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Notes: Background Local nasal immunotherapy (LNIT) with extracts in powder has been detnonstrated clinically effective and devoid of side-effects in several controlled trials; nevertheless, no data concerning the long-term effects of LNIT are presently available.Methods In a recent double-blind, placebo-controlled study of LNIT to Parietaria pollen we observed, by means of specific nasal provocation test (SNPT) that LNIT is able to modify the local allergic inflammatory response. In the present study we followed up the same patients in open fashion for 2 further years.Results The results confirmed the clinical efficacy of LNIT and showed that it is strictly dependent on pre-seasonal administration: in fact, after LNIT discontinuation a clinical relapse was observed. A certain long-lasting protective effect on SNPT parameters (nasal symptoms and neutrophils infiltration) was also observed, whereas an increase of eosinophils count and ICAM-1 expression on nasal epithelial cells appeared as possible markers of clinical relapse.Conclusion The present study suggests that pre-seasonal LNIT can be taken in consideration in selected subjects as prophylactic treatment for pollen-induced rhinitis. In addition, the results obtained provide informations about the duration of clinical efficacy and add data about the local allergic inflammation and its modulation.

Notes: Background The intercellular adhesion molecule ICAM-1 has been detected by immunohistochemical methods on epithelial cells of the conjunctiva and nose during allergic inflammation.Objective The aim of the present study was to evaluate whether ICAM-1 expression on conjunctival epithelium derives from endogenous synthesis or is merely due to passive uptake of soluble ICAM-1 released from inflammatory cells.Methods In situ hybridization was performed using a 3’end dygoxygenin-labelled specific DNA oligonucleotide probe on fixed conjunctival smears from allergic subjects challenged with, or naturally exposed to the allergen, and from healthy subjects. Immunocytochemistry for ICAM-1 was performed by alkaline phosphatase antialkaline phosphatase.Results Results In allergic patients, both naturally exposed to the allergen and after specific challenge, a clear hybridization pattern on epithelial cells was apparent. Out of allergen exposure, some symptomfree pollinosic subjects, as well as a few healthy volunteers showed mild ICAM-1 mRNA cytoplasmic staining in the absence of immunohistochemically detectable ICAM-1. This finding may explain the very early appearance of ICAM-1 on conjunctival epithelium following specific challenge in allergic individuals.Conclusions These results indicate that the presence of ICAM-1 on conjunctival epithelium during allergic inflammation derives from endogenous synthesis and not from uptake of soluble ICAM-l.

Notes: Background Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis.Objective We evaluated the possible effects of levocabastine eye drops on early (EPR) and late phase (LPR) inflammatory changes induced by allergen-specific conjunctival challenge (ASCC). We focused our attention on the possible effect of levocubastine on expression of the intracellular adhesion molecule-1 (ICAM-1) on epithelial cells. Such a phenomenon is likely to play an important role in allergic inflammation.Methods The study was a double-blind, placebo-controlled, randomized trial, performed in cross-over, outside the pollen season. Ten out-patients suffcring from allergic rhinoconjunctivitis due to Parietaria Judaica (wall parietary) were enrolled. Patients randomly received levocabastine eye drops (0.5 mg/mL) or placebo eyedrops, one drop in the left eye (right eye as control), 30 min before ASCC. Clinical evaluation (hyperaemia, burning-itching, lacrimation and eyelid swelling) and cytological assessment (number of neutrophils, eosinophils and lymphocytes, and ICAM-1 expression on conjunctival epithelium) were evaluated at baseline, 30min and 6h after ASCC. In parallel, we evaluated the in vitro effect of levocabastine at concentrations ranging from 2 × 10−9 M to 2 × 10−5M on ICAM-l expression and shedding by a continuously cultured differentiated epithelial cell line (WK).Results Levocabastine reduced symptom scores during EPR (15min and 30min, P 〈 0.002), inflammatory cell infiltration duritig FPR (P 〈 0.002 for neutrophils, eosinophils and lymphocytes) and ICAM-1 expression on epithelium both during EPR (P 〈 0.002) and LPR (P 〈 0.02). LPR symptom scores and inflammatory cell infiltration were only slightly modified by levocabastine treatment. In vitro levocabastine at 2 ± 10−5 M concentration was able to down-regulate basal ICAM-1 expression, although it exerted no effect on ICAM-1 expression by interferon-γ (IFNγ)-stimulated WK cells and on soluble ICAM-1 release by epithelium.Conclusion Levocabastine exerts anti-allcrgJc activity, in that it reduces in vivo inflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium. The latter phenomenon may be due, at least in part, to a direct effect of levocabastine on epithelial cells.

Notes: Inhaled corticosteroids in the treatment of asthma have been shown to produce marked reductions in the number of inflammatory cells (mainly mast cells and eosinophils) and their products at bronchial level (such as cytokines). Recently, it has been demonstrated that epithelial cells express ICAM-1/CD54 in allergic patients both during natural allergen exposure and after allergen challenge. We have previously demonstrated that deflazacort (a systemic steroid) reduces the expression of ICAM-1 on conjunctival epithelial cells. The present study aimed to evaluate the effects exerted by budesonide on adhesion molecule expression by a human epithelial cell line (lung carcinoma: DM) and on soluble ICAM-1. Budesonide was added at concentrations corresponding to 10−8, 10−7, and 10−6 mol/1 in cultured epithelial cells, either in the absence of any stimulus or in the presence of interferon-gamma (IFN-y) at 500 U/ml. After 24 h of incubation, cytofluorometric analysis was performed for ICAM-1 and CD29/VLAP1. The 24–h supernatants of the same cultures were collected and then evaluated for soluble ICAM-1 (sICAM-1). The results showed that budesonide inhibits ICAM-1 and CD29 basal expression on the cells studied (P〈0.05): budesonide was effective in a dose-dependent manner. In addition, budesonide reduced surface ICAM-1 upregulation induced by IFN-γ at 500 U/ml (p〈0.05). Finally, cell cultures with budesonide showed decreased levels of soluble ICAM-1 in basal condition, but not after IFN-γ stimulation.

Notes: The possibility of local hyposensitization in allergies was envisaged since the first decades of the century and then sporadically employed, whereas controlled clinical trials of local nasal immunotherapy (LNIT) were performed only during the last 20 years. Studies currently available agree on the clinical efficacy of the treatment. LNIT was demonstrated capable of reducing symptoms both in pollen- and mite-induced rhinitis, and of modifying the specific target organ responsivity. Indeed, aqueous extracts appeared to be more effective than modified ones but were also charged by troublesome local side effects, while the recently introduced powdered extracts seemed to overcome this problem, maintaining a favourable clinical effectiveness. In a recent study we demonstrated a significant effect of LNIT on local allergic inflammation. LNIT reduced both the inflammatory infiltration and ICAM-1 expression on nasal epithelial cells upon specific nasal challenge. The effects on specific challenge appeared long-lasting, but the clinical efficacy seemed to depend strictly upon preseasonal treatment. LNIT with powdered extracts appears an effective, safe and well-tolerated treatment for allergic rhinitis. Nevertheless, its particular administration technique requires a careful choice of patients. Finally, a socioeconomical analysis shows a favourable costbenefit ratio for LNIT if compared to classic subcutaneous immunotherapy.

Notes: Lodoxamide is an antiallergic drug acting as a mast-cell stabilizer, which is effective in the treatment of allergic conjunctivitis. The study aimed to evaluate the effect of lodoxamide eye-drops on the inflammatory early-phase reaction (EPR) changes induced by allergen-specific conjunctival challenge (ASCC). This was a cross-over, double-blind, placebo-controlled, randomized study, including 10 outpatients suffering from allergic rhinoconjunctivitis due to Parietaria judaica. Patients received one drop of lodoxamide tromethamine 0.1% or placebo 30 min before each ASCC. Clinical evaluation and cytologic assessment were done at baseline and 30 min after each ASCC. Lodoxamide induced a reduction in total symptom score and hyperemia during the EPR (P 〈 0.05). Lacrimation, itching/ burning, and eyelid swelling were only slightly (nonsignificantly) reduced. Lodoxamide induced a reduction in the total number of inflammatory cells and neutrophils during the EPR (P 〈 0.02). Eosinophil and lymphocyte number and ICAM-1 expression showed only a slight, not statistically significant decrease. Placebo did not affect the studied parameters. Lodoxamide reduced early clinical events and cellular changes after ASCC consistently with its activity as mast-cell stabilizer. Moreover, lodoxamide was able to downregulate in vitro ICAM-1 expression on the continuously cultured, differentiated conjunctival cell line WK. This was shown both in basal conditions (P 〈 0.05) and upon interferon-gamma stimulation (P 〈 0.03), although at high concentration.

Notes: Paolieri F, Battifora M, Riccio AM, Pesce G, Canonica GW, Bagnasco M. Intercellular adhesion molecule-1 on cultured human epithelial cell lines: influence of proinflammatory cytokines.The expression of intercellular adhesion molecule-1 ‘CD54 or ICAM-1’ on epithelial cells during acute or chronic inflammation may favor the interaction between epithelial cells and leukocytes expressing the natural ligands of ICAM-1, LFA-1 ‘CD11a/CD18’, and Mac-1 ‘CD11b/CD18’. We have evaluated in vitro the expression of ICAM-1 by a conjunctival ‘WK’ and an intestinal ‘1407’ human continuous epithelial cell line. Cells were cultured for 24 h in the presence or absence of IFN-γ, TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-10, and TGF-Jβ1. Both epithelial cell lines showed a constitutive expression of ICAM-1. IFN-γ at 500 U/ml and TNF-α at 200 ng/ml upregulated ICAM-1 expression; IL-1β at 100 pg/ml upregulated ICAM-1 on WK cells only. Cells cultured in the presence of both IFN-γ and TNF-α exhibited a mean fluorescence intensity far greater than those cultured with IFN-γ or TNF-α alone. 1407 and WK cells were able to release soluble ICAM-1. IFN-γ and TNF-α enhanced the release of sICAM-1. IL-4, IL-6, IL-8, IL-10, and TGF-β1 did not affect either ICAM-1 expression or sICAM-1 release. In conclusion, continuously cultured human epithelial cells may express ICAM-1 on their surface and release it in culture medium. These phenomena are upregulated by proinflammatory cytokines.

Notes: Abstract. In this paper we analyze the efficiency of some stiff ode solvers, applied to the coupled solution of vertical turbulent diffusion and chemical kinetics in Air Quality Models. We consider four general-purpose solvers, based on bdf or Rosenbrock methods, and two special-purpose solvers, developed for odes from atmospheric chemistry, and compare their performance on three test problems using different chemical models. The general-purpose solvers have been modified to take advantage of the sparsity of the Jacobian matrices arising in the application of implicit methods. The obtained results show that general-purpose solvers, provided with suitable sparse matrix techniques, perform generally better than special-purpose ones. Our analysis extends to the diffusion-reaction equations the recent work of other research groups, comparing ode solvers on atmospheric chemical kinetics equations.