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The mitochondrial metabolite succinate is a key driver of ischemia/reperfusion injury (IRI). Targeting succinate metabolism by inhibiting succinate dehydrogenase (SDH) upon reperfusion using malonate is an effective therapeutic strategy to achieve cardioprotection in the short term (< 24 h reperfusion) in mouse and pig in vivo myocardial infarction (MI) models. We aimed to assess whether inhibiting IRI with malonate given upon reperfusion could prevent post-MI heart failure (HF) assessed after 28 days. Male C57BL/6 J mice were subjected to 30 min left anterior coronary artery (LAD) occlusion, before reperfusion for 28 days. Malonate or without-malonate control was infused as a single dose upon reperfusion. Cardiac function was assessed by echocardiography and fibrosis by Masson's trichrome staining. Reperfusion without malonate significantly reduced ejection fraction (~ 47%), fractional shortening (~ 23%) and elevated collagen deposition 28 days post-MI. Malonate, administered as a single infusion (16 mg/kg/min for 10 min) upon reperfusion, gave a significant cardioprotective effect, with ejection fraction (~ 60%) and fractional shortening (~ 30%) preserved and less collagen deposition. Using an acidified malonate formulation, to enhance its uptake into cardiomyocytes via the monocarboxylate transporter 1, both 1.6 and 16 mg/kg/min 10 min infusion led to robust long-term cardioprotection with preserved ejection fraction (> 60%) and fractional shortening (~ 30%), as well as significantly less collagen deposition than control hearts. Malonate administration upon reperfusion prevents post-MI HF. Acidification of malonate enables lower doses of malonate to also achieve long-term cardioprotection post-MI. Therefore, the administration of acidified malonate upon reperfusion is a promising therapeutic strategy to prevent IRI and post-MI HF.
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AIM: The study assessed the relationship between vitamin D status in infants and the presence of allergic and/or respiratory disorders. MATERIALS AND METHODS: The study cohort comprised 81 hospitalized infants presenting at the Pediatric Clinic, University Clinical Center Kragujevac, Serbia, between January 2011 and June 2016. RESULTS: The age of the infants ranged from 29 days to 12 months. All infants received prophylactic doses of vitamin D3 of 400 IU/daily until the end of the first year of life regardless of whether they are fed with adapted infant formula (n = 20) or breast milk (n = 37) or concurrently both (n = 24), up to the 5th month of life. The mean level of plasma 25(OH)D was 29.65 ng/mL. Hypovitaminosis D (mean serum level of 25(OH)D < 30 ng/mL) was found in n = 38 infants of which 6 presented with severe vitamin D deficiency (level below 10 ng/mL), 13 presented with vitamin D deficiency (level between 10 and 20 ng/mL) and 19 had vitamin D insufficiency (levels between 20 and 30 ng/mL). The median vitamin D serum level in infants with allergic disease (n = 16) was 32.35 ng/mL and in infants with respiratory disease (n = 65) 28.99 ng/mL. CONCLUSION: Daily vitamin D3 supplementation with 400 IU in infants until the end of the first year of life is too low to provide optimal defense against respiratory and/or allergic conditions.
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Hipersensibilidad , Deficiencia de Vitamina D , Niño , Femenino , Lactante , Humanos , Recién Nacido , Vitamina D , Incidencia , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Colecalciferol , Hipersensibilidad/epidemiología , Hipersensibilidad/prevención & control , Hipersensibilidad/complicaciones , Suplementos DietéticosRESUMEN
Growth differentiation factor 11 (GDF11) and GDF8 (MSTN) are closely related TGF-ß family proteins that interact with nearly identical signaling receptors and antagonists. However, GDF11 appears to activate SMAD2/3 more potently than GDF8 in vitro and in vivo. The ligands possess divergent structural properties, whereby substituting unique GDF11 amino acids into GDF8 enhanced the activity of the resulting chimeric GDF8. We investigated potentially distinct endogenous activities of GDF11 and GDF8 in vivo by genetically modifying their mature signaling domains. Full recoding of GDF8 to that of GDF11 yielded mice lacking GDF8, with GDF11 levels â¼50-fold higher than normal, and exhibiting modestly decreased muscle mass, with no apparent negative impacts on health or survival. Substitution of two specific amino acids in the fingertip region of GDF11 with the corresponding GDF8 residues resulted in prenatal axial skeletal transformations, consistent with Gdf11-deficient mice, without apparent perturbation of skeletal or cardiac muscle development or homeostasis. These experiments uncover distinctive features between the GDF11 and GDF8 mature domains in vivo and identify a specific requirement for GDF11 in early-stage skeletal development.
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Desarrollo Óseo , Factores de Diferenciación de Crecimiento , Músculo Esquelético , Miostatina , Animales , Femenino , Ratones , Embarazo , Aminoácidos/química , Aminoácidos/genética , Desarrollo Óseo/genética , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Factores de Diferenciación de Crecimiento/genética , Factores de Diferenciación de Crecimiento/química , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Miostatina/genética , Miostatina/química , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: The human heart has limited capacity to generate new cardiomyocytes and this capacity declines with age. Because loss of cardiomyocytes may contribute to heart failure, it is crucial to explore stimuli of endogenous cardiac regeneration to favorably shift the balance between loss of cardiomyocytes and the birth of new cardiomyocytes in the aged heart. We have previously shown that cardiomyogenesis can be activated by exercise in the young adult mouse heart. Whether exercise also induces cardiomyogenesis in aged hearts, however, is still unknown. Here, we aim to investigate the effect of exercise on the generation of new cardiomyocytes in the aged heart. METHODS: Aged (20-month-old) mice were subjected to an 8-week voluntary running protocol, and age-matched sedentary animals served as controls. Cardiomyogenesis in aged hearts was assessed on the basis of 15N-thymidine incorporation and multi-isotope imaging mass spectrometry. We analyzed 1793 cardiomyocytes from 5 aged sedentary mice and compared these with 2002 cardiomyocytes from 5 aged exercised mice, followed by advanced histology and imaging to account for ploidy and nucleation status of the cell. RNA sequencing and subsequent bioinformatic analyses were performed to investigate transcriptional changes induced by exercise specifically in aged hearts in comparison with young hearts. RESULTS: Cardiomyogenesis was observed at a significantly higher frequency in exercised compared with sedentary aged hearts on the basis of the detection of mononucleated/diploid 15N-thymidine-labeled cardiomyocytes. No mononucleated/diploid 15N-thymidine-labeled cardiomyocyte was detected in sedentary aged mice. The annual rate of mononucleated/diploid 15N-thymidine-labeled cardiomyocytes in aged exercised mice was 2.3% per year. This compares with our previously reported annual rate of 7.5% in young exercised mice and 1.63% in young sedentary mice. Transcriptional profiling of young and aged exercised murine hearts and their sedentary controls revealed that exercise induces pathways related to circadian rhythm, irrespective of age. One known oscillating transcript, however, that was exclusively upregulated in aged exercised hearts, was isoform 1.4 of regulator of calcineurin, whose regulation and functional role were explored further. CONCLUSIONS: Our data demonstrate that voluntary running in part restores cardiomyogenesis in aged mice and suggest that pathways associated with circadian rhythm may play a role in physiologically stimulated cardiomyogenesis.
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Miocitos Cardíacos , Condicionamiento Físico Animal , Animales , Calcineurina/metabolismo , Humanos , Lactante , Ratones , Miocitos Cardíacos/citología , Timidina/metabolismoRESUMEN
Hyperinsulinemia is a condition with extremely high levels of insulin in the blood. Various factors can lead to hyperinsulinemia in children and adolescents. Puberty is a period of significant change in children and adolescents. They do not have to have explicit symptoms for prediabetes, and certain health indicators may indicate a risk of developing this problem. The scientific study is designed as a cross-sectional study. In total, 674 children and adolescents of school age from 12 to 17 years old participated in the research. They received a recommendation from a pediatrician to do an OGTT (Oral Glucose Tolerance test) with insulinemia at a regular systematic examination. In addition to factor analysis, the study of the influence of individual factors was tested using RBF (Radial Basis Function) and SVM (Support Vector Machine) algorithm. The obtained results indicated statistically significant differences in the values of the monitored variables between the experimental and control groups. The obtained results showed that the number of adolescents at risk is increasing, and, in the presented research, it was 17.4%. Factor analysis and verification of the SVM algorithm changed the percentage of each risk factor. In addition, unlike previous research, three groups of children and adolescents at low, medium, and high risk were identified. The degree of risk can be of great diagnostic value for adopting corrective measures to prevent this problem and developing potential complications, primarily type 2 diabetes mellitus, cardiovascular disease, and other mass non-communicable diseases. The SVM algorithm is expected to determine the most accurate and reliable influence of risk factors. Using factor analysis and verification using the SVM algorithm, they significantly indicate an accurate, precise, and timely identification of children and adolescents at risk of hyperinsulinemia, which is of great importance for improving their health potential, and the health of society as a whole.
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Mitochondria are essential signaling organelles that regulate a broad range of cellular processes and thereby heart function. Multiple mechanisms participate in the communication between mitochondria and the nucleus that maintain cardiomyocyte homeostasis, including mitochondrial reactive oxygen species (ROS) and metabolic shifts in TCA cycle metabolite availability. An increased rate of ROS generation can cause irreversible damage to the cell and proposed to be a leading cause of many pathologies, including accelerated aging and heart disease. Myocardial impairments are also characterised by specific coordinated metabolic changes and dysregulated inflammatory responses. Hence, the mitochondrial respiratory chain is an important mediator between health and disease in the heart. This review will first outline the sources of ROS in the heart, mitochondrial metabolite dynamics, and provide an overview of their implications for heart disease. In addition, we will concentrate our discussion around current cardioprotective strategies relevant to mitochondrial ROS. Thorough understanding of mitochondrial signaling and the complex interplay with vital signaling pathways in the heart might allow us to develop novel therapeutic approaches to cardiovascular disease.
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Mitocondrias , Estrés Oxidativo , Ciclo del Ácido Cítrico , Mitocondrias/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24-30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age-related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF.
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Envejecimiento/genética , Ecocardiografía Doppler/métodos , Ejercicio Físico/fisiología , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/fisiología , Animales , Humanos , Masculino , Ratones , FenotipoRESUMEN
The adult mammalian heart is incapable of clinically relevant regeneration. The regenerative deficit in adult mammalian heart contrasts with the fetal and neonatal heart, which demonstrate substantial regenerative capacity after injury. This deficiency in adult mammals is attributable to the lack of resident stem cells after birth, combined with an inability of pre-existing cardiomyocytes to complete cytokinesis. Studies of neonatal heart regeneration in mammals suggest that latent regenerative potential can be re-activated. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation is key to stimulating true regeneration in adult humans. Here, we review recent advances in our understanding of cardiomyocyte proliferation that suggest molecular approaches to heart regeneration.
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Corazón/fisiología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Regeneración , Animales , Proliferación Celular , Humanos , Células Madre/citología , Células Madre/metabolismoRESUMEN
Calorie restriction (CR) improved health span in 2 longitudinal studies in nonhuman primates (NHPs), yet only the University of Wisconsin (UW) study demonstrated an increase in survival in CR monkeys relative to controls; the National Institute on Aging (NIA) study did not. Here, analysis of left ventricle samples showed that CR did not reduce cardiac fibrosis relative to controls. However, there was a 5.9-fold increase of total fibrosis in UW hearts, compared with NIA hearts. Diet composition was a prominent difference between the studies; therefore, we used the NHP diets to characterize diet-associated molecular and functional changes in the hearts of mice. Consistent with the findings from the NHP samples, mice fed a UW or a modified NIA diet with increased sucrose and fat developed greater cardiac fibrosis compared with mice fed the NIA diet, and transcriptomics analysis revealed diet-induced activation of myocardial oxidative phosphorylation and cardiac muscle contraction pathways.
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Grasas de la Dieta/efectos adversos , Sacarosa en la Dieta/efectos adversos , Corazón/fisiopatología , Contracción Miocárdica/fisiología , Miocardio/patología , Adolescente , Factores de Edad , Anciano , Envejecimiento/fisiología , Animales , Restricción Calórica , Niño , Modelos Animales de Enfermedad , Femenino , Fibrosis , Ventrículos Cardíacos/patología , Humanos , Macaca mulatta , Masculino , Ratones , Fosforilación Oxidativa , Especificidad de la Especie , Adulto JovenRESUMEN
Administration of active growth differentiation factor 11 (GDF11) to aged mice can reduce cardiac hypertrophy, and low serum levels of GDF11 measured together with the related protein, myostatin (also known as GDF8), predict future morbidity and mortality in coronary heart patients. Using mice with a loxP-flanked ("floxed") allele of Gdf11 and Myh6-driven expression of Cre recombinase to delete Gdf11 in cardiomyocytes, we tested the hypothesis that cardiac-specific Gdf11 deficiency might lead to cardiac hypertrophy in young adulthood. We observed that targeted deletion of Gdf11 in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation when compared with control mice carrying only the Myh6-cre or Gdf11-floxed alleles, suggesting a possible etiology for dilated cardiomyopathy. However, the mechanism underlying this finding remains unclear because of multiple confounding effects associated with the selected model. First, whole heart Gdf11 expression did not decrease in Myh6-cre; Gdf11-floxed mice, possibly because of upregulation of Gdf11 in noncardiomyocytes in the heart. Second, we observed Cre-associated toxicity, with lower body weights and increased global fibrosis, in Cre-only control male mice compared with flox-only controls, making it challenging to infer which changes in Myh6-cre;Gdf11-floxed mice were the result of Cre toxicity versus deletion of Gdf11. Third, we observed differential expression of cre mRNA in Cre-only controls compared with the cardiomyocyte-specific knockout mice, also making comparison between these two groups difficult. Thus, targeted Gdf11 deletion in cardiomyocytes may lead to left ventricular dilation without hypertrophy, but alternative animal models are necessary to understand the mechanism for these findings. NEW & NOTEWORTHY We observed that targeted deletion of growth differentiation factor 11 in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation compared with control mice carrying only the Myh6-cre or growth differentiation factor 11-floxed alleles. However, the mechanism underlying this finding remains unclear because of multiple confounding effects associated with the selected mouse model.
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Proteínas Morfogenéticas Óseas/genética , Cardiomiopatía Dilatada/genética , Eliminación de Gen , Factores de Diferenciación de Crecimiento/genética , Integrasas/genética , Miocitos Cardíacos/metabolismo , Factores de Edad , Animales , Proteínas Morfogenéticas Óseas/deficiencia , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/fisiopatología , Progresión de la Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Predisposición Genética a la Enfermedad , Factores de Diferenciación de Crecimiento/deficiencia , Integrasas/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/patología , Cadenas Pesadas de Miosina/genética , Fenotipo , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
Microvascular dysfunction in the heart and its association with periarteriolar fibrosis may contribute to the diastolic dysfunction seen in heart failure with preserved ejection fraction. Interleukin-33 (IL-33) prevents global myocardial fibrosis in a pressure overloaded left ventricle by acting via its receptor, ST2 (encoded by the gene, Il1rl1); however, whether this cytokine can also modulate periarteriolar fibrosis remains unclear. We utilized two approaches to explore the role of IL-33/ST2 in periarteriolar fibrosis. First, we studied young and old wild type mice to test the hypothesis that IL-33 and ST2 expression change with age. Second, we produced pressure overload in mice deficient in IL-33 or ST2 by transverse aortic constriction (TAC). With age, IL-33 expression increased and ST2 expression decreased. These alterations accompanied increased periarteriolar fibrosis in aged mice. Mice deficient in ST2 but not IL-33 had a significant increase in periarteriolar fibrosis following TAC compared to wild type mice. Thus, loss of ST2 signaling rather than changes in IL-33 expression may contribute to periarteriolar fibrosis during aging or pressure overload, but manipulating this pathway alone may not prevent or reverse fibrosis.
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Fibrosis/genética , Insuficiencia Cardíaca/genética , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-33/genética , Animales , Modelos Animales de Enfermedad , Fibrosis/fisiopatología , Regulación de la Expresión Génica/genética , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Humanos , Ratones , Miocardio/metabolismo , Miocardio/patología , Transducción de Señal/genéticaRESUMEN
The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change in culture, often preserving some but not all of their in vivo characteristics in culture. At least some of the in vivo microenvironment may be mimicked by providing specific cues to cultured cells. Here, we show that after isolation and during maintenance in culture, adherent rat islets reduce expression of key ß-cell transcription factors necessary for ß-cell function and that soluble pancreatic decellularized matrix (DCM) can enhance ß-cell gene expression. Following chromatographic fractionation of pancreatic DCM, we performed proteomics to identify soluble factors that can maintain ß-cell stability and function. We identified Apolipoprotein E (ApoE) as an extracellular protein that significantly increased the expression of key ß-cell genes. The ApoE effect on beta cells was mediated at least in part through the JAK/STAT signaling pathway. Together, these results reveal a role for ApoE as an extracellular factor that can maintain the mature ß-cell gene expression profile.
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Apolipoproteínas E/metabolismo , Espacio Extracelular/metabolismo , Regulación de la Expresión Génica/fisiología , Células Secretoras de Insulina/metabolismo , Animales , Células Cultivadas , Proteoglicanos de Heparán Sulfato/metabolismo , Islotes Pancreáticos/metabolismo , Quinasas Janus/metabolismo , Proteoma , Proteómica , Ratas Sprague-Dawley , Receptores de LDL/metabolismo , Factores de Transcripción STAT/metabolismo , Técnicas de Cultivo de TejidosRESUMEN
Loss of cardiomyocytes is a major cause of heart failure, and while the adult heart has a limited capacity for cardiomyogenesis, little is known about what regulates this ability or whether it can be effectively harnessed. Here we show that 8 weeks of running exercise increase birth of new cardiomyocytes in adult mice (~4.6-fold). New cardiomyocytes are identified based on incorporation of 15N-thymidine by multi-isotope imaging mass spectrometry (MIMS) and on being mononucleate/diploid. Furthermore, we demonstrate that exercise after myocardial infarction induces a robust cardiomyogenic response in an extended border zone of the infarcted area. Inhibition of miR-222, a microRNA increased by exercise in both animal models and humans, completely blocks the cardiomyogenic exercise response. These findings demonstrate that cardiomyogenesis can be activated by exercise in the normal and injured adult mouse heart and suggest that stimulation of endogenous cardiomyocyte generation could contribute to the benefits of exercise.
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Corazón/fisiología , Infarto del Miocardio/rehabilitación , Miocitos Cardíacos/fisiología , Condicionamiento Físico Animal/fisiología , Regeneración , Animales , Proliferación Celular/genética , Células Cultivadas , Modelos Animales de Enfermedad , Ecocardiografía , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Miocardio/citología , Cultivo Primario de Células , RatasRESUMEN
AIM: Antimicrobial resistance and inappropriate use of antibiotics in children are important issues. Consequently, there is a need to develop comprehensive stewardship programs even in hospitals with limited resources starting with children's hospitals. METHODS: Retrospective observational analysis of antimicrobial utilization and resistance patterns over 5 years in a tertiary care children's hospital in Serbia. RESULTS: Cumulative antimicrobial resistance decreased but was still high, with high cumulative resistance rates among the most widely used antibiotics in the hospital. Total antibiotic use decreased from 2010 to 2014 although there was still high prescribing of reserved antibiotics. CONCLUSION: Concerns with inappropriate use and high resistance rates among some antibiotics used in the hospital are being used to develop guidance on future antibiotic use in this hospital, building on the recently introduced antibiotic stewardship program, as well as encourage other hospitals in Serbia to review their policies.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Peninsula Balcánica , Niño , Farmacorresistencia Microbiana , Utilización de Medicamentos , Escherichia coli/aislamiento & purificación , Hospitalización/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Prescripción Inadecuada , Estudios Retrospectivos , Serbia , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Centros de Atención Terciaria/estadística & datos numéricosRESUMEN
Genetic and functional analyses of 120 mouse strains have identified a heart regeneration candidate gene that modulates the contractile sarcomeric apparatus. This gene, Tnni3k, controls the frequency of the mononuclear, diploid cardiomyocyte population, which affects cardiomyocyte proliferative potential after injury.
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Corazón/fisiología , Mamíferos/fisiología , Regeneración/genética , Animales , Diferenciación Celular/genética , Quimera , Células Gigantes/metabolismo , Humanos , Mamíferos/genética , Ratones , Ratones Endogámicos C57BL , Desarrollo de Músculos/genética , Miocitos Cardíacos/fisiologíaRESUMEN
BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor ß (TGFß) family. While GDF8 has been recognized as a negative regulator of muscle growth and differentiation, there are conflicting studies on the function of GDF11 and whether GDF11 has beneficial effects on age-related dysfunction. To address whether GDF8 and GDF11 are functionally identical, we compared their signaling and structural properties. RESULTS: Here we show that, despite their high similarity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8. Resolution of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 crystal structures reveals unique properties of both ligands, specifically in the type I receptor binding site. Lastly, substitution of GDF11 residues into GDF8 confers enhanced activity to GDF8. CONCLUSIONS: These studies identify distinctive structural features of GDF11 that enhance its potency, relative to GDF8; however, the biological consequences of these differences remain to be determined.
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Proteínas Morfogenéticas Óseas/química , Factores de Diferenciación de Crecimiento/química , Miostatina/química , Miostatina/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Proteínas Morfogenéticas Óseas/metabolismo , Células Cultivadas , Cristalografía por Rayos X , Folistatina/metabolismo , Genes Reporteros , Factores de Diferenciación de Crecimiento/antagonistas & inhibidores , Factores de Diferenciación de Crecimiento/metabolismo , Humanos , Inyecciones Intravenosas , Ligandos , Luciferasas/metabolismo , Ratones , Modelos Moleculares , Mioblastos/metabolismo , Miocardio/metabolismo , Miostatina/antagonistas & inhibidores , Fosforilación , Unión Proteica , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Alineación de Secuencia , Transducción de Señal , Proteínas Smad/metabolismo , Homología Estructural de Proteína , Relación Estructura-ActividadRESUMEN
Cardiac rhabdomyomas are common in tuberous sclerosis. We report a child who developed rhabdomyoma related arrhythmia refractory to antiarrhythmic drug therapy. Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. As per our knowledge, this is the first time that sirolimus has been successfully used in this setting.
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Rabdomioma/complicaciones , Rabdomioma/tratamiento farmacológico , Sirolimus/uso terapéutico , Taquicardia Atrial Ectópica/complicaciones , Taquicardia Atrial Ectópica/tratamiento farmacológico , Preescolar , Femenino , Humanos , Inmunosupresores/uso terapéutico , Resultado del TratamientoRESUMEN
Kosutic J, Prijic S, Stajevic M, Kalaba M, Ninic S, Mikovic Z, Vujic A, Popovic S. Clinical implications of prenatal diagnosis of aorto-left ventricular tunnel on postnatal treatment and final outcome. Turk J Pediatr 2017; 59: 342-344. There are no more than 20 antenatally diagnosed aorto-left ventricular tunnel cases reported in the literature. In most of them the diagnosis was made indirectly and only after multiple fetal scans based on findings such as thick and dilated left ventricle and grossly dilated ascending aorta. We present a patient in whom a direct tunnel visualization and aorto-left ventricular tunnel diagnosis was made at the 30th gestation week after a single fetal scan using the recently introduced `cockade sign`. Clinical implications of antenatal diagnosis on postnatal treatment and outcome are also discussed.
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Aorta/anomalías , Cardiopatías Congénitas/diagnóstico , Ventrículos Cardíacos/anomalías , Ultrasonografía Prenatal/métodos , Adulto , Aorta/diagnóstico por imagen , Aorta/cirugía , Ecocardiografía/métodos , Femenino , Cardiopatías Congénitas/cirugía , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Humanos , Recién Nacido , EmbarazoRESUMEN
Using induced pluripotent stem cells, Ang et al. elucidate how a mutation in the transcription factor GATA4 causes congenital heart disease. They find that, although the recruitment of GATA4 to cardiac super-enhancers is retained, it no longer functions in partnership with another key transcription factor, leading to misexpression of non-cardiomyocyte genes.
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Factor de Transcripción GATA4/genética , Crisis de Identidad , Corazón , Humanos , Miocitos Cardíacos/metabolismo , Factores de Transcripción/genéticaRESUMEN
INTRODUCTION: Henoch-Schönlein purpura (HSP) is a small blood vessel vasculitis, which usually manifests during childhood. The exact cause of the disease is unknown. CASE REPORT: We reported a 14-year-old girl who had been admitted to our clinic due to the appearance of red macules on her extremities and face, vomiting, and pain in the abdomen and joints. The patient was initially diagnosed with Henoch-Schönlein purpura. At the end of the fourth week of illness, larvae of Strongyloides stercoralis were detected in stool samples. The patient was therefore treated with mebendazole, after which all symptoms permanently withdrew. About a month later laboratory examinations were repeated demonstrating increasing signs of renal damage. Kidney biopsy was performed, showing mesangioproliferative glomerulonephritis with crescents and IgA and C3 positive staining in the mesangium. Upon reviewing the clinical presentation, biochemically demonstrated progressive renal damage and biopsy results, the patient was diagnosed with HSP nephritis. CONCLUSION: The time course of the disease and present knowledge concerning the pathogenic mechanisms of HSP suggest that Strongyloides stercoralis infection could have caused HSP in the presented patient, which was complicated by nephritis.