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Notizen: Background Adverse reactions to non-steroidal anti-inflammatory drugs (NSAID)s are frequent, and the need to identify a safe alternative drug is a common problem in clinical practice.Objective To assess the tolerability of rofecoxib, a drug that specifically inhibits COX-2, in a group of NSAID-sensitive patients.Methods One-hundred and four subjects (29 males and 75 females, mean age 35.6 ± 14.1) were enrolled. All subjects had experienced one or more episode characterized by cutaneous symptoms (erythema, and/or urticaria angioedema) following the assumption of NSAIDs; 92 subjects experienced reactions to only one NSAID (single intolerance: SI) and 12 subjects had reactions to multiple NSAIDs (multiple intolerance: MI). Rofecoxib was challenged at the following dosages: ¼ of 25 mg (6.25 mg), ¼ of 25 mg, and ½ of 25 mg (12.5 mg), at intervals of 1 h if no symptoms had developed with the previous administration, in order to reach a cumulative dose of 25 mg. All subjects underwent two double-blind, placebo-controlled challenges in two consecutive days.Results No reactions against placebo were observed. Similarly, no reactions were observed in all subjects both after the first and after the second challenge to rofecoxib.Conclusions The present study demonstrated that rofecoxib does not have cross-reactivity to NSAIDs. Rofecoxib is a safe alternative in subjects with previous adverse cutaneous reaction to NSAIDs.

Notizen: Background Initial attempts to evaluate the association between allergic rhinitis and nonspecific bronchial responsiveness has produced conflicting results. In fact, some studies showed a strong correlation and other failed to find an association. However, little is known about the effect of natural specific allergen exposure on the bronchial reactivity of mono-sensitive patients with rhinitis in the southern Mediterranean area, in relation to skin reactivity to allergens, total serum IgE levels and blood eosinophiis.Objectives The significance of the association between allergic rhinitis, and abnormal airway responsiveness with regard to the pathogenesis of asthma is unclear. For this reason, we have studied non-specific bronchiai hyperreactivity. in patients with seasonal allergic rhinitis, with reference to the responsible allergen. The aim of the study was to correlate the responsiveness to bronchoprovocation with methacholine in subjects a with allergic rhinitis during and out of the pollen season with total serum IgE and blood eosinophils.Methods Fourty-nine non-smoking patients with clinical diagnosis of allergic rhinitis and mono-sensitive skinprick tests to pollen allergens were enrolled in the study. Twenty patients suffered from seasonal rhinitis to Parietaria pollen. 15 patients to Gramineae pollen and 14 patients to Olea pollen. In all patients lung function measurements (assessed as response to methacholine). tolal serum IgE and blood eosinophii counts were measured during and out of the pollen season.Results During pollen season. 16 out of 49 rhinitis patients demonstrated values of bronchial responsiveness measured as response to inhaled metbacholine in the asthmatic range whereas out of the pollen season only eight patients were in the asthmatic range. By analysing the results with reference to the responsible allergen, during the pollen season 5 out of 16 patients were Parietaria -sensitive and out of the pollen season seven out of eight patients. Finally, in Parietaria -sensitive rhinitis bronchial responsiveness signifi-cantly correlated, during and out of the pollen season, with total serum IgE and with blood eosinophil counts.Conclusions Our results are consistent with the hypothesis that Parietaria is more important than Olea and Gramineae as a risk for developing non- specific bronchial hyperresponsiveness. On the whole, present observations provide further evidence that there is an interrelationship of allergen kind, total serum IgE. eosinophil and bronchial hyperressponsiveness suggesting that they may play a role in the development of bronchial asthma in rhinitis patients.

Notizen: Background In atopic asthma there is strong evidence of eosinophils playing an active role in pathogencsis. Some investigations demonstrated that eosinophil cationic protein (ECP) serum levels increased in atopic patients with asthma during pollen season.Objective The aim of the study was to evaluate the effects of short-term (1 week) β2-agonist treatment on lung function and eosinophil activity in asthmatic patients. Methods We used an open, randomized, cross-over design to compare the effects of salbutamol (200μg q.i.d.) and salmeterol (50μg b.i.d.) on peak expiratory flow rate (PEFR), blood eosinophil count and serum levels of ECP as a measure of eosinophil activity in 20 mild atopic asthmatics.Results Morning and evening PEFR values were both significantly higher during salmeterol treatment than during the salbutamol period. Conversely, both morning and evening daily asthma symptom scores were significantly lower during salmeterol treatment compared with those recorded during the salbutamol period. The mean basal eosinophil blood count on salmeterol treatment (601 ± 189mm3) was not higher than the mean count on salbutamol treatment (612 ± 204 mm3). After both treatments the mean eosinophil blood counts were unchanged (619 ± 189mm3 and 576 ±212 mm3, respectively). No significant differences in blood eosinophil counts were observed between or within treatments at any time. No significant difference was observed in baseline mean ECP serum concentration (43.8 ± 263 μg L on salmeterol treatment and 41.7 ± 29.8 μg L on salbutamol treatment, respectively). After salmeterol treatment the mean ECP serum concentration had fallen significantly to 20.9± 18.6μg/L (P 〈 0.01), whereas after salbutamol treatment it was unchanged (42.0 ± 25.1 μg /L). Salmeterol treatment produced a decrease in ECP serum levels without any changes in blood eosinophil count.Conclusion This study demonstrates that salmeterol affords a significant improvement in asthma control during the pollen season, measured by both subjective and objective parameters, compared with salbutamol. This greater efficacy may be related to inhibition of eosinophil degranulation during the pollen season.

Notizen: Background Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms.Objective We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 μg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season.Methods One hundred patients aged 12–50 years (mean±SD 31.8±9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 μg once daily (n=20) or with FPANS 200 μg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 μg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage.Results All treatments showed significant differences (P〈0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P〈0.001) and nasal congestion daily (P〈0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P〈0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P〈0.001) and for nasal congestion on daily (P〈0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P〈0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P〈0.001) compared with PLA. Besides, there were significant differences (P〈0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK.Conclusion The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.

Notizen: Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H1-receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives.Patients and methods A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms.Results MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P 〈 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P 〈 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P 〈 0.001, and 20 days, P 〈 0.001, respectively). Finally, a low incidence of adverse events was observed in this study.Conclusion The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

Notizen: Background Atopic dermatitis (AD) is a chronic allergic inflammatory disease, which manifests itself with eczematous skin lesions.Objective We compared the clinical efficacy of tacrolimus ointment (0.1%) given twice a day and oral cyclosporine (3 mg/kg) given once daily. Rescue medication for itching included cetirizine 10–20 mg (equal to one or two tables).Methods Thirty patients, aged 13–45 years (mean±SD 27.1±10.9), with a history of moderate-to-severe AD were randomized to treatments, 15 patients for each treatments. Assessment of efficacy was based on SCORAD, on scores of daily itching, erythema, interference with sleep, due to the skin condition and days without use of cetirizine tablets. SCORAD, measured on a scale (0–103), was evaluated before treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment. Similarly, the means of daily symptoms, on a scale (0–3), were evaluated before the treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment; finally, on day without use of cetirizine tablets. The safety of the study treatments was assessed through haematologic, biochemical and urinary testing and on systolic and diastolic blood pressures and heart rate measurements.Results SCORAD decreased in the two treatment groups 14 days after the beginning of the period study. However, the patients in tacrolimus ointment group reported significantly lower SCORAD than those treated with oral cyclosporine. Overall SCORAD, as assessed by the area under the curve (AUC) day0–42 (score/day), was significantly lower in the tacrolimus ointment group when compared with oral cyclosporine (P〈0.001). Similarly, AUC day0–42 (score/day) for itching, erythema and number of nights without interference with the sleep due to skin condition were significantly lower in the group of patients treated with tacrolimus compared with those treated with cyclosporine (P=0.003, 0.005 and 0.01, respectively). As regards the use of rescue medication, expressed by median of number of days without use of anti-H1, it was significantly lower in the group treated with tacrolimus (82.5) than in the cyclosporine group (76.5) (P=0.03). There were no appreciable changes in haematological and biochemical indices, in both treatments groups.Conclusion The results of this comparative study demonstrate that tacrolimus ointment twice daily and cyclosporine administered orally once daily are effective on SCORAD, daily symptoms and anti-H1 rescue. When we compared tacrolimus and cyclosporine there was a faster onset of action in the group treated with tacrolimus. The two drugs presented the same safety. However, these data support the preferential use of topical tacrolimus 0.1% in AD, because cyclosporine has potential side-effects.

Notizen: Branca, C, De Lorenzo, G. and Cervone, F. 1988. Competitive inhibition of the auxin-induced elongation by α-D-oligogalacturonides in pea stem segments. - Physiol. Plant. 72: 499–504.α-D-galacturonide oligomers (OG) were prepared by partial hydrolysis of sodium polypectate with an homogeneous Aspergillus niger endopolygalacturonase (EC 3.2.1.15). OG, obtained after digestion for 10, 20, 30, 60, 120 min and 24 h, were assayed for their ability to interfere with the IAA-induced elongation of pea (Pisum sativum L. cv. Alaska) stems. Maximum inhibiting activity was exhibited by oligomers with an approximate degree of polymerization higher than 8. Inhibition by longer OG was much lower, and the products of the 24 h digestion and the unhydrolysed polypectate were ineffective. The addition of OG to pea stems caused a parallel shift to the right of the IAA dose-effect curve. The shift depended on the amount of OG used, showing that oligogalacturonides behave as competitive antagonists of IAA. The presence of OG caused the disappearance of the second maximum of the elongation rate and reduced the first maximum. OG were also tested for their ability to inhibit IAA-induced ethylene evolution of pea stem segments. Maximal inhibition was obtained with OG of the same size as those that interfered with IAA-induced elongation. Inhibition of the auxin action seemed to be specific as OG did not interfere with the activity of gibberellic acid (GA3) or kinetin. It was concluded that oligogalacturonides strongly interfere with the activity of IAA, although they are by themselves incapable to influence the elongation of pea stem segments directly.

Notizen: Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, double-blind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 μg, once daily (n=97), or topical levocabastine, 200 μg, given twice daily (n=96), or matched placebo (n=95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P〈0.02 and P〈0.01) and rhinorrhea (P〈0.01) than levocabastine. In addition, fewer patients treated with FPANS used rescue medication (P〈0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 μg, once daily, provides a better clinical effect than levocabastine 200 μg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.