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Rodriguez-Romero A.,National Autonomous University of Mexico | Hernandez-Santoyo A.,National Autonomous University of Mexico | Fuentes-Silva D.,National Autonomous University of Mexico | Palomares L.A.,National Autonomous University of Mexico | And 3 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2014

Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyro-glutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein. © 2014 International Union of Crystallography.

De Colsa-Ranero A.,Instituto Nacional Of Pediatria
Revista de Investigacion Clinica | Year: 2012

Purpose. Upper respiratory infections (URIs) are one of the most common infectious diseases in children. Macrolides had been considered one of the best options of treatment. Instead of clarithromycin is one of the macrolides most used, meta-analysis about the safety and efficacy of this drug has not been published. Materials and methods. A systematic review with meta-analysis of randomized controlled trials (RCTs) was conducted. Studies in subjects ≤ 12 years of age with URIs were included. Central Cochrane Registry, MEDLINE, EMBASE, Lilacs and Artemisa from 1966 to January of 2011 were reviewed. Clinical cure, clinical success, bacteriological eradication, relapse risk and adverse events risks were analyzed. Risks ratios (RR) with 95% confidence intervals (CI 95%) were calculated, using a fixed effects model. Results. 24 studies, from a total of 76 RCTs were included. Clarithromycin was therapeutically equivalent to other antibiotics studied with respect to clinical cure [RR 1.02 (0.98 to 1.06), p NS], clinical success [RR 1.01 (0.99 to 1.03), p NS] and relapse risk [RR 1.34 (0.81 to 2.21), p NS], but was associated with a better bacteriological eradication [RR 1.06 (1.02 to 1.09), p 0.001], and a lower risk for related adverse events [RR 0.77 (0.65 to 0.90), p = 0.001]. Conclusions. High quality evidence showed that Clarithromycin is a safe and effective alternative for the treatment of URIs in pediatric patients. Is superior to other antibiotics in relation to bacterial eradication. Its equivalence profile related to clinical cure, clinical success and relapse risk, let to consider it as an important alternative.

Garcia-Ortiz H.,Instituto Nacional Of Medicina Genomica | Velazquez-Cruz R.,Instituto Nacional Of Medicina Genomica | Espinosa-Rosales F.,Instituto Nacional Of Pediatria | Jimenez-Morales S.,Instituto Nacional Of Medicina Genomica | And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objective: Variations in gene copy number (CNV) have been recognised as a hereditable source of susceptibility in human complex diseases. Recent studies have shown that Tlr7 gene dosage has a significant contribution in the autoimmune-enhancing effect in mouse models of systemic lupus erythematosus (SLE). A study was therefore performed to investigate whether CNVs in TLR7 contribute to the genetic component of childhood-onset SLE. Methods: A case-control association study was performed in 328 Mexican children with SLE and 403 healthy controls. Determination of CNVs of TLR7 was achieved by real-time PCR using the ΔΔCt method. Expression levels of TLR7 and interferon α (IFNα) were determined in 23 patients. In addition, a stratification analysis was performed to investigate the association of TLR7 gene copy number (CN) with lupus nephritis. Results: A significant increase was found in the relative TLR7 gene CN in females patients with SLE compared with female controls (p<0.0001). However, logistic regression analysis by gender showed a higher OR (OR 6.61, p=0.005) in male patients with >1 copy of TLR7 than in female patients with >2 copies (OR 3.07, p<0.0001). This association was not observed with lupus nephritis. TLR7 mRNA levels correlated significantly with TLR7 CN and with IFNα mRNA levels. Conclusion: These results show that an increase in TLR7 CN is a risk factor for childhood-onset SLE and provide new evidence for a role for X-linked gene dosage in SLE susceptibility. There is also evidence to suggest that TLR7 may be involved in the pathogenesis of SLE through the induction of IFNα.

Hadinegoro S.R.,University of Indonesia | Arredondo-Garcia J.L.,Instituto Nacional Of Pediatria | Capeding M.R.,Institute of Tropical Medicine | Deseda C.,Caribbean Travel Medicine Clinic | And 17 more authors.
New England Journal of Medicine | Year: 2015

Background: A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses. Methods: We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15. Results: Follow-up data were available for 10,165 of 10,275 participants (99%) in CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for 3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group. Pooled relative risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56 to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or older. During year 3, hospitalization for severe dengue, as defined by the independent data monitoring committee criteria, occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group. Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to 69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for those younger than 9 years of age. Conclusions: Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up, the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group. Copyright © 2015 Massachusetts Medical Society.

Palacios-Macedo-Quenot A.,Instituto Nacional Of Pediatria
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición | Year: 2012

Treatment of aortic coarctation with hypoplastic aortic arch is still a surgical challenge. The aortic arch advancement surgery has shown less re-coarctation frequency. To determine the re-coarctation frequency in patients who underwent aortic arch advancement technique for aortic coarctation with hypoplastic aortic arch and analyze the results. Retrospective and observational study of 38 patients who underwent aortic arch advancement in a third level Institution from 2002 to 2010. Twenty four males and 14 females all with aortic arch Z index diameter of < or = -2 were found. The median age was 2.6 months and the median weight was 3.8 kg. Twelve patients (31.5%) did not show post operative complications. Eighteen (47%) had only one complication; one patient (2.6%) had 2 complications and 2 (5.2%) had 3 complications. After a follow up of 3.7 years the frequency of re-coarctation was O%. With the previously mentioned technique the recoarctation frequency on medium and long term basis was 0%. From the anatomical and functional point of view, we believe this technique offers the best possible results.

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