SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms.

BACKGROUND: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. OBJECTIVE: To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease and report the AR results. METHODS: Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). RESULTS: In the subgroup, the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was -0.78 (95% confidence interval -1.47 to -0.07, relative difference 28.8%, P = .0357). Furthermore, a significant difference was found for the total score of the Rhinitis Quality of Life Questionnaire with Standardized Activities RQLQ(S) and for the individual domains: activities, sleep, non-nose and non-eye symptoms, and nasal symptoms. For the TCRS and Rhinitis Quality of Life Questionnaire score, a dose response was seen, with numerically lower, nonsignificant differences for 1 and 3 SQ-HDM. The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups. No safety concerns were observed. CONCLUSION: Efficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Questionnaire score in subjects with AR present at baseline. The treatment was well tolerated. TRIAL REGISTRATION: EudraCT, no 2006-001795-20; ClinicalTrials.gov, identifier NCT00389363.

Extensive IgE cross-reactivity towards the Pooideae grasses substantiated for a large number of grass-pollen-sensitized subjects.

BACKGROUND: Allergy to taxonomically related species is a common phenomenon caused by the same immunological receptor cross-reacting to homologous allergens from different species. Knowledge of patterns of cross-reactivity is crucial for the selection of optimal products for diagnosis and for specific immunotherapy. The objective of this study was to investigate patterns of serum IgE cross-reactivity towards pollens from various grass species. METHODS: With grass group 1 allergens as the representative group, amino acid sequence alignment, structural modelling and comparison of 3D surface characteristics were performed to exemplify the molecular basis of IgE cross-reactivity. IgE binding to extracts from ten different grass species was determined (total number of data pairs >19,000), and IgE inhibition experiments using Phleum pratense were performed. RESULTS: Analysis of surface topography for group 1 grass allergens demonstrated ample space for IgE binding epitopes in surface areas conserved among Pooideae grasses. Significant correlation was observed between the serum IgE response to P. pratense extract and extracts from the other Pooideae grasses analyzed. P. pratense extract was demonstrated to inhibit the binding of IgE to the allergens in all of the extracts included in the investigation, indicating patient IgE to be primarily directed towards common epitopes. CONCLUSION: Extensive IgE cross-reactivity was observed towards the allergens of the Pooideae grasses, meaning that the immune system does not appear to distinguish based on the IgE level between the different species of this subfamily. The data suggest equal effect upon use of any of the Pooideae species for diagnostic as well as therapeutic purposes.

Allergy immunotherapy: the future of allergy treatment.

Allergic respiratory disease represents a significant and expanding health problem worldwide. Allergic symptoms, such as asthma and hay fever, cause sleep impairment and reduce school and work performance. The cost to society is substantial. Allergen avoidance and pharmacotherapy cannot control the disease. Only allergy immunotherapy has disease-modifying potential and should be included in optimal treatment strategies. Allergy immunotherapy was first administered as subcutaneous injections and has been practiced for the past 100 years or so. Recently, tablet-based sublingual allergy immunotherapy (SLIT) was introduced with comprehensive clinical documentation. SLIT tablets represent a more patient-friendly concept because they can be used for self-treatment at home.

Cobalt Cage Complexes with N(3)S(3) Donor Sets and Differing Cavity Sizes: A Novel Macrobicyclic Cage with a Contracted Cap.

Treatment of the cobalt(III) complex of the hexadentate tripodal N(3)S(3) ligand ten (4,4',4' '-ethylidynetris(3-thiabutan-1-amine) with propanal and paraformaldehyde under basic conditions, followed by borohydride reduction and reoxidation of the metal center, leads largely to the encapsulated (red) metal complex cation [Co(Me(2)-N(3)S(3)sar)](3+) (Me(2)-N(3)S(3)sar = 1,8-dimethyl-3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]icosane). Unexpectedly, significant amounts of the homologous (yellow) complex cation [Co(Me(2)-N(3)S(3)absar)](3+) (Me(2)-N(3)S(3)absar = 1,8-dimethyl-3,13,16-trithia-6,10,19-triazabicyclo[6.6.5]nonadecane) were also obtained. This macrobicyclic complex has a contracted cavity resulting from a cap containing one fewer methylene units than Me(2)-N(3)S(3)sar. The structures of both cobalt(III) complexes have been determined by X-ray crystallography. [Co(Me(2)-N(3)S(3)sar)]Cl.ZnCl(4).H(2)O crystallizes in the cubic space group P2(1)3 with Z = 4, a = 13.9683(11) Å. [Co(Me(2)-N(3)S(3)absar)](ClO(4))(3).0.5CH(3)CN.0.5H(2)O crystallizes in the triclinic space group P&onemacr; with Z = 4, a = 12.036(4) Å, b = 15.932(9) Å, c = 17.212(14) Å, alpha = 64.93(7) degrees, beta = 72.77(5) degrees, gamma = 88.91(7) degrees. The surprising structural rearrangement is examined, along with the spectral and redox properties of both cobalt complexes. The influence of the reduced cavity size in the absar type cage is reflected in a shift of the bands in the electronic spectrum of both the cobalt(II) and cobalt(III) complexes to higher energy, and a more negative value for the Co(III/II) redox potential. The demetalation of the complexes is also described.

Bowl adamanzanes--bicyclic tetraamines: syntheses and crystal structures of complexes with cobalt(III) and chelating coordinated oxo-anions.

Seven cobalt(III) complexes of the macrobicyclic tetraamine ligand [2(4).3(1)]adamanzane ([2(4).3(1)]adz) are reported along with the crystal structure of six of these complexes. The solid state and solution structures are discussed, and a detailed assignment of the NMR spectra of the sulfato complex is provided. Four of the seven complexes contain a chelate coordinating oxo-anion (sulfate, formiate, nitrate, carbonate). Equilibration of these species with the corresponding diaqua complex is generally slow. The rates of equilibration in 5 mol dm(-3) perchloric acid at 25 degrees C have been measured, yielding half lives of 20 min, 10 min and 3 h for the sulfato, formiato and carbonato species respectively. The corresponding reaction for the nitrato complex occurs with a half life of less than 3 min. The concentration acid dissociation constant for the Co([2(4).3(1)]adz)(HCO(3))(2+) ion has been measured to K(a) = 0.33 mol dm(-3) [25 degrees C, I = 2 mol dm(-3)] and K(a) = 0.15 mol dm(-3) [25 degrees C, I = 5 mol dm(-3)]. The propensity for coordination of sulfate was found to be large enough for a quantitative conversion of the carbonato complex to the sulfato complex to occur in 3 mol dm(-3) triflic acid containing a small sulfate contamination. On this basis the decarboxylation in 5 mol dm(-3) triflic acid of the corresponding cobalt(III) carbonato complex of the larger macrobicyclic tetraamine ligand [3(5)]adz was reinvestigated and found to lead to the sulfato complex as well. The difference in exchange rate of the oxo-anion ligands for the cobalt(III) complexes of the two adamanzane ligands is discussed and attributed to fundamental differences in the molecular structure where an inverted configuration of the secondary non-bridged amine groups is seen for the complexes of the larger [3(5)]adz ligand. The high affinity for chelating coordination of oxo-anions for these two cobalt(iii)-adamanzane-moieties is rationalised on basis of the N-Co-N angles. N-Co-N angles are compared for a series of adamanzane complexes, and the structural consequences are discussed.