PubMed Health⌕ Search

Biomedical subjects

G W Canonica

Publications and source records attributed to G W Canonica.

At least 145 records · Page 8Linked to original sources
PubMed1997

Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti-allergic activity.

BACKGROUND: Azelastine is a selective H1-receptor antagonist, which has previously been demonstrated to be effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical and inflammatory events following nasal allergen challenge. Particularly, we focused our attention on ICAM-1 expression on epithelial cells, since it is the natural ligand of LFA-1, 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, eosinophils. 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, azelastine 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-1 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-1 expression on epithelial conjunctival cells, confirming the results obtained at nasal level.

Adolescent↗
PubMed1997

[ICAM-1 and allergic inflammation].

Recent progress in the understanding of the physiopathology of asthma makes possible the revision of the objectives of treatment, to pass from short-term symptomatic control to a prolonged control of the illness. L'ICAM-1 is an excellent potential target for preventative treatment of asthma of viral origin. When there are agents available of both inhibiting histamine and positively regulating ICAM-1 there is no longer reason to use simple antihistamines.

Allergens↗
PubMed1997

In situ hybridization analysis of ICAM-1 (CD54) mRNA on conjunctival epithelium during allergic inflammation.

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: 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-1.

3T3 Cells↗
PubMed1997

Long-term follow-up of nasal immunotherapy to Parietaria: clinical and local immunological effects.

BACKGROUND: Local nasal immunotherapy (LNIT) with extracts in powder has been demonstrated 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.

Administration, Intranasal↗
PubMed1997

Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its antiallergic activity.

BACKGROUND: Cetirizine is an antihistamine, largely used in the treatment of allergic rhinoconjunctivitis, which also exerts anti-allergic activity. OBJECTIVE: To evaluate cetirizine as treatment for children with rhinitis due to pollen allergy, and to evaluate its anti-allergic activity in such a clinical condition. METHODS: The study was designed as parallel groups, double-blind, placebo-controlled, randomized. Twenty allergic children were enroled and subdivided in two groups, receiving a 4 week treatment during the pollen season. The following parameters were monitored: clinical symptoms evaluated by the allergist before and after treatment and by the patients through a daily diary card, inflammatory cells count, expression of ICAM-1 on nasal epithelial cells, inflammatory mediator levels in nasal lavage and peripheral blood before and after treatment, and pollen counts. RESULTS: This study shows that cetirizine treatment is able to reduce: clinical symptoms (P < 0.01), inflammatory cell infiltrate (P < 0.03), ICAM-1 expression on epithelial cells (P < 0.05), and soluble ICAM-1 (P < 0.05) and ECP (P < 0.05) in nasal lavage. CONCLUSION: Cetirizine is able to clinically improve nasal symptoms due to pollen allergy and to reduce allergic inflammation, which is related to allergen exposure.

Adolescent↗
PubMed1997

Loratadine treatment of rhinitis due to pollen allergy reduces epithelial ICAM-1 expression.

BACKGROUND: Loratadine and cetirizine are new generation antihistamines, which are clinically effective in the treatment of allergic rhinitis. OBJECTIVE: The aim of the study was to evaluate antiallergic activity of loratadine compared with cetirizine, over a 2 week period under natural allergen exposure, in a double-blind parallel groups, randomized, controlled trial. METHODS: Twenty patients, sensitized to grass and/or Parietaria pollen, were subdivided into two groups, one receiving loratadine the other cetirizine respectively. Both were dosed at 10 mg/day. Evaluated parameters were: clinical symptoms, nasal inflammatory cell (such as neutrophil, eosinophil and metachromatic cells) counts, ICAM-1 expression on nasal epithelial cells, and nasal mediators (e.g. histamine, ECP, EPO and MPO). RESULTS: Loratadine and cetirizine significantly improved symptoms (P < 0.002), significantly reduced eosinophil (P < 0.016) and metachromatic cell (P < 0.01) infiltration, levels of ECP (P < 0.002), EPO (P < 0.006) and histamine (P < 0.01) and ICAM-1 expression on nasal epithelial cells (P < 0.02). No difference was demonstrated between the two drugs. CONCLUSION: The antiallergic activity of loratadine and cetirizine is documented by their actions on the inflammatory and clinical parameters, especially ICAM-1 modulation.

Adolescent↗
PubMed1996

Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: an antiallergic activity.

BACKGROUND: It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray). OBJECTIVE: The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction. METHODS: The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental). RESULTS: Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Koch's split-plot statistical analysis. CONCLUSION: Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.

Administration, Topical↗
PubMed1996

Antiallergic activity of topical lodoxamide on in vivo and in vitro models.

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.

Adolescent↗
PubMed1996

Cetirizine reduces ICAM-I on epithelial cells during nasal minimal persistent inflammation in asymptomatic children with mite-allergic asthma.

It has been recently demonstrated that individuals who suffer from mite allergy present mucosal inflammation even when asymptomatic. This situation is characterized by infiltration of inflammatory cells (eosinophils and neutrophils) and by ICAM-I expression on epithelial cells. It has been called 'minimal persistent inflammation' (MPI) for its relationship with natural exposure to allergen, which is continuous in the case of mite allergy. ICAM-I (or CD54) expression on epithelial cells is relevant for several reasons: (a) healthy individuals and patients with pollen allergy out of the pollen season do not express this molecule; (b) ICAM-I is the natural ligand of LFA-1 (an integrin expressed on granulocytes), and (c) ICAM-I is also receptor for rhinoviruses. It is well known that viral infections precede asthmatic attacks; consequently, this correlation is more frequent in cases of mite allergy. Cetirizine is an antiallergic drug that can reduce both inflammatory infiltrate and ICAM-I expression induced by allergen-specific conjunctival challenge. The aim of this study was to evaluate the effect of cetirizine on MPI in 20 children (5-14 years old) with mite allergy. All the children suffered from mild asthma and 9 also had rhinitis (they had been asymptomatic, and thus not treated, for 2 months). The study was double-blind, placebo controlled and randomized and children took Cetirizine or placebo for 15 days. At the beginning and end of the study, nasal scrapings were performed to evaluate inflammatory cell infiltration (eosinophils and neutrophils) and ICAM-I expression on epithelial cells. Cetirizine-treated children showed a significant reduction (or even total absence) of ICAM-I expression on epithelial cells (p less than 0.002) and a reduction trend in inflammatory cell counts compared with placebo. In conclusion, Cetirizine might be envisaged as fruitful for the prolonged treatment of allergic children, including during clinical latency, to prevent possible relapse or rhinovirus infections.

Adolescent↗
PubMed1996

Intraepithelial gamma/delta-positive T lymphocytes and intestinal villous atrophy.

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.

Animals↗
PubMed1996

Adhesion molecules in allergy.

Cell adhesion molecules have been recognized to play a major role in a variety of physiological and pathophysiological phenomena, such as embryogenesis, maintenance of tissue architecture and tissue damage repair, recruitment of leukocytes into tissues, immunological reactions requiring cell-to-cell contact. Their role in inflammatory reactions is crucial, in particular their involvement in allergic inflammation has been extensively studied. It has become apparent that the expression patterns and cell localization of certain adhesion molecules are related to the dynamic of allergic inflammation, and specifically to selective migration of eosinophils and interactions with epithelial cells of the target organs. In some instances, cell adhesion molecules by themselves may be regarded as reliable markers for clinical purposes. In addition, the pharmacological modulation of expression and release of adhesion molecules may provide new insight about the mechanisms of action and effectiveness of antiallergic drugs.

Cell Adhesion Molecules↗
PubMed1996

Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro.

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 levocabastine 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 suffering 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, 30 min and 6 h after ASCC. In parallel, we evaluated the in vitro effect of levocabastine at concentrations ranging from 2 x 10(-9) M to 2 x 10(-5) M on ICAM-1 expression and shedding by a continuously cultured differentiated epithelial cell line (WK). RESULTS: Levocabastine reduced symptom scores during EPR (15 min and 30 min, P < 0.002), inflammatory cell infiltration during EPR (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 x 10(-5) M concentration was able to down-regulate basal ICAM-1 expression, although it exerted no effect on ICAM-1 release by epithelium. CONCLUSION: Levocabastine exerts anti-allergic 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.

Acute-Phase Reaction↗
PubMed1996

Increase of asthma and allergic rhinitis prevalence in young Italian men.

Our previous studies have reported that the prevalence of asthma was 2.89% and of allergic rhinitis 1.54% in Ligurian conscripts for the army during 1983. Since several authors reported an increasing prevalence of these diseases in different geographic areas, the aim of the present study was to evaluate the trend of prevalence rates in a same homogeneous group of Ligurian conscripts. The prevalence of asthma and allergic rhinitis was assessed in a group of 4310 young Ligurian men (18 years old) who had undergone medical examination for call-up to the navy during 1993, 1994 and 1995. Subjects were investigated by history, clinic visit, spirometry, metacholine bronchial challenge and skin prick test. The prevalence of asthma is 4.39% and of allergic rhinitis 2.2%. Comparing these results with previous data, a significant increase appears in this area 12 years later (respectively, p < 0.001 and p < 0.006). In addition, the association with asthma in allergic rhinitics increases from 41 to 77%, as well as an increasing trend appears for perennial allergens (i.e. mites and cat) and the polysensitizations increase from 48 to 67%. Possible explanations for these phenomena might be due to environmental factors (i.e. pollutants, viral infections, changes in domestic microenvironment).

Adolescent↗
PubMed1996

[Anti-leukotriene agents: rationale for and prospects of use].

Leukotrienes (LT) are synthesized from arachidonic acid by several enzymes such as phospholipase A2, 5-lipoxygenase, LTC4 synthase, as a consequence of a wide range of inflammatory stimuli. Leukotrienes seem to play a pivotal role in the maintenance of the inflammatory processes as they exert numerous biological activities, i.e. chemotactic action on polymorphonuclear cells, bronchospastic action, vasodilator and secretagogue effects. Thus, the inhibition of LT activity may result in antiinflammatory action. Several compounds capable of blocking either LT synthesis or LT receptors have recently been developed and clinically tested in different experimental models. In particular, encouraging results have been obtained in the asthma model, but interesting clinical observations have also been performed in psoriasis, ulcerative colitis and rheumatoid arthritis. Although further studies and optimization of this kind of treatment are required, a possible clinical role of LT antagonists as antiinflammatory therapy for selected diseases may be envisaged.

Humans↗
PubMed1995

Infiltrating gamma/delta T-cell receptor-positive lymphocytes in Hashimoto's thyroiditis, Graves' disease and papillary thyroid cancer.

In the present study we have evaluated the expression of different molecular forms of the antigen receptor (TcR) on lymphocytes derived from thyroid tissue of patients with Graves' disease, Hashimoto thyroiditis and papillary cancer both in situ by APAAP technique and on isolated lymphocytes by indirect immunofluorescence. A panel of monoclonal antibodies (mAbs) recognizing alpha/beta and gamma/delta TcR-positive subsets was used. The results showed that the large majority of T-cells in thyroid infiltrates were alpha/beta TcR+, gamma/delta TcR+ ones being very rare or nearly absent, whatever the disease (autoimmune or neoplastic). No difference between gamma/delta TcR+ T-cell subsets (V delta 1+ or V delta 2+) was observed. Thus, neither in autoimmune thyroid diseases nor in papillary cancer gamma/delta TcR+ cells are likely to be a major effector-T cell population.

Adult↗