Antagonistic interactions between azoles and amphotericin B with yeasts depend on azole lipophilia for special test conditions in vitro.

The interactions of the azole antifungal agents fluconazole, itraconazole, ketoconazole, or miconazole with amphotericin B (AmB) in their effect on Candida albicans were investigated. These four azoles antagonized the fungistatic activity of AmB at sub-MICs if both substances acted simultaneously. This coincubation test was primarily developed to observe the azole-mediated demethylase inhibition quantitatively by bioassay. Interestingly, the occurrence of azole-AmB antagonism depended on azole lipophilia if specially selected test conditions were applied. By a consecutive incubation regimen, preincubation at high azole concentrations (1 to 50 micrograms/ml) and then subsequent incubation with AmB (1 microgram/ml), only preincubation with the three lipophilic azoles decreased the fungicidal activity of AmB but not that of FCZ. It was shown that yeasts absorb only lipophilic azoles to a remarkable extent. This fact might be responsible for the absence of antagonism of FCZ to AmB when yeasts were incubated consecutively. It can be concluded with caution that consecutive treatment of candidiasis with FCZ and AmB does not necessarily result in a clinically relevant antagonism.

Exploratory study of the decongestive effect of Rhinopront syrup in adults and in children with acute rhinitis.

The decongestive effect of Rhinopront syrup was assessed in 18 adults and 18 children with acute rhinitis, by comparison to a matching placebo syrup and to a commercial standard decongestant (Triaminic tablets or drops). The evolution of symptoms following single dose administration of each treatment was estimated both by objective measurements of nasal resistance using bilateral rhinomanometry and by subjective evaluation of nasal congestion and aspect of the mucosa. In children, the treatment was continued over the next 4 days and the global clinical efficacy of the formulations was subjectively evaluated by the parents. In adult patients, a significant decrease in nasal resistance was obtained after a single dose of Rhinopront (15 g). The effect was already important after 0.5 h and reached a minimum of approximately 50% of baseline within 1 to 2 h; the drop in nasal resistance was significantly less intense for Triaminic (p < 0.05; 0.5-1-h period) and for the placebo (p < 0.05; 0.5-2-h period). In children, the scatter of rhinomanometric measurements precluded the observation of any significant within- or between-group differences; however, a significantly lower nasal congestion score was observed for Rhinopront than placebo, between 4 and 10 h after single dose administration (1 g per year of age). The present work suggests that Rhinopront is an effective nasal decongestant in adults and children with acute congestive rhinitis and supports the adequacy of the proposed twice-daily dosing rate.

[Treatment of rheumatoid arthritis. Open parallel study with the non-steroidal antirheumatics piroxicam and diclofenac]. / Zur Behandlung de chronischen Polyarthritis. Offene Paralleluntersuchung der nichtsterioidalen Antirheumatika Piroxicam und Diclofenac.

Piroxicam and diclofenac were compared for 4 weeks in an open parallel study in 20 rheumatoid arthritis patients each. Both preparations showed good efficacy and were well tolerated, piroxicam appearing to be slightly superior in both respects. Piroxicam exercised a significant action on the inflammation-specific parameters (reduction of BSR by 6.15 mm maximum and of the alpha 2-globulin fraction by 0.75%), whereas diclofenac did not. Another advantage of piroxicam is its low effective dosage level achieved by a single daily dose.

Influence of the trypsin activity by the side chain of arginine homologues.

The N-alpha-tosyl-p-nitroanilides of homoarginine and of the two shorter arginine homologues were synthesized. These compounds behave as specific, chromogenic substrates for trypsin.

Effects of arginine homologous and other guanidino compounds on the ATP level and glucose oxidation in isolated fat cells.

The arginine homologues 2-amino-3-guanidinopropionic acid, 2-amino-4-guanidino-butyric acid and 2-amino-6-guanidinocaproic acid (= homoarginine) were synthesized and transformed into their methyl esters. The latter, together with arginine methyl esters. The latter, together with arginine methyl ester, arginine diethylamide and some guanidino compounds without the arginyl structure (agmatine, isopentyl-guanidine and n-butylbiguanide) were examined with regard to their behaviour on isolated fat cells, concerning the adrenalin-induced depression of the ATP level and the stimulation of glucose oxidation. The homoarginyl and arginyl derivatives counteracted the effect of adrenalin by re-elevating the ATP level, and thus they exerted an insulin-like activity. The esters were slightly active, whereas the arginine diethylamide and agmatine had a marked effect. The shorter homologues of arginine were totally inactive. However isopentyl-guanidine and butylbiguanide followed the effect of adrenalin: they additionally lowered the ATP level and therefore they acted in opposition to insulin. For comparative reasons the same compounds were tested with regard to their effects on glucose oxidation. The results were consistent with those quoted above: the homoarginyl and arginyl derivatives (agmatine included) forced the glucose oxidation similarly to insulin, the shorter homologues were inactive, isopentylguanidine and butylbiguanide decreased it.