Biomedical subjects

Harry Moseley

Publications and source records attributed to Harry Moseley.

12 recordsLinked to original sources

PubMed2006

A photoactivated trans-diammine platinum complex as cytotoxic as cisplatin.

The synthesis and X-ray structure (as the tetrahydrate) of the platinum(IV) complex trans,trans,trans-[Pt(N(3))(2)(OH)(2)(NH(3))(2)] 3 are described and its photochemistry and photobiology are compared with those of the cis isomer cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(2)] 4. Complexes 4 and 3 are potential precursors of the anticancer drug cisplatin and its inactive trans isomer transplatin, respectively. The trans complex 3 is octahedral, contains almost linear azide ligands, and adopts a layer structure with extensive intermolecular hydrogen bonding. The intense azide-to-platinum(IV) charge-transfer band of complex 3 (285 nm; epsilon=19 500 M(-1) cm(-1)) is more intense and bathochromically shifted relative to that of the cis isomer 4. In contrast to transplatin, complex 3 rapidly formed a platinum(II) bis(5'-guanosine monophosphate) (5'-GMP) adduct when irradiated with UVA light, and did not react in the dark. Complexes 3 and 4 were non-toxic to human skin cells (keratinocytes) in the dark, but were as cytotoxic as cisplatin on irradiation for a short time (50 min). Damage to the DNA of these cells was detected by using the "comet" assay. Both trans- and cis-diammine platinum(IV) diazide complexes therefore have potential as photochemotherapeutic agents.

Antineoplastic Agents↗

PubMed2005

The pH-dependent conformational transition of beta-lactoglobulin modulates the binding of protoporphyrin IX.

We have investigated the interaction between PPIX and beta-lactoglobulin (beta-lg) as a function of the pH of the solution. beta-lg is a small globular protein (MW approximately 18 kDa) with a very well characterized structure that reveals several possible binding sites for ligands. The interaction with beta-lg affects the photophysical properties of PPIX. The shift of PPIX emission maximum, excitation maximum and the increase of the fluorescence intensity is an indicator that binding between the porphyrin and beta-lg occurs. The binding constant appears to be modulated by the pH of the solution. Spectroscopic measurements do not reveal any significant energy transfer between the Trp residues of beta-lg and PPIX, however, fluorescence anisotropy decay measurements confirm the binding and the modulation introduced by the pH of the solution. Since beta-lg has been shown to be stable within the range of pH adopted in our experiments (5.0-9.0), the results suggest that PPIX binds a site affected by the pH of the solution. Because of the crystallographic evidence an obvious site is near the aperture of the interior beta-barrel however an alternative (or concurrent) binding site may still be present.

Animals↗

PubMed2005

Light distribution and calibration of commercial PDT LED arrays.

Commercial photodynamic therapy (PDT) light sources are supplied with no evidence of traceability to national measurements standards to validate indicated delivered dose. Also, the spatial distribution of the radiant energy is not disclosed. This means that there is no way for the user to be able to verify that the required dose is being delivered to the appropriate area of the lesion. To this end, a simple method, traceable to national standards, is described and applied to an investigation of two commercial LED arrays. In one case, the dose fell to 38% of that received at the central area at a distance of only 2 cm. In the other, the output was more uniform over a larger area but the maximum irradiance was not at the centre of the field. All of these inhomogenieties were taken into account when the actual light dose delivered to the patient was calculated in the method described. This ensured transparent traceability in PDT dosimetry.

Algorithms↗

PubMed2005

A randomised, blinded, controlled study of the clinical relevance of matching pulse duration to thermal relaxation time when treating facial telangiectasia.

The theory of selective photo-thermolysis (SP) suggests the occurrence of optimal damage when the laser pulse duration (PD) equals the target thermal relaxation time (Tr). This study examines the clinical relevance of this theory. The study design and methods consisted of prospective, randomised, blinded, controlled study of KTP 532-nm laser treatment of 28 telangiectatic facial vessels. The PD varied from 0.13 to 1.71 times Tr (factor of 13). All vessels achieved marked improvement or clearance. The analysis of proportions reaching clearance over marked improvement for small and large calibre vessels shows a better outcome when the PD is nearer to the Tr (86% vs 57%; P = 0.09, 95% CI for difference -3% to 60%). Logistic regression analysis shows that, as the ratio of PD to Tr increases (PD near to or higher than Tr), the chance of clearing improves (P = 0.169; 95% CI 0.34 to 341). This study has shown that, for the range of vessels investigated: (1) marked improvement or clearance may be achieved using PDs that range between 0.13 and 1.71 times the Tr; and (2) it also reveals an overall trend towards a higher proportion of clearance when the PD is near to or higher than the Tr.

Adult↗

PubMed2005

Clustered outbreak of skin and eye complaints among catering staff.

In August 2002, kitchen staff at a hotel in Central Scotland experienced skin and eye problems believed to be related to their working environment. Of a total of 20 staff, eight cooks reported problems with a painful red skin affecting the face, eyelids, side and front of neck as well as burning, gritty eyes. Five of the affected individuals were clinically assessed in April 2003. The overall clinical impression was of conjunctivitis and sunburn-like erythema. Examination of the data sheets of all cleaning agents and sprays used within the kitchen pointed against an environmental phototoxin. The kitchen area was inspected and two electric fly killers positioned on the ceiling and sidewalls were found to be incorrectly fitted with UVC tubes. The output of these tubes was spectroradiometrically assessed. The recommended unprotected skin and eye exposure limit was reached in 14 s at a distance of 30 cm from the tubes. An exposure of about 60 s would be sufficient to induce minimal erythema in someone of skin type I/II. These results demonstrate the importance of exposure to ultraviolet radiation as a possible cause of facial erythema and conjunctivitis, no matter how unlikely this may seem. It is recommended that there should be increased awareness of the need to fit the correct type of lamps to electric fly killers and other devices that incorporate UV lamps.

Adult↗

PubMed2004

Characterization of the photoproducts of protoporphyrin IX bound to human serum albumin and immunoglobulin G.

Clinically useful photosensitisers (PSs) are likely bound to subcellular and molecular targets during phototherapy. Binding to a macromolecule has the potential to change the photophysical and photochemical characteristics of the PSs that are crucial for their phototoxicity and cell-killing activity. We investigated the effects of binding of a specific PS (protoporphyrin IX or PPIX) to two proteins, human serum albumin (HSA) and a commercially available immunoglobulin (IgG). These two proteins provide two different environments for PPIX. The albumin binds PPIX in hydrophobic binding sites located in subdomain IIA and IIIA, conversely IgG leaves PPIX exposed to the solvent. We show that photophysical parameters such as emission maxima and fluorescence lifetime depend on the binding site. Our results indicate that the different binding site yields very different rates of formation of photoproducts (more than three times higher for PPIX bound to HSA than to IgG) and that different mechanisms of formation may be occurring. Our characterization shows the relevance of protein binding for the photochemistry and ultimately the phototoxicity of PSs.

Dermatitis, Phototoxic↗

PubMed2004

Operator error is the key factor contributing to medical laser accidents.

Useful lessons can often be learned from studying laser accidents. Although most countries require such accidents to be reported to the relevant authority, often such information is not accessible to laser users. Consequently, it was decided to collect detailed accounts of incidents from the British Medical Laser Association's Internet mailing list. Twelve incidents were reported by e-mail after a request for information sent to the BMLA mailing list in 2003. Although these are of a diverse nature, operator error accounted for 67% of the cases. This factor should be recognized when developing laser safety programs.

Accident Prevention↗

PubMed2004

Photopatch testing: a consensus methodology for Europe.

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.

Dermatitis, Photoallergic↗

PubMed2004

The characteristics of erythema induced by topical 5-aminolaevulinic acid photodynamic therapy.

BACKGROUND: Topical photodynamic therapy (PDT) is increasingly used to treat superficial non-melanoma skin cancers. Knowledge of the characteristics of 5-aminolaevulinic acid (ALA)-induced phototoxicity will increase our understanding of PDT and may facilitate optimisation of treatment regimes. METHODS: We examined the characteristics of ALA-induced erythema in 10 healthy subjects and investigated the effect of light source and body site. RESULTS AND CONCLUSIONS: Maximal erythema occurred within 1-2 h of PDT and inter-individual variation in ALA-induced phototoxicity was seen. No detectable differences were seen in the phototoxicity on back or leg sites or between coherent and non-coherent light sources. These data provide further information to allow us to optimise topical PDT regimes.

Aminolevulinic Acid↗

PubMed2003

Ultraviolet protection factors for clothing: an intercomparison of measurement systems.

In recent years the need to standardize measurement protocols for quantifying the degree of ultraviolet radiation (UVR) protection provided by clothing has led to the introduction of a number of standards around the world. To date, these standards have specified spectral measurements of UVR transmission by clothing and fabrics. Development of a standard test method has become an important part of the testing process, and this article presents results from an intercomparison involving 10 independent testing laboratories and 11 different UVR transmission measurement instruments. In addition to comparing the measured ultraviolet protection factors (UPF), this intercomparison also incorporates detailed scan results from all 10 laboratories and highlights differences in performance of the various instruments in different wavelength regions. Careful examination of these differences can indicate where changes to the systems could be made to allow improvements both in equipment performance and in agreement of the final results. The variability in the measurements of UPF in this study suggest that the protection categories in standards may need to be broadened.

Clothing↗

PubMed2002

The use of diode array spectroradiometers for dosimetry in phototherapy.

An evaluation of two diode array radiometers, an UV spectroradiometer, Type SC-MP-A, from 4D Controls (Redruth, UK) and an USB2000-UV-VIS spectrometer from Ocean Optics (Duiven, NL), was carried out at the Photobiology Unit, University of Dundee. Three parameters of the instruments' performance were investigated, having been identified as the most likely sources of error in phototherapy dosimetry: (1) calibration, (2) stray light rejection, (3) angular response. An assessment was then made of the reliability of this type of instrument for dosimetry in clinical practice by measurement of a selection of phototherapy sources, in direct comparison with calibrated radiometers. Both instruments were found to have significant stray light levels (SC: 13% and USB: 39%). The use of stray light compensation and a high output calibration source improves accuracy to within acceptable limits. Angular responses were satisfactory: f2 values (+/- 60 degrees) of 5.9% and 7.8% for SC and USB, respectively. The SC spectroradiometer is supplied as a calibrated instrument. Using the supplied calibration resulted in errors in measuring phototherapy sources of up to 44% in UVA. Alternative calibration reduced the error in measuring UVA and UVB sources to within 12%. The USB spectrometer was found to have insufficient responsivity in both UVB and UVA to provide reproducible measurements of most phototherapy sources.

Equipment Failure Analysis↗

PubMed2002

Effects of photoproducts on the binding properties of protoporphyrin IX to proteins.

Photosensitisers are the photoactive molecules used in photodynamic therapy (PDT) of cancer. Despite the importance of their interaction with polypeptides, only the binding to plasma proteins has been investigated in some detail. In our study we compared the binding of Protoporphyrin IX (a clinically useful photosensitiser) to an immunoglobulin G, with the binding to albumins. Binding to IgG is relevant because a possible method of increasing tumour specificity of photosensitisers is to bind them to tumour-specific antibodies. Binding constants to albumins and the immunoglobulin were comparable ( congruent with6 x 10(-6) M(-1)). The apparent number of PPIX molecules bound to each protein was also within a similar range (from 4 to 7). The absence of a shift in the emission spectrum of PPIX bound to IgG, however, indicates that either larger aggregates of PPIX bind to the immunoglobulin or that the binding site leaves PPIX exposed to the buffer. We observed that PPIX photoproducts compete with PPIX for the same binding sites. The number of PPIX molecules bound to each protein in the presence of photoproducts decreased by 50-80%. Due to the spectral overlap between PPIX and its photoproducts, the binding in the presence of photoproducts was investigated using Derivative Synchronous Fluorescence Spectroscopy (DSFS) to improve the spectral separation between chromophores in solution. We also concluded that fluorescence measurements underestimate the number of PPIX molecules binding each protein. In fact, non-linear Scatchard plots (in the case of albumin binding) by definition yield a minimum number of molecules attached to a protein. Moreover, the binding of large aggregates, formed by an unknown number of PPIX molecules, to IgG results in the underestimate of the number of molecules bound. The number of PPIX molecules bound to these proteins is also much larger than the number of sites estimated by protein fluorescence quenching.

Albumins↗