2,207 research outputs found

    The Presence of Inducible Cytochrome P450 Types 1A1 and 1A2 in the BeWo Cell Line

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    Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.The activity and inducibility of cytochrome P450 systems (CYP1A1:1A2) of the human placenta were assessed in a representative human trophoblast-like cell line, BeWo. The activity of CYP1A1 and CYP1A2 in microsome preparations from human liver, placenta, primary cultures of human cytotrophoblast, and BeWo cells was measured by O-dealkylation of 7-ethoxyresorufin (EROD) and 7-methoxyresorufin O-demethylation (MROD), respectively. Results indicated high EROD and MROD activity associated with human liver microsomes, sometimes comparable activities in human placenta microsomes prepared from smokers, and relatively low activities in human placenta microsomes from nonsmokers and in the primary cultures of cytotrophoblasts isolated from nonsmokers. Microsomes from BeWo cell monolayers exhibited the lowest EROD and MROD activities relative to all other microsome preparations. However, compared to primary cultures of normal trophoblasts, the EROD activity of the BeWo cells was far more sensitive to typical inducers, 3-methylcholanthrene, 1,2-benzanthracene, and β-naphthoflavone. EROD activity in BeWo cells was induced approximately 200-fold by 3-methylcholanthrene. Both EROD and MROD activity in BeWo cells was readily induced by 1,2-benzanthracene, 100-fold and 60-fold, respectively. After induction with 1,2-benzanthracene, the CYP1A1 selective inhibitor, α-naphthoflavone, and the CYP1A2 selective inhibitor, furafylline, effectively inhibited enzyme activities with IC50’s of 2.4μM and 12.8μM, respectively, in microsomes from both trophoblasts culture systems. These results show that major cytochrome P450 forms present in human placenta are present and inducible in BeWo cells, a potential model for investigation of drug metabolism mechanisms in the human trophoblast

    SMAF: A Soil Health Assessment Tool

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    The Soil Management Assessment Framework (SMAF) was developed to help quantify soil quality/health effects of tillage, crop rotation, and other soil management practices. Our objective was to determine if the SMAF could detect soil health differences after growing a single winter triticale (X Triticosecale Wittmack) crop. Soil samples were collected from 0 to 7.5- and 7.5 to 15- cm depth increments during the 2003 – 2004 and 2004 – 2005 growing seasons near Ames and Lewis, IA, and analyzed for several potential soil quality indicators. The SMAF analysis showed higher soil quality ratings for surface than subsurface samples. It also showed that a single winter grain crop can significantly improve soil quality after either corn (Zea mays L.) or soybean (Glycine max [L.] Merr.). Finally, in response to increasing interest in soil health assessments, a detailed appendix is attached to provide guidance for future soil health assessments

    Comparisons between Canadian prairie MF radars, FPI (green and OH lines) and UARS HRDI systems

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    Learning in large learning spaces:the academic engagement of a diverse group of students

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    Teaching larger groups of students is a growing phenomenon in HE and this brings with it, its own challenges not least for the students themselves but also their lecturers. Demographic factors as well as the experiences that characterise us as individuals will impact upon our ability to learn. The pilot study reported here considered the “academic engagement” of a diverse group of students where their course is delivered in large learning environments. As a pilot study, the paper concludes with the identification of two areas which are worthy of further research. Firstly, the study highlighted that mature students were more likely to engage in learning strategies that are associated with surface learning – the binary opposite to which practitioners often strive to achieve. Secondly, the research suggests that students who appear to know their tutors well indicate a preference for study approaches that are likely to develop deeper learning

    Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial.

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    BACKGROUND: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). METHODS: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. RESULTS: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. CONCLUSIONS: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013

    The relationship between the insulin-like growth factor-1 axis, weight loss, an inflammation-based score and survival in patients with inoperable non-small cell lung cancer

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    <b>Background & aims:</b> The involvement of a systemic inflammatory response, as evidenced by the Glasgow Prognostic Score (GPS), is associated with weight loss and poor outcome in patients with non-small cell lung cancer. There is good evidence that nutritional and functional decline in patients with advanced malignant disease is associated with catabolic changes in metabolism. However, defects in anabolism may also contribute towards nutritional decline in patients with cancer. The aim of the present study was to examine the relationship between IGF-1 and IGFBP-3, performance status, mGPS and survival in patients with inoperable NSCLC. <b>Methods:</b> 56 patients with inoperable NSCLC were studied. The plasma concentrations of IGF-1, IGFBP-3 and leptin were measured using ELISA and RIA. <b>Results:</b> The patients were predominantly male (61%), over 60 years old (80%), with advanced (stage III or IV) disease (98%), with a BMI≥20 (84%), an ECOG-ps of 0 or 1 (79%), a haemoglobin (59%) and white cell count (79%) in the reference range. On follow-up 43 patients died of their cancer. On univariate analysis, BMI (p<0.05), Stage (p<0.05), ECOG-ps (p<0.05), haemoglobin (p<0.05), white cell count (p<0.05) and mGPS (p<0.05) were associated with cancer specific survival. There was no association between age, sex, treatment, IGF-1, IGFBP-3, IGF-1:IGFBP-3 ratio, or leptin and cancer specific survival. With an increasing mGPS concentrations of haemoglobin (p<0.005) and IGFBP-3 (p<0.05) decreased. mGPS was not associated with either IGF-1(p>0.20), or leptin (p>0.20). <b>Conclusions:</b> In summary, the results of this study suggest that anabolism (IGF-1 axis) does not play a significant role in the relationship between nutritional and functional decline, systemic inflammation and poor survival in patients with inoperable NSCLC
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