bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time‐Resolved Study of the Sensitized Formation and Decay of 1O2(1δg) in the Presence of Cyclodextrins*
Authors: Sanramé Carlos N. , Rossi Rita H. de , Argüello Gustavo A. 
Published: January 2008

AbstractThe effect of β‐cyclodextrin and β‐hydroxypropyl‐cyclodextrin on some properties of the aromatic ketone 1‐H‐phenalen‐1‐one and its sulfonate derivative 1‐H‐phen‐alen‐1‐one‐2‐sulfonic acid was measured in aqueous solution. From the changes in the UV‐visible range of the absorption spectra, the association equilibrium constants for the formation of inclusion complexes were determined. Because these ketones are very efficient sensitizers for the generation of singlet oxygen, time‐resolved infrared luminescence was used to measure the lifetime of singlet oxygen in D2O. Cyclodextrins are weak deactivating agents of singlet oxygen; the upper limits for the bimolecular deactivation constants are 2 times 105M−1s−1 and 1 times 105M−1s−1 for β‐cyclodextrin and β‐hydroxypropyl‐cyclodextrin, respectively. Besides, they do not affect noticeably the extent of formation of singlet oxygen; this result is explained in terms of relocation of the sensitizer (exit from the cyclodextrin cavity) in the triplet excited state.
Photoaddition to DNA by Nonintercalated Chlorpromazine Molecules
Authors: Kochevar Irene E. , Garcia Carmelo , Geacintov Nicholas E. 
Published: January 2008

AbstractChlorpromazine (CPZ) forms photoadducts with DNA and photosensitizes DNA strand breaks. These reactions may be responsible for the reported photomutagenicity of CPZ and for the well‐known cutaneous and ocular phototoxicity associated with this drug. We have investigated whether CPZ molecules that are intercalated between base pairs in double‐stranded (ds) DNA are the absorbing species for the photoaddition reaction. Quenching of CPZ fluorescence by ds‐DNA gave nonlinear Stern‐Volmer plots, indicating that more than one type of complex is formed. Linear dichroism spectra of CPZ in the presence of ds‐DNA showed a minimum at 345 nm, indicating that the absorption maxima of intercalation complex(es) are red‐shifted compared to the absorption maximum of free CPZ at 307 nm. The sum of the absorption of all CPZ complexes with ds‐DNA, obtained from dialysis experiments, was broadened and maximized at about 315 nm, indicating that complexes not involving intercalation dominate the absorption spectrum at X < 350 nm. The wavelength dependence for covalent binding of CPZ to DNA was determined by irradiating 3H‐CPZ in the presence of ds‐DNA at 310, 322, 334, 346, 358 and 370 nm. The resulting spectrum correlated closely with the absorption spectrum of nonintercalated CPZ rather than with the spectrum of intercalated CPZ, indicating that the latter species is not the chromophore for the photoaddition reaction.
Identification and Quantification of Intrinsic Optical Contrast for Near‐infrared Mammography
Authors: Quaresima Valentina , Matcher Stephen J. , Ferrari Marco 
Published: January 2008

ABSTRACTNear‐infrared spectroscopy has been used to quantify the composition of healthy female breast tissue in vivo. By collecting transillumination spectra in the wavelength range 680–1100 nm at 7–9 positions on the breasts of five female volunteers, an attempt was made to quantify the intra‐ and intersubject variability of breast composition. The dominant absorbers are water, lipids and hemoglobin. Hemoglobin concentration in the breast is substantially lower than that in the brain or muscle (less than 10 μM). The measured deoxyhemoglobin concentration can vary by up to 100% between different positions on the same breast. Water and lipid concentrations can show similar variability. Phantom and simulation studies demonstrate that this variability is not due to the effects of tissue boundaries on the measurements. The low hemoglobin concentration implies that optical breast imaging should be performed at wavelengths below about 850 nm to ensure that the image contrast comes predominantly from hemoglobin. Intrasubject variability could have implications for the ability of optical imaging to discern tumors from background contrast variations.
Phantoms for Noninvasive Blood Glucose Sensing with Near Infrared Transmission Spectroscopy
Authors: Burmeister Jason J. , Chung Hoeil , Arnold Mark A. 
Published: January 2008

ABSTRACT In vivo spectra from human subjects can be simulated with a phantom composed of different layers of water, fat and muscle tissue. All three components are necessary to simulate in vivo spectra collected over the combination spectral region (5000–4000 cm−1). Muscle tissue is not required, however, to accurately simulate overtone spectra (6600–5400 cm−1). The near‐IR spectral characteristics of fat and muscle tissue from several animal sources are essentially identical to those found for human tissue, hence, the animal source for these phantom components is not critical. Thickness of each tissue layer can be determined by a regression analysis where the in vivo spectrum of interest is regressed against standard absorbance spectra of the necessary model components (water, fat and muscle). In general, in vivo overtone spectra collected across human webbing tissue with a thickness of 6.7 mm can be simulated with water layer thicknesses ranging from 5.0 to 6.4 mm combined with fat layer thicknesses from 1.4 to 4.2 mm.
Photoinduced Electron Transfer in Dry Gelatin Containing Bound Methylene Blue
Authors: Smith Gerald J. , Harriman Anthony , Woolhouse Anthony D. , Haskell Timothy G. , Barnes Thomas H. 
Published: January 2008

ABSTRACTExcited states of methylene blue bound to dry gelatin undergo electron‐transfer quenching reactions with neighboring amino acid residues to give reduced, methylene blue‐free radicals. At the low loadings of methylene blue bound to gelatin used in this work, the absorption spectra indicated that the methylene blue existed principally in its monomeric form. The rates of methylene blue fluorescence quenching depended on the temperature at which the gelatin was dried. There was no detectable fluorescence characteristic of the localized excited singlet state of methylene blue when the dye is bound to gelatin dried at 15°C, where a significant proportion of the protein exists in its a‐helical form. Instead, weak emission with a maximum at 645 nm is observed. It is inferred from this that the rate of quenching of any localized excited singlet states of the dye bound to a‐helical gelatin is very fast thereby competing efficiently with radiative relaxation. The weak emission at 645 nm is ascribed to a fluorescent exciplex formed between bound methylene blue and a neighboring electron/proton donor residue of the gelatin. While fluorescence characteristic of the localized methylene blue singlet state was observed from dyed gelatin dried at 50°C, i.e. in its random coil form, the triplet state is subject to rapid quenching by electron/proton transfer with protein moieties.
Furocoumarin‐induced Epidermal Melanogenesis Does Not Protect Against Skin Photocarcinogenesis in Hairless Mice
Authors: Kipp Christian , Lewis Emma J. , Young Antony R. 
Published: January 2008

ABSTRACTTopical 6,4,4′‐trimethylangelicin (TMA) plus UVA was used to induce intense epidermal pigmentation in inbred HRA.HRII‐c/+/Skh hairless pigmented mice over a 13 day period. Subsequent UVB/UVA exposure was used to assess the photoprotective properties of this tan using skin tumors as an endpoint. Comparisons were always made with sibling albino mice. The TMA/UVA treatment was shown to be not carcinogenic when treated mice were compared with untreated control mice over 25 weeks. The tan faded despite daily exposure to UVB/UVA and did not afford any protection when TMA/UVA‐treated mice with subsequent UVB/UVA were compared with pigmented mice treated with UVB/UVA only. In one group, the TMA‐induced tan was maintained by application of TMA three times a week prior to UVB/UVA for the duration of the experiment. This treatment was associated with a significant increase in tumor risk in both pigmented and albino mice compared to groups treated with UVB/UVA alone. Although pigmented mice had a significant photoprotective advantage, it was shown to be outweighed by the carcinogenic risks of the TMA maintenance treatment when they were compared with mice that did not have this treatment. Nonpretanned pigmented mice developed mild pigmentation during UVB/UVA treatment that was shown to have no protective effect when those mice were compared with albinos. We conclude that induced epidermal tanning with or without furocoumarin enhancement is not an effective way to prevent skin cancer in the HRA.HRII‐c/+/Skh mouse model.
GRP78 Induction by Calcium lonophore Potentiates Photodynamic Therapy Using the Mitochondrial Targeting Dye Victoria Blue BO
Authors: Morgan Janet , Whitaker James E. , Oseroff Allan R. 
Published: January 2008

ABSTRACTThe cationic photosensitizing triaryl methane dye Victoria Blue BO (VBBO) localizes in mitochondria and causes oxidative damage to this organelle during photodynamic therapy (PDT). Oxidative stresses from other photosensitizers induce a variety of stress proteins. The endoplasmic reticulum (ER)‐based, calcium‐binding stress protein GRP78 is a putative protective factor for photo‐sensitizers such as Photofrin® that damage multiple intracellular sites and for several cytotoxic agents. In the current study VBBO‐PDT was found to induce glucose‐regulated protein (GRP)78. However, in contrast to other drugs, rather than being protected, human squamous carcinoma cells (FaDu) induced to express GRP78 by calcium ionophore A23187 became more sensitive to PDT. A line of Chinese hamster ovary cells (C.‐1) constitutively overexpressing GRP78 also were more sensitive. Cytotoxicity of the A23187 treatment and VBBO was synergistic, with more than 11‐fold potentiation with light irradiation, but was only additive in the dark. The in‐creased cell killing was not due to differences in VBBO uptake or to changes in the intracellular localization of VBBO caused by calcium ionophore or GRP78. Thus, GRP78 appears to enhance rather than protect against VBBO‐induced mitochondrial photodamage and contributes to cell death. This novel finding possibly may stem from the effects of GRP78, ER Ca2+ stores and ATP consumption on the Ca2+ and ATP‐dependent mitochondrial permeability transition that may be evoked by PDT damage to the mitochondrial respiratory chain. The work suggests interventions that may potentiate PDT with mitochondrial targeting sensitizers and potential enhancements in efficacy when GRP78 is upregulated biologically or pharmacologically.
Photodynamic Treatment with Benzoporphyrin Derivative Monoacid Ring A Produces Protein Tyrosine Phosphorylation Events and DNA Fragmentation in Murine P815 Cells
Authors: Granville David J. , Levy Julia G. , Hunt David W. C. 
Published: January 2008

ABSTRACTTreatment with benzoporphyrin derivative monoacid ring A (BPD‐MA, verteporfin) and broad‐spectrum fluorescent light rapidly produced apoptosis in murine P815 mastocytoma cells. Fragmentation of DNA, a fundamental characteristic of cells undergoing apoptosis, was evident within 3 h following the photodynamic treatment. Western immunoblot analysis using the specific antiphosphotyrosine monoclonal antibody 4G10 indicated that molecular species of >200 kDa were phosphorylated on tyrosine residues during or immediately following the irradiation of cells loaded with BPD‐MA. Increased tyrosine phosphorylation of a 15 kDa protein was evident by 15 min postirradiation. In the absence of light, BPD‐MA did not affect the status of cellular protein tyrosine phosphorylation or cause DNA fragmentation. The protein kinase inhibitor staurosporine prevented tyrosine phosphorylation of the >200 kDa species but did not affect tyrosine phosphorylation of the 15 kDa protein or the level of DNA fragmentation produced by the photo‐dynamic treatment. The protein tyrosine phosphorylation events observed for P815 cells treated with cytotoxic levels of BPD‐MA and light may not be directly related to the induction of the apoptotic cell death pathway.
Early Induction of Binucleated Cells by Ultraviolet A (UVA) Radiation: A Possible Role of Microfilaments‡
Authors: Bånrud Hilde , Moan Johan , Berg Kristian 
Published: January 2008

AbstractThe effects of UVA (365 nm) radiation on the cellular distribution of F‐actin and formation of binucleated cells have been studied using 3T3 Swiss albino mouse fibroblasts and V79 Chinese hamster fibroblasts. Ultraviolet A at biologically relevant fluences was found to disintegrate the actin filaments in the cells shortly (5 min) after irradiation, concomitant with the formation of cells with two nuclei. In 76–100% of the bi‐ and multinucleated cells the distribution of F‐actin was clearly altered. Cells in G| phase of the cell cycle were most probably involved in the formation of binucleated cells. The disintegration of F‐actin was presumably not due to depolymerization of F‐actin to G‐actin, as the amount of F‐actin in the cells was unaltered after UVA exposure but rather due to direct breakage of the actin filaments. Ultraviolet B (297/ 302 nm) had no effect on the cellular distribution of microfilaments, not even at highly lethal fluences.
Interaction of Acrylodan with Human Serum Albumin. A Fluorescence Spectroscopic Study
Authors: Moreno Fermin , Cortijo Manuel , González‐Jiménez José 
Published: January 2008

AbstractThe binding of the fluorescent probe acrylodan (AC) to human serum albumin (HSA) was studied by fluorescence spectroscopy. The binding isotherms could be fitted to two types of sites. Competition experiments using io‐doacetamide suggested that AC binds tightly on HSA by the cysteine‐34. Attempts were made to find the location of the second site using high concentrations of warfarin, phenylbutazone, diazepam, indomethacin, palmitic acid or bilirubin in order to displace the bound AC to the HSA. Bilirubin was the only ligand able to displace the bound AC. This result suggests that AC, which is a very hydrophobic molecule also capable of labeling lysine residues, should also bind the human albumin in the primary site of bilirubin, but with less affinity than to the cysteine‐34.
Development of Intracellular Calcium Measurement by Time‐resolved Photon‐counting Fluorescence
Authors: Schoutteten Laetitia , Denjean Patrick , Joliff‐Botrel Gouenael , Bernard Christine , Pansu Danielle , Pansu Robert B. 
Published: January 2008

AbstractCalcium green I, a ratiometric probe based on fluorescence lifetime measurements, was used to monitor intracellular calcium activity ([Ca2+]1) in RINm5F cells using a time‐resolved fluorescence confocal microscope. The probe affinity constant has been recalibrated in single cells using ionomycin as a calcium ionophore and eth‐ylenebis(oxyethylenenitrilo)tetraacetic acid as a calcium buffer; KA was found to equal 150 nmol/L. The kinetics of ionomycin equilibration showed that the calcium release from calcium stores occurs before equilibration with extracellular calcium. The response to the muscarinic agonist carbachol, measured on 17 cells receiving three consecutive applications was characterized both by a [Ca2+]1 peak lasting 50 s without any trailing plateau and by desensitization with a 30% decrease in the response. The dose‐dependent response was obtained for a carbachol concentration from 5 μmol/L to 0.5 mmol/L. The ability of our set‐up to obtain a value every 10 ms enabled us to record asynchronous spikes of [Ca2+]1 in the RINm5F cells. The spikes, lasting less than 1 s, are significantly bigger than the noise, and they are not observed in the colonic HT29 cells.
Parabolic Quantitative Structure‐Activity Relationships and Photodynamic Therapy: Application of a Three‐Compartment Model with Clearance to the In Vivo Quantitative Structure‐Activity Relationships of a Congeneric Series of Pyropheophorbide Derivatives Used as Photosensitizers for Photodynamic Therapy
Authors: Potter W. R. , Henderson B. W. , Bellnier D. A. , Pandey R. K. , Vaughan L. A. , Weishaupt K. R. , Dougherty T. J. 
Published: January 2008

AbstractAn open three‐compartment pharmacokinetic model was applied to the in vivo quantitative structure‐activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0+. The measured octanol‐water partition coefficients, P1 (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three‐compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic‐based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose‐response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.
p53 Mutations in Basal Cell Carcinomas Arising in Routine Users of Sunscreens
Authors: Rosenstein Barry S. , Phelps Robert G. , Weinstock Martin A. , Bernstein Jonine L. , Gordon Marsha L. , Rudikoff Donald , Kantor Irwin , Shelton Ronald , Lebwohl Mark G. 
Published: January 2008

AbstractSun exposure histories were obtained from a series of patients age 35 or younger following diagnosis and removal of a basal cell carcinoma (BCC). The DNA was extracted from tumor biopsy samples derived from BCC of 10 patients who reported that they did not use sunscreens during youth (age 18 or younger) and 10 patients who routinely employed sunscreens during this age period. Exons 5–9 of the p53 gene were then amplified in three fragments from these samples using a nested polymerase chain reaction (PCR) approach and screened for mutations using an RNA heteroduplex assay. All PCR products displaying evidence of a mutation were sequenced. It was found that 6 of the 10 patients who were not routine sunscreen users displayed mutations in these pS3 exons. All of the mutations were located at dipyr‐imidine sites, five of the six were C ← T transitions and one mutation was a tandem double mutation, consistent with a role for solar UVB in BCC formation. In contrast, only one p53 mutation was detected in the group of 10 patients who routinely employed sunscreens during childhood and adolescence. Hence, a significantly (P= 0.029) lower level of p53 mutations was detected in the BCC obtained from sunscreen users compared with tumors derived from nonusers. These findings suggest that the mechanisms involved in the etiology of skin carcinogenesis differ in sunscreen users compared with people who did not routinely employ sunscreens. These data are also indicative of a protective effect associated with sunscreen use against the formation of p53 mutations. It is possible that the patients who were diagnosed with BCC despite their use of sunscreens possessed a genetic susceptibility for skin cancer formation and developed BCC through a p53‐independent pathway. Alternatively, solar U V A wavelengths, that were generally not blocked by the suncare products employed by the sunscreen users, may have played a significant role in BCC development through induction of a mutation(s) in an oncogene and/ or a tumor suppressor gene, other than p53, for these patients.
Measurement of In Vivo Sunscreen Immune Protection Factors in Humans
Authors: Damian Diona L. , Barnetson Ross StC. , Halliday Gary M. 
Published: January 2008

AbstractThis study investigates the level of protection provided by sunscreens against solar‐simulated UV radiation‐induced immunosuppression in humans. The in vivo immune protection factors (IPF) of two broad‐spectrum sunscreens were determined by assessing their ability to prevent UV‐induced suppression of nickel contact hypersensitivity (CHS) in 15 nickel‐allergic volunteers. Each volunteer was irradiated on unprotected skin of the back with different doses of UV daily for 4 days. Multiples of these UV doses were concurrently delivered to sunscreen‐treated sites on the contralateral back. Nickel patches were then applied to both irradiated sites and adjacent, unirradiated control sites. Nickel‐induced erythema at each site was measured 72 h later with a reflectance spectrometer. Comparison of the nickel reactions of irradiated and unirradiated skin revealed linear UV dose–responses for immunosuppression in both unprotected and sunscreen‐treated skin. The minimum level of immunosuppression that can be reliably detected with this method is 20%. Therefore, the UV dose that reduces mean nickel CHS by 20% is the minimal immune suppression dose (MISD). Sunscreen IPF were determined by dividing the mean MISD of sunscreen‐treated skin by that of unprotected skin. The sunscreens, with sun protection factors of 9 and 24, had IPF of 6.5 and >25, respectively.
The Phototumorigenic Fluoroquinolone Lomefloxacin Photosensitizes Pyrimidine Dimer Formation in Human Keratinocytes In Vitro
Authors: Traynor Nicola J. , Gibbs Neil K. 
Published: January 2008

AbstractThe fluoroquinolone antibiotic lomefloxacin is phototoxic, photogenotoxic, photomutagenic and photosensitizes tu‐morigenesis in mouse skin. We have used T4 endonucle‐ase V to demonstrate that lomefloxacin photosensitizes pyrimidine dimer formation in a human keratinocyte line (HaCaT). A possible mechanism for this effect would be triplet‐triplet energy transfer. However, there is indirect evidence that the lomefloxacin triplet yield is very low, making this reaction less likely. The finding that lomefloxacin photosensitizes production of highly mutagenic pyrimidine dimers correlates with its ability to initiate skin tumor formation in mice. Until the potential of other fluoroquinolones to photosensitize dimer formation is explored it may be unadvisable to prescribe these antibiotics to patients with defective DNA repair capacity (e.g. xeroderma pigmentosum).