1 This study aimed to evaluate the effects of phosphodiesterase (PDE) inhibitors and currently prescribed anti-asthma drugs for their ability to inhibit inflammatory cell activation in vitro. 2 Alveolar macrophages and eosinophils were isolated from the bronchoalveolar lavage (BAL) fluid of ovalbumin (Ovalb)-sensitized guinea-pigs. Opsonized zymosan (OZ) and PAF stimulated leukotriene B4 (LTB4) release from eosinophils was measured by radioimmunoassay. Ovalb-induced superoxide generation was measured by reduction of cytochrome C. 3 Monocytes were separated from human peripheral venous blood and mast cells were dispersed from human lung fragments. Lipopolysaccharide (LPS)-induced tumour necrosis factor-a (TNF-a) release from monocytes was measured by ELISA and anti-IgE stimulated histamine release from mast cells was measured by a radioenzymatic method. 4 The fl2 agonist, salbutamol inhibited TNF-a release from monocytes and histamine release from mast cells whilst having no effect on eosinophil-derived LTB4 release or macrophage superoxide generation. 5 The PDE 3 inhibitor, milrinone produced a concentration-related inhibition of TNF-a release from monocytes which achieved statistical significance at 10-5 M but inhibited LTB4 release from eosinophils and superoxide generation from macrophages only at the highest concentration (10-3 M) examined. Milrinone had no effect on histamine release from mast cells. 6 The selective PDE 4 inhibitors, denbufylline and rolipram and the corticosteroid, beclomethasone produced a concentration-related inhibition of LTB4 release from eosinophils, TNF-ax release from monocytes and superoxide generation from alveolar macrophages whilst having no effect on histamine release from mast cells. 7 The mixed PDE 3/4 inhibitor, benzafentrine produced a concentration-related inhibition of LTB4 release from eosinophils, TNF-a release from monocytes, superoxide generation from alveolar macrophages and histamine release from mast cells. 8 In conclusion these data clearly show that both established anti-asthma medication as well as PDE inhibitors have the potential to inhibit inflammatory cell activation in vitro but that the anti-secretory actions of fl2 agonists, corticosteroids and PDE inhibitors are distinct.

The spiropiperidylrifamycin LM 427 (4-deoxo-3,4-[2-spiro-N-isobutyl-4-piperidyl]-(1H)-imidazo-(2,5-dihydro)rifamycin S) displays a broad spectrum of potent antibacterial activity in vitro. In vivo it is particularly effective in the therapy of experimental tubercular infections of mice.Three schedules of treatment were employed and the best results were obtained when intermittent administrations were used (ED51 of LM 427; 7 times lower than rifampicin).LM 427 is well distributed in tissues of mice and rats, with lung concentrations 10-20 times higher than plasma levels.In a previous papery we described the antibacterial activity of a new class of rifamycin S derivatives: the spiropiperidylrifamycins.One member of this class (4-N-isobutylspiropiperidylrifamycin S; see structure below) whose code number is LM 427 (compound 11 in the earlier paper), showed remarkable activity against Mycobacterium tuberculosis in vitro and in vivo, together with an interesting profile of tissue distribution in rats.Recent research') carried out at the Center for Disease Control in Atlanta, Georgia, USA, demon- Portions of these data were presented at the 12th International Congress of Chemotherapy (Florence, 1981, Abstracts No. 956 & 960). Materials and MethodsIn Vitro Activity The minimal inhibitory concentration (MIC) on Gram-positive and Gram-negative bacteria, both standard and clinical isolates, was determined by the serial dilution technique in Bacto Antibiotic Medium No. 3 (Difco) supplemented with 1.5 % of Agar (Difco) for aerobic strains and in Bacto FTM (Difco) for the anaerobic strains. The inoculum consisted of about 105 cells per plate or per ml. Incubation was at 37°C for 1-2 days. The MIC on M. tuberculosis was determined by the serial dilution technique in Bacto Albumin Dubos Medium (Difco) inoculated with about 101 cells/ml and incubated for 7-10 days at 37°C.Rifampicin was taken as a reference compound. The antibiotics were dissolved in dimethylform-

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After 30 years of therapeutic use, thiamphenicol glycinate acetylcysteinate (CAS 20192-91-0) is still widely employed in the treatment of upper and lower respiratory tract infections. This is due to its particular characteristic to exert at pulmonary level, either the antibacterial activity of thiamphenicol (CAS 15318-45-3) and the mucolytic activity of N-acetylcysteine (CAS 616-91-1). The aim of this study was to evaluate the present pattern of susceptibility of several clinical isolates to thiamphenicol and the interference of N-acetylcysteine on this parameter. The studies have been performed in vitro. Equimolar concentrations of N-acetylcysteine and even higher concentrations did not interfere with the antibacterial activity of thiamphenicol against Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae. The spectrum of activity of thiamphenicol was similar to that observed in the past and was superior to that of erythromycin and amoxicillin. The activity of thiamphenicol was greater than that of erythromycin against H. influenzae and streptococci and equivalent versus Branhamella catarrhalis. In comparison with amoxicillin the activity of thiamphenicol was higher against H. influenzae and B. catarrhalis and slightly lower against streptococci. The results demonstrate that thiamphenicol maintains its therapeutic value confirming the importance of thiamphenicol glycinate acetylcysteinate in the treatment of respiratory tract infections.