Intracellular localisation of mTHPC and effect of photodynamic therapy in cells of the mammalian peripheral nervous system

Fewer nerve-related side effects have been noted after treating head and neck cancer with photodynamic therapy (PDT) compared to conventional cancer therapy. Our aim is to investigate the biological basis for any such nerve-sparing effect. In this study the intracellular localisation and effect on cell viability of the photosensitiser meta-tetrahydroxylphenylchlorin (mTHPC) was investigated in cell culture models using peripheral nerve cells. Primary cells from adult rat dorsal root ganglia (containing both neurons and glia) were used in these experiments. Localisation of mTHPC was detected using fluorescence and confocal microscopy. Levels of mTHPC fluorescence were quantified using digital image analysis. Immunocytochemistry with anti-?-III-tubulin and anti-S100 was used to distinguish neuronal and glial cell populations respectively. A cell-death assay using propidium iodide was used to evaluate neural cell susceptibility to PDT following incubation with mTHPC. The results showed that mTHPC was localised in cytoplasmic regions of neurons and glia, but was not detected in neuronal axons. Necrotic cell death was detected after PDT in these neural cell types. These results suggest that the cells of the peripheral nervous system are susceptible to PDT-mediated necrosis, but that the sparing of nerves observed during clinical PDT may be related to the heterogeneous distribution of mTHPC within neurons

Assessing the Effect of Photodynamic Therapy on Peripheral Nerve and Cancer Cells Using a Thin Tissue Engineered Collagen Culture Model

Abstract not available

Coulomb Distortion Effects for Electron or Positron Induced (e,e′)(e,e') Reactions in the Quasielastic Region

In response to recent experimental studies we investigate Coulomb distortion effects on $(e,e')$ reactions from medium and heavy nuclei for the case of electrons and positrons. We extend our previously reported full DWBA treatment of Coulomb distortions to the case of positrons for the $^{208}Pb(e,e')$ reaction in the quasielastic region for a particular nuclear model. In addition, we use previously reported successful approaches to treating Coulomb corrections in an approximate way to calculate the Coulomb distortion effects for $(e,e')$ reactions for both electrons and positrons for the case of a simple nuclear model for quasielastic knock-out of nucleons. With these results in hand we develop a simple {\em ad-hoc} approximation for use in analyzing experiments, and discuss methods of extracting the ``longitudinal structure function" which enters into evaluation of the Coulomb sum rule. These techniques are generally valid for lepton induced reactions on nuclei with momentum transfers greater than approximately 300 $MeV/c$.Comment: 18 pages, 6 figure

Differences in sensitivity to mTHPC-mediated photodynamic therapy of neurons, glial cells and MCF7 cells in a 3-dimensional cell culture model

The effect of photodynamic therapy (PDT) on the cells of the nervous system is an important consideration in the treatment of tumours that are located within or adjacent to the brain, spinal cord and peripheral nerves. Previous studies have reported the sparing of nerves during PDT using meta-tetrahydroxyphenylchlorin (mTHPC, Foscan®) in patients and in animal models. The aim of this study was to investigate the effects of mTHPC on key nervous system cells using a 3-dimensional cell culture system for the accurate detection of differences in sensitivity

Two-body anticorrelation in a harmonically trapped ideal Bose gas

We predict the existence of a dip below unity in the second-order coherence function of a partially condensed ideal Bose gas in harmonic confinement, signaling the anticorrelation of density fluctuations in the sample. The dip in the second-order coherence function is revealed in a canonical-ensemble calculation, corresponding to a system with fixed total number of particles. In a grand-canonical ensemble description, this dip is obscured by the occupation-number fluctuation catastrophe of the ideal Bose gas. The anticorrelation is most pronounced in highly anisotropic trap geometries containing small particle numbers. We explain the fundamental physical mechanism which underlies this phenomenon, and its relevance to experiments on interacting Bose gases.Comment: 10 pages, 5 figures. v2: Minor changes and corrections to figures and text. To appear in PR

Secular trends in under-reporting in young people

Original article can be found at: http://journals.cambridge.org/action/displayJournal?jid=BJN Copyright The Authors. DOI: 10.1079/BJN20041307National survey data show that reported energy intake has decreased in recent decades despite a rise in the prevalence of obesity. This disparity may be due to a secular increase in under-reporting or a quantitatively greater decrease in energy expenditure. This study examines the extent of under-reporting of energy intake in the National Diet and Nutrition Survey (NDNS) in young people aged 4–18 years in 1997 using published equations to calculate estimated energy requirements. It explores secular changes by comparison with the Diets of British School Children (DBSC) survey in 10–11- and 14–15-year-olds in 1983. In the NDNS, under-reporting (estimated energy requirements – energy intake) represented 21 % of energy needs in girls and 20 % in boys. The magnitude of under-reporting increased significantly with age (P<0·001) and was higher in overweight than lean individuals over 7 years of age. To compare reported energy intake in DBSC and NDNS, the estimated physical activity level from dietary records (dPAL=reported energy intake/predicted BMR) was calculated. If there were no under-reporting, dPAL would represent the subject's true activity level. However, dPAL from the NDNS was significantly lower than that from the DBSC by 8 % and 9 % in boys and girls for those aged 10–11 years, and by 14 % and 11 % for 14–15-year-olds respectively, reaching physiologically implausible levels in the 14–15-year-old girls (dPAL=1·17). If activity levels have remained constant between the two surveys, under-reporting has increased by 8–14 %. The evidence supports a secular trend towards increased under-reporting between the two surveys, but the precise magnitude cannot be quantified in the absence of historical measures of energy expenditure.Peer reviewe

Impulsive phase flare energy transport by large-scale Alfven waves and the electron acceleration problem

The impulsive phase of a solar flare marks the epoch of rapid conversion of energy stored in the pre-flare coronal magnetic field. Hard X-ray observations imply that a substantial fraction of flare energy released during the impulsive phase is converted to the kinetic energy of mildly relativistic electrons (10-100 keV). The liberation of the magnetic free energy can occur as the coronal magnetic field reconfigures and relaxes following reconnection. We investigate a scenario in which products of the reconfiguration - large-scale Alfven wave pulses - transport the energy and magnetic-field changes rapidly through the corona to the lower atmosphere. This offers two possibilities for electron acceleration. Firstly, in a coronal plasma with beta < m_e/m_p, the waves propagate as inertial Alfven waves. In the presence of strong spatial gradients, these generate field-aligned electric fields that can accelerate electrons to energies on the order of 10 keV and above, including by repeated interactions between electrons and wavefronts. Secondly, when they reflect and mode-convert in the chromosphere, a cascade to high wavenumbers may develop. This will also accelerate electrons by turbulence, in a medium with a locally high electron number density. This concept, which bridges MHD-based and particle-based views of a flare, provides an interpretation of the recently-observed rapid variations of the line-of-sight component of the photospheric magnetic field across the flare impulsive phase, and offers solutions to some perplexing flare problems, such as the flare "number problem" of finding and resupplying sufficient electrons to explain the impulsive-phase hard X-ray emission.Comment: 31 pages, 6 figure

Logical equivalence between generalized urn models and finite automata

To every generalized urn model there exists a finite (Mealy) automaton with identical propositional calculus. The converse is true as well.Comment: 9 pages, minor change