Omalizumab is currently used in severe asthma and has been tried in other allergic disorders. The authors report two patients with multiple food allergies and eosinophilic esophagitis on a very restrictive diet who have been treated with omalizumab, in order to improve food intolerance--the major distressing factor in their lives. The patients significantly improved in the reported symptoms. However, no improvement was seen regarding esophageal endoscopy and histology. Given the poor histological and endoscopy response, eosinophilic esophagitis persistence is unlikely to be IgE dependent. Omalizumab may improve the quality of life of patients with severe food allergy by improving symptoms, but it does not appear to change endoscopic and histological features of eosinophilic esophagitis in a short follow-up.

Background and Purpose-Mortality statistics indicate that Portugal has the highest stroke mortality in Western Europe.Data on stroke incidence in Northern Portugal, the region with the highest mortality, are lacking. This study was designed to determine stroke incidence and case fatality in rural and urban populations in Northern Portugal. Methods-All suspected first-ever-in-a-lifetime strokes occurring between October 1998 and September 2000 in 37 290 residents in rural municipalities and 86 023 living in the city of Porto were entered in a population-based registry. Standard definitions and comprehensive sources of information were used for identification of patients who were followed-up at 3 and 12 months after onset of symptoms. Results-During a 24-month period, 688 patients with a first-ever stroke were registered, 226 in rural and 462 in urban areas. The crude annual incidence was 3.05 (95% CI, 2.65 to 3.44) and 2.69 per 1000 (95% CI, 2.44 to 2.93) for rural and urban populations, respectively; the corresponding rates adjusted to the European standard population were 2.02 (95% CI, 1.69 to 2.34) and 1.73 (95% CI, 1.53 to 1.92). Age-specific incidence followed different patterns in rural and urban populations, reaching major discrepancy for those 75 to 84 years old, 20.2 (95% CI, 16.1 to 25.0) and 10.9 (95% CI, 9.0 to 12.8), respectively. Case fatality at 28 days was 14.6% (95% CI, 10.2 to 19.3) in rural and 16.9% (95% CI, 13.7 to 20.6) in urban areas. Conclusions-Stroke incidence in rural and urban Northern Portugal is high compared to that reported in other WesternEurope regions. The high official mortality in our country, which could be explained by a relatively high incidence, was not because of a high case fatality rate.

Background & Aims:The l i v e r , being the major site of i r o n storage, is particularly exposed to the toxic effects of iron. Tran-scription factor NRF2 is critical for protecting the l i v e r a g a i n s t disease by activating the transcription of genes encoding detoxification/antioxidant enzymes. We aimed to determine if the NRF2 pathway plays a significant role in the protection against hepatic iron overload. Methods: Wild type and Nrf2 _ /_ mouse primary hepatocytes Wereincubated with ferric ammonium citrate. Wild type and Nrf2 -/-mice w e r e fed s t anda rd rodent chow or iron-rich diet for 2 weeks, with or without daily i n j e c t i o n of the a n t i o x i d a n t mito-TEMPOL. Results: In mouse hepatocytes, iron induced the nuclear translo-cation of NRF2 and the expression of cytoprotective genes in an NRF2-dependent manner. Moreover, Nrf2 _ /_ hepatocytes were highly susceptible to i r o n -induced cell d e a t h . Wild-type and Nrf2 _ /_ mice fed iron-rich diet accumulated similar amounts of iron in the liver and were equally able to increase the expression of hepatic hepcidin and ferritin. Nevertheless, in Nrf2-null mice the iron loading resulted in progressive liver injury, ranging from mild confluent necrosis to s e v e r e necroinflammatory lesio ns. Hepatocytic cell death was associated with gross ul t r a s t r u c t u r a l damage to the mitochondria. Notably, liver injury was prevented in iron-fed animals that received mito-TEMPOL. Conclusions: NRF2 protects the m o u s e liver against the t o x i c i t y of dietary iron o v e r l o a d by p r e v e n t i n g hepatocytic cell d e a t h . We identify NRF2 as a potential modifier of liver disease in iron overload pathology and show the beneficial effect of the antiox-idant mito-TEMPOL in a mouse model of dietary iron-induced liver injury. ©2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 INTRODUCTIONIron is a component of several metalloproteins involved in crucial metabolic processes such as oxygen sensing and transport, energy metabolism and DNA synthesis. However, iron in excess is detrimental, as it can catalyze the formation of damaging radical species via Fenton-type reactions [1]. In normal conditions, iron toxicity is prevented by the binding of extracellular iron in the plasma to transferrin and by storage of intracellular iron in a protein with high storage capacity, ferritin [2]. In addition, plasma iron levels are tightly regulated by the action of the peptide hormone hepcidin. Hepcidin, which is mostly secreted in the liver, promotes the degradation of the iron exporter ferroportin expressed on the surface of iron-releasing cells, thus reducing intestinal iron absorption and its mobilization fr...