A quantitative comparison of 5-aminolaevulinic acid- and methyl aminolevulinate-induced fluorescence, photobleaching and pain during photodynamic therapy

The characteristics of protoporphyrin IX (PPIX) fluorescence in superficial basal cell carcinoma (sBCC) and carcinoma in situ (Bowen's Disease, BD) following application of 5-aminolaevulinic acid (5-ALA) and its methyl ester (methyl aminolevulinate [MAL]) before, during and after photodynamic therapy (PDT) were investigated in 40 patients. Photosensitizer prodrug penetration can limit PDT efficacy and understanding the characteristics of PPIX fluorescence through fluorescence spectroscopy, may improve knowledge of photosensitizer delivery. Fluorescence intensity was assessed quantitatively, and the rate of photobleaching was determined by fitting an exponential decay. As a secondary end-point, PDT-induced pain was also measured continuously during treatment using a novel hand-held device, known as a pain logger. In vivo PPIX fluorescence was shown to decrease during irradiation, allowing the in vivo photobleaching of PPIX to be monitored. No significant difference was found between ALA- or MAL-induced PPIX fluorescence in lesions of sBCC and BD (P>0.05), indicating no detectable difference in PPIX kinetics for the two prodrugs as assessed by these measures. Pain, as assessed by the logger device, showed high interindividual variability and pain levels tended to be higher initially, decreasing during treatment. No difference was seen in pain experienced during ALA-or MAL-PDT (P>0.05).     

Metal-free and dicopper(II) complexes of Schiff base [2 + 2] macrocycles derived from 2,2'-iminobisbenzaldehyde: syntheses, structures, and electrochemistry

Three new bis-terdentate Schiff base [2 + 2] macrocycles (H(2)L(Et), H(2)L(Pr), and H(2)L(Bu)) have been prepared in high yields by 1:1 condensation of 2,2'-iminobisbenzaldehyde with 1,2-diaminoethane, 1,3-diaminopropane, and 1,4-diaminobutane, respectively. Metalation of these macrocycles yields the corresponding dicopper(II) acetate (1, 2, and 3) and tetrafluoroborate (4, 5, and 6) complexes. The structures of H(2)L(Et), H(2)L(Pr), H(2)L(Bu), [Cu(II)(2)L(i)(OAc)(2)]·solvents (where i is Et, Pr or Bu) and [Cu(II)(2)L(Pr)(DMF)(4)] (BF(4))(2)·0.5H(2)O are reported. Intramolecular hydrogen bonding is a feature of the metal-free macrocycles. The copper(II) centers in [Cu(II)(2)L(i)(OAc)(2)]·solvents are four coordinate, and the macrocycles have U-shaped (Et, Bu) or stepped (Pr) conformations. Complex 5 crystallizes with two dimethylformamide (DMF) molecules bound per five coordinate copper(II) center. Electrochemical studies revealed ligand based oxidations for all of the macrocycles and complexes. Complexes 1 and 2 undergo two quasi-reversible oxidations in DCM which are associated with the deposition of a visible film on the electrode after multiple scans in this oxidative region, suggestive of electropolymerization. Complexes 4-6, studied in MeCN, have Cu(II) → Cu(I) redox potentials at more positive potentials than for 1-3.     

New time-differential Mössbauer emission measurements on the high-spin→low-spin relaxation in [57Co/Co(phen)3](ClO4)2

Using our new spectrometer for time-differential Mössbauer emission spectroscopy we reinvestigated the high-spin→low-spin relaxation following the⁵⁷Co(EC)⁵⁷Fe process in [⁵⁷Co/Co(phen)₃](ClO₄)₂ (phen=1,10-phenanthroline). In contrast to former investigations we found a temperature dependent initial population less than 1 for the metastable high-spin states. The results and the data evaluation method are presented.     

Topical Application of Photofrin® for Oral Neoplasms in Animal

Early diagnosis improves oral cancer prognosis. Exact demarcation of tumor margins improves surgical outcomes. This study evaluates Photofrin^® fluorescence: a new diagnostic procedure for detection of oral neoplasms in animal models. Fourteen male Golden Syrian hamsters were used. 0.5% D.M.B.A (9,10 dimethyl1-1,2-benzanethracene) was brushed onto cheek pouches bilaterally daily for 2,weeks. Hamsters with oral neoplasms received 2.5,mg/ml Photofrin^® solution topically. After 3h the neoplasms underwent fluorescence illumination (λex=380–420,nm). A quantitative analysis of the fluorescence contrast between the neoplastic and surrounding tissue was performed using the RGB Mode and the Gray Scale. (GS) Statistical analysis was performed using the ANOVA test. Analysis of the 14 hamsters’ 28 biopsies revealed 4 (14.3%) displayed squamous hyperplasia (1 mild, 3 severe) and 24 (85.7%) displayed squamous cell carcinoma. The sensitivity of neoplasms evaluated using the RGB and GS modes combined resulted in 92.15% (in vivo macroscopic image) and 93.45% (histological). The specificity of neoplasms evaluated via RGB and GS modes combined resulted in 94.78% (in vivo macroscopic image) and 97.30% (histological). The difference between healthy tissue and the lesions as a group is statistically significant. Photofrin^® fluorescence provides a sensitive, non-invasive technique for early identification of malignant neoplasms in the oral cavities of animal models.     

Accuracy of the IOS approximation for highly inelastic R-T collisional energy transfer

Rate constants for rotational excitation of CO by collisions with He atoms computed within the infinite order sudden (IOS) approximation are compared with accurate quantum (coupled-states) and classical trajectory values. Taking the IOS energy as the initial kinetic energy for upward. 0 → J, transitions is found to overestimate the rates, especially for higher J (larger inelasticity). Taking the IOS energy as the initial energy for downward, J → 0, transitions underestimates the rates by a comparable amount. The geometric average of IOS rates computed in these two ways is found to provide accurate values.     

Investigating quartz optically stimulated luminescence dose–response curves at high doses

Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose–response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose–response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the ‘325 °C’ thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses that is not recorded by the sensitivity to a subsequent test dose, and which results in a change in the sensitivity-corrected dose–response curve.     

Book review

Probability in Social Science by Samuel Goldberg