Background Allergic bronchial asthma is a chronic inflammatory disease of the airways. The transcription factor GATA-3 was shown to play an important role in TH 2 cell activation, but also in the ...regulation of other cell types involved in bronchial asthma including mast cells, eosinophils, and epithelial cells. DNAzymes represent a new class of antisense molecules that combines the specificity of DNA base pairing with an inherent RNA-cleaving enzymatic activity. Objective To develop a GATA-3 mRNA-specific DNAzyme and analyze its allergy-preventing activity in murine models of experimental allergic asthma. Methods The most active DNAzyme (termed gd21 ) was selected by in vitro cleavage assays. Allergic airway inflammation was assessed by inflammatory cell and cytokine analysis within bronchoalveolar lavage. Lung histology, including goblet cell hyperplasia and lung function, was analyzed using head-out body-plethysmography. Results Intranasal administration of gd21 prevented airway inflammation and mucus production and inhibited development of airway hyperresponsiveness to methacholine in models of acute allergic airway inflammation. Similar effects were also detected in a model of chronic experimental asthma. Interestingly, gd21 was at least as effective as other antisense molecules, and off-target effects were not detected. Further experiments indicated that pulmonary surfactant may facilitate the cellular uptake of gd21 by acting as an endogenous transfectant. Conclusion These results indicate that topical application of the GATA-3–specific DNAzyme is a promising novel approach for the treatment of allergic bronchial asthma.
Background It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants. Objective To investigate the ...relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences. Methods As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-γ, IL-10, and TNF-α. Results Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-γ production, but not with IL-5 and IL-10. Conclusion Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-γ production.
Abstract Background context Cervical involvement due to spinal brucellosis is quite rare. Although surgery usually is not necessary in spinal brucellosis, most of the patients with cervical ...involvement require surgical treatment because of the high rate of neurological involvement and spinal cord compression. Purpose To present a unique case with cervical spinal brucellosis with epidural and paravertebral abscesses and to discuss the treatment alternatives of this disease. Study design A case report. Methods A 61-year-old patient with spinal cord compression syndrome due to cervical spinal brucellosis was reported. He was treated by triplet antibiotherapy for 24 weeks. On magnetic resonance imaging, spinal cord compression caused by epidural abscess and granulation tissue, and prevertebral abscess were seen. Results At the end of the treatment, there were no complaints, neurological findings, or positive infection markers. There was not epidural compression on control magnetic resonance imaging. Conclusions Surgery may not be required in all cervical spinal brucellosis cases with epidural compression and neurological involvement. Conservative treatment with close observation may be sufficient in these patients who are usually older people.
Background Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, ...epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent. Objective To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis. Methods A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR. Results Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis. Conclusion Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth.
