Respuesta: Infarto de miocardio y reloj biológico: papel de la melatonina / Reply: Myocardial infarction and biological clock: Role of melatonin

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Host and environmental factors influencing respiratory secretion of pro-wheezing biomarkers in preterm children.

Cytokines are actively secreted by the respiratory mucosa of preterm children and participate in the pathogenesis of wheezing. This study aimed to identify the factors that could potentially influence respiratory secretion of cytokines in these children. A nasopharyngeal aspirate (NPA) was collected from 77 preterm children 1 yr after birth. NPAs from 14 healthy, 1-yr-old term children were collected in parallel. 27 cytokines were measured in the NPAs using a multiplex assay. Multivariate stepwise regression analysis with Bonferroni correction evidenced that the variable [daycare attendance] was associated with higher levels of [monocyte chemoattractant protein-1 (MCP-1), IL-6, vascular endothelial growth factor (VEGF), IL-1ß, IL-10, tumor necrosis factor (TNF)-α]; [male sex] with higher levels of (MCP-1, VEGF, and IL-1ß); [smokers at home] was associated with higher levels of MCP-1 (p < 0.0013). In turn, [prophylaxis with palivizumab] was associated with lower levels of (IL-6, IL-7) (p < 0.0013). All these mediators participate in the pathogenesis of asthma and recurrent wheezing. Preterm children secreted higher levels of chemokines (interferon-gamma inducible protein-10, macrophage inflammatory protein-1α, Eotaxin, MCP-1), growth factors (platelet-derived growth factor-bb, VEGF, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor), Th1 (IL12, interferon-γ), Th2 (IL-9, IL-13), Th17 (IL-6, IL-17) cytokines, and immunomodulatory mediators (IL1RA and granulocyte colony-stimulating factor) than term children. In conclusion, we have identified for the first time a group of individual and environmental factors influencing respiratory secretion of cytokines in preterm children at the long term after birth. To know these factors could help to prevent the instauration of conditions linked to the appearance of chronic respiratory diseases such as wheezing or asthma.

Melatonin in epilepsy and febrile seizures.

A study on melatonin rhythm in children with generalized idiopathic epilepsy and simple fever is presented in this article. A population of 40 children was divided into 4 groups, namely, epilepsy, febrile seizure, and 2 control groups. Salivary melatonin was measured by means of radioimmunoassay. Friedman 2-way analysis of variance (ANOVA) and Wilcoxon tests were employed to assess the existence of melatonin rhythm. Comparison across groups was performed by means of ANOVA and Mann-Whitney tests. Higher melatonin levels were found at night, with a peak at 04:00 h in all groups. Significant diurnal rhythm was also detected for these levels. No significant overall differences between case and control groups were found for melatonin levels, though patients showed lower peak melatonin values than controls at 04:00 h with a significant difference in the febrile seizure group (10.70 vs 19.5 pg/mL respectively; P<.04). Our data support the presence of diurnal rhythm in blood melatonin concentrations in children with epileptic and febrile seizures. Comparison between case and control groups showed lower peak concentrations in the febrile seizure group with respect to healthy controls.

Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is an important cause of recurrent wheezing in infants. Nevertheless, the link between RSV infection and wheezing has yet to be elucidated at the molecular level. Here, we present a preliminary study on the evolution of the immune response in the respiratory tract at long-term after RSV infection. Twenty-seven immune mediators were profiled in nasopharyngeal aspirates (NPAs) obtained from 20 children hospitalized due to a severe infection by RSV at discharge from hospital and again 1 yr later. The same mediators were profiled in parallel in NPAs from 12 healthy controls. In the year following discharge, 85% (17/20) of children of the RSV group suffered at least one episode of wheezing documented by the pediatrician. On the contrary, wheezing episodes were observed only in 25% (3/12) of children in the control group. While most of the mediators profiled returned to normal levels by 1 yr after discharge from hospital, RSV children showed a persistent nasal hyper-secretion of VEGF, G-CSF, IL-10, IL-6, IFN-gamma, IL-7 and IL-13. In previous works VEGF, IL-10 and IFN-gamma have been put in relation with the pathogenesis of post-virus induced asthma. G-CSF, IL-6, IL-7 and IL-13 are increased in respiratory and plasma samples of asthmatic patients. Here, we evidence for the first time a persistent elevation of these mediators as late as 1 yr after severe RSV disease resolution, reinforcing their possible implication in the pathogenesis of wheezing.

Similar cytokine profiles in response to infection with respiratory syncytial virus type a and type B in the upper respiratory tract in infants.

Human respiratory syncytial virus (RSV) is the leading viral cause of severe respiratory illness in infants and young children worldwide. RSV isolates can be divided into 2 subgroups, type A and type B. Here, we compare for the first time the nasal profiles of 27 immune mediators in response to both viral subtypes in 14 children infected with RSV/A, 8 children infected with RSV/B, 11 children coinfected with RSV/A plus other respiratory viruses, and finally, 27 control children, all <2 years old. Our results evidence that children's infection with both RSV subtypes induces very similar profiles of immune mediators in the upper respiratory tract, characterized by the elevation of Th1 and Th2 cytokines, chemokines and growth factors. Interestingly, no major differences in the profiles of the immune mediators were found between the children infected exclusively with RSV/A and those infected with RSV/A plus other respiratory viruses.

Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children.

UNLABELLED: Profiling of immune mediators in both nasal and plasma samples is a common approach to the study of pathogenesis in respiratory viral infections. Nevertheless, mucosal immunity functions essentially independently from peripheral immunity. In our study, 27 immune mediators were profiled in parallel, in nasopharyngeal aspirates (NPAs) and plasma from 22 < 2 year-old children with a severe respiratory syncytial virus infection involving the lower respiratory tract, using a multiplex assay. NPAs from 22 children with innocent heart murmurs were used as controls. Differences in mediator concentrations between NPAs from patients and controls were assessed using the Mann-Whitney test. Ratios of innate/adaptive-immunity mediators, Th2/Th1-cytokines and CXC/CC-chemokines were calculated for NPAs and plasmas and differences were assessed using the Wilcoxon test. Associations mediators, severity and leukocyte counts were studied using the Spearman-Karber test. RESULTS: increased levels of Th1 cytokines (IL-1beta, IL-2, IL-12p70, IFNgamma, TNFalpha), Th2 cytokines (IL-13, IL-4, IL-6, IL-10), chemokines (IP-10, IL-8, MIP1alpha, MIP-1beta), growth factors (FGFb, PDGFbb, GCSF) and IL-1RA, IL-17 were observed in patient NPAs in comparison to controls. In the relative comparisons between patient NPAs and plasmas, a predominance of innate immunity mediators, Th2 cytokines and CXC chemokines was found at the mucosal level. No association between the level of each mediator in NPAs and plasma was found. In plasma, PDGFbb, VEGF, MIP-1alpha, IL-8 correlated with severity; RANTES and IL-6 correlated with leukocyte counts. CONCLUSIONS: acute respiratory syncytial virus infection induces a relative predominance of innate-immunity mediators, Th2 cytokines and CXC chemokines in the mucosal compartment in infected children.

Does mild valvular aortic stenosis progress during childhood?

BACKGROUND AND AIM OF THE STUDY: An increased gradient in congenital valvular aortic stenosis (AS) during follow up remains the subject of controversy, and may determine a need for treatment in pediatric patients. It is hypothesized that a valvular gradient < 40 mmHg indicates a stable tendency at follow up for congenital valvular AS. METHODS: Twenty-five cases with valvular AS, isolated but not treated, were followed for eight years (range: 0.14-18.8 years). Clinical and complementary tests (electrocardiography, X-radiography) were undertaken. The gradient anatomy and function were measured using M-mode, two-dimensional, and Doppler echocardiography. RESULTS: No significant changes were noted in symptoms or at physical examination. Signs of cardiac enlargement were decreased (p < 0.001), and the functional status and gradient remained stable during the follow up period (mean difference 2.38 mmHg; p = 0.74). The relationship between gradient and age showed a slowly increasing trend (r = 0.20). CONCLUSION: The trend in gradient confirmed the stable nature of mild AS. Patients in whom gradients were < 40 mmHg at the time of diagnosis remained stable and required no treatment. Subsequent follow up control and clinical management of these patients may be performed at intervals of two years, or more.

Does mild pulmonary stenosis progress during childhood? A study of its natural course.

BACKGROUND: Increase in the gradient in congenital pulmonary valvular stenosis during follow-up is a subject of controversy and could determine the need for treatment in pediatric patients. HYPOTHESIS: It is postulated that a gradient <50 mmHg shows a stable or decreasing tendency at follow-up for congenital pulmonary valvular stenosis. METHODS: Thirty-five patients with pulmonary stenosis, isolated and not treated, were followed for 7 years (interquartilic rank 5.7 years) at 1.5-year intervals. Clinical and complementary tests (electrocardiogram, x-ray, Doppler echocardiogram) were undertaken. The gradient was measured by Doppler and by using the clinical formula derived from the New England Study (Ellison). The changes observed from the initial to the final consultation were analyzed by means of the Student's t-test, paired Wilcoxon, and Pearson correlation coefficient. RESULTS: No significant changes were noted on symptoms or physical examination. Signs of cardiac enlargement diminished on both ECG (R wave in V1, p<0.0001) and x-ray (cardiothoracic ratio, p<0.0007), with a decreasing gradient trend during the follow-up period (p<0.026) as well. CONCLUSIONS: The gradient trend confirms the stable nature of mild pulmonary stenosis. In our study, we found that patients aged >6 months, whose gradients were below 40 mmHg at the time of diagnosis, remained stable and required no treatment. Furthermore, the follow-up control and clinical management of these patients may then be performed at intervals of 2 years or more.

Congenital anophthalmia: a circadian rhythm study.

A circadian rhythm of heart rate and respiratory rate was seen at 1, 8, and 12 months of age in an infant born without ocular tissue, which supports the possibility that the time cues were nonphotic. No melatonin circadian rhythm was detected at any age up to 9 years of age, and this is most likely associated with the anophthalmia and lack of photic input to the suprachiasmatic nucleus. Usually circadian organization is present after the neonatal period and approaches adult levels with development.

Emergence and evolution of the circadian rhythm of melatonin in children.

OBJECTIVE: To assess the age at which the circadian rhythm of melatonin begins. METHODS: 55 children, divided into groups from the neonatal period to 24 months of life, were studied. Urine samples were taken from 28 newborn babies to measure 6-sulfatoxymelatonin (aMT6s). Salivary samples were collected from infants (27 cases), to measure melatonin (aMT). aMT was measured by RIA and aMT6s by ELISA using commercial kits. Changes in the levels of aMT6s and aMT were evaluated using the Friedman test and Wilcoxon matched pair test. RESULTS: The group aged 27-41 days showed statistically significant differences in daily aMT6s and aMT concentrations. The highest values were always found between 24.00 and 8.00 h. This day/night difference persisted from 2-3 to 13-24 months of age. CONCLUSION: The data indicate that the circadian melatonin rhythm appears at the end of the neonatal period and persists thereafter.