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Background Azelastine is a selective Hi-receptor antagonist. which has previously been demonstrated to he effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical anti inflammatory events following nasal allergen challenge. Particularly, we focused our attention on [CAM-I expression on epithelial cells, since it is the natural ligand of LEA-I. an adhesion molecule expressed by leucocytes, including eosinophils. Objective Since azelastine ocular drops are now available, the aim of the present study was the evaluation of the anti-allergic activity in the model of allergen specific conjunctival challenge (ASCC). Methods Twenty outpatients with allergic rhinoconjunctivitis due to Parietaria Judaica (Wall Parietary) were included outside the pollen season. The study was designed as randomized. placebo-controlled, double-blind and parallel group. developed in two parts. The former investigated the onset of effect of a single dose of azelastine eye drops administered 20 min after clinical response due to ASCC. The latter evaluated the clinical and inflammatory parameters following ASCC after 7-days treatment with azelastine. Clinical parameters (hyperaemia. itching. lacrimation and eyelid swelling) were evaluated at baseline. 5. 10, 20 and 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. Cytological assessment (number of neutrophils, cosinophils, monocytes and lymphocytes) and ICAM-1 expression on conjunctival epithelial cells were evaluated at baseline, 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR after ASCC. Results When administered 30 min after ASCC, azelastine produced a clinical effect ranging between 10 and 20 min after eye drops administration (P <0.01). After 7 days of treatment, 30 min after ASCC, azelastinc induced a reduction of symptom scores during EPR and LPR (P <0.01), a reduction of inflammatory cell infiltration during both EPR (P < 0.01) and LPR (P < 0.01). and a reduction of ICAM-I expression during EPR and LPR (both P < 0.01), Placebo did not modify any of the studied parameters. Conclusion. Azelastine eye drops exert anti-allergic activity, inducing a rapid improvement of clinical events when administered after ASCC, and reducing both symptoms and cellular infiltration when administered before ASCC. Finally, azelastine down-regulates ICAM-I expression on epithelial conjunctival cells, confirming the results obtained at nasal level. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Invasive mosquito species (IMS) of the genus Aedes are a cause of increasing concern in Europe owing to their ability to vector important human viral diseases. Entomological surveillance to early detect alien mosquito and flavivirus circulation in Liguria, northwest Italy, has been carried out since 2011., Results: The invasive species Aedes koreicus was first detected in Genoa in September 2015, when a male specimen was caught near the international airport; species identity was confirmed by genetic analysis. Over the next three years, 86 more adult specimens were trapped at sites throughout the city, accounting for 0.50% of all mosquitoes and 1.04% of Aedes sp. mosquitoes trapped in Genova in the four-year period 2015-2018. So far, no other monitored sites in Liguria have revealed the presence of this species. Ovitraps at two sites became positive for the species in July-August 2017. All female Ae. koreicus pools analysed were negative in biomolecular assays for Flavivirus., Conclusions: Our findings of Ae. koreicus in Genoa constitute, to the best of our knowledge, the first report of the species in northwest Italy and in a Mediterranean port city. The species appears to be established; trapping and climatic data support survival of Ae. koreicus in the area through three consecutive winters. Monitoring of adult mosquitoes detected the species two years before its discovery with ovitraps; trapping for adult specimens appears to be a more effective tool for the early detection of IMS. The airport (located near the commercial port area) and the flower market are the most probable sites of introduction; however, the exact time and place of arrival of this IMS in Liguria remain unknown. Based on morphological and genetic data, a common origin for most of the Ae. koreicus populations established in Europe is suspected. So far, no control measures have been adopted in Genoa and the species will probably colonize an even wider area in the next few years.

Background: We have previously shown aberrant expression of the 'leukocyte' integrin LFA-1 on epithelial cells in chronic autoimmune thyroiditis. In the present study we investigated whether conjunctival epithelial cells, which bear the adhesion molecule ICAM-1 on their surface during allergic inflammation, may also aberrantly express its natural ligand, the 'leukocyte' integrin LFA-1., Methods: We studied 13 patients with rhinoconjunctivitis allergic to mites, chronically exposed to the allergen, 11 patients allergic to pollen tested out of the pollen season and 8 normal volunteers. Single and double immunocytochemical staining of conjunctival smears was employed., Results: LFA-1 staining on epithelial cells was demonstrated in 12/13 patients allergic to mites and not in normal controls or in patients allergic to pollen tested out of the pollen season. The epithelial localization of LFA-1 was confirmed by double staining with anti-LFA-1 and anti-cytokeratin antibodies (both immunocytochemical and immunofluorescence)., Conclusions: Coexpression of LFA-1 and ICAM-1 during persistent allergen stimulation may be relevant for interaction between epithelial cells and activated effector cells, such as eosinophils, which bear on their surface both ICAM-1 and its beta2 integrin ligands., (Copyright 2001 S. Karger AG, Basel)

The molecules of the B7 family play a major role in T-lymphocyte costimulation through interaction with their counterreceptors CD28 and CTLA4. In the present study, we analyzed the possible expression of B7 molecules on surgically removed thyroid tissue of patients with autoimmune [Hashimoto's thyroiditis (HT) or Graves' disease (GD)] or nonautoimmune [nontoxic goiter (NTG) or papillary cancer (PC)] thyroid diseases. We found clear positivity of thyroid follicular cells for B7.1 in HT but not in GD, nor in nonautoimmune specimens (NTG, PC) using in situ analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Double immunostaining experiments in combination with an anti-human thyroglobulin antibody confirmed follicular B7.1 localization. On the contrary, no follicular B7.2 expression was observed in any specimen analyzed. These findings were confirmed by immunofluorescence flow cytometry on isolated follicular cells. The cytokines IL1beta and LPS were able to induce de novo B7.1 expression on cultured thyroid follicular cells. Intrathyroid T cells proved responsive to stimulation via the B7 ligand CD28, even in the absence of IL2. Moreover preliminary evidence was obtained for an inhibitory effect of anti-B7.1 mAb on T-cell proliferation in coculture with isolated thyroid follicular cells. It is conceivable that in HT, expression of B7.1 on follicular cells, together with MHC class II antigens and ICAM1, could provide a local costimulatory signal for T-lymphocyte differentiation toward the type 1 cytokine secretion pattern and maintenance of the autoimmune process.

Background: Azelastine is a topical antihistamine, clinically demonstrated to be effective in allergic rhinitis., Objective: We evaluated the clinical efficacy and the antiallergic activity of azelastine nasal spray, administered 0.56 mg per day, 0.28 mg per day, or on demand over a 3-month period during natural allergen exposure, in a double-blind, placebo-controlled fashion., Methods: Thirty patients, sensitized to grass or Parietaria pollen, were allocated to three treatment groups: those receiving the standard dosage (0.14 mg/nostril two times a day), half the dosage (0.07 mg/nostril two times a day), or placebo daily for 3 months. All patients were allowed to take additional doses of azelastine when needed. Evaluation parameters were as follows: clinical symptoms recorded on a diary card, number of additional, on-demand azelastine puffs, nasal inflammatory cell count, intercellular adhesion molecule-1 expression on nasal epithelial cells, and pollen count., Results: This study showed the following: (1) the half dose (0.28 mg/day) and the standard dose (0.56 mg/day) were equally effective in reducing clinical symptoms (p = NS), although the standard dosage required fewer additional puffs during times of peak pollen counts (p < 0.05); (2) both dosages were able to reduce the allergic inflammation (p < 0.05 vs placebo); and (3) on-demand use achieved acceptable clinical control but did not significantly reduce allergic inflammation., Conclusion: Continuous treatment was more effective than on-demand use as assessed by both clinical evaluation and antiinflammatory action.

We have evaluated the expression of different molecular forms of T cell antigen receptor (TcR) in duodenal biopsies of pediatric patients with different forms of villous atrophy: celiac disease, autoimmune enteropathy, intractable diarrhea of unknown origin, and severe cow milk intolerance. A panel of monoclonal antibodies recognizing alpha/beta and gamma/delta TcR (and gamma/delta TcR subsets) was used for immunostaining. The results showed an increase of T cells with gamma/delta-type TcR in celiac patients and also in patients with other forms of villous atrophy with respect to normal controls. Amongst the gamma/delta TcR-positive cells, the subset expressing the molecular product of V delta 1 region was the most represented. The gamma/delta TcR-positive T cells were mainly located within the epithelium: few of them were observed in the lamina propria. On the basis of these results, we hypothesize that the increased homing of gamma/delta TcR-positive T lymphocytes in gut epithelium observed in celiac disease is, at least in part, related to villous atrophy per se.