The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1ß), and complement.

Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1ß), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1ß and MIP-1ß/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1ß; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.

Functional characterization of the vitellogenin promoter in the silkworm, Bombyx mori.

Genetic transformation and genome editing technologies have been successfully established in the lepidopteran insect model, the domesticated silkworm, Bombyx mori, providing great potential for functional genomics and practical applications. However, the current lack of cis-regulatory elements in B. mori gene manipulation research limits further exploitation in functional gene analysis. In the present study, we characterized a B. mori endogenous promoter, Bmvgp, which is a 798-bp DNA sequence adjacent to the 5'-end of the vitellogenin gene (Bmvg). PiggyBac-based transgenic analysis shows that Bmvgp precisely directs expression of a reporter gene, enhanced green fluorescent protein (EGFP), in a sex-, tissue- and stage-specific manner. In transgenic animals, EGFP expression can be detected in the female fat body from larval-pupal ecdysis to the following pupal and adult stage. Furthermore, in vitro and in vivo experiments revealed that EGFP expression can be activated by 20-hydroxyecdysone, which is consistent with endogenous Bmvg expression. These data indicate that Bmvgp is an effective endogenous cis-regulatory element in B. mori.

Thrombolysis of acute ischaemic stroke in a district general hospital: are we doing enough?

Thrombolysis of acute ischaemic stroke is safe, efficacious and licensed for use in the UK. To date, few studies have looked at the rates of thrombolysis within a district general hospital setting. The aim of the study was to identify whether local thrombolysis protocols for stroke are adhered to; the rate of thrombolysis and strategies for implementation focused at improving the provision of thrombolysis of patients with acute ischaemic stroke. The methodology involved in this was a retrospective study within a district general hospital in the South of England. Data on patients admitted between 15 April 2008 and 14 April 2009 including demographics, use of the local thrombolysis protocol and reasons for non-thrombolysis were collected and analysed. Out of a total of 599 patients with a primary presentation of acute stroke, 18 were considered for thrombolysis. Six patients out of these 18 were thrombolysed without complications. Four out of these six patients had an improved National Institutes of Health Stroke Scale (NIHSS) post-thrombolysis and one eventually died due to the extensiveness of the stroke sustained, despite a slightly improved NIHSS. The rate of thrombolysis of acute ischaemic stroke is low in this hospital (1.001%). Various measures will need to be considered for implementation in order to improve the provision of this service.

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

[A matched case-control study on the relations between beta-carotene and lung cancer].

In order to discover the relationship between dietary nutrients intake and risk of lung cancer 1:1 matched case-control study on 156 recent histologiclly diagnosed primary lung cancer patients and 156 patients with respiratory tumour and other related diseases as controls, was conducted in Wuhan. All cases and controls were asked to participate in the nutritional assessment program and a food frequency questionnaire containing 64 food items was filled in. The findings showed that there was a statistically significant difference between dietary intake of beta-carotene between the two groups (2877.13 +/- 393.43 vs. 3445 +/- 430.98 micrograms/day). Having controled the confounding factor of cigarette smoking, a significant linear trend for lower dietary carotene intake toward higher lung cancer risk was observed.

[A case-control study of serum beta-carotene and lung cancer].

A 1:2 matched case-control study was conducted in Wuhan area with conditional logistic regression model to study the relationship between occurrence of primary lung cancer and serum levels of beta-carotene. The results showed the lower the serum levels of beta-carotene, the higher the risk of lung cancer. It suggested the increase of serum beta-carotene with dietary intake could lower the risk of lung cancer.

The effects of sterilization and storage treatments on the stress-strain behavior of aortic valve leaflets.

An investigation was made of the feasibility of using tensile tests to detect alterations in the molecular structure of aortic valve tissue brought about by sterilizing or storage treatments. Stress-strain tests were carried out on fresh valve leaflets from pigs and repeated with the same specimens after specified sterilization or storage treatments. It was found that the stress at a given strain was increased by treatment with ethylene oxide, buffered formalin, and tissue culture solution and decreased by treatment with antibiotics. The least change was with tissue culture solution and antibiotics. It has been suggested that the best method of allograft sterilization should involve minimal structural alteration to the collagen and elastic components of the tissue. Thus, treatment with tissue culture solution and antibiotics seems appropriate.