and pathogenic factors. NOS2 targeting to mitochondria and contractile fibers suggests a relationship of NO with contractile function and energy production in the cardiac muscle.

  15. Arrhythmias in viral myocarditis and pericarditis.

    PubMed

    Baksi, A John; Kanaganayagam, G Sunthar; Prasad, Sanjay K

    2015-06-01

    Acute viral myocarditis and acute pericarditis are self-limiting conditions that run a benign course and that may not involve symptoms that lead to medical assessment. However, ventricular arrhythmia is frequent in viral myocarditis. Myocarditis is thought to account for a large proportion of sudden cardiac deaths in young people without prior structural heart disease. Identification of acute myocarditis either with or without pericarditis is therefore important. However, therapeutic interventions are limited and nonspecific. Identifying those at greatest risk of a life-threatening arrhythmia is critical to reducing the mortality. This review summarizes current understanding of this challenging area in which many questions remain.

  16. MUMPS MYOCARDITIS: A FORGOTTEN DISEASE?

    PubMed

    Hussain, Sheraz; Zahid, Mohammad Faizan; Rahman, Arshalooz Jamila; Ahmed, Mehnaz Atiq; Ibrahim, Shahnaz Hamid

    2016-01-01

    Mumps is an acute viral illness that follows a self-limiting course but up to 10% of cases have a complicated course with the involvement of other organ systems. Myocarditis is reported as a complication but the incidence has greatly fallen ever since the development of the mumps vaccine. A child presented to our department with parotid swelling and fever. Persistent tachycardia with irregular pulse led to further cardiac work up which showed decreased ejection fraction and raised serum cardiac enzymes, indicating myocardial damage. With ionotropic agents and supportive care, there was complete normalization of ejection fraction and serum cardiac enzyme levels. He was discharged within a week of admission. This case highlights the importance of suspecting myocarditis in the setting of mumps, a diagnosis that precludes early suspicion in mumps patients suffering from cardiac symptoms not explained by other potential aetiologies. Early suspicion and timely supportive care are essential to ensure favourable outcomes.

  17. Autoimmune myocarditis: a clinical entity.

    PubMed Central

    Dragatakis, L. N.; Klassen, J.; Hüttner, I.; Fraser, D. G.; Poirier, N. L.; Klassen, G. A.

    1979-01-01

    In a case of myocarditis electron microscopic and immunoflourescent studies of a transmural myocardial biopsy specimen indicated an autoimmune process. Extensive inflammatory cell infiltration, immunoglobulin and complement deposition along the sarcolemma and in the interstitium, and capillary endothelial injury were found. After a short course of immunosuppressive therapy the inflammatory process was replaced by collagenous scarring and lymphocytic depletion; the blood vessels were then normal. Earlier therapy in such cases may be lifesaving. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:427670

  18. Idiopathic Giant Cell Myocarditis: A Case Report

    PubMed Central

    Kumari M.K., Kalpana; Mysorekar, Vijaya V.; S., Praveen

    2012-01-01

    Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. The patients usually die of heart failure and ventricular arrhythmia unless a cardiac transplantation is performed. We are reporting here an autopsy case of idiopathic giant cell myocarditis with no symptoms in a 27-year old -worker who died suddenly. The purpose of this report was to emphasize that idiopathic giant cell myocarditis was a rare disease and that it could exist in the absence of any symptomatic heart disease. PMID:23205365

  19. Right Cervical Vagotomy Aggravates Viral Myocarditis in Mice Via the Cholinergic Anti-inflammatory Pathway

    PubMed Central

    Li-Sha, Ge; Xing-Xing, Chen; Lian-Pin, Wu; De-Pu, Zhou; Xiao-Wei, Li; Jia-Feng, Lin; Yue-Chun, Li

    2017-01-01

    The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-α, IL-1β, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on α7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment. PMID:28197102

  20. Myocarditis

    MedlinePlus

    ... may also be done to help make the diagnosis. Other tests that may be needed include: Blood ... biopsy (the most accurate way to confirm the diagnosis, but not always needed) Special tests to check ...

  1. Argonaute proteins in cardiac tissue contribute to the heart injury during viral myocarditis.

    PubMed

    Sun, Shougang; Ma, Jialiang; Zhang, Quan; Wang, Qiongying; Zhou, Lei; Bai, Feng; Hu, Hao; Chang, Peng; Yu, Jing; Gao, Bingren

    2016-01-01

    MicroRNAs (miRNAs) are a group of short, noncoding, regulatory RNA molecules the dysregulation of which contributes to the pathogenesis of myocarditis. Argonaute proteins are essential components of miRNA-induced silencing complex and play important roles during miRNA biogenesis and function. However, the expression pattern of four AGO family members has not yet been detected in the coxsackievirus B3 (CVB3)-induced myocarditis tissue samples. In this study, we detected the expression of four AGOs in the CVB3-infected mouse heart tissues and found that AGO1 and AGO3 up-regulated significantly at 4 and 8h after CVB3 infection. Further in vitro research indicated that up-regulated AGO1 and AGO3 are related to the down-regulated TNFAIP3, which is a negative regulator of NF-κB pathway. Subsequently, we confirmed that TNFAIP3 is a direct target of miR-19a/b, and during CVB3 infection, the expression of miR-19a/b and miR-125a/b is not significantly changed. TNFAIP3 level is mainly reduced by up-regulated AGO1 and AGO3. This research sheds light on the relationship between overexpressed AGO proteins and CVB3-induced myocarditis, and this provides potential therapeutic target for viral myocarditis.

  2. Drugs Targeting the Canonical NF-κB Pathway to Treat Viral and Autoimmune Myocarditis.

    PubMed

    Valaperti, Alan

    2016-01-01

    Myocarditis, which is commonly known as heart inflammation, is a multifaceted disease that includes at least three phases. The host's immune system is mostly active during the first viral and the second autoimmune phase, when several inflammatory pathways are activated. One of the pivotal transcription factors that regulate immune responses is the nuclear factor kappa B (NF-κB). If, on one side, the acute response to heart injury activates the production of inflammatory cytokines to protect and limit host damage, on the other side sustained and long-term inflammation is one of the leading causes of cardiac hypertrophy and chronic heart failure. An update on the current knowledge of inhibitors and treatments that limit excessive inflammation in experimental and viral autoimmune myocarditis, and therapeutic approaches to cure patients with myocarditis, are described and discussed in this review.

  3. Fulminant lymphocytic myocarditis associated with orbital myositis and diaphragmatic paralysis.

    PubMed

    Kwon, Oh Hong; Kim, Mi-Na; Kim, Su-A; Seok, Hung Youl; Park, Seong-Mi; Kim, Byung-Jo; Kim, Chul-Hwan; Shim, Wan-Joo; Shim, Ju Sung; Lee, Min-Gu

    2016-01-01

    Although the clinical presentation of myocarditis is very diverse, ranging from mild dyspnea to hemodynamic collapse, myocarditis accompanied with extracardiac myositis is extremely rare. We report a single case of fulminant myocarditis associated with orbital myositis and diaphragmatic paralysis in a 40-year-old man, which was successfully managed by immunosuppressive therapy with steroid.

  4. Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis.

    PubMed

    Wang, Yan; Gao, Bo; Xiong, Sidong

    2014-11-15

    Viral myocarditis, which is most prevalently caused by coxsackievirus B3 (CVB3) infection, is a serious clinical condition characterized by cardiac inflammation. Inflammasome plays an essential role in the regulation of diverse inflammatory responses by serving as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of IL-1β. Although inflammasome has been reported to be crucial for the development of many inflammatory diseases, its role in the pathogenesis of viral myocarditis is still elusive. The present study aims to investigate whether CVB3 infection activates inflammasome and whether the activation of inflammasome contributes to CVB3-induced myocarditis. Our results showed that CVB3 infection induced inflammasome activation both in vitro and in vivo. With the inhibition of inflammasome activation, the severity of CVB3-induced myocarditis was significantly alleviated as evidenced by less weight loss, decreased serological indexes of creatine kinase and creatinekinase-MB activities, as well as less severe myocardial injury. Of importance, echocardiography results showed that inhibition of inflammasome activation also efficiently improved cardiac function as revealed by enhanced left ventricular ejection fraction and left ventricular fractional shortening. Despite that CVB3 infection significantly increased the expression of both retinoic acid-inducible gene 1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3) in cardiac myocytes, CVB3-induced inflammasome activation was NLRP3-, but not retinoic acid-inducible gene 1, dependent. Further study showed that reactive oxygen species production and K(+) efflux were critical for the activation of NLRP3 inflammasome upon CVB3 infection. Collectively, our study demonstrated a crucial role of the NLRP3 inflammasome in the pathogenesis of CVB3-induced myocarditis, and modulation of inflammasome activation might represent a promising therapeutic strategy for viral

  5. Improving outcomes of acute myocarditis in children.

    PubMed

    Di Filippo, Sylvie

    2016-01-01

    Acute viral myocarditis may impair prognosis in children of all ages. Its true incidence is underestimated because of heterogeneity of presentation and outcome. Patients may either recover or progress to chronic cardiomyopathy or death. Improving short-term and long-term prognosis is challenging but can probably be achieved by new diagnostic techniques and novel targeted therapies. The objectives of this review are: (1) to detail the current state of knowledge of the pathophysiological mechanisms of acute myocarditis; (2) to provide an update on diagnostic tools such as magnetic resonance imaging and endomyocardial biopsy; and (3) to present new insights in therapeutic strategies, targeted therapies and management of fulminant cases. Options for improving outcomes in acute myocarditis in the pediatric population are discussed.

  6. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

  7. Myocarditis and inflammatory cardiomyopathy: from diagnosis to treatment.

    PubMed

    Escher, Felicitas; Tschöepe, Carsten; Lassner, Dirk; Schultheiss, Heinz-Peter

    2015-12-01

    Based on the definition in the European Society of Cardiology statement, myocarditis is an inflammatory disease of the myocardium diagnosed by established histological, immunological, and immunohistochemical criteria, whereas inflammatory cardiomyopathy is myocarditis in association with cardiac dysfunction. Actual incidences of myocarditis and CMi are difficult to determine. Studies addressing the issue of sudden cardiac death in young people report a highly variable autopsy prevalence of myocarditis, ranging from 2-42% of cases. Similarly, biopsy-proven myocarditis has been reported in 9-16% of adult patients with unexplained nonischemic dilated cardiomyopathy (DCM). In up to 30% of cases, biopsy-proven myocarditis can progress to DCM and is associated with a poor prognosis. Prognosis in myocarditis patients also varies according to underlying etiology.

  8. Infant acute myocarditis mimicking acute myocardial infarction

    PubMed Central

    Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel

    2016-01-01

    Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569

  9. 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.

  10. 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...

  11. Myocarditis associated with Reovirus in Turkey Poults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis associated with Reovirus in Turkey Poults H. L. ShivaprasadA, M. S. FrancaA, P. R. WoolcockA, R. NordhausenB, M. DayC and M. Pantin-JackwoodC California Animal Health and Food Safety Laboratory System, AFresno and BDavis Branches, University of California, Davis, 2789 South Orange Av...

  12. Detecting and quantifying parasite-induced host mortality from intensity data: method comparisons and limitations

    PubMed Central

    Wilber, Mark Q.; Weinstein, Sara B.; Briggs, Cheryl J.

    2016-01-01

    Parasites can significantly impact animal populations by changing host behavior, reproduction and survival. Detecting and quantifying these impacts is critical for understanding disease dynamics and managing wild animal populations. However, for wild hosts infected with macroparasites, it is notoriously difficult to quantify the fatal parasite load and number of animals that have died due to disease. When ethical or logistical constraints prohibit experimental determination of these values, examination of parasite intensity and distribution data may offer an alternative solution. In this study we introduce a novel method for using intensity data to detect and quantify parasite-induced mortality in wildlife populations. Using simulations, we show that this method is more reliable than previously proposed methods while providing quantitative estimates of parasite-induced mortality from empirical data that are consistent with previously published qualitative estimates. However, we stress that this method, and all techniques that estimate parasite-induced mortality from intensity data alone, have several critical assumptions that limit their applicability in the real world. Due to these limitations, these methods should only be used as an exploratory tool to inform more rigorous studies of parasite-induced host mortality. PMID:26475963

  13. Detecting and quantifying parasite-induced host mortality from intensity data: method comparisons and limitations.

    PubMed

    Wilber, Mark Q; Weinstein, Sara B; Briggs, Cheryl J

    2016-01-01

    Parasites can significantly impact animal populations by changing host behaviour, reproduction and survival. Detecting and quantifying these impacts is critical for understanding disease dynamics and managing wild animal populations. However, for wild hosts infected with macroparasites, it is notoriously difficult to quantify the fatal parasite load and number of animals that have died due to disease. When ethical or logistical constraints prohibit experimental determination of these values, examination of parasite intensity and distribution data may offer an alternative solution. In this study we introduce a novel method for using intensity data to detect and quantify parasite-induced mortality in wildlife populations. We use simulations to show that this method is more reliable than previously proposed methods while providing quantitative estimates of parasite-induced mortality from empirical data that are consistent with previously published qualitative estimates. However this method, and all techniques that estimate parasite-induced mortality from intensity data alone, have several important assumptions that must be scrutinised before applying those to real-world data. Given that these assumptions are met, our method is a new exploratory tool that can help inform more rigorous studies of parasite-induced host mortality.

  14. Fatal Epstein-Barr virus myocarditis in a child with repetitive myocarditis.

    PubMed

    Hebert, M M; Yu, C; Towbin, J A; Rogers, B B

    1995-01-01

    Fatal Epstein-Barr virus (EBV) myocarditis occurred in a 9-year-old female with a history of two prior discrete episodes of myocarditis, the first associated with chicken pox and the second of undetermined origin. Serologic studies during the fatal episode were characteristic of acute EBV infection, and EBV genome was detected by polymerase chain reaction (PCR) amplification of DNA extracted from autopsy heart and liver. PCRs for enteroviruses and cardiac viral culture were negative. An intense mononuclear cell infiltrate in the myocardium consisted entirely of T cells, without identifiable B cells. Human leukocyte antigen HLA-DR analysis using frozen tissue obtained postmortem revealed antigens DR4 and DR13. DR4 is associated with some autoimmune disorders, as well as idiopathic dilated cardiomyopathy. We postulate that an aberrant immune response, possibly associated with the DR4 locus, was responsible for the repetitive episodes of myocarditis in this patient.

  15. Gonococcaemia with arthritis, dermatitis and myocarditis

    PubMed Central

    Fraser, H. S.; Figueroa, J. P.; James, O. B. O'L.; Liburd, A. L.; Nicholson, G. A.; Whitbourne, F.; Alleyne, G. A. O.

    1974-01-01

    Six cases of gonococcaemia seen at the University Hospital of the West Indies are described. All presented with polyarthritis and all but one had skin lesions. They varied widely in severity and chronicity and included one case with rigors and myocarditis. Emphasis is placed on the diagnostic value of the scanty skin lesions, and the importance of repeated examination of cervical swabs. ImagesFig. 1 PMID:4219856

  16. 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

  17. 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.

  18. 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

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

    PubMed

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

    2016-03-02

    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-15(5-/-) 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.

  20. Anti-inflammatory role of obestatin in autoimmune myocarditis.

    PubMed

    Pamukcu, Ozge; Baykan, Ali; Bayram, Latife Cakir; Narin, Figen; Cetin, Nazmi; Narin, Nazmi; Argun, Mustafa; Ozyurt, Abdullah; Uzum, Kazim

    2016-01-01

    Obestatin is a popular endogeneous peptide, known to have an autoimmune regulatory effect on energy metabolism and the gastrointestinal system. Studies regarding the anti-inflammatory effects of obestatin are scarce. The aim of this study was to show the anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with subcutaneous administration of porcine cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with obestatin (50 μg/kg) was started before the induction of myocarditis and continued for 3 weeks. The severity of myocarditis was evidenced by clinical, echocardiographic and histological findings. In addition, by-products of neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory cytokines were measured in serum. Obestatin significantly ameliorated the clinical and histopathological severity of autoimmune myocarditis. Therapeutic effects of obestatin in myocarditis were associated with reduced lipid peroxidation, suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis, inhibition of serum inflammatory and activation of anti-inflammatory cytokines. Histopathologically, the left ventricle was significantly dilated, and its wall thickened, along with widespread lymphocytic and histocytic infiltration. The myocardium was severely infiltrated with relatively large mononuclear cells. These histopathological changes were observed in lesser degrees in obestatin-treated rats. This study demonstrated a novel anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis. Consequently, obestatin administration may represent a promising therapeutic approach for myocarditis and dilated cardiomyopathy in the future.

  1. 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

  2. Sudden death of a child due to pyogenic bacterial myocarditis.

    PubMed

    Sikary, Asit K; Mridha, Asit R; Behera, Chittaranjan

    2016-01-01

    Bacterial myocarditis is an uncommon condition and only a few fatal cases in adults are reported in the scientific literature. Death from acute bacterial myocarditis in children is extremely rare. We report an unusual case of fatal bacterial myocarditis in a seven-year-old girl, who had a history of cough for a month and fever for two days. She was given symptomatic treatment by a local physician without suspecting her clinical condition. Her condition rapidly deteriorated and she was brought in dead to the hospital. Autopsy revealed pyogenic bacterial myocarditis associated with bilateral lobar pneumonia caused by Gram-positive cocci. Death from bacterial myocarditis can be prevented by early diagnosis and appropriate antibiotics.

  3. Strain difference in rats with experimental giant cell myocarditis.

    PubMed

    Shioji, K; Kishimoto, C; Nakayama, Y; Sasayama, S

    2000-04-01

    Immunogenetic mechanisms may be involved in the pathogenesis of myocarditis and dilated cardiomyopathy. The present study investigated the incidence, histopathology and histocompatibility characteristics of experimental giant cell myocarditis in various strains of rats. Experimental giant cell myocarditis was induced by immunization with porcine cardiac myosin in Lewis (RT-1(l)), Dahl (DIR/Eis) (RT-1(l)), Fisher (RT-1(lv 1)) rats, but not in Dahl (DIS/Eis) (RT-1(l)) or Brown Norway (RT-1(n)). Myocarditis was most severe in the Lewis rats and their heart weight/body weight ratio was significantly higher than that of control rats immunized with Freund's complete adjuvant alone. In conclusion, this study provides evidence that the expression and severity of experimental giant cell myocarditis may be determined mainly by genetic factors, including both major histocompatibility complex genes as well as other genes, which may be controlled by an immune mechanism.

  4. Heart muscle performance after experimental viral myocarditis.

    PubMed Central

    Adesanya, C O; Goldberg, A H; Phear, W P; Thorp, K A; Young, N A; Abelmann, W H

    1976-01-01

    As part of an inquiry into possible antecedents of idiopathic cardiomyopathy, acute experimental coxsackie virus myocarditis was studied for late structural and functional sequelae. Myocarditis was induced in 12- and 22-day-old hamsters by inoculation with coxsackie virus B3. Early viremia occurred, followed by virus replication in heart muscle. Maximum peak developed tension (Tpd) of isometrically contracting isolated heart muscle was depressed 17 and 43% in the animals inoculated at 12 days, and studied 18 and 90 days later, respectively, as compared to their uninoculated controls. In both infected groups, less muscle stretch was required to reach the length at which Tpd was produced. Animals studied 180 days after inoculation did not differ from controls. The muscles from animals inoculated at 22 days of age and studied 18 days later showed a 15% depression of Tpd compared to their controls. Glycerinated muscles from this infected group developed 50% less tension than their controls. The muscles of hamsters inoculated with virus at 22 days and studied 90 and 180 days later showed no change in Tpd. The data suggest that contractility and compliance of heart muscle are decreased 18 days after inoculation, but recover by 90 days if the animals are inoculated at age 22 days. However, if the animals are inoculated at a younger age (12 days), depression of myocardial performance persists for at least an additional 90 days. It is concluded that the inflammatory stage of experimental acute coxsackie virus B3 myocarditis in the Syrian golden hamster may be followed by residual alterations in contractile proteins and myocardial function. PMID:1249200

  5. Fatal pyogranulomatous myocarditis in 10 Boxer puppies.

    PubMed

    Detmer, Susan E; Bouljihad, Mostafa; Hayden, David W; Schefers, Jeremy M; Armien, Anibal; Wünschmann, Arno

    2016-03-01

    Over a period of 5 years, 10 pure-bred Boxer puppies, 9-16 weeks old, were presented with a history of sudden death and were diagnosed with pyogranulomatous myocarditis. The myocarditis was characterized by a mixed infiltrate composed predominantly of neutrophils and macrophages. In our retrospective study, original case records and archived materials were examined. All dogs were positive for Borrelia burgdorferi on immunohistochemistry (IHC). There was no evidence of infectious agents in formalin-fixed, paraffin-embedded (FFPE) heart tissue sections stained with hematoxylin and eosin, Ziehl-Neelsen, Gram, Grocott methenamine silver, Warthin-Starry, Von Kossa, and Steiner-Chapman stains. IHC for Chlamydia sp., Toxoplasma gondii, Neospora caninum, West Nile virus, and canine parvovirus also yielded a negative result in all dogs. Polymerase chain reaction testing for vector-borne pathogens on heart tissue from 9 of the dogs (1 frozen and 8 FFPE samples) yielded positive results for 1 dog with B. burgdorferi as well as Anaplasma phagocytophilum in another dog. Subsequently, 2 additional cases were found in a French Bulldog and a French Bulldog-Beagle mix that had identical morphology, test results, age, and seasonality to these 10 Boxer dogs. The similarities in the seasonality, signalment of the affected dogs, and the gross and microscopic lesions suggest a common etiology. Positive IHC and morphologic similarities to human Lyme carditis indicate that B. burgdorferi is likely the agent involved. An additional consideration for these cases is the possibility of a breed-specific autoimmune myocarditis or potential predisposition for cardiopathogenic agents in young Boxers.

  6. 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

  7. Current treatment options in (peri)myocarditis and inflammatory cardiomyopathy.

    PubMed

    Maisch, B; Pankuweit, S

    2012-09-01

    In inflammatory dilated cardiomyopathy and myocarditis there is--apart from heart failure and antiarrhythmic therapies--no alternative to an aetiologically driven specific treatment. Prerequisite are noninvasive and invasive biomarkers including endomyocardial biopsy and PCR on cardiotropic agents. This review deals with the different etiologies of myocarditis and inflammatory cardiomyopathy including the genetic background, the predisposition for heart failure and inflammation. It analyses the epidemiologic shift in pathogenetic agents in the last 20 years, the role of innate and aquired immunity including the T- and B-cell driven immune responses. The phases and clinical faces of myocarditis are summarized. Up-to-date information on current treatment options starting with heart failure and antiarrhythmic therapy are provided. Although inflammation can resolve spontaneously, specific treatment directed to the causative aetiology is often required. For fulminant, acute and chronic autoreactive myocarditis immunosuppressive treatment is beneficial, while for viral cardiomyopathy and myocarditis ivIg can resolve inflammation and is as successful as interferon therapy in enteroviral and adenoviral myocarditis. For Parvo B19 and HHV6 myocarditis eradication of the virus is still a problem by any of these treatment options. Finally, the potential of stem cell therapy has to be tested in future trials. In virus-negative, autoreactive perimyocardial disease a locoregional approach with intrapericardial instillation of high local doses of triamcinolone acetate has been shown to be highly efficient and with few systemic side-effects.

  8. Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis

    PubMed Central

    McCarthy, Mary K.; Procario, Megan C.; Twisselmann, Nele; Wilkinson, J. Erby; Archambeau, Ashley J.; Michele, Daniel E.; Day, Sharlene M.

    2014-01-01

    ABSTRACT Adenoviruses are frequent causes of pediatric myocarditis. Little is known about the pathogenesis of adenovirus myocarditis, and the species specificity of human adenoviruses has limited the development of animal models, which is a significant barrier to strategies for prevention or treatment. We have developed a mouse model of myocarditis following mouse adenovirus 1 (MAV-1) infection to study the pathogenic mechanisms of this important cause of pediatric myocarditis. Following intranasal infection of neonatal C57BL/6 mice, we detected viral replication and induction of interferon gamma (IFN-γ) in the hearts of infected mice. MAV-1 caused myocyte necrosis and induced substantial cellular inflammation that was composed predominantly of CD3+ T lymphocytes. Depletion of IFN-γ during acute infection reduced cardiac inflammation in MAV-1-infected mice without affecting viral replication. We observed decreased contractility during acute infection of neonatal mice, and persistent viral infection in the heart was associated with cardiac remodeling and hypertrophy in adulthood. IFN-γ is a proinflammatory mediator during adenovirus-induced myocarditis, and persistent adenovirus infection may contribute to ongoing cardiac dysfunction. IMPORTANCE Studying the pathogenesis of myocarditis caused by different viruses is essential in order to characterize both virus-specific and generalized factors that contribute to disease. Very little is known about the pathogenesis of adenovirus myocarditis, which is a significant impediment to the development of treatment or prevention strategies. We used MAV-1 to establish a mouse model of human adenovirus myocarditis, providing the means to study host and pathogen factors contributing to adenovirus-induced cardiac disease during acute and persistent infection. The MAV-1 model will enable fundamental studies of viral myocarditis, including IFN-γ modulation as a therapeutic strategy. PMID:25320326

  9. Pathology of Toxoplasma myocarditis in acquired immunodeficiency syndrome.

    PubMed

    Sahasrabudhe, Neil S; Jadhav, M V; Deshmukh, S D; Holla, V V

    2003-10-01

    Involvement of the myocardium by Toxoplasma gondii is seen in patients of acquired immunodeficiency syndrome (AIDS), mostly in association with toxoplasma encephalitis. Only few patients die as a direct result of cardiac dysfunction. Clinico-pathological findings of three cases of toxoplasma myocarditis are reported, one of which presented and died due to massive pericardial effusion. All cases showed diffuse myocarditis with parasites on histopathological examination. Incidence of toxoplasma myocarditis in patients dying with AIDS was 8.3% (3 out of 36 cases).

  10. Acute right ventricular myocarditis presenting with chest pain and syncope

    PubMed Central

    Mancio, Jennifer; Bettencourt, Nuno; Oliveira, Marco; Pires-Morais, Gustavo; Ribeiro, Vasco Gama

    2013-01-01

    Myocarditis is assumed to involve both ventricles equally. Right ventricular predominant involvement is rarely described. A case of acute viral right ventricular myocarditis presenting with chest pain and syncope, grade 3 atrioventricular block, right ventricular dilatation and free wall hypokinesia is reported. Cardiac MRI showed late enhancement of the right ventricular free wall without involvement of the left ventricle. Anti-Coxsackie A9 virus neutralising IgM-type antibodies titre was elevated. This case emphasises that manifestations of myocarditis can be limited to the right ventricle and should be considered in the differential diagnosis of right ventricular enlargement. PMID:24096068

  11. Myocarditis in sibling boxer puppies associated with Citrobacter koseri infection.

    PubMed

    Cassidy, J P; Callanan, J J; McCarthy, G; O'Mahony, M C

    2002-05-01

    Two sibling Boxer puppies presented with severe suppurative myocarditis in the absence of additional disseminated suppurative foci. The identification of gram-negative bacteria within areas of myocarditis in both puppies and the pure growth of large numbers of Citrobacter koseri from the myocardial lesions in one of the dogs were consistent with a bacterial etiology. The fact that C. koseri is an opportunist pathogen suggested intercurrent immunosuppression. The finding of a concomitant bacterial myocarditis in two canine siblings is novel. The case is also unusual in that syncope could be related to the myocardial injury.

  12. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction

    PubMed Central

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Éric; Gaudreault, Valérie

    2014-01-01

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause. PMID:25276306

  13. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction.

    PubMed

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Eric; Gaudreault, Valérie

    2014-09-26

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

  14. 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.

  15. 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.

  16. Viral myocarditis--diagnosis, treatment options, and current controversies.

    PubMed

    Pollack, Ari; Kontorovich, Amy R; Fuster, Valentin; Dec, G William

    2015-11-01

    Myocarditis--a frequent cause of dilated cardiomyopathy and sudden cardiac death--typically results from cardiotropic viral infection followed by active inflammatory destruction of the myocardium. Characterization of this disease has been hampered by its heterogeneous clinical presentations and diverse aetiologies. Advances in cardiac MRI and molecular detection of viruses by endomyocardial biopsy have improved our ability to diagnose and understand the pathophysiological mechanisms of this elusive disease. However, therapeutic options are currently limited for both the acute and chronic phases of myocarditis. Several randomized, controlled trials have demonstrated potential benefit with immunosuppressive and immunomodulatory therapies, but further investigations are warranted. In this Review, we explore the pathophysiology, natural history, and modes of diagnosis of myocarditis, as well as evidence-based treatment strategies. As novel imaging techniques and human in vitro models of the disease emerge, the landscape of therapies for myocarditis is poised to improve.

  17. Myocarditis in puppies: clinical, pathological and virological findings.

    PubMed

    Gagnon, A N; Crowe, S P; Allen, D G; Downey, R S

    1980-07-01

    The clinical, pathological and virological findings in puppies affected with myocarditis are reported. A parvo-like virus was isolated from pooled heart specimens, which is similar to the virus isolated from gastroenteritis cases.

  18. Diagnostic Approach to Myocarditis Mimicking Myocardial Infarction at Initial Presentation

    PubMed Central

    Basman, Craig; Agrawal, Pratik R.; McRee, Chad; Saravolatz, Louis; Chen-Scarabelli, Carol; Scarabelli, Tiziano M.

    2016-01-01

    We present a case of a 35-year-old male patient with a 12-hour history of sudden-onset, crushing chest pain and associated complaints of profuse diaphoresis, nausea and vomiting. The patient was transferred to our institution from an outside hospital for evaluation and possible emergent catheterization. Left heart catheterization was conclusive for normal coronary arteries and a ventriculogram revealed a left ventricular ejection fraction of approximately 45%. Due to a suspicion of myocarditis based on clinical history, pertinent serology tests were ordered, which were found to be negative. Cardiac magnetic resonance on delayed enhancement imaging showed typical sub-epicardial enhancement in a pattern most consistent with myocarditis. The patient was eventually diagnosed with myocarditis and discharged home later, without needing a myocardial biopsy. We present and discuss here the indications of myocardial biopsy and compare the relative utility of cardiac magnetic resonance imaging in formulating the diagnosis of myocarditis. PMID:28197294

  19. Fatal Dengue Myocarditis despite the Use of Extracorporeal Membrane Oxygenation

    PubMed Central

    2016-01-01

    Dengue is an important mosquitoes-borne viral disease which is endemic in tropics and subtropics region. Rapid spreading of disease to previously unaffected region was found in recent years. Atypical manifestations, such as myocarditis, were reported during large outbreak. There is a wide range of clinical manifestations of cardiac involvement in dengue, but rarely fatal. Here we reported a case of fulminant dengue myocarditis in fatal outcome despite cardiac mechanical support. PMID:28018687

  20. A Pitfall in the Diagnosis of Eosinophilic Myocarditis in a Patient who Received Steroid Therapy

    PubMed Central

    Watanabe, Yusuke; Wada, Hiroshi; Sakakura, Kenichi; Fujita, Hideo; Momomura, Shin-ichi

    2017-01-01

    Eosinophilic myocarditis is a rare form of myocardial inflammation that is characterized by the infiltration of eosinophilic cells into the myocardium. The clinical symptoms of eosinophilic myocarditis are similar to those of acute coronary syndrome, and eosinophilic myocarditis sometimes occurs in combination with bronchial asthma. We herein present a case of eosinophilic myocarditis in which additional time was required to make a definitive diagnosis because the patient received steroid therapy. The diagnosis of eosinophilic myocarditis is challenging, especially when a patient has other inflammatory diseases, such as bronchial asthma. We should pay attention to the possibility that steroid therapy may mask the presentation of eosinophilic myocarditis. PMID:28090045

  1. Acute myocarditis associated with novel Middle east respiratory syndrome coronavirus.

    PubMed

    Alhogbani, Tariq

    2016-01-01

    The novel Middle east respiratory syndrome coronavirus (MeRS-CoV) has been identified as a cause of pneumonia; however, it has not been reported as a cause of acute myocarditis. A 60-year-old man presented with pneumonia and congestive heart failure. On the first day of admission, he was found to have an elevated troponin-l level and severe global left ventricular systolic dysfunction on echo-cardiography. The serum creatinine level was found mildly elevated. Chest radiography revealed in the lower lung fields accentuated bronchovascular lung markings and multiple small patchy opacities. Laboratory tests were negative for viruses known to cause myocarditis. Sputum sample was positive for MeRS-CoV. Cardiovascular magnetic resonance revealed evidence of acute myocarditis. the patient had all criteria specified by the international Consensus Group on CMR in Myocarditis that make a clinical suspicion for acute myocarditis. this was the first case that demonstrated that MeRS-CoV may cause acute myocarditis and acute-onset heart failure.

  2. Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy.

    PubMed

    Dominguez, Fernando; Kühl, Uwe; Pieske, Burkert; Garcia-Pavia, Pablo; Tschöpe, Carsten

    2016-02-01

    Myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure, sudden death, and dilated cardiomyopathy. Viruses account for most cases of myocarditis or inflammatory cardiomyopathy, which could induce an immune response causing inflammation even when the pathogen has been cleared. Other etiologic agents responsible for myocarditis include drugs, toxic substances, or autoimmune conditions. In the last few years, advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis, but toxic, infectious-inflammatory, infiltrative, or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent. Furthermore, after the generalization of immunohistochemical and viral genome detection techniques, endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy. Endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons, but both right- and left endomyocardial biopsies have very low complication rates when performed by experienced operators. This document provides a state-of-the-art review of myocarditis and inflammatory cardiomyopathy, with special focus on the role of endomyocardial biopsy to establish specific treatments.

  3. "Parasite-induced aposematism" protects entomopathogenic nematode parasites against invertebrate enemies.

    PubMed

    Jones, Rebecca S; 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."

  4. Fructus Amomi Cardamomi Extract Inhibit Coxsackievirus-B3 Induced Myocarditis in Murine Myocarditis Model.

    PubMed

    Lee, Yun-Gyeong; Park, Jung-Ho; Jeon, Eun-Seok; Kim, Jin-Hee; Lim, Byung-Kwan

    2016-11-28

    Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations (100-10 µg/ml). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract (100 µg/ml) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus.

  5. Autonomic Nervous System in Viral Myocarditis: Pathophysiology and Therapy.

    PubMed

    Cheng, Zheng; Li-Sha, Ge; Yue-Chun, Li

    2016-01-01

    Myocarditis, which is caused by viral infection, can lead to heart failure, malignant arrhythmias, and even sudden cardiac death in young patients. It is also one of the most important causes of dilated cardiomyopathy worldwide. Although remarkable advances in diagnosis and understanding of pathophysiological mechanisms of viral myocarditis have been gained during recent years, no standard treatment strategies have been defined as yet. Fortunately, recent studies present some evidence that immunomodulating therapy is effective for myocarditis. The immunomodulatory effect of the autonomic nervous system has raised considerable interest over recent decades. Studying the influence on the inflammation and immune system of the sympathetic and parasympathetic nervous systems will not only increase our understanding of the mechanism of disease but could also lead to the identification of potential new therapies for viral myocarditis. Studies have shown that the immunomodulating effect of the sympathetic and parasympathetic nervous system is realized by the release of neurotransmitters to their corresponding receptors (catecholamine for α or β adrenergic receptor, acetylcholine for α7 nicotinic acetylcholinergic receptor). This review will discuss the current knowledge of the roles of both the sympathetic and parasympathetic nervous system in inflammation, with a special focus on their roles in viral myocarditis.

  6. Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesis.

    PubMed

    Huber, Sally A

    2016-01-01

    Myocarditis is an inflammation of the myocardium which often follows microbial infections and is a significant cause of sudden unexpected death in the young (<40 years of age) and an underlying cause of dilated cardiomyopathy. Although histologically, the disease is usually associated with infiltration of the myocardium with either eosinophils or leukocytes, use of immunosuppression is controversial outside of giant cell myocarditis and has been found to be of limited value in lymphocytic myocarditis. The relatively limited response might reflect the need for host immunity to control persistent virus infection in the heart which may be the predominant cause of the chronic myocarditis and dilated cardiomyopathy. Treating the persistent virus infection with interferon-beta improved cardiac function in a clinical trial. However, classic immunosuppressive drugs, such as cyclosporine A and cyclophosphamide, are not effective against all types of immunity and experimental myocarditis models have shown that certain immunopathogenic forms of the disease are resistant to these immunosuppressive agents. Understanding the molecular mechanisms underlying the pathogenesis of this disease and the various infectious agents which can cause it will be essential for developing effective therapeutic agents.

  7. Influenza A virus infection complicated by fatal myocarditis.

    PubMed

    Nolte, K B; Alakija, P; Oty, G; Shaw, M W; Subbarao, K; Guarner, J; Shieh, W J; Dawson, J E; Morken, T; Cox, N J; Zaki, S R

    2000-12-01

    Influenza virus typically causes a febrile respiratory illness, but it can present with a variety of other clinical manifestations. We report a fatal case of myocarditis associated with influenza A infection. A previously healthy 11-year-old girl had malaise and fever for approximately 1 week before a sudden, witnessed fatal collapse at home. Autopsy revealed a pericardial effusion, a mixed lymphocytic and neutrophilic myocarditis, a mild lymphocytic interstitial pneumonia, focal bronchial/bronchiolar mucosal necrosis, and histologic changes consistent with asthma. Infection with influenza A (H3N2) was confirmed by virus isolation from a postmortem nasopharyngeal swab. Attempts to isolate virus from heart and lung tissue were unsuccessful. Immunohistochemical tests directed against influenza A antigens and in situ hybridization for influenza A genetic material demonstrated positive staining in bronchial epithelial cells, whereas heart sections were negative. Sudden death is a rare complication of influenza and may be caused by myocarditis. Forensic pathologists should be aware that postmortem nasopharyngeal swabs for viral culture and immunohistochemical or in situ hybridization procedures on lung tissue might be necessary to achieve a diagnosis. Because neither culturable virus nor influenza viral antigen could be identified in heart tissue, the pathogenesis of influenza myocarditis in this case is unlikely to be the result of direct infection of myocardium by the virus. The risk factors for developing myocarditis during an influenza infection are unknown.

  8. Outcome of acute fulminant myocarditis in children

    PubMed Central

    Amabile, N; Fraisse, A; Bouvenot, J; Chetaille, P; Ovaert, C

    2006-01-01

    Objectives To highlight clinical features and outcome of acute fulminant myocarditis (AFM) in children. Methods Diagnostic criteria were (1) the presence of severe and acute heart failure; (2) left ventricular dysfunction on echocardiography; (3) recent history of viral illness; and (4) no history of cardiomyopathy. Results Eleven children were included between 1998 and 2003, at a median age of 1 (0 to 9) year. Their mean left ventricular ejection fraction (LVEF) was 22 (SD 9)% at presentation. A virus was identified in five patients: human parvovirus B19 (n  =  2), Epstein–Barr (n  =  1), varicella zoster (n  =  1), and coxsackie (n = 1). The median intensive care unit course was 13 (2–34) days. Intravenous inotropic support was required by nine patients and eight were mechanically ventilated. All patients received corticosteroid, associated with intravenous immunoglobulin in seven. Five patients experienced cardiocirculatory arrest that was successfully resuscitated in four. At a median follow up of 58.7 (33.8–83.1) months, the 10 survivors are asymptomatic with normalised LVEF. Conclusion Despite a severe presentation, the outcome of AFM is favourable. Aggressive symptomatic management is warranted and heart transplantation should be considered only when maximal supportive therapy does not lead to improvement. PMID:16449512

  9. Malignant ventricular arrhythmias in chronic chagasic myocarditis.

    PubMed

    Chiale, P A; Halpern, M S; Nau, G J; Przybylski, J; Tambussi, A M; Lázzari, J O; Elizari, M V; Rosenbaum, M B

    1982-03-01

    We studied 28 cases of chronic chagasic myocarditis (CCM) with frequent ventricular arrhythmias. Two-hundred and three conventional ECGs recorded during 3 months showed ventricular extrasystoles (VE) ranging between 0.2 and 6 per ten beats in 100%; multiform VE in 97.04%; couplets in 79.31%; ventricular tachycardia (VT) in 42.85%; and R on T in 21.67%. A 24-hour continuous recording showed that VE ranged between 3780 and 61733 (mean 16618 +/- 2627); multiform VE and couplets were present in 100% of patients, and VT was present in 78.5%. In 16 patients (group I) the frequency of VE was persistently high, without diurnal variation; 11 patients showed sustained reduction during sleeping hours and only one showed an increase during night sleep (group II). Even in group II, VE never disappeared for periods longer than 10 minutes. In five patients, four 24-hour recordings were obtained at weekly intervals, and in five other patients a second 24-hour recording was performed 10 to 24 months later. The remarkable frequency, persistence and low variability of ventricular arrhythmias in CCM suggest that such arrhythmias can be used as a most stable, reliable, but highly demanding model for testing the efficacy of antiarrhythmic drugs.

  10. Usefulness of immunosuppression for giant cell myocarditis.

    PubMed

    Cooper, Leslie T; Hare, Joshua M; Tazelaar, Henry D; Edwards, William D; Starling, Randall C; Deng, Mario C; Menon, Santosh; Mullen, G Martin; Jaski, Brian; Bailey, Kent R; Cunningham, Madeleine W; Dec, G William

    2008-12-01

    Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 +/- 15 years, and the mean time from symptom onset to presentation was 27 +/- 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.

  11. Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

    Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition. PMID:28210568

  12. 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.

  13. [Fetal death caused by myocarditis and isolated congenital auriculoventricular block].

    PubMed

    Herreman, G; Ferme, I; Morel, S; Batisse, J; Vuon, N P; Meyer, O

    1985-09-07

    A 26-year old woman gave birth, at term, to a child with isolated complete heart block. A second pregnancy was interrupted by foetal death. Among other immunological abnormalities, this young woman had an antibody resembling the anti-SS-B antibody. At pathological examination the foetus' heart was found to be free of malformation but presented with subacute myocarditis associated with microcalcifications of the conductive tissue. Such findings suggest that an incipient myocarditis may either result in foetal death or lead to fibrosis of conduction pathways with isolated complete heart block.

  14. Climate warming may cause a parasite-induced collapse in coastal amphipod populations.

    PubMed

    Mouritsen, Kim N; Tompkins, Daniel M; Poulin, Robert

    2005-12-01

    Besides the direct impact on the general performance of individual organisms, the ecological consequences of climate change in terrestrial and marine ecosystems are expected to be determined by complex cascading effects arising from modified trophic interactions and competitive relationships. Recently, the synergistic effect of parasitism and climate change has been emphasised as potentially important to host population dynamics and community structure, but robust empirical evidence is generally lacking. The amphipod Corophium volutator is an ecologically important species in coastal soft-bottom habitats of the temperate North Atlantic, and commonly serves as host to microphallid trematodes that cause intensity-dependent and temperature-dependent mortality in the amphipod population. Using a simulation model parameterised with experimental and field data, we demonstrate that a 3.8 degrees C increase in ambient temperature will likely result in a parasite-induced collapse of the amphipod population. This temperature increase is well within the range predicted to prevail by the year 2075 in the International Wadden Sea region from where the model data are obtained. Due to the amphipods' ecological importance, their population decline may impact the coastal ecosystem as a whole.

  15. 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

  16. Idiopathic giant cell myocarditis in childhood: A case report.

    PubMed

    Pehlivan, Sultan; Akçan, Ramazan; Heybet, Eyup Ruşen; Cavlak, Mehmet; Pehlivan, Ali

    2016-03-01

    Idiopathic giant cell myocarditis is a rare entity of unknown origin, which causes sudden death in more than half of the affected patients. It is rarely seen in childhood, and might result in death due to heart failure and ventricular arrhythmias. Idiopathic giant cell myocarditis is mostly diagnosed at autopsy incidentally. Here we present a rare case of childhood idiopathic giant cell myocarditis. A 10-year old boy found dead in his bed in the morning. Interview with family members revealed death the boy was in good health conditions apart from being overweight. At autopsy, external examination was completely normal. Internal examination revealed normal findings; the heart was 297g and macroscopically normal. No traces of any toxic agents detected in complete toxicological analyses. Areas characterized with granulomatous lesions, lymphocytes, histiocytes, and multinucleated giant cells were observed in myocardium at histopathological examination. No necrosis was observed in granulomatous areas. Tuberculosis was negative in the PCR assays. There were no signs indicative of fungal infection, and clinical status of the case was not compatible with the sarcoidosis. In this respect death was attributed to idiopathic giant cell myocarditis.

  17. Diagnosis of myocarditis: Current state and future perspectives.

    PubMed

    Biesbroek, P Stefan; Beek, Aernout M; Germans, Tjeerd; Niessen, Hans W M; van Rossum, Albert C

    2015-07-15

    Myocarditis, i.e. inflammation of the myocardium, is one of the leading causes of sudden cardiac death (SCD) and dilated cardiomyopathy (DCM) in young adults, and is an important cause of symptoms such as chest pain, dyspnea and palpitations. The pathophysiological process of disease progression leading to DCM involves an ongoing inflammation as a result of a viral-induced auto-immune response or a persisting viral infection. It is therefore crucial to detect the disease early in its course and prevent persisting inflammation that may lead to DCM and end-stage heart failure. Because of the highly variable clinical presentation, ranging from mild symptoms to severe heart failure, and the limited available diagnostic tools, the evaluation of patients with suspected myocarditis represents an important clinical dilemma in cardiology. New approaches for the diagnosis of myocarditis are needed in order to improve recognition, to help unravel its pathophysiology, and to develop new therapeutic strategies to treat the disease. In this review, we give a comprehensive overview of the current diagnostic strategies for patients with suspected myocarditis, and demonstrate several new techniques that may help to improve the diagnostic work-up.

  18. Case report: A presumptive case of vaccinia myocarditis.

    PubMed

    Guerdan, Bruce R; Shumway, Gail Janet

    2004-11-01

    A 26-year-old male medical technician who received the smallpox (vaccinia) vaccination developed a clinical case of myocarditis 11 days after vaccination. The medical literature has little information on this complication of vaccination. The individual was admitted for evaluation and pain control. At discharge, he appeared to have had no long-term effects and has returned to duty.

  19. Myocarditis induced by coxsackie B3 virus in mature mice.

    PubMed

    Jaśkiewicz, K; Mrozińska, B

    1975-01-01

    Forty female mice during breast-feeding were infected intraperitoneally with coxackie B3 virus. Gross and microscopic examination of the hearts of the mice 7, 20, 44 and 120 days after infection revealed myocarditis typical of the acute stage of the disease, not reported previously, and gradually increasing intensity of immunologic changes in the chronic stage.

  20. Giant cell myocarditis mimicking idiopathic fascicular ventricular tachycardia.

    PubMed

    Weidenbach, Michael; Springer, Tina; Daehnert, Ingo; Klingel, Karin; Doll, Susanne; Janousek, Jan

    2008-02-01

    We report an adolescent with giant cell myocarditis (GCM) mimicking tachycardia-induced cardiomyopathy. His electrocardiogram (ECG) was typical for an incessant form of fascicular ventricular tachycardia. The patient rapidly deteriorated and required support using extracorporeal membrane oxygenation (ECMO). Biopsy revealed GCM with massive myocyte necrosis. He was successfully heart transplanted 6 days after admission.

  1. Inhibition of Drp1 attenuates mitochondrial damage and myocardial injury in Coxsackievirus B3 induced myocarditis.

    PubMed

    Lin, Lin; Zhang, Ming; Yan, Rui; Shan, Hu; Diao, Jiayu; Wei, Jin

    2017-03-11

    Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackievirus B3 (CVB3) and treated with mdivi1 (a Drp1 inhibitor). Protein expression of Drp1 was increased in mitochondria while decreased in cytoplasm and accompanied by excessive mitochondrial fission in VMC mice. In addition, midivi1 treatment attenuate inflammatory cells infiltration in myocardium of the mice, serum Cardiac troponin I (CTnI) and Creatine kinase-MB (CK-MB) level. Mdivi1 also could improved the survival rate of mice and mitochondrial dysfunction reflected as the up-regulated mitochondrial marker enzymatic activities of succinate dehydrogenase (SDH), cytochrome c oxidase (COX) and mitochondrial membrane potential (MMP). At the same time, mdivi1 rescued the body weight loss, myocardial injury and apoptosis of cardiomyocyte. Furthermore, decease in LVEDs and increase in EF and FS were detected by echocardiogram, which indicated the improved myocardial function. Thus, Drp1-linked excessive mitochondrial fission contributed to VMC and midivi1 may be a potential therapeutic approach.

  2. Gallium-67 imaging in patients with dilated cardiomyopathy and biopsy-proven myocarditis

    SciTech Connect

    O'Connell, J.B.; Henkin, R.E.; Robinson, J.A.; Subramanian, R.; Scanlon, P.J.; Gunnar, R.M.

    1984-07-01

    Current standards for detection of myocarditis in a clinical setting rely on endomyocardial biopsy for accurate diagnosis. With this technique a subset of patients with dilated cardiomyopathy show unsuspected myocarditis histologically. Endomyocardial biopsy, despite its specificity, may lack sensitivity due to sampling error if the inflammation is patchy or focal. Therefore, inflammation-sensitive radioisotopic imaging may be a useful adjunct in the diagnosis of myocarditis. This study was designed to evaluate the applicability of gallium-67 (67Ga) myocardial imaging as an adjunct to endomyocardial biopsy in the diagnosis of myocarditis. Sixty-eight consecutive patients referred for evaluation of dilated cardiomyopathy underwent 71 parallel studies with 67Ga imaging and biopsies that served as the basis of comparison for this study. Histologic myocarditis was identified in 8% of biopsy specimens. Clinical and hemodynamic parameters could not be used to predict the presence of myocarditis. Five of six biopsy samples (87%) with myocarditis showed dense 67Ga uptake, whereas only nine of 65 negative biopsy samples (14%) were paired with equivocally positive 67Ga scans. The single patient with myocarditis and no myocardial 67Ga uptake had dense mediastinal lymph node uptake that may have obscured cardiac uptake. The incidence of myocarditis on biopsy with a positive 67Ga scan was 36% (5/14); however, the incidence of myocarditis with a negative 67Ga scan was only 1.8% (1/57). Follow-up scans for three patients showed close correlation of 67Ga uptake with myocarditis on biopsy. In conclusion 67Ga may be a useful screening test for identifying patients with a high yield of myocarditis on biopsy, and serial scans may eliminate the need for frequent biopsies in patients with proven myocarditis.

  3. Hypersensitivity myocarditis confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

    PubMed

    Park, Yumi; Ahn, Sung Gyun; Ko, Anna; Ra, Sang Ho; Cha, Jaehwang; Jee, Yong Gwan; Lee, Ji Hyun

    2014-03-01

    Myocarditis often occurs due to viral infections and postviral immune-mediated responses. Hypersensitivity myocarditis is a rare form of myocarditis. Numerous drugs can induce myocarditis, which is typically reversible after withdrawal of the causative agent. Here, we report a case of hypersensitivity myocarditis that was probably triggered by amoxicillin and that resolved completely with heart failure management as well as discontinuation of the drug. A 68-year-old woman presented with acute chest pain mimicking acute coronary syndromes, but the coronary angiography was normal. A recent history of taking medications, skin rash, and peripheral eosinophilia suggested a diagnosis of hypersensitivity myocarditis, which was confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

  4. Patterns and clinical manifestations of tuberculous myocarditis: a systematic review of cases.

    PubMed

    Michira, Brian Nyasani; Alkizim, Faraj Omar; Matheka, Duncan Mwangangi

    2015-01-01

    Tuberculosis is a rare cause of myocarditis. It is however associated with a high mortality when it occurs and is often diagnosed at post-mortem. Tuberculous myocarditis prevalence in males is twice that in females. Most of the reported cases of tuberculous myocarditis are predominantly in immunocompetent patients. Out of the reported fatalities (sudden cardiac deaths), eighty one percent (81%) occur in the 'young' patients (below 45years). Antituberculosis drug therapy does not appear to offer mortality benefit against sudden cardiac deaths.

  5. 11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis.

    PubMed

    Maya, Yoshifumi; Werner, Rudolf A; Schütz, Claudia; Wakabayashi, Hiroshi; Samnick, Samuel; Lapa, Constantin; Zechmeister, Christina; Jahns, Roland; Jahns, Valérie; Higuchi, Takahiro

    2016-12-01

    Myocarditis represents a major cause of dilated cardiomyopathy and sudden cardiac death in younger adults. Currently, definitive diagnosis of myocarditis requires endomyocardial biopsy, which is highly invasive and has the drawback of variable sensitivity due to inherent sampling error. Therefore, reliable noninvasive methods to detect and monitor cardiac inflammation are clinically relevant. In this study, we explored the potential of radiolabeled methionine to assess myocardial inflammatory activity in a rat model of experimental autoimmune myocarditis (EAM).

  6. Recent advances in the management of autoimmune myocarditis: insights from animal studies.

    PubMed

    Tajiri, Kazuko; Yasutomi, Yasuhiro; Aonuma, Kazutaka

    2016-01-01

    A growing body of evidence has been accumulating to demonstrate that human myocarditis and dilated cardiomyopathy involve a complex interaction with autoimmunity triggered by cardiotropic microbial infections. Animal experiments have provided direct evidence that infections with a particular microbe can incite autoimmune myocarditis, and this autoimmune response can be mimicked by immunization with the cardiac autoantigen, α- myosin. Animal models greatly advanced our understanding of the molecular mechanisms of myocarditis, and various novel therapeutic strategies have been reported during the last two decades. In this review we present animal models of autoimmune myocarditis and describe the outlook of possible drug targets by showing the latest findings from animal studies.

  7. [Myocarditis in the differential diagnosis of cardiomyopathies. Endomyocardial biopsy or MRI?].

    PubMed

    Besler, C; Schuler, G; Lurz, P

    2015-06-01

    Myocarditis is an inflammatory disease of the heart muscle commonly caused by viral pathogens. Dilated cardiomyopathy is a major long-term sequela of myocarditis and at least in part related to post-viral immune-mediated responses. Establishing a diagnosis of myocarditis represents a major challenge because of the variable clinical picture and the lack of readily available, non-invasive diagnostic tests. In recent years, cardiac magnetic resonance imaging (cMRI) has emerged as a promising additional diagnostic tool in patients with suspected myocarditis: cMRI not only provides important insights into structural and functional abnormalities of the heart but relevant tissue pathologies can also be visualized. The diagnostic accuracy of three tissue criteria, i.e. the edema ratio, early gadolinium enhancement ratio and late gadolinium enhancement, has been characterized in several studies. Endomyocardial biopsy (EMB) is widely considered to be the reference standard for diagnosis of myocarditis. Although limited by sampling error, EMB is the only diagnostic procedure that can be used to confirm myocarditis. Laboratory analyses of EMB may provide information about specific causes of myocarditis and are, at least in part, of prognostic relevance. In a subset of patients the results of EMB may guide therapeutic decision-making. Additional efforts are needed in cardiac imaging, molecular characterization of EMB and evaluation of serum biomarkers to improve the diagnostic work-up in patients with suspected myocarditis and to identify potential novel targets for a cause-specific therapy of myocarditis.

  8. Relevance of Molecular Mimicry in the Mediation of Infectious Myocarditis

    PubMed Central

    Massilamany, Chandirasegaran; Huber, Sally A.; Cunningham, Madeleine W.

    2014-01-01

    Heart disease, the leading cause of death in humans, is estimated to affect one in four American adults in some form. One predominant cause of heart failure in young adults is myocarditis, which can lead to the development of dilated cardiomyopathy, a major indication for heart transplantation. Environmental microbes, including viruses, bacteria, and fungi that are otherwise innocuous, have the potential to induce inflammatory heart disease. As the list is growing, it is critical to determine the mechanisms by which microbes can trigger heart autoimmunity and, importantly, to identify their target antigens. This is especially true as microbes showing structural similarities with the cardiac antigens can predispose to heart autoimmunity by generating cross-reactive immune responses. In this review, we discuss the relevance of molecular mimicry in the mediation of infectious myocarditis. PMID:24263348

  9. [Bioenergetics of the myocardiocytes in infectious-allergic myocarditis].

    PubMed

    Odinokova, V A; Smirnov, V B; Gurevich, M A

    1989-01-01

    The role of myoglobin in myocardial bio-energetics was analyzed in cases of infectious-allergic myocarditis (38 endomyocardial biopsies and 18 autopsies). Myoglobin content is found to be directly related to the severity of the disease and the degree of circulatory compensation or decompensation. In conditions of progressive muscular cell dystrophy, an abrupt drop in myoglobin, detectable around the A discs, can be seen. In hypertrophic myocardiocytes of compensated circulation, myoglobin is detected as distinctly outlined large and small granules.

  10. Nitric oxide synthase in experimental autoimmune myocarditis dysfunction.

    PubMed

    Goren, N; Leiros, C P; Sterin-Borda, L; Borda, E

    1998-11-01

    This study reports the expression of inducible nitric oxide synthase (NOS) in heart from autoimmune myocarditis mice associated with an alteration in their contractile behavior. By mean of the production of [U-14C]citrulline from [U-14C]arginine and immunoblot assay, the expression of iNOS was demonstrated in autoimmune atria that was normally absent. The iNOS activity decreased with administration of dexamethasone and in mice treated with monoclonal anti-interferon-gamma antibody (anti-IFN-gamma mAb). The inhibitors of protein kinase C activity (staurosporine) but not calcium/calmodulin (trifluoperazine) attenuated the iNOS activity. Moreover, autoimmune atria presented contractile alterations (lower values of dF/dt than control). The in vivo treatment with inhibitors of NOS activity or anti-IFN-gamma mAb or dexamethasone improved the contractile activity of autoimmune atria with no change in the contractility of normal atria. The results suggest that the infiltrative cells in myocarditis heart have a potential role in cardiac dysfunction by production of IFN-gamma and subsequent expression of iNOS, that in turn alter the contractile behavior of the heart. The data indicate that cytokines induced activation of L-arginine nitric oxide pathway in myocarditis atria leading to contractile dysfunction.

  11. Myocarditis in patients with subarachnoid hemorrhage: A histopathologic study.

    PubMed

    van der Bilt, Ivo A C; Vendeville, Jean-Paul; van de Hoef, Tim P; Begieneman, Mark P V; Lagrand, Wim K; Kros, Johan M; Wilde, Arthur A M; Rinkel, Gabriel J E; Niessen, Hans W M

    2016-04-01

    Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis. In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P < .005), CD45-positive (P < .0005), and CD68-positive (P < .0005) cells was significantly higher compared to controls. Thrombi in intramyocardial arteries were found in 22 SAH patients and 1 control. Myocytolysis was found in 6 SAH patients but not in controls. Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment.

  12. Role of the innate immune system in acute viral myocarditis.

    PubMed

    Huang, Chien-Hua; Vallejo, Jesus G; Kollias, George; Mann, Douglas L

    2009-05-01

    Although the adaptive immune system is thought to play an important role in the pathogenesis of viral myocarditis, the role of the innate immune system has not been well defined. To address this deficiency, we employed a unique line of mice that harbor a genomic "knock in" of a mutated TNF gene lacking the AU rich element (TNF(ARE/ARE)) that is critical for TNF mRNA stability and translation, in order to examine the contribution of the innate immune system in encephalomyocarditis-induced myocarditis (EMCV). Heterozygous mice (TNF(ARE/+)) were infected with 500 plaque-forming units of EMCV. TNF(ARE/+)mice had a significantly higher 14-day mortality and myocardial inflammation when compared to littermate control mice. Virologic studies showed that the viral load at 14 days was significantly lower in the hearts of TNF(ARE/+) mice. TNF(ARE/+) mice had an exaggerated proinflammatory cytokine and chemokine response in the heart following EMCV infection. Modulation of the innate immune response in TNF(ARE/+) mice by the late administration of prednisolone resulted in a significant improvement in survival and decreased cardiac inflammation, whereas early administration of prednisolone resulted in a blunted innate response and increased mortality in littermate control mice. Viewed together, these data suggest that the duration and degree of activation of the innate immune system plays a critical role in determining host outcomes in experimental viral myocarditis.

  13. 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.

  14. 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

  15. Overview on chronic viral cardiomyopathy/chronic myocarditis.

    PubMed

    Schultheiss, H P; Kühl, U

    2006-01-01

    Myocarditis is most often induced by cardiotropic viruses and often resolves with minimal cardiac remodelling and without discernable prognostic impact. Acute myocarditis has a highly diverse clinical presentation (asymptomatic, infarct-like presentation, atrioventricular (AV)-block, atrial fibrillation, sudden death due to ventricular tachycardia, fulminant myocarditis with severely depressed contractility). Progression of myocarditis to its sequela, dilated cardiomyopathy (DCM), has been documented in 20% of cases and is pathogenically linked to chronic inflammation and viral persistence. Persistence of cardiotropic viruses (enterovirus, adenovirus) constitutes one of the predominant aetiological factors in DCM. Additionally, circulating autoantibodies to distinct cardiac autoantigens have been described in patients with DCM, providing evidence for autoimmune involvement. Since clinical complaints of myocarditis and DCM are unspecific, a positive effect of any specific therapy depends on an accurate biopsy-based diagnosis and characterization of the patients with histological, immunohistological and molecular biological methods (PCR), which have developed into sensitive tools for the detection of different viruses, active viral replication, and myocardial inflammation. The immunohistochemical characterization of infiltrates has supported a new era in the diagnosis of myocardial inflammation compared with the Dallas criteria, which has led to a new entity of secondary cardiomyopathies acknowledged by the WHO, the inflammatory cardiomyopathies (DCMi). Immunohistochemically quantified lymphocytes significantly better reflect troponin levels and correlate with findings by anti-myosin scintigraphy compared with the histological analysis. Furthermore, the orchestrated induction of endothelial cell adhesion molecules (CAMs) in 65% of DCM patients has confirmed that CAM induction is a prerequisite for lymphocytic infiltration in DCMi. The combination of these

  16. 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...

  17. Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression.

    PubMed

    Zhao, Zhao; Cai, Tian-Zhi; Lu, Yan; Liu, Wen-Jun; Cheng, Man-Li; Ji, Yu-Qiang

    2015-04-01

    In the present study, we investigated the potential pathogenesis of coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty mice were included in the study, and 30 mice were intraperitoneally inoculated with CVB3 to establish an acute viral myocarditis model. The survival rate was observed for the CVB3-infected mouse model (MOD), and myocardial injury was examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and Western blot assay were selected to detect the toll-like receptor 4 (TLR4) expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice, and the effects of this treatment were observed. The results indicate that the expression of TLR4 mRNA and the protein significantly and persistently increased during the progression of CVB3-induced myocarditis. The activities of cardiac enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3-induced TLR4 production was significantly decreased and the severity of myocarditis was significantly lessened. In conclusion, CVB3 may induce viral myocarditis by upregulating toll-like receptor 4 expression. The viral myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral myocarditis model, which may be a feasible therapeutic method for treatment of viral myocarditis.

  18. Fas-FasL expression and myocardial cell apoptosis in patients with viral myocarditis.

    PubMed

    Huang, T F; Wu, X H; Wang, X; Lu, I J

    2016-06-20

    The aim of the current study was to investigate Fas and FasL expression and myocardial cell apoptosis in viral myocarditis patients. Human heart specimens were selected from patients who were autopsied between February 2012 and February 2015; of these, 25 patients were diagnosed with viral myocarditis. Another 15 cases with no diagnosis of myocarditis were selected for the control group. All tissue specimens were divided into two parts, one for reverse transcription-polymerase chain reaction analysis and the other for immunohistochemical and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. In situ detection of apoptosis was performed by the TUNEL method, which revealed that myocardial cells from the viral myocarditis group exhibited significant apoptosis, whereas no apoptotic cells were observed in the control group. The number of cells staining positive for Fas and FasL protein in the viral myocarditis group was significantly higher than that in the control group (P < 0.05). There was also a correlation between Fas and FasL protein expression levels and scores (r = 0.92, P < 0.05). The mRNA expression of Fas and FasL was significantly higher in the viral myocarditis group than in the control group (P < 0.05). In conclusion, the Fas-FasL system may be involved in the pathogenesis of viral myocarditis. Furthermore, cytotoxic T lymphocytes may mediate cardiac muscle cells apoptosis via Fas-FasL signaling, and thus participate in the pathogenesis of viral myocarditis.

  19. TandemHeart as a Bridge to Recovery in Legionella Myocarditis.

    PubMed

    Briceño, David F; Fernando, Rajeev R; Nathan, Sriram; Loyalka, Pranav; Kar, Biswajit; Gregoric, Igor D

    2015-08-01

    Legionnaires' disease is the designation for pneumonia caused by the Legionella species. Among the rare extrapulmonary manifestations, cardiac involvement is most prevalent, in the forms of myocarditis, pericarditis, postcardiotomy syndrome, and prosthetic valve endocarditis. Mechanical circulatory support has proved to be a safe and effective bridge to myocardial recovery in patients with acute fulminant myocarditis; however, to our knowledge, this support has not been used in infectious myocarditis specifically related to Legionellosis. We describe a case of Legionella myocarditis associated with acute left ventricular dysfunction and repolarization abnormalities in a 48-year-old man. The patient fully recovered after left ventricular unloading with use of a TandemHeart percutaneous ventricular assist device. In addition, we review the English-language medical literature on Legionella myocarditis and focus on cardiac outcomes.

  20. [Endomyocardial biopsy should be performed in selected patients with suspected myocarditis].

    PubMed

    Ammirati, Enrico; Cipriani, Manlio; Bonacina, Edgardo; Garascia, Andrea; Oliva, Fabrizio

    2015-10-01

    Endomyocardial biopsy (EMB) is the gold standard for the diagnosis of myocarditis. Patients with clinical presentation consistent with myocarditis and acute heart failure should undergo EMB, in particular to exclude giant-cell myocarditis or necrotizing eosinophilic myocarditis that are life-threatening conditions. The indication for EMB is debatable in case of suspected myocarditis with infarct-like presentation and preserved left ventricular ejection fraction. In fact, in this group of patients the prognosis is fairly good, and the clinical advantage to reach a histological diagnosis by means of an invasive procedure with potential complications such as EMB is limited. In this article we discuss the indication for EMB in the light of current guidelines based on existing consensus documents.

  1. Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection

    PubMed Central

    Yajima, Toshitaka

    2011-01-01

    Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity. PMID:21585262

  2. Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis

    PubMed Central

    Kuchynka, Petr; Palecek, Tomas; Masek, Martin; Cerny, Vladimir; Lambert, Lukas; Vitkova, Ivana; Linhart, Ales

    2016-01-01

    Eosinophilic myocarditis (EM) represents a rare form of myocardial inflammation with very heterogeneous aetiology. In developed countries, the most prevalent causes of EM are hypersensitivity or allergic reactions, as well as hematological diseases leading to eosinophilia. The disease may have a variable clinical presentation, ranging from asymptomatic forms to life-threatening conditions. Most patients with EM have marked eosinophilia in peripheral blood. Endomyocardial biopsy needs to be performed in most cases in order to establish a definitive diagnosis of EM. The therapy depends on the underlying aetiology. Immunosuppressive therapy represents the treatment mainstay in the majority of EM forms. PMID:26885504

  3. 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

  4. Recurrent Acute Nonrheumatic Streptococcal Myocarditis Mimicking STEMI in a Young Adult

    PubMed Central

    2014-01-01

    Myocarditis consists of an inflammation of the cardiac muscle, definitively diagnosed by endomyocardial biopsy. The causal agents are primarily infectious: in developed countries, viruses appear to be the main cause, whereas in developing countries rheumatic carditis, Chagas disease, and HIV are frequent causes. Furthermore, myocarditis can be indirectly induced by an infectious agent and occurs following a latency period during which antibodies are created. Typically, myocarditis observed in rheumatic fever related to group A streptococcal (GAS) infection occurs after 2- to 3-week period of latency. In other instances, myocarditis can occur within few days following a streptococcal infection; thus, it does not fit the criteria for rheumatic fever. Myocarditis classically presents as acute heart failure, and can also be manifested by tachyarrhythmia or chest pain. Likewise, GAS-related myocarditis reportedly mimics myocardial infarction (MI) with typical chest pain, electrocardiograph changes, and troponin elevation. Here we describe a case of recurrent myocarditis, 5 years apart, with clinical presentation imitating an acute MI in an otherwise healthy 37-year-old man. Both episodes occurred 3 days after GAS pharyngitis and resolved quickly following medical treatment. PMID:24963417

  5. 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.

  6. Coxsackievirus-induced chronic myocarditis in murine models.

    PubMed

    Gauntt, C J; Tracy, S M; Chapman, N; Wood, H J; Kolbeck, P C; Karaganis, A G; Winfrey, C L; Cunningham, M W

    1995-12-01

    Challenge of several murine strains with two highly myocarditic variants of coxsackievirus B3 (CVB3) induced acute and chronic myocarditis, detectable at 21 and 45 days post-inoculation (p.i.). In-situ hybridization of coronal heart sections showing chronic inflammation with a radiolabelled CVB3 probe detected viral genomic RNA at day 7 p.i. but rarely at 21 or 45 days p.i., suggesting few murine heart cells actively replicate virus during chronic myocardial inflammation. Data will be presented that favour an alternative hypothesis, i.e. autoimmune responses to shared epitopes among CVB3 proteins, cardiac myosin and myocardial cell surface proteins (molecular mimicry) can affect the severity of chronic inflammation. Mice inoculated with human cardiac myosin (HM) prior to a CVB3m challenge develop less myocarditis than mice inoculated with virus only, suggesting that antibodies stimulated by HM bind virus, reduce the virus burden and provide protection. Mice inoculated with HM only develop non-neutralizing antibodies against purified CVB3m particles. Several strains of mice inoculated with specific synthetic peptides of HM produce antibodies against CVB3m and/or develop cardiomyopathy. Thus antigen-challenged mice can produce antibodies which cross-react among CVB3m HM or cardiac cells to protect or exacerbate heart disease.

  7. Native T1 Mapping Demonstrating Apical Thrombi in Eosinophilic Myocarditis Associated with Churg-Strauss Syndrome

    PubMed Central

    Beck, Kyongmin Sarah; Jeong, Soh Yong; Lee, Kyo Young; Chang, Kiyuk

    2016-01-01

    Eosinophilic myocarditis is a disease characterized by eosinophilic infiltration of the myocardium, consisting of acute necrotic stage, thrombotic stage, and fibrotic stage. Although T1 mapping has been increasingly used in various cardiac pathologies, there has been no report of T1 mapping in eosinophilic myocarditis. We report a case of 75-year-old female with eosinophilic myocarditis, whose cardiac magnetic resonance imaging included native T1 mapping, in which apical thrombi were distinctly seen as areas with decreased T1 values, next to areas of inflammation seen as increased T1 value in subendocardium. PMID:27826352

  8. Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

    PubMed

    Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

    2017-03-27

    Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

  9. Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats

    PubMed Central

    Arumugam, Somasundaram; Thandavarayan, Rajarajan A.; Veeraveedu, Punniyakoti T.; Ma, Meilei; Giridharan, Vijayasree V.; Arozal, Wawaimuli; Sari, Flori R.; Sukumaran, Vijayakumar; Lakshmanan, Arunprasath; Soetikno, Vivian; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi

    2012-01-01

    Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects. Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure. Hence we investigated the cardioprotective effect of mulberry leaf powder in rats with experimental autoimmune myocarditis. Eight-week-old Lewis rats immunized with cardiac myosin were fed with either normal chow or a diet containing 5% mulberry leaf powder and were examined on day 21. ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca2+ ATPase2, p22phox, receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH2-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats. These results may suggest that mulberry diet can preserve the cardiac function in experimental autoimmune myocarditis by modulating oxidative stress induced MAPK activation and further afford protection against endoplasmic reticulum stress mediated apoptosis. PMID:22448095

  10. Verapamil ameliorates the clinical and pathological course of murine myocarditis.

    PubMed Central

    Dong, R; Liu, P; Wee, L; Butany, J; Sole, M J

    1992-01-01

    The effects of the calcium channel blocking agent, verapamil, were studied in a murine model of viral myocarditis. Three groups of 8-wk-old DBA/2 mice (n = 25 each) were inoculated with 10 plaque-forming units of encephalomyocarditis virus and randomized to three treatment regimens. Group 1 mice received verapamil intraperitoneally (5 mg/kg per d) for 7 d before infection, followed by verapamil orally (mean dose of 3.5 mg/mouse per d) in drinking water during infection. Group 2 mice received only verapamil orally starting on day 4 after infection, coincident with peak viremia. Group 3 (infected control) received no verapamil in regular drinking water after viral inoculation. Additional control animals were studied in group 4 (n = 21), consisting of uninfected control animals receiving intraperitoneal and oral verapamil at doses identical to group 1, and in group 5 (n = 21), consisting of uninfected and untreated controls. Animals were randomly killed from each group (n = 7) at 7, 14, and 28 d after infection. Routine histology was performed blindly on an apical slice of each heart and semi-quantitatively graded for inflammation, necrosis, calcification, and fibrosis on a scale of 0-4. Digital planimetry was performed to measure the absolute and relative areas of inflammation and necrosis. The pretreated animals in group 1 showed marked reduction in inflammation and necrosis (score of 3.7 +/- 1.4 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05) and were indistinguishable from the posttreated group 2 mice (score of 4.0 +/- 1.5 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05). All the uninfected control animals (groups 4 and 5) showed no myocardial lesions whether treated with verapamil or not. Quantitative planimetry confirmed decreased inflammation and necrosis (2.0 +/- 3.3% in group 1 and 3.5 +/- 3.1% in group 2 vs. 21.9 +/- 22.6% in group 3 on day 14). Untreated infected hearts injected with liquid silicone rubber exhibited extensive areas of focal microvascular

  11. 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

  12. Unusual Presentation of Listerial Myocarditis and the Diagnostic Value of Cardiac Magnetic Resonance

    PubMed Central

    Ladani, Amit P.; Vaghasia, Nishit; Generalovich, Thomas

    2015-01-01

    Listeria monocytogenes is an infrequent cause of bacterial myocarditis. Myocarditis without evidence of endocarditis is even rarer. Management in such cases involves early diagnosis, antibiotic therapy, and emergency treatment of arrhythmias. We report the case of a 47-year-old man who presented with features of acute ST-segment-elevation myocardial infarction complicated by ventricular tachycardia that necessitated urgent electrical cardioversion. Contrast-enhanced cardiac magnetic resonance images revealed hypertrophy, necrosis, and a mass that was determined to be an abscess caused by L. monocytogenes. Antibiotic treatment led to resolution of the listerial myocarditis. In addition to reporting our patient's case, we discuss the comparative advantages of cardiac magnetic resonance versus transthoracic echocardiography in characterizing myocarditis, upon presentation and in follow-up evaluation. PMID:26175642

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

    PubMed

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

    2015-04-01

    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.

  14. A Case of Fulminant Myocarditis With Preceding Repeated Episodes of Congestive Heart Failure

    PubMed Central

    Tada, Yuko; Uto, Kenta; Wada, Hiroshi; Sakakura, Ken-ichi; Suzuki, Jun-ichi; Nishikawa, Toshio; Ako, Junya; Momomura, Shin-ichi

    2013-01-01

    We report a rare case of fulminant myocarditis that was considered to have smoldered for a few months before it finally exteriorized. An 80-year-old man had had two episodes of mild congestive heart failure with preserved ejection function (HFPEF) within 3 months before he was finally admitted for the treatment of rapidly progressive heart failure. Cardiac function deteriorated remarkably on the final admission. Extracorporeal cardiopulmonary support was used because of pump failure and conduction disability, however, the patient died on the 16th day. Endomyocardial biopsy revealed numerous inflammatory infiltrates in myocardium compatible with fulminant myocarditis. However, advanced fibrosis and increased number of B lymphocytes and plasma cells found in the present case were not typical for fulminant myocarditis. Considering several distinctive findings in clinical and laboratory findings together, two preceding HFPEF episodes were highly likely to be associated with myocarditis.

  15. Rare Presentation of Lupus Myocarditis With Acute Heart Failure-A Case Report.

    PubMed

    Malhotra, Gurveen; Chua, Serafin; Kodumuri, Vamsi; Sivaraman, Sivashankar; Ramdass, Priya

    Systemic lupus erythematosus is an autoimmune disease with diffuse organ involvement. The cardiac complications include pericarditis, myocarditis, pulmonary hypertension, coronary vasculitis, and Libman-Sacks endocarditis. Symptomatic lupus myocarditis presenting with left ventricular dysfunction, acute heart failure, and pulmonary edema, although rare, is a life-threatening complication. We report the occurrence of acute lupus myocarditis in a 38-year-old postpartum female who had a cesarean section a week before presentation for preeclampsia. Initially she was managed for pneumonia but later found to have acute pericarditis and myocarditis related to systemic lupus erythematosus. She had a complicated hospital course including acute respiratory failure and cardiogenic shock. She was started on pulse dose steroids besides the treatment for heart failure and had a dramatic improvement within days.

  16. Unusual presentation of listerial myocarditis and the diagnostic value of cardiac magnetic resonance.

    PubMed

    Ladani, Amit P; Biswas, Abhishek; Vaghasia, Nishit; Generalovich, Thomas

    2015-06-01

    Listeria monocytogenes is an infrequent cause of bacterial myocarditis. Myocarditis without evidence of endocarditis is even rarer. Management in such cases involves early diagnosis, antibiotic therapy, and emergency treatment of arrhythmias. We report the case of a 47-year-old man who presented with features of acute ST-segment-elevation myocardial infarction complicated by ventricular tachycardia that necessitated urgent electrical cardioversion. Contrast-enhanced cardiac magnetic resonance images revealed hypertrophy, necrosis, and a mass that was determined to be an abscess caused by L. monocytogenes. Antibiotic treatment led to resolution of the listerial myocarditis. In addition to reporting our patient's case, we discuss the comparative advantages of cardiac magnetic resonance versus transthoracic echocardiography in characterizing myocarditis, upon presentation and in follow-up evaluation.

  17. Near-fatal myocarditis complicating typhoid fever in a traveler returning from Nepal.

    PubMed

    Palombo, Michal; Margalit-Yehuda, Reuma; Leshem, Eyal; Sidi, Yechezkel; Schwartz, Eli

    2013-01-01

    We report a 27-year-old traveler who returned from Nepal suffering from typhoid fever. His disease was complicated by life-threatening myocarditis and ventricular fibrillation, a rare manifestation in travelers.

  18. Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma

    PubMed Central

    Thavendiranathan, P; Verhaert, D; Kendra, K L; Raman, S V

    2011-01-01

    High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T2 weighted imaging and T1 weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T1 and T2 weighted CMRI techniques to diagnose IL-2 induced myocarditis. PMID:21511746

  19. A Case of Fetal Parvovirus B19 Myocarditis That Caused Terminal Heart Failure

    PubMed Central

    2014-01-01

    Parvovirus B19 is a well-established cause of fetal anemia and nonimmune fetal hydrops in pregnancy. Fetal parvovirus infection can cause severe destruction of erythroid progenitor cells, resulting in fetal anemia, hydrops, and intrauterine death. However, viral myocarditis with subsequent heart failure is another possible mechanism for hydrops formation as viral infection of fetal myocardial cells has been reported in postmortem examinations. We herein report a case of fetal cardiomegaly and massive pericardial effusion secondary to myocarditis as a result of parvovirus B19 infection. The case developed hydrops as consequence of severe anemia and experienced terminal heart failure, which led to the fetus dying an intrauterine death at 22 weeks of gestation. This case demonstrates that there may be an association between myocarditis caused by intrauterine parvovirus B19 infection and a poor outcome. The presence of viral myocarditis may be the determining prognostic factor in that situation. PMID:25328731

  20. The organisms reported to cause infective myocarditis and pericarditis in England and Wales.

    PubMed

    Fairley, C K; Ryan, M; Wall, P G; Weinberg, J

    1996-05-01

    It is difficult to acquire an overall perspective of the range of organisms responsible for infective myocarditis or pericarditis, and their relative importance, as most studies have involved only case reports or case series of a single organism. This study analyses reports to the Communicable Disease Surveillance Centre, of the Public Health Laboratory Service. Reports where myocarditis or pericarditis was included as the main clinical features between 1990 and 1993 were studied. Between 1990 and 1993, 368 cases of myocarditis and/or pericarditis were reported to CDSC. Viruses were reported to cause 253 (69%) cases, bacteria were responsible for 49 (13%) cases, mycoplasma for 32 (9%) cases, chlamydia for 16 (4%) cases and Mycobacterium tuberculosis for nine (2%) cases. Infection with coxsackie B virus was most frequently associated with a mixed picture of myo/pericarditis, whereas influenzae virus was associated with pericarditis or myocarditis alone. This information will provide clinicians with details of the more likely pathogens responsible for these conditions.

  1. High cardiac troponin I plasma concentration in a calf with myocarditis

    PubMed Central

    Karapinar, Tolga; Dabak, Durrin Ozlem; Kuloglu, Tuncay; Bulut, Hakan

    2010-01-01

    A 15-day-old Brown Swiss calf, whose dam had suffered from foot-and-mouth disease, was presented with a history of depression and failure to suckle. The calf had an irregular cardiac rhythm and increased plasma cardiac troponin I (cTnI) detected with a commercial human immunoassay. The calf died the following day and myocarditis was detected. The cTnI assay may be useful in diagnosis of myocarditis in cattle. PMID:20592829

  2. [Endomyocardial biopsy should be performed in every patient with suspected myocarditis].

    PubMed

    Testolina, Martina; Schiavo, Alessandro; Marcolongo, Renzo; Iliceto, Sabino

    2015-10-01

    The diagnosis of myocarditis is difficult because there is no pathognomonic clinical presentation and the disease may mimic other non-inflammatory diseases. Thus, current classifications on cardiomyopathies (e.g., the World Health Organization and the International Society and Federation of Cardiology [WHO/ISFC], the European Society of Cardiology [ESC], and the 2013 Expert Myocarditis ESC Task Force) define myocarditis as an inflammatory disease of the myocardium, which is diagnosed on endomyocardial biopsy (EMB) based upon histological, immunological, immunohistochemical and molecular tools. This will identify etiology, and differentiate between infectious, mainly viral, and non-infectious, immune-mediated forms. The term "inflammatory cardiomyopathy" may be applied in biopsy-proven myocarditis with associated left, right or biventricular dysfunction. Myocarditis may resolve spontaneously, relapse or become chronic progressing to dilated cardiomyopathy, death or heart transplantation. The 2013 Myocarditis ESC Task Force consensus document recommends consideration of EMB and selective coronary angiography in all patients with clinically suspected myocarditis according to the Task Force criteria. It is recommended that EMB analysis includes not only histology (Dallas criteria), but also immunohistology and detection of the genome of infectious agents by molecular tools. EMB should be performed by expert teams. The rationale for this diagnostic effort is the availability of a wide range of immunosuppressive or immunomodulatory agents that, as shown in systemic extracardiac autoimmune disease and in many clinical studies, can be used in infection-negative myocarditis patients to stop or at least stabilize chronic cardiac tissue damage mediated by the immune system, and thus prevent fibrosis and progression to irreversible end-stage dilated cardiomyopathy.

  3. [Thiamine diphosphate level and metabolism in allergic myocarditis and treatment with peloid].

    PubMed

    Leus, N F

    1986-01-01

    Enzymatic systems involved in thiamin metabolism were studied in experimental allergic myocarditis. Development of inflammation in myocardium was accompanied by a distinct activation of thiamin pyrophosphatase which catalyzed the most important step responsible for deterioration of the coenzyme functions. The stabilizing effect of peloid on the intracellular pool and compartmentalization of thiamin in myocarditis involved equilibration of the anabolic and catabolic reactions in the coenzyme metabolism, mainly due to selective inhibition of the thiamin pyrophosphatase activity stimulated under these conditions.

  4. Ventricular aneurysms complicating coxsackievirus group B, types 1 and 4 murine myocarditis.

    PubMed

    El-Khatib, M R; Chason, J L; Lerner, A M

    1979-02-01

    Suckling Swiss Webster mice were inoculated with 10(4)TCD50 of coxsackieviruses, group B types 1 or 4. Virulent necrotizing myocarditis resulted in 185 infected mice. Of the latter group, three (14.3%) nurslings on the 17th and 23rd day after inoculations had left ventricular aneurysms postmortem. None of 61 concurrently matched control mice developed aneurysms. Ventricular aneurysm is a suggested but previously undocumented complication of murine, and possibly human necrotizing transmural coxsackievirus myocarditis.

  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

    2015-09-03

    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.

  6. Percutaneous cardioscopy of the left ventricle in patients with myocarditis

    NASA Astrophysics Data System (ADS)

    Uchida, Yasumi; Tomaru, Takanobu; Nakamura, Fumitaka; Oshima, Tomomitsu; Fujimori, Yoshiharu; Hirose, Junichi

    1992-08-01

    The morphology and function of the cardiac chambers have been evaluated clinically using cineventriculography, computed tomography, magnetic resonance imaging, and endomyocardial biopsy. Excluding the invasive technique of biopsy where tissue is actually removed, these other non-invasive techniques reveal only indirect evidence of endocardial and subendocardial pathology and, therefore, allow the potential for misdiagnosis from insufficient data. Fiberoptic examinations, as recently demonstrated in coronary, pulmonary, and peripheral vessels, allow direct observation of pathology otherwise unobtainable. Recently, similar techniques have been applied to examine the cardiac chambers of dogs and the right heart of humans. In this study, we examine the feasibility and safety of percutaneous fiberoptic cardioscopy of the left ventricle in patients with myocarditis.

  7. Fatal myocarditis-associated Bartonella quintana endocarditis: a case report

    PubMed Central

    2009-01-01

    Introduction Bartonella spp. infection is not rare and must be considered with great care in patients with suspected infective endocarditis, particularly if regular blood cultures remain sterile. Management of these infections requires knowledge of the identification and treatment of these bacteria. Case presentation A 50-year-old Senegalese man was admitted to our Department of Cardiac Surgery with a culture-negative endocarditis. Despite valvular surgery and adequate antibiotic treatment, recurrence of the endocarditis was observed on the prosthetic mitral valve. Heart failure required circulatory support. Weaning off the circulatory support could not be attempted owing to the absence of heart recovery. Bacteriological diagnosis of Bartonella quintana endocarditis was performed by molecular methods retrospectively after the death of the patient. Conclusions This case report underlines the severity and difficulty of the diagnosis of Bartonella quintana endocarditis. The clinical picture suggested possible Bartonella quintana associated myocarditis, a feature that should be considered in new cases. PMID:19830188

  8. Murine heart gene expression during acute Chagasic myocarditis

    PubMed Central

    Henao-Martínez, Andrés F.; Parra-Henao, Gabriel

    2015-01-01

    Chagas disease is transmitted by the parasite, Trypanosoma cruzi. Acute infection is characterized by acute myocarditis, although it is largely asymptomatic. Initial cardiac insult could be a determinant to the posterior development of chronic Chagasic cardiomyopathy, usually after 10 years in only approximately 30% of chronically infected patients. Herein, we characterized the acute gene expression profiling in heart tissue of two strains of mice infected with T. cruzi (tulahuen strain) at 4 weeks and their respective controls. Gene sequence data are available at NCBI under GEO accession number: GSE63847. The output of the genes expression suggests differences in involvement of protein kinase B (AKT), NCAM1, HLA-DRA, and ubiquitin C genes networks. These gene activation differences may correlate with myocardial contractility during the acute infection. PMID:26484182

  9. Eosinophil-derived IL-4 drives progression of myocarditis to inflammatory dilated cardiomyopathy.

    PubMed

    Diny, Nicola L; Baldeviano, G Christian; Talor, Monica V; Barin, Jobert G; Ong, SuFey; Bedja, Djahida; Hays, Allison G; Gilotra, Nisha A; Coppens, Isabelle; Rose, Noel R; Čiháková, Daniela

    2017-04-03

    Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. Patients with eosinophilia frequently develop cardiomyopathies. In this study, we used the experimental autoimmune myocarditis (EAM) model to determine the role of eosinophils in myocarditis and DCMi. Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi. Eosinophil-deficient ΔdblGATA1 mice, in contrast to WT mice, showed no signs of heart failure by echocardiography. Induction of EAM in hypereosinophilic IL-5Tg mice resulted in eosinophilic myocarditis with severe ventricular and atrial inflammation, which progressed to severe DCMi. This was not a direct effect of IL-5, as IL-5TgΔdblGATA1 mice were protected from DCMi, whereas IL-5(-/-) mice exhibited DCMi comparable with WT mice. Eosinophils drove progression to DCMi through their production of IL-4. Our experiments showed eosinophils were the major IL-4-expressing cell type in the heart during EAM, IL-4(-/-) mice were protected from DCMi like ΔdblGATA1 mice, and eosinophil-specific IL-4 deletion resulted in improved heart function. In conclusion, eosinophils drive progression of myocarditis to DCMi, cause severe DCMi when present in large numbers, and mediate this process through IL-4.

  10. An MRI myocarditis index defined by a PCA-based object recognition algorithm

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    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 myocarditis index, defined as the ratio between enhanced pixels, representing an inflammation, and the total pixels of myocardial muscle, is presented. 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 10 patients, referred to MRI with presumptive, clinical diagnosis of myocarditis. To assess intra- and interobserver variability, two observers blindly analyzed data related to the 10 patients by delimiting myocardial region and selecting enhanced pixels. After 5 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 = 0:94) between myocarditis indexes and the radiologists' clinical judgments. Furthermore, a good intraobserver and interobserver reproducibility was obtained.

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

    PubMed Central

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

    2015-01-01

    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

  12. 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.

  13. 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

  14. Variation in Pseudonocardia antibiotic defence helps govern parasite-induced morbidity in Acromyrmex leaf-cutting ants.

    PubMed

    Poulsen, Michael; Cafaro, Matías J; Erhardt, Daniel P; Little, Ainslie E F; Gerardo, Nicole M; Tebbets, Brad; Klein, Bruce S; Currie, Cameron R

    2010-08-01

    Host-parasite associations are potentially shaped by evolutionary reciprocal selection dynamics, in which parasites evolve to overcome host defences and hosts are selected to counteract these through the evolution of new defences. This is expected to result in variation in parasite-defence interactions, and the evolution of resistant parasites causing increased virulence. Fungus-growing ants maintain antibiotic-producing Pseudonocardia (Actinobacteria) that aid in protection against specialized parasites of the ants' fungal gardens, and current evidence indicates that both symbionts have been associated with the ants for millions of years. Here we examine the extent of variation in the defensive capabilities of the ant-actinobacterial association against Escovopsis (parasite-defence interactions), and evaluate how variation impacts colonies of fungus-growing ants. We focus on five species of Acromyrmex leaf-cutting ants, crossing 12 strains of Pseudonocardia with 12 strains of Escovopsis in a Petri plate bioassay experiment, and subsequently conduct subcolony infection experiments using resistant and non-resistant parasite strains. Diversity in parasite-defence interactions, including pairings where the parasites are resistant, suggests that chemical variation in the antibiotics produced by different actinobacterial strains are responsible for the observed variation in parasite susceptibility. By evaluating the role this variation plays during infection, we show that infection of ant subcolonies with resistant parasite strains results in significantly higher parasite-induced morbidity with respect to garden biomass loss. Our findings thus further establish the role of Pseudonocardia-derived antibiotics in helping defend the ants' fungus garden from the parasite Escovopsis, and provide evidence that small molecules can play important roles as antibiotics in a natural system.

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

    PubMed

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

    2015-10-01

    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.

  16. A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.

    PubMed

    Hirakawa, Hiroyuki; Zempo, Hirofumi; Ogawa, Masahito; Watanabe, Ryo; Suzuki, Jun-Ichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2015-01-01

    Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis.

  17. 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

  18. Cinnamaldehyde Derivatives Inhibited Coxsackievirus B3-Induced Viral Myocarditis.

    PubMed

    Li, Xiao-Qiang; Liu, Xiao-Xiao; Wang, Xue-Ying; Xie, Yan-Hua; Yang, Qian; Liu, Xin-Xin; Ding, Yuan-Yuan; Cao, Wei; Wang, Si-Wang

    2016-10-17

    The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

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

    PubMed Central

    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

  20. Cellular immune mechanisms in Coxsackievirus group B, type 3 induced myocarditis in Balb/C mice

    SciTech Connect

    Huber, S.A.; Job, L.P.

    1983-01-01

    Coxsackie B viruses are a common cause of viral myocarditis in humans. A murine model of the human disease has been developed using Coxsackievirus group B, type 3 and inbred Balb/c mice. Infection of T lymphocyte deficient mice does not result in significant myocarditis indicating the importance of T cells in this disease. The virus can be isolated from the hearts of T cell deficient and normal mice in equal concentrations. Virus elimination presumably is mediated by virus specific neutralizing antibody induced in both groups. T lymphocytes, natural killer cells and macrophage obtained from normal virus infected mice are all capable of lysing myofibers in vitro. Maximum lysis is obtained with the cytolytic T cells. When these cell populations or Coxsackievirus immune antibody were adoptively transferred into T lymphocyte deficient animals infected with the virus, only animals given T cells developed significant myocarditis.

  1. Clinical and pathologic findings of myocarditis in two families with dilated cardiomyopathy

    SciTech Connect

    O'Connell, J.B.; Fowles, R.E.; Robinson, J.A.; Subramanian, R.; Henkin, R.E.; Gunnar, R.M.

    1984-01-01

    The use of endomyocardial biopsy and gallium-67 scans in patients with dilated cardiomyopathy (DCM) has demonstrated the presence of myocardial inflammation in a subset of patients. A family with DCM was studied with endomyocardial biopsy and gallium-67 scanning; both identified the presence of myocarditis in the proband. Evaluation of histologic sections from deceased family members revealed myocarditis as the principal pathologic finding. This patient identified during life demonstrated a defect in suppressor lymphocytic function and improved with immunosuppressive therapy. A second family with DCM was discovered when postmortem examination of the proband and his father's heart showed myocarditis. A living sibling was identified with asymptomatic myocardial dysfunction. Longitudinal follow-up of surviving members of both families are in progress. This study indicates that thorough diagnostic evaluation of all patients with familial DCM should be pursued to identify subgroups with potentially treatable inflammation.

  2. Myocarditis in Mediterranean spotted fever: a case report and a review of the literature

    PubMed Central

    Siracusa, Lucia; Trizzino, Marcello; Gioè, Claudia; Giammanco, Anna; Cascio, Antonio

    2016-01-01

    Introduction: Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii. Most cases follow a benign course, with a case fatality rate of 3–7 % among hospitalized patients. Complications are described mainly in adult patients and include hepatic, renal, neurological and cardiac impairment. Among cardiac complications, pericarditis, myocarditis and heart rhythm disorders are uncommon complications in MSF and only a few cases have been reported in the literature. Case Presentation: We describe a new case of acute myocarditis complicating MSF in an immunocompetent adult patient without risk factors for severe MSF. Conclusion: Myocarditis is an uncommon but severe complication of MSF. Clinicians should be aware of a possible cardiac involvement in patients with MSF. Close monitoring and an aggressive approach are essential to reduce mortality rates of MSF. PMID:28348768

  3. Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis.

    PubMed Central

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

    1982-01-01

    Sera of 177 patients with acute myocarditis (10 coxsackie B 3/4, four influenza, four mumps, 15 cytomegalovirus, 144 undefined) were tested by indirect immunofluorescence for autoantibodies against heart and skeletal muscle and vital or air-dried adult cardiocytes. Antibody-dependent cytolysis, lymphocytotoxicity and antibody-dependent cellular lymphocytotoxicity were assessed using viral adult rat cardiocytes as target cells. Muscle-specific anti-sarcolemmal antibodies of the anti-myolemmal type--often associated with non-organ-specific anti-endothelial antibodies--were demonstrated in nine out of 10 patients with coxsackie B, in all patients with influenza and mumps and in 65 out of 144 patients with undefined myocarditis. In contrast, 13 out of 15 patients with cytomegalovirus myocarditis lacked anti-sarcolemmal antibodies but had low titre anti-inter fibrillary antibodies instead. In the presence of complement, anti-myolemmal antibodies induced cytolysis of vital cardiocytes, whereas hepatocytes remained unaffected. Titres of anti-myolemmal antibodies correlated with the degree of cardiocytolysis. The anti-myolemmal immunofluorescent pattern and the cytolytic serum activity could be absorbed with the respective viral antigens suggesting that these antibodies cross-react with moieties of the virus itself and may be both diagnostic and aetiological markers in acute viral myocarditis. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells could not be observed in our patients with myocarditis of proven viral aetiology. However, lymphocyte-mediated cytotoxicity was demonstrated in 10 ASA-positive and one ASA-negative patient with myocarditis of unknown origin. ASA-positive sera blocked lymphocytotoxicity in three of these patients. PMID:6288291

  4. Mast Cell Inhibition Attenuates Myocardial Damage, Adverse Remodeling and Dysfunction during Fulminant Myocarditis in Rat

    PubMed Central

    Mina, Yair; Rinkevich-Shop, Shunit; Konen, Eli; Goitein, Orly; Kushnir, Tammar; Epstein, Frederick H.; Feinberg, Micha S.; Leor, Jonathan; Landa-Rouben, Natalie

    2013-01-01

    Background Myocarditis is a life-threatening heart disease characterized by myocardial inflammation, necrosis and chronic fibrosis. While mast cell inhibition has been suggested to prevents fibrosis in rat myocarditis, little is known about its effectiveness in attenuating cardiac remodeling and dysfunction in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition will attenuate the inflammatory reaction and associated left ventricular (LV) remodeling and dysfunction after fulminant autoimmune myocarditis. Methods and Results To induce experimental autoimmune myocarditis, we immunized 30 rats with porcine cardiac myosin twice at a 7-day interval. On day 8 animals were randomized into treatment either with an intraperitoneal (IP) injection of 25mg/kg of cromolyn sodium (n=13), or an equivalent volume (~0.5ml IP) of normal saline (n=11). All animals were scanned by serial echocardiography studies before treatment (baseline echocardiogram) and after 20 days of cromolyn sodium (28 days after immunization). Furthermore, serial cardiac magnetic resonance was performed in a subgroup of 12 animals. After 20 days of treatment (28 days from first immunization), hearts were harvested for histopathological analysis. By echocardiography, cromolyn sodium prevented LV dilatation and attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts showed that cromolyn sodium reduced myocardial fibrosis, as well as the number and size of cardiac mast cells in the inflamed myocardium, compared with controls. Conclusions Our study suggests that mast cell inhibition with cromolyn sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This mechanism-based therapy is clinically relevant and could improve the outcome of patients at risk for inflammatory cardiomyopathy and heart failure. PMID:23172937

  5. The Protective Effects of Ivabradine in Preventing Progression from Viral Myocarditis to Dilated Cardiomyopathy

    PubMed Central

    Yue-Chun, Li; Guang-Yi, Chen; Li-Sha, Ge; Chao, Xing; Xinqiao, Tian; Cong, Lin; Xiao-Ya, Dai; Xiangjun, Yang

    2016-01-01

    To study the beneficial effects of ivabradine in dilated cardiomyopathy (DCM) mice, which evolved from coxsackievirus B3-induced chronic viral myocarditis. Four-to-five-week-old male balb/c mice were inoculated intraperitoneally with coxsackievirus B3 (Strain Nancy) on days 1, 14, and 28. The day of the first virus inoculation was defined as day 1. Thirty-five days later, the surviving chronic viral myocarditis mice were divided randomly into two groups, a treatment group and an untreated group. Ivabradine was administered by gavage for 30 consecutive days in the treatment group, and the untreated group was administered normal saline. Masson’s trichrome stain was used to evaluate the fibrosis degree in myocardial tissue. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), collagen I, collagen III and p38-MAPK signaling pathway proteins were detected by Western blot. Electrocardiogram was used to investigate the heart rate and rhythm. The thickness of the ventricular septum and left ventricular posterior wall, left ventricular end diastolic dimension, left ventricular end systolic dimension, left ventricular ejection fractions and fractional shortening were studied by echocardiography. Compared with the untreated chronic viral myocarditis mice, ivabradine significantly increased the survival rate, attenuated the myocardial lesions and fibrosis, improved the impairment of the left ventricular function, diminished the heart dimension, decreased the production of collagen I and collagen III, reduced the expression of the proinflammatory cytokines TNF-α, IL-1β, and IL-6, and lowered the production of phospho-p38 MAPK. The findings indicate the therapeutic effect of ivabradine in preventing the progression from viral myocarditis to DCM in mice with chronic viral myocarditis induced by coxsackievirus B3, is associated with inhibition of the p38 MAPK pathway, downregulated inflammatory responses and decreased

  6. The prostacyclin agonist iloprost aggravates fibrosis and enhances viral replication in enteroviral myocarditis by modulation of ERK signaling and increase of iNOS expression.

    PubMed

    Gruhle, Stefan; Sauter, Martina; Szalay, Gudrun; Ettischer, Nicole; Kandolf, Reinhard; Klingel, Karin

    2012-09-01

    Enteroviruses, such as coxsackieviruses of group B (CVB), are able to induce a chronic inflammation of the myocardium, which may finally lead to the loss of functional tissue, remodeling processes and the development of fibrosis, thus affecting the proper contractile function of the heart. In other fibrotic diseases like scleroderma, the prostacyclin agonist iloprost was found to inhibit the extracellular signal-regulated kinase (ERK, p44/42 MAPK), a mitogen-activated protein kinase, and consecutively, the expression of the profibrotic cytokine connective tissue growth factor (CTGF), thereby preventing the development of fibrosis. As CTGF was found to mediate fibrosis in chronic CVB3 myocarditis as well, we evaluated whether the in vivo application of iloprost is capable to reduce the development of ERK/CTGF-mediated fibrosis in enteroviral myocarditis. Unexpectedly, the application of iloprost resulted in a prolonged myocardial inflammation and an aggravated fibrosis and failed to reduce activation of ERK and expression of CTGF at later stages of the disease. In addition, viral replication was found to be increased in iloprost-treated mice. Notably, the expression of cardiac inducible nitric oxide synthase (iNOS), which is known to aggravate myocardial damage in CVB3-infected mice, was strongly enhanced by iloprost. Using cultivated bone marrow macrophages (BMM), we confirmed these results, proving that iloprost potentiates the expression of iNOS mRNA and protein in CVB3-infected and IFN-gamma stimulated BMM. In conclusion, these results suggest a critical reflection of the clinical use of iloprost, especially in patients possibly suffering from an enteroviral myocarditis.

  7. Characterization of a murine model of myocarditis induced by a reactivated coxsackievirus B3.

    PubMed Central

    Zhang, H.; Yousef, G. E.; Ouyang, X.; Archard, L. C.

    1994-01-01

    A transfection-reactivated Coxsackievirus B3 (rCVB3), from a full-length cDNA clone of Nancy strain, has previously been shown to be as cardiovirulent as the wild-type virus. Myocarditis induced by this genetically defined virus was compared in SWR mice with the traditional Balb/c model. SWR mice inoculated with rCVB3 developed more severe myocarditis but less severe pancreatitis than Balb/c mice. In contrast to the poor general health and frequent mortality of Balb/c mice following CVB3 infection, the body weight of SWR mice was not affected by CVB3 inoculation and no mortality occurred at titres of 10(2)-10(7) plaque forming units (PFU). Typical myocarditis developed in SWR mice 7 days post infection. Myocarditic foci consisting of necrotic myocardial fibres and mononuclear cell infiltrates resolved by day 30, similar to that observed in Balb/c. However, SWR mice were more sensitive to rCVB3-induced myocarditis than were Balb/c mice: mild myocarditis was induced (4/4) by as low as 10(2) PFU of the virus (ID50 < 10(1.5) PFU), and more severe myocarditis was seen at higher PFU of virus in a dose-dependent manner. The SWR model was tested with attenuated variants derived from cardiovirulent rCVB3. The ID50 for myocarditis was 10(7) PFU for a large plaque-size attenuant and 10(6) PFU for a minute plaque-size attenuant, indicating loss of cardiovirulence by a factor of more than 10(4)-10(5). rCVB3-induced SWR mouse is a sensitive and reliable model for myocarditis. It is useful in assessing the cardiovirulence of different CVB3 variants and evaluating the efficacies of anti-viral therapies. It will allow follow-up study after high dose infection with cardiovirulent rCVB3. Images Figure 1 Figure 2 p104-a Figure 4 p106-a Figure 5 PMID:8199011

  8. 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

  9. Time course of gene expression in rat experimental autoimmune myocarditis.

    PubMed

    Hanawa, Haruo; Abe, Satoru; Hayashi, Manabu; Yoshida, Tsuyoshi; Yoshida, Kaori; Shiono, Takaaki; Fuse, Koichi; Ito, Masahiro; Tachikawa, Hitoshi; Kashimura, Takeshi; Okura, Yuji; Kato, Kiminori; Kodama, Makoto; Maruyama, Seitaro; Yamamoto, Tadashi; Aizawa, Yoshifusa

    2002-12-01

    Genetic responses that characterize experimental autoimmune myocarditis (EAM) have not yet been determined. To investigate gene expression in the myocardium of EAM, absolute copy numbers of 44 mRNA species [calcium-handling proteins, contractile proteins, natriuretic peptides (NPs), cytokines, chemokines, growth factors, renin-angiotensin-aldosterone (RAA) system, endothelins (ETs) and extracellular matrix] in synthesized cDNA from a fixed quantity of total heart RNA were assessed using real-time reverse-transcriptase PCR at days 0, 14, 21 and 28 after immunization. alpha-Cardiac myosin showed a 26.3-fold decrease and beta-cardiac myosin a 3.75-fold increase at day 14. Atrial NP and brain NP increased 47.7- and 6.35-fold at days 21 and 14 respectively. Angiotensin II type 1 receptor, angiotensin-converting enzyme and ET1 increased 22.3-fold at day 21, 6.30-fold at day 21 and 16.8-fold at day 14 respectively. Aldosterone receptor decreased 2.15-fold at day 14, but aldosterone synthetase was detected only at days 14 and 21. Interleukin (IL)-2, IL-10, interferon-gamma and monocyte chemo-attractant protein-1 increased 9.08-fold at day 14, 398-fold at day 21, 43.1-fold at day 14 and 142-fold at day 14 respectively. Collagen type 3, collagen type 1 and fibronectin increased 34.6-, 1.74- and 44.4-fold respectively at day 21. Interestingly, osteopontin showed a 4540-fold increase and it was the highest mRNA of all at day 14. An isoform of cardiac myosin and NP are dramatically changed in EAM. RAA system and ET expressions are changed differently during the EAM time course. Cytokine, chemokine and extracellular matrix greatly increase and, in particular, large numbers of osteopontin mRNA are expressed in early EAM.

  10. Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model.

    PubMed

    Liu, Xuefei; Zhang, Xinghua; Ye, Lin; Yuan, Haitao

    2016-04-01

    Berberine, an alkaloid derivative extracted from numerous plants of the general Berberis and Coptis, has been reported to have immunomodulatory effects against immune-mediated disorders in emerging studies. In this study, the effects of berberine and its underlying molecular mechanisms were investigated from the myosin-induced myocardial injury in rats. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM), treated with berberine and specific JAK inhibitor AG490 as a positive control. Our data showed that both berberine and AG490 significantly reduced the impaired cardiac function and the pathophysiological severity, impeded high levels of anti-cardiac myosin antibody of EAM rats. Th17 and Th1 cells as well as their cytokines IL-17 and IFN-γ were up-regulated in EAM. However, the excessive increase of Th17/Th1 responses was restored by berberine and AG490. We also examined the expression level of phosphorylated proteins of JAK-STAT pathway which has a key role in the Th17 and Th1 lineage commitment. The phosphorylated (p)-STAT1,STAT3 and STAT4 increased significantly in EAM, while berberine notably attenuated their excessive expression. This effect of berberine was equivalent to that of AG490 blockade. Our current study demonstrated that berberine could ameliorate EAM and the underling mechanisms may be due to the fact that berberine differentially modulates the activities of p-STAT1, p-STAT3 and p-STAT4 to suppress Th17 and Th1 cell differentiation.

  11. 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.

  12. In vivo delivery of interleukin-35 relieves coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells.

    PubMed

    Hu, Yadong; Dong, Chunsheng; Yue, Yan; Xiong, Sidong

    2014-09-01

    Interleukin (IL)-35 is a new member of the IL-12 cytokine family. The suppressive role of IL-35 in the immune response to parasitic and bacterial infections and in autoimmunity has been demonstrated in terms of its anti-inflammatory properties. However, the functional role of IL-35 in viral myocarditis has not been investigated. In this study, IL-35 expression was measured in heart tissues with coxsackievirus B3 (CVB3)-induced myocarditis. It was significantly reduced in the late stage of viral infection and correlated negatively with disease severity. To examine the therapeutic role of IL-35 in viral myocarditis, an IL-35-expressing plasmid (pIL-35-FC) was packaged with polyethyleneimine and delivered intraperitoneally to BALB/c male mice before and after CVB3 infection. The severity of myocarditis was assessed 7 days after infection. The in vivo delivery of IL-35 significantly ameliorated the severity of viral myocarditis, reflected in an increased survival rate and increased bodyweights, and reduced serum creatine kinase (CK) and CK-MB activities, cardiac pathological scores, and viral replication. We also show that the overexpression of IL-35 reduced splenic Th17 cells and Th17-related proinflammatory cytokines in heart tissues. In conclusion, our data indicate that IL-35 effectively protects the myocardium from the pathogenesis of CVB3-induced viral myocarditis, which may be attributable to reduced Th17 production. This suggests that supplementation with IL-35 could be a novel therapeutic treatment for viral myocarditis.

  13. High Frequency of Detection by PCR of Viral Nucleic Acid in The Blood of Infants Presenting with Clinical Myocarditis.

    PubMed

    Simpson, Kathleen E; Storch, Gregory A; Lee, Caroline K; Ward, Kent E; Danon, Saar; Simon, Catherine M; Delaney, Jeffrey W; Tong, Alan; Canter, Charles E

    2016-02-01

    Specific viruses are associated with pediatric myocarditis, but the prevalence of viral DNAemia detected by blood polymerase chain reaction (PCR) is unknown. We evaluated the prevalence of known cardiotropic viruses (enterovirus, adenovirus, human herpesvirus 6, and parvovirus B19) in children with clinical myocarditis (n = 21). Results were compared to pediatric controls with similar viral PCR testing. The majority of positive PCR (89 %) was noted in children ≤12 months of age at diagnosis compared to older children. Infant myocarditis patients (8/10) had increased the prevalence of PCR positivity compared to infant pediatric controls (4/114) (p < 0.0001). Other than age, patient characteristics at diagnosis were similar between PCR-positive and PCR-negative patients. Both PCR-negative myocarditis infants had clinical recovery at follow-up. Of the PCR-positive myocarditis infants, 4 had clinical recovery, 2 developed chronic cardiomyopathy, 1 underwent heart transplant, and 1 died. Infants with clinical myocarditis have a high rate of blood viral positivity, which is higher compared to older children with myocarditis and healthy infant controls. Age-related differences in PCR positivity may be due to differences in host and/or virus characteristics. Our findings suggest that viral blood PCR may be a useful diagnostic tool and identify patients who would potentially benefit from virus-specific therapy.

  14. Transmissible endoplasmic reticulum stress from myocardiocytes to macrophages is pivotal for the pathogenesis of CVB3-induced viral myocarditis

    PubMed Central

    Zhang, Hui; Yue, Yan; Sun, Tianle; Wu, Xuejie; Xiong, Sidong

    2017-01-01

    Infiltrating macrophages have been proven as a pivotal pathological inflammatory cell subset in coxsackievirus B3 (CVB3) induced viral myocarditis. However, the mechanisms underlying the initiation and promotion of macrophage pro-inflammatory responses are still blur. We previously reported that cardiac ER stress contributed to CVB3-induced myocarditis by augmenting inflammation. In this study, we focused on the influence of ER stress on the macrophage inflammatory responses in the viral myocarditis. We found that ER stress was robustly induced in the cardiac infiltrating macrophages from CVB3-infected mice, and robustly facilitated the production of pro-inflammatory cytokines (IL-6, IL-12, MCP-1 and IP-10). Consistently, adoptive transfer of ER stressed macrophages significantly worsened the viral myocarditis; while transfer of ER stress-inhibited macrophages obviously alleviated the myocarditis. To our surprise, this significantly activated ER stress was not directly caused by the virus stimulation, but was transferred from the CVB3-infected, ER stressed myocardiocytes via soluble molecules in a TLR2, 4-independent way. In the present study, we reported that the transmissible ER stress from the infected myocardiocytes to macrophages could augment the pro-inflammatory responses and promoted the pathogenesis of viral myocarditis. Blocking ER stress transmission, instead of inhibiting its initiation, may represent novel therapeutic strategies against viral myocarditis. PMID:28176833

  15. 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

  16. Percutaneous extracorporeal membrane oxygenation for cardiogenic shock due to acute fulminant myocarditis.

    PubMed

    Fayssoil, Abdallah; Nardi, Olivier; Orlikowski, David; Combes, Alain; Chastre, Jean; Annane, Djillali

    2010-02-01

    Percutaneous extracorporeal membrane oxygenation is an invasive technique that provides emergent circulatory support for patients with cardiogenic shock. We report a favorable outcome of an acute fulminant myocarditis in a 25-year-old myasthenia patient with cardiogenic shock supported by percutaneous extracorporeal membrane oxygenation.

  17. Brugada pattern in toxic myocarditis due to severe aluminum phosphide poisoning.

    PubMed

    Nayyar, Sachin; Nair, Mohan

    2009-11-01

    Brugada pattern electrocardiogram (ECG) unmasking can occur due to various drugs. There are old reports of the acute infarction pattern in aluminum phosphide (rodenticide)-related toxic myocarditis. The given case illustrates the Brugada pattern and various other ECG abnormalities in a patient with this poisoning. The old reported cases of the acute infarction pattern are also likely the Brugada pattern.

  18. Immune-mediated and autoimmune myocarditis: clinical presentation, diagnosis and management.

    PubMed

    Caforio, Alida L P; Marcolongo, Renzo; Jahns, Roland; Fu, Michael; Felix, Stephan B; Iliceto, S

    2013-11-01

    According to the current WHO classification of cardiomyopathies, myocarditis is an inflammatory disease of the myocardium and is diagnosed by endomyocardial biopsy using established histological, immunological and immunohistochemical criteria; it may be idiopathic, infectious or autoimmune and may heal or lead to dilated cardiomyopathy (DCM). DCM is characterized by dilatation and impaired contraction of the left or both ventricles; it may be idiopathic, familial/genetic, viral and/or immune. The diagnosis of DCM requires exclusion of known, specific causes of heart failure, including coronary artery disease. On endomyocardial biopsy, there is myocyte loss, compensatory hypertrophy, fibrous tissue and immunohistochemical findings consistent with chronic inflammation (myocarditis) in 30-40 % of cases. In a patient subset, myocarditis and DCM represent the acute and chronic stages of an inflammatory disease of the myocardium, which can be viral, post-infectious immune or primarily organ-specific autoimmune. Here, we review the clinical presentation, etiopathogenetic diagnostic criteria, and management of immune-mediated and autoimmune myocarditis.

  19. Myocarditis, Disseminated Infection, and Early Viral Persistence Following Experimental Coxsackievirus B Infection of Cynomolgus Monkeys

    PubMed Central

    Cammock, Cheryl E.; Halnon, Nancy J.; Skoczylas, Jill; Blanchard, James; Bohm, Rudolf; Miller, Christopher J.; Lai, Chi; Krogstad, Paul A.

    2013-01-01

    Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis. PMID:24040287

  20. 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.

  1. ST-segment elevation mimicking myocardial infarction after hydrochloric acid ingestion: Acute caustic myocarditis.

    PubMed

    San Antonio, Rodolfo; Pujol López, Margarida; Perea, Rosario Jesús; Sabaté, Manel

    ST-segment elevation after hydrochloric acid ingestion has barely been described in the literature, without identification of its causal mechanism. We hypothesize that acute caustic myocarditis, by direct contact between necrotic upper gastrointestinal tract and pericardium may induce the ECG findings.

  2. Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis.

    PubMed

    Li, Min; Yan, Kepeng; Wei, Lin; Yang, Jie; Lu, Chenyu; Xiong, Fei; Zheng, Chunfu; Xu, Wei

    2015-11-01

    The host Zinc finger antiviral protein (ZAP) has been reported exhibiting antiviral activity against positive-stranded RNA viruses (Togaviridae), negative-stranded RNA viruses (Filoviridae) and retroviruses (Retroviridae). However, whether ZAP restricts the infection of enterovirus and the development of enterovirus mediated disease remains unknown. Here, we reported the antiviral properties of ZAP against coxsackievirus B3 (CVB3), a single-stranded RNA virus of the Enterovirus genus within the Picornaviridae as a major causative agent of viral myocarditis (VMC). We found that the expression of ZAP was significantly induced after CVB3 infection in heart tissues of VMC mice. ZAP potently inhibited CVB3 replication in cells after infection, while overexpression of ZAP in mice significantly increased the resistance to CVB3 replication and viral myocarditis by significantly reducing cardiac inflammatory cytokine production. The ZAP-responsive elements (ZREs) were mapped to the 3'UTR and 5'UTR of viral RNA. Taken together, ZAP confers resistance to CVB3 infection via directly targeting viral RNA and protects mice from acute myocarditis by suppressing viral replication and cardiac inflammatory cytokine production. Our finding further expands ZAP's range of viral targets, and suggests ZAP as a potential therapeutic target for viral myocarditis caused by CVB3.

  3. 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.

  4. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    PubMed Central

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  5. Acute myocarditis with normal wall motion detected with 2D speckle tracking echocardiography

    PubMed Central

    Niel, Johannes; Aichinger, Josef; Ebner, Christian

    2016-01-01

    Summary We present the case of a 26-year-old male with acute tonsillitis who was referred for coronary angiography because of chest pain, elevated cardiac biomarkers, and biphasic T waves. The patient had no cardiovascular risk factors. Echocardiography showed no wall motion abnormalities and no pericardial effusion. 2D speckle tracking revealed distinct decreased regional peak longitudinal systolic strain in the lateral and posterior walls. Ischemic disease was extremely unlikely in view of his young age, negative family history regarding coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram. Coronary angiography was deferred as myocarditis was suspected. To confirm the diagnosis, cardiac magnetic resonance tomography (MRT) was performed, showing subepicardial delayed hyperenhancement in the lateral and posterior walls correlating closely with the strain pattern obtained by 2D speckle tracking echocardiography. With a working diagnosis of acute myocarditis associated with acute tonsillitis, we prescribed antibiotics and nonsteroidal anti-inflammatory drugs. The patient’s clinical signs resolved along with normalization of serum creatine kinase (CK) levels, and the patient was discharged on the third day after admission. Learning points Acute myocarditis can mimic acute coronary syndromes.Conventional 2D echocardiography lacks specific features for detection of subtle regional wall motion abnormalities.2D speckle tracking expands the scope of echocardiography in identifying myocardial dysfunction derived from edema in acute myocarditis. PMID:27249814

  6. 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...

  7. 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

  8. 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

  9. Successful clearance of human parainfluenza virus type 2 viraemia with intravenous ribavirin and immunoglobulin in a patient with acute myocarditis.

    PubMed

    Kalimuddin, Shirin; Sessions, October M; Hou, Yan'An; Ooi, Eng Eong; Sim, David; Cumaraswamy, Sivathasan; Tan, Teing Ee; Lai, Siang Hui; Low, Chian Yong

    2013-01-01

    Human parainfluenza virus (HPIV) infection as an aetiology of acute viral myocarditis is rare, with only few cases reported in the literature to date. Here we report a case of fulminant HPIV-2 myocarditis in a 47 year-old man with viraemia who was successfully treated with intravenous ribavirin and intravenous immunoglobulin (IVIG). There are currently no recommendations on the treatment of HPIV myocarditis. We are, to our knowledge, the first to report a patient with a documented HPIV-2 viraemia that subsequently cleared after the initiation of antiviral therapy. Although it is difficult to definitively attribute the patient's clinical improvement to ribavirin or IVIG alone, our case does suggest that clinicians may wish to consider initiating ribavirin and IVIG in patients with HPIV myocarditis and persistent viraemia not responding to supportive measures alone.

  10. Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis

    PubMed Central

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

    2016-01-01

    Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4+ T cells in AVMC patients and healthy controls. After transfecting purified CD4+ T cells with CVB3 in vitro, the Th17 cell frequency, IL-17 secretion, and RORγT synthesis were increased while the Nup98 levels were decreased. Furthermore, down-regulating Nup98 expression by siRNA-Nup98 in CD4+ T cells resulted in the elevated Th17 cell frequency and IL-17 secretion, along with enhanced levels of RORγT, dissociative p300/CBP, and acetylated Stat3. Up-regulation of Nup98 expression by pcDNA3.1-Nup98 showed the opposite effects. Our results suggested that CVB3 directly induced CD4+ T cell differentiation into Th17 cells by inhibiting Nup98 expression, representing a therapeutic target in AVMC. PMID:28018858

  11. Noninvasive Imaging of Myocardial Inflammation in Myocarditis using 68Ga-tagged Mannosylated Human Serum Albumin Positron Emission Tomography

    PubMed Central

    Lee, Seung-Pyo; Im, Hyung-Jun; Kang, Shinae; Chung, Seock-Jin; Cho, Ye Seul; Kang, Hyejeong; Park, Ho Seon; Hwang, Do-Won; Park, Jun-Bean; Paeng, Jin-Chul; Cheon, Gi-Jeong; Lee, Yun-Sang; Jeong, Jae Min; Kim, Yong-Jin

    2017-01-01

    The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with 68Ga. The efficacy of 68Ga-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model. A significant number of mannose receptor-positive inflammatory cells infiltrated the myocardium in both human and rat myocarditis tissue. 68Ga-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31~0.33) for normal versus 1.02 (0.86~1.06) for myocarditis (median (range), SUV); n=4~6 per group, p-value=0.01). 68Ga-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42~3.40) for normal versus 4.18 (3.43~6.15) for myocarditis (median (range), average standard uptake value ratio against paraspinal muscle); n=6 per group, p-value<0.01), which was downregulated in rats with cyclosporine-A treated myocarditis (3.69 (2.59~3.86) for myocarditis versus 2.28 (1.76~2.60) for cyclosporine-A treated myocarditis; n=6 per group, p-value<0.01). The specificity of the tracer was verified by administration of excess non-labeled MSA. 68Ga-NOTA-MSA uptake was significantly enhanced earlier in the evolution of myocarditis before any signs of inflammation could be seen on echocardiography. These results demonstrate the potential utility of visualizing infiltration of mannose receptor-positive macrophages with 68Ga-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis. PMID:28042344

  12. Panax Notoginseng Saponins Ameliorates Coxsackievirus B3-Induced Myocarditis by Activating the Cystathionine-γ-Lyase/Hydrogen Sulfide Pathway.

    PubMed

    Pan, Lulu; Zhang, Yuanhai; Lu, Jiacheng; Geng, Zhimin; Jia, Lianhong; Rong, Xing; Wang, Zhenquan; Zhao, Qifeng; Wu, Rongzhou; Chu, Maoping; Zhang, Chunxiang

    2015-12-01

    This study is to determine the therapeutic effects of Panax notoginseng saponins (PNSs) on coxsackievirus B3 (CVB3)-induced myocarditis, and whether cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S) pathway is involved. Mouse model of myocarditis was induced by CVB3 infection, and the mice were subjected to vehicle (saline) or drug treatments (sodium bisulfide (NaHS), propargylglycine (PAG), or PNSs). The results showed that there were inflammatory cell infiltrations, interstitial edemas, and elevated inflammatory cytokines, in CVB3-induced myocarditis. PAG administration increased, whereas NaHS treatment decreased the severity of the myocarditis. PNS treatment dramatically alleviated these myocardial injuries and decreased the viral messenger RNA (mRNA) expression by the enhanced expression of CSE/H2S pathway. Moreover, the therapeutic effects of PNSs on myocarditis were stronger than those of NaHS. Finally, the effect of PNSs on CSE/H2S pathway and cardiac cell protection were verified in cultured cardiac cells. PNSs may be a promising medication for viral myocarditis therapy.

  13. Myocarditis in a traveler returning from the Dominican Republic: an unusual presentation of dengue fever.

    PubMed

    Zea, Diego; Foley, Kimberly; Carey, Jeanne

    2014-07-01

    Myocarditis is an uncommon manifestation of dengue fever. We describe a case of a 69-year-old Hispanic male who presented to an emergency room in New York City 3 days after returning from a trip to the Dominican Republic complaining of a 1-day history of chest pain and fever. His first electrocardiogram showed a new left bundle branch block, and initial cardiac enzymes included troponin of 5 ng/dL, creatine kinase-MB of 9 ng/mL, and myoglobin of 234 ng/mL. Dengue fever antibodies were found to be elevated: immunoglobulin M (IgM) titer was 2.48 (reference range < 0.9), and immunoglobulin G (IgG) titer was 4.26 (reference range < 0.9). The patient was diagnosed with myocarditis caused by dengue fever. He improved after 1 week with conservative management in a telemetry unit and was discharged home.

  14. [A case of eosinophilic myositis presenting with myocarditis and cardiac embolism].

    PubMed

    Madokoro, Yuta; Kato, Hideki; Yuasa, Hiroyuki; Ootaka, Naoya; Mori, Yoshiko; Mitake, Shigehisa

    2015-01-01

    We report the case of a 72-year-old male who presented with the complaints of muscular pain and weakness. The patient showed marked eosinophilia, elevated levels of myogenic enzymes and pathological abnormalities including eosinophil infiltration obtained from the muscle biopsy. Based on these findings, the patient was diagnosed with eosinophilic myositis. During follow-up, left ventricular wall motion abnormalities with transient electrocardiographic abnormalities were identified; these were believed to be concurrent with eosinophilic myocarditis. Further, notable complications included cardiogenic cerebral embolism. Eosinophilic myositis has been found to cause a wide spectrum of complications. Our findings indicate that in cases of suspected eosinophilic myositis, it is crucial to identify myocarditis immediately and to select an anticoagulant therapy to prevent cerebral embolism.

  15. Interleukin-1 Receptor Blockade Rescues Myocarditis-Associated End-Stage Heart Failure

    PubMed Central

    Cavalli, Giulio; Foppoli, Marco; Cabrini, Luca; Dinarello, Charles A.; Tresoldi, Moreno; Dagna, Lorenzo

    2017-01-01

    Support measures currently represent the mainstay of treatment for fulminant myocarditis, while effective and safe anti-inflammatory therapies remain an unmet clinical need. However, clinical and experimental evidence indicates that inhibition of the pro-inflammatory cytokine interleukin 1 (IL-1) is effective against both myocardial inflammation and contractile dysfunction. We thus evaluated treatment with the IL-1 receptor antagonist anakinra in a case of heart failure secondary to fulminant myocarditis. A 65-year-old man with T cell lymphoma developed fulminant myocarditis presenting with severe biventricular failure and cardiogenic shock requiring admittance to the intensive care unit and mechanical circulatory and respiratory support. Specifically, acute heart failure and cardiogenic shock were initially treated with non-invasive ventilation and mechanical circulatory support with an intra-aortic balloon pump. Nevertheless, cardiac function deteriorated further, and there were no signs of improvement. Treatment with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, was started at a standard subcutaneous dose of 100 mg/day. We observed a dramatic clinical improvement within 24 h of initiating anakinra. Prompt, progressive amelioration of cardiac function allowed weaning from mechanical circulatory and respiratory support within 72 h of anakinra administration. Recent studies point at inhibition of IL-1 activity as an attractive treatment option for both myocardial inflammation and contractile dysfunction. Furthermore, IL-1 receptor blockade with anakinra is characterized by an extremely rapid onset of action and remarkable safety and may thus be suitable for the treatment of patients critically ill with myocarditis. PMID:28232838

  16. The Role of Protease-Activated Receptors for the Development of Myocarditis: Possible Therapeutic Implications.

    PubMed

    Weithauser, Alice; Witkowski, Marco; Rauch, Ursula

    2016-01-01

    Protease-activated receptors (PARs) are a unique group of four G-protein coupled receptors. They are widely expressed within the cardiovascular system and the heart. PARs are activated via cleavage by serine proteases. In vitro and in vivo studies showed that the activation of PAR1 and PAR2 plays a crucial role in virus induced inflammatory diseases. The receptors enable cells to recognize pathogen-derived changes in the extracellular environment. An infection with Coxsackie-virus B3 (CVB3) can cause myocarditis. Recent studies have been shown that PAR1 signaling enhanced the antiviral innate immune response via interferon β (IFNβ) and thus limited the virus replication and cardiac damage. In contrast, PAR2 signaling decreased the antiviral innate immune response via IFNβ und thus increased the virus replication, which caused severe myocarditis. Along with CVB3 other viruses such as influenza A virus (IAV) and herpes simplex virus (HSV) can induce myocarditis. The role of PAR signaling in IAV infections is contrarily discussed. During HSV infections PARs facilitate the virus infection of the host cell. These studies show that PARs might be interesting drug targets for the treatment of virus infections and inflammatory heart diseases. First studies with PAR agonists, antagonists, and serine protease inhibitors have been conducted in mice. The inhibition of thrombin the main PAR1 activating protease decreased the IFNβ response and increased the virus replication in CVB3-induced myocarditis. This indicates that further studies with direct PAR agonists and antagonists are needed to determine whether PARs are useful drug targets for the therapy of virus-induced heart diseases.

  17. Transformation of myocarditis and inflammatory cardiomyopathy to idiopathic dilated cardiomyopathy: facts and fiction.

    PubMed

    Figulla, Hans R

    2004-05-01

    There is broad evidence that enteroviruses and adenoviruses can induce an acute inflammation of the myocardium without cardiac dysfunction (i.e. myocarditis) or with cardiac dysfunction (i.e. inflammatory cardiomyopathy) that can transform to a virus-negative dilated cardiomyopathy. In the adult patient neither other viruses (parvo-B 19 virus, hepatitis C virus, cytomegalovirus) nor post-infection autoimmunity are likely to induce idiopathic dilated cardiomyopathy.

  18. 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.

  19. Coxsackie Myocarditis and Hepatitis with Reactivated Epstein-Bar Virus (EBV): A Case Report

    PubMed Central

    Atti, Varunsiri; Anderson, Nathan M.; Day, Mathew B.

    2017-01-01

    Patient: Female, 57 Final Diagnosis: Coxsackie myocarditis and hepatitis Symptoms: Fever • headache • general malaise • sob. Medication: — Clinical Procedure: Echocardiography • cardiac MRI Specialty: Cardiology Objective: Unusual clinical course Background: Myocarditis, defined as inflammation of myocardial tissue of the heart, is an uncommon cardiac presentation and is due to a variety of causes. It affects 1% of the US population, 50% of which is caused by coxsackie B virus. Cardiac tissue is the prime target, and destruction of myocardium results in cardiac failure with fluid overload. Case Report: Our patient was a 57-year-old woman with fever, headache, neck pain, and generalized malaise. Her white blood cell count was 13×103 cells/mm3. Interestingly, lumbar puncture ruled out meningitis. An echocardiogram to evaluate elevated troponin revealed an ejection fraction of 30% with severe left ventricular global hypokinesis without valvular vegetations consistent with new-onset systolic heart failure. Cardiac MRI showed a small pericardial effusion with bilateral pleural effusion. As she continued to be febrile, a viral panel was ordered, revealing coxsackie B4 antibody titer of 1: 640 (reference: >1: 32 indicates recent infection) with positive Epstein-Barr virus deoxyribonucleic acid by PCR, consistent with viral myocarditis. Conclusions: Coxsackie B virus myocarditis is rarely recognized and reported by the general internist in clinical practice, so we would like present our experience with an interesting clinical presentation of the viral prodrome. An estimated 95% people in the US are infected with Epstein-Barr virus by adulthood, but it remains dormant in memory B lymphocytes. Recirculation of these B cells in lymphoid tissue stimulated by antigens, which in our case is coxsackie B virus; they differentiate into plasma cells, and the production of Z Epstein-Barr replication activator protein (ZEBRA) increases viral replication, thus explaining the

  20. Idiopathic giant cell myocarditis--a distinctive clinico-pathological entity.

    PubMed Central

    Davies, M J; Pomerance, A; Teare, R D

    1975-01-01

    Eleven cases of idiopathic giant cell myocarditis are described, The pathological features are unmistakable with serpiginous areas of myocardial necrosis, at the margins of which giant cells can be seen on histological examination. The aetiology of the condition remains obscure but associated pathology suggests that altered immunity may be a factor. The rapid clinical course is, however, highly suggestive of an infective cause though none has been found. Images PMID:1122272

  1. Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

    PubMed

    Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

    2016-04-01

    This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

  2. Myocardial dysfunction in an experimental model of autoimmune myocarditis: role of IFN-gamma.

    PubMed

    Pérez Leirós, C; Goren, N; Sterin-Borda, L; Borda, E S

    1997-01-01

    Experimental autoimmune myocarditis obtained in mice by immunization with heart antigens is characterized by the presence of lymphomononuclear infiltrates in atria and ventricles. Here we show the ability of soluble factors released by immune cells from mice immunized with heart antigens to decrease heart contractility in a similar way to a muscarinic agonist. These effects appear to be mediated by IFN-gamma since all of them could be blocked by an anti-IFN-gamma monoclonal antibody. Moreover, the negative inotropic effect induced by immune cell-conditioned media was blocked by atropine, confirming previous findings that IFN acts as a muscarinic agonist on isolated atria. The role of locally released cytokines and especially of IFN-gamma was also evaluated in infiltrated autoimmune myocarditis hearts; thus, the addition of monoclonal anti-IFN-gamma antibody reversed the decreased contractility characteristics of this model. We conclude that IFN released both systemically and locally by autoreactive T cells may contribute to the impaired cardiac function in this experimental model of autoimmune myocarditis.

  3. 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.

  4. Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

    PubMed

    Chiale, P A; Przybylski, J; Laiño, R A; Halpern, M S; Sánchez, R A; Gabrieli, A; Elizari, M V; Rosenbaum, M B

    1982-01-01

    Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

  5. The diagnostic value of transthoracic echocardiography for eosinophilic myocarditis: A single center experience from China.

    PubMed

    Xie, Mingxing; Cheng, Tsung O; Fei, Hongwen; Ren, Pingping; He, Yale; Wang, Xinfang; Lu, Qing; Han, Wei; Li, Ke; Li, Ling; Yang, Yali; Chen, Oudi

    2015-12-15

    The aim of this study is to explore the value of transthoracic echocardiography in the diagnosis of eosinophilic myocarditis. The echocardiographic characteristics of nine patients with eosinophilic myocarditis in our hospital between January 2004 and January 2012 were retrospectively reviewed. In our study, four of the nine patients were diagnosed to have small pericardial effusion. The obliteration of the apical cavity was observed in five of the nine patients. There were six patients with both mitral and tricuspid regurgitation, one patient with only mitral regurgitation, and one patient with only tricuspid regurgitation. Transthoracic echocardiography showed that the diameters of the left and right atria were both increased in eight of the nine patients. The diameter of the left ventricle was increased in five patients, and the right ventricular diameter was increased in four patients. The left ventricular ejection fraction was decreased in two of the nine patients. Five of the nine patients had pulmonary hypertension, and one patient had severe pulmonary hypertension. Transthoracic echocardiography is the primary method for the diagnosis of eosinophilic myocarditis and is also useful in follow-up of the disease.

  6. A case report and literature review of Churg–Strauss syndrome presenting with myocarditis

    PubMed Central

    Qiao, Lu; Gao, Dengfeng

    2016-01-01

    Abstract Background: Churg–Strauss syndrome (CSS) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. Case summary: Here we report a case of CSS presenting with acute myocarditis and heart failure and review the literature on CSS with cardiac involvement. A 59-year-old man with general fatigue, numbness of limbs, and a 2-year history of asthma was admitted to the department of orthopedics. Eosinophilia, history of asthma, lung infiltrates, peripheral neurological damage, and myocarditis suggested the diagnosis of CSS. Transthoracic echocardiography revealed a dilated hypokinetic left ventricle (left ventricular ejection fraction ∼40%) with mild segmental abnormalities in the septal and apical segments. Conclusion: By reviewing the present case reports, we concluded that (1) the younger age of CSS, the greater occurrence rate of complicating myocarditis and the poorer prognosis; (2) female CSS patients are older than male patients; (3) patients with cardiac involvement usually have a history of severe asthma; (4) markedly increased eosinophil count suggests a potential diagnosis of CSS (when the count increases to 20% of white blood cell counts or 8.1 × 109/L, eosinophils start to infiltrate into myocardium); and (5) negative ANCA status is associated with heart disease in CSS. PMID:28002315

  7. Two case reports of severe myocarditis associated with the initiation of dolutegravir treatment in HIV patients

    PubMed Central

    Mahlab-Guri, Keren; Asher, Ilan; Rosenberg-Bezalel, Shira; Elbirt, Daniel; Burke, Michael; Sthoeger, Zev M.

    2016-01-01

    Abstract Rationale: The integrase inhibitor dolutegravir is now recommended as first-line treatment for HIV. A single case of myocarditis after treatment with dolutegravir was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis that occurred shortly after the initiation of dolutegravir treatment. Patients concerns: The first case is a 45-year-old female who developed severe congestive heart failure and died, weeks after the initiation of dolutegravir treatment (for simplification of her antiretroviral regimen). The second case was a 51-year-old male who presented with effort dyspnea 3 weeks after the initiation of dolutegravir treatment and was later diagnosed as severe congestive heart failure. The treatment was changed and the patient survived, but he still suffers from severe heart failure with functional impairment. Diagnosis and Outcome: Patient 1 died, patient 2 suffers from severe heart failure. Lessons: We discuss here the possible relationship between the initiation of dolutegravir treatment and the development of lymphocytic myocarditis in our patients, and we suggest a possible mechanism. PMID:27893693

  8. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

    PubMed Central

    Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

    2017-01-01

    Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

  9. 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.

  10. 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.

  11. Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection; however the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mono...

  12. Pathological Substratum for a Case of Fulminant Myocarditis Treated with Extracorporeal Membrane Oxygenation and Subsequent Heart Transplantation.

    PubMed

    Kim, In Ae; Yang, Hyun Suk; Kim, Wan Seop; Chee, Hyun Keun

    2015-09-01

    Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 23-yr-old woman with pathology-proven fulminant lymphocytic myocarditis presenting shock with elevated cardiac troponin I and ST segments in V1-2, following sustained ventricular tachycardia and a complete atrioventricular block. About 55 min of intensive cardio-pulmonary resuscitation, with extracorporeal membrane oxygenation support, bridged the patient to orthotopic heart transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls. Aggressive mechanical circulatory support may be an essential bridge for recovery or even transplantation in patients with fulminant myocarditis with shock.

  13. Acute Fulminant Myocarditis Successfully Bridged to Recovery with Left Ventricular Assist Device and Complicated by Flail Mitral Valve

    PubMed Central

    Duyuler, Pınar Türker; Duyuler, Serkan; Şahan, Ekrem; Küçüker, Şeref Alp

    2016-01-01

    Acute fulminant myocarditis is a life-threatening inflammatory disease of the myocardium characterized by the rapid deterioration of the hemodynamic status of the affected individual. With prompt recognition and appropriate management, complete recovery of ventricular function is likely within a few weeks. We introduce a 28-year-old man with acute fulminant myocarditis, who experienced circulatory collapse following acute angina and dyspnea. The patient had high troponin levels with low ejection fraction and normal coronary arteries. He was successfully bridged to recovery with a left ventricular assist device but was complicated by flail mitral valve. Perioperative myocardial biopsy was also compatible with myocarditis. At 4 months’ follow-up, the patient was stable with functional capacity I according to the New York Heart Association’s classification. A possible mechanism for this very rare complication is the rupture of the chordal structure secondary to the fragility of an inflamed subvalvular apparatus stretched by a recovered ventricle. PMID:27403189

  14. Hitch-hiker taken for a ride: an unusual cause of myocarditis, septic shock and adult respiratory distress syndrome

    PubMed Central

    Kushawaha, Anurag; Brown, Mark; Martin, Ismael; Evenhuis, Walther

    2013-01-01

    Rocky Mountain spotted fever (RMSF) is a serious tick-borne illness caused by Rickettsia rickettsii that is endemic in southeastern USA. Although RMSF has been described as causing the classic clinical triad of fever, headache and a characteristic rash, serious and potentially life-threatening manifestations can occur. Cardiopulmonary involvement, although infrequent, may occur with severe cases of RMSF. Rickettsial myocarditis is an uncommon occurrence. We present a case of a previously healthy 26-year-old man, who was hitch-hiking across the southeastern USA, with serologically proven RMSF causing adult respiratory distress syndrome, septic shock and myocarditis manifested by elevated cardiac enzymes and decrease in myocardial function. After treatment with antibiotics, the myocarditis resolved. Therefore, although unusual, clinicians should be aware of possible myocardial involvement in patients with appropriate tick-exposure histories or other clinical signs of RMSF. PMID:23314875

  15. 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

  16. Expression of miR-98 in myocarditis and its influence on transcription of the FAS/FASL gene pair.

    PubMed

    Zhang, B Y; Zhao, Z; Jin, Z

    2016-06-03

    Myocarditis is a common cardiovascular disease and frequently occurs in children and teenagers. It is believed to be caused by both endogenous and exogenous factors, among which FAS/FASL gene pair-induced cell apoptosis is a major mechanism of myocardial cell injury. A previous study has detected low expression of microRNA (miR)-98 in myocarditis patients. Therefore, in this study we investigated the functional implications of miR-98 with respect to the disease. We carried out a case-control study including 50 myocarditis patients and 50 healthy individuals. Total RNA was extracted from peripheral blood plasma. Expression levels of miR-98 and the FAS/FASL gene pair were determined by real-time fluorescent quantitative polymerase chain reaction. The interaction between miR-98 and the FAS/FASL pair was visualized by dual-luciferase reporter assay. The expression of the FAS/FASL gene pair was further detected by transfecting with an miR-98 mimic or an miR-98 inhibitor. The content of miR-98 in the peripheral blood of the myocarditis patients was significantly lower than in the healthy individuals. However, the FAS/FASL genes were upregulated by 1.68-fold in the myocarditis patients. miR-98 was shown to interact with the 3'-untranslated region of the FAS/FASL gene pair. The inhibition/facilitation of miR-98 expression in myocardial cells can modulate apoptosis. miR-98 was downregulated in the peripheral blood of myocarditis patients. It may interact with the FAS/FASL gene pair to further modulate cell apoptosis.

  17. Markedly Elevated Cardiac Bio-Markers at Presentation With Normal Ventricular Function: A Novel Clinical Subset of Myocarditis Manifestation

    PubMed Central

    Palla, Amruth R; Sontineni, Siva; Mani, Susan

    2011-01-01

    We present a case of a 19-year-old woman with myocarditis who had significantly elevated cardiac markers at presentation even before any myocardial damage ensued. The patient had complicated clinical course with ventricular arrhythmia and cardiac arrest requiring resuscitation but eventually recovered completely. Though there is limited information available regarding such cases, the significantly elevated initial cardiac markers in the absence of left ventricular decompensation may probably represent a clinical subset of myocarditis and may portend an impending complicated clinical course. Further systematic research is required to define the clinical phenotype and elucidate underlying mechanisms.

  18. Severe Legionnaires' disease with pneumonia and biopsy-confirmed myocarditis most likely caused by Legionella pneumophila serogroup 6.

    PubMed

    Ishimaru, Naoto; Suzuki, Hiromichi; Tokuda, Yasuharu; Takano, Tomoko

    2012-01-01

    We herein describe the successful treatment of a patient with possible Legionella pneumophila serogroup 6 infection complicated by pneumonia and myocarditis. A 32-year-old man presented with a five-day history of cough, dyspnea and chest pain. Chest radiography revealed patchy opacities in both lungs suggestive of bilateral pneumonia, and a urinary antigen test for Legionella pneumophila was positive. After admission, the patient developed congestive heart failure due to pathologically confirmed myocarditis. He was successfully treated with minocycline, macrolide, steroids and noninvasive positive-pressure ventilation (NPPV). He eventually recovered with a normalized cardiac function. L. pneumophila serogroup 6 was isolated from the bathwater in the patient's home.

  19. [Myocarditis in a cachectic female, nonsteroidal anti-inflammatory drugs abuser, in a course of progressive systemic sclerosis].

    PubMed

    Wozakowska-Kapłon, Beata; Gorczyca, Iwona; Maciejowska-Roge, Maria

    2009-11-01

    A case of 70-year-old cachectic female, nonsteroid anti-inflammatory drugs abuser, with progressive systemic sclerosis, who was admitted to our hospital due to joint pain and fatigue is presented. During hospitalisation the patient developed symptoms of acute myocarditis. Angiography of coronary arteries did not reveal narrowing of the vessels. Alimentary supplementation and therapy for heart failure (diuretics, vasodilators, angiotensin-converting enzyme inhibitor and beta-blocker) were used. In repeated echocardiography examinations ejection fraction systematically improved and hemodynamic stabilisation was obtained. Scleroderma, malnutrition, toxicity of nonsteroid anti-inflammatory drugs and infectious agents were considered as a cause of myocarditis.

  20. Moesin is activated in cardiomyocytes in experimental autoimmune myocarditis and mediates cytoskeletal reorganization with protrusion formation.

    PubMed

    Miyawaki, Akimitsu; Mitsuhara, Yusuke; Orimoto, Aya; Nakayasu, Yusuke; Tsunoda, Shin-Ichi; Obana, Masanori; Maeda, Makiko; Nakayama, Hiroyuki; Yoshioka, Yasuo; Tsutsumi, Yasuo; Fujio, Yasushi

    2016-08-01

    Acute myocarditis is a self-limiting disease. Most patients with myocarditis recover without cardiac dysfunction in spite of limited capacity of myocardial regeneration. Therefore, to address intrinsic reparative machinery of inflamed hearts, we investigated the cellular dynamics of cardiomyocytes in response to inflammation using experimental autoimmune myocarditis (EAM) model. EAM was induced by immunization of BALB/c mice with α-myosin heavy chain peptides twice. The inflammatory reaction was evoked with myocardial damage with the peak at 3 wk after the first immunization (EAM3w). Morphological and functional restoration started from EAM3w, when active protrusion formation, a critical process of myocardial healing, was observed in cardiomyocytes. Shotgun proteomics revealed that cytoskeletal proteins were preferentially increased in cardiomyocytes at EAM3w, compared with preimmunized (EAM0w) hearts, and that moesin was the most remarkably upregulated among them. Immunoblot analyses demonstrated that the expression of both total and phosphorylated moesin was upregulated in isolated cardiomyocytes from EAM3w hearts. Immunofluorescence staining showed that moesin was localized at cardiomyocyte protrusions at EAM3w. Adenoviral vectors expressing wild-type, constitutively active and inactive form of moesin (wtMoesin, caMoesin, and iaMoesin, respectively) were transfected in neonatal rat cardiomyocytes. The overexpression of wtMoesin and caMoesin resulted in protrusion formation, while not iaMoesin. Finally, we found that cardiomyocyte protrusions were accompanied by cell-cell contact formation. The expression of moesin was upregulated in cardiomyocytes under inflammation, inducing protrusion formation in a phosphorylation-dependent fashion. Moesin signal could be a novel therapeutic target that stimulates myocardial repair by promoting contact formation of cardiomyocytes.

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

    PubMed

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

    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.

  3. Peripheral Veno-Arterial Extracorporeal Membrane Oxygenation as a Bridge to Decision for Pediatric Fulminant Myocarditis.

    PubMed

    Okada, Noritaka; Murayama, Hiroomi; Hasegawa, Hiroki; Kawai, Satoru; Mori, Hiromitsu; Yasuda, Kazushi

    2016-08-01

    It is essential to establish an appropriate initial treatment strategy for pediatric fulminant myocarditis. We reviewed eight cases of pediatric fulminant myocarditis that required extracorporeal membrane oxygenation (ECMO) from 2012 to 2015. The median age was 8 years (range 3 months-13 years), and the median body surface area was 0.89 m(2) (range 0.35-1.34 m(2) ). Peripheral veno-arterial ECMO was initially applied, and we evaluated whether heart decompression was sufficient. If the pump flow was insufficient, central cannulation was performed via median sternotomy (central ECMO). The need for subsequent ventricular assist device (VAD) support was determined 72 h after ECMO initiation. Six patients were bridged to recovery using peripheral ECMO support only (for 3-11 days), whereas two required VAD support. One patient was switched to central ECMO before VAD implantation. Three patients died of multiorgan failure, even though cardiac function recovered in two of those patients. The duration from hospital arrival to ECMO initiation was shorter in the survival (3.3 ± 1.3 h; range 1.6-4.7 h) than in the nonsurvival group (32 ± 28 h; range 0.7-55 h). Peripheral ECMO can be useful as a bridge to decision for pediatric fulminant myocarditis, which is frequently followed by a successful bridge to recovery. It is important to determine whether ECMO support should be initiated before organ dysfunction advances to preserve organ function, which provides a better bridge to subsequent VAD therapy and heart transplant or recovery.

  4. Promising effects of Chinese traditional treatment for child typhoid complicated by myocarditis

    PubMed Central

    Tian, Jing; An, Xinjiang; Fu, Mingyu; Wang, Qingwen

    2016-01-01

    The clinical effects were compared and analyzed of traditional Chinese medicine (TCM) ‘Ling Gui Long Mu soup’ combined with the conventional Western medications in treating child typhoid complicated by myocarditis. From July, 2010 to May, 2014, 54 children suffering from typhoid complicated by myocarditis were enrolled in the present study. The patients were divided into the observation and control groups (n=27 cases per group) according to the random number table. Patients in the observation group were treated with basic Western medicine combined with TCM ‘Ling Gui Long Mu soup’ while patients in the control group were treated only with Western medicine. We analyzed the final curative effects in the two groups. The total effective rate in the observation group was significantly higher than that of the control group and the difference was statistically significant (P<0.05). The improvement rate of the syndrome in the TCM observation group was significantly higher than that in the control group and the difference was statistically significant (P<0.05). Although the C-reactive protein (CRP) and creatinine kinase-MB (CK-MB) levels in the two groups were decreased following the treatment, CRP and CK-MB levels in the observation group were further reduced, and the difference was statistically significant (P<0.05). In conclusion, for child typhoid complicated by myocarditis, TCM ‘Ling Gui Long Mu soup’ significantly improved the clinical efficiency of the treatment and improved the syndrome. Therefore, ‘Ling Gui Long Mu soup’ is useful in clinical practice. PMID:28101150

  5. Ly6C- Monocytes Regulate Parasite-Induced Liver Inflammation by Inducing the Differentiation of Pathogenic Ly6C+ Monocytes into Macrophages

    PubMed Central

    Laoui, Damya; Van Overmeire, Eva; Guilliams, Martin; Schouppe, Elio; Tacke, Frank; deVries, Carlie J.; De Baetselier, Patrick; Beschin, Alain

    2015-01-01

    Monocytes consist of two well-defined subsets, the Ly6C+ and Ly6C– monocytes. Both CD11b+ myeloid cells populations have been proposed to infiltrate tissues during inflammation. While infiltration of Ly6C+ monocytes is an established pathogenic factor during hepatic inflammation, the role of Ly6C– monocytes remains elusive. Mice suffering experimental African trypanosome infection die from systemic inflammatory response syndrome (SIRS) that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/necrosis of liver myeloid and parenchymal cells that reduces host survival. C57BL/6 mice are considered as trypanotolerant to Trypanosoma congolense infection. We have reported that in these animals, IL-10, produced among others by myeloid cells, limits the liver damage caused by pathogenic TNF-producing Ly6C+ monocytes, ensuring prolonged survival. Here, the heterogeneity and dynamics of liver myeloid cells in T. congolense-infected C57/BL6 mice was further dissected. Moreover, the contribution of Ly6C– monocytes to trypanotolerance was investigated. By using FACS analysis and adoptive transfer experiments, we found that the accumulation of Ly6C– monocytes and macrophages in the liver of infected mice coincided with a drop in the pool of Ly6C+ monocytes. Pathogenic TNF mainly originated from Ly6C+ monocytes while Ly6C– monocytes and macrophages were major and equipotent sources of IL-10 within myeloid cells. Moreover, Nr4a1 (Nur77) transcription factor-dependent Ly6C– monocytes exhibited IL-10-dependent and cell contact-dependent regulatory properties contributing to trypanotolerance by suppressing the production of TNF by Ly6C+ monocytes and by promoting the differentiation of the latter cells into macrophages. Thus, Ly6C– monocytes can dampen liver damage caused by an extensive Ly6C+ monocyte-associated inflammatory immune response in T. congolense trypanotolerant animals. In a more general context, Ly6C– or Ly6C+ monocyte targeting may represent a therapeutic approach in liver pathogenicity induced by chronic infection. PMID:26020782

  6. Phosphoinositide hydrolysis mediated by H1 receptors in autoimmune myocarditis mice

    PubMed Central

    Goren, Nora; Leiros, Claudia Perez; Sterin-Borda, Leonor

    1993-01-01

    Stimulation of phosphoinositide hydrolysis in myocardium from autoimmune myocarditis mice by ThEA and histamine was assayed. Myocardium from autoimmune heart, but not the normal forms, specifically increased phosphoinositide turnover in the presence of histaminergic agonists. This increment was blocked by a specific H1 antagonist mepyramine and to the same extent by the phospholipase C inhibitor NCDC. By using a binding assay H1 histaminergic receptors were detected in autoimmune heart membrane preparations, but this was not observed in normal heart. These data suggest that autoimmune myocardium expressed a functional H1 receptor that could involve a distinctive mechanism operating in the disease. PMID:18475540

  7. Typhoid fever, complicated by myocarditis, in a traveller returning to the UK

    PubMed Central

    Shah, Shreena; Dubrey, Simon William

    2013-01-01

    A 25-year-old male returning traveller presented with sudden onset chest pain. An ECG showed infero-lateral ischaemic changes, with an elevated troponin and inflammatory markers. An echocardiogram showed a normal size left ventricle, dynamic systolic function, structurally normal valves and no regional wall motion abnormality. Angiography revealed normal coronary arteries. A diagnosis of myocarditis was made. Five days later, he developed a significant pyrexia and diarrhoea. Salmonella typhi was isolated from blood cultures. The fever and symptoms resolved after 2 weeks of an intravenous third generation cephalosporin and the patient was discharged. PMID:23417944

  8. 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

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

    SciTech Connect

    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.

  10. 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

  11. Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle.

    PubMed Central

    Kolattukudy, P. E.; Quach, T.; Bergese, S.; Breckenridge, S.; Hensley, J.; Altschuld, R.; Gordillo, G.; Klenotic, S.; Orosz, C.; Parker-Thornburg, J.

    1998-01-01

    To explore the possible role of monocyte chemotactic protein (MCP-1) in inflammatory diseases of the heart, we expressed the murine MCP-1(JE) gene under the control of the alpha-cardiac myosin heavy chain promoter to attempt to target MCP-1 expression to the adult heart muscle. The five lines of transgenic mice thus produced showed targeted expression of MCP-1 transcripts and protein in the adult heart muscle and pulmonary vein but not in skeletal muscle. MCP-1 level in the transgenic hearts increased up to 30 to 45 days of age, and leukocyte infiltration into interstitium between cardiomyocytes increased up to 60 to 75 days. The infiltrate was mainly macrophages but not T cells. The presence of MCP-1 in the transgenic hearts did not induce cytokine production indicative of leukocyte activation. Echocardiographic analysis of 1-year-old mice that express MCP-1 in the myocardium and of age-matched controls revealed cardiac hypertrophy and dilation, increases in left ventricular (LV) mass, and systolic and diastolic left ventricular internal diameters. A significant decline in M-mode shortening fraction showed depressed contractile function. Transgenic hearts were 65% heavier, and histological analysis showed moderate myocarditis, edema, and some fibrosis. Thus, MCP-1 expression in the heart muscle may provide a model to investigate myocarditis and cardiomyopathy. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9422528

  12. Requirement for Pathogenic IL-23 Signaling Is Restricted to Initiation of Autoimmune Myocarditis

    PubMed Central

    Wu, Lei; Diny, Nicola L.; Ong, SuFey; Barin, Jobert G.; Hou, Xuezhou; Rose, Noel R.; Talor, Monica V.; Čiháková, Daniela

    2016-01-01

    Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4+ T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4+ T cells, and becomes dispensable once autoreactivity is established. Il23a−/− mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4+ T cells raised from Il23a−/− donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL-23 induced GM-CSF mediates the pathogenicity of CD4+ T cells in EAM. The neutralization of GM-CSF abrogated cardiac inflammation. However, sustained IL-23 signaling is required to maintain IL-17A production in CD4+ T cells. Despite inducing inflammation in Il23a−/− recipients comparable to WT, autoreactive CD4+ T cells downregulated IL-17A production without persistent IL-23 signaling. This divergence on the controls of GM-CSF-dependent pathogenicity on one side and IL-17A production on the other side may contribute to the discrepant efficacies of anti-IL-23 therapy in different autoimmune diseases. PMID:26660726

  13. [Cardiogenic shock after ingestion of amphetamines on a ground of Mycoplasma myocarditis].

    PubMed

    Berger, K; Hérault, M-C; Danel, V; Vincent, F; Jacquot, C

    2008-03-01

    Amphetamines are considered as narcotics in France. Their use induces modifications of the central nervous system and of the cardiovascular, respiratory and urinary systems by a sympathomimetic indirect effect. Here is reported the observation of a young woman who absorbed amphetamines causing a cardiogenic shock on a ground of acute myocarditis. The constitution of haemodynamic, respiratory and neurologic distresses lead to the endotracheal intubation of the patient. The haemodynamic status remaining shaky, despite the use of vasoactive drugs, a circulatory assistance by intra-aortic counter pulsation balloon was carried out. The initial echocardiography showed a left ventricular ejection fraction lower than 20%. Amphetamine's toxicity mechanisms still remain complicated; on cardiovascular plan, some cases of coronary artery spasm have been described. The coronarography, not accomplished immediately, was normal. Toxicological samples revealed an abnormally high amphetamines concentration. The severity of the cardiac attack was amplified by a Mycoplasma pneumoniae myocarditis. There was a positive evolution in eight days. Intoxication and infection can difficultly be dissociated in this case of cardiogenic shock.

  14. Rapidly fatal community-acquired pneumonia due to Klebsiella pneumoniae complicated with acute myocarditis and accelerated idioventricular rhythm.

    PubMed

    Chuang, Tzu-Yi; Lin, Chou-Jui; Lee, Shih-Wei; Chuang, Chun-Pin; Jong, Yuh-Shiun; Chen, Wen-Jone; Hsueh, Po-Ren

    2012-08-01

    We describe a previously healthy 52-year-old man with rapidly fatal community-acquired pneumonia caused by Klebsiella pneumoniae. The patient developed acute renal dysfunction, accelerated idioventricular rhythm (acute myocarditis), lactic acidosis and septic shock. He died within 15 hours after admission despite intravenous levofloxacin (750 mg daily) and aggressive medical treatment.

  15. A case report of lethal post-viral lymphocytic myocarditis with exclusive location in the right ventricle.

    PubMed

    Crudele, Graziano Domenico Luigi; Amadasi, Alberto; Marasciuolo, Laura; Rancati, Alessandra; Gentile, Guendalina; Zoja, Riccardo

    2016-03-01

    The inflammatory involvement of vital organs may represent a dangerous and life-threatening situation: in particular, the inflammation of the myocardial tissue of the heart may lead to severe consequences since the clinical history of the disease may be completely asymptomatic, any clinical sign may be lacking, thus preventing correct diagnosis and treatment. This may occur even in the case of myocarditis and may lead to unexpected death whose cause can be assessable only by means of a thorough histopathological examination. The article reports the case of 61-year old female who developed a flu-like syndrome with very few symptoms, followed by sudden death in three weeks. The autopsy and following histopathological investigations identified the cause of death in a post-viral lymphocytic myocarditis, probably related to the previous infectious disease, and alternative causes (as arrhythmic ventricular dysplasia, vasculitis, sarcoidosis and giant cell myocarditis) were excluded. The exclusive location in the right ventricle was a peculiar finding. The case highlights the importance of the myocardium of the right ventricle, a tissue which is often less considered even in histopathological surveys. The exclusive location of myocarditis in the right ventricle is a rare event but in this case fully responsible for death.

  16. Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype.

    PubMed

    Caldas, Ivo Santana; Diniz, Livia de Figueiredo; Guedes, Paulo Marcos da Matta; Nascimento, Álvaro Fernando da Silva do; Galvão, Lúcia Maria da Cunha; Lima, Wanderson Geraldo de; Caldas, Sérgio; Bahia, Maria Terezinha

    2017-03-01

    This study was designed to verify the relationship between IgG antibodies isotypes and myocarditis in Trypanosoma cruzi infection using mice and dogs infected with different T. cruzi strains. The animals were infected with benznidazole-susceptible Berenice-78 and benznidazole-resistant AAS and VL-10 strains. The IgG subtypes were measured in serum samples from dogs (IgG, IgG1, and IgG2) and mice (IgG, IgG1, IgG2a, and IgG2b). The infection of dogs with VL-10 strain induced the highest levels of heart inflammation while intermediate and lower levels were detected with Berenice-78 and AAS strains, respectively. Similar results were found in mice infected with VL-10, but not in those infected with AAS or Berenice-78 strains. The AAS strain induced higher levels of heart inflammation in mice, while Berenice-78 strain was not able to induce it. Correlation analysis between myocarditis and antibody reactivity index revealed very interesting results, mainly for IgG and IgG1, the latter being the most exciting. High IgG1 showed a significant correlation with myocarditis in both experimental models, being more significant in dogs (r=0.94, p<0.0001) than in mice (r=0.58, p=0.047). Overall, our data suggest that IgG1 could be a good marker to demonstrate myocarditis intensity in Chagas disease.

  17. Unexpected hazard of illegal immigration: Outbreak of viral myocarditis exacerbated by confinement and deprivation in a shipboard cargo container.

    PubMed

    Li, Melissa K; Beck, Melinda A; Shi, Qing; Harruff, Richard C

    2004-06-01

    We present a group of 18 illegal immigrant stowaways who arrived in a shipboard cargo container suffering from gastroenteritis, dehydration, and malnutrition and showing evidence of viral myocarditis in 3 of 4 fatalities. Our investigation included an evaluation of the 2-week ocean voyage, analysis of medical records and laboratory results of the survivors, autopsies on the decedents, and viral studies on their heart tissue. Of 3 stowaways who died shipboard, 2 showed lymphocytic myocarditis and 1 could not be evaluated histologically due to decomposition. A fourth stowaway died 4 months after arrival with dilated cardiomyopathy and lymphocytic myocarditis. Reverse-transcriptase polymerase chain reaction and nucleotide sequencing of viral isolates from the decedents' heart tissues demonstrated Coxsackie virus B3 genome. We believe that these cases represent an outbreak of viral myocarditis, exacerbated by acute dehydration and malnutrition, due to confinement within the shipping container. Our evidence indicates that close confinement promoted the spread of the virus, and nutritional deprivation increased the stowaways' vulnerability. Furthermore, our observations support the conclusion, based on experimental studies, that nutritionally induced oxidative stress increased the virulence of the etiologic viral agent. In summary, these cases represent a potential infectious disease hazard of illegal immigration.

  18. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

    DOE PAGES

    Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; ...

    2015-03-20

    Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a

  19. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

    SciTech Connect

    Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.; Horwitz, Marc S.

    2015-03-20

    Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that

  20. A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination

    PubMed Central

    Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.

    2015-01-01

    Background Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. Purpose The study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. Methods New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. Conclusions Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post

  1. Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem

    PubMed Central

    2012-01-01

    Background Viral myocarditis is a major cause of sudden unexpected death in children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the most commonly implicated virus in myocarditis. At present, no standard diagnosis is generally accepted due to the insensitivity of traditional diagnostic tests. This has prompted health professionals to seek new diagnostic approaches, which resulted in the emergence of new molecular pathological tests and a more detailed immunohistochemical and histopathological analysis. When supplemented with immunohistochemistry and molecular pathology, conventional histopathology may provide important clues regarding myocarditis underlying etiology. Methods This study is based on post-mortem samples from sudden unexpected death victims and controls who were investigated prospectively. Immunohistochemical investigations for the detection of the enteroviral capsid protein VP1 and the characterization and quantification of myocardial inflammatory reactions as well as molecular pathological methods for enteroviral genome detection were performed. Results Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37 cases of unnatural traffic accident victims were studied. Enterovirus was detected in 6 sudden unexpected death cases (12.5 %). The control samples were completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1 in the myocardium was detected in enterovirus-positive cases revealed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples, immunohistochemical investigations showed a significant presence of T and B lymphocytes in sudden unexpected death victims. Conclusions Our findings demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden unexpected death compared to control subjects, suggesting that coxsackie B enterovirus may contribute to myocarditis pathogenesis significantly. PMID:22966951

  2. 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.

  3. Low-Dose Inorganic Mercury Increases Severity and Frequency of Chronic Coxsackievirus-Induced Autoimmune Myocarditis in Mice

    PubMed Central

    Nyland, Jennifer F.; Fairweather, DeLisa; Shirley, Devon L.; Davis, Sarah E.; Rose, Noel R.; Silbergeld, Ellen K.

    2012-01-01

    Mercury is a widespread environmental contaminant with neurotoxic impacts that have been observed over a range of exposures. In addition, there is increasing evidence that inorganic mercury (iHg) and organic mercury (including methyl mercury) have a range of immunotoxic effects, including immune suppression and induction of autoimmunity. In this study, we investigated the effect of iHg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3 (CVB3). We examined the role of timing of iHg exposure on disease; in some experiments, mice were pretreated with iHg (200 μg/kg, every other day for 15 days) before disease induction with virus inoculation, and in others, they were treated with iHg after the acute (viral) phase of disease but before the development of dilated cardiomyopathy (DCM). iHg alone had no effect on heart pathology. Pretreatment with iHg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared with control animals receiving vehicle alone. In contrast, treatment with iHg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by iHg pretreatment were not due to increased viral replication in the heart, which was unaltered by iHg treatment. iHg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin (IL)-12, IL-17, interferon-γ, and tumor necrosis factor-α levels. IL-17 levels were also significantly increased in the spleen during chronic disease. Thus, we show for the first time that low-dose Hg exposure increases chronic myocarditis and DCM in a murine model. PMID:21984480

  4. Protective effect of captopril against clozapine-induced myocarditis in rats: role of oxidative stress, proinflammatory cytokines and DNA damage.

    PubMed

    Abdel-Wahab, Basel A; Metwally, Metwally E; El-khawanki, Mohamed M; Hashim, Alaa M

    2014-06-05

    Clozapine (CLZ) is the most effective therapeutic alternative in the treatment of resistant schizophrenia. However, the cardiotoxicity of CLZ, particularly in young patients, has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with antioxidant properties effective in treating hypertension and heart failure. The aim of this study was to investigate the protective effect of captopril against clozapine-induced myocarditis in rats and the possible mechanisms behind this effect. The effect of captopril treatment [5 or 10mg/kg/d, injected intraperitoneally (i.p.) for 21days] on the cardiotoxic effect of coadministered CLZ (25mg/kg/d, i.p.) was assessed. Myocarditis was assessed histopathologically, immunohistochemically and biochemically. Frozen heart specimens were used to determine the amount of lipid peroxides product (MDA), nitric oxide (NO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) activity, proinflammatory cytokines (TNF-α and IL-10) and DNA degradation product(8-OHdG). Coadministration of captopril with the tested doses of CLZ decreased the histological hallmarks and biochemical markers (CK-MP and LDH) of myocarditis. In addition, captopril attenuated the effects of CLZ on oxidative stress parameters, NO and serum and cardiac 8-OHdG levels. Captopril significantly attenuated the effect of CLZ on all measured parameters in a dose-dependent manner. These results suggested that captopril exerts a protective action against CLZ-induced myocarditis. Multiple mechanisms contribute to this effect, including a decrease in cardiac oxidative stress and proinflammatory cytokines production, modulation of antioxidant status and protection from oxidative DNA damage. Hence, captopril may be effective in reducing the incidence and severity of CLZ-induced myocarditis in humans.

  5. 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.

  6. Autoanti-idiotypes exhibit mimicry of myocyte antigens in virus-induced myocarditis.

    PubMed Central

    Paque, R E; Miller, R

    1991-01-01

    Mice infected with coxsackievirus B develop immunologically mediated inflammatory myocarditis in heart tissue that results in the development of autoantibodies with multiple idiotypes. The specificity and temporal development of autoantibodies produced during coxsackievirus B3 infection were assessed. Antiviral idiotypes and anti-idiotypic antibodies against coxsackievirus B3 idiotypes were detected and quantitated over 21- and 42-day periods, respectively. Both polyclonal and monoclonal anti-idiotypes exhibited greater but nonspecific binding to heart, liver, kidney, and spleen cells from virus-exposed animals and normal tissue. Binding of anti-idiotypes was also demonstrated to myosin and to solubilized heart-associated antigens but not to virus. Western immunoblot analysis revealed that monoclonal and polyclonal anti-idiotypes selectively bound to hypertonic, salt-extracted, solubilized proteins of myocyte extracts of virus-exposed animals. Images PMID:1845881

  7. 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

  8. Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from Coxsackievirus B3-induced myocarditis.

    PubMed

    Yao, Hai-Lan; Song, Juan; Sun, Peng; Song, Qin-Qin; Sheng, Lin-Jun; Chi, Miao-Miao; Han, Jun

    2016-02-02

    To investigate the innate immune injury and repair mechanism during recovery from Coxsackievirus B3 (CVB3) induced myocarditis, we established an acute viral myocarditis recovery model by infecting BALB/c mice with CVB3. Histopathological examination of cardiac tissues after infection showed a gradual increase of myocardial injury to the maximum degree at 8 dpi (days post infection), followed by a recovery process with reduced viral replication. We also measured expression changes of innate immune genes in heart after 4, 8 and 12 days of infection using innate immune real-time PCR array. The results showed expression alterations in many Pattern Recognition Receptors (PRRs) genes upon CVB3 infection, which activated multiple important signaling pathways during recovery process. The expression of TLRs, RLRs, PKR and cytokines were strongly induced and reached the peak at 4 dpi in early myocarditis stage, followed by a gradual reduction in recovery stage, during which the levels were even lower than normal at 12 dpi. The strong correlation between cardiac histopathology score and chemokine expression level suggested that the chemokines might play a role in pathological changes during early myocarditis stage. In addition, we also found that both cell survival signaling pathways (AKT1, p38MAPK) and antiviral signaling pathways (IKKα/β/ε) were activated and promoted the recovery during late myocarditis stage. Altogether, our observations improved the understanding of formation and progression of the pathological lesions, as well as the repair mechanism for acute viral myocarditis.

  9. Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats

    PubMed Central

    Nakagawa, Pablo; Liu, Yunhe; Liao, Tang-Dong; Chen, Xiaojuan; González, Germán E.; Bobbitt, Kevin R.; Smolarek, Derek; Peterson, Ed L.; Kedl, Ross; Yang, Xiao-Ping; Rhaleb, Nour-Eddine

    2012-01-01

    Myocarditis is commonly associated with cardiotropic infections and has been linked to development of autoimmunity. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring tetrapeptide that prevents inflammation and fibrosis in hypertension and other cardiovascular diseases; however, its effect on autoimmune-mediated cardiac diseases remains unknown. We studied the effects of Ac-SDKP in experimental autoimmune myocarditis (EAM), a model of T cell-mediated autoimmune disease. This study was conducted to test the hypothesis that Ac-SDKP prevents autoimmune myocardial injury by modulating the immune responses. Lewis rats were immunized with porcine cardiac myosin and treated with Ac-SDKP or vehicle. In EAM, Ac-SDKP prevented both systolic and diastolic cardiac dysfunction, remodeling as shown by hypertrophy and fibrosis, and cell-mediated immune responses without affecting myosin-specific autoantibodies or antigen-specific T cell responses. In addition, Ac-SDKP reduced cardiac infiltration by macrophages, dendritic cells, and T cells, pro-inflammatory cytokines [interleukin (IL)-1α, tumor necrosis factor-α, IL-2, IL-17] and chemokines (cytokine-induced neutrophil chemoattractant-1, interferon-γ-induced protein 10), cell adhesion molecules (intercellular adhesion molecule-1, L-selectin), and matrix metalloproteinases (MMP). Ac-SDKP prevents autoimmune cardiac dysfunction and remodeling without reducing the production of autoantibodies or T cell responses to cardiac myosin. The protective effects of Ac-SDKP in autoimmune myocardial injury are most likely mediated by inhibition of 1) innate and adaptive immune cell infiltration and 2) expression of proinflammatory mediators such as cytokines, chemokines, adhesion molecules, and MMPs. PMID:22923621

  10. 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

  11. Virus myocarditis in a 1-month-old boy presenting as two types of paroxysmal supraventricular tachycardia.

    PubMed

    Fujita, Shuhei; Futatani, Takeshi; Kubo, Tatsuya; Itamochi, Masae; Yachi, Yusuke; Iwasaki, Hidenori; Shimao, Ayako; Ina, Shihomi; Higashiyama, Hiroyuki; Igarashi, Noboru; Hatasaki, Kiyoshi

    2017-04-12

    Herein we describe the case of a 1-month-old boy with acute viral myocarditis, who presented with two kinds of paroxysmal supraventricular tachycardia, and who was cured after medical treatment. He was brought to the emergency room with poor feeding due to fever. On the third day of hospitalization, a narrow QRS tachycardia (180-200 beats/min) was detected. Echocardiography showed a high echoic area at the atrial septum around the atrioventricular node. The patient was clinically diagnosed with acute myocarditis. The narrow QRS tachycardia was diagnosed as incessant junctional ectopic tachycardia. The patient was treated with propranolol and landiolol. The frequency of the tachycardia decreased, but a different narrow QRS tachycardia was detected on the 15th day of hospitalization on electrocardiogram (220 beats/min), which was ascribed to atrioventricular nodal re-entrant tachycardia. Atenolol was effective for the tachycardia. At 2 years follow up, cardiac function was normal and tachycardia had not recurred.

  12. Long-term follow-up on cardiac function following fulminant myocarditis requiring percutaneous extracorporeal cardiopulmonary support.

    PubMed

    Ishida, Kohki; Wada, Hiroshi; Sakakura, Kenichi; Kubo, Norifumi; Ikeda, Nahoko; Sugawara, Yoshitaka; Ako, Junya; Momomura, Shin-ichi

    2013-01-01

    Fulminant myocarditis is a rapidly progressive, life-threatening disease with severe impairment of systolic left ventricle function in the acute phase. However, the long-term prognosis of patients who survive the acute phase with percutaneous extracorporeal cardiopulmonary support (PCPS) is not established. The purpose of this study was to elucidate the long-term follow-up on chronic cardiac function and long-term outcome. Twenty consecutive patients with fulminant myocarditis in the acute phase supported by PCPS were enrolled between January 1995 and March 2010. Echocardiography was performed at least three times; acute phase (within 3 days from onset), predischarge (days 3-30), and chronic phase (>6 months, 2.67 ± 2.19 years, mean ± SD). The clinical events were queried by their medical record and questionnaires. Eight patients (40%) died in the acute phase. The time course of ejection fraction (%) by echocardiography was 22.7 ± 9.8, 53.1 ± 7.2, and 57.2 ± 9.6 in acute, predischarge, and chronic phase, respectively. Diastolic dimension (mm) was 46.8 ± 7.4, 51.3 ± 2.9, and 50.4 ± 1.8, and systolic dimension (mm) was 41.4 ± 7.7, 36.8 ± 4.0, and 35.2 ± 3.3 in acute, predischarge, and chronic phase, respectively. There was no recurrence or admission related to heart failure during the follow-up period. The cardiac function of patients with fulminant myocarditis recovers rapidly during their stay in hospital. The cardiac function of predischarge patients remains unchanged in the chronic phase. The long-term survival of fulminant myocarditis appears favorable in the chronic phase.

  13. Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

    PubMed Central

    Omura, Seiichi; Kawai, Eiichiro; Sato, Fumitaka; Martinez, Nicholas E.; Chaitanya, Ganta V.; Rollyson, Phoebe A.; Cvek, Urska; Trutschl, Marjan; Alexander, J. Steven; Tsunoda, Ikuo

    2015-01-01

    Background Myocarditis is an inflammatory disease of the cardiac muscle and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into 3 phases: the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the 3 phases. Theiler’s murine encephalomyelitis virus belongs to the genus Cardiovirus and can cause myocarditis in susceptible mouse strains. Methods and Results Using this novel model for viral myocarditis induced with Theiler’s murine encephalomyelitis virus, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray to identify the biomarker candidates that can discriminate the 3 phases. Using C3H mice infected with Theiler’s murine encephalomyelitis virus on 4, 7, and 60 days post infection, we conducted bioinformatics analyses, including principal component analysis and k-means clustering of microarray data, because our traditional cardiac and serum assays, including 2-way comparison of microarray data, did not lead to the identification of a single biomarker. Principal component analysis separated heart samples clearly between the groups of 4, 7, and 60 days post infection. Representative genes contributing to the separation were as follows: 4 and 7 days post infection, innate immunity–related genes, such as Irf7 and Cxcl9; 7 and 60 days post infection, acquired immunity–related genes, such as Cd3g and H2-Aa; and cardiac remodeling–related genes, such as Mmp12 and Gpnmb. Conclusions Sets of molecules, not single molecules, identified by unsupervised principal component analysis, were found to be useful as phase-specific biomarkers. PMID:25031303

  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.

  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. Use of the Impella 5.0 Device as a Bridge to Recovery in Adult Fulminant Viral Myocarditis.

    PubMed

    Burns, Daniel J P; Quantz, Mackenzie A

    2015-01-01

    We present a case of a 48-year-old female patient successfully bridged to recovery with the Impella 5.0 microaxial pump (Abiomed, Danvers, MA USA) after presenting with cardiogenic shock secondary to acute fulminant viral myocarditis. After 1 week of flu-like symptoms, the patient presented to her community emergency department with chest pain and hypotension. A diagnosis of inferior ST elevation myocardial infarction was made; subsequent angiography demonstrated normal coronary arteries and a left ventricular ejection fraction of 10%. A provisional diagnosis of viral myocarditis was made. As her condition deteriorated further, she underwent insertion of an Impella 5.0 after failure of supportive medical therapy. Myocardial recovery occurred, and the Impella was removed after 1 week. After a prolonged cardiac intensive care unit stay requiring temporary hemodialysis, the patient recovered sufficiently to tolerate device explant, transfer to the recovery ward, and ultimate discharge home. This case report highlights the benefit of mechanical circulatory support in a patient with cardiogenic shock from viral myocarditis as well as some of the complications that can occur in this critically ill subset of patients.

  17. Demographic, clinical and pathological features of sudden deaths due to myocarditis: Results from a state-wide population-based autopsy study.

    PubMed

    Li, Liliang; Zhang, Yang; Burke, Allen; Xue, Aimin; Zhao, Ziqin; Fowler, David; Shen, Yiwen; Li, Ling

    2017-03-01

    Causes of sudden cardiac deaths have been widely reported with limited data focused specifically on myocarditis. A retrospective review of cases from the Office of the Chief Medical Examiner (OCME), State of Maryland yielded a total of 103 sudden unexpected deaths (SUDs) due to myocarditis (0.17% of all SUDs and 0.70% of autopsied SUDs) from 2005 through 2014. Most deaths occurred in patients <30 years of age with a male:female ratio 1.3:1. Of the 103 cases, 45 (43.7%) patients were witnessed collapsed. Four deaths occurred during exertion, such as exercising at the gym or performing heavy physical work, and 2 deaths were associated with emotional stress. The common cardiac macroscopic findings included ventricular dilatation (39.8%), mild coronary stenosis (17.5%), mottled myocardial appearance (15.5%), and myocardial fibrosis (10.7%). The histological classification of myocarditis was based on the predominant type of inflammatory cell infiltration. In our study group, lymphocytic myocarditis was most common, accounting for 56 cases (54.4%), followed by neutrophilic (32 cases, 31.7%), eosinophilic (13 cases, 12.6%) and giant cell type (2 cases, 1.9%). Microscopic examination revealed myocyte necrosis in 69 cases (67.0%) and interstitial or perivascular fibrosis in 48 cases (46.6%). The percentage of myocyte necrosis was 75.0% (42/58 cases) in lymphocytic, 65.6% (21/31 cases) in neutrophilic, 30.8% (4/13 cases) in eosinophilic, and 100% (2/2 cases) in giant cell myocarditis. Determination of myocarditis as cause of death continues to present a major challenge to forensic pathologists, because histopathologic findings can be subtle and the diagnosis of myocarditis remains difficult.

  18. 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

  19. 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.

  20. Toxoplasma gondii Myocarditis after Adult Heart Transplantation: Successful Prophylaxis with Pyrimethamine

    PubMed Central

    Strabelli, Tania Mara V.; Siciliano, Rinaldo Focaccia; Vidal Campos, Silvia; Bianchi Castelli, Jussara; Bacal, Fernando; Bocchi, Edimar A.; Uip, David E.

    2012-01-01

    Toxoplasma gondii primary infection/reactivation after solid organ transplantation is a serious complication, due to the high mortality rate following disseminated disease. We performed a retrospective study of all cases of T. gondii infections in 436 adult patients who had received an orthotopic cardiac transplant at our Institution from May 1968 to January 2011. Six patients (1.3%) developed T. gondii infection/reactivation in the post-operative period. All infections/reactivations occurred before 1996, when no standardized toxoplasmosis prophylactic regimen or co-trimoxazole prophylaxis was used. Starting with the 112th heart transplant, oral pyrimethamine 75 mg/day was used for seronegative transplant recipients whose donors were seropositive or unknown. Two patients (33.3%) presented with disseminated toxoplasmosis infection, and all patients (100%) had myocarditis. Five patients (83.3%) were seronegative before transplant and one patient did not have pre-transplant serology available. Median time for infection onset was 131 days following transplantation. Three patients (50%) died due to toxoplasmosis infection. After 1996, we did not observe any additional cases of T. gondii infection/reactivation. In conclusion, toxoplasmosis in heart allographs was more frequent among seronegative heart recipients, and oral pyrimethamine was highly effective for the prevention of T. gondii infection in this population. PMID:23209479

  1. Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.

    PubMed

    Tam, Patricia E

    2006-01-01

    Coxsackievirus (CVB) infection is a significant cause of myocarditis and dilated cardiomyopathy (DCM). Heart disease may be caused by direct cytopathic effects of the virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. CVB interacts with its host at multiple stages during disease development. Signaling through viral receptors may alter the intracellular environment in addition to facilitating virus entry. Viral genetic determinants that encode cardiovirulence have been mapped and may change depending on the nutritional status of the host. Virus persistence is directly associated with pathology, and recent work demonstrates that CVB evolves into a slowly replicating form capable of establishing a low-grade infection in the heart. The innate immune response to CVB has taken on increasing importance because of its role in shaping the development of the adaptive immune response that is responsible for cardiac pathology. Studies of T cell responsiveness and the development of autoimmunity at the molecular level are beginning to clarify the mechanisms through which CVB infection causes inflammatory heart disease.

  2. 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

  3. 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.

  4. Presence of Antigen-Experienced T Cells with Low Grade of Differentiation and Proliferative Potential in Chronic Chagas Disease Myocarditis

    PubMed Central

    Cabeza-Meckert, Patricia; Viotti, Rodolfo; Garelli, Fernando; Favaloro, Liliana E.; Favaloro, Roberto R.; Laguens, Rubén; Laucella, Susana A.

    2014-01-01

    Background The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. Methodology/Principal Findings The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57−, CD45RA−, PD-1−). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. Conclusions/Significance The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. PMID:25144227

  5. Acute necrotizing eosinophilic myocarditis in a patient taking Garcinia cambogia extract successfully treated with high-dose corticosteroids.

    PubMed

    Allen, Scott F; Godley, Robert W; Evron, Joshua M; Heider, Amer; Nicklas, John M; Thomas, Michael P

    2014-12-01

    A previously healthy 48-year-old woman was evaluated for lightheadedness and chest heaviness 2 weeks after starting the herbal supplement Garcinia cambogia. She was found to be hypotensive and had an elevated serum troponin level. The patient had a progressive clinical decline, ultimately experiencing fulminant heart failure and sustained ventricular arrhythmias, which required extracorporeal membrane oxygenation support. Endomyocardial biopsy results were consistent with acute necrotizing eosinophilic myocarditis (ANEM). High-dose corticosteroids were initiated promptly and her condition rapidly improved, with almost complete cardiac recovery 1 week later. In conclusion, we have described a case of ANEM associated with the use of Garcinia cambogia extract.

  6. Reduced-energy diet improves survival of obese KKAy mice with viral myocarditis: induction of cardiac adiponectin expression.

    PubMed

    Kanda, Tsugiyasu; Saegusa, Seiichiro; Takahashi, Takashi; Sumino, Hiroyuki; Morimoto, Shigeto; Nakahashi, Takeshi; Iwai, Kunimitsu; Matsumoto, Masayuki

    2007-07-31

    Obesity is an important risk factor for heart disease. Whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. We hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. We examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese KKAy mice. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) into KKAy mice fed ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). The 14-day survival rate was 0% in FF, whereas it was 23% in RF (P<0.01). Heart weight/body weight ratio in RF was lower than that in FF on day 5 after viral inoculation (P<0.05). Histological scores for myocardial necrosis and inflammation on day 5 were significantly lower in RF than in FF (P<0.05). Circulating adiponectin level on day 0 was significantly elevated in RF compared with that in FF (32+9 vs. 22+2 microg/mL, P<0.05). Comparative expression of cardiac adiponectin mRNA in RF was significantly higher than that in FF (5.1+0.3 vs. 1+0.2, P<0.05). Cardiac tumor necrosis factor-alpha (TNF-alpha) mRNA in RF was significantly decreased compared with that in FF on day 5 (P<0.05). Cardiac expression of nuclear factor kappa B was reduced and that of peroxisome proliferator-activated receptor gamma mRNA was increased in RF in comparison with FF on day 0. Cardiac adiponectin mRNA was negatively correlated with cardiac TNF-alpha mRNA (r=-0.555; P=0.0097). Weight loss improved the survival and myocardial damage in obese mice with viral myocarditis, with cardiac induction of adiponectin. The induction of adiponectin might provide benefit through a cardioprotective effect against acute heart failure due to viral myocarditis in obese subjects.

  7. 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.

  8. Biventricular support using a centrifugal pump in a 6 year old with fulminant myocarditis.

    PubMed

    Kehara, Hiromu; Takano, Tamaki; Terasaki, Takamitsu; Okada, Kenji

    2016-12-01

    We experienced a case of ventricular assist with both a pulsatile-flow and a continuous-flow pump in a pediatric patient, and herein report the clinical course and characteristics of the pumps. A 6-year-old female was diagnosed with fulminant myocarditis and transferred to our hospital for mechanical support. After 12 days of extracorporeal membrane oxygenation, we implanted a left ventricular assist device (LVAD) and a right ventricular assist device (RVAD) using centrifugal Gyro pumps with a membrane oxygenator in a paracorporeal fashion. The membrane oxygenator was removed on postoperative day (POD) 4, and the patient was weaned from the respirator on POD 6. The LVAD was exchanged on POD 13 and 17, and the RVAD was exchanged on POD 14 because of thrombus formation inside the pumps. The RVAD was removed on POD 25. On POD 32, the patient experienced cerebral infarction and the centrifugal Gyro pump was switched to an extracorporeal pulsatile pump. No thromboembolic event occurred after pump conversion, although continuous administration of vasodilators was required to avoid hypertension. She underwent successfully heart transplantation in the USA after 8 months of ventricular support. A centrifugal pump is considered useful for pediatric patients, as pump flow and blood pressure can be relatively easily controlled in the postoperative acute phase compared with the pulsatile pump. However, special care should be taken to monitor for thrombus formation when support length becomes longer than 13 days, and a switch to a pulsatile pump should be considered once the hemodynamic status stabilizes.

  9. 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

  10. A child with influenza A (H1N1)-associated myocarditis rescued by extracorporeal membrane oxygenation.

    PubMed

    Oda, Takeshi; Yasunaga, Hiroshi; Tsutsumi, Yoshimitsu; Shojima, Takahiro; Zaima, Yasuyuki; Nishino, Hiroshi; Ito, Shinichi; Todo, Kageshige

    2010-12-01

    A 6-year-old boy had cold-like symptoms and was diagnosed with influenza A at a clinic. Administration of oseltamivir and azithromycin did not improve the symptoms. He was referred to our hospital and was diagnosed with H1N1 pneumonia. The patient required ventilator support. However, hypoxia and hypercapnia were uncontrollable. To oxygenate and reduce the carbon dioxide concentration, veno-venous extracorporeal membrane oxygenation (ECMO) was applied 24 h after admission. We established outflow via the right internal jugular vein and inflow via the right femoral vein. Six hours later, an electrical storm of ventricular fibrillation occurred, probably due to influenza myocarditis. Chest compression was started immediately. Both cardioversion and medication were ineffective in treating the electrical storm. Therefore, we decided to switch the veno-venous ECMO to veno-arterial ECMO to maintain systemic flow. During chest compression, a 6-mm graft was anastomosed to the left common femoral artery, and an outflow tube was connected to the graft. Consequently, veno-arterial ECMO was established via outflow through the left common femoral artery and inflow through both the right jugular vein and right femoral vein. Veno-arterial ECMO terminated the electrical storm, and cardiac output improved. Veno-arterial ECMO was provided for 107 h, and was then replaced by veno-venous ECMO. Forty-three hours later, veno-venous ECMO was discontinued. The patient was successfully weaned from the mechanical ventilator on the 9th day after admission. Unfortunately, spinal infarction appeared as a complication. The patient was discharged from the hospital on the 86th day, and has now returned to primary school.

  11. Intracellular viral localization in murine coxsackievirus-B3 myocarditis. Ultrastructural study by electron microscopic in situ hybridization.

    PubMed Central

    Ukimura, A.; Deguchi, H.; Kitaura, Y.; Fujioka, S.; Hirasawa, M.; Kawamura, K.; Hirai, K.

    1997-01-01

    Group B Coxsackieviruses are a common cause of myocarditis. To detect the viral genome and its localization in the myocardium, we examined C3H/He mice with Coxsackievirus B3 (CVB3) myocarditis on days 5, 8, and 14 after inoculation by the reverse transcriptase polymerase chain reaction and by in situ hybridization. Sense and antisense CVB3 RNA were detected in the myocardium of all mice up to day 14 by reverse transcriptase polymerase chain reaction. Light microscopic in situ hybridization with a cDNA probe for CVB3 showed clusters of positive signals in the areas of myocardial necrosis and cell infiltration. With electron microscopic in situ hybridization, CVB3 RNA was detected in the cytoplasm of cardiocytes, between the myofibrils, near the mitochondria, and in tubular or vesicular structures. Viral RNA was also detected in necrotic debris, in the cytoplasm of macrophages, and in the cytoplasm of interstitial fibroblasts. These findings suggest that CVB3 RNA is replicated in the cytoplasm of cardiocytes, transferred into tubular or vesicular structures, released into the interstitium, and phagocytosed by macrophages. Some positive signals were also detected in the cytoplasm of cardiocytes showing close contact with infiltrating lymphocytes, suggesting that the lymphocytes recognized virus-infected cardiocytes and caused cell-mediated immune cardiocyte damage. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:9176398

  12. A Role for Toll-like Receptor 3 Variants in Host Susceptibility to Enteroviral Myocarditis and Dilated Cardiomyopathy*

    PubMed Central

    Gorbea, Carlos; Makar, Kimberly A.; Pauschinger, Matthias; Pratt, Gregory; Bersola, Jeathrina L. F.; Varela, Jacquelin; David, Ryan M.; Banks, Lori; Huang, Chien-Hua; Li, Hua; Schultheiss, Heinz-Peter; Towbin, Jeffrey A.; Vallejo, Jesús G.; Bowles, Neil E.

    2010-01-01

    The innate antiviral response is mediated, at least in part, by Toll-like receptors (TLRs). TLR3 signaling is activated in response to viral infection, and the absence of TLR3 in mice significantly increases mortality after infection with enteroviruses that cause myocarditis and/or dilated cardiomyopathy. We screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy and identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls. Expression of either variant resulted in significantly reduced TLR3-mediated signaling after stimulation with synthetic double-stranded RNA. Furthermore, Coxsackievirus B3 infection of cell lines expressing mutated TLR3 abrogated activation of the type I interferon pathway, leading to increased viral replication. TLR3-mediated type I interferon signaling required cellular autophagy and was suppressed by 3-methyladenine and bafilomycin A1, by inhibitors of lysosomal proteolysis, and by reduced expression of Beclin 1, Atg5, or microtubule-associated protein 1 light chain 3β (MAP1LC3β). However, TLR3-mediated signaling was restored upon exogenous expression of Beclin 1 or a variant MAP1LC3β fusion protein refractory to RNA interference. These data suggest that individuals harboring these variants may have a blunted innate immune response to enteroviral infection, leading to reduced viral clearance and an increased risk of cardiac pathology. PMID:20472559

  13. Intein-mediated backbone cyclization of VP1 protein enhanced protection of CVB3-induced viral myocarditis

    PubMed Central

    Qi, Xingmei; Xiong, Sidong

    2017-01-01

    CVB3 is a common human pathogen to be highly lethal to newborns and causes viral myocarditis and pancreatitis in adults. However, there is no vaccine available for clinical use. CVB3 capsid protein VP1 is an immunodominant structural protein, containing several B- and T-cell epitopes. However, immunization of mice with VP1 protein is ineffective. Cyclization of peptide is commonly used to improve their in vivo stability and biological activity. Here, we designed and synthesizd cyclic VP1 protein by using engineered split Rma DnaB intein and the cyclization efficiency was 100% in E. coli. As a result, the cyclic VP1 was significantly more stable against irreversible aggregation upon heating and against carboxypeptidase in vitro and the degradation rate was more slowly in vivo. Compared with linear VP1, immunization mice with circular VP1 significantly increased CVB3-specific serum IgG level and augmented CVB3-specific cellular immune responses, consequently afforded better protection against CVB3-induced viral myocarditis. The cyclic VP1 may be a novel candidate protein vaccine for preventing CVB3 infection and similar approaches could be employed to a variety of protein vaccines to enhance their protection effect. PMID:28148910

  14. Clinical Outcomes in Pediatric Patients Hospitalized with Fulminant Myocarditis Requiring Extracorporeal Membrane Oxygenation: A Meta-analysis.

    PubMed

    Xiong, Haolan; Xia, Bingqing; Zhu, Jingyu; Li, Binfei; Huang, Wenqi

    2017-02-01

    We conducted a meta-analysis to provide the survival rates for pediatric patients hospitalized with fulminant myocarditis requiring ECMO. The literature search was conducted using Embase, PubMed, MEDLINE and Elsevier for studies published before April 1, 2016. We focus on survival rates for pediatric patients hospitalized with fulminant myocarditis requiring ECMO, and studies that reported only on adult patients were excluded. Summary of the survival rates was obtained using fixed-effect or random-effect meta-analysis which determined by I (2). Six studies were included in the analysis, encompassing 172 patients. The minimum and maximum reported rates of survival to hospital discharge were 53.8 and 83.3%, respectively. The cumulative rate was 107/172. The calculated Cochran Q value was 3.73, which was not significant for heterogeneity (P = 0.588). The I (2) value was 0%. The pooled estimate rate was 62.9% with a 95% confidence interval of 55.3-69.8%. In pediatric patients with cardiac failure who have failed conventional therapies in FM, venoarterial ECMO should be considered. In total, 62.9% of patients with FM and either cardiogenic shock and/or cardiac arrest survived to hospital discharge with ECMO.

  15. Beneficial effects of low-dose benidipine in acute autoimmune myocarditis: suppressive effects on inflammatory cytokines and inducible nitric oxide synthase.

    PubMed

    Yuan, Zuyi; Kishimoto, Chiharu; Shioji, Keisuke

    2003-06-01

    Excessive production of nitric oxide (NO) by inducible NO synthase (iNOS) contributes to the progression of myocardial damage in myocarditis. Some dihydropyridine calcium channel blockers reportedly inhibit NO production and proinflammatory cytokines and the present study sought to clarify if a low dose of benidipine, a novel dihydropyridine calcium channel blocker, would ameliorate experimental autoimmune myocarditis (EAM). Rats with or without myocarditis were administered oral benidipine at a dose of 3 mg. kg(-1). day(-1) for 3 weeks. Low-dose benidipine did not decrease blood pressure significantly compared with the untreated group, but markedly reduced the severity of myocarditis. Myocardial interleukin-1beta (IL-1beta) expression and IL-1beta-positive cells were significantly less in rats with EAM that were treated with low-dose benidipine compared with untreated rats. Also, myocardial iNOS expression and iNOS-positive cells were markedly reduced in in the treated rats compared with the untreated group. Furthermore, myocardial NO production and nitrotyrosine expression were suppressed by the treatment in rats with EAM. The cardioprotection of low-dose benidipine may be caused by suppression of inflammatory cytokines and inhibition of NO production.

  16. 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...

  17. AIM2 co-immunization favors specific multifunctional CD8(+) T cell induction and ameliorates coxsackievirus B3-induced chronic myocarditis.

    PubMed

    Chai, Dafei; Yue, Yan; Xu, Wei; Dong, Chunsheng; Xiong, Sidong

    2015-07-01

    Coxsackievirus B3 (CVB3) infection can cause acute myocarditis and chronic myocarditis, leading to dilated cardiomyopathy (DCM) with no effective therapeutic strategy. Therefore, we investigated the potential of absent in melanoma 2 (AIM2) to enhance the therapeutic efficacy of DNA vaccine against CVB3-induced chronic myocarditis. Mice were infected with CVB3 and then intranasally immunized with chitosan-pcDNA3.1 (mock), chitosan-pAIM2 (CS-pAIM2), chitosan-pVP1 (CS-pVP1), or chitosan-pAIM2 plus chitosan-pVP1 (CS-pAIM2/CS-pVP1) at 7, 21, and 35d. Therapeutic efficacies of various vaccines were evaluated at day 56d. Compared with CS-pVP1 immunization, CS-pAIM2/CS-pVP1 co-immunization significantly increased survival rate, improved cardiac function, as well as decreased myocardial injury and fibrosis, this result indicated that CVB3-induced chronic myocarditis was alleviated. CVB3-specific T lymphocyte proliferation and cytotoxic T lymphocyte responses of the CS-pAIM2/CS-pVP1 co-immunization group were also increased. More interestingly, CS-pAIM2/CS-pVP1 co-immunization could facilitate CVB3-specific multifunctional CD8(+) T cell induction in the intestinal mucosa, and this induction was closely correlated with myocardial scores, this result indicated that CS-pAIM2/CS-pVP1 vaccine exhibits therapeutic efficacy by enhancing multifunctional CD8(+) T cells. This study may represent a novel therapy for CVB3-induced chronic myocarditis.

  18. Oleanolic acid modulates the immune-inflammatory response in mice with experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic implications for the human disease.

    PubMed

    Martín, R; Cordova, C; San Román, J A; Gutierrez, B; Cachofeiro, V; Nieto, M L

    2014-07-01

    Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the

  19. Effect of hydrodynamics-based delivery of IL-18BP fusion gene on rat experimental autoimmune myocarditis.

    PubMed

    Chang, He; Wang, Yan; Li, Gang; Zhang, Le; Zhang, Guang Wei; Liao, Yan Chun; Hanawa, Haruo; Zou, Jun

    2014-11-01

    Interleukin-18 (IL-18) is a powerful and important cytokine in myocarditis. IL-18-binding protein (IL-18BP), a naturally occurring antagonist of IL-18, is presumed to play a vital regulatory function in IL-18-mediated immune responses. The purpose of this study was to evaluate the alterations of IL-18 and its related protein expressions and the effect of hydrodynamics-based delivery of the IL-18BP gene for treatment of rat experimental autoimmune myocarditis (EAM).Rats were immunized on Day 0 and killed on 2, 3 and 4 weeks to determine IL-18 and its related protein expression and target cells in EAM hearts. On Day 6, rats were injected with a recombinant plasmid encoding IL-18BP-Ig or SP-Ig. On Day 17, rats were detected with echocardiography and then be killed. IL-18BP gene therapy was effective in controlling EAM, as monitored by a decreased ratio of heart weight to body weight, reduced myocarditis areas, reduced expression of atrial natriuretic peptide, brain natriuretic peptide, IL-17, IFN-γ, IL-6 and IL-10. Furthermore, the effect of serum containing IL-18BP on the expression of immune-relevant genes in IL-1α-stimulated NC cells and splenocytes cultured from EAM rats was examined. The results showed that IL-18BP significantly suppressed the expression of IL-17 as well as other proinflammatory genes such as transforming growth factor-β, prostaglandin E2 synthase, cyclooxygenase-2 in IL-1α-stimulated NC cells, and IL-18BP also significantly suppressed the expression of IL-17, IL-17R, IL-21 and IL-17-related transcriptional factor retinoic acid-related orphan nuclear receptor, signal transducer and activator of transcription-3 and Foxp3 in IL-1α-stimulated splenocytes cultured from EAM rats. IL-18 and its related protein played an important role on the development of EAM. IL-18BP effectively prevented progression of EAM by blocking IL-17 and related inflammatory genes expression. This might be a possible mechanism of the amelioration of EAM by IL-18BP

  20. A retrospective study: cardiac MRI of fulminant myocarditis in children—can we evaluate the short-term outcomes?

    PubMed Central

    Wang, Haipeng; Zhao, Bin; Jia, Haipeng; Gao, Fei; Zhao, Junyu

    2016-01-01

    Background Fulminant myocarditis (FM) is an inflammatory disease of the myocardium that results in ventricular systolic dysfunction and causes acute-onset heart failure. Cardiac magnetic resonance (CMR) has become the primary noninvasive tool for the diagnosis and evaluation of myocarditis. The aim of our study was to assess the CMR findings at different course of FM and the short-term outcomes of fulminant myocarditis (FM) in children. Methods Eight FM children with CMR examinations were included in our study. Initial baseline CMR was performed 10 days (range, 7–20 days) after onset of FM and follow-up CMR after 55 days (range, 33–75 days). Cardiac morphology and function and myocardial tissue characterization at baseline and follow-up CMR were compared using paired T-test and Mann–Whitney U test. The clinical data and initial CMR findings were also compared to predict short-term outcomes. Results The median age of eight FM children was 8.5 years old (range, 3–14). The initial CMR findings were most common with early gadolinium enhancement (EGE, 100%), followed by signal increasing on T2WI and late gadolinium enhancement (LGE, 87.5%), increased septal thickness (75.0%) and increased left ventricle ejection fraction (LVEF, 50.0%). Only three LGE (37.5%), one signal increasing on T2WI (12.5%) and one increased LVEF (12.5%) were found at follow-up. Statistically significant differences were found between initial and follow-up CMR abnormalities in the septal thickness, left ventricular end-diastolic diameter (LVEDD), end-systolic volume (ESV), LVEF, left ventricular mass, T2 ratio and LGE area (P = 0.011, P = 0.042, P = 0.016, P = 0.001, P = 0.003, P = 0.011, P = 0.020). The children with full recovery performed higher incidence of III° atrioventricular block (AVB, five cases VS 0 case) and smaller LGE area (104.0 ± 14.5 mm2 VS 138.0 ± 25.2 mm2) at baseline CMR. Discussion The CMR findings of FM in children were characteristic and

  1. [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.

  2. Evidence of canine distemper and suggestion of preceding parvovirus-myocarditis in a Eurasian badger (Meles meles).

    PubMed

    Burtscher, Hugo; Url, Angelika

    2007-03-01

    An approximately 1.5-yr-old free-ranging male Eurasian badger (Meles meles) from the eastern part of Austria had macroscopic and microscopic lesions consistent with canine distemper virus infection, including nonsuppurative meningoencephalitis, interstitial pneumonia with accumulation of macrophages in alveoli that contained intranuclear inclusion bodies, vesicular exanthema of the ventral abdomen, and atrophy of lymphoid tissues. Canine distemper virus-antigen was demonstrable in a variety of organs by using immunohistology. In addition, there were widespread areas of fibrosis in the myocardium that were rich in collagen and paucicellular. Because such changes are comparable with sequelae of the acute cardiac form of canine parvovirus (CPV) infection in dogs, it was speculated that this badger may have experienced CPV myocarditis as a cub but that the corresponding antigen or DNA was not detectable due to resolution of the disease.

  3. Correlation of left ventricular wall thickness, heart mass, serological parameters and late gadolinium enhancement in cardiovascular magnetic resonance imaging of myocardial inflammation in an experimental animal model of autoimmune myocarditis.

    PubMed

    Kromen, Wolfgang; Korkusuz, Huedayi; Korkusuz, Yuecel; Esters, Philip; Bauer, Ralf W; Huebner, Frank; Lindemayr, Sebastian; Vogl, Thomas J

    2012-12-01

    For a definitive diagnosis of myocarditis, different strategies like analysis of late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) up to invasive endomyocardial biopsy have been applied. The objective of the study was to investigate inflammatory changes like left ventricular wall thickening and increase of ventricular mass and to quantitatively analyse their correlation with extent and localisation of myocardial damage in CMR and with subsequent changes of serological markers in an animal model of an experimental autoimmune myocarditis (EAM). In the current study, an EAM was induced in 10 male Lewis rats, 10 rats served as control. On day 21, animals were examined with four CMR protocols to assess the extent of LGE in a 12 segment model of the rat heart. Left myocardial wall thickness and mass and histological grade of inflammation were measured to determine localisation and severity of the induced myocarditis. Depending on the CMR sequence, LGE was mostly found in the left anterior (9.6%) and left lateral (8.7%) myocardial wall segments. Wall thickness correlated with the LGE area in CMR imaging and the histopathological severity of myocarditis for the left lateral myocardial wall segment. In a similar way, the heart mass correlated to the extent of LGE for the left lateral segment. We conclude that in our animal model left ventricular wall thickness and mass reflect the severity of myocardial changes in myocarditis and that the EAM rat model is well suited for further investigations of myocarditis.

  4. The comparison of α-bromo-4-chlorocinnamaldehyde and cinnamaldehyde on coxsackie virus B3-induced myocarditis and their mechanisms.

    PubMed

    Zhang, Ya; Cao, Wei; Xie, Yan-Hua; Yang, Qian; Li, Xiao-Qiang; Liu, Xin-Xin; Wang, Si-Wang

    2012-09-01

    Early experiments showed cinnamaldehyde had obvious therapeutic effect on viral myocarditis, but cinnamaldehyde was unstable in vivo. To overcome this limitation, we used cinnamaldehyde as a lead compound to synthesize α-bromo-4-chlorocinnamaldehyde (BCC). In the present study, we compared the therapeutic effects of BCC with cinnamaldehyde on coxsackie virus B3 (CVB3)-induced viral myocarditis (VMC), as well as investigated the possible mechanism. The antiviral and cytotoxic effects in vitro were evaluated on HeLa cells infected by CVB3 and rat cardiomyocytes respectively. Our results showed that IC50 were 0.78±0.13 μM and 48.16±5.79 μM in BCC and cinnamaldehyde-treated cells. 50% toxic concentration (TC) in BCC-treated cells was 22-fold higher than in the cinnamaldehyde group. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. The results demonstrated that BCC reduced the viral titers and cardiac pathological changes in a dose-dependent manner. Myocardial virus titers were significantly lower in the 50 mg/kg BCC-treated group than in cinnamaldehyde groups. In addition, BCC could significantly inhibit the replication of CVB3 mRNA and the secretion of inflammatory cytokines TNF-α, IL-β and IL-6 in CVB3-infected cardiomyocytes. We further observed that BCC suppressed CVB3-induced NF-κB activation, IκB-α degradation and phosphorylation in a concentration-dependent manner, and reduced Toll like receptor (TLR) 4 protein level in hearts. These results suggest that BCC had a promising therapeutic effect on VMC with a highly significant favorable effects and less toxicity than cinnamaldehyde. Furthermore, the effect of BCC on VMC might be through inhibition of inflammatory signaling.

  5. 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

  6. Coxsackievirus B3-induced myocarditis: Infection of females during the estrus phase of the ovarian cycle leads to activation of T regulatory cells

    PubMed Central

    Huber, S.A.

    2008-01-01

    Transgenic female mice expressing the TNFα gene under the cardiac myosin promoter (TNF1.6) develop substantially increased myocarditis and increased numbers of CD4+Th1 (interferon gamma+) cells when infected with coxsackievirus B3 (CVB3) during the diestrus and proestrus phases of the estrus cycle compared to females infected during the estrus and metestrus phases. Cardiac virus titers were increased in females infected in estrus compared to females infected during the other phases. T regulatory cells (CD4+CD25+FoxP3+) were increased in both peripheral blood and inflammatory cells in the heart in females infected during estrus. Exogenous administration of 200 ng/mouse 17-β-estradiol to females protected against CVB3 induced myocarditis and increased CD4+CD25+FoxP3+ cells. These results demonstrate that hormonal fluctuations occurring in normally cycling females can determine T regulatory cell response and control virus-induced pathogenesis. PMID:18586295

  7. 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.

  8. 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.

  9. 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

  10. Efficacy of amiodarone during long-term treatment of malignant ventricular arrhythmias in patients with chronic chagasic myocarditis.

    PubMed

    Chiale, P A; Halpern, M S; Nau, G J; Tambussi, A M; Przybylski, J; Lázzari, J O; Elizari, M V; Rosenbaum, M B

    1984-04-01

    Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

  11. Cases from the aerospace medicine residents' teaching file. Case report of an aviator with focal myocarditis mimicking myocardial infarction with normal coronaries.

    PubMed

    Huff, Lester Andrew; Kruyer, William B

    2002-12-01

    A military aviator was initially diagnosed with myocardial infarction following a viral syndrome. Confusion about recurrence of chest pain versus gastritis led to his continued cardiac patient status until this was clarified diagnostically. He was presumed to have had coronary vasospasm, and was treated with a calcium channel blocker. Absent his strong desire to return to flying duties, he may have continued in that diagnostic pathway indefinitely. After thorough aeromedical evaluation, resolved focal viral myocarditis was felt to be the most likely diagnosis and he was returned to military flying duties.

  12. New Echocardiographic Findings Correlate with Intramyocardial Inflammation in Endomyocardial Biopsies of Patients with Acute Myocarditis and Inflammatory Cardiomyopathy

    PubMed Central

    Escher, Felicitas; Kasner, Mario; Kühl, Uwe; Heymer, Johannes; Wilkenshoff, Ursula; Tschöpe, Carsten; Schultheiss, Heinz-Peter

    2013-01-01

    Background. The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. Methods and Results. N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, −8.36 ± −3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (−9.4 ± 1.4 versus −16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). Conclusion. Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi. PMID:23576857

  13. Pharmacodynamic monitoring of (immuno)proteasome inhibition during bortezomib treatment of a critically ill patient with lupus nephritis and myocarditis

    PubMed Central

    de Groot, Karina A; Tsang a Sjoe, Michel; Niewerth, Denise; Cloos, Jacqueline; Blank, Jonathan L; Niessen, Hans W M; Zweegman, Sonja; Voskuyl, Alexandre E; Jansen, Gerrit; van der Heijden, Joost W

    2015-01-01

    Objective To describe the pharmacodynamic monitoring of (immuno)proteasome inhibition following treatment with bortezomib in a therapy-refractory systemic lupus erythematosus (SLE) patient with life-threatening myocarditis and lupus nephritis. Patient and methods Inhibition of catalytic activities of the proteasome subunits β5 (constitutive proteasome), β5i and β1i (immunoproteasome) were measured in peripheral blood mononuclear cells using subunit-specific fluorogenic peptide substrates in a patient who received three cycles of bortezomib (1.3 mg/m2 subcutaneously, days 1, 4, 8 and 11; every three weeks) along with plasma exchange during the first two cycles. Results Proteasome β5, β5i and β1i subunit activities were readily inhibited 1 h after bortezomib administration. Twenty-four hours post-bortezomib administration, β5 and β5i activities were largely restored, whereas inhibition of β1i activity was sustained. Clinically, after three cycles, cardiac function had improved, with concurrent improvement of haemodynamic stability during haemodialysis. Anti-ds-DNA dropped from >400 to 12 IU/mL along with normalisation of complement C3 and C4. Bortezomib therapy was well tolerated, and patient now has a sustained remission for >16 months. Conclusions This case illustrates the potential benefit of pharmacodynamic monitoring of (immune)proteasome subunit-specific activity after bortezomib dosing in patients with therapy refractory SLE. This tool may hold potential to guide personalised/precision dosing aiming to achieve maximal efficacy and minimal toxicity. PMID:26719810

  14. High yield production of an inactivated coxsackie B3 adjuvant vaccine with protective effect against experimental myocarditis.

    PubMed

    Fohlman, J; Pauksen, K; Morein, B; Bjare, U; Ilbäck, N G; Friman, G

    1993-01-01

    Dilated cardiomyopathy, perhaps chronic postviral fatigue syndrome as well as juvenile diabetes could be triggered by enteroviral infections. The frequency of sudden death after myocarditis and its relationship to enteroviral infections is disputed. Neonatal enteroviral disease is rare, but can be severe. It is also possible that enteroviruses pose a threat to immunocompromised patients, like bone marrow transplant recipients. Consequently, the emergence of chronic enteroviral diseases as a concept, prompted our attempts to produce an enteroviral vaccine. 1. Live attenuated enterovirus strains were previously in some cases shown to be suitable as vaccine candidates. We obtained neutralizing antibody titres ranging from 40-2560 against Coxsackie B3 virus (RD strain). Animals were protected to 90% against challenge infection. 2. Inactivated whole vaccine. We used beta-propiolactone to inactive Coxsackie B3 virus. 74% of the animals survived if the vaccine was prepared with Quil A matrix as adjuvant. The neutralisation antibody titres varied from < 5 to 320. By comparison aluminium hydroxide (p = 0.06) and Freund's adjuvant were inferior (p < 0.01). 3. Subunit vaccines. We have previously used the ISCOM (immunostimulatory complex) technology to produce a Coxsackie B3 subunit vaccine. High levels of neutralizing antibodies were obtained (512)-comparable to natural infection. All animals survived challenge infection after two booster doses with 16 nanogram of the ISCOM preparation. Limiting for this technique was the availability to include sufficient amount of antigenic protein material. In addition to neutralizing antibodies a cellular response might be obtainable. In conclusion we have shown that vaccine can be made against Coxsackie B3 virus with good protective effect and significant neutralisation antibody titre.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Novel application of a percutaneous left ventricular assist device as a bridge to transplant in a paediatric patient with severe heart failure due to viral myocarditis.

    PubMed

    Perry, Paul; David, Elizabeth; Atkins, Broadus; Raff, Gary

    2017-03-01

    A 13-year obese female with suspected viral myocarditis presented with acute decompensated heart failure. Due to her body habitus, she was a poor candidate for immediate heart transplantation. A peripherally inserted left ventricular assist device (LVAD) was implanted via the right axillary artery. Following device insertion the patient experienced rapid improvement in symptoms. The LVAD provided effective left ventricular unloading for 50 days, promoting myocardial recovery and maintaining excellent patient performance status. The device placement strategy allowed for a high level of activity including completion of school-work and participation in a weight loss program. The patient achieved a 28-pound weight loss, thus improving candidacy for transplantation. Removal of the device was well tolerated and post-removal echocardiography revealed an improvement in the left ventricular ejection fraction (LVEF) from 21% at baseline to 38% after device removal. This case represents a successful application of a peripherally inserted LVAD as a bridge to transplant in a pediatric patient with severe heart failure due to suspected viral myocarditis. For select patients with this condition, a transaxillary LVAD should be considered as a therapeutic option as it is well tolerated and provides effective left ventricle unloading to promote myocardial recovery and maintain performance status.

  16. 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

  17. Wnt11 gene therapy with adeno-associated virus 9 improves the survival of mice with myocarditis induced by coxsackievirus B3 through the suppression of the inflammatory reaction.

    PubMed

    Aoyama, Yutaka; Kobayashi, Koichi; Morishita, Yoshihiro; Maeda, Kengo; Murohara, Toyoaki

    2015-07-01

    The wnt signaling pathway plays important roles in development and in many diseases. Recently several reports suggest that non-canonical Wnt proteins contribute to the inflammatory response in adult animals. However, the effects of Wnt proteins on virus-induced myocarditis have not been explored. Here, we investigated the effect of Wnt11 protein in a model of myocarditis induced by coxsackievirus B3 (CVB3) using recombinant adeno-associated virus 9 (rAAV9). The effect of Wnt11 gene therapy on a CVB3-induced myocarditis model was examined using male BALB/c mice. Mice received a single intravenous injection of either rAAV9-Wnt11 or rAAV9-LacZ 2 weeks before intraperitoneal administration of CVB3. Intravenous injection of the rAAV9 vector resulted in efficient, durable, and relatively cardiac-specific transgene expression. Survival was significantly greater among rAAV9-Wnt11 treated mice than among mice treated with rAAV9-LacZ (87.5% vs. 54.1%, P < 0.05). Wnt11 expression also reduced the infiltration of inflammatory cells, necrosis of the myocardium, and suppressed the mRNA expression of inflammatory cytokines. This is the first report to show that Wnt11 expression improves the survival of mice with CVB3-induced myocarditis. AAV9-mediated Wnt11 gene therapy produces beneficial effects on cardiac function and increases the survival of mice with CVB3-induced myocarditis through the suppression of both infiltration of inflammatory cells and gene expression of inflammatory cytokines.

  18. Relation between trace element levels in plasma and myocardium during coxsackievirus B3 myocarditis in the mouse.

    PubMed

    Funseth, E; Lindh, U; Friman, G; Ilbäck, N G

    2000-12-01

    During most infections the plasma levels of trace elements change, but it is not clear if this reflects changes in the infected tissues. Coxsackievirus B3 (CB3) infection may result in viral replication, subsequent inflammation and changed trace element levels in the myocardium. In the present study, the trace element levels in the plasma and heart of adult male A/J mice were determined during the pre-inflammatory stage (day 4) of CB3 myocarditis for the following trace elements: aluminium (Al), arsenic (As), calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se), silver (Ag), vanadium (V) and zinc (Zn). The severity of the infection was assessed through clinical signs of disease and trace element levels were measured through inductively-coupled plasma mass-spectrometry (ICP-MS). In the heart, the levels decreased for V (59%; p < 0.01), Co (38%; p < 0.01), Al (81%; p < 0.01), As (66%; p < 0.01) and Se (16%; p < 0.01). Increased levels were detected for Mn (13%; p < 0.05), Fe (48%; p < 0.01), Cu (34%; p < 0.01) and Ag (46%; p < 0.01). In the plasma, decreases were detected in the level of Zn (32%; p < 0.05), whereas increases were seen in Mn (362%; p < 0.05), Fe (272%; p < 0.01), Co (71%; p < 0.05), Cu (25%; n.s.) and Mg (43%; p < 0.01) levels. A correlation was found between the levels in plasma and myocardium for Co (r(s) = -0.636; p < 0.05), Fe (r(s) = 0.764; p < 0.05), Mn (r(s) = 0.682; p < 0.05) and Mg (r(s) = -0.791; p < 0.05). Thus, determination of some of these trace elements in the plasma may be useful to indicate target tissue involvement in the early pre- inflammatory stage of an infectious disease. Some of these elements are important nutrients for the immune system, while others may be associated with the development of disease complications, such as cardiac arrhythmias.

  19. 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.

  20. M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

    PubMed

    Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

    2014-07-31

    Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development.

  1. FTY720 (Gilenya) treatment prevents spontaneous autoimmune myocarditis and dilated cardiomyopathy in transgenic HLA-DQ8-BALB/c mice.

    PubMed

    Boldizsar, Ferenc; Tarjanyi, Oktavia; Olasz, Katalin; Hegyi, Akos; Mikecz, Katalin; Glant, Tibor T; Rauch, Tibor A

    2016-01-01

    Although dilated cardiomyopathy (DCM) is often caused by viral infections, it frequently involves autoimmune mechanisms associated with particular HLA-DR and DQ alleles. Our homozygous HLA-DQ8Ab(0) transgenic mice in the BALB/c background (HLA-DQ8(BALB/c)-Tg) developed early and progressive fatal heart failure from 4 to 5 weeks of age. Clinical signs of the disease included cyanotic eyes, tachycardia with dyspnea (from pale to cyanotic limbs), and terminal whole body edema. Sick mice had extremely dilated hearts, enlarged liver and spleen, and pleural/peritoneal effusion. Histology of the heart showed extensive heart muscle destruction with signs of fibrosis. The autoimmune nature of the disease was shown by high titers of antimyosin antibodies in the sera and IgG deposits in sick heart muscles, as well as focal neutrophil, T cell, and macrophage infiltration of the heart muscle. The sera of the sick mice showed a granular staining pattern on sections of healthy heart muscle. Quantitative analyses of DCM-specific gene expression studies revealed that sets of genes are involved in inflammation, hypoxia, and fibrosis. Treatment with FTY720 (Fingolimod/Gilenya) protected animals from the development of cardiomyopathy. HLA-DQ8(BALB/c)-Tg mice represent a spontaneous autoimmune myocarditis model that may provide a useful tool for studying the autoimmune mechanism of DCM and testing immunosuppressive drugs.

  2. Feature Tracking-Derived Peak Systolic Strain Compared to Late Gadolinium Enhancement in Troponin-Positive Myocarditis: A Case-Control Study.

    PubMed

    Weigand, Justin; Nielsen, James C; Sengupta, Partho P; Sanz, Javier; Srivastava, Shubhika; Uppu, Santosh

    2016-04-01

    Cardiac magnetic resonance (CMR) assesses myocardial involvement in myocarditis (MYO). Current techniques are qualitative, subjective, and prone to interpretation error. Feature tracking (FT) analyzes myocardial strain using CMR and has not been examined in MYO. We hypothesize that regional left ventricular (LV) strain is abnormal in MYO. Regional strain by FT was compared to late gadolinium enhancement (LGE) and troponin leak as measures of myocardial involvement. This single-center, retrospective CMR study reviewed patients with clinical MYO and structurally normal hearts who underwent CMR at our institution. Young adults with normal cardiac anatomy, function, and absent LGE served as controls. MYO patients with documented troponin leak and normal global ejection fraction (EF > 50 %) were included in comparison. FT determined regional myocardial peak systolic strain (pkS) in longitudinal and circumferential distributions. T tests compared strain values between cases and controls. Receiver operating characteristic curves determined pkS values with highest sensitivity and specificity for concurrent troponin leak and LGE. FT was performed on 57 patients: 37 MYO and 20 controls. Twenty-eight cases with normal EF, and 20 control patients were included in final analysis. Nearly all cases with normal function demonstrated abnormal regional pkS (27/28, 96 %). Cases had significantly diminished pkS when compared to controls in all regions except the longitudinal 2C distribution. FT-derived longitudinal and circumferential pkS is sensitive and specific in identifying myocardial involvement, namely the presence of troponin leak and LGE. FT may be a useful adjunctive, objective measure of myocardial involvement in patients with MYO and normal LV function.

  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.

  4. 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

  5. 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.

  6. Cinétique de la troponine Ic et valeurs seuils pour le diagnostic d'infarctus du myocarde après chirurgie cardiaque sous circulation extracorporelle

    PubMed Central

    Kallel, Samy; Jarraya, Anwar; Ellouze, Maged; Frikha, Imed; Karoui, Abbdelhamid

    2012-01-01

    Introduction L'objectif de ce travail était d’étudier la cinétique de la Troponine Ic (TnIc) après chirurgie cardiaque sous circulation extracorporelle (CEC) et établir des valeurs seuils de TnIc pour le diagnostic d'infarctus du myocarde (IDM) post opératoire. Il s'agissait d'une étude prospective type cohorte observationnelle. Méthodes Nous avons inclus 37 patients âgés de plus de 18 ans proposés pour chirurgie valvulaire ou pontage aorto coronarien sous CEC. Nous avons suivi la cinétique de TnIc par des dosages immunoenzymatique sur mini-vidas® avant et après la CEC, à H4 et H12 postopératoire puis tous les jours les 4 premiers jours. Le cutoff pour le diagnostic d'IDM post opératoire a été défini comme la valeur moyenne de troponine + deux déviations standards des patients indemnes de complications cardiaques. Résultats Les valeurs de TnIc en préopératoire étaient toutes inférieures au seuil de détection de la méthode de dosage (<0,01µg/l). Les valeurs de TnIc augmentent en postopératoire immédiat pour atteindre un maximum à H4 puis diminuent progressivement pour se normaliser après 4 à 5 jours. Les valeurs seuils ont été déterminées pour H0, H4,H12, H24, H48, H72, H96 et ont été respectivement 1.36, 2.58, 3.1, 3.23, 2.13, 1.53, 1.17 pour la chirurgie coronaire et 3.75, 5.39, 4.22, 3.41, 1.65, 1.3 1.19 pour la chirurgie valvulaire. Conclusion La connaissance de la cinétique de TnIc lors de chirurgie cardiaque non compliquée et la fixation de valeur seuil ou Cutoff permet aux cliniciens de distinguer entre dommage myocardique secondaire à la chirurgie et IDM. PMID:23396754

  7. Cellular immune mechanisms in myocarditis.

    PubMed

    Noutsias, M; Patil, V J; Maisch, B

    2012-12-01

    The introduction of immunohistological techniques enabled a substantially more reliable diagnosis of inflammatory cardiomyopathy (DCMi) in endomyocardial biopsies (EMB) compared to the histological Dallas criteria. Decisive progress has been made in the understanding of cellular immune mechanisms in DCMi using immunohistological techniques, which apart from the field of diagnosis refinement have had prognostic implications and an influence on the selection criteria of DCMi patients who will likely benefit from immunosuppressive treatment. Digital image analysis systems have been employed to standardize quantification of immunohistological EMB stainings. Quantification of T cell-related genes by a methodologically validated preamplified real-time RT-PCR revealed that the T cells are characterized by differential expression of Th1-, Treg-, and CTL-related markers, while no major role could be confirmed for Th17 cells. The reported virus-associated differential T cell receptor Vbeta dominance suggests an antiviral specificity of virus-induced T cell responses in human DCMi.

  8. 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)

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

    PubMed

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

    2015-02-02

    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.

  10. 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

  11. 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.

  12. Mice with Genetic Deletion of Group VIA Phospholipase A2β Exhibit Impaired Macrophage Function and Increased Parasite Load in Trypanosoma cruzi-Induced Myocarditis

    PubMed Central

    Sharma, Janhavi; Blase, Jennifer R.; Hoft, Daniel F.; Marentette, John O.; Turk, John

    2016-01-01

    Trypanosoma cruzi infection, which is the etiological agent of Chagas disease, is associated with intense inflammation during the acute and chronic phases. The pathological progression of Chagas disease is influenced by the infiltration and transmigration of inflammatory cells across the endothelium to infected tissues, which are carefully regulated processes involving several molecular mediators, including adhesion molecules and platelet-activating factor (PAF). We have shown that PAF production is dependent upon calcium-independent group VIA phospholipase A2β (iPLA2β) following infection of human coronary artery endothelial cells (HCAECs) with T. cruzi, suggesting that the absence of iPLA2β may decrease the recruitment of inflammatory cells to the heart to manage parasite accumulation. Cardiac endothelial cells isolated from iPLA2β-knockout (iPLA2β-KO) mice infected with T. cruzi demonstrated decreased PAF production compared to that by cells isolated from wild-type (WT) mice but demonstrated increases in adhesion molecule expression similar to those seen in WT mice. Myocardial inflammation in iPLA2β-KO mice infected with T. cruzi was similar in severity to that in WT mice, but the iPLA2β-KO mouse myocardium contained more parasite pseudocysts. Upon activation, macrophages from iPLA2β-KO mice produced significantly less nitric oxide (NO) and caused less T. cruzi inhibition than macrophages from wild-type mice. Thus, the absence of iPLA2β activity does not influence myocardial inflammation, but iPLA2β is essential for T. cruzi clearance. PMID:26857573

  13. Temperature regulation.

    PubMed

    Cabanac, M

    1975-01-01

    The general way of looking at short-term temperature regulation has not fundamentaly changed since 1968. Some points nevertheless have been developed and deserve special attention: 1. The influence of water on the skin surface inhibits sweat secretion (55, 106). This fact may be the explanation of sweating fatigue and of discordant conclusions regarding the functioning of the regulator, particularly during exercise in man. 2. Since a large number of studies have shown that appropriate behaviors occur in response to all the stimuli that activate autonomic responses, behavior itself should be considered as an integral part of the thermoregulatory system (1, 2, 16, 18, 19, 21, 23, 25, 31, 32, 34-36, 48, 88, 89, 98, 99, 122, 126, 127, 137). 3. The description of the peripheral input for the control of sweating with regard to mean skin temperature (104) and time dependence (159) has been improved. Among internal temperature sensors those of the spinal cord have been extensively studies (25, 27, 32, 36, 42, 59-63, 71-75, 82, 83, 86, 113-115, 121, 150, 158) and demonstrated to have a sensitivity equal to that of the hypothalamic sensors (73, 75). 4. New hypotheses have been proposed describing the overall mechanism responsible for a constant temperature in the core (58, 96, 97, 135). These stimulating theories have been discussed briefly herein. Mechanisms for the defense against heat and against cold can be dissociated completely from one another. In the same way the control of autonomic responses can be dissociated from the control of behavioral responses. This suggests that temperature regulation is brought about by multiple independent feedback loops. The overall system is well described, in the author's opinion, by the theory of the adjustable set point with proportional control (47).

  14. Regulated Pollutant

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  15. PSD Regulations

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  16. 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

  17. Parasites Induced Skin Allergy: A Strategic Manipulation of the Host Immunity

    PubMed Central

    Bakiri, Alketa Hysni; Mingomataj, Ervin Cerciz

    2010-01-01

    The absence of a consistent link between parasitoses and skin allergic symptoms in the clinical investigations contrasts to the fact that some parasites are the most potent inducers of immunoglobulin E that exist in nature. To shed some light into this question, this review is focused on the actual knowledge regarding parasites life cycle, interactions with host immunity, the influence on host behavior, and finally the role of all these factors on the skin allergy. The collected data demonstrate that parasites could manipulate the host behavior for its own benefit in different ways, altering its (epi)genetic, biochemical, immunologic or physiologic functions as well as altering its behavior and activity. In this context, skin allergy may be associated with certain stages of the parasites' life cycle and migration into biological barriers, but not necessarily with presence of the parasitosis in the host organism. As compared to T helper (Th) 1 response, the Th2 one, the eosinophilic infiltration and the complement inhibition could assure better conditions for the development of some parasites. Taken together, the suggested hypotheses could be a plausible explanation for the epidemiological puzzle regarding urticaria occurrence, Th2 response and parasitoses, but further studies are necessary to provide better-based conclusions. Keywords Eosinophilic Infiltration; Host behavior; Parasites life cycle; Skin allergy; Th1/Th2 response PMID:22043257

  18. Parasite-induced changes in the diet of a freshwater amphipod: field and laboratory evidence.

    PubMed

    Médoc, V; Piscart, C; Maazouzi, C; Simon, L; Beisel, J-N

    2011-04-01

    Trophically transmitted parasites are likely to strongly influence food web-structure. The extent to which they change the trophic ecology of their host remains nevertheless poorly investigated and field evidence is lacking. This is particularly true for acanthocephalan parasites whose invertebrate hosts can prey on other invertebrates and contribute to leaf-litter breakdown. We used a multiple approach combining feeding experiments, neutral lipids and stable isotopes to investigate the trophic ecology of the freshwater amphipod Gammarus roeseli parasitized by the bird acanthocephalan Polymorphus minutus. Infected compared to uninfected amphipods consumed as many dead isopods, but fewer live isopods and less leaf material. Infection had no influence on the total concentration of neutral lipids. Contrary to what we expected based on laboratory findings, the nitrogen isotope signature, which allows for the estimation of consumer's trophic position, was not influenced by infection status. Conversely, the carbon isotope signature, which is used to identify food sources, changed with infection and suggested that the diet of infected G. roeseli includes less perilithon (i.e. fixed algae on rocks, stones) but more terrestrial inputs (e.g. leaf material) than that of uninfected conspecifics. This study shows evidence of changes in the trophic ecology of P. minutus-infected G. roeseli and we stress the need to complement feeding experiments with field data when investigating top-down effects of infection in an opportunistic feeder which adapts its diet to the available food sources.

  19. 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.

  20. Vaccination using live attenuated Leishmania donovani centrin deleted parasites induces protection in dogs against Leishmania infantum.

    PubMed

    Fiuza, Jacqueline Araújo; Gannavaram, Sreenivas; Santiago, Helton da Costa; Selvapandiyan, Angamuthu; Souza, Daniel Menezes; Passos, Lívia Silva Araújo; de Mendonça, Ludmila Zanandreis; Lemos-Giunchetti, Denise da Silveira; Ricci, Natasha Delaqua; Bartholomeu, Daniella Castanheira; Giunchetti, Rodolfo Cordeiro; Bueno, Lilian Lacerda; Correa-Oliveira, Rodrigo; Nakhasi, Hira L; Fujiwara, Ricardo Toshio

    2015-01-03

    Live attenuated Leishmania donovani parasites such as LdCen(-/-) have been shown elicit protective immunity against leishmanial infection in mice and hamster models. Previously, we have reported on the induction of strong immunogenicity in dogs upon vaccination with LdCen(-/-) including an increase in immunoglobulin isotypes, higher lymphoproliferative response, higher frequencies of activated CD4(+) and CD8(+) T cells, IFN-γ production by CD8(+) T cells, increased secretion of TNF-α and IL-12/IL-23p40 and, finally, decreased secretion of IL-4. To further explore the potential of LdCen(-/-) parasites as vaccine candidates, we performed a 24-month follow up of LdCen(-/-) immunized dogs after challenge with virulent Leishmania infantum, aiming determination of parasite burden by qPCR, antibody production (ELISA) and cellular responses (T cell activation and cytokine production) by flow cytometry and sandwich ELISA. Our data demonstrated that vaccination with a single dose of LdCen(-/-) (without any adjuvant) resulted in the reduction of up to 87.3% of parasite burden after 18 months of virulent challenge. These results are comparable to those obtained with commercially available vaccine in Brazil (Leishmune(®)). The protection was associated with antibody production and CD4(+) and CD8(+) proliferative responses, as well as T cell activation and significantly higher production of IFN-γ, IL-12/IL-23p40 and TNF-α, which was comparable to responses induced by immunization with Leishmune(®), with significant differences when compared to control animals (Placebo). Moreover, only animals immunized with LdCen(-/-) expressed lower levels of IL-4 when compared to animals vaccinated either with Leishmune(®) or PBS. Our results support further studies aiming to demonstrate the potential of genetically modified live attenuated L. donovani vaccine to control L. infantum transmission in endemic areas for CVL.

  1. Stocking methods and parasite-induced reductions in capture: modelling Argulus foliaceus in trout fisheries.

    PubMed

    McPherson, N J; Norman, R A; Hoyle, A S; Bron, J E; Taylor, N G H

    2012-11-07

    Argulus foliaceus is a macroparasite which can have a significant impact on yield in recreational trout fisheries, partly by increasing fish mortalities but also by reducing the appetite of infected fish, making them less likely to respond to bait. The aim of this paper is to determine the impact of four commonly used fish stocking methods both on the parasite dynamics, and on fisheries' yields. The wider consequences of the resultant reduction in host feeding are also of interest. To this end four different stocking methods were incorporated into Anderson and May's macroparasite model, which comprises three differential equations representing the host, attached parasite and free-living parasite populations. To each of these a reduction in the fish capture rate, inversely linked to the mean parasite burden, is added and the effects interpreted. Results show that (1) the common practise of increasing the stocking rate as catches drop may be counterproductive; (2) in the absence of any wild population of reservoir hosts, the parasite will be unable to survive if the stocking rate does not exceed the rate of capture; (3) compensatory stocking to account for fish mortalities can have disastrous consequences on yield; and (4) the parasite can, under certain circumstances, maintain the host population by preventing their capture.

  2. Parasite-induced increases in the energy costs of movement of host freshwater fish.

    PubMed

    Slavík, Ondřej; Horký, Pavel; Douda, Karel; Velíšek, Josef; Kolářová, Jitka; Lepič, Pavel

    2017-03-15

    Parasitization by the larvae (glochidia) of freshwater mussels can cause harm to a fish's gills, resulting in less effective respiration and/or reduced activity by the host fish. The impact of glochidia infections on the host's physiology remains poorly understood, and no information is available concerning energy consumption in parasitized fish. Hence, we obtained glochidia of the invasive unionid mussel Sinanodonta (Anodonta) woodiana and experimentally infected common carp, Cyprinus carpio, tagged with physiological sensors to measure energy consumption. We tested the hypothesis that parasitization affects energy consumption in the host fish, reflected as higher energy costs for movement and reduced movement activity over eight days post-infection within a twenty-four-hour cycle. Parasitized fish showed higher energy costs of movement; however, no changes in movement activity were found compared with activity in control fish. Significantly increased biochemical indices were measured in host fish blood samples, including aspartate (AST) and alanine (ALT) aminotransferase levels, indicating liver injury, and high concentrations of potassium (K(+)), signifying kidney injury (hyperkalemia). Increased Cl(-) concentrations indicate gill dysfunction. Our results show that the energy costs due to glochidia parasitization are independent of overall movement activity patterns and vary in time according to the parasitic phase and the diurnal cycle. Moreover, the side effects of parasitization have a more important impact on fish hosts than has been shown in previous reports.

  3. Parasite-induced risk of mortality elevates reproductive effort in male Drosophila.

    PubMed

    Polak, M; Starmer, W T

    1998-11-22

    A trade-off between sex and somatic maintenance is fundamental to life-history theory. Tests of this trade-off usually emphasize deleterious consequences of increased reproduction on life span. Here we show the reverse effect, that reductions in the expected life span elevate sexual activity. Experimentally parasitized male Drosophila nigrospiracula lived shorter lives, but before dying, they courted females significantly more than unparasitized controls. This greater courtship resulted in increased mating speed, and potentially greater reproductive success than parasitized males would have achieved otherwise. The results show that an environmental reduction in life span increases reproductive effort, and support the hypothesis of a trade-off between these key life-history traits.

  4. 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.

  5. Multimedia regulated chemicals

    SciTech Connect

    Lee, C.C.; Huffman, G.L.; Mao, Y.L.

    1999-10-01

    This article examines those chemicals that are listed in either environmental laws or regulations. Its objective is to help readers determine which laws regulate what types of chemicals and which types of chemicals are regulated by what laws. It is multimedia in scope, describing the various chemicals that are regulated in the different media (i.e., air, water, or land).

  6. 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

  7. 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.

  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. Emotion Regulation in Parenthood

    PubMed Central

    Rutherford, Helena J.V.; Wallace, Norah S.; Laurent, Heidemarie K.; Mayes, Linda C.

    2015-01-01

    Emotion regulation, defined as the capacity to influence one’s experience and expression of emotion, is a complex skill now recognized to evolve throughout the lifetime. Here we examine the role of emotion regulation in parenthood, and propose that regulatory function during this period is distinct from the emotion regulation skills acquired and implemented during other periods of life. In this review, we consider the unique demands of caring for a child and recognize that parents have to maintain a regulated state as well as facilitate regulation in their child, especially early in development. We examine neurobiological, hormonal and behavioral shifts during the transition to parenthood that may facilitate parental regulation in response to infant cues. Furthermore, we consider how parents shape emotion regulation in their child, and the clinical implications of regulatory functioning within the parent-child relationship. PMID:26085709

  10. 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.

  11. 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.

  12. 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.

  13. Novel regulators of spermatogenesis.

    PubMed

    Fok, Kin Lam; Chen, Hao; Ruan, Ye Chun; Chan, Hsiao Chang

    2014-05-01

    Spermatogenesis is a multistep process that supports the production of millions of sperm daily. Understanding of the molecular mechanisms that regulate spermatogenesis has been a major focus for decades. Yet, the regulators involved in different cellular processes of spermatogenesis remain largely unknown. Human diseases that result in defective spermatogenesis have provided hints on the molecular mechanisms regulating this process. In this review, we have summarized recent findings on the function and signaling mechanisms of several genes that are known to be associated with disease or pathological processes, including CFTR, CD147, YWK-II and CT genes, and discuss their potential roles in regulating different processes of spermatogenesis.

  14. Federal, State, and Local regulations

    SciTech Connect

    Kelly, J.M.; Brandenburg, B.L. )

    1991-08-01

    This article is a review of federal, state, and local regulations pertinent treatment of leachate from hazardous materials landfills in California. The topics covered include under federal regulations: pretreatment, whole-effluent toxicity, hazardous waste regulation; under state regulations: hazardous waste regulations, air toxics, environmental quality act; under local regulations: local limits, toxicity-regional water quality board, air emissions and district code.

  15. The Right to Regulate

    NASA Technical Reports Server (NTRS)

    Vittek, J. F.

    1972-01-01

    An introduction to the historical and constitutional framework of industry regulation by local and Federal Governments is presented. Problems of the confiscation of private property without due process, government control and the rights and duties of the regulated industry are discussed.

  16. 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)

  17. Child Care Center Regulations.

    ERIC Educational Resources Information Center

    Nebraska State Dept. of Health and Human Services, Lincoln.

    This guide enumerates regulations for anyone caring for four or more children, from families other than their own, for compensation and on a regular basis, in the state of Nebraska. The purpose of the regulations is to protect and promote the health and safety of children in child care facilities. The first section of the guide lists specific…

  18. Metabolite turns master regulator

    PubMed Central

    Rabinowitz, Joshua D.; Silhavy, Thomas J.

    2014-01-01

    The phenomenon of catabolite repression enables microorganisms to use their favourite carbon source first. New work reveals α-ketoacids as key effectors of this process, with their levels regulating gene expression. PMID:23925111

  19. 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)

  20. Output-Based Regulations: A Handbook for Air Regulators

    EPA Pesticide Factsheets

    This handbook assists air regulators in developing emission regulations that recognize the pollution prevention benefits of CHP, and to assist CHP project owners in understanding and complying with output-based environmental regulations.

  1. In regulation we trust.

    PubMed

    Wiig, Siri; Tharaldsen, Jorunn Elise

    2012-01-01

    The role of trust has been argued to play an increasingly important role in modern, complex, and ambivalent risk societies. Trust within organizational research is anticipated to have a general strategic impact on aspects such as organizational performance, communication and knowledge exchange, and learning from accidents. Trust is also an important aspect related to regulation of risk. Diverse regulatory regimes, their contexts and risks influence regulators use of trust and distrust in regulatory practice. The aim of this paper is to discuss the relationship between risk regulation and trust across diverse risk regulation regimes. By drawing from studies of risk regulation, risk perception, and trust the purpose is to discuss how regulation and trust are linked and used in practice to control risk across system levels in socio-technical systems in high risk industries. This paper provides new knowledge on 1) how functional and dysfunctional trust and distrust are grounded in the empirical realities of high risk industries, 2) how different perspectives on trust and distrust act together and bring new knowledge on how society control risk.

  2. Epigenetic regulation in Drosophila.

    PubMed

    Lyko, F; Beisel, C; Marhold, J; Paro, R

    2006-01-01

    Epigenetic regulation of gene transcription relies on molecular marks like DNA methylation or histone modifications. Here we review recent advances in our understanding of epigenetic regulation in the fruit fly Drosophila melanogaster. In the past, DNA methylation research has primarily utilized mammalian model systems. However, several recent landmark discoveries have been made in other organisms. For example, the interaction between DNA methylation and histone methylation was first described in the filamentous fungus Neurospora crassa. Another example is provided by the interaction between epigenetic modifications and the RNA interference (RNAi) machinery that was first reported in the fission yeast Schizosaccharomyces pombe. Another organism with great experimental power is the fruit fly Drosophila. Epigenetic regulation by chromatin has been extensively analyzed in the fly and several of the key components have been discovered in this organism. In this chapter, we will focus on three aspects that represent the complexity of epigenetic gene regulation. (1) We will discuss the available data about the DNA methylation system, (2) we will illuminate the interaction between DNA methylation and chromatin regulation, and (3) we will provide an overview over the Polycomb system of epigenetic chromatin modifiers that has proved to be an important paradigm for a chromatin system regulating epigenetic programming.

  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. Appetite regulation: an overview.

    PubMed

    Dhillo, Waljit S

    2007-05-01

    Obesity is a major public health problem associated with morbidity and mortality and continues to increase worldwide. This review focuses on the regions of the brain that are important in appetite regulation and the circulating factors implicated in the control of food intake. The hypothalamus is critical in the regulation of food intake containing neural circuits, which produce a number of peptides that influence food intake. The arcuate nucleus of the hypothalamus produces both orexigenic peptides (agouti-related protein and neuropeptide Y) and anorectic peptides (alpha-melanocyte-stimulating hormone and cocaine- and amphetamine-related transcript). The lateral hypothalamus produces the orexigenic peptides (melanin-concentrating hormone and orexins). Other hypothalamic factors recently implicated in appetite regulation include the endocannabinoids, brain-derived neurotrophic factor, nesfatin-1, AMP-activated protein kinase, mammalian target of rapamycin protein, and protein tyrosine phosphatase. Circulating factors that affect food intake mediate their effects by signaling to the hypothalamus and/or brainstem. A number of circulating factors are produced by peripheral organs, for example, leptin by adipose tissue, insulin and pancreatic polypeptide by the pancreas, gut hormones (e.g., ghrelin, obestatin, glucagon-like peptide-1, oxyntomodulin, peptide YY), and triiodothyronine by the thyroid gland. Circulating carbohydrates, lipids, and amino acids also affect appetite regulation. Knowledge regarding appetite regulation has vastly expanded in recent years providing targets for antiobesity drug design.

  5. Mechanisms Regulating Protein Localization.

    PubMed

    Bauer, Nicholas C; Doetsch, Paul W; Corbett, Anita H

    2015-10-01

    Cellular functions are dictated by protein content and activity. There are numerous strategies to regulate proteins varying from modulating gene expression to post-translational modifications. One commonly used mode of regulation in eukaryotes is targeted localization. By specifically redirecting the localization of a pool of existing protein, cells can achieve rapid changes in local protein function. Eukaryotic cells have evolved elegant targeting pathways to direct proteins to the appropriate cellular location or locations. Here, we provide a general overview of these localization pathways, with a focus on nuclear and mitochondrial transport, and present a survey of the evolutionarily conserved regulatory strategies identified thus far. We end with a description of several specific examples of proteins that exploit localization as an important mode of regulation.

  6. Mechanisms regulating melanogenesis*

    PubMed Central

    Videira, Inês Ferreira dos Santos; Moura, Daniel Filipe Lima; Magina, Sofia

    2013-01-01

    Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options. PMID:23539007

  7. 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.

  8. 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…

  9. 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…

  10. 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.

  11. Adaptation with transcriptional regulation

    NASA Astrophysics Data System (ADS)

    Shi, Wenjia; Ma, Wenzhe; Xiong, Liyang; Zhang, Mingyue; Tang, Chao

    2017-02-01

    Biochemical adaptation is one of the basic functions that are widely implemented in biological systems for a variety of purposes such as signal sensing, stress response and homeostasis. The adaptation time scales span from milliseconds to days, involving different regulatory machineries in different processes. The adaptive networks with enzymatic regulation (ERNs) have been investigated in detail. But it remains unclear if and how other forms of regulation will impact the network topology and other features of the function. Here, we systematically studied three-node transcriptional regulatory networks (TRNs), with three different types of gene regulation logics. We found that the topologies of adaptive gene regulatory networks can still be grouped into two general classes: negative feedback loop (NFBL) and incoherent feed-forward loop (IFFL), but with some distinct topological features comparing to the enzymatic networks. Specifically, an auto-activation loop on the buffer node is necessary for the NFBL class. For IFFL class, the control node can be either a proportional node or an inversely-proportional node. Furthermore, the tunability of adaptive behavior differs between TRNs and ERNs. Our findings highlight the role of regulation forms in network topology, implementation and dynamics.

  12. 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…

  13. Adaptation with transcriptional regulation.

    PubMed

    Shi, Wenjia; Ma, Wenzhe; Xiong, Liyang; Zhang, Mingyue; Tang, Chao

    2017-02-24

    Biochemical adaptation is one of the basic functions that are widely implemented in biological systems for a variety of purposes such as signal sensing, stress response and homeostasis. The adaptation time scales span from milliseconds to days, involving different regulatory machineries in different processes. The adaptive networks with enzymatic regulation (ERNs) have been investigated in detail. But it remains unclear if and how other forms of regulation will impact the network topology and other features of the function. Here, we systematically studied three-node transcriptional regulatory networks (TRNs), with three different types of gene regulation logics. We found that the topologies of adaptive gene regulatory networks can still be grouped into two general classes: negative feedback loop (NFBL) and incoherent feed-forward loop (IFFL), but with some distinct topological features comparing to the enzymatic networks. Specifically, an auto-activation loop on the buffer node is necessary for the NFBL class. For IFFL class, the control node can be either a proportional node or an inversely-proportional node. Furthermore, the tunability of adaptive behavior differs between TRNs and ERNs. Our findings highlight the role of regulation forms in network topology, implementation and dynamics.

  14. 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.

  15. Neuroendocrine regulation of inflammation

    PubMed Central

    Padro, Caroline J.; Sanders, Virginia M.

    2014-01-01

    The interaction between the sympathetic nervous system and the immune system has been documented over the last several decades. In this review, the neuroanatomical, cellular, and molecular evidence for neuroimmune regulation in the maintenance of immune homeostasis will be discussed, as well as the potential impact of neuroimmune dysregulation in health and disease. PMID:24486056

  16. 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.

  17. Adaptation with transcriptional regulation

    PubMed Central

    Shi, Wenjia; Ma, Wenzhe; Xiong, Liyang; Zhang, Mingyue; Tang, Chao

    2017-01-01

    Biochemical adaptation is one of the basic functions that are widely implemented in biological systems for a variety of purposes such as signal sensing, stress response and homeostasis. The adaptation time scales span from milliseconds to days, involving different regulatory machineries in different processes. The adaptive networks with enzymatic regulation (ERNs) have been investigated in detail. But it remains unclear if and how other forms of regulation will impact the network topology and other features of the function. Here, we systematically studied three-node transcriptional regulatory networks (TRNs), with three different types of gene regulation logics. We found that the topologies of adaptive gene regulatory networks can still be grouped into two general classes: negative feedback loop (NFBL) and incoherent feed-forward loop (IFFL), but with some distinct topological features comparing to the enzymatic networks. Specifically, an auto-activation loop on the buffer node is necessary for the NFBL class. For IFFL class, the control node can be either a proportional node or an inversely-proportional node. Furthermore, the tunability of adaptive behavior differs between TRNs and ERNs. Our findings highlight the role of regulation forms in network topology, implementation and dynamics. PMID:28233824

  18. Federal Gasoline Regulations

    EPA Pesticide Factsheets

    The Clean Air Act requires EPA to regulate fuels and fuel additives for use in mobile sources if such fuel, fuel additive or any emission products causes or contributes to air or water pollution that may endanger the public health or welfare.

  19. Nondissipative optimum charge regulator

    NASA Technical Reports Server (NTRS)

    Rosen, R.; Vitebsky, J. N.

    1970-01-01

    Optimum charge regulator provides constant level charge/discharge control of storage batteries. Basic power transfer and control is performed by solar panel coupled to battery through power switching circuit. Optimum controller senses battery current and modifies duty cycle of switching circuit to maximize current available to battery.

  20. Regulation of Energy Balance.

    ERIC Educational Resources Information Center

    Bray, George A.

    1985-01-01

    Explains relationships between energy intake and expenditure focusing on the cellular, chemical and neural mechanisms involved in regulation of energy balance. Information is referenced specifically to conditions of obesity. (Physicians may earn continuing education credit by completing an appended test). (ML)

  1. REGULATIONS AND SYLLABUSES, 1968.

    ERIC Educational Resources Information Center

    Associated Examining Board, Aldershot, Hampshire (England).

    EXAMINATIONS USED IN AWARDING EDUCATIONAL CERTIFICATES TO STUDENTS IN ENGLISH SECONDARY SCHOOLS IN 1968 ARE DESCRIBED IN THIS MANUAL. IT IS WRITTEN PRIMARILY FOR HEADS OF COLLEGES AND SCHOOLS AND DESCRIBES IN DETAIL THE PROCEDURES AND REGULATIONS FOR THE ADMINISTRATION OF EXAMINATIONS IN ALL SUBJECT AREAS. EXAMINATIONS MAY BE TAKEN AT THE ORDINARY…

  2. REGULATIONS AND SYLLABUSES 1966.

    ERIC Educational Resources Information Center

    JOHNSON, ARTHUR L.; AND OTHERS

    DESCRIBED IN THIS MANUAL ARE EXAMINATIONS USED IN 1966 IN AWARDING EDUCATIONAL CERTIFICATES TO STUDENTS IN ENGLISH SECONDARY SCHOOLS AND ESTABLISHMENTS FOR FURTHER EDUCATION. IT IS WRITTEN PRIMARILY FOR HEADS OF COLLEGES AND SCHOOLS AND DESCRIBES IN DETAIL THE PROCEDURES AND REGULATIONS FOR THE ADMINISTRATION OF EXAMINATIONS IN ALL SUBJECT AREAS.…

  3. REGULATIONS AND SYLLABUSES 1967.

    ERIC Educational Resources Information Center

    Associated Examining Board, Aldershot, Hampshire (England).

    DESCRIBED IN THIS MANUAL ARE EXAMINATIONS USED IN 1967 IN AWARDING EDUCATIONAL CERTIFICATES TO STUDENTS IN ENGLISH SECONDARY SCHOOLS AND ESTABLISHMENTS FOR FURTHER EDUCATION. IT IS WRITTEN PRIMARILY FOR HEADS OF COLLEGES AND SCHOOLS AND DESCRIBES IN DETAIL THE PROCEDURES AND REGULATIONS FOR THE ADMINISTRATION OF EXAMINATIONS IN ALL SUBJECT AREAS.…

  4. Regulation of Genetic Tests

    MedlinePlus

    ... En Español: Regulación de pruebas genéticas Regulation of Genetic Tests Overview of Genetic Testing Introduction to Genetic ... Statements Congressional Activity Genetic Testing Resources Overview of Genetic Testing As the science of genomics advances, genetic ...

  5. Federal Regulation of Education.

    ERIC Educational Resources Information Center

    Shapiro, Martin

    Fresh light might be shed on problems of federal education policy by treating them not only as problems of intergovernmental relations but of government regulation of enterprise, given that they involve the attempts of a central government to influence the conduct of enterprises that it does not own nor directly operate. Using well-established…

  6. Photovoltaic power regulation system

    SciTech Connect

    Jaster, D.R.

    1986-02-18

    This patent describes a multi-solar module direct current battery charging arrangement consisting of: a group of solar cells; a reverse current blocking diode; a first relay having an energizing winding; and a set of contacts; the diode, the energizing winding and the solar module connected across the battery; a second relay having a second set of contacts; the first relay contacts operate upon a predetermined current flow through the first relay winding to close the first relay and contacts to operate the second relay. A voltage regulator has a set of contacts. The regulator contacts operate upon the battery reaching a predetermined state of charge as indicated by the voltage level; solar cells and a third relay having a set of contacts; the second relay make contacts, the voltage regulator make contacts, the third relay and the second group of solar cells connected in series; the third relay operated upon the second relay operating indicating the solar cells are functioning, and the voltage regulator operating its associated contacts indicating the batteries require further charging to operate the third relay; and the third relay operated to close the associated contacts to connect the second plurality of solar cells across the battery.

  7. Variable male potential rate of reproduction: high male mating capacity as an adaptation to parasite-induced excess of females?

    PubMed Central

    Moreau, Jérôme; Rigaud, Thierry

    2003-01-01

    Numerous animals are known to harbour intracytoplasmic symbionts that gain transmission to a new host generation via female eggs and not male sperm. Bacteria of the genus Wolbachia are a typical example. They infect a large range of arthropod species and manipulate host reproduction in several ways. In terrestrial isopods (woodlice), Wolbachia are responsible for converting males into females (feminization (F)) in some species, or for infertility in certain host crosses in other species (cytoplasmic incompatibility (CI)). Wolbachia with the F phenotype impose a strong excess of females on their host populations, while Wolbachia expressing CI do not. Here, we test the possibility that male mating capacity (MC) is correlated with Wolbachia-induced phenotype. We show that males of isopod hosts harbouring F Wolbachia possess a strong MC (i.e. are able to mate with several females in a short time), while those of species harbouring CI Wolbachia possess a weaker MC. This pattern may be explained either by the selection of high MC following the increase in female-biased sex ratios, or because the F phenotype would lead to population extinction in species where MC is not sufficiently high. This last hypotheses is nevertheless more constrained by population structure. PMID:12965021

  8. Sexual, habitat-constrained and parasite-induced dimorphism in the shell of a freshwater mussel (Anodonta anatina, Unionidae).

    PubMed

    Zieritz, Alexandra; Aldridge, David C

    2011-11-01

    Intraspecific trends in freshwater mussel (unionoid) shells that are consistently associated with differences in the mussels' sex and/or parasitic infestation can potentially be used to reconstruct sex ratios or parasitic levels of modern and ancient unionoid populations. In contrast to morphological patterns within mammal species, such dimorphic trends within unionoid species are, however, poorly understood. This study investigates, for the first time, to what extent sex, trematode infection and indirect habitat effects determine shell morphology in the freshwater mussel Anodonta anatina. Three of the five study populations displayed significant sexual shell width dimorphism. Here, shells of females were significantly wider than males, probably as a result of altered shell growth to accommodate marsupial gills. In two of these populations, female shells were additionally significantly thinner than those of males, which could be a result of resource depletion by offspring production. Two other A. anatina populations showed no significant dimorphic patterns, and our results indicate that this interpopulational difference in the degree of sexual dimorphism may reflect the overarching effect of habitat on morphology. Thus, populations in the most favourable habitats exhibit faster growth rates, attain larger maximum sizes and produce more offspring, which results in more swollen gills and consequently more inflated shells of gravid females compared to less fecund populations. None of the populations showed any evidence for sexual dimorphism in overall size, growth rate, sagittal shape and density of shells. In addition to sexual dimorphisms, infestation by bucephalid trematode parasites (Rhipidocotyle sp.) significantly altered sagittal and lateral shell shape of A. anatina in one of the populations, with infected specimens growing wider and more elongated.

  9. Functional significance of parasitism-induced suppression of juvenile hormone esterase activity in developmentally delayed Choristoneura fumiferana larvae.

    PubMed

    Cusson, M; Laforge, M; Miller, D; Cloutier, C; Stoltz, D

    2000-03-01

    The parasitic wasp Tranosema rostrale transmits a polydnavirus (PDV) to its host, Choristoneura fumiferana, during oviposition. Last-instar C. fumiferana larvae parasitized by T. rostrale early in the stadium fail to undergo metamorphosis, and injection of the wasp's calyx fluid (CxF; contains PDV) into healthy caterpillars induces a dose-dependent delay in initiation of metamorphosis (D. Doucet and M. Cusson, 1996, Entomol. Exp. Appl. 81, 21-30). In the present work, parasitization and injection of CxF (0.5 female equivalent) on the first day of the last stadium both prevented the rise in hemolymph 20-hydroxyecdysone (20HE) titer observed between day 4 and day 7 in control and saline-injected larvae. Similarly, juvenile hormone esterase (JHE) activity was depressed following parasitization or CxF injection, whereas control larvae displayed a peak on day 4. However, neither parasitism nor injection of CxF on day 1 prevented the JH-producing glands from turning off during the first half of the last stadium. Likewise, low but clearly detectable JH titers were observed in the first hours following the molt but very low titers, at or near the detection limit of our radioimmunoassay, were seen in both control and parasitized larvae on day 4. Prothoracic glands showed no apparent sign of degeneration 4 days after injection of CxF but had significantly smaller cells than saline-injected larvae 7 days postinjection. It is not clear whether this was a direct effect of T. rostrale PDV. Thus, disruption of spruce budworm metamorphosis by T. rostrale CxF involves depression of 20HE titers but is not associated with a measurable increase in the level of JH, as shown for some other host-parasitoid systems. In view of the latter observation, we put forward three hypotheses regarding the functional significance of the observed suppression of JHE activity in developmentally arrested C. fumiferana larvae.

  10. 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

  11. Risk and regulation

    NASA Astrophysics Data System (ADS)

    Porter, Joan P.

    1994-12-01

    Regulation of the health care industry and development of drugs, biologics and devices has developed, in part, to ensure public safety. There are numerous forces that promote regulatory efforts and those that work against formal regulatory measures. This presentation provides an overview of the following: What is risk? What is risk assessment? What drives regulatory activity to ensure public safety? What are the issue areas surrounding cost benefit analysis? How is technology helpful in assessing and managing risks? How does health care reform drive new technologies which, in turn, must be assessed for risk and cost/benefit? A force field analysis model of factors contributing to regulatory activities and those that work against the promulgation of regulations is offered.

  12. 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

  13. 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.

  14. A regulated magnetron pulser

    SciTech Connect

    Rose, C.R.

    1997-09-01

    This paper describes and analysis of a 4.5-kV, 500-mA, regulated current pulser used to drive a Hitachi ZM130 magnetron in a particle-accelerator injector. In this application, precise beam from the injector. A high-voltage triode vacuum tube with active feedback is used to control the magnetron current. Current regulation and accuracy is better than 1%. The pulse width may be varied from as little as 5 {mu}m to cw by varying the width of a gate pulse. The current level can be programmed between 10 and 500 mA. Design of the pulser including circuit simulations, power calculations, and high-voltage issues are discussed.

  15. CNS regulation of appetite.

    PubMed

    Harrold, Joanne A; Dovey, Terry M; Blundell, John E; Halford, Jason C G

    2012-07-01

    This article reviews the regulation of appetite from a biopsychological perspective. It considers psychological experiences and peripheral nutritional systems (both episodic and tonic) and addresses their relationship with the CNS networks that process and integrate their input. Whilst such regulatory aspects of obesity focus on homeostatic control mechanisms, in the modern environment hedonic aspects of appetite are also critical. Enhanced knowledge of the complexity of appetite regulation and the mechanisms that sustain obesity indicate the challenge presented by management of the obesity epidemic. Nonetheless, effective control of appetite expression remains a critical therapeutic target for weight management. Currently, strategies which utilise a combination of agents to target both homeostatic and hedonic control mechanisms represent the most promising approaches. This article is part of a Special Issue entitled 'Central Control of Food Intake'.

  16. Ensembl regulation resources

    PubMed Central

    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

  17. Improving CS regulations.

    SciTech Connect

    Nesse, R.J.; Scheer, R.M.; Marasco, A.L.; Furey, R.

    1980-10-01

    President Carter issued Executive Order 12044 (3/28/78) that required all Federal agencies to distinguish between significant and insignificant regulations, and to determine whether a regulation will result in major impacts. This study gathered information on the impact of the order and the guidelines on the Office of Conservation and Solar Energy (CS) regulatory practices, investigated problems encountered by the CS staff when implementing the order and guidelines, and recommended solutions to resolve these problems. Major tasks accomplished and discussed are: (1) legislation, Executive Orders, and DOE Memoranda concerning Federal administrative procedures relevant to the development and analysis of regulations within CS reviewed; (2) relevant DOE Orders and Memoranda analyzed and key DOE and CS staff interviewed in order to accurately describe the current CS regulatory process; (3) DOE staff from the Office of the General Counsel, the Office of Policy and Evaluation, the Office of the Environment, and the Office of the Secretary interviewed to explore issues and problems encountered with current CS regulatory practices; (4) the regulatory processes at five other Federal agencies reviewed in order to see how other agencies have approached the regulatory process, dealt with specific regulatory problems, and responded to the Executive Order; and (5) based on the results of the preceding four tasks, recommendations for potential solutions to the CS regulatory problems developed. (MCW)

  18. [Sleep: regulation and phenomenology].

    PubMed

    Vecchierini, M-F

    2013-12-01

    This article describes the two-process model of sleep regulation. The 24-hour sleep-wake cycle is regulated by a homeostatic process and an endogenous, 2 oscillators, circadian process, under the influence of external synchronisers. These two processes are partially independent but influence each other, as shown in the two-sleep-process auto-regulation model. A reciprocal inhibition model of two interconnected neuronal groups, "SP on" and "SP off", explains the regular recurrence of paradoxical sleep. Sleep studies have primarily depended on observation of the subject and have determined the optimal conditions for sleep (position, external conditions, sleep duration and need) and have studied the consequences of sleep deprivation or modifications of sleep schedules. Then, electrophysiological recordings permitted the classification of sleep stages according to the observed EEG patterns. The course of a night's sleep is reported on a "hypnogram". The adult subject falls asleep in non-REM sleep (N1), then sleep deepens progressively to stages N2 and N3 with the appearance of spindles and slow waves (N2). Slow waves become more numerous in stage N3. Every 90minutes REM sleep recurs, with muscle atonia and rapid eye movements. These adult sleep patterns develop progressively during the 2 first years of life as total sleep duration decreases, with the reduction of diurnal sleep and of REM sleep. Around 2 to 4 months, spindles and K complexes appear on the EEG, with the differentiation of light and deep sleep with, however, a predominance of slow wave sleep.

  19. 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.

  20. Regulation of biomedical products.

    PubMed

    Gillett, Grant; Saville-Cook, Donald

    2010-05-01

    Two recent decisions, one from Australia and one from Canada, should cause us to examine the ethical issues surrounding the regulation of biomedical products. The protection of vulnerable consumers from variable quality and poorly prepared drugs with uncertain parameters of safety and efficacy is a priority for any community and should not have to be weighed against possible costs based on restrictions of trade. However, the possibility of an environment in which the multinational biomedical industry edges out any other players in the treatment of various illnesses has its own dangers. Not least is the apparent collusion between regulators and industry that ramps up the costs and intensity of licensing and risk management so that only an industry-type budget can sustain the costs of compliance. This has the untoward effect of delivering contemporary health care into the hands of those who make immense fortunes out of it. An approach to regulation that tempers bureaucratic mechanisms with a dose of common sense and realistic evidence-based risk assessment could go a long way in avoiding the Scylla and Charybdis awaiting the clinical world in these troubled waters.

  1. Cytokines in sleep regulation.

    PubMed

    Krueger, J M; Takahashi, S; Kapás, L; Bredow, S; Roky, R; Fang, J; Floyd, R; Renegar, K B; Guha-Thakurta, N; Novitsky, S

    1995-01-01

    The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infection and in the physiological regulation of sleep. We hypothesize that many cytokines, their cellular receptors, soluble receptors, and endogenous antagonists are involved in physiological sleep regulation. The expressions of some cytokines are greatly amplified by microbial challenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at different times during the course of the infectious process results from dynamic changes in various cytokines that occur during the host's response to infectious challenge. Removal of any one somnogenic cytokine inhibits normal sleep, alters the cytokine network by changing the cytokine mix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/autocrine fashion and is responsive to neuronal use. Finally, cytokines elicit their somnogenic actions via endocrine and neurotransmitter systems as well as having direct effects neurons and glia. Evidence in support of these postulates is reviewed in this essay.

  2. 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.

  3. Whither tobacco product regulation?

    PubMed

    McNeill, Ann; Hammond, David; Gartner, Coral

    2012-03-01

    Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets.

  4. 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...

  5. Using Science for Environmental Regulation

    EPA Science Inventory

    Scientists have helped apply environmental aquatic toxicology to develop regulations for EPA over many years. This presentation will highlight some historical changes in the aquatic environment and how EPA has used them to develop regulations for the Clean Water Act.

  6. 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.

  7. [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.

  8. Applicability of PSD Regulations

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  9. Epigenetic Regulation in Plants

    PubMed Central

    Pikaard, Craig S.; Mittelsten Scheid, Ortrun

    2014-01-01

    The study of epigenetics in plants has a long and rich history, from initial descriptions of non-Mendelian gene behaviors to seminal discoveries of chromatin-modifying proteins and RNAs that mediate gene silencing in most eukaryotes, including humans. Genetic screens in the model plant Arabidopsis have been particularly rewarding, identifying more than 130 epigenetic regulators thus far. The diversity of epigenetic pathways in plants is remarkable, presumably contributing to the phenotypic plasticity of plant postembryonic development and the ability to survive and reproduce in unpredictable environments. PMID:25452385

  10. Feeding regulation in Drosophila

    PubMed Central

    Pool, Allan-Hermann; Scott, Kristin

    2014-01-01

    Neuromodulators play a key role in adjusting animal behavior based on environmental cues and internal needs. Here, we review the regulation of Drosophila feeding behavior to illustrate how neuromodulators achieve behavioral plasticity. Recent studies have made rapid progress in determining molecular and cellular mechanisms that translate the metabolic needs of the fly into changes in neuroendocrine and neuromodulatory states. These neuromodulators in turn promote or inhibit discrete feeding behavioral subprograms. This review highlights the links between physiological needs, neuromodulatory states, and feeding decisions. PMID:24937262

  11. 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.

  12. Nitric oxide inhibits viral replication in murine myocarditis.

    PubMed Central

    Lowenstein, C J; Hill, S L; Lafond-Walker, A; Wu, J; Allen, G; Landavere, M; Rose, N R; Herskowitz, A

    1996-01-01

    Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo. PMID:8621766

  13. Rapamycin regulates biochemical metabolites

    PubMed Central

    Tucci, Paola; Porta, Giovanni; Agostini, Massimiliano; Antonov, Alexey; Garabadgiu, Alexander Vasilievich; Melino, Gerry; Willis, Anne E

    2013-01-01

    The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes. To investigate the metabolic changes that occur upon inhibition of the mTOR pathway and the role of p73 in this response primary mouse embryonic fibroblast from control and TAp73−/− were treated with the macrocyclic lactone rapamycin. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analysis were used to obtain a rapamycin-dependent global metabolome profile from control or TAp73−/− cells. In total 289 metabolites involved in selective pathways were identified; 39 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. PMID:23839040

  14. 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.

  15. [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.

  16. Regulations and Procedures Manual

    SciTech Connect

    Young, Lydia J.

    2011-07-25

    The purpose of the Regulations and Procedures Manual (RPM) is to provide LBNL personnel with a reference to University and Lawrence Berkeley National Laboratory (LBNL or Laboratory) policies and regulations by outlining normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory organizations. Much of the information in this manual has been condensed from detail provided in LBNL procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. RPM sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the LBNL organization responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which organization is responsible for a policy, please contact Requirements Manager Lydia Young or the RPM Editor.

  17. Regulations and Procedures Manual

    SciTech Connect

    Young, Lydia

    2010-09-30

    The purpose of the Regulations and Procedures Manual (RPM) is to provide Laboratory personnel with a reference to University and Lawrence Berkeley National Laboratory policies and regulations by outlining the normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory departments. Much of the information in this manual has been condensed from detail provided in Laboratory procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. The sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the department responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which department should be called, please contact the Associate Laboratory Director of Operations.

  18. 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.

  19. 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.

  20. Transcription Regulation in Archaea

    PubMed Central

    Gehring, Alexandra M.; Walker, Julie E.

    2016-01-01

    The known diversity of metabolic strategies and physiological adaptations of archaeal species to extreme environments is extraordinary. Accurate and responsive mechanisms to ensure that gene expression patterns match the needs of the cell necessitate regulatory strategies that control the activities and output of the archaeal transcription apparatus. Archaea are reliant on a single RNA polymerase for all transcription, and many of the known regulatory mechanisms employed for archaeal transcription mimic strategies also employed for eukaryotic and bacterial species. Novel mechanisms of transcription regulation have become apparent by increasingly sophisticated in vivo and in vitro investigations of archaeal species. This review emphasizes recent progress in understanding archaeal transcription regulatory mechanisms and highlights insights gained from studies of the influence of archaeal chromatin on transcription. PMID:27137495

  1. Immune Regulation of Cancer

    PubMed Central

    Disis, Mary L.

    2010-01-01

    Innate and adaptive immune system cells play a major role in regulating the growth of cancer. Although it is commonly thought that an immune response localized to the tumor will inhibit cancer growth, it is clear that some types of inflammation induced in a tumor may also lead to cancer proliferation, invasion, and dissemination. Recent evidence suggests, however, that some patients with cancer can mount an antitumor immune response that has the potential to control or eliminate cancer. Indeed, a so-called “immune response” signature has been described in malignancy that is associated with improved outcomes in several tumor types. Moreover, the presence of specific subsets of T cells, which have the capability to penetrate tumor stroma and infiltrate deep into the parenchyma, identifies patients with an improved prognosis. Immune-based therapies have the potential to modulate the tumor microenvironment by eliciting immune system cells that will initiate acute inflammation that leads to tissue destruction. PMID:20516428

  2. Regulation of cholesterol homeostasis.

    PubMed

    van der Wulp, Mariëtte Y M; Verkade, Henkjan J; Groen, Albert K

    2013-04-10

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia.

  3. Regulation of Transcript Elongation

    PubMed Central

    Belogurov, Georgiy A.; Artsimovitch, Irina

    2015-01-01

    Bacteria lack subcellular compartments and harbor a single RNA polymerase that synthesizes both structural and protein-coding RNAs, which are cotranscriptionally processed by distinct pathways. Nascent rRNAs fold into elaborate secondary structures and associate with ribosomal proteins, whereas nascent mRNAs are translated by ribosomes. During elongation, nucleic acid signals and regulatory proteins modulate concurrent RNA-processing events, instruct RNA polymerase where to pause and terminate transcription, or act as roadblocks to the moving enzyme. Communications among complexes that carry out transcription, translation, repair, and other cellular processes ensure timely execution of the gene expression program and survival under conditions of stress. This network is maintained by auxiliary proteins that act as bridges between RNA polymerase, ribosome, and repair enzymes, blurring boundaries between separate information-processing steps and making assignments of unique regulatory functions meaningless. Understanding the regulation of transcript elongation thus requires genome-wide approaches, which confirm known and reveal new regulatory connections. PMID:26132790

  4. Pubertal development and regulation

    PubMed Central

    Abreu, Ana Paula; Kaiser, Ursula B

    2016-01-01

    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. PMID:26852256

  5. Redox regulation: an introduction.

    PubMed

    Dietz, Karl-Josef; Scheibe, Renate

    2004-01-01

    The redox-state is a critical determinate of cell function, and any major imbalances can cause severe damage or death. The cellular redox status therefore needs to be sensed and modulated before such imbalances occur. Various redox-active components are involved in these processes, including thioredoxins, glutaredoxins and other thiol/disulphide-containing proteins. The cellular reactions for cytoprotection and for signalling are integrated with physiological redox-reactions in photosynthesis, assimilation and respiration. They also determine the developmental fate of the cell and finally decide on proliferation or cell death. An international workshop on redox regulation, organized by the research initiative FOR 387 of the Deutsche Forschungsgemeinschaft, was held in Bielefeld, Germany in 2002. A selection of articles originating from the meeting is printed in this issue of Physiologia Plantarum.

  6. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

  7. 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.

  8. [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.

  9. 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.

  10. 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.

  11. Endocannabinoids in cerebrovascular regulation

    PubMed Central

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

    2016-01-01

    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

  12. 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.

  13. Shame regulation in personality pathology.

    PubMed

    Schoenleber, Michelle; Berenbaum, Howard

    2012-05-01

    Drawing on extant work on shame and emotion regulation, this article proposes that three broad forms of maladaptive shame regulation strategies are fundamental in much of personality pathology: Prevention (e.g., dependence, fantasy), used preemptively, lessens potential for shame; Escape (e.g., social withdrawal, misdirection) reduces current or imminent shame; Aggression, used after shame begins, refocuses shame into anger directed at the self (e.g., physical self-harm) or others (e.g., verbal aggression). This article focuses on the contributions of shame regulation to the development and maintenance of personality pathology, highlighting how various maladaptive shame regulation strategies may lead to personality pathology symptoms, associated features, and dimensions. Consideration is also given to the possible shame-related constructs necessitating emotion regulation (e.g., shame aversion and proneness) and the points in the emotion process when regulation can occur.

  14. 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

  15. NCAM regulates cell motility.

    PubMed

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna; Hartmann-Petersen, Rasmus; Kawa, Anna; Walmod, Peter S; Belman, Vadym; Gallagher, Helen C; Berezin, Vladimir; Bock, Elisabeth; Pedersen, Nina

    2002-01-15

    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine inhibitor of NCAM-negative cell locomotion through a heterophilic interaction with a cell-surface receptor. As we showed that the two N-terminal immunoglobulin modules of NCAM, which are known to bind to heparin, were responsible for this inhibition, we presume that this receptor is a heparan sulfate proteoglycan. A model for the inhibitory effect of NCAM is proposed, which involves competition between NCAM and extracellular components for the binding to membrane-associated heparan sulfate proteoglycan.

  16. Phosphorylation regulates mycobacterial proteasome.

    PubMed

    Anandan, Tripti; Han, Jaeil; Baun, Heather; Nyayapathy, Seeta; Brown, Jacob T; Dial, Rebekah L; Moltalvo, Juan A; Kim, Min-Seon; Yang, Seung Hwan; Ronning, Donald R; Husson, Robert N; Suh, Joowon; Kang, Choong-Min

    2014-09-01

    Mycobacterium tuberculosis possesses a proteasome system that is required for the microbe to resist elimination by the host immune system. Despite the importance of the proteasome in the pathogenesis of tuberculosis, the molecular mechanisms by which proteasome activity is controlled remain largely unknown. Here, we demonstrate that the α-subunit (PrcA) of the M. tuberculosis proteasome is phosphorylated by the PknB kinase at three threonine residues (T84, T202, and T178) in a sequential manner. Furthermore, the proteasome with phosphorylated PrcA enhances the degradation of Ino1, a known proteasomal substrate, suggesting that PknB regulates the proteolytic activity of the proteasome. Previous studies showed that depletion of the proteasome and the proteasome-associated proteins decreases resistance to reactive nitrogen intermediates (RNIs) but increases resistance to hydrogen peroxide (H2O2). Here we show that PknA phosphorylation of unprocessed proteasome β-subunit (pre-PrcB) and α-subunit reduces the assembly of the proteasome complex and thereby enhances the mycobacterial resistance to H2O2 and that H2O2 stress diminishes the formation of the proteasome complex in a PknA-dependent manner. These findings indicate that phosphorylation of the M. tuberculosis proteasome not only modulates proteolytic activity of the proteasome, but also affects the proteasome complex formation contributing to the survival of M. tuberculosis under oxidative stress conditions.

  17. 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.

  18. Visibility: science and regulation.

    PubMed

    Watson, John G

    2002-06-01

    The 1999 Regional Haze Rule provides a context for this review of visibility, the science that describes it, and the use of that science in regulatory guidance. The scientific basis for the 1999 regulation is adequate. The deciview metric that tracks progress is an imperfect but objective measure of what people see near the prevailing visual range. The definition of natural visibility conditions is adequate for current planning, but it will need to be refined as visibility improves. Emissions from other countries will set achievable levels above those produced by natural sources. Some natural events, notably dust storms and wildfires, are episodic and cannot be represented by annual average background values or emission estimates. Sulfur dioxide (SO2) emission reductions correspond with lower sulfate (SO4(2-)) concentrations and visibility improvements in the regions where these have occurred. Non-road emissions have been growing more rapidly than emissions from other sources, which have remained stable or decreased since 1970. Simpler models representing transport, limiting precursor pollutants, and gas-to-particle equilibrium should be used to understand where and when emission reductions will be effective, rather than large complex models that have insufficient input and validation measurements. Examples of model-based source attribution show large differences among estimates from various modeling systems and with ambient measurements.

  19. [Ghrelin: beyond hunger regulation].

    PubMed

    Milke García, Maria del Pilar

    2005-01-01

    Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.

  20. Power-MOSFET Voltage Regulator

    NASA Technical Reports Server (NTRS)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  1. 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

  2. Post-translational regulation enables robust p53 regulation

    PubMed Central

    2013-01-01

    Background The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. Results We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Conclusions Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control. PMID:23992617

  3. 76 FR 43585 - Bank Secrecy Act Regulations; Definitions and Other Regulations Relating to Money Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Regulations; Definitions and Other Regulations Relating to Money Services Businesses AGENCY: Treasury... Proposed Rulemaking, Definitions and Other Regulations Relating to Money Services Businesses, 74 FR 22129... to the Bank Secrecy Act Regulations-- Definitions and Other Regulations Relating to Money...

  4. 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.

  5. 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…

  6. 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.

  7. 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)

  8. 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…

  9. 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…

  10. Frequency-controlled voltage regulator

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1980-01-01

    Converting input ac to higher frequency reduce size and weight and makes possible unique kind of regulation. Since conversion frequency is above range of human hearing, supply generated on audible noise. It also exploits highfrequency conversion features to regulate its output voltage in novel way. Circuit is inherently short-circuit proof.

  11. 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.

  12. Strategic automation of emotion regulation.

    PubMed

    Gallo, Inge Schweiger; Keil, Andreas; McCulloch, Kathleen C; Rockstroh, Brigitte; Gollwitzer, Peter M

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i.e., an if-then plan), and a no-self-regulation control group. Only implementation-intention participants succeeded in reducing their disgust and fear reactions as compared to goal-intention and control participants. In Study 3, electrocortical correlates (using dense-array electroencephalography) revealed differential early visual activity in response to spider slides in ignore implementation-intention participants, as reflected in a smaller P1. Theoretical and applied implications of the present findings for emotion regulation via implementation intentions are discussed.

  13. 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.

  14. 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.

  15. 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.

  16. 76 FR 35739 - Foreign Assets Control Regulations; Transaction Control Regulations (Regulations Prohibiting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... CFR part 500 (the ``FACR''), and the Transaction Control Regulations, 31 CFR part 505 (the ``TCR... FACR and TCR immediately prior to the issuance of Proclamation 8271 were those that related to North... TCR from 31 CFR chapter V. Public Participation Because the Regulations involve a foreign...

  17. 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.

  18. The regulation of ascorbate biosynthesis.

    PubMed

    Bulley, Sean; Laing, William

    2016-10-01

    We review the regulation of ascorbate (vitamin C) biosynthesis, focusing on the l-galactose pathway. We discuss the regulation of ascorbate biosynthesis at the level of gene transcription (both repression and enhancement) and translation (feedback inhibition of translation by ascorbate concentration) and discuss the eight proteins that have been demonstrated to date to affect ascorbate concentration in plant tissues. GDP-galactose phosphorylase (GGP) and GDP-mannose epimerase are critical steps that regulate ascorbate biosynthesis. These and other biosynthetic genes are controlled at the transcriptional level, while GGP is also controlled at the translational level. Ascorbate feedback on enzyme activity has not been observed unequivocally.

  19. 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.

  20. Emotional regulation strategies and negotiation.

    PubMed

    Yurtsever, Gülçimen

    2004-12-01

    This study examined the relationship between profit achievement and emotional regulation strategies, using Kelley's Negotiation Game to measure profit achievement. The game involves bargaining for the prices of three products. Emotional Regulation Strategies were measured by The Emotional Regulation Questionnaire. Scores were obtained from 104 lower level managers of a bank in Turkey. Their average age was 32.0 yr. (SD=3.7), (39 women and 65 men). A correlation of .65 (p<.01) was obtained between scores on profit achievement with scores on Cognitive Reappraisal strategy and -.50 (p<.01) with scores on Suppression strategy.

  1. 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.

  2. How is Pet Coke Regulated?

    EPA Pesticide Factsheets

    No emission standards apply specifically to the storage and handling of petroleum coke, but National Ambient Air Quality Standards (NAAQS) for particulate matter (PM10) do apply, so states have regulations as part of their Air State Implementation Plan.

  3. 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)

  4. Gastrointestinal regulation of food intake

    PubMed Central

    Cummings, David E.; Overduin, Joost

    2007-01-01

    Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes. PMID:17200702

  5. Regulation of TAZ in cancer.

    PubMed

    Zhou, Xin; Lei, Qun-Ying

    2016-08-01

    TAZ, a transcriptional coactivator with PDZ-binding motif, is encoded by WWTR1 gene (WW domain containing transcription regulator 1). TAZ is tightly regulated in the hippo pathway-dependent and -independent manner in response to a wide range of extracellular and intrinsic signals, including cell density, cell polarity, F-actin related mechanical stress, ligands of G protein-coupled receptors (GPCRs), cellular energy status, hypoxia and osmotic stress. Besides its role in normal tissue development, TAZ plays critical roles in cell proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), and stemness in multiple human cancers. We discuss here the regulators and regulation of TAZ. We also highlight the tumorigenic roles of TAZ and its potential therapeutic impact in human cancers.

  6. Targeting epigenetic regulations in cancer

    PubMed Central

    Ning, Bo; Li, Wenyuan; Zhao, Wei; Wang, Rongfu

    2016-01-01

    Epigenetic regulation of gene expression is a dynamic and reversible process with DNA methylation, histone modifications, and chromatin remodeling. Recently, groundbreaking studies have demonstrated the importance of DNA and chromatin regulatory proteins from different aspects, including stem cell, development, and tumor genesis. Abnormal epigenetic regulation is frequently associated with diseases and drugs targeting DNA methylation and histone acetylation have been approved for cancer therapy. Although the network of epigenetic regulation is more complex than people expect, new potential druggable chromatin-associated proteins are being discovered and tested for clinical application. Here we review the key proteins that mediate epigenetic regulations through DNA methylation, the acetylation and methylation of histones, and the reader proteins that bind to modified histones. We also discuss cancer associations and recent progress of pharmacological development of these proteins. PMID:26508480

  7. 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.

  8. 77 FR 13155 - Waste Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-05

    ... From the Federal Register Online via the Government Publishing Office NATIONAL SCIENCE FOUNDATION Waste Regulation AGENCY: National Science Foundation. ACTION: Notice of permit modification request... Martin personnel will be assuming responsibility for waste management activities. Those activities...

  9. 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.

  10. Chloroplast signaling: retrograde regulation revelations.

    PubMed

    Beale, Samuel I

    2011-05-24

    Developing chloroplasts are able to communicate their status to the nucleus and regulate expression of genes whose products are needed for photosynthesis. Heme is revealed to be a signaling molecule for this retrograde communication.

  11. 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

  12. Self Regulating Fiber Fuel Cell

    DTIC Science & Technology

    2010-08-16

    energy numbers are 2.3X and 5.7X the theoretical values for lithium thionyl chloride respectively (1100 Whr/liter and 590 Whr/kg), which has the...REPORT Self Regulating Fiber Fuel Cell 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: Advances in lithium primary battery technology, which serves as the...Prescribed by ANSI Std. Z39.18 - 16-Aug-2010 Self Regulating Fiber Fuel Cell Report Title ABSTRACT Advances in lithium primary battery technology

  13. 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....

  14. 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...

  15. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally. The uses of land within a flood hazard area shall be subject to regulation within one of the following... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Regulations...

  16. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally. The uses of land within a flood hazard area shall be subject to regulation within one of the following... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Regulations...

  17. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally. The uses of land within a flood hazard area shall be subject to regulation within one of the following... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Regulations...

  18. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally. The uses of land within a flood hazard area shall be subject to regulation within one of the following... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Regulations...

  19. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally. The uses of land within a flood hazard area shall be subject to regulation within one of the following... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Regulations...

  20. 75 FR 24394 - Somalia Sanctions Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... Other Laws and Regulations Sec. 551.101 Relation of this part to other laws and regulations. Subpart B... Laws and Regulations Sec. 551.101 Relation of this part to other laws and regulations. This part is... or issued pursuant to any other provision of law or regulation authorizes any transaction...

  1. 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

  2. Regulation Development for Drinking Water Contaminants

    EPA Pesticide Factsheets

    To explain what process and information underlies regulations including how the Safe Drinking Water Act applies to regulation development i.e. how does the drinking water law translate into regulations.

  3. 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.

  4. 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

  5. Thyroid Hormone Regulation of Metabolism

    PubMed Central

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    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. PMID:24692351

  6. 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....

  7. 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....

  8. 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....

  9. 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....

  10. 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....

  11. Redox regulation of intercellular transport.

    PubMed

    Benitez-Alfonso, Yoselin; Jackson, David; Maule, Andy

    2011-01-01

    Plant cells communicate with each other via plasmodesmata (PDs) in order to orchestrate specific responses to environmental and developmental cues. At the same time, environmental signals regulate this communication by promoting changes in PD structure that modify symplastic permeability and, in extreme cases, isolate damaged cells. Reactive oxygen species (ROS) are key messengers in plant responses to a range of biotic and abiotic stresses. They are also generated during normal metabolism, and mediate signaling pathways that modulate plant growth and developmental transitions. Recent research has suggested the participation of ROS in the regulation of PD transport. The study of several developmental and stress-induced processes revealed a co-regulation of ROS and callose (a cell wall polymer that regulates molecular flux through PDs). The identification of Arabidopsis mutants simultaneously affected in cell redox homeostasis and PD transport, and the histological detection of hydrogen peroxide and peroxidases in the PDs of the tomato vascular cambium provide new information in support of this novel regulatory mechanism. Here, we describe the evidence that supports a role for ROS in the regulation of callose deposition and/or in the formation of secondary PD, and discuss the potential importance of this mechanism during plant growth or defense against environmental stresses.

  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. 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.

  14. 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.

  15. 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

  16. Circadian regulation of lipid metabolism.

    PubMed

    Gooley, Joshua J

    2016-11-01

    The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

  17. 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.

  18. 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.

  19. Planned and proposed pipeline regulations

    SciTech Connect

    De Leon, C. )

    1992-04-01

    The Research and Special Programs Administration administers the Natural Gas Pipeline Safety Act of 1968 (NGPSA) and the Hazardous Liquid Pipeline Safety Act of 1979 (HLPSA). The RSPA issues and enforces design, construction, operation and maintenance regulations for natural gas pipelines and hazardous liquid pipelines. This paper discusses a number of proposed and pending safety regulations and legislative initiatives currently being considered by the RSPA and the US Congress. Some new regulations have been enacted. The next few years will see a great deal of regulatory activity regarding natural gas and hazardous liquid pipelines, much of it resulting from legislative requirements. The office of Pipeline Safety is currently conducting a study to streamline its operations. This study is analyzing the office's business, social and technical operations with the goal of improving overall efficiency, effectiveness, productivity and job satisfaction to meet the challenges of the future.

  20. 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

  1. Regulation of cellular chromatin state

    PubMed Central

    Mishra, Rakesh K; Dhawan, Jyotsna

    2010-01-01

    The identity and functionality of eukaryotic cells is defined not just by their genomic sequence which remains constant between cell types, but by their gene expression profiles governed by epigenetic mechanisms. Epigenetic controls maintain and change the chromatin state throughout development, as exemplified by the setting up of cellular memory for the regulation and maintenance of homeotic genes in proliferating progenitors during embryonic development. Higher order chromatin structure in reversibly arrested adult stem cells also involves epigenetic regulation and in this review we highlight common trends governing chromatin states, focusing on quiescence and differentiation during myogenesis. Together, these diverse developmental modules reveal the dynamic nature of chromatin regulation providing fresh insights into the role of epigenetic mechanisms in potentiating development and differentiation. PMID:20592864

  2. 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.

  3. Upstream regulation of mycotoxin biosynthesis.

    PubMed

    Alkhayyat, Fahad; Yu, Jae-Hyuk

    2014-01-01

    Mycotoxins are natural contaminants of food and feed products, posing a substantial health risk to humans and animals throughout the world. A plethora of filamentous fungi has been identified as mycotoxin producers and most of these fungal species belong to the genera Aspergillus, Fusarium, and Penicillium. A number of studies have been conducted to better understand the molecular mechanisms of biosynthesis of key mycotoxins and the regulatory cascades controlling toxigenesis. In many cases, the mycotoxin biosynthetic genes are clustered and regulated by one or more pathway-specific transcription factor(s). In addition, as biosynthesis of many secondary metabolites is coordinated with fungal growth and development, there are a number of upstream regulators affecting biosynthesis of mycotoxins in fungi. This review presents a concise summary of the regulation of mycotoxin biosynthesis, focusing on the roles of the upstream regulatory elements governing biosynthesis of aflatoxin and sterigmatocystin in Aspergillus.

  4. Chloroplast retrograde signal regulates flowering

    PubMed Central

    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

    2016-01-01

    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

  5. Calcium regulation of muscle contraction.

    PubMed Central

    Szent-Györgyi, A G

    1975-01-01

    Calcium triggers contraction by reaction with regulatory proteins that in the absence of calcium prevent interaction of actin and myosin. Two different regulatory systems are found in different muscles. In actin-linked regulation troponin and tropomyosin regulate actin by blocking sites on actin required for complex formation with myosin; in myosin-linked regulation sites on myosin are blocked in the absence of calcium. The major features of actin control are as follows: there is a requirement for tropomyosin and for a troponin complex having three different subunits with different functions; the actin displays a cooperative behavior; and a movement of tropomyosin occurs controlled by the calcium binding on troponin. Myosin regulation is controlled by a regulatory subunit that can be dissociated in scallop myosin reversibly by removing divalent cations with EDTA. Myosin control can function with pure actin in the absence of tropomyosin. Calcium binding and regulation of molluscan myosins depend on the presence of regulatory light chains. It is proposed that the light chains function by sterically blocking myosin sites in the absence of calcium, and that the "off" state of myosin requires cooperation between the two myosin heads. Both myosin control and actin control are widely distributed in different organisms. Many invertebrates have muscles with both types of regulation. Actin control is absent in the muscles of molluscs and in several minor phyla that lack troponin. Myosin control is not found in striated vertebrate muscles and in the fast muscles of crustacean decapods, although regulatory light chains are present. While in vivo myosin control may not be excluded from vertebrate striated muscles, myosin control may be absent as a result of mutations of the myosin heavy chain. PMID:806311

  6. 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

  7. 75 FR 68217 - Acquisition Regulation: Agency Supplementary Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... not impose any additional requirements on small businesses. Today's rule does not alter any... Federal Acquisition Regulation (FAR), remove out-of-date coverage, and update references. Today's rule... Under the Small Business Regulatory Enforcement Fairness Act of 1996 L. Approval by the Office of...

  8. Politics of public utility regulation

    SciTech Connect

    Gormley, W.T. Jr.

    1983-01-01

    Since the early 1970s, energy and telecommunications policies have emerged as increasingly complex and conflictual issues in state government and have, consequently, brought about change in the politics of public utilities regulation. In this analysis, Gormley shows that state public utilities commissions, in determining the rates that can be charged by private utility companies, must confront elected government officials, members of the state bureaucracy, citizens' groups, and the regulated industries themselves in a very visible, highly technical, costly, and controversial process that pits investors against consumers, business groups against residential consumers, consumer groups against environmentalists, and low-income consumers against consumers as a whole.

  9. Regulations against the human nature

    NASA Astrophysics Data System (ADS)

    Elizondo-Garza, Fernando J.

    2004-05-01

    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.

  10. Transcription regulation mechanisms of bacteriophages

    PubMed Central

    Yang, Haiquan; Ma, Yingfang; Wang, Yitian; Yang, Haixia; Shen, Wei; Chen, Xianzhong

    2014-01-01

    Phage diversity significantly contributes to ecology and evolution of new bacterial species through horizontal gene transfer. Therefore, it is essential to understand the mechanisms underlying phage-host interactions. After initial infection, the phage utilizes the transcriptional machinery of the host to direct the expression of its own genes. This review presents a view on the transcriptional regulation mechanisms of bacteriophages, and its contribution to phage diversity and classification. Through this review, we aim to broaden the understanding of phage-host interactions while providing a reference source for researchers studying the regulation of phage transcription. PMID:25482231

  11. The dyadic regulation of affect.

    PubMed

    Fosha, D

    2001-02-01

    Accelerated Experiential-Dynamic Psychotherapy integrates experiential, relational, and psychodynamic elements. Deep authentic affective experience and its regulation through coordinated emotional interchanges between patient and therapist are viewed as key transformational agents. When maintaining attachment with caregivers necessitates excluding particular affects, a patient's capacity to regulate emotion becomes compromised. Being in an emotionally alive therapeutic relationship enables patients to better tolerate and communicate affective states; doing so, in turn, fosters security, openness, and intimacy in their other relationships. A clinical vignette will illustrate how using the therapist's affect, and focusing on the patient's experience of it, contributes to the repair of affect regulatory difficulties.

  12. Bed Bug Laws and Regulations

    EPA Pesticide Factsheets

    21 states have some level of regulation with regard to bed bugs. Most of these requirements focus on hotels and landlords or other property managers. The Department of Housing and Urban Development has guidance on controlling bed bugs in public housing.

  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. BARC: A Novel Apoptosis Regulator

    DTIC Science & Technology

    2004-07-01

    turnover is normally achieved through programmed cell death , also known as apoptosis. Effects in apoptosis occur in breast cancers and other types of...malignancies, making tumor cells difficult to kill by chemotherapy, hormonal therapy, and radiation. Restoring function of cell death pathways is a strategy...These findings provide new insights into cell death regulation in breast cancer.

  15. Allosteric regulation of phenylalanine hydroxylase.

    PubMed

    Fitzpatrick, Paul F

    2012-03-15

    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  16. 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…

  17. Certificate Regulations for School Personnel.

    ERIC Educational Resources Information Center

    Kansas State Dept. of Education, Topeka.

    This certification handbook provides regulations and systematic procedures for initial issuance of educational certificates as well as renewal requirements in the state of Kansas. The certification topics include--secondary certificates, special certificates, elementary certificates, administrator certificates, vocational education certificates,…

  18. Epigenetic regulation of muscle development.

    PubMed

    Barreiro, Esther; Tajbakhsh, Shahragim

    2017-03-28

    In eukaryote cells, chromatin appears in several forms and is composed of genomic DNA, protein and RNA. The protein content of chromatin is composed primarily of core histones that are packaged into nucleosomes resulting in the condensation of the DNA. Several epigenetic mechanisms regulate the stability of the nucleosomes and the protein-protein interactions that modify the transcriptional activity of the DNA. Interestingly, epigenetic control of gene expression has recently emerged as a relevant mechanism involved in the regulation of many different biological processes including that of muscle development, muscle mass maintenance, function, and phenotype in health and disease. Recent investigations have shed light into the epigenetic control of biological mechanisms that are key regulators of embryonic muscle development and postnatal myogenesis. In the present review article, we provide a summary of the contents discussed in session 08, titled "Epigenetics of muscle regeneration", during the course of the 45th European Muscle Conference, which was celebrated in Montpellier (France) in September 2016. The main theme of that session was to highlight the most recent progress on the role of epigenetics in the regulation of muscle development and regeneration. The current mini-review has been divided into two major sections. On the one hand, a brief introduction on the topic of myogenesis is offered for the non-specialized reader. On the other, a brief overview of the most relevant epigenetic players that have been shown to control muscle development and regeneration is given.

  19. 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)

  20. Electropneumatic rheostat regulates high current

    NASA Technical Reports Server (NTRS)

    Haacker, J. F.; Jedlicka, J. R.; Wagoner, C. B.

    1965-01-01

    Electropneumatic rheostat maintains a constant direct current in each of several high-power parallel loads, of variable resistance, across a single source. It provides current regulation at any preset value by dissipating the proper amount of energy thermally, and uses a column of mercury to vary the effective length of a resistance element.

  1. 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…

  2. 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...

  3. Cell Therapy Regulation in Taiwan.

    PubMed

    Chen, Yuan-Chuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

    2017-03-13

    Cell therapy is not only a novel medical practice but also a medicinal product [cell therapy product (CTP)]. More and more CTPs are being approved for marketing globally because of the rapid development of biomedicine in cell culture, preservation, and preparation. However, regulation is the most important criterion for the development of CTPs. Regulations must be flexible to expedite the process of marketing for new CTPs. Recently, the Taiwan Food and Drug Administration (TFDA) updated the related regulations such as regulation of development, current regulatory framework and process, and the application and evaluation processes. When the quality of CTPs has been improved significantly, their safety and efficacy are further ensured. The treatment protocol, a new design for adaptive licensing to current clinical practice, is a rapid process for patients with life-threatening diseases or serious conditions for which there are no suitable drugs, medical devices, or other therapeutic methods available. The hospital can submit the treatment protocol to apply for cell therapy as a medical practice, which may result in easier and faster cell therapy development, and personalized treatment for individual patients will evolve quickly.

  4. 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…

  5. 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.

  6. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Related regulations. 25.4 Section 25.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Scope of Regulations § 25.4 Related regulations. Regulations relating...

  7. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Related regulations. 25.4 Section 25.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Scope of Regulations § 25.4 Related regulations. Regulations relating...

  8. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Related regulations. 25.4 Section 25.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating...

  9. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Related regulations. 25.4 Section 25.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating...

  10. 27 CFR 25.4 - Related regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Related regulations. 25.4 Section 25.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating...

  11. Thermal Regulation of Heat Transfer Processes

    DTIC Science & Technology

    2014-10-02

    Besides thermal regulation, we also develop an electrochemical method to regulate thermal conductivity in battery materials. Both experiments and modeling...potential applications including power generation, desalination, waste water treatment, and hygiene systems. 4. Electrochemical regulation of...We also develop electrochemical regulation of thermal conductivity in battery materials, which opens new direction for exploration. Both

  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. 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.

  14. Microtubule affinity-regulating kinase 4: structure, function, and regulation.

    PubMed

    Naz, Farha; Anjum, Farah; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2013-11-01

    MAP/Microtubule affinity-regulating kinase 4 (MARK4) belongs to the family of serine/threonine kinases that phosphorylate the microtubule-associated proteins (MAP) causing their detachment from the microtubules thereby increasing microtubule dynamics and facilitating cell division, cell cycle control, cell polarity determination, cell shape alterations, etc. The MARK4 gene encodes two alternatively spliced isoforms, L and S that differ in their C-terminal region. These isoforms are differentially regulated in human tissues including central nervous system. MARK4L is a 752-residue-long polypeptide that is divided into three distinct domains: (1) protein kinase domain (59-314), (2) ubiquitin-associated domain (322-369), and (3) kinase-associated domain (703-752) plus 54 residues (649-703) involved in the proper folding and function of the enzyme. In addition, residues 65-73 are considered to be the ATP-binding domain and Lys88 is considered as ATP-binding site. Asp181 has been proposed to be the active site of MARK4 that is activated by phosphorylation of Thr214 side chain. The isoform MARK4S is highly expressed in the normal brain and is presumably involved in neuronal differentiation. On the other hand, the isoform MARK4L is upregulated in hepatocarcinoma cells and gliomas suggesting its involvement in cell cycle. Several biological functions are also associated with MARK4 including microtubule bundle formation, nervous system development, and positive regulation of programmed cell death. Therefore, MARK4 is considered as the most suitable target for structure-based rational drug design. Our sequence, structure- and function-based analysis should be helpful for better understanding of mechanisms of regulation of microtubule dynamics and MARK4 associated diseases.

  15. PERIPHERAL MECHANISMS IN APPETITE REGULATION

    PubMed Central

    Camilleri, Michael

    2014-01-01

    Peripheral mechanisms in appetite regulation include the motor functions of the stomach, such as the rate of emptying and accommodation, which convey symptoms of satiation to the brain. The rich repertoire of peripherally released peptides and hormones provides feedback from the arrival of nutrients in different regions of the gut from where they are released to exert effects on satiation, or regulate metabolism through their incretin effects. Ultimately, these peripheral factors provide input to the highly organized hypothalamic circuitry and vagal complex of nuclei to determine cessation of energy intake during meal ingestion, and the return of appetite and hunger after fasting. Understanding these mechanisms is key to the physiological control of feeding and the derangements that occur in obesity and their restoration with treatment (as demonstrated by the effects of bariatric surgery). PMID:25241326

  16. 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.

  17. 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.

  18. 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.

  19. Regulating health: transcending disciplinary boundaries.

    PubMed

    Seddon, Toby

    2013-03-01

    Health and health care problems can be addressed from multiple disciplinary perspectives. This raises challenges for how to do cross-disciplinary scholarship in ways that are still robust, rigorous and coherent. This paper sets out one particular approach to cross-cutting research--regulation--which has proved extremely fertile for scholars working in diverse fields, from coal mine safety to tax compliance. The first part of the paper considers how regulatory ideas might be applied to health and health care research in general. The second part goes on to sketch out how a regulation perspective on one specific area, illicit drug policy, can open up new directions for research. In conclusion, a future research agenda is outlined for regulatory scholarship on health and health care.

  20. Redox regulation of Ran GTPase

    SciTech Connect

    Heo, Jongyun

    2008-11-21

    Ran, a small Ras-like GTP-binding nuclear protein, plays a key role in modulation of various cellular signaling events including the cell cycle. This study shows that a cellular redox agent (nitrogen dioxide) facilitates Ran guanine nucleotide dissociation, and identifies a unique Ran redox architecture involved in that process. Sequence analysis suggests that Dexras1 and Rhes GTPases also possess the Ran redox architecture. As Ran releases an intact nucleotide, the redox regulation mechanism of Ran is likely to differ from the radical-based guanine nucleotide modification mechanism suggested for Ras and Rho GTPases. These results provide a mechanistic reason for the previously observed oxidative stress-induced perturbation of the Ran-mediated nuclear import, and suggest that oxidative stress could be a factor in the regulation of cell signal transduction pathways associated with Ran.