Fungi Sensitization in Spain: Importance of the Alternaria alternata Species and Its Major Allergen Alt a 1 in the Allergenicity.

Prevalence of allergy to fungi is around 3-10%. The most prevalent species involved in sensitizations are Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, and Penicillium notatum. Our main objective was to estimate the prevalence of fungal sensitization and its variation across Spain. Following the ICH-GCP, we recruited 1156 patients from 15 allergy departments in Spain. Hospitals were selected by bioclimatic areas. Patients underwent a skin prick test (SPT) with fungi, pollens, house dust mites, and animal dander. Specific IgE to Alternaria alternata and Alt a 1 was assessed in patients with positive SPT to fungi. Of the 233 patients (20.2%) sensitized to at least one of the five fungi tested, 162 (69.5%) were sensitized to Alternaria alternata and Alt a 1, of whom 113 (69.8%) were children; 181 (77.7%) were also polysensitized to other allergens. Alternaria alternata and Alt a 1 sensitization was present in 25.4% of patients in the Continental area, 12.0% in the Mediterranean area, 7.0% in the Semidesertic area, and 2.3% in the Oceanic area. Prevalence of sensitization to the other tested sources was 63.8% to pollens, 60.5% to house dust mite, and 38.1% to animal dander. We concluded that the prevalence of fungal allergy is increasing. Fungi are still the fourth source of allergen sensitization. Alternaria alternata sensitization is the most prevalent in allergic patients to fungi. Alt a 1 is present in almost 90% of the patients sensitized to Alternaria alternata.

Intradermal Phleum pratense allergoid immunotherapy. Double-blind, randomized, placebo-controlled trial.

BACKGROUND: In allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy. OBJECTIVE: To evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde-polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen. METHODS: Multicentre, randomized, double-blind, placebo-controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 µg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale. RESULTS: The dose of 0.06 µg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded. CONCLUSION & CLINICAL RELEVANCE: Intradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.

Prospective Observational Cohort Study of the Efficacy of Bacterial Immune Prophylaxis in the Prevention of Uncomplicated, Recurrent Urinary Tract Infections.

OBJECTIVE: To investigate the long-term prophylactic effect of a vaccine on lower urinary tract infections (UTI) of bacterial and the impact of the intensity of the symptoms on the quality of life (QoL). METHODS: Adult female could be enrolled in this study if they had acute UTI at the enrolment visit and bacterial microbiological count of ≥103 CFU/mL of Escherichia coli. RESULTS: A total of 21 patients were included. Fifteen days after the administration of a vaccine for 3 months, the number of infections dropped almost to zero. Significant differences were observed in the QoL score (p < 0.05). The safety profile was good. CONCLUSIONS: In patients diagnosed with recurrent UTI and treated for 3 months with the vaccine the number of UTI episodes fell very quickly (15 days), and patients remained free of episodes and improved their QoL significantly for 1 year. These results suggest that bacterial vaccines are a possible effective alternative in the prevention of recurrent UTI.

Hypoxia signaling to genes: significance in Alzheimer's disease.

Aberrations in neural signaling, converging to and diverging from oxidative metabolism and blood supply, contribute to the initiation and maintenance of inflammatory responses, neuronal degeneration, and age-related cognitive decline in Alzheimer's disease (AD). Hypoxia/ischemia triggers phospholipase A2, leading to the accumulation of free arachidonic and docosahexaenoic acids (AA, DHA), as well as that of lysophospholipids. Some of these bioactive lipid messengers in turn give rise to several downstream lipid messengers, such as platelet-activating factor (PAF) and ecosanoids (prostaglandins and leukotrienes). Eicosanoid synthesis is highly regulated in hypoxia and in reperfusion subsequent to ischemia. As one of the consequences, mitochondrial function is disrupted and reactive oxygen species (ROS) both contribute to the expansion of cellular inflammatory responses and reduce the expression of genes required to maintain synaptic structure and function. On the other hand, pro-inflammatory genes are up-regulated. One of these, the inducible cyclooxygenase-2 (COX-2), along with oxygen-starved mitochondria, comprise the major sources of ROS in the brain during hypoxia, ischemia, and reperfusion. One outcome is a sustained metabolic stress that drives progressive dysfunction, apoptosis and/or necrosis, and brain cell death. How hypoxia modulates oxygen-sensitive gene expression is not well understood. Pro-inflammatory gene families that contribute to neurodegeneration are transiently activated in part by the heterodimeric oxygen-sensitive DNA-binding proteins nuclear factor for kappa B (NF-kappaB) and hypoxia-inducible factor-alpha (HIF-1alpha). Here the authors summarize current studies supporting the hypothesis that synaptically-derived lipid messengers play significant roles in ischemic stroke and that hypoxia is an important contributor to the onset and progression of AD neurodegeneration.