Aim: Superfluous reactive nitrogen and oxygen species generation is implicated in the damage of tissues at sites of inflammation where activated neutrophils and macrophages are involved. This study was conducted to investigate whether the beneficial effects of carvedilol involve modulation of respiratory burst, degranulation-myeloperoxidase release and inducible nitric oxide synthase (iNOS) expression. Methods: Spectrophotometry and chemiluminescence were used to evaluate the effect of carvedilol on opsonized zymosan (0.5 mg/ml)- or N-formyl-methionyl-leucyl-phenyl-alanine (fMLP, 0.1 µmol/l)-stimulated superoxide generation and myeloperoxidase release in human neutrophils. Western blot analysis was used for iNOS expression and Griess reagent for nitric oxide production in RAW 264.7 macrophages (lipopolysaccharide (0.1 µg/ml) stimulated). Results: Carvedilol (10 and 100 µmol/l) significantly decreased opsonized zymosan- and fMPL-stimulated superoxide generation and myeloperoxidase release. Carvedilol (100 µmol/l) enhanced the effect of wortmannin (50 nmol/l), a specific inhibitor of 1-phosphatidylinositol 3-kinase and decreased iNOS expression and nitric oxide production. Conclusion: Carvedilol appears to have a non-specific effect on membranes and to interfere with the phospholipase D signaling pathway, with subsequent inhibition of reactive oxygen species generation and myeloperoxidase release, without affecting iNOS expression.

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Seven amikacin-resistant strains of Enterobacteriaceae isolated in Slovakia and Germany were included in this study. The strains were also resistant in vitro to high levels of gentamicin, tobramycin, netilmicin and isepamicin. Phosphocellulose paper binding assays indicated that resistance to aminoglycosides was due to synthesis of aminoglycoside acetyltransferase AAC(6′)-I in combination with aminoglycoside phosphotransferase APH(2XXX), a mechanism until now only identified in staphylococci and streptococci. This mechanism of aminoglycoside resistance has also been found in two isolates of Klebsiella pneumoniae from Germany. The substrate profile suggested that in addition to AAC(6′)-I and APH(2XXX), several strains also produced AAC(3)-II. Aminoglycoside resistance was found to be transferable to Escherichia coli 3110 rif^r in all isolates, and R plasmids of 36-45 MD were detected in donor and transconjugant strains. All isolated plasmids from transconjugants encoded resistance to aminoglycosides by genes encoding the enzymes AAC(6′)-I and APH(2XXX).