Library

Notes: The present study was carried out to investigate the oral status of a group of 4-year-old children who had already been investigated as 3-year-olds 1 year previously. The children were examined for caries, gingivitis, extrinsic stains, supragingival calculus, signs of traumatic injury, occlusion, interdental spacing, and lactobacilli and C. albicans in plaque samples. The parents were interviewed regarding toothbrushing habits, fluoride prophylaxis, and oral habits in the children. The investigation was performed in association with a general physical examination of the children. Caries was demonstrated in 67 % of the children. The mean Gingival Index was 0.52. Lactobacilli in plaque were detected in 34 % of the children and C. albicans in 18 %. The children in whom lactobacilli were demonstrated had significantly more decayed surfaces than the other children. Various sucking habits were noted in 42 % and nocturnal grinding of the teeth in 28%. Most of the parents had received dental advice at the Child Health Centers, and 41 % had given their children fluoride tablets regularly for at least 2 years.

Notes: Mast cell degranulation, and the subsequent recruitment of infiltrating inflammatory cells, such as eosinophils, into the nasal mucosa has long been considered the most important model to explain allergic rhinitis. Several studies show a decrease in the number of eosinophils and possibly also mast cells during local corticosteroid treatment. Over the last decade, a new model to explain allergic inflammation has evolved. In this model, Langerhans’cells and T-cells play an important role. Langerhans’cells possess a high affinity receptor for IgE. In patients with allergic rhinitis, allergen provocation results in stimulation of T-cells by the IgE-positive Langerhans’cells. The T-cells produce a number of cytokines which stimulate IgE production as well as the inflammatory reaction. The number of T-cells is not usually influenced by corticosteroid treatment; however, the function of the T-cells, shown by the spectrum of cytokines produced, is clearly influenced. The cells that are most dramatically affected by local corticosteroid treatment are the Langerhans’cells, which completely disappear during treatment. This decrease suggests that there is a reduction in antigen presentation. The subsequent decrease in T-cell stimulation may result in a reduction of the reactions that are dependent on T-cell-derived mediators.

Notes: The effect of nasal corticosteroid therapy on allergic rhinitis is uncertain. In a double-blind, placebo-controlled study over 3 months, we investigated the influence of a new corticosteroid spray, fluticasone propionate aqueous nasal spray (FPANS), on Langerhans cells (CD1a+ cells), HLA-DR+ cells, and T cells in nasal mucosa. Efficacy was evaluated by nasal symptom score. This treatment significantly decreased the number of CDla+ cells and HLA-DR+ cells in the nasal mucosa. Furthermore, a clear trend of decreasing numbers of T cells in nasal epithelium was found. No change in nasal symptom score was found after the treatment period. These findings suggest that fluticasone propionate aqueous nasal spray decreases the antigen presentation in nasal allergy.

Notes: Topical corticosteroids have proved to be effective in the treatment of allergic rhinitis. The symptomatology of allergic rhinitis is considered to be the result of the accumulation and activation of inflammatory cells and cytokine release and hence the efficacy of corticosteroids is associated with their anti-inflammatory action. New advances in allergic inflammation now suggest that not only mast cells and eosinophils but also T-lymphocytes and antigen-presenting dendritic cells, play an important role in the inflammatory reaction. The effect of topical fluticasone propionate on cellular infiltration in the nasal mucosa is examined, with an emphasis on two studies performed in Rotterdam, The Netherlands. The cells influenced most by corticosteroid therapy were Langerhans' cells (antigen-presenting cells), which were almost completely eradicated, possibly resulting in diminished antigen presentation, and eosinophils. There was a reduction in the number of epithelial mast cells, but the number of T-lymphocytes only decreased following high doses of corticosteroid therapy or long-term treatment. However, T-lymphocyte function was influenced, as shown by the reduction in the T-helper, (ThJ-related cytokines, interleukin (1L)-4 and IL-5. Topical corticosteroid therapy had no effect on the accumulation of macrophages. The reduction in antigen presentation, and the decrease in T-lymphocyte stimulation and cytokine production, may cause a reduced influx of eosinophils and other inflammatory cells, resulting in diminished symptomatology.

Notes: Mycobacterium tuberculosis secretes several proteins into the extracellular environment, some of which are restricted to the M. tuberculosis complex. One of these antigens is MPT64. Recently, the authors showed that native as well as recombinant MPT64 is able to distinguish between an M. tuberculosis infection and a BCG Danish 1331 vaccination. Improved distinction between tuberculin purified protein derivative (PPD) sensitivity conferred by an M. tuberculosis infection and that induced by a BCG vaccination or infection with environmental mycobacteria would be useful in the control of tuberculosis. In this study, the authors report the mapping and characterization of a Dth-inducing epitope by the use of synthetic peptides in guinea-pigs vaccinated with BCG Danish 1331 or Tokyo. Studies with overlapping synthetic peptides have pinpointed the biological activity to a single Dth-inducing epitope at the carboxyterminal region of MPT64 consisting of 15 residues between amino acids Gly-173 and Ala-187, the core epitope (CE15). A fine mapping using truncated versions of CE15 indicates the epitope is restricted to 13 residues between amino acids Val-174 to Glu-186. However, the optimal Dth reactivity is obtained by CE15. Different modifications of CE15 revealed that a lysine tree construction improves the skin reactivity to a maximum level approaching that of the reactivity to tuberculin PPD.

Notes: The local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins.〈section xml:id="abs1-2"〉〈title type="main"〉MethodsThis single allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosa biopsies were taken twice before provocation (before and after 4 weeks of preventive treatment) and three times after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n = 9). Eosinophils and mRNA positive cells (in situ hybridization for IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ, RANTES and TNFα) were counted in the biopsies.〈section xml:id="abs1-3"〉〈title type="main"〉ResultsPreventive treatment with FPANS out of season resulted in a decrease in eosinophils and mRNA positive cells for IL-5 and IL-6. After allergen provocation, levels of most of the measured cytokines (IL-3, IL-5, IL-6, IL-13, IFNγ, RANTES and TNFα) and eosinophils were reduced using corticosteroids. The numbers of cells (eosinophils, IL-3, IL-6 and IL-8) correlated with nasal symptoms. Significant correlations in the early and late allergic phase were found between eosinophils and cytokines (IL-3, IL-10 and IL-13).〈section xml:id="abs1-4"〉〈title type="main"〉ConclusionThese results indicate that preventive treatment with FPANS prior to contact with grass pollen is effective in reducing the increase of cytokine mRNA positive cells in reaction to grass pollen contact.

Notes: Background The role of antigen presenting cells (APC) in allergic rhinitis is underexposed. Allergen presentation to T lymphocytes is probably an important aspect of the pathophysiological mechanism of allergic rhinitis.Objectives The aim of the study was to investigate the presence and dynamics of APC with special emphasis on Langcrhans cells (LC) in the nasal mucosa of patients with an isolated grass pollen allergy during an out-of-season 2-week allergen exposure, mimicking the natural grass pollen season.Methods Seventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with allergen during a 2-week period in the winter. Biopsy specimens were obtained once before, six times during and once after the provocation period. Biopsy sections were stained with monoclonal antibodies: OKT6 (CDla-Langerhans cells). Ki-M6 (CD68 macrophages), L25 (dendritic cells), anti-IgE, HLA-DR and HLA-DQ (Major Histoeompatibihty Complex Class II - antigen presenting eells), as well as staining with acid phosphatase.Results APC with different characteristics are present in the epithelium and lamina propria of the nasal mucosa. The number of LC increased significantly in epithelium and lamina propria. IgE+-LC were present in the nasal mucosa and increase during provocation, HLA-DR+ cells with dendritic and lymphocytic morphology and HLA-DQ+ cells were found. The number of these cells increased during provocation in epithelium and lamina propria. The number of HLA-DR+ epithelial cells did not change. A significant increase in the number of Ki-M6+ cells (macrophages) was found in the lamina propria. However, Ki-M6+ cells increased to the same extent in the lamina propria in the control group.Conclusion APC are influenced by allergen provocation. This study supports the hypothesis that (IgE+) LC are involved in allergic rhinitis. The role macrophages play remains doubtful.

Notes: Mast cell degranulation is thought to be an important component of the pathogenesis of allergic rhinitis. Quantitative studies on mast cells in nasal mucosa after allergen exposure have given widely divergent results, ranging from an overall decrease via redistribution to an overall increase. We investigated this problem by employing a combination of anti-IgE and toluidine blue staining of biopsy specimens. In allergic patients anti-IgE was found to identify all mast cells and toluidine blue to detect mast cells that were not (totally) degranulated.The study was composed of two parts done in different patient groups. In the first part of the study biopsies were performed in 23 patients with isolated grass-pollen allergy, once during natural provocation in the summer and once in the winter. Biopsies were also performed in 12 controls. Non-allergic controls were found to have the same number of mast cells in the lamina propria as asymptomatic allergic patients. The controls seldom have mast cells in the epithelium. The patients with isolated grass-pollen allergy showed an increase in the numbers of mast cells in the lamina propria during natural provocation and the same seemed to occur in the epithelium as well. During natural provocation almost all of the mast cells in the epithelium and half of those in the lamina propria were degranulated.In the second part of the study 17 patients with isolated grass-pollen allergy and four controls were challenged daily with allergen extract during a 2-week period in the winter. During this period biopsies were performed at eight different occasions, i.e. once before, six occasions during and once after the provocation period. The results of this part of the study showed that during provocation mast cells migrate to the surface of the nasal mucosa, where they become degranulated, and that the pool of mast cells in the lamina propria was apparently replenished by migration of mast cells from the vessels in the lamina propria. The total number of mast cells in the lamina propria remained approximately the same while the mast cells residing in an increasingly thick layer measured from the basal membrane into the lamina propria became degranulated. After 2 weeks, 82% of the mast cells in the lamina propria was degranulated and it was only in the deepest layers that some toluidine blue positive cells were found.This study can explain the seemingly conflicting reports in the literature on mast cell dynamics and degranulation and shows that the reported differences are due to differences in the techniques used and the time of evaluation.