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Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.

Summary Some 109tonnes of chlorophyll are destroyed each year on land and in the oceans. The fate of these chlorophylls is, however, largely unknown. This review describes the developmental stages at which chlorophyll breakdown occurs in aquatic and terrestrial biological systems, and the destruction arising from herbivory, disease, pollution and other physical hazards. At the cellular level, an attempt is made to separate the breakdown of chlorophyll during senescence from the many other events associated with cell destruction and death. A consideration of the more important chemical and biophysical properties of chlorophylls and their derivatives is provided, together with data on their spectral properties. The biosynthetic and biodegradative pathways of chlorophyll metabolism are, so far as is possible, described with some predictions as to the likely fate of the missing tonnes. Two types of degradation are recognized; the first involves up to five defined enzymes concerned with the early stages, the second covers the less well defined enzymic and non‐enzymic destruction of the macrocyclic structure. These degradative reactions are compared with the reactions implicated in the breakdown of other porphyrins including haems in plants and animals. A brief description is given of the occurrence of breakdown products of chlorophyll in past biomass, including those of geological significance and those in a more recent archaeological context. Finally, the economic significance of chlorophyll breakdown is considered in the context of agriculture and horticulture, veterinary and medical sciences, food colouring and cosmetic industries, and the multi‐million‐dollar attraction of autumn leaf fall to tourism.

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Despite major advances in medicine in the last 100 years, microbiologically-based diseases continue to present enormous global health problems. New approaches that are effective, affordable and widely applicable and that are not susceptible to resistance are urgently needed. The photodynamic approach is known to meet at least some of these criteria and, with the creation and testing of new photosensitisers, may develop to meet all of them. The approach, involving the combination of light and a photosensitising drug, is currently being applied to the treatment of diseases caused by bacteria, yeasts, viruses and parasites, as well as to sterilisation of blood and other products.

The photobleaching of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was investigated during superficial photodynamic therapy (PDT) in normal skin of the SKH HR1 hairless mouse. The effects of light dose and fluence rate on the dynamics and magnitude of photobleaching and on the corresponding PDT-induced damage were examined. The results show that the PDT damage cannot be predicted by the total light dose. Photobleaching was monitored over a wide range of initial PpIX fluorescence intensities. The rate of PpIX photobleaching is not a simple function of fluence rate but is dependent on the initial concentration of sensitizer. Also, at high fluence rates (50-150 mW/cm2, 514 nm) oxygen depletion is shown to have a significant effect. The rate of photobleaching with respect to light dose and the corresponding PDT damage both increase with decreasing fluence rate. We therefore suggest that the definition of a bleaching dose as the light dose that causes a 1/e reduction in fluorescence signal is insufficient to describe the dynamics of photobleaching and PDT-induced damage. We have detected the formation of PpIX photoproducts during the initial period of irradiation that were themselves subsequently photobleached. In the absence of oxygen, PpIX and its photoproducts are not photobleached. We present a method of calculating a therapeutic dose delivered during superficial PDT that demonstrates a strong correlation with PDT damage.

Previous studies have shown that a cationic water-soluble pyridinium zinc phthalocyanine (PPC) is a powerful photosensitizer that is able to inactivate Escherichia coli. In the current work incubation of E. coli cells with PPC in the dark caused alterations in the outer membrane permeability barrier of the cells, rendering the bacteria much more sensitive to hydrophobic compounds, with little effect seen with hydrophilic compounds. Addition of Mg 2؉ to the medium prior to incubation of the cells with PPC prevented these alterations in the outer membrane permeability barrier. The presence of Mg 2؉ in the medium also prevented the photoinactivation of E. coli cells with PPC. These results are consistent with the hypothesis that PPC gains access across the outer membrane of E. coli cells via the self-promoted uptake pathway, a mechanism of uptake postulated for the uptake of other cationic compounds across the outer membranes of gram-negative bacteria.

An investigation of the behavior of protoporphyrin IX, deuteroporphyrin IX, haematoporphyrin IX and coproporphyrin III in aqueous solution revealed extensive and complex aggregation processes. Protoporphyrin appears to be highly aggregated under all conditions studied. At concentrations below 4 muM, aggregation of deutero-, haemato- and coproporphyrin is probably restricted to dimerization. At approx. 4muM each of these three porphyrins exhibits sharp changes in spectra consistent with a "micellization" process to form large aggregates of unknown size. This critical concentration increases with increasing temperature and pH, but is not very sensitive to variation in ionic strength. Temperature-jump kinetic studies on deuteroporphyrin also imply an initial dimerization process, the rate constants for which are comparable with those for various synthetic porphyrins, followed by a further extensive aggragation. The ability of a particular porphyrin to dimerize appears to parallel that of the corresponding iron(III) complexes (ferrihaems), although it is thought that ferrihaems do not exhibit further aggregation under these conditions.