Evaluation of two commercial jet nebulisers and three compressors for the nebulisation of antibiotics

Nebulised antibiotics have been shown to be beneficial in the treatment of lung infections in cystic fibrosis. Studies on the efficiency of nebuliser systems are constantly required in view of the large number of compressor/drug/nebuliser combinations which are possible and the development of new systems and drugs. Six combinations of three commercially available compressors were compared (PortaNeb 50 (Medic-Aid; 5.4-6.1 l/min), Turboneb (Medix; 8.3-9.1 l/min), and CR 60 (Medic-Aid; 7.3-7.8 l/min)) and two jet nebulisers (Microneb III (Lifecare) and System 22 Acorn (Medic-Aid)) for the nebulisation of colomycin, gentamicin, and ciprofloxacin. Aerosol droplet size, nebulisation time, and aerosol output were determined. Turboneb and CR 60 reduced the nebulisation time and produced higher proportions of 'respirable' (< 5 microns diameter) antibiotic aerosols. The residual volume of the Microneb III was lower than that of the System 22 Acorn. It was found that the Turboneb and CR 60, when coupled with either Microneb III or System 22 Acorn, were suitable for the nebulisation of all three antibiotics. Of the equipment tested, Turboneb coupled with Microneb III was the most efficient combination. Even with this combination, only around 50% of the nominal dose was released as respirable aerosol.     

Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision repair

O6-Methylguanine (O6MeG) and O4-methylthymine (O4MeT) are potentially mutagenic DNA lesions that cause G:C-->A:T and A:T-->G:C transition mutations by mispairing during DNA replication, and the repair of O6MeG and O4MeT by DNA repair methyltransferases (MTases) is therefore expected to prevent methylation-induced transitions. The efficiency of O6MeG and O4MeT repair by different MTases can vary by several hundred- fold and the aim of this study was to establish the biological consequences of such differences in the efficiency of repair. The ability of three microbial and two mammalian MTases to prevent methylation-induced G:C-->A:T and A:T-->G:C transitions is taken as a measure of their ability to repair O6MeG and O4MeT in vivo respectively. All five MTases give complete protection against G:C-- >A:T transitions. However, while the microbial MTases give complete protection against A:T-->G:C transitions, the mammalian MTases actually sensitize cells to A:T-->G:C transitions. We hypothesize that the mammalian MTases bind O4MeT lesions in vivo but that, because they are extremely slow at subsequent methyl transfer, binding shields O4MeT from repair by the nucleotide excision repair pathway. Results are presented to support this hypothesis.