The effect of an emulsion of perfluorochemicals (PFC) (7 parts perfluorodecalin and 3 parts perfluorotripropylamine, 4.4 g PFC/kg body weight) on organ function was determined. Whereas maximal storage of PFC was reached in the spleen as early as 12 h after PFC administration, the liver attained a maximal PFC content only after 2 days. The increase in weight also differed: a maximum occurred in the spleen on the 4th day, in the liver on the 8th day. Indocyanine green (ICG) clearance showed a small decrease, statistically significant after 12 and 24 h. Colloidal carbon clearance, used as a measure of the function of the reticuloendothelial system (RES) decreased instantly after PFC to less than half the control value; after full recovery a second decrease was seen which lasted till the 4th day after PFC. Pretreatment with C 48/80 or with increasing doses of E. coli endotoxin could largely obviate the depressive effect of PFC-loading on carbon clearance. Serum transaminases increased to about twice the control levels but were normal by the 2nd day, and thereafter. Alkaline phosphatase showed a 2.5 fold increase but returned to control level after the 2nd day. It is concluded that while a severe disturbance of liver function did not occur, the reduction in the capacity of the RES can become a serious factor in the defence against a simultaneously appearing infection if not compensated by activating the RES.

In search of an improved treatment of pruritic dermatoses, we have studied azelastine, a novel H1-receptor antagonist, during a 2-week treatment period, using a double-blind, placebo-controlled design. The potent H1-antagonist cetirizine was used for comparison. Symptoms were recorded daily by the patients on a diary card, using a 4-point scale. The same parameters and adverse events were evaluated at weekly intervals, and global improvement was evaluated at the end of treatment. In all 230 evaluable patients with moderate to severe itching, azelastine caused an overall significant improvement in comparison to placebo (P = 0.02), with significance also for pruritus (P = 0.01 after 1 week and P = 0.02 after 2 weeks). Both drugs reduced itching more effectively in urticaria than in atopic eczema. Azelastine was superior to cetirizine in reducing pruritus, whereas cetirizine caused a more marked reduction of whealing. Both drugs rarely caused fatigue and dry mouth, but taste perversion occurred only in azelastine-treated patients (9.7%) and headaches only with cetirizine (10.4%). Therefore, the two H1-blockers exert differential effects on pruritus verses whealing and a distinctive adverse events pattern. The data also underline the low efficacy of antihistamines in atopic eczema, compared to urticaria.

1 The aim of this study was to provide evidence that anpirtoline, which is an agonist at 5-HTIB and 5-HT,D receptors and also displays submicromolar affinity for 5-HTlA recognition sites, in addition, acts as an antagonist at 5-HT3 receptors. 2 In radioligand binding studies on rat brain cortical membranes, anpirtoline inhibited specific binding of [3H]-(S)-zacopride to 5-HT3 receptor recognition sites (pKi: 7.53).3 In NIE-115 neuroblastoma cells in which ['4C]-guanidinium was used as a tool to measure cation influx through the 5-HT3 receptor channel, the 5-HT-induced influx was concentration-dependently inhibited by anpirtoline. In this respect, anpirtoline mimicked other 5-HT3 receptor antagonists; the rank order of potency was ondansetron>anpirtoline>metoclopramide. 4 The concentration-response curve for 5-HT as a stimulator of ['4C]-guanidinium influx was shifted to the right by anpirtoline (apparent pA2: 7.78). 5 In urethane-anaesthetized rats, anpirtoline inhibited (at lower potency than zacopride and tropisetron) the 5-HT-or phenylbiguanide-induced bradycardia (Bezold-Jarisch reflex), but did not induce this reflex by itself. 6 Intravenous infusion of cisplatin in the domestic pig caused a consistent emetic response which was antagonized by anpirtoline. 7 It is concluded that anpirtoline, which was previously characterized as a 5-HT, receptor agonist also proved to be a 5-HT3 receptor antagonist in several experimental models and, hence, exhibits a unique pattern of properties at different 5-HT receptors.

Background and Objectives: To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer^®, i.e. a multidose dry powder inhaler, or by the Pulmicort^® Turbuhaler^® in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment. Methods: A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV₁), need for anti-inflammatory therapy, inhalation of β₂-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 µg salbutamol. Primary variable was FEV₁, secondary were other pulmonary function test variables, PC₂₀FEV₁ for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables. Results: The comparison of the FEV₁ at study endpoint indicated that the Novolizer^® was at least as efficacious as the Turbuhaler^® (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler^®) discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups. Conclusions: The budesonide Novolizer^® is therapeutically equivalent to the Pulmicort^® Turbuhaler^® for the long-term treatment of patients with mild to moderate persistent asthma.

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