bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ca2+-dependent protein kinase C isoforms are critical to estradiol 17β-d-glucuronide–induced cholestasis in the rat
Authors: Crocenzi Fernando A. , Pozzi Enrique J. Sánchez , Ruiz María Laura , Zucchetti Andrés E. , Roma Marcelo G. , Mottino Aldo D. , Vore Mary 
Published: July 2008

Abstract

The endogenous estradiol metabolite estradiol 17β-d-glucuronide (E217G) induces an acute cholestasis in rat liver coincident with retrieval of the canalicular transporters bile salt export pump (Bsep, Abcc11) and multidrug resistance-associated protein 2 (Mrp2, Abcc2) and their associated loss of function. We assessed the participation of Ca2+-dependent protein kinase C isoforms (cPKC) in the cholestatic manifestations of E217G in perfused rat liver (PRL) and in isolated rat hepatocyte couplets (IRHCs). In PRL, E217G (2 μmol/liver; intraportal, single injection) maximally decreased bile flow, total glutathione, and [3H] taurocholate excretion by 61%, 62%, and 79%, respectively; incorporation of the specific cPKC inhibitor Gö6976 (500 nM) in the perfusate almost totally prevented these decreases. In dose-response studies using IRHC, E217G (3.75–800 μM) decreased the canalicular vacuolar accumulation of the Bsep substrate cholyl-lysylfluorescein with an IC50 of 54.9 ± 7.9 μM. Gö6976 (1 μM) increased the IC50 to 178.4 ± 23.1 μM, and similarly prevented the decrease in the canalicular vacuolar accumulation of the Mrp2 substrate, glutathione methylfluorescein. Prevention of these changes by Gö6976 coincided with complete protection against E217G-induced retrieval of Bsep and Mrp2 from the canalicular membrane, as detected both in the PRL and IRHC. E217G also increased paracellular permeability in IRHC, which was only partially prevented by Gö6976. The cPKC isoform PKCα, but not the Ca2+-independent PKC isoform, PKCε, translocated to the plasma membrane after E217G administration in primary cultured rat hepatocytes; Gö6976 completely prevented this translocation, thus indicating specific activation of cPKC. This is consistent with increased autophosphorylation of cPKC by E217G, as detected via western blotting.

Conclusion:

Our findings support a central role for cPKC isoforms in E217G-induced cholestasis, by inducing both transporter retrieval from the canalicular membrane and opening of the paracellular route. (Hepatology 2008;48:1885-1895.)
Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo
Authors: Lam Christopher X. F. , Hutmacher Dietmar W. , Schantz Jan‐Thorsten , Woodruff Maria Ann , Teoh Swee Hin 
Published: July 2008

AbstractThe use of polycaprolactone (PCL) as a biomaterial, especially in the fields of drug delivery and tissue engineering, has enjoyed significant growth. Understanding how such a device or scaffold eventually degrades in vivo is paramount as the defect site regenerates and remodels. Degradation studies of three‐dimensional PCL and PCL‐based composite scaffolds were conducted invitro (in phosphate buffered saline) and in vivo (rabbit model). Results up to 6 months are reported. All samples recorded virtually no molecular weight changes after 6 months, with a maximum mass loss of only about 7% from the PCL‐composite scaffolds degraded in vivo, and a minimum of 1% from PCL scaffolds. Overall, crystallinity increased slightly because of the effects of polymer recrystallization. This was also a contributory factor for the observed stiffness increment in some of the samples, while only the PCL‐composite scaffold registered a decrease. Histological examination of the in vivo samples revealed good biocompatibility, with no adverse host tissue reactions up to 6 months. Preliminary results of medical‐grade PCL scaffolds, which were implanted for 2 years in a critical‐sized rabbit calvarial defect site, are also reported here and support our scaffold design goal for gradual and late molecular weight decreases combined with excellent long‐term biocompatibility and bone regeneration. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase Rac
Authors: van Golen Kenneth L. , Ying Chi , Sequeira Linda , Dubyk Cara W. , Reisenberger Tracy , Chinnaiyan Arul M. , Pienta Kenneth J. , Loberg Robert D. 
Published: July 2008

AbstractNearly 85% of the men who will die of prostate cancer (PCa) have skeletal metastases present. The ability of PCa cells to interact with the microenvironment determines the success of the tumor cell to form metastatic lesions. The ability to bind to human bone marrow endothelial (HBME) cells and undergo transendothelial cell migration are key steps in allowing the PCa cell to extravasate from the bone microvasculature and invade the bone stroma. We have previously demonstrated that monoctyte chemoattractant protein 1 (MCP‐1; CCL2) is expressed by HBME cells and promotes PCa proliferation and migration. In the current study, we demonstrate that the CCL2 stimulation of PCa cells activates the small GTPase, Rac through the actin‐associated protein PCNT1. Activation of Rac GTPase is accompanied by morphologic changes and the ability of the cells to undergo diapedesis through HBME cells. These data suggest a role for HBME‐secreted CCL2 in promoting PCa cell extravasation into the bone microenvironment. J. Cell. Biochem. 104: 1587–1597, 2008. © 2008 Wiley‐Liss, Inc.
Latent effects of egg incubation temperature on growth in the lizard Anolis carolinensis
Authors: Goodman Rachel M. 
Published: July 2008

AbstractVaried egg incubation temperatures can result in immediate effects on the phenotype of reptiles, and also latent effects that can augment or contradict effects evident at egg hatching. I examined the effects of incubation temperature on embryonic development, hatching morphology, and subsequent growth in multiple populations of the lizard Anolis carolinensis. Eggs from wild‐caught females in four populations were incubated at up to three temperatures, 23.5, 27, and 30°C. Measures of body size were collected immediately after hatching and weekly thereafter, while juveniles were maintained in a common laboratory environment for 8 weeks. Cooler incubation temperatures resulted in longer incubation periods but did not affect conversion of egg mass to hatchling mass. Incubation temperature did not affect hatchling mass or snout vent length (SVL), but did affect subsequent growth in both mass and SVL, which varied by population. Cooler incubation temperatures generally resulted in greater overall growth over 8 weeks of housing all juveniles in a common environment. In A. carolinensis, egg incubation temperature had latent effects on juvenile growth despite the absence of any detected immediate effects on hatchling phenotype. Therefore, the total impact and evolutionary importance of developmental environment should not be assessed or assumed based solely on the phenotype of reptiles at birth or hatching. J. Exp. Zool. 309A:525–533, 2008. © 2008 Wiley‐Liss, Inc.
Characterization of high‐capacity adenovirus production by the quantitative real‐time polymerase chain reaction: a comparative study of different titration methods
Authors: Crettaz Julien , Olague Cristina , Vales Africa , Aurrekoetxea Igor , Berraondo Pedro , Otano Itziar , Kochanek Stephan , Prieto Jesús , González‐Aseguinolaza Gloria 
Published: July 2008

AbstractBackgroundHigh‐capacity adenoviruses (HC‐Ad) hold great promise for the treatment of many diseases. The major drawbacks for the clinical application of this vector concern difficulties with respect to large‐scale production, and the absence of standardized methods for production and titration. In the present study, we compare the different methods found in the literature for characterizing HC‐Ad production.MethodsTwo productions of the HC‐Ad carrying murine IL‐12 gene were obtained. The viral titer and adenovirus‐helper contamination as well as viral particle concentration of both productions were determined using different methods: (i) quantification of total viral particles by spectrophotometry and plaque assay to estimate first‐generation (FG)‐helper‐Ad contamination; (ii) quantification of HC‐Ad and FG‐helper‐Ad genomes by the quantitative polymerase chain reaction (qPCR) directly from viral stock; (iii) quantification of viral genomes after cell infection by the slot‐blot hybridization assay and (iv) qPCR.ResultsDramatic differences with respect to viral titer were found depending on the method used. The first method overestimates HC‐Ad titer and underestimates FG‐helper‐Ad contamination and no information on the infectivity of the HC‐Ad is obtained. qPCR analysis of viral stock is more sensitive and accurate, but information about infectivity remains unknown and FG‐helper‐Ad contamination is overestimated. Quantification of HC‐Ad and FG‐helper‐Ad infectious units by‐slot blot DNA hybridization and qPCR assay are found to be equally sensitive and accurate.ConclusionsThe results of the present study demonstrate that a standardized method should be developed for HC‐Ad characterization for future clinical applications of this vector. Quantification of HC‐Ad production by qPCR is a fast, safe and reliable method for determining HC‐Ad and FG‐helper‐Ad particles and infectious units. Copyright © 2008 John Wiley & Sons, Ltd.
Successful inhibition of excitotoxic neuronal damage and microglial activation after delayed application of interleukin‐1 receptor antagonist
Authors: Vogt Cornelia , Hailer Nils P. , Ghadban Chalid , Korf Horst‐Werner , Dehghani Faramarz 
Published: July 2008

AbstractInterleukin (IL)‐1 is an important mediator of neuronal demise and glial activation after acute central nervous system lesions and is antagonized by IL‐1 receptor antagonist (IL‐1RA). Here we determined the time window in which IL‐1RA elicits neuroprotective effects in rat organotypic hippocampal slice cultures (OHSC). OHSC were lesioned with N‐methyl‐D‐aspartate (NMDA) and treated with IL‐1RA (100 ng/ml) at different time points postinjury or were left untreated. Damaged neurons, microglial cells, and astrocytes were labelled with NeuN, propidium iodide, isolectin B4, or glial fibrillary acidic protein (GFAP), respectively, and were analyzed by confocal laser scanning microscopy. In lesioned OHSC, the most dramatic increase in microglial cell number occurred between 8 and 16 hr postinjury, and the maximal neuronal demise was found between 16 and 24 hr postinjury. The cellular source of IL‐1β was investigated by immunohistochemistry, and IL‐1β immunoreactivity was found in few microglial cells at 4 hr postinjury and in numerous microglial cells and astrocytes at 16 hr postinjury. In both glial populations, IL‐1β immunoreactivity peaked at 24 hr postinjury. IL‐1RA treatment potently suppressed neuronal damage by 55% when initiated within the first 16 hr postinjury (P < 0.05), and IL‐1RA treatment initiated at 24 hr postinjury resulted in weaker but still significant neuroprotection. IL‐1RA treatment also reduced the number of microglial cells significantly when initiated within 36 hr postinjury (P < 0.05). In conclusion, IL‐1RA exhibits significant neuroprotective effects in this in vitro model of excitotoxic injury even after delayed application. © 2008 Wiley‐Liss, Inc.
The influence of air temperature and atmospheric circulation on winter fog frequency over Northern Eurasia
Authors: Ye Hengchun 
Published: July 2008

AbstractThis study examines the relationship between the number of fog days with surface air temperature and with atmospheric circulation as represented by the Arctic Oscillation (AO) and Siberian High (SBH) Pressure index over northern Eurasia during the winters of 1936–1937 to 1989–1990. The results suggest that the number of fog days decreases as surface air temperature increases, the SBH weakens, and the AO strengthens over much of the study region, except for southern European Russia, where fog days may increase with air temperature. The most significant and dominant impact on fog day frequency is surface air temperature, followed by the intensity of the SBH which directly reflects atmospheric stability. The AO has some limited influence on fog frequency over northern European Russia and southwestern Siberia. The combination of air temperature with either SBH or AO index explained, on average, about 30–60% of the variability of winter fog days over Siberia. Copyright © 2008 Royal Meteorological Society
Pigment analysis by Raman microscopy of the non‐figurative illumination in 16th‐ to 18th‐century Islamic manuscripts
Authors: Burgio Lucia , Clark Robin J. H. , Muralha Vânia S. F. , Stanley Tim 
Published: July 2008

AbstractThe non‐figurative illumination in five Islamic religious manuscripts of the 16th to 18th centuries held in the National Art Library (NAL) at the Victoria and Albert Museum were analysed by Raman microscopy (RM) and X‐ray fluorescence (XRF) to determine the pigments used in each case and to establish whether the range of pigments evolved with time. The pigments identified include lazurite, red lead, vermilion, orpiment and a carbon‐based black, which were found on all five manuscripts without exception, as well as lead white, malachite, atacamite, haematite, pararealgar, indigo and Prussian blue, which were found on a more limited number of manuscripts. The presence of gold‐based gilding was also established. This range of pigments differs in only a few respects from those already established for Islamic secular manuscripts of the same period. We may conclude that the range of pigments remained stable during the 16th and 17th centuries and began to expand in the 18th century through the introduction of synthetic pigments. On a 16th‐century manuscript analysed in this study, the intermediate phase formed by the light‐induced degradation of realgar into pararealgar was also identified. Copyright © 2008 John Wiley & Sons, Ltd.
Raman spectroscopy and characterisation of α‐gallium oxyhydroxide and β‐gallium oxide nanorods
Authors: Zhao Yanyan , Frost Ray L. 
Published: July 2008

AbstractRaman spectroscopy complemented by infrared spectroscopy was used to characterise both gallium oxyhydroxide (α‐GaO(OH)) and gallium oxide (β‐Ga2O3) nanorods synthesised with and without the surfactants using a soft chemical methodology at low temperatures. Nano‐ to micro‐sized gallium oxyhydroxide and gallium oxide materials were characterised and analysed by both X‐ray diffraction and Raman spectroscopy. Rod‐like GaO(OH) crystals with average length of ∼2.5 µm and width of 1.5 µm were obtained. Upon thermally treating gallium oxyhydroxide GaO(OH) to 900 °C, β‐Ga2O3 was synthesised retaining the initial GaO(OH) morphology. Raman spectroscopy has been used to study the structure of nanorods of GaO(OH) and Ga2O3 crystals.Raman spectroscopy shows bands characteristic of GaO(OH) at 950 and ∼1000 cm−1 attributed to GaOH deformation modes. Bands at 261, 275, 433 and 522 cm−1 are assigned to vibrational modes involving GaOH units. Bands observed at 320, 346, 418 and 472 cm−1 are assigned to the deformation modes of Ga2O6 octahedra.Two sharp infrared bands at 2948 and 2916 cm−1 are attributed to the GaO(OH) symmetric stretching vibrations. Raman spectroscopy of Ga2O3 provides bands at 630, 656 and 767 cm−1 which are assigned to the bending and stretching of GaO4 units. Raman bands at 417 and 475 cm−1 are attributed to the symmetric stretching modes of GaO2 units. The Raman bands at 319 and 347 cm−1 are assigned to the bending modes of GaO2 units. Copyright © 2008 John Wiley & Sons, Ltd.
Mechanisms of drug–DNA recognition distinguished by Raman spectroscopy, ,
Authors: Benevides James M. , Kawakami Jessica , Thomas George J. 
Published: July 2008

AbstractThe highly chromophoric drugs, ethidium bromide (EtBr), 9‐aminoacridine (9AA) and proflavine (PF) (3,6‐diaminoacridine) bind to DNA by insertion of a polycyclic aromatic ring between adjacent base pairs of the double helix. Despite similar intercalative mechanisms, these drugs exhibit distinct DNA affinities and produce characteristic mutagenic effects. Complexes of the intercalants with small nucleotide fragments have been investigated by various methods, including X‐ray crystallography. However, the structural impact of drug intercalation on a DNA molecule of genetic consequence has not yet been reported. Here, we employ near‐infrared laser excitation (752 nm) and a DNA target of genomic size to obtain and compare Raman spectra of complexes of EtBr, 9AA and PF with DNA. Raman signatures of solution complexes have been analyzed by difference methods to reveal the specific structural changes induced at the drug/DNA intercalation sites. Perturbation of the DNA backbone geometry, as reflected in the Raman marker diagnostic of the phosphodiester group (800–880 cm−1), ranges from disruption of the B‐form duplex in favor of either the A‐form duplex, or separated strands, or a combination of altered DNA backbone geometries. The acridine intercalants, PF and 9AA, also perturb hydrogen‐bonding interactions between the paired bases of duplex DNA, although in distinct ways. Conversely, base pairing is relatively unperturbed by ethidium intercalation. The results are discussed in relation to frameshift mutagenic activities of the intercalating drugs. Copyright © 2008 John Wiley & Sons, Ltd.
Surgical technique and systemic inflammation influences long‐term disease‐free survival following hepatic resection for colorectal metastasis
Authors: Gomez Dhanwant , Morris‐Stiff Gareth , Wyatt Judy , Toogood Giles J. , Lodge J. Peter A. , Prasad K. Rajendra 
Published: July 2008

AbstractBackgroundTo date, there is limited data available on prognostic factors that influence long‐term disease‐free survival following hepatic resection for colorectal liver metastasis (CRLM). The aim of the study was to identify prognostic factors that were associated with long‐term disease‐free survival (>5 years) following resection for CRLM.MethodsPatients undergoing resection for CRLM from January 1993 to March 2007 were identified from the hepatobiliary database. Data analyzed included demographics, laboratory results, operative findings and histopathological data.ResultsSeven hundred five curative primary hepatic resections were performed, of which 434 patients developed disease recurrence within 5 years and 67 patients were disease‐free more than 5 years. There was a significant association between systemic inflammatory response (raised neutrophil to lymphocyte ratio and/or C‐reactive protein), blood transfusion, >2 tumors, bilobar disease and resection margin involvement with developing recurrence during the follow‐up period. On multivariate analysis, three independent predictors for recurrent disease within the 5‐year follow‐up were identified: pre‐operative inflammatory response; blood transfusion requirement; and status of resection margin.ConclusionAbsence of a systemic inflammatory response and surgical technique to minimize transfusion requirements and obtain a R0 resection margin, are associated with long‐term disease‐free survival. J. Surg. Oncol. 2008;98:371–376. © 2008 Wiley‐Liss, Inc.
Absence of Ras mutations in rat DMBA‐induced mammary tumors
Authors: Samuelson Emma , Nilsson Johanna , Walentinsson Anna , Szpirer Claude , Behboudi Afrouz 
Published: July 2008

AbstractAnimal cancer models reduce genetic background heterogeneity and thus, may facilitate identification and analysis of specific genetic aberrations in tumor cells. Rat and human mammary glands have high similarity in physiology and show comparable hormone responsiveness. Thus, spontaneous and carcinogen (e.g., NMU and DMBA)‐induced rat mammary models are valuable tools for genetic studies of breast cancer. In NMU‐induced rat mammary tumors, activating mutations in Hras codon 12 have frequently been reported and are supposed to contribute to the mammary carcinogenic process. Involvement of Ras mutations in DMBA‐induced tumors is less clear. In the present study we investigated the mutation status of the three Ras genes, Hras, Kras, and Nras, in DMBA‐induced rat mammary tumors. We examined codons 12, 13, and 61 of all three genes for mutations in 71 tumors using direct sequencing method that in experimental conditions is sensitive enough to detect single nucleotide mutations even when present in only 25% of the test sample. No activating Ras gene mutation was found. Thus, in contrast to NMU‐induced rat mammary tumor, tumorigenesis in DMBA‐induced rat mammary tumors seems to be independent on activating mutations in the Ras genes. Our finding suggests that the genetic pathways selected in mammary tumor development are influenced by and perhaps dependent on the identity of the inducing agent, again emphasizing the importance of tumor etiology on the genetic changes in the tumor cells. © 2008 Wiley‐Liss, Inc.
Postprandial lipid responses of butter blend containing fish oil in a single‐meal study in humans
Authors: Overgaard Julie , Porsgaard Trine , Guo Zheng , Lauritzen Lotte , Mu Huiling 
Published: July 2008

AbstractThe postprandial effects of a butter product containing fish oil were investigated in a single‐meal, randomized crossover study with a commercial butter product as the control. Twelve healthy males consumed two test meals with13C‐labelled cholesterol (45 mg) and either an interesterified butter blend with fish oil (352 mg n‐3 long‐chain PUFA (LCPUFA)) or the commercial butter blend. Blood samples were collected after the meals and in the fasting condition on the test day and the following morning, and were analysed for cholesterol absorption, plasma lipid profile and fatty acid composition. No significant difference in the postprandial plasma fatty acid composition was observed between the groups, neither difference in cholesterol absorption, plasma cholesterol or the cholesterol contents of plasma lipoproteins. The incorporation of fish oil in the butter resulted in a significant lower concentration of triacylglycerols in the plasma 2 h after the meal in comparison with the commercial butter blend (p= 0.02); there was, however, no significant difference 24 h after the meal. In conclusion, fish oil‐enriched butter blend provides a source to increase the intake of n‐3 LCPUFA in the population, but has no acute effect on cholesterol absorption and plasma cholesterol concentration in human.
Mediterranean diet and cardioprotection: Wild artichoke inhibits metalloproteinase 9
Authors: Bellosta Stefano , Bogani Paola , Canavesi Monica , Galli Claudio , Visioli Francesco 
Published: July 2008

AbstractMetalloproteinases (MMPs) are zinc‐dependent endopeptidases responsible for the hydrolysis of various component of extracellular matrix such as gelatin and collagen. MMPs, namely MMP‐2 and MMP‐9 correlate with cardiovascular events in patients. We sought to determine whether supplementation with polyphenol‐richCynara cardunculus(wild artichoke, traditional component of the Mediterranean diet) modulates MMP‐9 expression and activity in cell cultures. A fully characterizedC. cardunculusextract was able to inhibit, in a dose‐dependent manner, the gelatinolytic activity of secreted MMP‐9 and both secretion and human MMP‐9 promoter‐driven transcription. Analysis by HPLC of theCynaraextract identified polyphenols such as luteolin, apigenin, and caffeic acid, among others. However, testing a mix of the individual components suggested that the inhibitory effects ofC. cardunculusare due to minor constituent fraction(s) as a whole. In promoting the health benefits of the Mediterranean diet, the role of wild plants as important meal components deserves further reappraisal.