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Notes: The crystal structure of bovine seminal ribonuclease, a homodimeric enzyme closely related to pancreatic ribonuclease, has been refined at a nominal resolution of 1.9 Å employing data collected on an electronic area detector. The final model consists of two chains containing 1990 non-H atoms, seven sulfate anions and 113 water molecules per asymmetric unit. The unit-cell parameters are a = 36.5 (1), b = 66.7 (1) and c = 107.5 (2) Å, space group P22121. The R factor is 0.177 for 16 492 reflections in the resolution range 6.0–1.9 Å and the deviations from ideal values of bond lengths and bond angles are 0.020 Å and 3.7°, respectively. The molecule is formed by two pancreatic like chains, which have their N-terminal segments interchanged so that each active site is formed by residues from both subunits. The two chains are related by a non-crystallographic twofold symmetry and are covalently linked by two consecutive disulfide bridges, which form an unusual sixteen-membered ring across the dimer interface. The deviations from the molecular symmetry, the hydration shell and the sulfate-binding sites are also discussed in relation to the known structure of the pancreatic enzyme.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.