bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wavelength‐dependent Photoacoustic Calorimetry Study of Melanin
Authors: Forest Susan E. , Simon John D. 
Published: January 2008

ABSTRACTPhotoacoustic calorimetry is used to examine the energy dissipation in melanin under physiological conditions (pH 7.2) following irradiation by UV and visible (VIS) light. Four different excitation wavelengths were examined: 264 nm, representative of UVC radiation, 351 nm and 400 nm (UVA‐I radiation) and 527 nm, representative of VIS radiation. Following absorption at 527 nm, essentially all of the photon energy is released nonradiatively on a sub‐nanosecond of excitation. Similar results are observed at 400 nm. At 351 nm, most of the energy was released as heat; a small amount of energy was retained (5 ± 5%). When melanin is excited at 264 nm, 29 ± 7% of the photon energy is retained by the molecule for a time period longer than a few hundred nanoseconds. These results show that a long‐lived excited state or reactive intermediate is generated upon UV irradiation, whereas all of the excitation energy is dissipated nonradiatively in the visible portion of the spectrum. These results establish that the photochemistry of melanin is wavelength dependent.
UVB Radiation Induced Increase in Quercetin: Kaempferol Ratio in Wild‐Type and Transgenic Lines of Petunia
Authors: Ryan Ken G. , Markham Kenneth R. , Bloor Stephen J. , Bradley J. Marie , Mitchell Kevin A. , Jordan Brian R. 
Published: January 2008

ABSTRACTThe use of genetically modified plants offers unique opportunities to study the role of specific flavonoids in plant UVB protection. Along with a parental wild‐type Mitchell Petunia, two transgenic lines with altered flavonoids were also examined; Lc with enhanced levels of antho‐cyanins due to the action of a maize flavonoid regulatory gene Leaf color, and AFLS that carries an antisense fla‐vonol synthase construct and is known to have reduced flavonol levels in flowers. All three lines were grown in near ambient sunlight, sunlight lacking UVB (280–320 nm) radiation and sunlight with 25% added UVB. Ultra‐violet‐B radiation induced significant reductions in the rates of leaf expansion and seedling growth in all three lines. The presence of anthocyanins did not appear to afford Lc plants any special protection from UVB. Ul‐traviolet‐B treatment induced increases in total flavonol content in young plants of all three lines, and this effect decreased with increasing leaf age. Notably, increasing UVB levels led to an increase in the ratio of quercetin: kaempferol with all three cultivars. The AFLS transgenic, contrary to expectations based on its genetic construction, had normal levels of flavonols in the leaves and the highest Q:K ratio of the three cultivars. This transgenic was the least susceptible to UVB, which may indicate an enhanced protective role for quercetin. Because both quercetin and kaempferol have similar UVB screening properties, quercetin may exert this role by other means.
Optics of a Bifacial Leaf: 3. Implications for Photosynthetic Performance
Authors: Richter T. , Fukshansky L. 
Published: January 2008

ABSTRACTOn the basis of a preceding study of light and absorption gradients in a bifacial leaf, spatial patterns of photosynthetic rate and photosynthetic saturation have been analyzed for different cases of natural illumination and different distributions of photosynthetic capacity along the depth coordinate. Two quality criteria of the spatially extended leaf photosynthetic performance arose from this analysis. One of them characterizes the range of the acceptable incident quantum fluxes between the lowest economically acceptable one and the highest still not photodamaging one. The second criterion gives the limit for the fractional part of the leaf photosynthetic capacity that can be utilized before the first photoinhibition effect at some depth occurs. It is shown how the range of the acceptable fluxes can be affected by the interplay between light and capacity gradients.
Photomodification of Cardiac Membrane: Chaotic Currents and High Conductance States in Isolated Patches
Authors: Tarr Merrill , Valenzeno Dennis Paul 
Published: January 2008

ABSTRACTWe have demonstrated previously that photomodification permeabilizes cardiac cells as evidenced by activation of a whole‐cell leak current. In this paper we report that photomodification induces in cell‐attached and inside‐out cardiac membrane patches a chaotic current. Unlike current recordings from many protein ion channels that show stepwise amplitude changes associated with open and closed states of the channel, the chaotic current consists of variable amplitude spike‐like transitions. The amplitudes of these spikes can vary from tenths to tens of picoamperes at a constant transmembrane potential. We provide evidence that the chaotic current is transmembrane rather than trans‐seal and has a voltage dependency expected for current flow through nonspecific conductance pathways. Photomodification can also induce high conductance states (greater than 500 pS) in cell‐attached and inside‐out patches. We present evidence that the high conductance state is also not related to seal breakdown. Our results suggest that both the chaotic current activity in and high conductance state of photo‐modified cardiac membrane patches result from the opening of many small conductance, nonspecific pathways through the membrane.
Stationary Headband for Clinical Time‐of‐Flight Optical Imaging at the Bedside
Authors: Hintz Susan R. , Benaron David A. , van Houten John P. , Duckworth Joshua L. , Liu Frank W. H. , Spilman Stanley D. , Stevenson David K. , Cheong Wai‐Fung 
Published: January 2008

ABSTRACTConventional brain‐imaging modalities may be limited by high cost, difficulty of bedside use, noncontinuous operation, invasiveness or an inability to obtain measurements of tissue function, such as oxygenation during stroke. Our goal was to develop a bedside clinical device able to generate continuous, noninvasive, tomographic images of the brain using low‐power nonionizing optical radiation. We modified an existing stage‐based time‐of‐flight optical tomography system to allow imaging of patients under clinical conditions. First, a stationary headband consisting of thin, flexible optical fibers was constructed. The headband was then calibrated and tested, including an assessment of fiber lengths, the existing system software was modified to collect headband data and to perform simultaneous collection of data and image reconstruction, and the existing hardware was modified to scan optically using this headband. The headband was tested on resin models and allowed for the generation of tomographic images in vitro; the headband was tested on critically ill infants and allowed for optical tomographic images of the neonatal brain to be obtained in vivo.
Clinical Evaluation of the Cutaneous Phototoxicity of 5,10,15,20‐Tetra (m‐hydroxyphenyl)chlorin
Authors: Wagnieres Georges , Hadjur Christophe , Grosjean Pierre , Braichotte Daniel , Savary Jean‐François , Monnier Philippe , van den Bergh Hubert 
Published: January 2008

ABSTRACTThe cutaneous phototoxic reaction induced by intravenous injection of 5,‐10,‐15,‐20‐tetra(m‐hydroxyphenyl)chlorin (mTHPC) has been clinically evaluated in patients undergoing photodynamic therapy. These tests were performed on the backs of 23 patients with a solar simulator at various times after drug administration ranging from 5 h to 57 days. The mTHPC doses ranged from 0.1 to 0.3 mg/kg, and the illuminations lasted from 30 s up to 8 min. These tests have shown that the duration of the skin photosensitization induced after a typical therapeutic dose of mTHPC (0.15 mg/kg) is less important than with Photofrin®(2 mg/kg). The level of mTHPC in the skin was also assessed in vivo and at times corresponding to the irradiations using an optical fiber‐based spectrofiuorometer. This study indicates that the light‐induced fluorescence spectroscopy of mTHPC enables prediction of the degree of photosensitivity of the skin.
Possible Mechanisms of Vascular Relaxation Induced by Pulsed‐UV Laser
Authors: Morimoto Yuji , Arai Tsunenori , Matsuo Hirotaka , Kikuchi Makoto 
Published: January 2008

ABSTRACTThis study was designed to examine the mechanism of vasorelaxation induced by pulsed‐UV laser. Luminal diameters of rat femoral arteries were measured prior to and following krypton‐fluoride excimer laser irradiation of 248 nm in wavelength. The diameter was enlarged to 1.3 times the preirradiated size at 1 or 10 Hz irradiation when the fluence was over 2.0 mj/pulse/mm2, while the diameter reached 1.8 times at 100 Hz with a fluence of 0.8 mj/pulse/mm2. Vasorelaxation by the 100 Hz irradiation was inhibited when the artery was pretreated with methylene blue but was enhanced with superoxide dis‐mutase. Pathological analysis revealed an ablation crater and vacuole formation in the vessel at 1 or 10 Hz irradiation, but these changes were not remarkable in the 100 Hz‐exposed sample. These findings suggest that vasorelaxation induced by the pulsed UV irradiation at 1 or 10 Hz results from structural alteration of vascular smooth muscle by the ablation crater or vacuolization. On the other hand, a possible mechanism of vasorelaxation at the 100 Hz irradiation is partially related to nitric oxide.
Caspofungin Prolongs Survival of Transiently Neutropenic Rats with Advanced-Stage Invasive Pulmonary Aspergillosis
Authors: van de Sande Wendy W. J. , van Vianen Wim , ten Kate Marian T. , Vissers Jolanda , Laurijsens John , Tavakol Mehri , Rijnders Bart J. A. , Mathot Ron A. A. , Bakker-Woudenberg Irma A. J. M. 
Published: January 2008

ABSTRACT

A high-dose-step-down strategy for caspofungin treatment was evaluated in an experimental model of advanced-stage invasive pulmonary aspergillosis. The therapeutic efficacy of caspofungin in relation to the severity of invasive pulmonary infection caused by
Aspergillus fumigatus
in transiently neutropenic rats was investigated by using rat survival and the decrease in the fungal burden as the parameters of efficacy. When treatment was started at either 16 h or 24 h after fungal inoculation, caspofungin administered intraperitoneally at 4 mg/kg of body weight/day for 10 days was highly effective (100% and 93% rat survival, respectively). However, only 27% rat survival was obtained when treatment was started at 72 h, when the rats had advanced-stage infection. Increasing the dose from 4 to 10 mg/kg/day could compensate for the decrease in efficacy and resulted in 67% rat survival. The high dose of 10 mg/kg/day for 10 days did not appear to be necessary since a high-dose-step-down dosing schedule with 10 mg/kg/day for 3 days followed by 4 mg/kg/day for 7 days was equally effective. At 10 days after the end of treatment with 10 mg/kg/day caspofungin, the level of neither
A. fumigatus
DNA nor
A. fumigatus
galactomannan in the infected left lung was significantly decreased. In contrast,
A. fumigatus
galactomannan concentrations in serum were significantly decreased. The levels of creatinine, blood urea nitrogen, alanine aminotransferase, and asparate aminotransferase were not elevated during treatment. Caspofungin is effective for the treatment of invasive pulmonary aspergillosis in transiently neutropenic rats and is even effective in rats with advanced-stage infection. In this model, the administration of high-dose-step-down treatment was as effective as treatment with high doses for the whole treatment period.
Epigallocatechin Gallate Inactivates Clinical Isolates of Herpes Simplex Virus
Authors: Isaacs Charles E. , Wen Guang Y. , Xu Weimin , Jia Jun Hua , Rohan Lisa , Corbo Christopher , Di Maggio Vincenzo , Jenkins Edmund C. , Hillier Sharon 
Published: January 2008

ABSTRACTIn the absence of a fully effective herpes simplex virus (HSV) vaccine, topical microbicides represent an important strategy for preventing HSV transmission. (−)-Epigallocatechin gallate (EGCG) (molecular weight, 458.4) is the primary catechin in green tea. The present study shows that EGCG has greater anti-HSV activity than other green tea catechins and inactivates multiple clinical isolates of HSV type 1 (HSV-1) and HSV-2. EGCG reduced HSV-2 titers by ≥1,000-fold in 10 to 20 min and reduced HSV-1 titers by the same amount in 30 to 40 min. The anti-HSV activity of EGCG is due to a direct effect on the virion, and incubating Vero and CV1 cells with EGCG for 48 h prior to infection with HSV-1 and HSV-2, respectively, does not reduce HSV production. Electron microscopic (EM) studies showed that purified virions exposed to EGCG were damaged, and EM immunogold labeling of the envelope glycoproteins gB and gD was significantly reduced following EGCG treatment while capsid protein labeling was unchanged. When purified HSV-1 envelope glycoproteins gB and gD were incubated with EGCG and then examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, lower-molecular-weight gB and gD bands decreased and new higher-molecular-weight bands appeared, indicating the EGCG-dependent production of macromolecular complexes. gB and gD are essential for HSV infectivity, and these results suggest that EGCG could inactivate HSV virions by binding to gB, gD, or another envelope glycoprotein. EGCG is stable in the pH range found in the vagina and appears to be a promising candidate for use in a microbicide to reduce HSV transmission.
Conserved Water Molecules Stabilize the Ω-Loop in Class A β-Lactamases
Authors: Bös Fabian , Pleiss Jürgen 
Published: January 2008

ABSTRACTA set of 49 high-resolution (≤2.2 Å) structures of the TEM, SHV, and CTX-M class A β-lactamase families was systematically analyzed to investigate the role of conserved water molecules in the stabilization of the Ω-loop. Overall, 13 water molecules were found to be conserved in at least 45 structures, including two water positions which were found to be conserved in all structures. Of the 13 conserved water molecules, 6 are located at the Ω-loop, forming a dense cluster with hydrogen bonds to residues at the Ω-loop as well as to the rest of the protein. This layer of conserved water molecules is packed between the Ω-loop and the rest of the protein and acts as structural glue, which could reduce the flexibility of the Ω-loop. A correlation between conserved water molecules and conserved protein residues could in general not be detected, with the exception of the conserved water molecules at the Ω-loop. Furthermore, the evolutionary relationship between the three families, derived from the number of conserved water molecules, is similar to the relationship derived from phylogenetic analysis.
P-Glycoprotein Limits Oral Availability, Brain Penetration, and Toxicity of an Anionic Drug, the Antibiotic Salinomycin
Authors: Lagas Jurjen S. , Sparidans Rolf W. , van Waterschoot Robert A. B. , Wagenaar Els , Beijnen Jos H. , Schinkel Alfred H. 
Published: January 2008

ABSTRACT
Salinomycin is a polyether organic anion that is extensively used as a coccidiostatic antibiotic in poultry and commonly fed to ruminant animals to improve feed efficiency. However, salinomycin also causes severe toxicity when accidentally fed to animals in high doses. In addition, humans are highly sensitive to salinomycin and severe toxicity has been reported. Multidrug efflux transporters like P-glycoprotein (P-gp), BCRP, and MRP2 are highly expressed in the intestine and can restrict the oral uptake and tissue penetration of xenobiotics. The purpose of this study was to investigate whether the anionic drug salinomycin is a substrate for one or more of these efflux pumps. Salinomycin was actively transported by human MDR1 P-gp expressed in polarized MDCK-II monolayers but not by the known organic anion transporters human MRP2 and murine Bcrp1. Using P-gp-deficient mice, we found a marked increase in plasma salinomycin concentrations after oral administration and decreased plasma clearance after intravenous administration. Furthermore, absence of P-gp resulted in significantly increased brain penetration. P-gp-deficient mice also displayed clearly increased susceptibility to salinomycin toxicity. Thus far, P-gp was thought to affect mainly hydrophobic, positively charged or neutral drugs in vivo. Our data show that P-gp can also be a major determinant of the pharmacokinetic behavior and toxicity of an organic anionic drug. Variation in P-gp activity might thus directly affect the effective exposure to salinomycin and possibly to other anionic drugs and toxin substrates. Individuals with reduced or absent P-gp activity could therefore be more susceptible to salinomycin toxicity.
Comparative Efficacies of Rifaximin and Vancomycin for Treatment of
Clostridium difficile
-Associated Diarrhea and Prevention of Disease Recurrence in Hamsters
Authors: Kokkotou Efi , Moss Alan C. , Michos Athanasios , Espinoza Daniel , Cloud Jeffrey W. , Mustafa Nasima , O'Brien Michael , Pothoulakis Charalabos , Kelly Ciarán P. 
Published: January 2008

ABSTRACT

Clostridium difficile
-associated colitis is an increasing cause of morbidity and mortality in hospitalized patients, with high relapse rates following conventional therapy. We sought to determine the efficacy of rifaximin, a novel nonabsorbed antibiotic, in the hamster model of
C. difficile
-associated diarrhea (CDAD). Hamsters received clindamycin subcutaneously and 24 h later were infected by gavage with one of two
C. difficile
strains: a reference strain (VPI 10463) and a current epidemic strain (BI17). Vancomycin (50 mg/kg of body weight) or rifaximin (100, 50, and 25 mg/kg) were then administered orally for 5 days beginning either on the same day as infection (prevention) or 24 h later (treatment). Therapeutic effects were assessed by weight gain, histology, and survival. We found that rifaximin was as effective as vancomycin in the prevention and treatment of colitis associated with the two
C. difficile
strains that we examined. There was no relapse after treatment with vancomycin or rifaximin in hamsters infected with the BI17 strain. Hamsters infected with the VPI 10463 strain and treated with rifaximin did not develop relapsing infection within a month of follow-up, whereas the majority of vancomycin-treated animals relapsed (0% versus 75%, respectively;
P
< 0.01). In conclusion, rifaximin was found to be an effective prophylactic and therapeutic agent for CDAD in hamsters and was not associated with disease recurrence. These findings, in conjunction with the pharmacokinetic and safety profiles of rifaximin, suggest that it is an attractive candidate for clinical use for CDAD.
In Vitro Activities of 35 Double Combinations of Antifungal Agents against
Scedosporium apiospermum
and
Scedosporium prolificans
Authors: Cuenca-Estrella Manuel , Alastruey-Izquierdo Ana , Alcazar-Fuoli Laura , Bernal-Martinez Leticia , Gomez-Lopez Alicia , Buitrago Maria J. , Mellado Emilia , Rodriguez-Tudela Juan L. 
Published: January 2008

ABSTRACT

Activities of 35 combinations of antifungal agents against
Scedosporium
spp. were analyzed by a checkerboard microdilution design and the summation of fractional concentration index. An average indifferent effect was detected apart from combinations of azole agents and echinocandins against
Scedosporium apiospermum
. Antagonism was absent for all antifungal combinations against both species.
Effects on Gram-Negative and Gram-Positive Bacteria Mediated by 5-Aminolevulinic Acid and 5-Aminolevulinic Acid Derivatives
Authors: Fotinos Nicolas , Convert Maruska , Piffaretti Jean-Claude , Gurny Robert , Lange Norbert 
Published: January 2008

ABSTRACT

Due mainly to the extensive use of antibiotics, the spread of multiresistant bacterial strains is one of the most worrying threats to public health. One strategy that can be used to overcome potential shortcomings might be the inactivation of these microorganisms by 5-aminolevulinic acid (5-ALA) or 5-ALA derivative-mediated photodynamic therapy (PDT). 5-ALA has no photoactive properties, but when it is given exogenously, it acts as a precursor of photosensitive porphyrins predominantly in tissues or organisms that are characterized by a high metabolic turnover, such as tumors, macrophages, and bacteria. However, the weak ability of 5-ALA to cross biological barriers has led to the introduction of more lipophilic derivatives, such as methyl aminolevulinate or hexyl aminolevulinate, which display improved capacities to reach the cytoplasm. Starting from the hypothesis that more lipophilic compounds carrying only a permanent positive charge under physiological conditions may more easily cross the bacterial multilayer barrier, we have tested the efficacies of some 5-ALA
n
-alkyl esters for the inactivation of bacteria. For this purpose, different bacterial strains were incubated with 5-ALA or its corresponding esters of different lipophilicities. Then, the bacteria were irradiated with light and the numbers of CFU post-PDT were counted and compared to those for the controls, which were kept in the dark. Furthermore, the total amount of accumulated porphyrins was quantified by high-pressure liquid chromatography analysis. In our studies, analysis of the bacterial extracts revealed the presence of all the porphyrins involved in heme biosynthesis, from uroporphyrin to protoporphyin IX. The efficacy of bacterial inactivation was a function of the total amount of porphyrins produced, independently of their nature. The 5-ALA methyl and butyl esters were the most effective compounds with respect to the photodynamic inactivation of bacteria. We observed significant differences in terms of the optimal drug concentration, bactericidal activities, and porphyrin production.
Drug-Regulated Expression ofPlasmodium falciparumP-Glycoprotein Homologue 1: a Putative Role for Nuclear Receptors
Authors: Johnson David J. , Owen Andrew , Plant Nick , Bray Patrick G. , Ward Stephen A. 
Published: January 2008

ABSTRACTAcquired resistance to therapeutic agents is a major clinical concern in the prevention/treatment of malaria. The parasite has developed resistance to specific drugs through two mechanisms: mutations in target proteins such as dihydrofolate reductase and the bc1 complex for antifolates and nathoquinones, respectively, and alterations in predicted parasite transporter molecules such as P-glycoprotein homologue 1 (Pgh1) andPlasmodium falciparumCRT (PfCRT). Alterations in the expression of Pgh1 have been associated with modified susceptibility to a range of unrelated drugs. The molecular mechanism(s) that is responsible for this phenotype is unknown. We have shown previously (A. M. Ndifor, R. E. Howells, P. G. Bray, J. L. Ngu, and S. A. Ward, Antimicrob. Agents Chemother. 37:1318-1323, 2003) that the anticonvulsant phenobarbitone (PB) can induce reduced susceptibility to chloroquine (CQ) inP. falciparum, and in the current study, we provide the first evidence for a molecular mechanism underlying this phenomenon. We demonstrate that pretreatment with PB can elicit decreased susceptibility to CQ in both CQ-resistant and CQ-sensitive parasite lines and that this is associated with the increased expression of the drug transporter Pgh1 but not PfCRT. Furthermore, we have investigated the proximal promoter regions from bothpfmdr1andpfcrtand identified a number of putative binding sites for nuclear receptors with sequence similarities to regions known to be activated by PB in mammals. Whole-genome analysis has revealed a putative nuclear receptor gene, providing the first evidence that nuclear receptor-mediated responses to drug exposure may be a mechanism of gene regulation inP. falciparum.
Microdialysis Study of Imipenem Distribution in the Peritoneal Fluid of Rats with Experimental Acute Pancreatitis
Authors: Lefeuvre Sandrine , Marchand Sandrine , Pariat Claudine , Lamarche Isabelle , Couet William 
Published: January 2008

ABSTRACT
Imipenem distribution was characterized by microdialysis in the peritoneal fluid of rats with experimental pancreatitis. The ratios of peritoneal fluid to blood area under unbound concentration-versus-time curves were close to unity, suggesting that imipenem was not degraded in peritoneal fluid.