IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study.

BACKGROUND: We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut-allergic population characterized under a common protocol. METHODS: Sixty-eight peanut-allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting dose was established by double-blind placebo-controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. RESULTS: Seventy-eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut-allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early-onset peanut allergy. Peanut-tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA /l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA /l is significantly associated with the development of systemic reactions to peanut.

Intergeneric hybrid origin of the invasive tetraploid Cirsium vulgare.

The invasive tetraploid Cirsium vulgare hybridizes with both Cirsium and Lophiolepis. Its conflicted position in molecular phylogenies, and its peculiar combination of morphological, anatomical, and genomic features that are alternatively shared with representatives of Cirsium or Lophiolepis, strongly suggest its intergeneric hybrid origin. Genetic relationships of C. vulgare (8 samples) with genus Lophiolepis (11 species) and other representatives of genus Cirsium (12 species) were evaluated using restriction site-associated DNA sequencing (RADseq) and examined using analytical and imaging approaches, such as NeighborNet, Heatmap, and STRUCTURE, to identify nuclear genomes admixture. Estimation of the intensity of spontaneous hybridization within and between Cirsium and Lophiolepis was based on herbarium revisions and published data for all reported hybrids pertinent to taxa currently included in Cirsium or Lophiolepis. The genome of any examined Cirsium species is more similar to C. vulgare than to any Lophiolepis species, and vice versa. The nuclear genome of the tetraploid C. vulgare is composed of two equivalent parts, each attributable either to Lophiolepis or to Cirsium; the organellar RADseq data clustered C. vulgare with the genus Cirsium. Spontaneous hybridization between Cirsium and Lophiolepis is significantly less intensive than within these genera. Our analyses provide compelling evidence that the invasive species C. vulgare has an allotetraploid intergeneric origin, with the maternal parent from Cirsium and the paternal from Lophiolepis. For the purpose of delimiting monophyletic genera, we propose keeping Lophiolepis separate from Cirsium and segregating C. vulgare into the hybridogenous genus Ascalea.

Additional indications for the low allergenic properties of the apple cultivars Santana and Elise.

Patients with Oral Allergy Syndrome (OAS) to fresh apple may tolerate low allergenic apple cultivars. We aimed to investigate if the low allergenic properties of Elise and Santana, as previously identified in a Dutch population, could be generalised within North West Europe within the birch pollen region with regard to both the prevalence and degree of sensitization. Prick-to-prick tests (PTP) were performed in eighty-five adult patients with OAS to fresh apple in Great Britain, Switzerland and Northern Italy, before the birch pollen season, using the putatively low allergenic apple cultivars Elise, Santana, Granny Smith, Modi and Mcintosh, as well as the putatively high allergenic apple cultivars Golden Delicious and Kanzi. No significant differences in percentages of negative responses of PTPs were found between the three countries. Negative responses did not differ from negative responses to the different apple cultivars we previously found in 2006/2007 in the Netherlands. The size of the PTPs of all apple cultivars tested were correlated to the size of the skin prick tests with birch pollen. These results add to the indications for the low allergenic properties of the low allergenic apple cultivars Santana and Elise, as the number of negative responses were reproducible in three countries within the birch pollen region and were similar to previous results in the Netherlands. These results justify oral challenge studies with Elise and Santana within the birch pollen region, to establish the low allergenic properties for the benefit for apple allergic consumers for definite conclusions.

Prey-race drives differentiation of biotypes in ant-eating spiders.

1. Disruptive natural selection resulting from specialization on different hosts is recognized as one of the most important driving forces in the diversification of herbivores and parasites. It has been proposed that a similar mechanism could apply to carnivorous predators too, although the evidence is still lacking. 2. Here, we show that the differentiation of biotypes of specialized ant-eating spiders of the genus Zodarion has probably been induced by prey-shifting. We focused on two forms of one species Z. styliferum from the Iberian Peninsula that presumably represent ecological races. We conducted geographic, ecological, venom-oriented, reproductive and genetic divergence analysis among multiple populations collected at a number of sites across Portugal and Madeira. 3. Geographic analysis revealed that the two forms occur in mosaic sympatry. Each form was found to associate in nature with a different ant species in a different habitat. Specifically, the styliferum form hunted predominantly Messor ants, and the extraneum form hunted mainly Camponotus ants. Laboratory experiments revealed that the two forms exhibit a significant preference for attacking focal ants, demonstrating higher paralysis efficiency, and also show different venom composition. Cross-mating of the two forms was significantly less likely than between pairs of the same form, suggesting moderate assortative mating. Phylogenetic analyses indicate low genetic differentiation of the two forms and parallel-repeated evolution of biotypes. 4. Adaptive prey-shifting correlated with habitat preference are at present the most valid explanations for biotype formation in Zodarion. The speciation of ant-eating Zodarion spiders thus appears to follow a scenario similar to that of host-shifting in parasites and herbivores.

Surface modifications and molecular imprinting of polymers in medical and pharmaceutical applications.

Recent developments in the field of biomaterials are based on molecular design of polymers with improved surface and bulk properties. Novel techniques of surface modification by addition of tethered chains can lead to materials with the ability to recognize biological and pharmaceutical compounds. Methods based on molecular imprinting can increase the recognition capabilities of such systems. Chain tethering can also can improve the mucoadhesive behavior of a delivery device and the effectiveness of a drug by allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels are well-suited for mucoadhesion due to their flexibility and nonabrasive characteristics which reduce damage-causing attrition to the tissues in contact. However, the adhesive and drug delivery capabilities of these devices can continue to be improved as presently known bioadhesive materials are modified and more bioadhesive materials are discovered. Tethering of long PEG chains on PAA hydrogels and their copolymers can be achieved by grafting reactions involving thionyl chloride, followed by PEG grafting. The ensuing materials exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure.

Hydrogels in pharmaceutical formulations.

The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.

Methylated and demethylated tricyclic antidepressants and their binding to cell membranes.

We studied the binding of methylated and demethylated tricyclic antidepressants (TCA) to synaptic plasma brain membranes (SPM) and to lymphocyte, platelet and erythrocyte membranes. In the synaptic plasma membranes, more demethylated than methylated dibenzazepine derivatives were bound and the binding affinity was decreased. By contrast, in lymphocyte and platelet membranes more methylated derivatives were bound. Phosphatidylserine (PS) enhanced significantly the binding of methylated TCA in SPM without changing the dissociation constant (Kd). Lysophosphatidylserine did not affect the binding. PS also caused an increase of 3H-imipramine binding to lymphocyte membranes but the binding to platelet membranes was not affected. PS also enhanced 3H-5-HT uptake into platelets and 3H-noradrenaline uptake into lymphocytes.

Changes of ligand binding after membrane phosphorylation.

Phosphorylation of synaptic plasma brain membranes (SPM) causes a decrease of the specific binding of demethylated tricyclic antidepressants (TCA) and changes the affinity of 3H-imipramine and 3H-desmethylimipramine binding. The decrease of TCA binding was found also in lymphocyte membranes. In platelet membranes a decreased binding was found only with demethylated dibenzazepine derivatives. Bmax and Kd values are also decreased in the presence of phosphatidic acid or alpha-glycerolphosphate.

[Rapid detection and easy culture of Campylobacter pylori from human gastric mucosa]. / Príspevek k rychlému prukazu a snadné kultivaci Campylobacter pylori z lidské zaludecní sliznice.

96 gastric mucosal biopsy specimens collected at endoscopy and placed into 3 ml 20% glucose were examined histologically, microscopically (Gram staining), by urease test, and by cultivation. The rate of positive findings ws 62.5% by urease test, 34.4% by cultivation, and 27.0% microscopically. By using simple selective solid media, the number of positive cultivations increased to 58.7%. Positive microbiological findings were established by one of three microbiological methods at a high percentage in gastric ulcers (87.5%) and at the lowest rate in duodenal ulcers (57.1%). Remarkable were the positive findings in 60% of patients with normal endoscopic results. In chronic gastritis the highest positivity rate was established histologically (52.6%). Antibiotics without bismuth preparations were used in the treatment of six patients. Check-up examinations yielded negative histological and microbiological findings only in two patients. We failed to affect the inflammatory activity of the gastric mucosa even when consolidation of the ulcer lesion was achieved.

[The effect of cocaine on binding of tricyclic antidepressives in the synaptic plasma membranes in the brain]. / Vliv kokainu na vazbu tricyklických antidepresiv v SPM mozku.

Effect of cocaine on binding of 3H-imipramine, 3H-desmethylimipramine, 3H-didesmethylimipramine and 3H-amitriptyline to brain synaptic plasma membranes (SPM) was studied. Binding of methylated tricyclic antidepressants was more affected. Cocaine inhibits 3H-imipramine binding at concentrations higher than 10(-5) mol/l. Binding stimulated by phosphatidylserine was affected more significantly.

[Ca(2+)-channel blockers and binding of tricyclic antidepressive agents]. / Blokátory Ca(2+)-kanálu a vazba tricyklických antidepresív.

The interactions between Ca(2+)-channel blockers (verapamil and gallopamil) and synaptic plasma membranes (SPM) from bovine brain or human lymphocyte and platelet plasma membranes were studied. Changes in binding parameters of [3H]imipramine, [3H]desmethylimipramine and [3H]gallopamil were determined after addition of unlabelled verapamil or imipramine and after addition of phosphatidylserine (PS) (PS-stimulation). Specific binding of [3H]imipramine to SPM was decreased and [3H]desmethylimipramine binding was increased by 1 microM verapamil. [3H]gallopamil binds specifically to SPM as well as to platelet and lymphocyte membranes. [3H]gallopamil binding to SPM or lymphocyte plasma membranes was PS-stimulated in contrast to platelet plasma membranes without PS effect on binding. Imipramine inhibited both [3H]gallopamil binding and PS-stimulated [3H]gallopamil binding to SPM or lymphocyte plasma membranes. Mutual effects of tricyclic antidepressants and Ca(2+)-channel blockers on their binding sites require relatively high drug concentrations. Mechanism of Ca(2+)-channel blockers action in the treatment of depression may be connected rather with changes in signal transduction through serotonin and catecholamine receptor systems than with direct interaction of drugs with binding sites for tricyclic antidepressants.