A Quantitative Study of In Vivo Protoporphyrin IX Fluorescence Build Up During Occlusive Treatment Phases

C L Campbell acknowledges financial support from an UK EPSRC PhD studentship (EP/K503162/1), the Alfred Stewart Trust, the Russell trust award, the Santander mobility award and the FAPESP CEPOF grant 2013/07276.Background: Topical photodynamic therapy (PDT) is a non-invasive light based therapy used to treat non-melanoma skin cancer (NMSC) and dysplasia. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. PpIX is metabolised from a topically applied pro-drug and the strong fluorescence signal associated with PpIX can be utilised as an indicator of the amount of PpIX present within the tumour tissue. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics. Methods : Fluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3 hour long occlusive treatment prior to irradiation. The study included in vivo measurements of 38 lesions from 38 individual patients. Actinic keratosis (AK) and basal cell carcinoma (BCC) were the lesion types included in this study. The resulting data from the study was analysed using generalised linear mixed effects models. Results : It was found that the surface fluorescence signal linearly increased with occlusive treatment time. The predictive models suggest that there is a significant difference in PpIX production between lesion location, however no significant difference is demonstrated between different lesion types, gender and skin type. Conclusions : The study extends and supports previous knowledge of PpIX production during the occlusive treatment phase.PostprintPeer reviewe

Antimicrobial Photodynamic Therapy of the Respiratory Tract: From the Proof of Principles to Clinical Application

Antimicrobial resistance (AMR) and its relevant health consequences have been explicitly framed as a shared global problem and are estimated to be one of the largest causes of death worldwide by 2050. Antimicrobial photodynamic therapy (aPDT) proposes an alternative treatment for localized infections in response to AMR’s ever-growing problem. This technique combines molecular oxygen, a non-toxic photoactivatable photosensitizer (PS), and light of appropriate wavelength, leading to the formation of cytotoxic reactive oxygen species. Besides the ability to inactivate resistant pathogens via a non-selective approach (multiple targets), a relevant advantage of aPDT resides in the fact that no evidence of microorganism resistance has ever been reported to it. In this chapter, we address some efforts to use this technology to kill bacteria in the respiratory tract, from in vitro to clinical applications. We put forward three focuses: pharyngotonsillitis, pneumonia, and preventing secondary infections during the use of a photosensitizer-functionalized endotracheal tube. The results here presented offer a foundation for what may become a much larger clinical approach to treat respiratory tract infections

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Erratum: “The eighth data release of the Sloan Digital Sky Survey: first data from SDSS-III” (2011, ApJS, 193, 29)

Section 3.5 of Aihara et al. (2011) described various sources of systematic error in the astrometry of the imaging data of the Sloan Digital Sky Survey (SDSS). In addition to these sources of error, there is an additional and more serious error, which introduces a large systematic shift in the astrometry over a large area around the north celestial pole. The region has irregular boundaries but in places extends as far south as declination δ ≈ 41◦. The sense of the shift is that the positions of all sources in the affected area are offset by roughly 250 mas in a northwest direction. We have updated the SDSS online documentation to reflect these errors, and to provide detailed quality information for each SDSS field

SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2, which is now completed, measured medium-resolution (R=1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

Irradiated Cationic Mesoporphyrin Induces Larger Damage To Isolated Rat Liver Mitochondria Than The Anionic Form.

The action of irradiated cationic Fe(III)TMPyP and anionic Fe(III)TPPS4 forms of mesoporphyrins on mitochondrial functions was investigated using experimental conditions that caused minimal effects on mitochondria in the dark. Treatment of mitochondria with 1 microM Fe(III)TMPyP for 2 min decreased the respiratory control by 3% in the dark and 28% after irradiation. Fe(III)TPPS4 (1 microM) had no significant effect on respiratory control under any of the above conditions. Both porphyrins increased the mitochondrial production of reactive oxygen species in the presence of Ca2+; however, the effect of Fe(III)TMPyP was significantly stronger. In both cases, this overproduction was associated with membrane lipid peroxidation. It was also observed that the association constant of Fe(III)TMPyP with mitochondria was 11 times higher than that of Fe(III)TPPS4. In conclusion, the damage to isolated mitochondria induced by Fe(III)TMPyP under illumination was larger than by Fe(III)TPPS4, probably because its cationic charge favors association with the mitochondrial membrane. This is supported by the decrease in the association constant of Fe(III)TMPyP with mitochondria in higher salt medium.457217-2

A quantitative study of <i>in vivo</i> protoporphyrin IX fluorescence build up during occlusive treatment phases

Background: Topical photodynamic therapy (PDT) is a non-invasive light based therapy used to treat non-melanoma skin cancer (NMSC) and dysplasia. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. PpIX is metabolised from a topically applied pro-drug and the strong fluorescence signal associated with PpIX can be utilised as an indicator of the amount of PpIX present within the tumour tissue. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics.Methods: Fluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3 hour long occlusive treatment prior to irradiation. The study included in vivo measurements of 38 lesions from 38 individual patients. Actinic keratosis (AK) and basal cell carcinoma (BCC) were the lesion types included in this study. The resulting data from the study was analysed using generalised linear mixed effects models.Results: It was found that the surface fluorescence signal linearly increased with occlusive treatment time. The predictive models suggest that there is a significant difference in PpIX production between lesion location, however no significant difference is demonstrated between different lesion types, gender and skin type.Conclusions: The study extends and supports previous knowledge of PpIX production during the occlusive treatment phase

Inhibition of Macrophage Oxidative Stress Prevents the Reduction of ABCA-1 Transporter Induced by Advanced Glycated Albumin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.475443450Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Luminescent Mesoporous Silica Nanohybrid Based on Drug Derivative Terbium Complex

Mesoporous silica nanoparticles prepared by organic template-driven synthesis have been successfully explored as carriers of the drug-derivate green luminescent complex of terbium (III) with the nonsteroidal anti-inflammatory drug ketoprofen. The terbium (III) complex was synthesized by reacting ketoprofen sodium salt with terbium (III) chloride, which was further adsorbed onto the surface of mesoporous nanoparticles with a mean particle size of 47 &#177; 4 nm and pore size of 11 nm. The incorporation of the complex into mesoporous silica nanoparticles was tracked by the decrease in the surface area and pore size of the nanoparticles, and successfully demonstrated by substantial changes in the adsorption isotherms and thermal and vibrational spectroscopy results. The cytotoxicity assay and confocal microscopy have shown that the novel luminescent nanohybrid presents high cell viability and the characteristic terbium (III) emission can be assessed through two-photon excitation, which paves the way for bioimaging applications in nanomedicine