Background-Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.

BackgroundProlonged exposure to hyperoxia in neonates can cause hyperoxic acute lung injury (HALI), which is characterized by increased pulmonary permeability and diffuse infiltration of various inflammatory cells. Disruption of the epithelial barrier may lead to altered pulmonary permeability and maintenance of barrier properties requires intact epithelial tight junctions (TJs). However, in neonatal animals, relatively little is known about how the TJ proteins are expressed in the pulmonary epithelium, including whether expression of TJ proteins is regulated in response to hyperoxia exposure. This study determines whether changes in tight junctions play an important role in disruption of the pulmonary epithelial barrier during hyperoxic acute lung injury.MethodsNewborn rats, randomly divided into two groups, were exposed to hyperoxia (95% oxygen) or normoxia for 1–7 days, and the severity of lung injury was assessed; location and expression of key tight junction protein occludin and ZO-1 were examined by immunofluorescence staining and immunobloting; messenger RNA in lung tissue was studied by RT-PCR; transmission electron microscopy study was performed for the detection of tight junction morphology.ResultsWe found that different durations of hyperoxia exposure caused different degrees of lung injury in newborn rats. Treatment with hyperoxia for prolonged duration contributed to more serious lung injury, which was characterized by increased wet-to-dry ratio, extravascular lung water content, and bronchoalveolar lavage fluid (BALF):serum FD4 ratio. Transmission electron microscopy study demonstrated that hyperoxia destroyed the structure of tight junctions and prolonged hyperoxia exposure, enhancing the structure destruction. The results were compatible with pathohistologic findings. We found that hyperoxia markedly disrupted the membrane localization and downregulated the cytoplasm expression of the key tight junction proteins occludin and ZO-1 in the alveolar epithelium by immunofluorescence. The changes of messenger RNA and protein expression of occludin and ZO-1 in lung tissue detected by RT-PCR and immunoblotting were consistent with the degree of lung injury.ConclusionsThese data suggest that the disruption of the pulmonary epithelial barrier induced by hyperoxia is, at least in part, due to massive deterioration in the expression and localization of key TJ proteins.

Peanut OIT leads to decreases in pro-allergic cytokines, including IL-5, IL-13, and IL-9 and decreased basophil activation. No differences in T cell or basophil responses were found between subjects on low or high-dose maintenance OIT, which has implications for clinical dosing strategies.

[1] The focus of this paper is to study the relationship between sporadic Fe (Fe s ) and Na (Na s ) layers through simultaneous and common volume Fe and Na lidar observations. A total of 37 sporadic layering events were identified from one year (195 hours) of observations at Wuhan (30.5°N, 114.4°E), China. Out of the 37 events, 23 (62%) are characterized by the simultaneous formation of Fe s and Na s layers. The most prominent feature for each of the 23 events is that the Fe s and Na s layers occurred in overlapping altitude ranges and moved following almost the same track. On occasion the Fe s and Na s layers exactly simultaneously reached their maximum peak densities at nearly the same altitude. These observational results strongly suggest that Fe s and Na s layers are formed via the same or very similar mechanisms. This conclusion contradicts the previous suggestion based on those independent observations of Fe s and Na s layers, that the Fe s and Na s layers may be formed via different mechanisms. Out of the 37 events, 14 (38%) belong to single-species sporadic layering events. It is noticed that the formation of each single-species sporadic atom layer was usually accompanied by a weak density enhancement in the other metal atom. This supports the suggestion that Fe s and Na s layers are formed via the same or very similar mechanisms. Both the Fe s and Na s layers over Wuhan showed a tendency to strengthen with decreasing occurrence altitude. This tendency is consistent with the earlier Na s layer observations at high and low latitudes. Moreover, it is noticed by comparing the currently available Fe s and Na s layer characteristics, which came from the observations at five different locations (including Wuhan) during different periods, that a lower average altitude could link to a higher average peak density and vice versa. The statistics-based link might perhaps represent a universal feature of sporadic layers. From our simultaneous Fe and Na density data we have found that the undersides of the normal Fe and Na layers follow nearly the exact movements and occur at nearly the same altitude. The normal Fe layer tended to be narrower than the corresponding Na layer nearly at all times, and this difference was generally reflected in the extent of the upper edge of the layer. The nearly persistent underside overlap strongly suggests that on the undersides of these meteoric metal layers there exist some sink mechanisms leading to the concurrent removal of different sorts of free neutral metal atoms.