bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curcumin improves expression of SCF/c-kit through attenuating oxidative stress and NF-κB activation in gastric tissues of diabetic gastroparesis rats
Authors: Jin Qi-Hui , Shen Hong-Xia , Wang Hui , Shou Qi-Yang , Liu Qiang 
Published: March 2013

AbstractBackgroundDiabetes mellitus is associated with many kinds of complications. Recent studies have shown that oxidative stress and inflammatory reactions have critical roles in the pathogenesis of diabetic gastroparesis. Curcumin is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on diabetic gastric motility in a Sprague Dawley rat model of type 1 diabetes mellitus.MethodsMale SD rats were divided into a control group, a control group receiving curcumin, a diabetic group, and a diabetic group receiving curcumin. Diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin (150 mg/kg) was given intragastrically for 6 weeks, and blood glucose levels and body weights were measured. Stomachs were excised for analysis of gastric emptying rates, and levels of oxidative stress. NF-κB, I-κB, and stem cell factor (SCF)/c-kit protein levels were assessed by western blot analysis, while the apoptosis of interstitial cells of Cajal (ICCs) was assessed by TUNEL staining.ResultsCurcumin-treated diabetic rats showed significantly improved gastric emptying rates [(59.4 ± 7.5)%] compared with diabetic rats [(44.3 ± 5.7)%], as well as decreased levels of MDA [21.4 ± 1.8 (nmol/mg)vs27.9 ± 2.1 (nmol/mg)], and increased SOD activity [126.2 ± 8.8 (units/mg)vs107.9 ± 7.5 (units/mg)]. On the other hand, the gastric emptying level in the control group was not significantly different from that in the control group receiving curcumin treatment. In addition, curcumin-treated diabetic rats showed significantly increased levels of SCF/c-kit protein in stomach tissues, inhibited I-κB degradation and NF-κB activation, and reduced ICC apoptosis index [(26.2 ± 4.1)%vs(47.5 ± 6.2)%], compared with the diabetic group.ConclusionCurcumin treatment improved gastric emptying by blocking the production of oxidative stress, abolishing NF-κB signal transduction and enhancing expression of SCF/c-kit in rats with diabetic gastroparesis.
Diabetic status and the relation of the three domains of glycemic control tomortality in critically ill patients: an international multicenter cohort study
Authors: Krinsley James S , Egi Moritoki , Kiss Alex , Devendra Amin N , Schuetz Philipp , Maurer Paula M , Schultz Marcus J , van Hooijdonk Roosmarijn TM , Kiyoshi Morita , Mackenzie Iain MJ , Annane Djillali , Stow Peter , Nasraway Stanley A , Holewinski Sharon , Holzinger Ulrike , Preiser Jean-Charles , Vincent Jean-Louis , Bellomo Rinaldo 
Published: March 2013

Abstract
Introduction
Hyperglycemia, hypoglycemia, and increased glycemic variability have each beenindependently associated with increased risk of mortality in critically illpatients. The role of diabetic status on modulating the relation of these threedomains of glycemic control with mortality remains uncertain. The purpose of thisinvestigation was to determine how diabetic status affects the relation ofhyperglycemia, hypoglycemia, and increased glycemic variability with the risk ofmortality in critically ill patients.

Methods
This is a retrospective analysis of prospectively collected data involving 44,964patients admitted to 23 intensive care units (ICUs) from nine countries, betweenFebruary 2001 and May 2012. We analyzed mean blood glucose concentration (BG),coefficient of variation (CV), and minimal BG and created multivariable models toanalyze their independent association with mortality. Patients were stratifiedaccording to the diagnosis of diabetes.

Results
Among patients without diabetes, mean BG bands between 80 and 140 mg/dl wereindependently associated with decreased risk of mortality, and mean BG bands> 140 mg/dl, with increased risk of mortality. Among patients withdiabetes, mean BG from 80 to 110 mg/dl was associated with increased risk ofmortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. Aneffect of center was noted on the relation between mean BG and mortality.Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associatedwith increased risk of mortality among patients with and without diabetes andincreased glycemic variability, defined as CV > 20%, was independentlyassociated with increased risk of mortality only among patients without diabetes.Derangements of more than one domain of glycemic control had a cumulativeassociation with mortality, especially for patients without diabetes.

Conclusions
Although hyperglycemia, hypoglycemia, and increased glycemic variability is eachindependently associated with mortality in critically ill patients, diabeticstatus modulates these relations in clinically important ways. Our findingssuggest that patients with diabetes may benefit from higher glucose target rangesthan will those without diabetes. Additionally, hypoglycemia is independentlyassociated with increased risk of mortality regardless of the patient's diabeticstatus, and increased glycemic variability is independently associated withincreased risk of mortality among patients without diabetes.
See related commentary by Krinsley,http://ccforum.com/content/17/2/131
See related commentary by Finfer and Billot,http://ccforum.com/content/17/2/134
DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer
Authors: Bashashati Ali , Haffari Gholamreza , Ding Jiarui , Ha Gavin , Lui Kenneth , Rosner Jamie , Huntsman David G , Caldas Carlos , Aparicio Samuel A , Shah Sohrab P 
Published: March 2013

AbstractSimultaneous interrogation of tumor genomes and transcriptomes is underway in unprecedented global efforts. Yet, despite the essential need to separate driver mutations modulating gene expression networks from transcriptionally inert passenger mutations, robust computational methods to ascertain the impact of individual mutations on transcriptional networks are underdeveloped. We introduce a novel computational framework, DriverNet, to identify likely driver mutations by virtue of their effect on mRNA expression networks. Application to four cancer datasets reveals the prevalence of rare candidate driver mutations associated with disrupted transcriptional networks and a simultaneous modulation of oncogenic and metabolic networks, induced by copy number co-modification of adjacent oncogenic and metabolic drivers. DriverNet is available on Bioconductor or at http://compbio.bccrc.ca/software/drivernet/.
H. pylorivirulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model
Authors: Neal James T. , Peterson Tracy S. , Kent Michael L. , Guillemin Karen 
Published: March 2013

SummaryInfection with Helicobacter pylori is a major risk factor for the development of gastric cancer, and infection with strains carrying the virulence factor CagA significantly increases this risk. To investigate the mechanisms by which CagA promotes carcinogenesis, we generated transgenic zebrafish expressing CagA ubiquitously or in the anterior intestine. Transgenic zebrafish expressing either the wild type or a phosphorylation-resistant form of CagA exhibited significantly increased rates of intestinal epithelial cell proliferation and showed significant upregulation of the Wnt target genes cyclinD1, axin2 and the zebrafish c-myc ortholog myca. Coexpression of CagA with a loss-of-function allele encoding the β-catenin destruction complex protein Axin1 resulted in a further increase in intestinal proliferation. Coexpression of CagA with a null allele of the key β-catenin transcriptional cofactor Tcf4 restored intestinal proliferation to wild-type levels. These results provide in vivo evidence of Wnt pathway activation by CagA downstream of or in parallel to the β-catenin destruction complex and upstream of Tcf4. Long-term transgenic expression of wild-type CagA, but not the phosphorylation-resistant form, resulted in significant hyperplasia of the adult intestinal epithelium. We further utilized this model to demonstrate that oncogenic cooperation between CagA and a loss-of-function allele of p53 is sufficient to induce high rates of intestinal small cell carcinoma and adenocarcinoma, establishing the utility of our transgenic zebrafish model in the study of CagA-associated gastrointestinal cancers.
Diamine Derivatives Accelerate Photochemical C → U Transition in DNA Double Strand
Authors: Fujimoto Kenzo , Futamura Daiki , Sakamoto Takashi 
Published: March 2013

Abstract
For the improvement of the deamination reaction of cytosine in the photocrosslinked DNA double strand, the effect of additives on the deamination reaction was evaluated. The results indicated that diamine derivatives can accelerate the reaction in a concentration-dependent manner. This provides a new design of artificial oligonucleotides having higher photoediting activities.
Hydration of Adamantane Skeleton: Water Assembling around Amantadine and Halo-substituted Adamantanes
Authors: Doi Hideo , Aida Misako 
Published: March 2013

Abstract
We performed Monte Carlo simulations to reveal the water distributions around adamantane derivatives. Adamantane derivatives attract water molecules, and specific water distributions are observed around the skeleton. Perfluoroadamantane attracts water more than adamantane.
Giant Vesicles Containing Microspheres with High Volume Fraction Prepared by Water-in-oil Emulsion Centrifugation
Authors: Natsume Yuno , Toyota Taro 
Published: March 2013

Abstract
We aimed to obtain giant vesicles (GVs) confining microspheres with a volume fraction of 20–30 vol %, analogous to biological macromolecules contained in cytosols, through simple and quick steps. Through water-in-oil (W/O) emulsion centrifugation, we formed GVs containing 1-µm polystyrene microspheres with volume fractions in the range 0–45 vol %.
Preparation of Palladium-loaded Polymer Nanoparticles with Catalytic Activity for Hydrogenation and Suzuki Coupling Reactions
Authors: Seto Hirokazu , Morii Takato , Yoneda Tamami , Murakami Tatsuya , Hoshino Yu , Miura Yoshiko 
Published: March 2013

Abstract
Palladium-loaded polymer nanoparticles with basic functional groups were prepared. When palladium ions were adsorbed on the polymer nanoparticles, the maximum loading capacity on the nanoparticles depended on the basic functional groups in the particles. The reduced palladium had a nanoscale average diameter. The palladium-loaded polymer nanoparticles exhibited catalytic activity for hydrogenation and Suzuki coupling reactions. The catalytic activity of the nanosized palladium-loaded nanoparticles was higher than that of bulk palladium.
Temperature-dependent Upconversion Luminescence of NaYF4:Yb3+,Er3+ Nanoparticles
Authors: Zhao Junwei , Li Haitao , Zeng Qinghui , Song Kai , Wang Xiaofeng , Kong Xianggui 
Published: March 2013

Abstract
The temperature-dependent quenching characteristics of the upconversion luminescence in NaYF4:Yb3+,Er3+ nanoparticles under 980-nm excitation are reported. Intense green and red upconversion emissions corresponding to the (2H11/2, 4S3/2) → 4I15/2 and 4F9/2 → 4I15/2 transitions of the Er3+ ions were observed. The green emission at around 520 nm presents a continuous increase with increasing temperature, while the emission bands at around 545 and 657 nm decrease with the temperature change from 84 to 364 K. The temperature dependence of the intensity characteristics was analyzed systematically by using a simple three-level system.
Managing laboratory test ordering through test frequency filtering
Authors: Janssens Pim M.W. , Wasser Gerd 
Published: March 2013

Abstract

Background: Modern computer systems allow limits to be set on the periods allowed for repetitive testing. We investigated a computerised system for managing potentially overtly frequent laboratory testing, calculating the financial savings obtained.

Methods: In consultation with hospital physicians, tests were selected for which ‘spare periods’ (periods during which tests are barred) might be set to control repetitive testing. The tests were selected and spare periods determined based on known analyte variations in health and disease, variety of tissues or cells giving rise to analytes, clinical conditions and rate of change determining analyte levels, frequency with which doctors need information about the analytes and the logistical needs of the clinic.

Results: The operation and acceptance of the system was explored with 23 analytes. Frequency filtering was subsequently introduced for 44 tests, each with their own spare periods. The proportion of tests barred was 0.56%, the most frequent of these being for total cholesterol, uric acid and HDL-cholesterol. The financial savings were 0.33% of the costs of all testing, with HbA1c, HDL-cholesterol and vitamin B12 yielding the largest savings. Following the introduction of the system the number of barred tests ultimately decreased, suggesting accommodation by the test requestors.

Conclusions: Managing laboratory testing through computerised limits to prevent overtly frequent testing is feasible. The savings were relatively low, but sustaining the system takes little effort, giving little reason not to apply it. The findings will serve as a basis for improving the system and may guide others in introducing similar systems.
Native and Phosphorylated Bovine Adrenal Tyrosine 3-Monooxygenase. Interactions with Tetrahydropterins and Substrate and Stability of the Formed 4a-Hydroxy-Tetrahydrobiopterin
Authors: Haavik Jan , Andersson Kristoffer K. , Flatmark Torgeir , Petersson Leif 
Published: March 2013

Summary The catalytic activity of tyrosine 3-monooxygenase (tyrosine hydroxylase) is dependent on a tetrahydropterin cofactor and ezyme-bound iron. The oxidation of tetrahydrobiopterin by bovine adrenal tyrosine hydroxylase was studied by high performance liquid chromatography (HPLC). The first pterin product detected during catalytic turnover, 4a-hydroxy-tetrahydrobiopterin, was isolated by HPLC and the pseudo first-order rate constant of its dehydration to quinonoid dihydrobiopterin was estimated. The tl /2 was found to be 45 and 72 s in 100 and 5 mmol/L Tris-HCl, respectively, at pH 7.5 and 23 °C.The rate of the 4a-hydroxy-tetrahydropterin formation was found to increase on phosphorylation of the enzyme by cyclic AMP-dependent protein kinase. The phosphorylation did not significantly change the electron paramagnetic resonance (EPR) spectrum of tyrosine hydroxylase. However, in the presence of substrate or cofactor and dithiothreitol, the EPR spectral properties were strikingly different from those observed prior to phosphorylation. Our findings are in accordance with a mechanism in which the covalently bound phosphate activates the enzyme by facilitating changes in the redox-state of the enzyme-bound iron.
Studies and Comparison of Urinary Pteridine Patterns in Dogs and Cats and their Alteration in Various Neoplasias and Virus Infections
Authors: Goldberg M. , Gassner F. , Merkenschlager M. 
Published: March 2013

Summary Urinary excretion levels of five pteridines in healthy cats and dogs and in 14 groups of animals with tumours or virus infections were determined by HPLC after partial purification by ion exchange chromatography. Healthy cats and dogs produce species specific differences. In contrary to cats 6-hydroxymethylpterin was not detectable in dogs. Whereas in dogs biopterin presents the main part of pteridines (about 70%), cats contain about 53% catabolic isoxanthopterin in the pteridine pattern. In the various tumours no qualitative but quantitative alterations in the pteridine concentrations could be detected. The changes in the different tumours were not applied to all pteridines, so that each type of tumour shows an own pattern of pteridines.In the parvovirosis of the dog neopterin, biopterin and isoxanthopterin increased significantly. In the virusfree parvovirosis suspicious dogs only pterin was elevated. In the feline leucosis and feline infectious peritonitis a significant rise of all five measured pteridines were observed.Altogether, the data show, that increased urinary pteridines present a real additional aid for the suspicion of neoplasias or viral infections in the veterinary medicine.
Quantitation of the Folate Binding Protein in Human Cerebrospinal Fluid by an Enzyme-linked Immunosorbent Assay (ELISA)
Authors: Ingemann Hansen Steen , Holm Jan , Høier-Madsen Mimi 
Published: March 2013

Summary An enzyme-linked immunosorbent assay (ELISA) was calibrated and used for quantitation of the folate binding protein in human cerebrospinal fluid. The precision of the assay in terms of the coefficient of variation was 6.3% intra-assay (10 replicate single determinations) and 4.8% inter-assay (8 duplicate determinations). The concentration of folate binding protein in cerebrospinal fluid specimens from 20 patients with no complaints or diseases of neurological type was 0.14-0.38, 0.24 nmol FBP/I (range and median value). The gelfiltration profiles of radioligand bound and immunoreactive folate binding protein were identical, both consisting of one major peak (M, '" 25000) and one minor peak (M, '" 1 00000).
Synthesis and In Vitro Biological Evaluation of β,γ-Methano Analogues of Methotrexate and Aminopterin
Authors: Rosowsky Andre , Forsch Ronald A. , Moran Richard G. , Freisheim James H. 
Published: March 2013

Summaryβ,γ-Methano derivatives of methotrexate (MTX) and aminopterin (AMT) were synthesized with the aim of assessing the effect of this side-chain modification on dihydrofolate reductase (OHFR) inhibition, folylpolyglutamate synthetase (FPGS) inhibition, and tumor cell growth inhibition. Mixed carboxylic-carbonic anhydride (MCA) coupling of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) and dimethyl trans-α-(2-carboxycyclopropyl) glycinate, followed by alkaline hydrolysis, afforded N-( 4-amino-4-deoxy-N10-methylpteroyl)-α-( trans-2-carboxycyclopropyl)glycine (β,γ-methanoMTX) as a mixture of the four possible diastereomers with trans substitution on the cyclopropane ring. N-(4-Amino-4-deoxypteroyl)-trans-α.-(2-carboxycyclopropyl) glycine (β,γ-methanoAMT) , also as a diastereomer mixture, was obtained from 4-amino-4-deoxy-N10 - formylpteroic acid (fAPA) and dimethyl trans-α-(2-carboxycyclopropyl)-glycinate by MCA coupling and alkaline hydrolysis of the ester and N10-formyl groups. β,γ-MethanoMTX and β,γ-methanoAMT may be viewed as MTX and AMT analogues with a conformationally restricted side chain. In vitro biological activity data for these novel compounds support the view that the active site of DHFR, already known for its ability to tolerate modification of the γ-carboxyl group of MTX and AMT, can likewise accommodate substitution on the β- and γ-carbons.
An Enzyme Immunoassay for Neopterin and Biopterin Using a Microtitre Plate Linked with N2-(3-Aminopropyl) Derivatives of Pteridines
Authors: Sugimoto Takashi , Ogiwara Shoji , Kiuchi Kazutoshi , Nagatsu Toshiharu , Sakai Masao , Nagatsu Ikuko , Fujita Keisuke 
Published: March 2013

SummaryA novel and sensitive enzyme immunoassay for neopterin and biopterin using a microtitre plate has been developed. The antiserum against neopterin or biopterin was incubated with samples prepared from human urine or rat tissues, and was placed in a well of microtitre plate, where N2-(3-aminopropyl) derivative of neopterin or biopterin was kinked by poly-L-Iysine and glutaraldehyde. The antibody, which did not form the immunocomplex with the hapten in the sample, was bound to the fixed hapten on the plate, and then was measured with anti rabbit IgG and peroxidase anti-peroxidase complex. The detection limits of these pterins were both 0.1 pmol. The specificity of the assay was so high that this assay system with employing anti-neopterin antiserum completely distinguished neopterin from biopterin, as judged from the cross reactivity (0.002%) and vice versa. The amounts of neopterin and biopterin in human urine and rat tissues measured by the present assay showed a good agreement with those determined by high performance liquid chromatography.
Enzymatic Synthesis of Four Stereoisomers of 7-0xo-biopterin and Determination of the Absolute Structure of Ichthyopterin
Authors: Takikawa Shin Ichiro , Matsuura Sadao 
Published: March 2013

Summary Enzymatic conversion of stereoisomers of biopterin (3a-d) to the 7-oxo-biopterin isomers (4a-d) was performed with a new pterin 7-oxidase extracted from carp skin. The chiral centers of the 6-side chains of biopterin isomers were preserved during the conversion, and the four possible stereoisomers of 7-oxo-biopterin (4a-d) were obtained from the corresponding biopterin isomers (3a-d). HPLC and CD spectra studies showed that natural ichthyopterin is 2-amino-6-(L-erythro-1',2' -dihydroxypropyl)-4, 7(3H,8H)-pteridinedione (4a) which has the same L-erythro structure at the side chain as natural biopterin (3a). This fact suggests that ichthyopterin is biologically derived from biopterin in these fishes.
Tetrahydrobiopterin Deficiency: From Phenotype to Genotype
Authors: Blau Nenad , Thöny Beat , Heizmann Claus W. , Dhondt Jean-Louis 
Published: March 2013

Summary As a result of the selective screening worldwide during the last 18 years, approximately 250 patients with tetrahydrobiopterin deficiency were discovered. Most patients suffer from 6-pyruvoyl tetrahydropterin synthase deficiency (58%), followed by dihydropteridine reductase deficiency (35%), GTP cyclohydrolase I deficiency (3%), and “primapterinuria” (4%). The patients can be treated with neurotransmitter precursors, as well as with tetrahydrobiopterin. However, data on long term treatment are still scarce and it is therefore of great value to investigate all newborns with even mild hyperphenylalaninemia. Cloning of the enzymes involved in the biosynthesis and regeneration of tetrahydrobiopterin makes them to be easily accessible for biochemical and biological studies. So far, all proteins expressed heterologous are active in E. coli. Cloning of the wild type gene and mutant analysis of patients allow the rapid identification of the defective gene on the molecular level.
Pteridines XCVIII. Synthesis and Properties of 1-Methylpterins
Authors: Pfleiderer Wolfgang 
Published: March 2013

SummaryA series of 1-methyl-pterin derivatives (6-13) have been synthesized by condensation and methylation reactions. The compounds have been characterized by elemental analyses, pKa deterimations and UV spectra. Comparisons of the physical data of the corresponding N-1 and N-3 methyl-pterins indicate why the normal pterins exist in aqueous solution preferentially in the N3-H tautomeric configuration. The thermodynamical stability of the lactam group forces the acidic H-atom to adapt the nitrogen adjacent to the carhonyl function but no other vinylogous position. A lactam group does not participate in heteroaromatic cyclic resonance, in general.
Theoretical Stereostructure of the Neutral Form of Natural Tetrahydrobiopterin
Authors: Katoh Setsuko , Sueoka Terumi , Kurihara Teruo 
Published: March 2013

Summary The absolute conformation and the reactivity of atoms of the neutral form of natural tetrahydrobiopterin [(6R)-6-(L-erythro-1 ′,2′ -dihydroxypropyl)-5.6.7.8-tetrahydropterin] was determined by the Molecular-Orbital method within the MINDO/3 framework. Two different conformations (Form A and Form B) of the alkyl side chain relative to the pterin ring were obtained as the optimized form for the lowest energy conformation (ΔH= -174 kcal/lmol) of this molecular constitution with the same molecular width of 11.2 Å. Form A and B were distinguishable in the dihedral [01′ -C1′ -C6-H6J of - 88° and 30°. respectively. Net charges of atoms of Form A and B suggested that the predominant reactivity of the atoms of N1 C2. C4. O4, C4a. and C8a of the pterin ring and C1′. C2′. O1′ and O2′ of the side chain. It was also suggested that the position 2' is more active than the position 1′. in the alkyl side chain of Form A and B. toward NADP+ in the reverse reaction of sepiapterin reductase.