bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contact allergen nickel sensitizes primary human endothelial cells and keratinocytes to TRAIL‐mediated apoptosis
Authors: Schmidt Marc , Hupe Mike , Endres Nicole , Raghavan Badrinarayanan , Kavuri Shyam , Geserick Peter , Goebeler Matthias , Leverkus Martin 
Published: June 2009

AbstractPrimary endothelial cells are fully resistant to TNF‐related apoptosis‐inducing ligand (TRAIL)‐mediated apoptosis. Here, we demonstrate that certain environmental conditions, such as exposure to the widespread allergen nickel, can dramatically increase the susceptibility of naturally resistant primary endothelial cells or keratinocytes to TRAIL‐induced apoptosis. While nickel treatment increased surface expression of the apoptosis‐inducing TRAIL receptors TRAIL‐R1 and TRAIL‐R2, it also up‐regulated the apoptosis‐deficient TRAIL‐R4, suggesting that modulation of TRAIL receptor expression alone is unlikely to fully account for the dramatic sensitization effect of nickel. Further analysis of candidate mediators revealed that nickel strongly repressed c‐FLIP at mRNA and protein levels. Accordingly, increased activation of Caspase‐8 and Caspase‐3 following nickel treatment was observed. Importantly, depletion of c‐FLIP by RNA interference could largely recapitulate the effect of nickel and sensitize endothelial cells to TRAIL‐dependent apoptosis in the absence of nickel pre‐treatment. Conversely, ectopic expression of c‐FLIPL largely protected nickel‐treated cells from TRAIL‐mediated apoptosis. Our data demonstrate that one key mechanism of sensitization of primary human endothelial cells or keratinocytes is transcriptional down‐regulation of c‐FLIP. We hypothesize that environmental factors, exemplified by the contact allergen nickel, strongly modulate death ligand sensitivity of endothelial cells and keratinocytes thus influencing vascular and epidermal function and integrity under physiological and pathophysiological conditions.
Cutaneous metastases as the first clinical sign of metastatic gastric carcinoma
Authors: Frey Lidia , Vetter‐Kauczok Claudia , Gesierich Anja , Bröcker Eva‐B. , Ugurel Selma 
Published: June 2009

SummaryCutaneous metastases from gastric cancer are uncommon with a frequency of 7 % but can rarely be the presenting sign. A 54‐year‐old man complained of multiple pea‐sized scalp nodules which had been present for four months. Histology showed a metastatic adenocarcinoma. Initial evaluation revealed liver metastases and gastroscopy then identified a tumor involving the distal esophagus and gastric cardia that was diagnosed as a gastric tubular carcinoma. The patient had a good response to polychemotherapy. While gastric carcinoma generally metastasizes to the abdominal wall or lymph nodes, our patient showed an exceptional variant with distant cutaneous metastases as the first clinical sign.
Localization and Dynamic Change of Saponin in Vegetative Organs of Polygala tenuifolia
Authors: Teng Hong‐Mei , Fang Min‐Feng , Cai Xia , Hu Zheng‐Hai 
Published: June 2009

Abstract Anatomical, histochemical and phytochemical methods were used to investigate the structure, localization and dynamic changes of total saponin and senegenin of vegetative organs in Polygala tenuifolia Willd. Histochemical localization results showed that saponin accumulated mainly in parenchyma cells of vegetative organs. The phytochemical results also showed that the saponin accumulated in the vegetative organs of P. tenuifolia, with higher content in roots and lower content in the aerial parts that included stems and leaves. The saponin content and dry weight of the vegetative organs of P. tenuifolia had dynamic variance at the developmental stages and all reached the highest level in the post‐fruit period. Hence, the roots and aerial parts should be gathered in August to make full use of the plant. As the root is the main medicinal organ of P. tenuifolia, the content of total saponin and senegenin of different aged and different parts of the root were determined. The content of total saponin and senegenin exhibited a sustained decreasing trend with increasing root age; therefore, the annual roots had high quality. The content of total saponin and senegenin in different parts of the root showed obvious variation. The content in the “skin areas” was much higher than that of xylem. The results offer a theoretical basis for determining the appropriate harvesting stage and a reasonable harvest of P. tenuifolia.
Jasmonic Acid is Induced in a Biphasic Manner in Response of Pea Seedlings to Wounding
Authors: Yang Hao‐Ru , Tang Ke , Liu Hong‐Tao , Pan Qiu‐Hong , Huang Wei‐Dong 
Published: June 2009

Abstract The role of jasmonic acid (JA) in plant wounding response has been demonstrated. However, the source of JA in wound signaling remains unclear. In the present study, pea seedlings were used as material to investigate the systemic induction of JA and the activation of lipoxygenase (LOX)‐dependent octadecanoid pathway upon wounding. The results showed that endogenous JA could induce two peaks in the wounded leaves and the stalks, while only one peak in the systemic leaves. LOX activity and its protein amount were also induced and the stimulation mainly occurred in the late phase, while one peak of induction was present after pretreatment with JA. Applied nordihydroguaiaretic acid (NDGA), an inhibitor of LOX activity, only inhibited the induction of JA in the late phase, and the resistance of pea was impaired. Furthermore, 13(S)‐hydroperoxy‐9(Z), 11(E)‐octadecadienoic acid (13(S)‐H(P)ODE) was confirmed to be the main product of LOX throughout the experimental time. In addition, immunocytochemical analysis also revealed the occurrence of JA biosynthesis and transport upon wounding. These results demonstrated that wound‐induced JA in wounded leaves resulted from its biosynthesis and conversion from its conjugates, while in systemic leaves resulted from its transport and biosynthesis; and proved that the LOX pathway was vital to the wound‐induced defense response involved in JA biosynthesis.
DRYING OF CHILI PEPPER (CAPSCIUM FRUTSCENS)
Authors: TUNDE‐AKINTUNDE T.Y. , AFOLABI T.J. 
Published: June 2009

ABSTRACT Drying is one of the common methods of food preservation and is carried out on untreated/unblanched and treated/blanched chili pepper using sun, solar and hot‐air drying. The drying curves generated from the three methods showed that drying of treated/blanched pepper was faster than that of untreated/unblanched pepper. The drying rate period observed for all the methods and samples was the falling rate drying regime. This suggests that the blanching pretreatment assisted water loss and thus decreased the resistance to water loss at the surface of the product. The drying time of the dried pepper varied from 27 h for hot‐air drying to 144.5 h for sun drying respectively. The values of moisture diffusivity coefficient ranged from 2.163 × 10−9 m2/s for hot‐air drying to 1.125 × 10−9 m2/s for sun drying.PRACTICAL APPLICATIONSA common method of preserving pepper, a vegetable with versatile use, is drying and this is done by sun, solar and oven‐drying methods. Climatic variations of sun and solar drying make it unsuitable for large‐scale production. Hot‐air drying is thus considered as an alternative drying method because it decreases drying time and improves the hygienic quality of the dried product. Pretreating pepper by blanching increases its rate of drying. The effect of each drying method on the drying rate, equilibrium moisture content and moisture diffusivity coefficient were used to compare the drying methods. Hot‐air drying had the lowest drying time whereas pretreated samples also dried faster. The effective moisture diffusivity of oven dried samples as well as pretreated samples were highest. This indicates that oven drying reduces drying time and can be used to dry pepper samples for large‐scale production.
ISOLATION OF CAFFEINE FROM TEA WASTE USING SUBCRITICAL WATER EXTRACTION
Authors: SHALMASHI ANVAR , ABEDI MOHAMMAD , GOLMOHAMMAD FERESHTEH , EIKANI MOHAMMAD HASSAN 
Published: June 2009

ABSTRACT The aim of this study was to investigate the isolation of caffeine from tea waste using subcritical water extraction (SCWE) method. The effect of various operating conditions such as water temperature (100,125,150, 175 and 200C), water flow rate (1, 2 and 4 g/min), mean particle size (0.25, 0.5, 1 and 2 mm) and pressure (20, 30 and 40 bar) on extraction yield and rate were determined. SCWE at 175C, water flow rate of 4 g/min and mean particle size of 0.5 mm was found to be able to recover 0.77% (w/w) of caffeine present in the tea waste within 1.5 h of extraction. In comparison with the SCWE, conventional hot water extraction showed 0.46% (w/w) extraction yield. It was found also that pressure had no effect on extraction yield and rate. A sustainable and environmentally friendly procedure has been used for the Fourier transform infrared determination of caffeine in tea waste extracted samples. PRACTICAL APPLICATIONSSubcritical water extraction (SCWE), as a green solvent, can be used in many different fields of applications. It can be used to extract antioxidant compounds from rosemary plants as well as to extract whitening agents and azo dyes in samples. Additionally, soil can be remediated through SCWE of dioxins. Recently, subcritical water has become of great interest as an alternative solvent for extraction of natural active compounds. In recent years, extraction of flavors, fragrances and antioxidant components from plant materials, and hydrolysis of carbohydrates, vegetable oils and fatty acids have been widely investigated by many researchers. Using subcritical water as a reaction media are some other interesting fields for practical applications.
EFFECT OF SURIMI CONTAINING SPENT LAYING HEN BREAST ON THE QUALITY OF CRAB ANALOGUE
Authors: JIN S.K. , KIM I.S. , CHOI Y.J. , KIM B.G. , HUR S.J. 
Published: June 2009

ABSTRACT The crab analogue samples were made from Alaska pollack with golden threadfin bream surimi (Control), and a combination of Alaska pollack with golden threadfin bream surimi and a low amount of spent hen breast surimi (treatment 1, T1). Treatment 2 (T2) was made from Alaska pollack with golden threadfin bream surimi and a high amount of spent hen breast surimi, and treatment 3 (T3) was made from Alaska pollack with golden threadfin bream with mechanically deboned chicken meat (MDCM). T3 shows a significantly lower moisture amount compared with other samples. Crude protein was higher in T1 than in other samples at 4 weeks of storage. pH was significantly lower in control (C) than those of other samples until 2 weeks of storage, and cooking loss was higher in C than in other samples, while shear force and cholesterol were higher in T3 compared with other samples. In meat color, lightness (L*) was significantly higher in T2 than in other samples. Whiteness of T2 was significantly higher compared with that of other samples. In fatty acid composition, saturated fatty acid was significantly higher in T3, while unsaturated fatty acid was higher in C than in other samples. C showed significantly higher thiobarbituric acid‐reactive substances (TBARS) value, while TBARS value was lower in T2 compared with other samples. In sensory evaluation, the color and overall acceptability were significantly lower in T3 compared with other samples. These results demonstrated that the crab analogue product could be made from spent hen breast, although the quality of crab analogue containing MDCM sample (T3) is a little lower than other crab analogue samples.PRACTICAL APPLICATIONSThe application of the surimi technology in the production of a surimi‐based product from other meats such as chicken, pork and beef could provide a new approach toward increasing its value and utilization. In the present study, imitation crab analogue was made from surimi containing spent laying hen breast with various ingredients. Imitation crab analogue product can be made from spent laying hen breast, although the quality of imitation crab analogue containing mechanically deboned chicken meat is a little lower than that of other imitation crab analogue samples.
seqphase: a web tool for interconverting phase input/output files and fasta sequence alignments
Authors: FLOT J‐F. 
Published: June 2009

AbstractThe program phase is widely used for Bayesian inference of haplotypes from diploid genotypes; however, manually creating phase input files from sequence alignments is an error‐prone and time‐consuming process, especially when dealing with numerous variable sites and/or individuals. Here, a web tool called seqphase is presented that generates phase input files from fasta sequence alignments and converts phase output files back into fasta. During the production of the phase input file, several consistency checks are performed on the dataset and suitable command line options to be used for the actual phase data analysis are suggested. seqphase was written in perl and is freely accessible over the Internet at the address http://www.mnhn.fr/jfflot/seqphase.
Cytochrome P450 3A Inhibition by Atazanavir and Ritonavir, but Not Demography or Drug Formulation, Influences Saquinavir Population Pharmacokinetics in Human Immunodeficiency Virus Type 1-Infected Adults
Authors: von Hentig Nils , Lötsch Jörn 
Published: June 2009

ABSTRACTInadequate concentrations of the human immunodeficiency virus (HIV) protease inhibitor saquinavir jeopardize individual therapy success or produce side effects despite treatment according to the current guidelines. We performed a population pharmacokinetic analysis with NONMEM and determined that the steady-state pharmacokinetics of saquinavir in 136 HIV type 1-infected adults was modulated by a decrease in saquinavir CL following coadministration of the cytochrome P450 3A inhibitors ritonavir and atazanavir. In contrast, age, sex, weight, pregnancy, and the pharmaceutical formulation exerted only minor, nonsignificant effects.
New Semiphysiological Absorption Model To Assess the Pharmacodynamic Profile of Cefuroxime Axetil Using Nonparametric and Parametric Population Pharmacokinetics
Authors: Bulitta J. B. , Landersdorfer C. B. , Kinzig M. , Holzgrabe U. , Sorgel F. 
Published: June 2009

ABSTRACT

Cefuroxime axetil is widely used to treat respiratory tract infections. We are not aware of a population pharmacokinetic (PK) model for cefuroxime axetil. Our objectives were to develop a semiphysiological population PK model and evaluate the pharmacodynamic profile for cefuroxime axetil. Twenty-four healthy volunteers received 250 mg oral cefuroxime as a suspension after a standardized breakfast. Liquid chromatography-tandem mass spectrometry was used for drug analysis, NONMEM and S-ADAPT (results reported) were used for parametric population PK modeling, and NPAG was used for nonparametric population PK modeling. Monte Carlo simulations were used to predict the duration for which the non-protein-bound-plasma concentration was above the MIC (
f
T
>MIC
). A model with one disposition compartment, a saturable and time-dependent drug release from the stomach, and fast drug absorption from the intestine yielded precise (
r
> 0.992) and unbiased curve fits and an excellent predictive performance. The apparent clearance was 21.7 liters/h (19.8% coefficient of variation [CV]) and the volume of distribution 38.7 liters (18.3% CV). Robust (≥90%) probabilities of target attainment (PTAs) were achieved by 250 mg cefuroxime given every 12 h (q12h) or q8h for MICs of ≤0.375 mg/liter or ≤0.5 mg/liter, respectively, for the bacteriostasis target
f
T
>MIC
of ≥40% and for MICs of ≤0.094 mg/liter or ≤0.375 mg/liter, respectively, for the near-maximal-killing target
f
T
>MIC
of ≥65%. For the ≥40%
f
T
>MIC
target, the PTAs for 250 mg cefuroxime q12h were ≥97.8% for
S
treptococcus pyogenes
and penicillin-susceptible
S
treptococcus pneumoniae
. Cefuroxime at 250 mg q12h or q8h achieved PTAs below 73% or 92%, respectively, for
H
aemophilus influenzae
,
M
oraxella catarrhalis
, and penicillin-intermediate
S. pneumoniae
for susceptibility data from various countries. Depending on the MIC distribution, 250 mg oral cefuroxime q8h instead of q12h should be considered, especially for more-severe infections that require near-maximal killing by cefuroxime.
Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects
Authors: Ginsberg Ann M. , Laurenzi Martino W. , Rouse Doris J. , Whitney Karl D. , Spigelman Melvin K. 
Published: June 2009

ABSTRACT

PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant
Mycobacterium tuberculosis
. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic
Mycobacterium tuberculosis
. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant
Mycobacterium tuberculosis
, support the investigation of this novel compound for the treatment of tuberculosis.
In Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial Agent
Authors: Schaadt Ronda , Sweeney Debora , Shinabarger Dean , Zurenko Gary 
Published: June 2009

ABSTRACT

TR-701 is the prodrug of the microbiologically active molecule TR-700, a novel orally and intravenously administered oxazolidinone antibacterial agent. The in vitro activity of TR-700 was evaluated against 1,063 bacterial clinical isolates including staphylococci, enterococci, streptococci,
Moraxella catarrhalis
,
Haemophilus influenzae
, and a variety of anaerobic bacterial species. The test strains were recent (2005 to 2008) clinical isolates from diverse U.S. (80%) and non-U.S. (20%) sites. MIC assays were conducted using reference broth microdilution and agar dilution methods with the principal comparators linezolid and vancomycin. TR-700 was four- to eightfold more potent than linezolid against staphylococci and generally fourfold more potent against enterococci and streptococci. TR-700 was less active against
M. catarrhalis
and
H. influenzae
but was twofold more active than linezolid. Against anaerobic species, the activity of TR-700 was equivalent to or up to fourfold higher than that of linezolid. These results indicate that TR-700 is a promising new oxazolidinone antibacterial agent with greater in vitro potency than linezolid against clinically important gram-positive bacteria.
Efficacy of Combination Antifungal Therapy with Intraperitoneally Administered Micafungin and Aerosolized Liposomal Amphotericin B against Murine Invasive Pulmonary Aspergillosis
Authors: Takazono Takahiro , Izumikawa Koichi , Mihara Tomo , Kosai Kosuke , Saijo Tomomi , Imamura Yoshifumi , Miyazaki Taiga , Seki Masafumi , Kakeya Hiroshi , Yamamoto Yoshihiro , Yanagihara Katsunori , Kohno Shigeru 
Published: June 2009

ABSTRACTTargeted intrapulmonary delivery of drugs may reduce systemic toxicity and improve treatment efficacy. In the current study, we evaluated the effects of a combination treatment consisting of inhalation of aerosolized liposomal amphotericin B (L-AMB) with intraperitoneal administration of micafungin (MCFG) against murine invasive pulmonary aspergillosis. The combination of aerosolized L-AMB with intraperitoneal MCFG significantly improved the survival rate, and the fungal burdens and histopathology findings after this treatment were superior to those of the control and both monotherapy groups.
Genetics of Chromosomally Mediated Intermediate Resistance to Ceftriaxone and Cefixime in
Neisseria gonorrhoeae
Authors: Zhao Shuqing , Duncan Margaret , Tomberg Joshua , Davies Christopher , Unemo Magnus , Nicholas Robert A. 
Published: June 2009

ABSTRACT

All strains of
Neisseria gonorrhoeae
with reduced susceptibility to ceftriaxone and cefixime (cephalosporin-intermediate-resistant [Ceph
i
] strains) contain a mosaic
penA
allele encoding penicillin-binding protein 2 (PBP 2) with nearly 60 amino acid differences compared to the sequence of wild-type PBP 2, together with a set of resistance determinants (i.e.,
mtrR
,
penB
, and/or
ponA1
) that are required for high-level penicillin resistance. To define the individual contributions of these determinants to reduced susceptibility to ceftriaxone and cefixime, we created isogenic strains containing the mosaic
penA
allele from the Ceph
i
strain 35/02 (
penA35
) together with one or more of the other resistance determinants and determined the MICs of penicillin G, ceftriaxone, and cefixime. The majority of cefixime resistance is conferred by the
penA35
allele, with only a small contribution coming from
mtrR
and
penB
, whereas ceftriaxone resistance is nearly equally dependent upon
mtrR
and
penB
. Unlike high-level penicillin resistance, the
ponA1
allele does not appear to be important for Ceph
i
. A strain containing all four determinants has increased resistance to ceftriaxone and cefixime but not to the levels that the donor Ceph
i
strain does, suggesting that Ceph
i
strains, similar to high-level-penicillin-resistant strains, contain an additional unknown determinant that is required to reach donor levels of resistance. Our data also suggest that the original Ceph
i
strains arose from the transformation of
penA
genes from commensal
Neisseria
species into a penicillin-resistant strain already harboring
mtrR
,
penB
,
ponA1
, and the unknown gene(s) involved in high-level penicillin resistance.
VanA-Type
Staphylococcus aureus
Strain VRSA-7 Is Partially Dependent on Vancomycin for Growth
Authors: Moubareck Carole , Meziane-Cherif Djalal , Courvalin Patrice , Périchon Bruno 
Published: June 2009

ABSTRACT

VanA-type
Staphylococcus aureus
strain VRSA-7 was partially dependent on glycopeptides for growth. The
vanA
gene cluster, together with the
erm
(A) and the
ant(9)-Ia
resistance genes, was carried by the ca. 35- to 40-kb conjugative plasmid pIP848 present at five copies per cell. The chromosomal
ddl
gene had a mutation that led to a N
308
K substitution in the
d
-Ala:
d
-Ala ligase that resulted in a 1,000-fold decrease in activity relative to that of strain VRSA-6. Strain VRSA-7 grown in the absence or in the presence of vancomycin mainly synthesized precursors ending in
d
-Ala-
d
-Lac, indicating that the strain relied on the vancomycin resistance pathway for peptidoglycan synthesis. Greatly enhanced growth in the presence of glycopeptides and the absence of mutations in the genes for VanR and VanS indicated the inducible expression of resistance. Thus, a combination of loose regulation of the
vanA
operon by the two-component system and a gene dosage effect accounts for the partial glycopeptide dependence of VRSA-7. Since peptidoglycan precursors ending in
d
-Ala-
d
-Lac are not processed by PBP 2′, the strain was fully susceptible to oxacillin, despite the production of a wild-type PBP 2′.