New-Onset Atrial Fibrillation Predicts Long-Term Mortality After Coronary Artery Bypass Graft

ObjectivesWe sought to investigate the association between new-onset atrial fibrillation after coronary artery bypass graft (CABG) (post-operative atrial fibrillation [POAF]) and long-term mortality in patients with no history of atrial fibrillation.BackgroundPOAF predicts longer hospital stay and greater post-operative mortality.MethodsA total of 16,169 consecutive patients with no history of AF who underwent isolated CABG at our institution between January 1, 1996, and December 31, 2007, were included in the study. All-cause mortality data were obtained from Social Security Administration death records. A multivariable Cox proportional hazards regression model was constructed to determine the independent impact of new-onset POAF on long-term survival after adjusting for several covariates. The covariates included age, sex, race, pre-operative risk factors (ejection fraction, New York Heart Association functional class, history of myocardial infarction, index myocardial infarction, stroke, chronic obstructive pulmonary disease, peripheral arterial disease, smoking, diabetes, renal failure, hypertension, dyslipidemia, creatinine level, dialysis, redo surgery, elective versus emergent CABG, any valvular disorder) and post-operative adverse events (stroke, myocardial infarction, acute respiratory distress syndrome, and renal failure), and discharge cardiac medications known to affect survival in patients with coronary disease.ResultsNew-onset AF occurred in 2,985 (18.5%) patients undergoing CABG. POAF independently predicted long-term mortality (hazard ratio: 1.21; 95% confidence interval: 1.12 to 1.32) during a mean follow-up of 6 years (range 0 to 12.5 years). This association remained true after excluding from the analysis those patients who died in-hospital after surgery (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32). Patients with POAF discharged on warfarin experienced reduced mortality during follow-up.ConclusionsIn this large cohort of patients, POAF predicted long-term mortality. Warfarin anticoagulation may improve survival in POAF

Perinatal exposure to foodborne inorganic nanoparticles: A role in the susceptibility to food allergy?

Food allergy (FA) is an inappropriate immune response against dietary antigens. Various environmental factors during perinatal life may alter the establishment of intestinal homeostasis, thereby predisposing individuals to the development of such immune-related diseases. Among these factors, recent studies have emphasized the chronic dietary exposure of the mother to foodborne inorganic nanoparticles (NP) such as nano-sized silicon dioxide (SiO2), titanium dioxide (TiO2) or silver (Ag). Indeed, there is growing evidence that these inorganic agents, used as food additives in various products, as processing aids during food manufacturing or in food contact materials, can cross the placental barrier and reach the developing fetus. Excretion in milk is also suggested, hence continuing to expose the neonate during a critical window of susceptibility. Due to their immunotoxical and biocidal properties, such exposure may disrupt the host-intestinal microbiota's beneficial exchanges and may interfere with intestinal barrier and gut-associated immune system development in fetuses then the neonates. The resulting dysregulated intestinal homeostasis in the infant may significantly impede the induction of oral tolerance, a crucial process of immune unresponsiveness to food antigens. The current review focuses on the possible impacts of perinatal exposure to foodborne NP during pregnancy and early life on the susceptibility to developing FA

Assessment of the Sensitizing Potential of Processed Peanut Proteins in Brown Norway Rats: Roasting Does Not Enhance Allergenicity

Background: IgE-binding of process-modified foods or proteins is the most common method for examination of how food processing affects allergenicity of food allergens. How processing affects sensitization capacity is generally studied by administration of purified food proteins or food extracts and not allergens present in their natural food matrix. [br/] Objectives: The aim was to investigate if thermal processing increases sensitization potential of whole peanuts via the oral route. In parallel, the effect of heating on sensitization potential of the major peanut allergen Ara h 1 was assessed via the intraperitoneal route. Methods: Sensitization potential of processed peanut products and Ara h 1 was examined in Brown Norway (BN) rats by oral administration of blanched or oil-roasted peanuts or peanut butter or by intraperitoneal immunization of purified native (N-), heated (H-) or heat glycated (G-) Ara h 1. Levels of specific IgG and IgE were determined by ELISA and IgE functionality was examined by rat basophilic leukemia (RBL) cell assay. [br/] Results: In rats dosed orally, roasted peanuts induced significant higher levels of specific IgE to NAra h 1 and 2 than blanched peanuts or peanut butter but with the lowest level of RBL degranulation. However, extract from roasted peanuts was found to be a superior elicitor of RBL degranulation. Process-modified Ara h 1 had similar sensitizing capacity as NAra h 1 but specific IgE reacted more readily with process-modified Ara h 1 than with native. [br/] Conclusions: Peanut products induce functional specific IgE when dosed orally to BN rats. Roasted peanuts do not have a higher sensitizing capacity than blanched peanuts. In spite of this, extract from roasted peanuts is a superior elicitor of RBL cell degranulation irrespectively of the peanut product used for sensitization. The results also suggest that new epitopes are formed or disclosed by heating Ara h 1 without glucose

Effect of simulated gastro-duodenal digestion on the allergenic reactivity of beta-lactoglobulin

<p>Abstract</p> <p>Background</p> <p>Cow's milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of β-lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children.</p> <p>Methods</p> <p>Blg digesta were prepared using an <it>in vitro </it>digestion protocol simulating either gastric digestion alone or followed by duodenal digestion with or without phosphatidylcholine (PC). Biochemical analysis of blg digesta was performed by SDS-PAGE and their concentration was measured by a sandwich ELISA. Assessment of their allergenic reactivity was done <it>in vitro </it>by EAST inhibition, specific basophil activation (basotest) and lymphocyte proliferation (PCNA-flow cytometry) assays using sera and cells from patients allergic to blg and <it>in vivo </it>by skin prick testing (SPT) of these patients.</p> <p>Results</p> <p>Blg was only broken down to smaller peptides after gastro-duodenal digestion although a sizeable amount of intact protein still remained. Digestion did not modify the IgE binding capacity of blg except for gastro-duodenal digestion performed in the absence of PC. These results are consistent with the quantity of intact blg remaining in the digesta. Overall both gastric and gastroduodenal digestion enhanced activation of sensitized basophils and proliferation of sensitized lymphocytes by blg. However, there was a tendency towards reduction in mean diameter of SPT following digestion, the PC alone during phase 1 digestion causing a significant increase in mean diameter.</p> <p>Conclusions</p> <p>Digestion did not reduce the allergenic reactivity of blg to a clinically insignificant extent, PC inhibiting digestion and thereby protecting blg allergenic reactivity. SPT reactivity was reduced compared to blg immunoreactivity in <it>in vitro </it>tests.</p

Immunological and Metabolomic Impacts of Administration of Cry1Ab Protein and MON 810 Maize in Mouse

We have investigated the immunological and metabolomic impacts of Cry1Ab administration to mice, either as a purified protein or as the Cry1Ab-expressing genetically modified (GM) MON810 maize. Humoral and cellular specific immune responses induced in BALB/cJ mice after intra-gastric (i.g.) or intra-peritoneal (i.p.) administration of purified Cry1Ab were analyzed and compared with those induced by proteins of various immunogenic and allergic potencies. Possible unintended effects of the genetic modification on the pattern of expression of maize natural allergens were studied using IgE-immunoblot and sera from maize-allergic patients. Mice were experimentally sensitized (i.g. or i.p. route) with protein extracts from GM or non-GM maize, and then anti-maize proteins and anti-Cry1Ab–induced immune responses were analyzed. In parallel, longitudinal metabolomic studies were performed on the urine of mice treated via the i.g. route. Weak immune responses were observed after i.g. administration of the different proteins. Using the i.p. route, a clear Th2 response was observed with the known allergenic proteins, whereas a mixed Th1/Th2 immune response was observed with immunogenic protein not known to be allergenic and with Cry1Ab. This then reflects protein immunogenicity in the BALB/c Th2-biased mouse strain rather than allergenicity. No difference in natural maize allergen profiles was evidenced between MON810 and its non-GM comparator. Immune responses against maize proteins were quantitatively equivalent in mice treated with MON810 vs the non-GM counterpart and no anti-Cry1Ab–specific immune response was detected in mice that received MON810. Metabolomic studies showed a slight “cultivar” effect, which represented less than 1% of the initial metabolic information. Our results confirm the immunogenicity of purified Cry1Ab without evidence of allergenic potential. Immunological and metabolomic studies revealed slight differences in mouse metabolic profiles after i.g. administration of MON810 vs its non-GM counterpart, but no significant unintended effect of the genetic modification on immune responses was seen