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Biomedical subjects

D C Neckers

Publications and source records attributed to D C Neckers.

4 recordsLinked to original sources

Pharmacological studies of arrhythmias induced by rose bengal photoactivation.

Singlet oxygen and superoxide production by rose bengal photoactivation leads to rapid electrophysiological changes and arrhythmias. To investigate which intermediate is causative and to probe possible mechanisms, hearts (n = at least 6/group) were perfused aerobically for 10 min without rose bengal followed by 5 min with rose bengal before illumination for 20 min. In controls, all or most hearts exhibited ventricular premature beats, ventricular tachycardia, and complete atrioventricular block. Most antioxidants tested had no protective effect; histidine, however, significantly delayed the onset of electrocardiographic (ECG) changes. In further studies, two antiarrhythmic agents (quinidine and verapamil) had no little protective effect, whereas R56865 significantly delayed the onset of ECG changes and reduced the incidence of arrhythmias. However, spectrophotometric and laser pulse radiolysis studies showed that this apparent protective effect might have resulted from an interaction between R56865 and the rose bengal molecule, leading to a reduction in singlet oxygen production. In conclusion, the electrophysiological changes induced by rose bengal photoactivation are likely to be due to singlet oxygen; antiarrhythmic drugs appear to be unable to protect against the injury unless there is some interaction with the photoactivation process.

Animals

Readily available fluorescein isothiocyanate-conjugated antibodies can be easily converted into targeted phototoxic agents for antibacterial, antiviral, and anticancer therapy.

Fluorescein-labeled antibodies have little, if any, photodynamic effect because energy acquired by light absorption is rapidly dissipated in fluorescence. However, they can be easily and efficiently converted to selective photodynamic sensitizers by iodination under mild conditions. We have outlined general experimental procedures that can be used to turn a fluorescein-labeled anti-Escherichia coli antibody into a photodynamic sensitizer that selectively kills E. coli while sparing closely related Salmonella typhimurium. These results demonstrate that iodination did not destroy the specificity or activity of the antibody. This technique should be applicable to the large number of fluoresceinated antibodies that are commercially available. Thus, this strategy provides a simple way to rapidly prepare a large number of targeted phototoxic agents that can be used for the selective destruction with light of nearly any type of tissue or organism.

Anti-Bacterial Agents