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  1. Circulating leptin and osteoprotegerin levels affect insulin resistance in healthy premenopausal obese women.

    PubMed

    Ugur-Altun, Betul; Altun, Armagan

    2007-11-01

    We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women. PMID:17923273

  2. Common Variation in the β-Carotene 15,15′-Monooxygenase 1 Gene Affects Circulating Levels of Carotenoids: A Genome-wide Association Study

    PubMed Central

    Ferrucci, Luigi; Perry, John R.B.; Matteini, Amy; Perola, Markus; Tanaka, Toshiko; Silander, Kaisa; Rice, Neil; Melzer, David; Murray, Anna; Cluett, Christie; Fried, Linda P.; Albanes, Demetrius; Corsi, Anna-Maria; Cherubini, Antonio; Guralnik, Jack; Bandinelli, Stefania; Singleton, Andrew; Virtamo, Jarmo; Walston, Jeremy; Semba, Richard D.; Frayling, Timothy M.

    2009-01-01

    Low plasma levels of carotenoids and tocopherols are associated with increased risk of chronic disease and disability. Because dietary intake of these lipid-soluble antioxidant vitamins is only poorly correlated with plasma levels, we hypothesized that circulating carotenoids (vitamin A-related compounds) and tocopherols (vitamin E-related compounds) are affected by common genetic variation. By conducting a genome-wide association study in a sample of Italians (n = 1190), we identified novel common variants associated with circulating carotenoid levels and known lipid variants associated with α-tocopherol levels. Effects were replicated in the Women's Health and Aging Study (n = 615) and in the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) study (n = 2136). In meta-analyses including all three studies, the G allele at rs6564851, near the β-carotene 15,15′-monooxygenase 1 (BCMO1) gene, was associated with higher β-carotene (p = 1.6 × 10−24) and α-carotene (p = 0.0001) levels and lower lycopene (0.003), zeaxanthin (p = 1.3 × 10−5), and lutein (p = 7.3 × 10−15) levels, with effect sizes ranging from 0.10–0.28 SDs per allele. Interestingly, this genetic variant had no significant effect on plasma retinol (p > 0.05). The SNP rs12272004, in linkage disequilibrium with the S19W variant in the APOA5 gene, was associated with α-tocopherol (meta-analysis p = 7.8 × 10−10) levels, and this association was substantially weaker when we adjusted for triglyceride levels (p = 0.002). Our findings might shed light on the controversial relationship between lipid-soluble anti-oxidant nutrients and human health. PMID:19185284

  3. Ice sheet collapse affects ocean circulation

    NASA Astrophysics Data System (ADS)

    Tretkoff, Ernie

    2011-06-01

    As Earth's climate warms and ice melts, freshwater input to oceans could weaken the large-scale Atlantic meridional overturning circulation, which acts as an important conveyor of heat and has significant effects on climate. Green et al. used an intermediate complexity climate model to study how freshwater input to oceans can affect the meridional overturning circulation. They applied their model to the collapse of the Barents ice sheet about 140,000 years ago—the first study of this kind for the time period—which resulted in a huge influx of freshwater to the North Atlantic Ocean as large icebergs calved off of the ice sheet. (Paleoceanography, doi:10.1029/ 2010PA002088, 2011)

  4. Circulation factors affecting precipitation over Bulgaria

    NASA Astrophysics Data System (ADS)

    Nojarov, Peter

    2015-09-01

    The objective of this paper is to determine the influence of circulation factors on precipitation in Bulgaria. The study succeeds investigation on the influence of circulation factors on air temperatures in Bulgaria, as the focus here is directed toward precipitation amounts. Circulation factors are represented through two circulation indices, showing west-east or south-north transport of air masses over Bulgaria and four teleconnection indices (patterns)—North Atlantic Oscillation, East Atlantic, East Atlantic/Western Russia, and Scandinavian. Omega values at 700-hPa level show vertical motions in the atmosphere. Annual precipitation trends are mixed and not statistically significant. A significant decrease of precipitation in Bulgaria is observed in November due to the strengthening of the eastward transport of air masses (strengthening of EA teleconnection pattern) and anticyclonal weather (increase of descending motions in the atmosphere). There is also a precipitation decrease in May and June due to the growing influence of the Azores High. An increase of precipitation happens in September. All this leads to a redistribution of annual precipitation course, but annual precipitation amounts remain the same. However, this redistribution has a negative impact on agriculture and winter ski tourism. Zonal circulation has a larger influence on precipitation in Bulgaria compared to meridional. Eastward transport throughout the year leads to lower than the normal precipitation, and vice versa. With regard to the four teleconnection patterns, winter precipitation in Bulgaria is determined mainly by EA/WR teleconnection pattern, spring and autumn by EA teleconnection pattern, and summer by SCAND teleconnection pattern.

  5. Linkage analysis of circulating levels of adiponectin in hispanic children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VVA...

  6. Grazing Affects Exosomal Circulating MicroRNAs in Cattle

    PubMed Central

    Muroya, Susumu; Ogasawara, Hideki; Hojito, Masayuki

    2015-01-01

    Circulating microRNAs (c-miRNAs) are associated with physiological adaptation to acute and chronic aerobic exercise in humans. To investigate the potential effect of grazing movement on miRNA circulation in cattle, here we profiled miRNA expression in centrifugally prepared exosomes from the plasma of both grazing and housed Japanese Shorthorn cattle. Microarray analysis of the c-miRNAs resulted in detection of a total of 231 bovine exosomal miRNAs in the plasma, with a constant expression level of let-7g across the duration and cattle groups. Expression of muscle-specific miRNAs such as miR-1, miR-133a, miR-206, miR-208a/b, and miR-499 were undetectable, suggesting the mildness of grazing movement as exercise. According to validation by quantitative RT-PCR, the circulating miR-150 level in the grazing cattle normalized by the endogenous let-7g level was down-regulated after 2 and 4 months of grazing (P < 0.05), and then its levels in housed and grazing cattle equalized when the grazing cattle were returned to a housed situation. Likewise, the levels of miR-19b, miR-148a, miR-221, miR-223, miR-320a, miR-361, and miR-486 were temporarily lowered in the cattle at 1 and/or 2 month of grazing compared to those of the housed cattle (P < 0.05). In contrast, the miR-451 level was up-regulated in the grazing cattle at 2 months of grazing (P = 0.044). The elevation of miR-451 level in the plasma was coincident with that in the biceps femoris muscle of the grazing cattle (P = 0.008), which suggests the secretion or intake of miR-451 between skeletal muscle cells and circulation during grazing. These results revealed that exosomal c-miRNAs in cattle were affected by grazing, suggesting their usefulness as molecular grazing markers and functions in physiological adaptation of grazing cattle associated with endocytosis, focal adhesion, axon guidance, and a variety of intracellular signaling, as predicted by bioinformatic analysis. PMID:26308447

  7. Grazing Affects Exosomal Circulating MicroRNAs in Cattle.

    PubMed

    Muroya, Susumu; Ogasawara, Hideki; Hojito, Masayuki

    2015-01-01

    Circulating microRNAs (c-miRNAs) are associated with physiological adaptation to acute and chronic aerobic exercise in humans. To investigate the potential effect of grazing movement on miRNA circulation in cattle, here we profiled miRNA expression in centrifugally prepared exosomes from the plasma of both grazing and housed Japanese Shorthorn cattle. Microarray analysis of the c-miRNAs resulted in detection of a total of 231 bovine exosomal miRNAs in the plasma, with a constant expression level of let-7g across the duration and cattle groups. Expression of muscle-specific miRNAs such as miR-1, miR-133a, miR-206, miR-208a/b, and miR-499 were undetectable, suggesting the mildness of grazing movement as exercise. According to validation by quantitative RT-PCR, the circulating miR-150 level in the grazing cattle normalized by the endogenous let-7g level was down-regulated after 2 and 4 months of grazing (P < 0.05), and then its levels in housed and grazing cattle equalized when the grazing cattle were returned to a housed situation. Likewise, the levels of miR-19b, miR-148a, miR-221, miR-223, miR-320a, miR-361, and miR-486 were temporarily lowered in the cattle at 1 and/or 2 month of grazing compared to those of the housed cattle (P < 0.05). In contrast, the miR-451 level was up-regulated in the grazing cattle at 2 months of grazing (P = 0.044). The elevation of miR-451 level in the plasma was coincident with that in the biceps femoris muscle of the grazing cattle (P = 0.008), which suggests the secretion or intake of miR-451 between skeletal muscle cells and circulation during grazing. These results revealed that exosomal c-miRNAs in cattle were affected by grazing, suggesting their usefulness as molecular grazing markers and functions in physiological adaptation of grazing cattle associated with endocytosis, focal adhesion, axon guidance, and a variety of intracellular signaling, as predicted by bioinformatic analysis. PMID:26308447

  8. Factors affecting the enterohepatic circulation of oral contraceptive steroids.

    PubMed

    Orme, M L; Back, D J

    1990-12-01

    Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol. PMID:2256523

  9. Core Cracking and Hydrothermal Circulation Profoundly Affect Ceres' Geophysical Evolution

    NASA Astrophysics Data System (ADS)

    Neveu, Marc; Desch, Steven J.; Castillo-Rogez, Julie C.

    2014-11-01

    The dwarf planet (1)Ceres is about to be visited by the Dawn spacecraft [1]. In addition to a recent report of water vapor emission [2], observations and models of Ceres suggest that its evolution was shaped by interactions between liquid water and silicate rock [3,4].Hydrothermal processes in a heated core require both fractured rock and liquid. Using a new core cracking model coupled to a thermal evolution code [5], we find volumes of fractured rock always large enough for significant interaction to occur. Therefore, liquid persistence is key. It is favored by antifreezes such as ammonia [4], by silicate dehydration which releases liquid, and by hydrothermal circulation itself, which enhances heat transport into the hydrosphere. The heating effect from silicate hydration seems minor. Hydrothermal circulation can profoundly affect Ceres' evolution: it prevents core dehydration via “temperature resets”, global cooling events lasting ~50 Myr, followed by ~1 Gyr periods during which Ceres' interior is nearly isothermal and its hydrosphere largely liquid. Whether Ceres has experienced such extensive hydrothermalism may be determined through examination of its present-day structure. A large, fully hydrated core (radius 420 km) suggests that extensive hydrothermal circulation prevented core dehydration. A small, dry core (radius 350 km) suggests early dehydration from short-lived radionuclides, with shallow hydrothermalism at best. Intermediate structures with a partially dehydrated core seem ambiguous, compatible both with late partial dehydration without hydrothermal circulation, and with early dehydration with extensive hydrothermal circulation. Thus, gravity measurements by the Dawn orbiter [1] could help discriminate between scenarios for Ceres' evolution.References:[1] Russell C. T. & Raymond C. A. (2011) Sp. Sci. Rev. 163, 3-23.[2] Küppers M. et al. (2014) Nature 505, 525-527.[3] Rivkin A. et al. (2011) Sp. Sci. Rev. 163, 95-116.[4] Castillo-Rogez J. C. & Mc

  10. Elevated Levels of Circulating DNA in Cardiovascular Disease Patients: Metagenomic Profiling of Microbiome in the Circulation

    PubMed Central

    Dinakaran, Vasudevan; Rathinavel, Andiappan; Pushpanathan, Muthuirulan; Sivakumar, Ramamoorthy; Gunasekaran, Paramasamy; Rajendhran, Jeyaprakash

    2014-01-01

    Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An expanding body of evidence supports the role of human microbiome in the establishment of CVDs and, this has gained much attention recently. This work was aimed to study the circulating human microbiome in CVD patients and healthy subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD patients (n = 80) than in healthy controls (n = 40). More specifically, the relative levels of circulating bacterial DNA and the ratio of 16S rRNA/β-globin gene copy numbers were higher in the circulation of CVD patients than healthy individuals. In addition, we found a higher circulating microbial diversity in CVD patients (n = 3) in comparison to healthy individuals (n = 3) by deep shotgun sequencing. At the phylum level, we observed a dominance of Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that in healthy controls, where Proteobacteria was predominantly enriched, followed by Actinobacteria. The circulating virome in CVD patients was enriched with bacteriophages with a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages in contrast to that in healthy individuals, where a relatively greater abundance of eukaryotic viruses dominated by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the release of bacterial and viral DNA elements in the circulation could play a major role leading to elevated circDNA levels in CVD patients. The increased circDNA levels could be either the cause or consequence of CVD incidence, which needs to be explored further. PMID:25133738

  11. Helicobacter pylori infection and circulating ghrelin levels - A systematic review

    PubMed Central

    2011-01-01

    Background The nature of the association between ghrelin, an orexigenic hormone produced mainly in the stomach, and Helicobacter pylori (H pylori), a bacterium that colonises the stomach, is still controversial. We examined available evidence to determine whether an association exists between the two; and if one exists, in what direction. Methods We reviewed original English language studies on humans reporting circulating ghrelin levels in H pylori infected and un-infected participants; and circulating ghrelin levels before and after H pylori eradication. Meta-analyses were conducted for eligible studies by combining study specific estimates using the inverse variance method with weighted average for continuous outcomes in a random effects model. Results Seventeen out of 27 papers that reported ghrelin levels in H pylori positive and negative subjects found lower circulating ghrelin levels in H pylori positive subjects; while 10 found no difference. A meta-analysis of 19 studies with a total of 1801 participants showed a significantly higher circulating ghrelin concentration in H pylori negative participants than in H pylori positive participants (Effect estimate (95%CI) = -0.48 (-0.60, -0.36)). However, eradicating H pylori did not have any significant effect on circulating ghrelin levels (Effect estimate (95% CI) = 0.08 (-0.33, 0.16); Test for overall effect: Z = 0.67 (P = 0.5)). Conclusions We conclude that circulating ghrelin levels are lower in H pylori infected people compared to those not infected; but the relationship between circulating ghrelin and eradication of H pylori is more complex. PMID:21269467

  12. Upper-level circulation in the South Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Peterson, Ray G.; Stramma, Lothar

    In this paper we present a literature survey of the South Atlantic's climate and its oceanic upper-layer circulation and meridional heat transport. The opening section deals with climate and is focused upon those elements having greatest oceanic relevance, i.e., distributions of atmospheric sea level pressure, the wind fields they produce, and the net surface energy fluxes. The various geostrophic currents comprising the upper-level general circulation are then reviewed in a manner organized around the subtropical gyre, beginning off southern Africa with the Agulhas Current Retroflection and then progressing to the Benguela Current, the equatorial current system and circulation in the Angola Basin, the large-scale variability adn interannual warmings at low latitudes, the Brazil Current, the South Atlantic Current, and finally to the Antarctic Circumpolar Current system in which the Falkland (Malvinas) Current is included. A summary of estimates of the meridional heat transport at various latitudes in the South Atlantic ends the survey.

  13. Sex steroid hormones and circulating IgE levels.

    PubMed

    Mathur, S; Mathur, R S; Goust, J M; Williamson, H O; Fudenberg, H H

    1977-12-01

    The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies. PMID:606452

  14. Linkage analysis of circulating levels of adiponectin in Hispanic children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is produced exclusively by adipose tissue and is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to conduct a genome scan of circulating levels of adiponectin in Hispanic children. The present study included extended families with ...

  15. How Circulation of Water Affects Freezing in Ponds

    ERIC Educational Resources Information Center

    Moreau, Theresa; Lamontagne, Robert; Letzring, Daniel

    2007-01-01

    One means of preventing the top of a pond from freezing involves running a circulating pump near the bottom to agitate the surface and expose it to air throughout the winter months. This phenomenon is similar to that of the flowing of streams in subzero temperatures and to the running of taps to prevent pipe bursts in winter. All of these cases…

  16. Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

    PubMed Central

    Zhao, Jin-Ping; Levy, Emile; Fraser, William D.; Julien, Pierre; Delvin, Edgard; Montoudis, Alain; Spahis, Schohraya; Garofalo, Carole; Nuyt, Anne Monique; Luo, Zhong-Cheng

    2014-01-01

    Background Arachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies. Methods and Principal Findings In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity. Conclusion Low circulating DHA levels are associated with compromised

  17. Circulating levels of inflammatory cytokines and risk of colorectal adenomas

    PubMed Central

    Kim, Sangmi; Keku, Temitope O.; Martin, Christopher; Galanko, Joseph; Woosley, John T.; Schroeder, Jane C.; Satia, Jessie A.; Halabi, Susan; Sandler, Robert S.

    2009-01-01

    The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-α in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-α were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between levels of inflammatory cytokines, colorectal adenomas, and known risk factors. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines such as older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-α, and to a lesser degree, with CRP. For IL-6, adjusted odds ratios for colorectal adenomas were 1.78 (95% confidence interval [CI]: 1.18–2.68) for the second highest plasma level, and 1.84 (95% CI: 1.24– 2.74) for the highest level compared with the reference level. A similar association was found with TNF-α, with adjusted odds ratios of 1.54 (95% CI: 1.02–2.33) and 1.65 (95% CI: 1.09–2.50), respectively. Our findings indicate that inflammation might be involved in the early development of colorectal neoplasia, and suggest that systemic inflammatory cytokines might be an indicator of obesity and other risk factors for colorectal neoplasia. PMID:18172326

  18. Circulating Level of miR-378 Predicts Left Ventricular Hypertrophy in Patients with Aortic Stenosis

    PubMed Central

    Xu, Yuanning; Li, Yajiao; Yang, Hao; Rao, Li

    2014-01-01

    Aims Excessively high left ventricle mass is an independent predictor of adverse prognosis. MicroRNAs (miRs) play crucial roles in the regulation of left ventricle hypertrophy (LVH). However, few circulating miRs have been established as predictors of LVH in aortic stenosis (AS) patients. In this study, we aimed to investigate whether circulating levels of miR-1, miR-133, and miR-378 predict LVH in patients with AS. Methods and Results One-hundred twelve patients with moderate to severe AS and 40 healthy controls were included in the study. Levels of miR-1, miR-133, and miR-378 in the plasma were measured by qPCR. Compared with healthy controls, AS patients had significantly lower circulating levels of miR-1, miR-133, and miR-378. AS patients with LVH had significantly lower miR-378 but not miR-1 and miR-133 compared with those without LVH. Linear regression analysis showed circulating miR-378 had strong correlation with left ventricular mass index (r = 0.283, p = 0.002) and logistic regression showed that lower miR-378 was an independent predictor for LVH in patients with AS (p = 0.037, OR 4.110, 95% CI 1.086 to 15.558). Conclusion Circulating levels of miR-1, miR-133 and miR-378 were decreased in AS patients, and miR-378 predicts LVH independent of the pressure gradient. Further prospective investigations are needed to elucidate whether these circulating miRs affect clinical outcome. PMID:25157568

  19. The Dependence of the Low-Level Equatorial Easterly Jet on Hadley and Walker Circulations.

    NASA Astrophysics Data System (ADS)

    Battisti, David S.; Ovens, David D.

    1995-11-01

    How the time-mean Hadley and Walker circulations affect the formation of a low-level equatorial easterly jet is investigated. Experiments are conducted for equinoctial conditions using a general circulation model, the Community Climate Model (CCM1), that includes a Kuo convective scheme and a lower boundary that is specified to be water at a fixed sea surface temperature (SST). Several zonally symmetric SST forcings are used to determine how various Hadley circulations affect the tropical zonal wind field. A zonal wavenumber one equatorial SST anomaly superimposed on a zonally symmetric SST distribution forces a wind field that includes both Hadley and Walker circulations.The Hadley circulation experiments produce equatorial easterlies and low-level jets on the poleward sides of the intertropical convergence zone (ITCZ) 10° to 15° from the equator. In an experiment with a single, dominant off-equatorial ITCZ in the Northern Hemisphere, the Southern Hemisphere jet moves to within 7.5° of the equator; yet none of the Hadley circulation cases produce a low-level easterly jet on the equator because they lack a mechanism to vertically confine the flow.The experiment that includes a zonally overturning cell on the equator produces a low-level equatorial easterly jet in the cold tongue region that is similar to the observed jet over the central to eastern Pacific. That case shows that east of the equatorial warm pool the Walker circulation and its induced Kelvin wave response provide the necessary upper-level westerly flow and subsidence to vertically confine the low-level easterlies into a jet. Spring and fall climatological runs of the CCMI with land surfaces, seasonally varying SSTs and insolation, and a moist convective adjustment scheme support the hypothesis that the Walker circulation provides the vertical confinement necessary to form a low-level equatorial easterly jet in the region east of the equatorial convective center, regardless of the Hadley circulation

  20. Impacts of sea-level rise on estuarine circulation: An idealized estuary and San Francisco Bay

    NASA Astrophysics Data System (ADS)

    Chua, Vivien P.; Xu, Ming

    2014-11-01

    Estuaries lie at the interface of land and sea, and are particularly vulnerable to sea-level rise due to climate change that might lead to intrusion of salt water further upstream and affect circulation patterns. Climate change is also likely to have a major impact on hydrological cycles and consequently lead to changes in freshwater inflows into estuaries. An idealized estuary model is employed to investigate the effects of sea-level rise and freshwater inflows on estuarine circulation. Rising sea levels result in a stronger longitudinal salinity gradient ∂s/∂x, indicating an increase in the strength of the gravitational circulation UGC, higher longitudinal dispersion coefficients K and enhanced salinity intrusion. Under low-flow conditions, the effects of sea level rise on salinity intrusion are largest because sea-level rise has a greater impact due to weaker vertical stratification. Strong flows increase the strength of the gravitational circulation, resulting in higher vertical stratification, which leads to the nonlinear feedback between vertical mixing and stratification. The effect of sea-level rise on salinity intrusion is reduced owing to the suppression of mixing by stratification. Supporting three-dimensional simulations from northern San Francisco Bay are presented. The intrusion length scale L is used as a substitute for regulating inflows to ensure that sufficient fresh water is available to flush the Bay. Following a set of standards explicitly stated in the 1994 Bay-Delta Accord, a series of simulations is performed and we find that with sea-level rise stronger inflows are required to maintain L at the proposed locations.

  1. Late Holocene sea level variability and Atlantic Meridional Overturning Circulation

    USGS Publications Warehouse

    Cronin, Thomas M.; Farmer, Jesse R.; Marzen, R. E.; Thomas, E.; Varekamp, J.C.

    2014-01-01

    Pre-twentieth century sea level (SL) variability remains poorly understood due to limits of tide gauge records, low temporal resolution of tidal marsh records, and regional anomalies caused by dynamic ocean processes, notably multidecadal changes in Atlantic Meridional Overturning Circulation (AMOC). We examined SL and AMOC variability along the eastern United States over the last 2000 years, using a SL curve constructed from proxy sea surface temperature (SST) records from Chesapeake Bay, and twentieth century SL-sea surface temperature (SST) relations derived from tide gauges and instrumental SST. The SL curve shows multidecadal-scale variability (20–30 years) during the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA), as well as the twentieth century. During these SL oscillations, short-term rates ranged from 2 to 4 mm yr−1, roughly similar to those of the last few decades. These oscillations likely represent internal modes of climate variability related to AMOC variability and originating at high latitudes, although the exact mechanisms remain unclear. Results imply that dynamic ocean changes, in addition to thermosteric, glacio-eustatic, or glacio-isostatic processes are an inherent part of SL variability in coastal regions, even during millennial-scale climate oscillations such as the MCA and LIA and should be factored into efforts that use tide gauges and tidal marsh sediments to understand global sea level rise.

  2. Calcium Deficiency Reduces Circulating Levels of FGF23

    PubMed Central

    Rodriguez-Ortiz, María E.; Lopez, Ignacio; Muñoz-Castañeda, Juan R.; Martinez-Moreno, Julio M.; Ramírez, Alan Peralta; Pineda, Carmen; Canalejo, Antonio; Jaeger, Philippe; Aguilera-Tejero, Escolastico; Felsenfeld, Arnold; Almaden, Yolanda

    2012-01-01

    Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. PMID:22581996

  3. Examination of Physical Processes Influencing Coastal Circulation over the Inner Scotian Shelf using a Five-Level Nested-Grid Ocean Circulation Model

    NASA Astrophysics Data System (ADS)

    Sheng, J.

    2008-12-01

    A multiply nested-grid ocean circulation modeling system was developed for coastal waters of the Inner Scotian Shelf (ISS) by coupling a limited-area coastal circulation model to an operational shelf circulation model known as Dalcoast. The nested-grid system has five relocatable, dynamically-downscaling five sub- components. The outermost sub-component of the system has a coarse horizontal resolution of (1/12)o for simulating storm surges and two-dimensional barotropic shelf waves over the eastern Canadian shelf (ECS) from Labrador Shelf to the Gulf of Maine, and the innermost sub-component has a fine horizontal resolution of about ~180 m for simulating three-dimensional circulation and hydrographic distributions over Lunenburg Bay of Nova Scotia in the default setup. The nested-grid system is driven by meteorological and astronomical forcing. The meteorological forcing includes sea level air pressures, wind stress and surface heat/freshwater fluxes converted from the 3 hourly weather forecasts produced by the Meteorological Service of Canada. The astronomical forcing is the tidal sea levels and depth-mean currents produced by WebTide based on pre-calculated harmonic constants of five major tidal constitutes over the ECS. In this study, the nested-grid system is used to investigate main physical processes affecting the three-dimensional (3D) circulation and hydrographic distributions over the ISS in June and July 2006. Model results demonstrate that the coastal circulation and hydrographic distributions over the study region are affected significantly by tides, local wind forcing, remotely generated coastal waves during the study period.

  4. Changes in serum enzyme levels accompanying cardiac surgery with extracorporeal circulation

    PubMed Central

    Welbourn, Nora; Melrose, D. G.; Moss, D. W.

    1966-01-01

    Serum lactic dehydrogenase, alpha-hydroxy-butyrate dehydrogenase, iso-citric dehydrogenase, and glutamic oxaloacetic transaminase activities were measured daily for two weeks postoperatively in the serum of 22 patients undergoing cardiac surgery with extracorporeal circulation. The length of perfusion was found to be a major factor affecting the extent of increased post-operative enzyme activities. Significantly higher levels were demonstrated in patients perfused for over one hour compared with those perfused for under one hour. Hepatocellular damage, age, and type of operation were not considered to be major factors in determining the extent of this increased activity. A considerable increase in enzyme activity was found to occur during perfusion when the dilution introduced by mixing the patient's circulation with the priming fluid of the heart-lung machine was taken into account. This dilution, when accounted for, increased the observed enzyme activity by 30 to 50%. PMID:5937606

  5. CLIL Learning: Achievement Levels and Affective Factors

    ERIC Educational Resources Information Center

    Seikkula-Leino, Jaana

    2007-01-01

    The aim of the study was to investigate how successfully pupils had learned content in content and language integrated learning (CLIL) and to assess pupils' affective learning factors, such as motivation and self-esteem, in CLIL. Learning was presented in terms of achievement level, which was described as the relationship between measured levels…

  6. Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents

    PubMed Central

    Quiñones, Mar; Folgueira, Cintia; Sánchez-Rebordelo, Estrella; Al-Massadi, Omar

    2015-01-01

    Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance. PMID:26568663

  7. Differential Associations between CDH13 Genotypes, Adiponectin Levels, and Circulating Levels of Cellular Adhesive Molecules

    PubMed Central

    Teng, Ming-Sheng; Wu, Semon; Hsu, Lung-An; Chou, Hsin-Hua; Ko, Yu-Lin

    2015-01-01

    CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P < 0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P = 3.9 × 10−4 and interaction P = 0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases. PMID:26600672

  8. Core cracking and hydrothermal circulation can profoundly affect Ceres' geophysical evolution

    NASA Astrophysics Data System (ADS)

    Neveu, Marc; Desch, Steven J.; Castillo-Rogez, Julie C.

    2015-02-01

    Observations and models of Ceres suggest that its evolution was shaped by interactions between liquid water and silicate rock. Hydrothermal processes in a heated core require both fractured rock and liquid. Using a new core cracking model coupled to a thermal evolution code, we find volumes of fractured rock always large enough for significant interaction to occur. Therefore, liquid persistence is key. It is favored by antifreezes such as ammonia, by silicate dehydration which releases liquid, and by hydrothermal circulation itself, which enhances heat transport into the hydrosphere. The effect of heating from silicate hydration seems minor. Hydrothermal circulation can profoundly affect Ceres' evolution: it prevents core dehydration via "temperature resets," core cooling events lasting ˜50 Myr during which Ceres' interior temperature profile becomes very shallow and its hydrosphere is largely liquid. Whether Ceres has experienced such extensive hydrothermalism may be determined through examination of its present-day structure. A large, fully hydrated core (radius 420 km) would suggest that extensive hydrothermal circulation prevented core dehydration. A small, dry core (radius 350 km) suggests early dehydration from short-lived radionuclides, with shallow hydrothermalism at best. Intermediate structures with a partially dehydrated core seem ambiguous, compatible both with late partial dehydration without hydrothermal circulation, and with early dehydration with extensive hydrothermal circulation. Thus, gravity measurements by the Dawn orbiter, whose arrival at Ceres is imminent, could help discriminate between scenarios for Ceres' evolution.

  9. Circulating Levels of 25-hydroxyvitamin D and Prostate Cancer Prognosis

    PubMed Central

    Holt, Sarah K.; Kolb, Suzanne; Fu, Rong; Horst, Ronald; Feng, Ziding; Stanford, Janet L.

    2013-01-01

    Objectives Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer. Methods and Materials We conducted a population-based cohort study of 1,476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D]. Results There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/ progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes. Conclusions We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality. PMID:23972671

  10. How High Glucose Levels Affect Tendon Homeostasis.

    PubMed

    Snedeker, Jess G

    2016-01-01

    Among the many factors playing a role in tendon disease, unregulated biochemical reactions between glucose and the collagen extracellular matrix are coming increasingly into focus. We have shown that formation of advanced glycation end-products that cross-link the collagen extracellular matrix can drastically affect cellular level mechanical properties of the matrix, and in turn affect cell-level biomechanical stimuli during physiological loading of the tissue. We suggest that these may adversely affect tendon cell response to matrix damage, as well as the quality of the consequent repair. If such mechanical feedback loops are altered, the ability of tendon cells to maintain tissue in a functional, healthy state may be compromised. Although key foundational elements of biochemical, biomechanical, and biological understanding are now in place, the full extent of how these aspects interact, including the precise mechanisms by which advanced glycation end-products pathologically disrupt connective tissue homeostasis and damage repair, are only beginning to be adequately appreciated. PMID:27535261

  11. Decreased Circulating Levels of APRIL: Questioning Its Role in Diabetes

    PubMed Central

    Carvalho-Santos, Adriana; Ribeiro-Alves, Marcelo; Cardoso-Weide, Luciene Carvalho; Nunes, Joyce; Kuhnert, Lia Rafaella Ballard; Xavier, Analucia Rampazzo; Cunha, Samuel; Hahne, Michael; Villa-Verde, Déa Maria Serra; Carvalho-Pinto, Carla Eponina

    2015-01-01

    Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic β-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to β-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes. PMID:26469782

  12. Decreased Circulating Levels of APRIL: Questioning Its Role in Diabetes.

    PubMed

    Carvalho-Santos, Adriana; Ribeiro-Alves, Marcelo; Cardoso-Weide, Luciene Carvalho; Nunes, Joyce; Kuhnert, Lia Rafaella Ballard; Xavier, Analucia Rampazzo; Cunha, Samuel; Hahne, Michael; Villa-Verde, Déa Maria Serra; Carvalho-Pinto, Carla Eponina

    2015-01-01

    Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic β-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to β-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes. PMID:26469782

  13. Circulating CTRP1 Levels in Type 2 Diabetes and Their Association with FGF21

    PubMed Central

    Han, Sora; Kim, Jong Dai; Lee, Sunyi; Jeong, Ae Lee; Park, Jeong Su; Yong, Hyo Jeong; Boldbaatar, Ariundavaa; Ka, Hye In; Rhee, Eun-Jung; Lee, Won-Young; Yang, Young

    2016-01-01

    The goal of this study was to investigate whether circulating C1q/TNF-α-related protein 1 (CTRP1) levels are associated with diabetes. In addition, relationships between CTRP1 and other diabetes-related cytokines were elucidated, including adiponectin and fibroblast growth factor 21 (FGF21). A total of 178 subjects (78 men and 100 women) aged 29–70 years (mean age, 46.1 years) were randomly selected. The sera from a normal glucose tolerance group (n = 68) and a prediabetes/type 2 diabetes group (n = 110) were collected; then, circulating levels of CTRP1, adiponectin, and FGF21 were determined via enzyme-linked immunosorbent assay in all sera. Subjects with either prediabetes or diabetes exhibited higher circulating CTRP1 levels than healthy subjects. Sera analysis revealed that CTRP1 was positively correlated with age, body mass index, fasting blood glucose, and circulating FGF21 levels. However, CTRP1 was negatively correlated with total cholesterol and total circulating adiponectin levels in univariate analysis. In addition, multivariate analysis found that CTRP1 was independently associated with age, fasting blood glucose, and circulating FGF21 levels. CTRP1 was correlated with homeostasis model assessment-β (HOMA-β), but no correlation was observed with HOMA-insulin resistance. In conclusion, circulating CTRP1 levels are increased in subjects with type 2 diabetes and are positively associated with circulating FGF21 levels. PMID:27313611

  14. Circulating Irisin Levels Are Positively Associated with Metabolic Risk Factors in Sedentary Subjects

    PubMed Central

    Moreno, María; Moreno-Navarrete, José María; Serrano, Marta; Ortega, Francisco; Delgado, Elías; Sanchez-Ragnarsson, Cecilia; Valdés, Sergio; Botas, Patricia; Ricart, Wifredo; Fernández-Real, José Manuel

    2015-01-01

    Introduction A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans. Methods Circulating irisin levels (ELISA) and metabolic parameters were analyzed in 428 subjects (195 men/233 women). Participants were classified according to their self-reported physical activity and to their area of residence. Results Circulating irisin levels were higher in active than in sedentary subjects (p= 0.006). Rural inhabitants showed higher circulating irisin levels than urban subjects (p < 0.0001). The increase in irisin levels related to an active lifestyle was only observed in rural citizens (p = 0.014). Among sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides). The area of residence (β= - 0.592, p= < 0.0001) contributed independently to circulating irisin levels variance after controlling for age, gender, BMI, HOMAIR, triglycerides and physical activity. Conclusions In sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels. PMID:25897751

  15. Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation.

    PubMed

    Shiba, T; Inoguchi, T; Sportsman, J R; Heath, W F; Bursell, S; King, G L

    1993-11-01

    The increases in diacylglycerol (DAG) level and protein kinase C (PKC) activity have been characterized biochemically and functionally in the retina and the brain of diabetic rats as well as in cultured vascular cells. PKC specific activities were increased in the membraneous fraction of retina from streptozotocin (STZ)-induced diabetic rats and the genetically determined diabetic BB rats, respectively, after 1 or 2 wk of diabetes, compared with control. The ratio of total PKC activities from membraneous and cytosol fractions was also increased in the retina of diabetic rats. With diabetes, all the isoenzymes and the total DAG level were increased in the rat retina, whereas no changes were found in the rat brain. Insulin treatment normalized plasma glucose levels and partially prevented the increases in the membraneous PKC activity and all the isoenzymes in the retina. In the retinal endothelial cells, the total DAG level and PKC specific activities are increased by 36 and 22%, respectively, in the membraneous pool when the glucose levels are changed from 5.5 to 22 mM. Activation of PKC activity and isoform beta II by the vitreal injection of phorbol dibutyrate mimicked the abnormal retinal blood circulation observed in diabetic rats (2.22 +/- 0.24 vs. 1.83 +/- 0.40 s). Thus diabetes and elevated glucose levels will increase DAG level and PKC activities and its isoenzyme specifically in vascular cells and may affect retinal hemodynamics. PMID:8238505

  16. Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma.

    PubMed

    Bhat, Shweta; Jagadeeshaprasad, Mashanipalya G; Patil, Yugendra R; Shaikh, Mahemud L; Regin, Bhaskaran S; Mohan, Viswanathan; Giri, Ashok P; Balasubramanyam, Muthuswamy; Boppana, Ramanamurthy; Kulkarni, Mahesh J

    2016-06-01

    A Hyperglycemic condition in diabetes promotes formation of advanced glycation end products, which are known to elicit immune response and form complexes with immunoglobulins called circulating immune complexes. To investigate the involvement of advanced glycation end product (AGE)-modified proteins in the elicitation of an immune response, circulating immune complexes were isolated and proteins associated were identified and characterized. Label-free-based mass spectrometric analysis of circulating immune complexes in clinical plasma of prediabetic, newly diagnosed diabetes, and diabetic microalbuminurea revealed elevated levels of serum albumin in the circulating immune complexes, which were also observed to be AGE modified. Further, to examine the role of glycation, circulating immune complexeswere analyzed in the streptozotocin-induced diabetic mice treated with or without aminoguanidine, a prototype glycation inhibitor. Mass spectrometric analysis of circulating immune complexes showed elevated levels of serum albumin in plasma from diabetic mice over that of control animals. Aminoguanidine-treated diabetic mice displayed decreased AGE modification of plasma albumin, accompanied by a reduced level of albumin in the circulating immune complexes. In addition, elevated levels of proinflammatory cytokines such as IL-1b, IL-2, and TNF-alpha were observed in diabetes, which were reduced with aminoguanidine treatment, suggesting the involvement of glycation in the immune response. PMID:27056913

  17. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

    PubMed

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  18. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

    PubMed Central

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  19. Changes in circulating levels of fibroblast growth factor 23 induced by short-term dietary magnesium deficiency in rats.

    PubMed

    Matsuzaki, Hiroshi; Katsumata, Shinichi; Maeda, Yoshiaki; Kajita, Yasutaka

    2016-06-01

    Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphorus (P) and vitamin D metabolism. Long-term dietary magnesium (Mg) deficiency increases circulating levels of FGF23, whereas the effects of short-term dietary Mg deficiency are unclear. Thus, the present study investigated whether short-term dietary Mg deficiency affects circulating levels of FGF23. We also assessed changes in renal mRNA expression of vitamin D metabolizing enzymes and type II sodium-phosphate (Na/Pi) cotransporters, since these are regulated by FGF23. Rats were fed a control diet (control group) or an Mg-deficient diet (Mg-deficient group) for 2, 4 or 7 days. Serum Mg levels were significantly lower in the Mg-deficient group than in the control group at all time points. Serum FGF23 levels were significantly higher in the Mg-deficient group than in the control group at day 7. The 25-hydroxyvitamin D-24-hydroxylase (24(OH)ase) mRNA levels were significantly higher in the Mg-deficient group than in the control group at day 7 . No significant differences in types IIa and IIc Na/Pi cotransporter mRNA levels were observed between the control and Mg-deficient groups. These results suggest that dietary Mg deficiency causes a rapid increase in circulating levels of FGF23 and renal 24(OH)ase mRNA levels. PMID:27624533

  20. Coastal recirculation potential affecting air pollutants in Portugal: The role of circulation weather types

    NASA Astrophysics Data System (ADS)

    Russo, Ana; Gouveia, Célia; Levy, Ilan; Dayan, Uri; Jerez, Sonia; Mendes, Manuel; Trigo, Ricardo

    2016-06-01

    Coastal zones are under increasing development and experience air pollution episodes regularly. These episodes are often related to peaks in local emissions from industry or transportation, but can also be associated with regional transport from neighbour urban areas influenced by land-sea breeze recirculation. This study intends to analyze the relation between circulation weather patterns, air mass recirculation and pollution levels in three coastal airsheds of Portugal (Lisbon, Porto and Sines) based on the application of an objective quantitative measure of potential recirculation. Although ventilation events have a dominant presence throughout the studied 9-yrs period on all the three airsheds, recirculation and stagnation conditions occur frequently. The association between NO2, SO2 and O3 levels and recirculation potential is evident during summer months. Under high average recirculation potential and high variability, NO2 and SO2 levels are higher for the three airsheds, whilst for O3 each airshed responds differently. This indicates a high heterogeneity among the three airsheds in (1) the type of emission - traffic or industry - prevailing for each contaminant, and (2) the response to the various circulation weather patterns and recirculation situations. Irrespectively of that, the proposed methodology, based on iterative K-means clustering, allows to identify which prevailing patterns are associated with high recirculation potential, having the advantage of being applicable to any geographical location.

  1. Venus: Cloud level circulation during 1982 as determined from Pioneer cloud photopolarimeter images. II - Solar longitude dependent circulation

    NASA Technical Reports Server (NTRS)

    Limaye, Sanjay S.

    1988-01-01

    Pioneer Venus Orbiter images obtained in 1982 indicate a marked solar-locked dependence of cloud level circulation in both averaged cloud motions and cloud layer UV reflectivity. An apparent relationship is noted between horizontal divergence and UV reflectivity: the highest reflectivities are associated with regions of convergence at high latitudes, while lower values are associated with equatorial latitude regions where the motions are divergent. In solar-locked coordinates, the rms deviation of normalized UV brightness is higher at 45-deg latitudes than in equatorial regions.

  2. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia.

    PubMed

    Muñoz-Hernandez, Rocio; Miranda, Maria L; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M; Dominguez-Simeon, Maria J; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M

    2014-07-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

  3. DECREASED LEVEL OF CORD BLOOD CIRCULATING ENDOTHELIAL COLONY-FORMING CELLS IN PREECLAMPSIA

    PubMed Central

    Muñoz-Hernandez, Rocio; Miranda, Maria L.; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M.; Dominguez-Simeon, Maria J.; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M.

    2014-01-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

  4. Observed cloud level circulation on Venus - Temporal variations and solar longitude dependence

    NASA Technical Reports Server (NTRS)

    Limaye, Sanjay Shridhar

    1987-01-01

    This paper presents data on the atmospheric circulation of Venus, obtained by the Mariner 10 (1974) and Pioneer (1979-1986) observations. The results yielded evidence of relatively stable zonal circulation at the cloud level. On the other hand, changes on a yearly time scale appear in both the zonal and the meridional components of motion. Solar thermal tides and large-scale planetary waves are also seen in averaged zonal and meridional cloud motions. The relationship between the large-scale circulation and global cloud structure is discussed.

  5. Ocean circulation off east Antarctica affects ecosystem structure and sea-ice extent.

    PubMed

    Nicol, S; Pauly, T; Bindoff, N L; Wright, S; Thiele, D; Hosie, G W; Strutton, P G; Woehler, E

    2000-08-01

    Sea ice and oceanic boundaries have a dominant effect in structuring Antarctic marine ecosystems. Satellite imagery and historical data have identified the southern boundary of the Antarctic Circumpolar Current as a site of enhanced biological productivity. Meso-scale surveys off the Antarctic peninsula have related the abundances of Antarctic krill (Euphausia superba) and salps (Salpa thompsoni) to inter-annual variations in sea-ice extent. Here we have examined the ecosystem structure and oceanography spanning 3,500 km of the east Antarctic coastline, linking the scales of local surveys and global observations. Between 80 degrees and 150 degrees E there is a threefold variation in the extent of annual sea-ice cover, enabling us to examine the regional effects of sea ice and ocean circulation on biological productivity. Phytoplankton, primary productivity, Antarctic krill, whales and seabirds were concentrated where winter sea-ice extent is maximal, whereas salps were located where the sea-ice extent is minimal. We found enhanced biological activity south of the southern boundary of the Antarctic Circumpolar Current rather than in association with it. We propose that along this coastline ocean circulation determines both the sea-ice conditions and the level of biological productivity at all trophic levels. PMID:10952309

  6. Association between circulating adiponectin levels and polycystic ovarian syndrome

    PubMed Central

    2014-01-01

    Background Low adiponectin levels in polycystic ovarian syndrome (PCOS) have been largely attributed to obesity which is common among these patients. In addition, evidence also suggests that low adiponectin in PCOS may be related to insulin resistance (IR) in these women. However, studies on the role of adiponectin in younger and lean patients are limited. Therefore, the aim of the present study was to examine the association of adiponectin levels in young and lean women with PCOS. Methods A case–control study was conducted at the Dow University of Health Sciences, Karachi, Pakistan. Cases were 75 patients of PCOS with Body Mass Index (BMI) &23 aged 16–35 years and 75 healthy age and BMI matched controls were selected from family and friends of the cases. Demographic details, family history and past medical history were obtained through interview by a physician. Anthropometric measurements included weight and height of the participants. Fasting glucose, total cholesterol, high-density lipoprotein (HDL), insulin, adiponectin, and androgen levels were determined. IR was calculated using homeostasis model assessment for insulin resistance (HOMA-IR). Logistic regression models were used to assess the association between adiponectin and PCOS after adjusting for co-variates. Results On multivariable analysis, PCOS cases were 3.2 times more likely to have low adiponectin level (OR = 3.2, 95% CI 1.49-6.90, p-value 0.003) compared to the controls after adjustment for age, BMI, family history, marital status, total cholesterol, HDL level and IR. Females with a family history of PCOS were significantly more likely to have lower adiponectin (OR = 3.32, 95% CI 1.27-8.67, p-value 0.014) compared to those who did not have a family history of PCOS. The associations of IR and family history with low adiponectin level also remained statistically significant after adjustments for covariates. Conclusion Serum adiponectin levels are independently associated with PCOS and

  7. Plasma components affect accuracy of circulating cancer-related microRNA quantitation.

    PubMed

    Kim, Dong-Ja; Linnstaedt, Sarah; Palma, Jaime; Park, Joon Cheol; Ntrivalas, Evangelos; Kwak-Kim, Joanne Y H; Gilman-Sachs, Alice; Beaman, Kenneth; Hastings, Michelle L; Martin, Jeffrey N; Duelli, Dominik M

    2012-01-01

    Circulating microRNAs (miRNAs) have emerged as candidate biomarkers of various diseases and conditions including malignancy and pregnancy. This approach requires sensitive and accurate quantitation of miRNA concentrations in body fluids. Herein we report that enzyme-based miRNA quantitation, which is currently the mainstream approach for identifying differences in miRNA abundance among samples, is skewed by endogenous serum factors that co-purify with miRNAs and anticoagulant agents used during collection. Of importance, different miRNAs were affected to varying extent among patient samples. By developing measures to overcome these interfering activities, we increased the accuracy, and improved the sensitivity of miRNA detection up to 30-fold. Overall, the present study outlines key factors that prevent accurate miRNA quantitation in body fluids and provides approaches that enable faithful quantitation of miRNA abundance in body fluids. PMID:22154918

  8. Demographic, socioeconomic and environmental changes affecting circulation of neglected tropical diseases in Egypt.

    PubMed

    Abou-El-Naga, Iman F

    2015-11-01

    Egypt has been plagued by many neglected tropical diseases since Pharaonic time. These diseases are Schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis, leishmaniasis and fascioliasis beside the epidermal parasitic skin diseases. Indeed, theses diseases still persist as public health problem in the country by the influence of demographic, socioeconomic and environmental obstacles. This study seeks for understanding the contribution of each factor in each obstacle in neglected tropical diseases perpetuation which in turn could help the governorate in planning integrated control strategies. It was found that poverty, unregulated urbanization and inadequate sanitation are important socioeconomic factors that have great effect on the transmission dynamics of the diseases. The environmental factors which affect the epidemiology of these diseases in the country are scarcity of water, construction of dams, land reclamation for agriculture beside the climate factors. Unfortunately, the panic increase in the population growth rate minimizes the efforts done by the governorate to elevate the public health services. These conditions also affect the transmission of epidermal parasitic skin diseases including scabies, head lice and hookworm-related cutaneous larva migrans. The control programs and the recommendations to combat the diseases were discussed. The present study showed that the ecological factors affecting each neglected tropical disease in Egypt are somewhat similar which makes it worthy to develop an integrated control approaches aiming at improving the leading factors of neglected tropical diseases circulation in the country. PMID:26614986

  9. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head

    PubMed Central

    Zhu, H-Y.; Gao, Y-C.; Wang, Y.

    2016-01-01

    Objectives Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). Methods We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis. Results The circulating exosome level of the ONFH group was significantly lower than that of control group. The area under the curve was 0.72, suggesting that the level of serum exosomes has moderate diagnostic accuracy for steroid-induced ONFH. Conclusion Circulating exosome levels are valuable in the diagnosis of steroid-induced ONFH. Cite this article: H-Y. Zhu, Y-C. Gao, Y. Wang, C-Q. Zhang. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. Bone Joint Res 2016;5:276–279. DOI: 10.1302/2046-3758.56.BJR-2015-0014.R1. PMID:27357384

  10. Role of the Qinghai-Xizang plateau in feedback mechanisms affecting the planetary circulation

    SciTech Connect

    Reiter, E.R.; Yi-Hui, D.

    1980-01-01

    It has been recognized for some time that the Qinghai-Xizang plateau is of great importance in generating planetary long-waves which, in resonance with similar waves induced by the Rocky Mountains, lead to the familiar pattern of quasi-stationary Rossby waves observed on monthly-mean upper level pressure charts. Seasonal forcing of flow patterns also appears to be particularly strong in the Qinghai-Xizang plateau region. Recent investigations suggest that the Qinghai-Xizang plateau may also be involved in feedback mechanisms which control in an important way the interannual variability of the general circulation of the atmosphere. It appears that the effects of the Qinghai-Xizang plateau on the interannual variability of the atmospheric circulation over Asia are but one important manifestation of a network of feedback mechanisms, ranging from the El Nino problems along the Peruvian coast to droughts in the Sahel region. A better understanding of each of the mechanisms involved will lead us closer to successful long-range forecasting of some of the weather phenomena which have a considerable effect on local and regional economics.

  11. Circulating Levels of Irisin in Hypopituitary and Normal Subjects

    PubMed Central

    Pena-Bello, Lara; Pértega-Diaz, Sonia; Sangiao-Alvarellos, Susana; Outeiriño-Blanco, Elena; Eiras-Leal, Raquel; Varela-Rodriguez, Bárbara; Juiz-Valiña, Paula; Pérez-Fontán, Miguel; Cordido, María; Cordido, Fernando

    2016-01-01

    Context The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP) is a situation characterized by decreased GH secretion and an altered body composition. Objective Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects. Participants and Methods Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 μg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-β were calculated. Results Fasting irisin levels (ng/ml) were similar in normal [208.42 (168.44–249.23)] and HP patients [195.13 (178.44–241.44)]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-β, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-β. Conclusions We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH. PMID:27472279

  12. Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients. Influence of ACE inhibition.

    PubMed

    Ferri, C; Laurenti, O; Bellini, C; Faldetta, M R; Properzi, G; Santucci, A; De Mattia, G

    1995-01-01

    To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7734095

  13. Modulation of Circulating MicroRNAs Levels during the Switch from Clopidogrel to Ticagrelor

    PubMed Central

    Carino, Annarita; De Rosa, Salvatore; Sorrentino, Sabato; Polimeni, Alberto; Sabatino, Jolanda; Caiazzo, Gianluca; Torella, Daniele; Spaccarotella, Carmen; Mongiardo, Annalisa; Strangio, Antonio; Filippis, Carol; Indolfi, Ciro

    2016-01-01

    Background. Circulating microRNAs are appealing biomarkers to monitor several processes underlying cardiovascular diseases. Platelets are a major source for circulating microRNAs. Interestingly, the levels of specific microRNAs were reported to correlate with the level of platelet activation. The aim of the present study was to test whether the treatment with the novel antiplatelet agent, ticagrelor, is associated with modulation in the levels of key platelet-derived microRNAs. Methods and Results. Patients were randomly selected from those participating in the SHIFT-OVER study, in which we had previously evaluated the effect of the therapeutic switch from clopidogrel to ticagrelor on platelet aggregation. Circulating levels of selected microRNAs were measured before and after the therapeutic switch from a dual antiplatelet therapy including acetylsalicylic acid (ASA) and clopidogrel to the more potent ticagrelor. Interestingly, the circulating levels of miR-126 (p = 0.030), miR-223 (p = 0.044), and miR-150 (p = 0.048) were significantly reduced, while the levels of miR-96 were increased (p = 0.038). No substantial differences were observed for the remaining microRNAs. Conclusions. Switching from a dual antiplatelet treatment with clopidogrel to ticagrelor is associated with significant modulation in the circulating levels of specific microRNAs. If confirmed in larger, independent cohorts, our results pave the way for the use of circulating microRNAs as biomarkers of platelets activity in response to specific pharmacological treatments. PMID:27366745

  14. Effects of polychlorinated biphenyls on mourning dove reproduction and circulating progesterone levels

    SciTech Connect

    Koval, P.J.; Peterle, T.J.; Harder, J.D.

    1987-10-01

    PCBs acquired in sublethal doses increase activation of the liver's microsomal action and hepatic mixed function oxidase (MFO) enzymes. Physiological effects of increase in the MFO system may delay, if not eliminate, avian reproductive behavior and nesting success. No evidence is yet available to clearly link PCBs to lowered levels of circulating steroids in birds. However, data concerning the effects of PCBs on avian reproduction are abundant. Increased degradation of circulating steroids might alter essential hormone dynamics associated with nesting behavior and ovulation. Alternatively, normal feedback regulation by the pituitary-gonadal axis might lead to a full compensatory response to increased MFO such that hormone profiles remain unaltered, suggesting alternative modes of action for PCBs in reproductive disorders. Therefore, the authors investigated the effect of dietary PCBs on circulating progesterone levels prior to and during egg laying in wild-trapped mourning doves (Zenaida macroura).

  15. Prognostic value of circulating DNA levels in critically ill and trauma patients.

    PubMed

    Rodrigues Filho, Edison Moraes; Ikuta, Nilo; Simon, Daniel; Regner, Andrea Pereira

    2014-01-01

    The number of studies investigating circulating nucleic acids as potential biomarkers has increased in recent years. The detection of such biomarkers is a minimally invasive alternative for the diagnosis and prognosis of various clinical conditions. The value of circulating DNA levels as a predictive biomarker has been demonstrated in patients suffering from numerous acute pathologies that have a high risk of intensive care needs and in-hospital deaths. The mechanism by which circulating DNA levels increase in patients with these conditions remains unclear. In this review, we focused on the potential use of this biomarker for prognosis prediction in critically ill and trauma patients. The literature review was performed by searching MedLine using PubMed in the English language. PMID:25295826

  16. Levels of circulating TNF-related apoptosis-inducing ligand in celiac disease

    PubMed Central

    CELEGHINI, CLAUDIO; NOT, TARCISIO; NORCIO, ALESSIA; MONASTA, LORENZO; SECCHIERO, PAOLA

    2014-01-01

    It has previously been demonstrated that the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL) are significantly lower in patients with type 1 diabetes (T1D) than in normal age- and gender-matched controls. Since celiac disease (CD) is often associated with T1D, a retrospective study was performed to analyze the sera of a cohort of pediatric subjects: i) patients with CD at onset (n=100); ii) patients with potential CD (n=45); iii) patients with CD associated with other auto-immune diseases (n=17); and iv) patients with eosinophilic esophagitis (n=15). Among the patients with CD, 49 were also analyzed after six months on a gluten-free diet, while data were also available for 13 patients after one year on a gluten-free diet. No significant differences were found in the circulating levels of TRAIL between the patients with CD and the patients with either eosinophilic esophagitis or potential CD. Patients with CD associated with other auto-immune diseases showed significantly lower levels of TRAIL when compared with patients with CD alone. The gluten-free diet did not significantly modify the levels of circulating TRAIL at 6 or 12 months. Thus, although T1D and CD share common immunological features, the circulating levels of TRAIL show a significant difference between the two pathologies, and do not appear to be modulated in CD. PMID:25371753

  17. Impact of negative affectivity and trait forgiveness on aortic blood pressure and coronary circulation.

    PubMed

    Sanchez-Gonzalez, Marcos A; May, Ross W; Koutnik, Andrew P; Fincham, Frank D

    2015-02-01

    Prior research suggests that negative affectivity (NA) may have a direct adverse effect on coronary circulation, whereas forgiveness may provide cardioprotection. This study examined whether NA and forgiveness were independently related to aortic hemodynamics and the subendocardial viability index (SVI), a marker of coronary perfusion. A sample of 131 adults (M = 21.11 years, SD = 2.52) were evaluated for NA (depression, anxiety, and anger symptoms) and forgiveness (Tendency to Forgive Scale; TTF). Aortic hemodynamic parameters via applanation tonometry were assessed at rest and during sympathostimulation (cold pressor test; CPT). Hierarchical multiple regression analyses of resting values showed that NA was related to higher aortic blood pressure (ABP) and lower SVI. After controlling for demographics and for NA, TTF scores were significantly associated with decreased ABP, but increased SVI. CPT changes from baseline indicated that, after controlling for demographics and NA, TTF scores were significantly associated with SVI. Results indicate that NA significantly predicts ABP and decreased SVI. Conversely, forgiveness seems to provide cardioprotection by evoking decreased ABP while improving SVI. PMID:25195798

  18. Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.

    PubMed

    Stelzer, I; Kröpfl, J M; Fuchs, R; Pekovits, K; Mangge, H; Raggam, R B; Gruber, H-J; Prüller, F; Hofmann, P; Truschnig-Wilders, M; Obermayer-Pietsch, B; Haushofer, A C; Kessler, H H; Mächler, P

    2015-10-01

    Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration. PMID:25438993

  19. Structural coloration signals condition, parental investment, and circulating hormone levels in Eastern bluebirds (Sialia sialis).

    PubMed

    Grindstaff, Jennifer L; Lovern, Matthew B; Burtka, Jennifer L; Hallmark-Sharber, Alesia

    2012-08-01

    Many of the brilliant plumage coloration displays of birds function as signals to conspecifics. One species in which the function of plumage ornaments has been assessed is the Eastern bluebird (Sialia sialis). Studies of a population breeding in Alabama (USA) have established that plumage ornaments signal quality, parental investment, and competitive ability in both sexes. Here we tested the additional hypotheses that (1) Eastern bluebird plumage ornamentation signals nest defense behavior in heterospecific competitive interactions and (2) individual variation in plumage ornamentation reflects underlying differences in circulating hormone levels. We also tested the potential for plumage ornaments to signal individual quality and parental investment in a population breeding in Oklahoma (USA). We found that Eastern bluebirds with more ornamented plumage are in better condition, initiate breeding earlier in the season, produce larger clutches, have higher circulating levels of the stress hormone corticosterone, and more ornamented males have lower circulating androgen levels. Plumage coloration was not related to nest defense behavior. Thus, plumage ornamentation may be used by both sexes to assess the physiological condition and parental investment of prospective mates. Experimental manipulations of circulating hormone levels during molt are needed to define the role of hormones in plumage ornamentation. PMID:22622467

  20. Simulation of the Low-Level-Jet by general circulation models

    SciTech Connect

    Ghan, S.J.

    1996-04-01

    To what degree is the low-level jet climatology and it`s impact on clouds and precipitation being captured by current general circulation models? It is hypothesised that a need for a pramaterization exists. This paper describes this parameterization need.

  1. A January angular momentum balance in the OSU two-level atmospheric general circulation model

    NASA Technical Reports Server (NTRS)

    Kim, J.-W.; Grady, W.

    1982-01-01

    The present investigation is concerned with an analysis of the atmospheric angular momentum balance, based on the simulation data of the Oregon State University two-level atmospheric general circulation model (AGCM). An attempt is also made to gain an understanding of the involved processes. Preliminary results on the angular momentum and mass balance in the AGCM are shown. The basic equations are examined, and questions of turbulent momentum transfer are investigated. The methods of analysis are discussed, taking into account time-averaged balance equations, time and longitude-averaged balance equations, mean meridional circulation, the mean meridional balance of relative angular momentum, and standing and transient components of motion.

  2. Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

    PubMed

    Lascano, V; Hahne, M; Papon, L; Cameron, K; Röeder, C; Schafmayer, C; Driessen, L; van Eenennaam, H; Kalthoff, H; Medema, J P

    2015-01-01

    We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression. PMID:25622308

  3. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    PubMed

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  4. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    PubMed Central

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  5. General circulation model simulations of winter and summer sea-level pressures over North America

    USGS Publications Warehouse

    McCabe, G.J., Jr.; Legates, D.R.

    1992-01-01

    In this paper, observed sea-level pressures were used to evaluate winter and summer sea-level pressures over North America simulated by the Goddard Institute for Space Studies (GISS) and the Geophysical Fluid Dynamics Laboratory (GFDL) general circulation models. The objective of the study is to determine how similar the spatial and temporal distributions of GCM-simulated daily sea-level pressures over North America are to observed distributions. Overall, both models are better at reproducing observed within-season variance of winter and summer sea-level pressures than they are at simulating the magnitude of mean winter and summer sea-level pressures. -from Authors

  6. Pharmacologic Resuscitation Decreases Circulating CINC-1 Levels and Attenuates hemorrhage-Induced Acute Lung Injury

    PubMed Central

    Fukudome, Eugene Y.; Li, Yongqing; Kochanek, Ashley R.; Lu, Jennifer; Smith, Eleanor J.; Liu, Baoling; Kim, Kyuseok; Velmahos, George C.; deMoya, Marc A.; Alam, Hasan B.

    2016-01-01

    Background Acute lung injury (ALI) is a complication of hemorrhagic shock (HS). Histone deacetylase inhibitors (HDACI) such as valproic acid (VPA) can improve survival following HS, however, their effects on late organ injury are unknown. Here, we have investigated the effects of HS and VPA treatment on ALI as well as circulating cytokines that may serve as biomarkers for the development of organ injury. Materials and Methods Anesthetized Wistar-Kyoto rats (250-300g) underwent 40% blood volume hemorrhage over 10 minutes followed by 30 minutes of un-resuscitated shock and were treated with 1) VPA 300mg/kg or 2) vehicle control. Blood samples were obtained at baseline, following shock, and prior to sacrifice (1h, 4h, and 20h; n=3-4/timepoint/group). Serum samples were screened for possible biomarkers using a multiplex electrochemiluminescence detection assay, and results were confirmed using ELISA. Additionally, lung tissue lysate was examined for chemokine and myeloperoxidase (MPO) levels as a marker for neutrophil infiltration and ALI. Additionally, lung CINC-1 (a chemokine belonging to the IL-8 family that promotes neutrophil chemotaxis) mRNA levels were measured by real-time PCR. Results Serum screening revealed that hemorrhage rapidly altered levels of circulating CINC-1. ELISA confirmed that CINC-1 protein was significantly elevated in the serum as early as 4h, and in the lung at 20h following hemorrhage, without any significant changes in the CINC-1 mRNA expression. Lung MPO levels were also elevated 4h and 20h after hemorrhage. VPA treatment attenuated these changes Conclusions Hemorrhage resulted in development of ALI, which was prevented with VPA treatment. Circulating CINC-1 levels rose rapidly after hemorrhage, and serum CINC-1 levels correlated with lung CINC-1 and MPO levels. This suggests that circulating CINC-1 could be used as an early marker for the subsequent development of organ inflammation and injury. PMID:22657731

  7. The effect of the sea breeze circulation on surface ozone levels at Wallops Island, Virginia

    NASA Technical Reports Server (NTRS)

    Parsons, C. L.; Williams, M. E.

    1979-01-01

    Surface measurements of windspeed, direction, and ozone concentration collected at Wallops Island, Virginia, during the summers of 1977 and 1978 are analyzed to study the effects of the dominant mesoscale sea breeze circulation on the local photochemical oxidant levels. A bimodality in the atmospheric dynamics is linked to systematic variations in ozone concentration. It is concluded that during certain phases of the two circulation modes, increased wind speed reduces the resistance of the earth's surface to the deposition of ozone, and decreased ozone concentration levels result. For other phases, light winds occur, signifying high resistance to deposition and high ozone levels. This modulation by the local dynamics is a major impediment for pollutant studies in coastal environments, especially those centering on transport, because it tends to mask other processes that may be occurring.

  8. Genetic Determinants of Circulating Interleukin-1 Receptor Antagonist Levels and Their Association With Glycemic Traits

    PubMed Central

    Nuotio, Marja-Liisa; Shah, Sonia; Blankenberg, Stefan; Brunner, Eric J.; Carstensen, Maren; Gieger, Christian; Grallert, Harald; Jula, Antti; Kähönen, Mika; Kettunen, Johannes; Kivimäki, Mika; Koenig, Wolfgang; Kristiansson, Kati; Langenberg, Claudia; Lehtimäki, Terho; Luotola, Kari; Marzi, Carola; Müller, Christian; Peters, Annette; Prokisch, Holger; Raitakari, Olli; Rathmann, Wolfgang; Roden, Michael; Salmi, Marko; Schramm, Katharina; Swerdlow, Daniel; Tabak, Adam G.; Thorand, Barbara; Wareham, Nick; Wild, Philipp S.; Zeller, Tanja; Hingorani, Aroon D.; Witte, Daniel R.; Kumari, Meena; Perola, Markus; Salomaa, Veikko

    2014-01-01

    The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10−21] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10−17]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA–raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA–raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance. PMID:24969107

  9. Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits.

    PubMed

    Herder, Christian; Nuotio, Marja-Liisa; Shah, Sonia; Blankenberg, Stefan; Brunner, Eric J; Carstensen, Maren; Gieger, Christian; Grallert, Harald; Jula, Antti; Kähönen, Mika; Kettunen, Johannes; Kivimäki, Mika; Koenig, Wolfgang; Kristiansson, Kati; Langenberg, Claudia; Lehtimäki, Terho; Luotola, Kari; Marzi, Carola; Müller, Christian; Peters, Annette; Prokisch, Holger; Raitakari, Olli; Rathmann, Wolfgang; Roden, Michael; Salmi, Marko; Schramm, Katharina; Swerdlow, Daniel; Tabak, Adam G; Thorand, Barbara; Wareham, Nick; Wild, Philipp S; Zeller, Tanja; Hingorani, Aroon D; Witte, Daniel R; Kumari, Meena; Perola, Markus; Salomaa, Veikko

    2014-12-01

    The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10(-21)] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10(-17)]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA-raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA-raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance. PMID:24969107

  10. Circulating IGF1 regulates hippocampal IGF1 levels and brain gene expression during adolescence

    PubMed Central

    Yan, Han; Mitschelen, Matthew; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Han, Song; Freeman, Willard M; Sonntag, William E

    2012-01-01

    GH and its anabolic mediator, IGF1, are important not only in somatic growth but also in the regulation of brain function. Even though GH treatment has been used clinically to improve body composition and exercise capacity in adults, its influence on central nervous system function has only recently been recognized. This is also the case for children with childhood-onset GH deficiency (GHD) where GH has been used to stimulate bone growth and enhance final adult height. Circulating IGF1 is transported across the blood–brain barrier and IGF1 and its receptors are also synthesized in the brain by neurons and glial and endothelial cells. Nevertheless, the relationship between circulating IGF1 and brain IGF1 remains unclear. This study, using a GH-deficient dwarf rat model and peripheral GH replacement, investigated the effects of circulating IGF1 during adolescence on IGF1 levels in the brain. Our results demonstrated that hippocampal IGF1 protein concentrations during adolescence are highly regulated by circulating IGF1, which were reduced by GHD and restored by systematic GH replacement. Importantly, IGF1 levels in the cerebrospinal fluid were decreased by GHD but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF1 levels did not modify the transcription of Igf1 or its receptor in the hippocampus but did regulate genes that are involved in microvascular structure and function, brain development, and synaptic plasticity, which potentially support brain structures involved in cognitive function during this important developmental period. PMID:21750148

  11. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis

    PubMed Central

    LI, ZHI-JUN; YANG, XUE-LING; YAO, YAN; HAN, WEI-QING; LI, BO

    2016-01-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were −1.96 (−2.60, −1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (−0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (−0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of −2.27 (−4.36, −0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of −1.52 (−3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer. PMID:27284314

  12. Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients

    PubMed Central

    Vargas-Robles, Hilda; Serrano, Alberto Maceda; Lozano-Nuevo, Jose Juan; Escalante-Acosta, Bruno Alfonso

    2009-01-01

    Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in normotensive type-2 diabetic patients. Results: We found significant correlations between ICAM-1 (r = 0.69, p < 0.001 95% IC 0.65 to 0.82) and VCAM-1 (r = 0.4, p < 0.03, 95% IC 0.65 to 0.82) levels and maximal carotid artery intimal-medial thickness, whereas no correlation was observed with E-selectin. Methods: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. Conclusion: Our results suggest that ICAM-1 and VCAM-1 are markers associated, and correlated with the degree of atherosclerosis in normotensive type-2 diabetic patients. PMID:19717975

  13. Increased Circulating miR-21 Levels Are Associated with Kidney Fibrosis

    PubMed Central

    Gnemmi, Viviane; Buob, David; Van der Hauwaert, Cynthia; Lo-Guidice, Jean-Marc; Bouyé, Sébastien; Hazzan, Marc; Pottier, Nicolas; Perrais, Michaël

    2013-01-01

    MicroRNAs (miRNAs) are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA). Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001). By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03), and between miR-21 levels and aMDRD (ß = −0.398, p = 0.006). Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis. PMID:23469132

  14. Altered membrane lipid composition and functional parameters of circulating cells in cockles (Cerastoderma edule) affected by disseminated neoplasia.

    PubMed

    Le Grand, Fabienne; Soudant, Philippe; Marty, Yanic; Le Goïc, Nelly; Kraffe, Edouard

    2013-01-01

    Membrane lipid composition and morpho-functional parameters were investigated in circulating cells of the edible cockle (Cerastoderma edule) affected by disseminated neoplasia (neoplastic cells) and compared to those from healthy cockles (hemocytes). Membrane sterol levels, phospholipid (PL) class and subclass proportions and their respective fatty acid (FA) compositions were determined. Morpho-functional parameters were evaluated through total hemocyte count (THC), mortality rate, phagocytosis ability and reactive oxygen species (ROS) production. Both morpho-functional parameters and lipid composition were profoundly affected in neoplastic cells. These dedifferentiated cells displayed higher THC (5×), mortality rate (3×) and ROS production with addition of carbonyl cyanide m-chloro phenylhydrazone (1.7×) but lower phagocytosis ability (½×), than unaffected hemocytes. Total PL amounts were higher in neoplastic cells than in hemocytes (12.3 and 5.1 nmol×10(-6) cells, respectively). However, sterols and a particular subclass of PL (plasmalogens; 1-alkenyl-2-acyl PL) were present in similar amounts in both cell type membranes. This led to a two times lower proportion of these membrane lipid constituents in neoplastic cells when compared to hemocytes (20.5% vs. 42.1% of sterols in total membrane lipids and 21.7% vs. 44.2% of plasmalogens among total PL, respectively). Proportions of non-methylene interrupted FA- and 20:1n-11-plasmalogen molecular species were the most impacted in neoplastic cells when compared to hemocytes (⅓× and ¼×, respectively). These changes in response to this leukemia-like disease in bivalves highlight the specific imbalance of plasmalogens and sterols in neoplastic cells, in comparison to the greater stability of other membrane lipid components. PMID:23333874

  15. A multi-level adaptation model of circulation for the western Indian Ocean

    NASA Astrophysics Data System (ADS)

    Shaji, C.; Bahulayan, N.; Dube, S. K.; Rao, A. D.

    1999-12-01

    A three-dimensional, fully non-linear semi-diagnostic (adaptation) model is described. This model is used to compute the climatological mean circulation and to understand the role of local, steady forcing of the wind and thermohaline forcing on the observed circulation in the western tropical Indian Ocean. The model consists of equations of motion and continuity, sea surface topography, equations of state and temperature, and salinity diffusion equations. While the sea surface topography equation is solved by a successive overrelaxation technique, the other model equations are solved by a leap-frog numerical scheme. Two versions of the model, having 18 and 33 levels in the vertical direction, were prepared to study climatological mean circulation in the western tropical Indian Ocean. The first numerical experiment is carried out with the 18-level adaptation model to study the sensitivity of the solution to different values of eddy coefficients. The main scientific rationale behind these numerical experiments was to obtain the most appropriate values of the eddy coefficients for the realistic computation of climatological circulation in the western tropical Indian Ocean. Three numerical experiments were conducted for the month of February to understand the sensitivity of the model solution to different eddy coefficients. The model reproduced the circulation features during February, even with low values of horizontal and vertical eddy coefficients. In the second experiment, the adaptation model, with 33 levels in the vertical direction, is applied to study the seasonal mean climatological circulation at selected depths during Spring in the western tropical Indian Ocean. Adapted (steady state) results of currents, sea surface topography, temperature and salinity anomaly fields are presented. Reasonable agreement is obtained between the model results on currents and the observational data. The computed anomaly fields for temperature and salinity at selected depths

  16. IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women

    PubMed Central

    D’Aloisio, Aimee A.; Schroeder, Jane C.; North, Kari E.; Poole, Charles; West, Suzanne L.; Travlos, Gregory S.; Baird, Donna D.

    2010-01-01

    Circulating insulin-like growth factor-one (IGF-I) and IGF binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNPs) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians = 631 ng/ml, 95% confidence interval: 398, 864; African Americans = 897 ng/ml, 95% confidence interval: 656, 1138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than referent diplotypes with the CG genotype, while IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (−202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with 5% or greater differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with 10% or greater differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians, but provides less evidence that IGF-I SNPs affect plasma IGF-I levels. PMID:19240240

  17. Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines.

    PubMed

    Fichna, Marta; Fichna, Piotr; Gryczyńska, Maria; Czarnywojtek, Agata; Żurawek, Magdalena; Ruchała, Marek

    2015-03-01

    Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7 ± 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile, and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR, DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the control group was 24.1 ± 3.9 kg/m(2) and 23.7 ± 3.9 kg/m(2) in the PAI cohort. Serum leptin and adiponectin levels were similar in both groups, whereas resistin appeared significantly lower among affected subjects (p = 0.0002). Its levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently correlated with fasting insulin, HOMA-IR, BMI, and body fat (p < 0.001). At the multiple regression analysis only weight (p = 0.017), total and HDL cholesterol (p < 0.001) appeared significant predictors of adiponectin level. No adipokine correlations with serum cortisol or daily hydrocortisone dose were found. Patients receiving DHEA substitution displayed lower leptin and adiponectin levels (p < 0.05). In conclusion, our study did not provide evidence of an adverse adipokine profile in patients with PAI under conventional glucocorticoid replacement. Serum adipokines in treated PAI follow similar correlations to those reported in healthy subjects. Further prospective studies are warranted to verify and explain plausible excess of cardiovascular mortality in PAI. PMID:25129652

  18. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age

    PubMed Central

    Poggioli, Tommaso; Vujic, Ana; Yang, Peiguo; Macias-Trevino, Claudio; Uygur, Aysu; Loffredo, Francesco S.; Pancoast, James R.; Cho, Miook; Goldstein, Jill; Tandias, Rachel M.; Gonzalez, Emilia; Walker, Ryan G.; Thompson, Thomas B.; Wagers, Amy J.; Fong, Yick W.; Lee, Richard T.

    2016-01-01

    Rationale Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies. PMID:26489925

  19. Circulating Cytokine Levels as Markers of Inflammation in Philadelphia Negative Myeloproliferative Neoplasms: Diagnostic and Prognostic Interest

    PubMed Central

    Mondet, Julie; Hussein, Kais; Mossuz, Pascal

    2015-01-01

    Cytokines are well known mediators of numerous physiological and pathological processes. They contribute to the regulation of normal hematopoiesis but increasing data suggest that they also have a clinical impact in some hematopoietic malignancies. In particular, there is evidence that cytokines are implicated in the functional symptoms of Philadelphia negative myeloproliferative neoplasms (Ph− MPNs), suggesting that evaluation of circulating levels of cytokines could be of clinical interest for the characterization of patients at the time of diagnosis and for disease prognosis. In this review, we present the current knowledge on alteration of circulating cytokine profiles in MPNs and their role in myelofibrosis pathogenesis. Phenotypic correlation, prognostic value of cytokines, and impact of JAK inhibitors are also discussed. PMID:26525644

  20. High levels of circulating extracellular vesicles with altered expression and function during pregnancy.

    PubMed

    Nardi, Fabiola da Silva; Michelon, Tatiana Ferreira; Neumann, Jorge; Manvailer, Luis Felipe Santos; Wagner, Bettina; Horn, Peter A; Bicalho, Maria da Graça; Rebmann, Vera

    2016-07-01

    Extracellular vesicles (EVs) are widely considered important modulators of cell-cell communication and may interact with target cells locally and on a systemic level. Several studies had shown that circulating EVs' levels are increased during pregnancy. However, EVs characteristics, composition and biological functions in pregnancy still need to be clarified. This study aims to determine if circulating EVs during pregnancy are modified regarding levels, markers and cytokine profile as well as their reactivity towards peripheral blood cells. 26 pregnant women (PW) being in the second gestational trimester and 59 non-pregnant women (NPW) were investigated. EVs enrichment was performed by ExoQuick™ or ultracentrifugation; nanoparticle tracking analysis, SDS-PAGE followed by Western Blotting and densitometry, and IFN-γ, IL-10 and TGF-β1 ELISA for EVs characterization; imaging flow cytometry to analyze EVs' uptake by peripheral blood cells and flow cytometry were performed to analyze EVs function regarding induction of caspase-3 activity. Circulating EVs' levels were increased during pregnancy [26.9×10(6)EVs/ml (range: 6.4-46.3); p=0.003] vs NPW [18.9×10(6)EVs/ml (range: 2.5-61.3)]. Importantly, the immunosuppressive TGF-β1 and IL-10 cytokine cargo were increased in EVs of PW even after normalization to 1 million EVs [TGF-β1: 0.25pg/10(6)EVs (range: 0.0-2.0); p<0.0001] and [IL-10: 0.21pg/10(6)EVs (range: 0.0-16.8); p=0.006] vs NPW. Although EVs derived from non-pregnant and pregnant women were taken up by NK cells, the latter exclusively enhanced the caspase-3 activity in CD56(dim) NK cells (8.2±0.9; p=0.02). The qualitative and quantitative pregnancy-related alterations of circulating EVs provide first hints for an immune modulating role of circulating EVs during pregnancy. PMID:27005781

  1. Modulation of Circulating Cytokine-Chemokine Profile in Patients Affected by Chronic Venous Insufficiency Undergoing Surgical Hemodynamic Correction

    PubMed Central

    Tisato, Veronica; Zauli, Giorgio; Gianesini, Sergio; Menegatti, Erica; Brunelli, Laura; Manfredini, Roberto; Zamboni, Paolo; Secchiero, Paola

    2014-01-01

    The expression of proinflammatory cytokines/chemokines has been reported in in vitro/ex vivo settings of chronic venous insufficiency (CVI), but the identification of circulating mediators that might be associated with altered hemodynamic forces or might represent innovative biomarkers is still missing. In this study, the circulating levels of 31 cytokines/chemokines involved in inflammatory/angiogenic processes were analysed in (i) CVI patients at baseline before surgical hemody namic correction, (ii) healthy subjects, and (iii) CVI patients after surgery. In a subgroup of CVI patients, in whom the baseline levels of cytokines/chemokines were analyzed in paired blood samples obtained from varicose vein and forearm vein, EGF, PDGF, and RANTES were increased at the varicose vein site as compared to the general circulation. Moreover, while at baseline, CVI patients showed increased levels of 14 cytokines/chemokines as compared to healthy subjects, 6 months after surgery, 11 cytokines/chemokines levels were significantly reduced in the treated CVI patients as compared to the CVI patients before surgery. Of note, a patient who exhibited recurrence of the disease 6 months after surgery, showed higher levels of EGF, PDGF, and RANTES compared to nonrecurrent patients, highlighting the potential role of the EGF/PDGF/RANTES triad as sensitive biomarkers in the context of CVI. PMID:24741602

  2. Simulation of the great plains low-level jet and associated clouds by general circulation models

    SciTech Connect

    Ghan, S.J.; Bian, X.; Corsetti, L.

    1996-07-01

    The low-level jet frequently observed in the Great Plains of the United States forms preferentially at night and apparently influences the timing of the thunderstorms in the region. The authors have found that both the European Centre for Medium-Range Weather Forecasts general circulation model and the National Center for Atmospheric Research Community Climate Model simulate the low-level jet rather well, although the spatial distribution of the jet frequency simulated by the two GCM`s differ considerably. Sensitivity experiments have demonstrated that the simulated low-level jet is surprisingly robust, with similar simulations at much coarser horizontal and vertical resolutions. However, both GCM`s fail to simulate the observed relationship between clouds and the low-level jet. The pronounced nocturnal maximum in thunderstorm frequency associated with the low-level jet is not simulated well by either GCM, with only weak evidence of a nocturnal maximum in the Great Plains. 36 refs., 20 figs.

  3. Level of circulated microRNA-421 in gastric carcinoma and related mechanisms

    PubMed Central

    Zhao, Guodong; Xu, Liang; Hui, Limei; Zhao, Jianjun

    2015-01-01

    As one of the most popular and deadly malignant tumors, gastric cancer still has difficulty in early-diagnosis. Recently the level of circulated DNA related with tumors can be used for diagnosis. MicroRNA-421 (miR-421) has been found to be up-regulated in tumor cells. Whether peripheral miR-421 can be used as a marker for diagnosis of gastric carcinoma, however, remains unclear. The expression level of miR-421 in both gastric cancer and normal people were firstly quantified. We then performed in vitro transfection of gastric carcinoma cell line to potentiate or silence miR-421 level. Cell apoptosis and apoptotic protein levels were quantified by flow cytometry and Western blotting, respectively. MiR-421 level in the peripheral blood of gastric cancer patients was significantly elevated. In gastric cancer cell line, the up-regulation of miR-421 significantly inhibited cell apoptosis. The silencing of miR-421 promoted cell apoptosis. Such anti-apoptotic role of miR-421 was accomplished by inhibiting caspase 3, up-regulating Bcl-2 and inhibiting Bax. MiR-421 was up-regulated in both tumor tissue and peripheral blood, and can modulate cell apoptosis. Circulated miR-421 can work as a serological marker for early diagnosis of gastric cancer. PMID:26823741

  4. Recent increases in Arctic freshwater flux affects Labrador Sea convection and Atlantic overturning circulation

    PubMed Central

    Yang, Qian; Dixon, Timothy H.; Myers, Paul G.; Bonin, Jennifer; Chambers, Don; van den Broeke, M. R.

    2016-01-01

    The Atlantic Meridional Overturning Circulation (AMOC) is an important component of ocean thermohaline circulation. Melting of Greenland's ice sheet is freshening the North Atlantic; however, whether the augmented freshwater flux is disrupting the AMOC is unclear. Dense Labrador Sea Water (LSW), formed by winter cooling of saline North Atlantic water and subsequent convection, is a key component of the deep southward return flow of the AMOC. Although LSW formation recently decreased, it also reached historically high values in the mid-1990s, making the connection to the freshwater flux unclear. Here we derive a new estimate of the recent freshwater flux from Greenland using updated GRACE satellite data, present new flux estimates for heat and salt from the North Atlantic into the Labrador Sea and explain recent variations in LSW formation. We suggest that changes in LSW can be directly linked to recent freshening, and suggest a possible link to AMOC weakening. PMID:26796579

  5. Recent increases in Arctic freshwater flux affects Labrador Sea convection and Atlantic overturning circulation

    NASA Astrophysics Data System (ADS)

    Yang, Qian; Dixon, Timothy H.; Myers, Paul G.; Bonin, Jennifer; Chambers, Don; van den Broeke, M. R.

    2016-01-01

    The Atlantic Meridional Overturning Circulation (AMOC) is an important component of ocean thermohaline circulation. Melting of Greenland's ice sheet is freshening the North Atlantic; however, whether the augmented freshwater flux is disrupting the AMOC is unclear. Dense Labrador Sea Water (LSW), formed by winter cooling of saline North Atlantic water and subsequent convection, is a key component of the deep southward return flow of the AMOC. Although LSW formation recently decreased, it also reached historically high values in the mid-1990s, making the connection to the freshwater flux unclear. Here we derive a new estimate of the recent freshwater flux from Greenland using updated GRACE satellite data, present new flux estimates for heat and salt from the North Atlantic into the Labrador Sea and explain recent variations in LSW formation. We suggest that changes in LSW can be directly linked to recent freshening, and suggest a possible link to AMOC weakening.

  6. Recent increases in Arctic freshwater flux affects Labrador Sea convection and Atlantic overturning circulation.

    PubMed

    Yang, Qian; Dixon, Timothy H; Myers, Paul G; Bonin, Jennifer; Chambers, Don; van den Broeke, M R

    2016-01-01

    The Atlantic Meridional Overturning Circulation (AMOC) is an important component of ocean thermohaline circulation. Melting of Greenland's ice sheet is freshening the North Atlantic; however, whether the augmented freshwater flux is disrupting the AMOC is unclear. Dense Labrador Sea Water (LSW), formed by winter cooling of saline North Atlantic water and subsequent convection, is a key component of the deep southward return flow of the AMOC. Although LSW formation recently decreased, it also reached historically high values in the mid-1990s, making the connection to the freshwater flux unclear. Here we derive a new estimate of the recent freshwater flux from Greenland using updated GRACE satellite data, present new flux estimates for heat and salt from the North Atlantic into the Labrador Sea and explain recent variations in LSW formation. We suggest that changes in LSW can be directly linked to recent freshening, and suggest a possible link to AMOC weakening. PMID:26796579

  7. Prospective study of familial canine dermatomyositis. Correlation of the severity of dermatomyositis and circulating immune complex levels.

    PubMed Central

    Hargis, A. M.; Prieur, D. J.; Haupt, K. H.; McDonald, T. L.; Moore, M. P.

    1986-01-01

    Familial canine dermatomyositis in collie dogs is a newly recognized spontaneous disease that resembles dermatomyositis in children. A litter of 9 collie dogs was studied from birth to 7.5 months of age. The onset and severity of dermatitis and myositis correlated with elevated serum levels of circulating immune complexes (CICs) and IgG. The immunoglobulin component of the CICs consisted principally of IgG. All dogs developed elevated levels of CIC before or concurrent with the onset of dermatitis. Myositis developed later. The CIC tended to peak between 14-18 weeks of age in all dogs except the most severely affected dog, in which the CICs continued to increase to 238 micrograms/ml (controls 30 micrograms/ml) at 7 months of age. In the moderately affected dogs the CICs tended to stabilize at the levels reached at 14-18 weeks, and in the mildly affected dogs the CICs tended to decrease to normal levels after 14-18 weeks. Although the dogs had electromyographic and repetitive nerve stimulation abnormalities, the abnormalities did not correlate with severity of dermatomyositis or degree of elevation of CICs or IgG. Necropsy at 7.5 months of age revealed that all dogs had myositis and 8 of 9 had dermatitis. Except for 1 dog, the severity of dermatomyositis correlated positively with higher levels of CICs. A strong positive association between elevated levels of CICs and IgG, but not IgM or IgA, was generally present. Elevated levels of CICs appear to be involved in the mechanisms that control the development, severity, and progression of dermatomyositis in collie dogs. Images Figure 1 Figure 2 PMID:3717300

  8. Chasing a ghost? - Issues with the determination of circulating levels of endotoxin in human blood.

    PubMed

    Gnauck, Anne; Lentle, Roger Graham; Kruger, Marlena Cathorina

    2016-06-01

    Reliable quantification of bacterial products such as endotoxin is important for the diagnosis of Gram-negative infection and for the monitoring of its treatment. Further, it is important to identify patients with persistent subclinical level of bacterial products in their systemic circulation as data from animal studies also suggest this may be correlated with the onset of metabolic syndrome. In this review, we first aim to describe the principles of the Limulus amoebocyte lysate (LAL) test, an assay that is used to quantify endotoxin, and the various shortcomings that must be addressed before it can become a reliable means of quantifying endotoxin in samples derived from blood. We then review published data regarding endotoxin levels in healthy subjects and those with sepsis, inflammatory bowel disease, liver disorders and metabolic disorders such as obesity and diabetes. We also review the evidence regarding influence of macronutrients in augmenting the levels of systemic endotoxin. The results of this review show that reported mean levels of endotoxin in the systemic circulation of healthy humans and of those with various clinical disorders vary over a wide range. Further, this review shows that a significant proportion of this variation can be related to the method that was used to prepare plasma and serum samples prior to assay and its ability to reduce the effect of various blood borne factors that interfere with the LAL assay. PMID:26732012

  9. Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

    PubMed Central

    Rinaldi, Arturo Ottavio; Sanseverino, Isabella; Purificato, Cristina; Cortese, Antonio; Mechelli, Rosella; Francisci, Silvia; Salvetti, Marco; Millefiorini, Enrico; Gessani, Sandra; Gauzzi, Maria Cristina

    2015-01-01

    Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS. PMID:25590278

  10. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

    SciTech Connect

    Shin, Andrew C.; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A.; Zielinski, Elizabeth; Zhou, Jianying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J.; Lapworth, Amanda L.; Llkayeva, Olka; Knippschild, Uwe; Wolf, Anna M.; Scheja, Ludger; Grove, Kevin L.; Smith, Richard D.; Qian, Weijun; Lynch, Christopher J.; Newgard, Christopher B.; Buettner, Christoph

    2014-11-04

    Circulating branched-chain amino acid (BCAA) levels are elevated in obesity and diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of protein expression and activity of branched-chain alpha keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway in the liver. Selective induction of hypothalamic insulin signaling in rats as well as inducible and lifelong genetic modulation of brain insulin receptor expression in mice both demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Further, short-term overfeeding impairs the ability of brain insulin to lower circulating BCAA levels in rats. Chronic high-fat feeding in primates and obesity and/or type 2 diabetes in humans is associated with reduced BCKDH protein expression in liver, further supporting the concept that decreased hepatic BCKDH is a primary cause of increased plasma BCAA levels in insulin-resistant states. These findings demonstrate that neuroendocrine pathways control BCAA homeostasis and that hypothalamic insulin resistance can be a cause of impaired BCAA metabolism in obesity and diabetes.

  11. Plasma Circulating Nucleic Acids Levels Increase According to the Morbidity of Plasmodium vivax Malaria

    PubMed Central

    Franklin, Bernardo S.; Vitorino, Barbara L. F.; Coelho, Helena C.; Menezes-Neto, Armando; Santos, Marina L. S.; Campos, Fernanda M. F.; Brito, Cristiana F.; Fontes, Cor J.; Lacerda, Marcus V.; Carvalho, Luzia H.

    2011-01-01

    Background Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. Methods and Findings CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Conclusions Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity. PMID:21611202

  12. Affective State Level Recognition in Naturalistic Facial and Vocal Expressions.

    PubMed

    Meng, Hongying; Bianchi-Berthouze, Nadia

    2014-03-01

    Naturalistic affective expressions change at a rate much slower than the typical rate at which video or audio is recorded. This increases the probability that consecutive recorded instants of expressions represent the same affective content. In this paper, we exploit such a relationship to improve the recognition performance of continuous naturalistic affective expressions. Using datasets of naturalistic affective expressions (AVEC 2011 audio and video dataset, PAINFUL video dataset) continuously labeled over time and over different dimensions, we analyze the transitions between levels of those dimensions (e.g., transitions in pain intensity level). We use an information theory approach to show that the transitions occur very slowly and hence suggest modeling them as first-order Markov models. The dimension levels are considered to be the hidden states in the Hidden Markov Model (HMM) framework. Their discrete transition and emission matrices are trained by using the labels provided with the training set. The recognition problem is converted into a best path-finding problem to obtain the best hidden states sequence in HMMs. This is a key difference from previous use of HMMs as classifiers. Modeling of the transitions between dimension levels is integrated in a multistage approach, where the first level performs a mapping between the affective expression features and a soft decision value (e.g., an affective dimension level), and further classification stages are modeled as HMMs that refine that mapping by taking into account the temporal relationships between the output decision labels. The experimental results for each of the unimodal datasets show overall performance to be significantly above that of a standard classification system that does not take into account temporal relationships. In particular, the results on the AVEC 2011 audio dataset outperform all other systems presented at the international competition. PMID:23757552

  13. Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome.

    PubMed

    Calan, Mehmet; Yilmaz, Ozgur; Kume, Tuncay; Unal Kocabas, Gokcen; Yesil Senses, Pinar; Senses, Yasar Mehmet; Temur, Muzaffer; Gursoy Calan, Ozlem

    2016-07-01

    Betatrophin is a newly identified hormone determined to be a potent inducer of pancreatic beta cell proliferation in response to insulin resistance in mice. Polycystic ovary syndrome (PCOS) is an inflammatory-based metabolic disease associated with insulin resistance. However, no evidence is available indicating whether betatrophin is involved in women with PCOS. The objective of this study was to ascertain whether betatrophin levels are altered in women with PCOS. This study was conducted in secondary referral center. This cross-sectional study included 164 women with PCOS and 164 age- and BMI-matched female controls. Circulating betatrophin levels were measured using ELISA. Metabolic and hormonal parameters were also determined. Circulating betatrophin levels were significantly elevated in women with PCOS compared with controls (367.09 ± 55.78 vs. 295.65 ± 48.97 pg/ml, P < 0.001). Betatrophin levels were positively correlated with insulin resistance marker homeostasis model assessment of insulin resistance (HOMA-IR), free-testosterone, high-sensitivity C-reactive protein (hs-CRP), atherogenic lipid profiles, and BMI in PCOS. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.51 for patients in the highest quartile of betatrophin compared with those in the lowest quartile (95 % CI 1.31-4.81, P = 0.006). Multivariate regression analyses showed that HOMA-IR, hs-CRP, and free-testosterone were independent factors influencing serum betatrophin levels. Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, hs-CRP, and free-testosterone in these patients. Elevated betatrophin levels were found to increase the odds of having PCOS. Further research is needed to elucidate the physiologic and pathologic significance of our findings. PMID:26832343

  14. Association between winter precipitation and water level fluctuations in the Great Lakes and atmospheric circulation patterns

    SciTech Connect

    Rodionov, S.N.

    1994-11-01

    Atmospheric precipitation in the Great Lakes basin, as a major mediating variable between atmospheric circulation and lake levels, is analyzed relative to both. The effect of cumulative winter precipitation on lake levels varies from lake to lake and depends on both the state of the lake level itself and air temperature. For periods with a quasi-stable temperature regime, the correlation coefficient between winter precipitation and changes in lake levels from November to spring months reaches 0.8. An analysis of composite maps of mean winter 700-mb heights and sea level pressure for the years with well-above and well-below normal precipitation in the lower Great Lakes basin (Lakes Michigan-Huron, St. Clair, Erie, and Ontario) has shown that changes in precipitation are associated with the wave train structure in the lower and midtroposphere that is similar to the Pacific/North American (PNA) teleconnection pattern. During the positive phase of the PNA-like pattern, when the upper-atmospheric ridge/trough system is amplified, cyclones passing over the Great Lakes basin are frequently of Alberta (Canada) origin and carry relatively small amounts of precipitation. As a result, lake levels tend to decline. On the contrary, during the negative phase of the pattern when the atmospheric circulation is more zonal, the main storm track is oriented from the southwest to the northeast and cyclones bring enough precipitation to induce a rise in lake levels. The effect of the position of the upper-atmospheric trough over the east coast of North America on the precipitation regime in the Great Lakes basin is also demonstrated. 42 refs., 11 figs., 4 tabs.

  15. Exposure to low levels of hydrogen sulfide elevates circulating glucose in maternal rats

    SciTech Connect

    Hayden, L.J.; Goeden, H.; Roth, S.H. )

    1990-09-01

    Although the lethal effect of hydrogen sulfide (H{sub 2}S) has long been known, the results of exposure to low levels of H{sub 2}S have not been well documented. Rat dams and pups were exposed to low levels of H{sub 2}S (less than or equal to 75 ppm) from d 1 of gestation until d 21 postpartum and analyzed for changes in circulating enzymatic activity and metabolites. Blood glucose was significantly elevated in maternal blood on d 21 postpartum at all exposure levels. This increase in glucose was accompanied by a possible decrease in serum triglyceride in the pups and in the dams on d 21 postpartum. There was no evidence of alterations in serum alkaline phosphatase, lactate dehydrogenase, or serum glutamate oxaloacetate transaminase.

  16. Circulating endothelin-1 levels in obese patients with the metabolic syndrome.

    PubMed

    Ferri, C; Bellini, C; Desideri, G; Baldoncini, R; Properzi, G; Santucci, A; De Mattia, G

    1997-01-01

    We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome. PMID:9288542

  17. Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease

    PubMed Central

    Tseng, Ping-Huei; Yang, Wei-Shiung; Liou, Jyh-Ming; Lee, Yi-Chia; Wang, Hsiu-Po; Lin, Jaw-Town; Wu, Ming-Shiang

    2015-01-01

    Objective The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD. Methods One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett’s esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects. Results All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25th-75th percentile), 80.1 (49.8–108.3) vs. 99.4 (65.8–131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0–120.8) vs. 32.8 (28.7–84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6–9.3) vs. 9.9 (9.6–10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1–9.2) vs. 9.2 (7.1–11.2) μg/ml, p = 0.026] than those without BE. Conclusions Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD

  18. Circulating levels of p,p'-DDE are related to prevalent hypertension in the elderly

    SciTech Connect

    Lind, P. Monica; Penell, Johanna; Salihovic, Samira; Bavel, Bert van; Lind, Lars

    2014-02-01

    Background: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women. Methods: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, and/or use of antihypertensive medication. Results: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 1.35 for a 1 SD change, 95% CI 1.17–1.56, p<0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06–1.43, p=0.006). Conclusion: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure. - Highlights: • We evaluated the relation between POPs and hypertension. • Cross sectional data from a cohort of elderly men and women were analyzed. • The main exposure was circulating levels of 23 different POPs. • Hypertension was defined as ≥140/90 mmHg and/or antihypertensive treatment. • High levels of p,p'-DDE were associated with prevalent hypertension.

  19. Do GSM 900MHz signals affect cerebral blood circulation? A near-infrared spectrophotometry study

    NASA Astrophysics Data System (ADS)

    Wolf, Martin; Haensse, Daniel; Morren, Geert; Froehlich, Juerg

    2006-06-01

    Effects of GSM 900MHz signals (EMF) typical for a handheld mobile phone on the cerebral blood circulation were investigated using near-infrared spectrophotometry (NIRS) in a three armed (12W/kg, 1.2W/kg, sham), double blind, randomized crossover trial in 16 healthy volunteers. During exposure we observed borderline significant short term responses of oxyhemoglobin and deoxyhemoglobin concentration, which correspond to a decrease of cerebral blood flow and volume and were smaller than regular physiological changes. Due to the relatively high number of statistical tests, these responses may be spurious and require further studies. There was no detectable dose-response relation or long term response within 20min. The detection limit was a fraction of the regular physiological changes elicited by functional activation. Compared to previous studies using PET, NIRS provides a much higher time resolution, which allowed investigating the short term effects efficiently, noninvasively, without the use of radioactive tracers and with high sensitivity.

  20. Changes in atmospheric circulation patterns affect midcontinent wetlands sensitive to climate

    USGS Publications Warehouse

    LaBaugh, J.W.; Winter, T.C.; Swanson, G.A.; Rosenberry, D.

    1996-01-01

    Twenty-seven years of data from midcontinent wetlands indicate that the response of these wetlands to extremes in precipitation-drought and deluge-persists beyond the extreme events. Chemical changes transcend such simple relations as increased salinity during dry periods because drought provides mechanisms for removal of salt by deflation and seepage to groundwater. Inundation of vegetation zones including rooted or floating mats of cattail (Typha glauca) can stimulate sulfate reduction and shift the anion balance from sulfate to bicarbonate dominance. Disruptions in the circulation of moisture-laden air masses over the midcontinent, as in the drought of 1988 and the deluge of 1993, have a major effect on these wetlands, which are representatives of the primary waterfowl breeding habitat of the continent.

  1. AB154. Circulating levels of adipocytokine omentin-1 in patients with renal cell cancer

    PubMed Central

    Shen, Xudong; Zhang, Li

    2016-01-01

    Objective Renal cell carcinoma (RCC) is the fifth most common cancer worldwide, and becomes one of the leading causes of genitourinary cancer-related death in both males and females. Genetic alternations, alcohol consumption, occupationally harmful exposure and even obesity are well-established risk factors of RCC. Omentin-1 is a plasma adipokine synthesized in visceral adipose tissue, and its circulating serum concentration alters not only in conditions associated with insulin resistance such as Polycystic Ovary Syndrome (PCOS), but also in colorectal cancer and prostate cancer. To our best knowledge, the relationship between omentin-1 and RCC has not been clarified previously. Methods Thus, we evaluated serum omentin-1 levels in RCC patients in the current matched case-control study. Forty-one patients newly diagnosed with RCC and forty-two healthy controls confirmed by the comprehensive medical examination were assessed. Results The omentin-1 concentrations were determined via utilizing enzyme-linked immunosorbent assays (ELISA) in the paired groups, in which the patients and healthy controls had no statistically significant differences in gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), estimate glomerular filtration rate (eGFR), body-mass index (BMI) and biochemical parameters. The omentin-1 levels in healthy people were 9.86±1.44 ng/mL and the circulating omentin-1 levels were dramatically decreased to 3.62±0.76 ng/mL in RCC patients (P<0.001). Besides, we revealed a negative correlation between omentin-1 with WHR (r=−0.261, P=0.017) and BMI (r=−0.310, P=0.004), further indicating BMI was the main influential factor on omentin-1 levels (P=0.0091). Conclusions Follow-up studies would be conducted to establish the concrete mechanisms underlying the altered circulating levels of omentin-1 and elucidate the interaction between ‘‘RCC complex system” and adipose tissues, which may together provide

  2. Increased levels of circulating adrenomedullin following treatment with TU‑100 in patients with Crohn's disease.

    PubMed

    Kominato, Ken; Yamasaki, Hiroshi; Mitsuyama, Keiichi; Takedatsu, Hidetoshi; Yoshioka, Shinichiro; Kuwaki, Kotaro; Kobayashi, Teppei; Yamauchi, Ryosuke; Fukunaga, Shuhei; Tsuruta, Osamu; Torimura, Takuji

    2016-09-01

    Daikenchuto (TU‑100) is a traditional Japanese medicine that is widely used to treat intestinal symptoms. The mechanisms underlying it effects on the circulating levels of adrenomedullin (ADM) are of interest. In addition, the effect of TU‑100 in the treatment of Crohn's disease (CD) in humans remains to be elucidated. The primary objective of the present study was to evaluate the effect of TU‑100 on the circulating ADM levels in patients with active CD. An additional objective was to assess the effect of the drug on the disease activity and its potential side effects. In an open‑label study, 10 patients with active CD received 15 g TU‑100 per day for 8 consecutive weeks, and baseline anti‑inflammatory therapy was continued. The pre‑ and post‑treatment blood plasma levels of total ADM (t‑ADM) and mature‑ADM (m‑ADM) were determined using enzyme‑linked immunosorbent assays. The response of patients to the treatment was evaluated clinically using the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score. The plasma levels of t‑ADM (16.4±1.1 vs. 20.2±1.7 fmol/ml, P=0.0218) and m‑ADM (1.7±0.1 vs. 2.2±0.1 fmol/ml, P=0.0284) increased following 8 weeks of TU‑100 treatment, compared with control. The IOIBD score of patients also improved, with a significant decrease in the score from 3.9±0.5 at 0 weeks to 2.4±0.4 at 8 weeks (P=0.0284). Out of the 10 components of the IOIBD scoring system, the scores for abdominal pain and tenderness, decreased significantly (P=0.014 and P=0.046). Therefore, TU‑100 was safe and well‑tolerated by the patients that participated in the current study. The present study determined that the pharmacologic action of TU‑100 is associated with changes in the circulating ADM levels and that treatment with TU‑100 may aid in the management of CD. These promising findings warrant further investigation in larger, multicenter studies. PMID:27432470

  3. An evaluation of circulating bovine viral diarrhea virus type 2 maternal antibody level and response to vaccination in Angus calves.

    PubMed

    Downey, E D; Tait, R G; Mayes, M S; Park, C A; Ridpath, J F; Garrick, D J; Reecy, J M

    2013-09-01

    Vaccination against viruses has been shown to help prevent bovine respiratory disease in cattle. However, both passively acquired maternal antibody concentration and calf age have been shown to impact the ability of the immune system of a calf to respond to vaccination. The objectives of this study were to identify and evaluate environmental and management factors that affect 1) passively acquired bovine viral diarrhea virus (BVDV) type 2 antibody level, 2) decay rate of passively acquired BVDV type 2 antibody level, and 3) responses to BVDV type 2 vaccinations. A 2-shot modified live vaccine was administered to 1,004 Angus calves that were weaned at either the initial vaccination (n = 508) or the booster vaccination (n = 496). Calves weaned at the initial vaccination averaged 139 d whereas calves weaned at booster vaccination averaged 128 d of age. Bovine viral diarrhea virus type 2 antibodies were measured in 3 approximately 21-d intervals, serially collected serum samples to quantify antibody levels at initiation and end of vaccination protocol in addition to responses to initial, booster, and overall vaccination protocol. Amount of passively transferred antibody in the calf increased as dam age increased from 2 to 6 yr (P < 0.05) with no differences after dams reached 6 yr (P > 0.05). Calf age nested within birth year-season and dam age affected both initial and final antibody level, initial response, booster response, and overall antibody response to vaccination. The level of circulating, passively acquired maternal antibodies present at the time of vaccination had a significant (P < 0.05) negative effect on antibody responses to vaccination (initial response, booster response, and overall response). Calves that were weaned at the time of initial vaccination had significantly (P < 0.05) greater final antibody level, initial response, and overall response to vaccination than animals weaned at booster vaccination. In order for a calf to mount an overall antibody

  4. The January and July performance of the OSU two-level atmospheric general circulation model

    NASA Technical Reports Server (NTRS)

    Schlesinger, M. E.; Gates, W. L.

    1980-01-01

    A modified version of the two-level atmospheric general circulation model has been developed and employed in the simulation of January and July global climates. The overall physical and numerical formation of the Oregon State University model is the same as that described by Gates and Schlesinger (1977), but in the new version water vapor at the upper level has been made a prognostic variable, the parameterizations of cumulus convection, large-scale condensation and evaporation, clouds, and radiative transfer have been changed, the surface snow mass and ground temperature have been made prognostic variables, and the treatment of the surface boundary layer has been revised. It is found that the model simulates most features of the large-scale distributions of observed January and July climate more accurately than before.

  5. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure

    PubMed Central

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = −0.376, P = 0.005), C-reactive protein (CRP) (R = −0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = −0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = −0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = −0.218, P = 0.029) and LVEF (R = −0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  6. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure.

    PubMed

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = -0.376, P = 0.005), C-reactive protein (CRP) (R = -0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = -0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = -0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = -0.218, P = 0.029) and LVEF (R = -0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  7. Sex Hormones in Allergic Conjunctivitis: Altered Levels of Circulating Androgens and Estrogens in Children and Adolescents with Vernal Keratoconjunctivitis

    PubMed Central

    Sacchetti, Marta; Lambiase, Alessandro; Moretti, Costanzo; Bonini, Stefano

    2015-01-01

    Purpose. Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. Methods. 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. Results. Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). Conclusions and Relevance. VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC. PMID:25756057

  8. Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

    PubMed Central

    Yüksel, Arif; Bilgir, Ferda; Bilgir, Oktay; Calan, Mehmet; Bozkaya, Giray

    2015-01-01

    BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. PMID:26017646

  9. Increased circulating urocortin-3 levels is associated with polycystic ovary syndrome.

    PubMed

    Temur, Muzaffer; Yilmaz, Özgür; Aksun, Saliha; Özün Özbay, Pelin; Calan, Mehmet; Küme, Tuncay; Karakulak, Murat; Korkmaz, Hüseyin Anıl

    2016-01-01

    This study was aimed to compare serum urocortin-3 (UCN3) levels in women with polycystic ovary syndrome (PCOS) and healthy women, and establish what role UCN3 levels play in PCOS. Fifty-two patients with PCOS and 55 healthy women were included in the study, matched for age and body mass index. Fasting blood glucose (FBG), insulin, hs-CRP, UCN3 and free-testosterone levels of the all participants were measured. HOMA-IR was used to calculate the insulin resistance. Circulating UCN3 levels were significantly increased in women with PCOS than in control subjects (54.49 ± 5.77 versus 51.28 ± 5.86 pmol/l, p = 0.005). Serum insulin, hs-CRP and HOMA-IR levels were higher in women with PCOS than in control group. UCN3 levels positively correlated with hs-CRP in PCOS group (r = 0.391, p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curves were 0.732 (95% CI 0.634-0.830, p < 0.001) for UCN3 levels. The optimal cut-off value of UCN3 for detecting PCOS was ≥51.46 pmol/l, at which the sensitivity was 75% and specificity was 68%. Our results suggest that there is a potential link between PCOS and UCN3 levels. The results of this study support the presence of increased UCN3 levels for the association of inflammation with PCOS. PMID:26488073

  10. Association between the level of circulating adiponectin and prediabetes: A meta-analysis

    PubMed Central

    Lai, Huasheng; Lin, Nie; Xing, Zhenzhen; Weng, Huanhuan; Zhang, Hua

    2015-01-01

    Aims/Introduction Adiponectin has been proposed to have an essential role in the regulation of insulin sensitivity and metabolism, but previous studies on levels of adiponectin in prediabetes remain inconsistent. The present study aimed to assess the differences of adiponectin levels between prediabetes patients and healthy controls by carrying out a meta-analysis. Materials and Methods We carried out a systematic literature search of PubMed, EMBASE, and other databases for case–control studies and cohort studies measuring adiponectin levels in serum or plasma from prediabetes patients and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between adiponectin levels and prediabetes. Results Three cohort studies and 15 case–control studies with a total of 41,841 participants were included in the meta-analysis. The results showed that circulating adiponectin levels in prediabetes patients were significantly lower than that of healthy controls (WMD –1.694 μg/mL; 95% CI –2.151, –1.237; P < 0.001). Subgroup analysis showed more significant differences between prediabetes patients and healthy controls when the ratio of the homeostatic model assessment of insulin resistance was >2.12 (WMD −2.95 μg/mL; 95% CI –4.103, –1.806; P < 0.001) and average age was >60 years (WMD −2.20 μg/mL; 95% CI –3.207, –1.201; P < 0.001). Additionally, WMD in adiponectin showed a trend of direct correlation in subgroups of homeostatic model assessment of insulin resistance ratio, body mass index and age. Conclusions The present meta-analysis supports adiponectin levels in prediabetes patients being lower than that of healthy controls,indicating that the level of circulating adiponectin decreases before the onset of diabetes. PMID:26221520

  11. Circulating serum irisin levels in obesity and type 2 diabetes mellitus.

    PubMed

    Shoukry, Amira; Shalaby, Sally M; El-Arabi Bdeer, Shereen; Mahmoud, Amira A; Mousa, Mayada M; Khalifa, Ashraf

    2016-07-01

    Irisin is an exercise-regulated myokine inducing browning of white adipose tissue and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM). The aim of this study is to evaluate the circulating serum irisin levels in obesity and T2DM and also to elucidate possible relationships between serum irisin levels with anthropometric and metabolic parameters of obesity and T2DM. One hundred fifty newly diagnosed T2DM patients as well as 150 nondiabetic control subjects were enrolled in this study. Nondiabetic controls were then stratified according to their body mass index (BMI) into three subgroups; lean, overweight, and obese. Serum irisin levels were evaluated by enzyme-linked immunosorbent assay. Serum irisin levels were significantly decreased in T2DM patients compared with nondiabetic controls. Obese nondiabetic controls had significantly higher serum irisin levels compared with lean nondiabetic controls. In both nondiabetic controls and T2DM patients, serum irisin was significantly positively correlated with BMI (r = 0.985, P < 0.001 and r = 0.218, P = 0.007, respectively), fat mass (r = 0.959, P < 0.001 and r = 0.202, P = 0.013, respectively), fat-free mass (r = 0.606, P < 0.001 and r = 0.194, P = 0.017, respectively), fat-free mass index (r = 0.820, P < 0.001 and r = 0.179, P = 0.028, respectively), waist-to-hip ratio (r = 0.880, P < 0.001 and r = 0.194, P = 0.017, respectively), fasting insulin (r = 0.989, P < 0.001 and r = 0.207, P = 0.011, respectively), and HOMA-IR (r = 0.989, P < 0.001 and r = 0.185, P = 0.023, respectively), whereas; significantly negatively correlated with insulin sensitivity (r = -0.992, P < 0.001 and r = -0.187, P = 0.022, respectively). In this study, we demonstrated that circulating serum irisin levels were increased in obese nondiabetic subjects, while decreased in T2DM patients. Moreover, serum irisin levels were correlated

  12. Factors affecting the level of success of community information systems.

    PubMed

    Coombs, C R; Doherty, N F; Loan-Clarke, J

    1999-01-01

    The factors that influence the ultimate level of success or failure of systems development projects have received considerable attention in the academic literature. However, previous research has rarely targeted different instances of a common type of system within a homogeneous organisational sector. This paper presents the results of a survey of IM&T managers within Community Trusts to gain insights into the factors affecting the success of Community Information Systems. The results demonstrate that the most successful operational systems were thoroughly tested prior to implementation and enjoyed high levels of user and senior management commitment. Furthermore, it has been shown that there is a relationship between the level of organisational impact and systems success, with the most successful systems engendering changes to the host organisation's culture, level of empowerment and clinical working practices. In addition to being of academic interest, this research provides many important insights for practising IM&T managers. PMID:10747445

  13. Natural Circulation Level Optimization and the Effect during ULOF Accident in the SPINNOR Reactors

    SciTech Connect

    Abdullah, Ade Gafar; Su'ud, Zaki; Kurniadi, Rizal; Kurniasih, Neny; Yulianti, Yanti

    2010-12-23

    Natural circulation level optimization and the effect during loss of flow accident in the 250 MWt MOX fuelled small Pb-Bi Cooled non-refueling nuclear reactors (SPINNOR) have been performed. The simulation was performed using FI-ITB safety code which has been developed in ITB. The simulation begins with steady state calculation of neutron flux, power distribution and temperature distribution across the core, hot pool and cool pool, and also steam generator. When the accident is started due to the loss of pumping power the power distribution and the temperature distribution of core, hot pool and cool pool, and steam generator change. Then the feedback reactivity calculation is conducted, followed by kinetic calculation. The process is repeated until the optimum power distribution is achieved. The results show that the SPINNOR reactor has inherent safety capability against this accident.

  14. Natural Circulation Level Optimization and the Effect during ULOF Accident in the SPINNOR Reactors

    NASA Astrophysics Data System (ADS)

    Abdullah, Ade Gafar; Su'ud, Zaki; Kurniadi, Rizal; Kurniasih, Neny; Yulianti, Yanti

    2010-12-01

    Natural circulation level optimization and the effect during loss of flow accident in the 250 MWt MOX fuelled small Pb-Bi Cooled non-refueling nuclear reactors (SPINNOR) have been performed. The simulation was performed using FI-ITB safety code which has been developed in ITB. The simulation begins with steady state calculation of neutron flux, power distribution and temperature distribution across the core, hot pool and cool pool, and also steam generator. When the accident is started due to the loss of pumping power the power distribution and the temperature distribution of core, hot pool and cool pool, and steam generator change. Then the feedback reactivity calculation is conducted, followed by kinetic calculation. The process is repeated until the optimum power distribution is achieved. The results show that the SPINNOR reactor has inherent safety capability against this accident.

  15. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    PubMed

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. PMID:26849997

  16. Increased Levels of Circulating Advanced Glycation End-Products in Menopausal Women with Osteoporosis

    PubMed Central

    Yang, Deng-Ho; Chiang, Tsay-I; Chang, I-Chang; Lin, Fu-Huang; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-01-01

    Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis. PMID:24688308

  17. Aquifer-Circulating Water Curtain Cultivation System To Recover Groundwater Level And Temperature

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Ko, K.; Chon, C.; Oh, S.

    2011-12-01

    Groundwater temperature, which generally ranges 14 to 16 degree of Celsius all year long, can be said to be 'constant' compared to the amplitude of daily variation of air temperature or surface water. Water curtain cultivating method utilizes this 'constant' groundwater temperature to warm up the inside of greenhouse during winter night by splash groundwater on the roof of inner greenhouse. The area of water curtain cultivation system have increased up to 107.5 square kilometers as of 2006 since when it is first introduced to South Korea in 1984. Groundwater shortage problem became a great issue in a concentrated water curtain cultivation area because the pumped and splashed groundwater is abandoned to nearby stream and natural recharge rate is reduced by greenhouses. The amount of groundwater use for water curtain cultivation system in South Korea is calculated to be 587 million cubic meters which is 35% of national agricultural use of groundwater. A new water curtain cultivation system coupled with aquifer circulating of the splashed groundwater and greenhouse roof-top rainwater harvesting is developed and applied to field site in Nonsan-si, Chungnam province to minimize groundwater shortage problem and recover groundwater level. The aquifer circulating water curtain cultivation system is consist of a pumping well and a injection well of 80 m deep, groundwater transfer and splashing system, recovery tank and rainwater collecting waterway. The distance between injection and pumping well is 15 m and an observation well is installed in the middle of the wells. To characterize hydrogeological properties of this site, hydraulic test such as pumping tests and tracer tests with dye tracer, thermal tracer and ion tracer. Once the integrated system is constructed in this site, hydraulic head in all the wells and temperature of air, recovery tank and groundwater in all the wells are monitored during the operation for 3months in winter season. Hydraulic test and tracer

  18. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.

    PubMed Central

    Bonini, S; Lambiase, A; Bonini, S; Angelucci, F; Magrini, L; Manni, L; Aloe, L

    1996-01-01

    Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma. Images Fig. 2 PMID:8855290

  19. Circulating growth arrest-specific protein 6 levels are associated with erythropoietin resistance in hemodialysis patients.

    PubMed

    Chen, Miao-Pei; Chen, Chien-Wen; Chen, Jin-Shuen; Mao, Hung-Chung; Chou, Chu-Lin

    2016-01-01

    Growth arrest-specific protein 6 (Gas6) works synergistically with erythropoietin (EPO) to increase the proliferation and maturation of erythroblasts. However, the role of Gas 6 levels on EPO resistance in hemodialysis (HD) patients remains unclear. Therefore, the objective of this study was the first to examine the correlation between plasma Gas6 levels and EPO resistance in HD patients. We enrolled 134 HD patients and 85 healthy individuals. The HD patients were divided into 2 groups: 98 non-EPO-resistant patients and 36 EPO-resistant patients. Plasma levels of Gas6, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and albumin were quantified. Compared with non-EPO-resistant patients, EPO-resistant patients had elevated plasma concentrations of Gas6 (15.4 ± 3.3 vs. 13.7 ± 3.2 ng/mL, P = 0.006), IL-6 (3.1 ± 3.1 vs. 2.1 ± 1.5 pg/mL, P = 0.009), and hs-CRP (12.7 ± 25.2 vs. 4.5 ± 5.5 mg/L, P = 0.002). In EPO-resistant HD patients, plasma Gas6 levels were negatively correlated with albumin levels (r = -0.388, P < 0.021). Elevated Gas6 levels are associated with EPO resistance in HD patients. Also, EPO resistance is related to inflammation and malnutrition. Thus, circulating Gas6 levels could be used as the potential marker in HD patients with EPO resistance. PMID:26788441

  20. Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study

    PubMed Central

    Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

    2015-01-01

    Background Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. Methods and Results We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. Conclusions African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in

  1. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

    PubMed

    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

  2. Exploring Secondary Students' Epistemological Features Depending on the Evaluation Levels of the Group Model on Blood Circulation

    ERIC Educational Resources Information Center

    Lee, Shinyoung; Kim, Heui-Baik

    2014-01-01

    The purpose of this study is to identify the epistemological features and model qualities depending on model evaluation levels and to explore the reasoning process behind high-level evaluation through small group interaction about blood circulation. Nine groups of three to four students in the eighth grade participated in the modeling practice.…

  3. Sleep Restriction Enhances the Daily Rhythm of Circulating Levels of Endocannabinoid 2-Arachidonoylglycerol

    PubMed Central

    Hanlon, Erin C.; Tasali, Esra; Leproult, Rachel; Stuhr, Kara L.; Doncheck, Elizabeth; de Wit, Harriet; Hillard, Cecilia J.; Van Cauter, Eve

    2016-01-01

    Study Objectives: Increasing evidence from laboratory and epidemiologic studies indicates that insufficient sleep may be a risk factor for obesity. Sleep curtailment results in stimulation of hunger and food intake that exceeds the energy cost of extended wakefulness, suggesting the involvement of reward mechanisms. The current study tested the hypothesis that sleep restriction is associated with activation of the endocannabinoid (eCB) system, a key component of hedonic pathways involved in modulating appetite and food intake. Methods: In a randomized crossover study comparing 4 nights of normal (8.5 h) versus restricted sleep (4.5 h) in healthy young adults, we examined the 24-h profiles of circulating concentrations of the endocannabinoid 2-arachidonoylglycerol (2-AG) and its structural analog 2-oleoylglycerol (2-OG). We concomitantly assessed hunger, appetite, and food intake under controlled conditions. Results: A robust daily variation of 2-AG concentrations with a nadir around the middle of the sleep/overnight fast, followed by a continuous increase culminating in the early afternoon, was evident under both sleep conditions but sleep restriction resulted in an amplification of this rhythm with delayed and extended maximum values. Concentrations of 2-OG followed a similar pattern, but with a lesser amplitude. When sleep deprived, participants reported increases in hunger and appetite concomitant with the afternoon elevation of 2-AG concentrations, and were less able to inhibit intake of palatable snacks. Conclusions: Our findings suggest that activation of the eCB system may be involved in excessive food intake in a state of sleep debt and contribute to the increased risk of obesity associated with insufficient sleep. Commentary: A commentary on this article appears in this issue on page 495. Citation: Hanlon EC, Tasali E, Leproult R, Stuhr KL, Doncheck E, de Wit H, Hillard CJ, Van Cauter E. Sleep restriction enhances the daily rhythm of circulating levels of

  4. Circulating microRNAs correlated with the level of coronary artery calcification in symptomatic patients

    PubMed Central

    Liu, Wei; Ling, Shukuan; Sun, Weijia; Liu, Tong; Li, Yuheng; Zhong, Guohui; Zhao, Dingsheng; Zhang, Pengfei; Song, Jinping; Jin, Xiaoyan; Xu, Zi; Song, Hailin; Li, Qi; Liu, Shujuan; Chai, Meng; Dai, Qinyi; He, Yi; Fan, Zhanming; Zhou, Yu Jie; Li, Yingxian

    2015-01-01

    The purpose of this study was to find the circulating microRNAs (miRNAs) co-related with the severity of coronary artery calcification (CAC), and testify whether the selected miRNAs could reflect the obstructive coronary artery disease in symptomatic patients. Patients with chest pain and moderated risk for coronary artery disease (CAD) were characterized with coronary artery calcium score (CACS) from cardiac computed tomography (CT). We analyzed plasma miRNA levels of clinical matched 11 CAC (CACS > 100) and 6 non-CAC (CACS = 0) subjects by microarray profile. Microarray analysis identified 34 differentially expressed miRNAs between CAC and non CAC groups. Eight miRNAs (miR-223, miR-3135b, miR-133a-3p, miR-2861, miR-134, miR-191-3p, miR-3679-5p, miR-1229 in CAC patients) were significantly increased in CAC plasma in an independent clinical matched cohort. Four miRNAs (miR-2861, 134, 1229 and 3135b) were correlated with the degree of CAC. Validation test in angiographic cohort showed that miR-134, miR-3135b and miR-2861 were significantly changed in patients with obstructive CAD . We identified three significantly upregulated circulating miRNAs (miR-134, miR-3135b and 2861) correlated with CAC while detected obstructive coronary disease in symptomatic patients. PMID:26537670

  5. Prognostic Value of Circulating MicroRNA-210 Levels in Patients with Moderate to Severe Aortic Stenosis

    PubMed Central

    Røsjø, Helge; Dahl, Mai Britt; Bye, Anja; Andreassen, Johanna; Jørgensen, Marit; Wisløff, Ulrik; Christensen, Geir; Edvardsen, Thor; Omland, Torbjørn

    2014-01-01

    Background Circulating micro-RNAs have been proposed as a novel class of cardiovascular (CV) biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. miR-210 levels are increased in subjects with low VO2 max, which is a recognized risk factor in patients with aortic stenosis (AS), and we hypothesized that circulating miR-210 levels may be increased in patients with AS and associated with a poor prognosis. Methods We measured circulating miR-210 levels by real-time PCR in 57 patients with moderate to severe AS and in 10 age- and gender-matched healthy controls. The merit of miR-210 as a biomarker was assessed according to established criteria, including by comparing miR-210 levels with NT-proBNP and miR-22 levels, which is another miRNA biomarker candidate. Results All patients and control subjects had miR-210 levels within the range of detection (Cq<35) and the analytical variability was low. Circulating miR-210 levels were 2.0±0.2 [mean±SEM] fold increased in AS patients compared to controls (p = 0.002), whereas miR-22 levels were not differently expressed in the AS patients (0.12±0.06 fold increase, p = 0.45). The increase in miR-210 levels in AS patients was comparable to the increment in NT-proBNP levels: [AUC] 0.82 (95% CI 0.70–0.90) vs. 0.85 (0.75–0.93), respectively, p = 0.71. During a median follow-up of 1287 days, 15 patients (26%) died. There was a significant association between higher circulating levels of miR-210 and increased mortality during follow-up: hazard ratio [supra- vs. inframedian levels] 3.3 (95% CI 1.1–10.5), p = 0.039. Adjusting for other risk indices in multivariate analysis did not attenuate the prognostic merit of circulating miR-210 levels. Conclusion Circulating miR-210 levels are increased in patients with AS and provide independent prognostic information to established risk indices. Analytical characteristics were also

  6. Circulating Levels of Adipokines Predict the Occurrence of Acute Graft-versus-host Disease

    PubMed Central

    Kim, Jin Sook; You, Da-Bin; Lim, Ji-Young; Lee, Sung-Eun; Kim, Yoo-Jin; Kim, Hee-Je; Min, Chang-Ki

    2015-01-01

    Currently, detecting biochemical differences before and after allogeneic stem cell transplantation (SCT) for improved prediction of acute graft-versus-host disease (aGVHD) is a major clinical challenge. In this pilot study, we analyzed the kinetics of circulating adipokine levels in patients with or without aGVHD before and after allogeneic SCT. Serum samples were obtained and stored at -80℃ within 3 hours after collection, prior to conditioning and at engraftment after transplantation. A protein array system was used to measure the levels of 7 adipokines of patients with aGVHD (n=20) and without aGVHD (n=20). The resistin level at engraftment was significantly increased (p<0.001) after transplantation, regardless of aGVHD occurrence. In the non-aGVHD group, the concentrations of the hepatocyte growth factor (HGF) (mean values±SD; 206.6±34.3 vs. 432.3±108.9 pg/ml, p=0.040) and angiopoietin-2 (ANG-2) (mean values±SD; 3,197.2±328.3 vs. 4,471.8±568.4 pg/ml, p=0.037) at engraftment were significantly higher than those of the pre-transplant period, whereas in the aGVHD group, the levels of adipokines did not change after transplantation. Our study suggests that changes in serum HGF and ANG-2 levels could be considered helpful markers for the subsequent occurrence of aGVHD. PMID:25922595

  7. Variability in Solomon Sea circulation derived from altimeter sea level data

    NASA Astrophysics Data System (ADS)

    Melet, Angélique; Gourdeau, Lionel; Verron, Jacques

    2010-08-01

    The Solomon Sea is a key region in the Pacific Ocean where equatorial and subtropical circulations are connected. The region exhibits the highest levels in sea level variability in the entire south tropical Pacific Ocean. Altimeter data was utilized to explore sea level and western boundary currents in this poorly understood portion of the ocean. Since the geography of the region is extremely intricate, with numerous islands and complex bathymetry, specifically reprocessed along-track data in addition to standard gridded data were utilized in this study. Sea level anomalies (SLA) in the Solomon Sea principally evolve at seasonal and interannual time scales. The annual cycle is phased by Rossby waves arriving in the Solomon Strait, whereas the interannual signature corresponds to the basin-scale ENSO mode. The highest SLA variability are concentrated in the eastern Solomon Sea, particularly at the mouth of the Solomon Strait, where they are associated with a high eddy kinetic energy signal that was particularly active during the phase transition during the 1997-1998 ENSO event. Track data appear especially helpful for documenting the fine structure of surface coastal currents. The annual variability of the boundary currents that emerged from altimetry compared quite well with the variability seen at the thermocline level, as based on numerical simulations. At interannual time scales, western boundary current transport anomalies counterbalance changes in western equatorial Pacific warm water volume, confirming the phasing of South Pacific western boundary currents to ENSO. Altimetry appears to be a valuable source of information for variability in low latitude western boundary currents and their associated transport in the South Pacific.

  8. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

    PubMed Central

    Shin, Andrew C.; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A.; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J.; Lapworth, Amanda L.; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M.; Scheja, Ludger; Grove, Kevin L.; Smith, Richard D.; Qian, Wei-Jun; Lynch, Christopher J.; Newgard, Christopher B.; Buettner, Christoph

    2014-01-01

    Summary Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in non-human primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs, and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes. PMID:25307860

  9. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings.

    PubMed

    Garcia, J F; Ebbe, S N; Hollander, L; Cutting, H O; Miller, M E; Cronkite, E P

    1982-05-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 microliters of sample, the essay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases in circulating Ep levels in physiological and clinical conditions known to be associated with stimulation of suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RIA inthe hematology clinic, which will most certainly be expanded with its more extensive use. PMID:7069267

  10. Neural Affective Mechanisms Predict Market-Level Microlending

    PubMed Central

    Genevsky, Alexander; Knutson, Brian

    2015-01-01

    Humans sometimes share with others whom they may never meet or know, in violation of the dictates of pure self-interest. Research has not established which neuropsychological mechanisms support lending decisions, nor whether their influence extends to markets involving significant financial incentives. In two studies, we found that neural affective mechanisms influence the success of requests for microloans. In a large Internet database of microloan requests (N = 13,500), we found that positive affective features of photographs promoted the success of those requests. We then established that neural activity (i.e., in the nucleus accumbens) and self-reported positive arousal in a neuroimaging sample (N = 28) predicted the success of loan requests on the Internet, above and beyond the effects of the neuroimaging sample’s own choices (i.e., to lend or not). These findings suggest that elicitation of positive arousal can promote the success of loan requests, both in the laboratory and on the Internet. They also highlight affective neuroscience’s potential to probe neuropsychological mechanisms that drive microlending, enhance the effectiveness of loan requests, and forecast market-level behavior. PMID:26187248

  11. Serum Amyloid A Circulating Levels and Disease Activity in Patients with Juvenile Idiopathic Arthritis

    PubMed Central

    Giani, Teresa; Fioravanti, Antonella; Iacoponi, Francesca; Simonini, Gabriele; Pagnini, Ilaria; Spreafico, Adriano; Chellini, Federico; Galeazzi, Mauro; Cimaz, Rolando

    2012-01-01

    The aim of our study was to evaluate the association between circulating levels of serum amyloid A protein (SAA) and disease activity in patients with juvenile idiopathic arthritis (JIA). Our study group included 41 JIA patients (9 male, 32 female), classified according to the International League of Associations for Rheumatology (ILAR) criteria (5); 16 had polyarticular onset disease and 25 had oligoarticular onset disease. Among 25 patients with oligoarticular disease, three had extended oligoarthritis. Serum amyloid A (SAA), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured in both patients and 26 healthy controls. SAA levels were higher in JIA patients versus healthy controls (p<0.001). Significant positive correlations were found between SAA and the presence of active joints (rho=0.363, p<0.05), the number of active joints (rho=0.418, p<0.05), ESR (R=0.702, p<0.05) and CRP (R=0.827, p<0.05). No significant correlations between ESR and the presence of active joints (rho=0.221, p=0.225) or between ESR and the number of active joints (rho=0.118, p=0.520) were demonstrated in JIA patients. No significant correlations were obtained between CRP and the presence of active joints (rho=0.034, p=0.855) or between CRP and the number of active joints (rho=0.033, p=0.859). We discovered a significant increase in SAA levels in JIA patients, compared to controls, and a strong positive correlation between SAA level and JIA disease activity. We also discerned SAA to be a more sensitive laboratory marker than ESR and CRP for evaluating the presence and number of active joints. We suggest that SAA can be used as an additional indicator of disease activity in JIA. PMID:22869491

  12. Diet quality is associated with circulating C-reactive protein but not irisin levels in humans

    PubMed Central

    Park, Kyung Hee; Zaichenko, Lesya; Peter, Patricia; Davis, Cynthia R.; Crowell, Judith A.; Mantzoros, Christos S.

    2015-01-01

    Objective Adherence to a healthy diet has been shown to decrease the incidence of obesity and associated comorbidities. C-reactive protein (CRP) is an established inflammatory marker and irisin was recently identified as a molecule which may play a role in energy regulation and obesity but whether diet alters irisin levels remains unknown. We aimed to investigate the association between circulating irisin, leptin, and CRP levels and dietary quantity and quality using the Alternate Healthy Eating Index (AHEI) and the Alternate Mediterranean Diet Score (aMED). Materials/Methods The study evaluated dietary data and biomarker levels of 151 participants between 2009 and 2011 (71 male vs. 80 female, over 35 years old, obese 43.7%). AHEI and aMED scores were calculated based on data derived from self-administered 110-item food-frequency questionnaires estimating usual nutrient intake over the past year. Cross-sectional associations between dietary quantity, quality, body composition by bioelectric impedance, and biomarker levels including irisin, leptin, and CRP after fasting were assessed. Results CRP, but not irisin, was negatively correlated with AHEI (r = −0.34) and aMED (r = −0.31). Irisin was positively correlated with BMI (r = 0.22), fat mass (r = 0.21), waist circumference (r = 0.24), waist-hip ratio (r = 0.20), leptin (r = 0.32), and CRP (r = 0.25). Participants with the highest AHEI scores tended to have 11.6% lower concentrations of irisin (P for trend =0.09), but they were not significant after adjustment for potential confounders. Better diet quality was associated with lower CRP concentrations (P for trend=0.02) in multivariate model. Percentage of energy from carbohydrate was inversely associated with CRP. Conclusions Unlike CRP, irisin is not associated with dietary quality or quantity. PMID:24315778

  13. CIRCULATING LEVELS OF SOLUBLE RAGE AND RAGE-LIGANDS IN PATIENTS WITH ACUTE LIVER FAILURE

    PubMed Central

    Basta, Giuseppina; Turco, Serena Del; Navarra, Teresa; Lee, William M

    2016-01-01

    Animal studies suggest that receptor for advanced glycation end-product (RAGE)-dependent mechanisms contribute to acetaminophen-induced liver damage. We examined whether circulating levels of soluble RAGE (sRAGE) or RAGE ligands including extracellular newly identified RAGE binding protein (EN-RAGE), High-Mobility Group Box 1 (HMGB1) and Nɛ-(Carboxymethyl) lysine-adducts (CML), could aid prognostication following acetaminophen overdose. Sixty well-characterized acetaminophen-related acute liver failure (ALF) patients (30 spontaneous survivors and 30 transplanted and/or died) enrolled in the NIH-sponsored Acute Liver Failure Study Group, matched for age and meeting standard criteria of encephalopathy and INR > 1.5, were retrospectively studied. HMGB1, EN-RAGE, CML and sRAGE were detected by ELISA methods in sera from ALF patients as well as in 30 healthy controls. Levels of sRAGE, EN-RAGE and HMGB1, but not CML, were significantly greater (p < 0.0001) in ALF patients than normal controls. The levels of sRAGE, HMGB1 and EN-RAGE were significantly higher (p = 0.029, p = 0.083, p = 0.033) in patients with systemic inflammatory response syndrome score (SIRS) > 2 than in patients with SIRS ≤ 2. Nevertheless, only sRAGE levels were significantly higher in patients who were transplanted and/or died than in spontaneous survivors (p = 0.0005) and were positively associated with conventional markers of liver disease severity. Multivariate logistic regression identified the encephalopathy grade > 2 as independent predictors of adverse outcome on admission (odds ratio = 13, 95% CI 2.3–73, p = 0.00038). The RAGE-ligand axis may interfere with liver regeneration and should be a promising objective for further research. PMID:25825217

  14. Circulating levels of human salusin-β, a potent hemodynamic and atherogenesis regulator.

    PubMed

    Fujimoto, Kazumi; Hayashi, Akinori; Kamata, Yuji; Ogawa, Akifumi; Watanabe, Takuya; Ichikawa, Raishi; Iso, Yoshitaka; Koba, Shinji; Kobayashi, Youichi; Koyama, Takatoshi; Shichiri, Masayoshi

    2013-01-01

    Using bioinformatics analysis, we previously identified salusin-β, an endogenous bioactive peptide with diverse physiological activities. Salusin-β is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-β acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-β concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA). Salusin-β was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-β peak coincided with synthetic authentic salusin-β. Plasma salusin-β concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-β concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-β levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-β levels and for confirming the presence of authentic salusin-β in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin-β concentrations

  15. Removal of salt from high-level waste tanks by density-driven circulation or mechanical agitation

    SciTech Connect

    Kiser, D.L.

    1981-01-01

    Twenty-two high-level waste storage tanks at the Savannah River Plant are to be retired in the tank replacement/waste transfer program. The salt-removal portion of this program requires dissolution of about 19 million liters of salt cake. Steam circulation jets were originally proposed to dissolve the salt cake. However, the jets heated the waste tank to 80 to 90/sup 0/C. This high temperature required a long cooldown period before transfer of the supernate by jet, and increased the risk of stress-corrosion cracking in these older tanks. A bench-scale investigation at the Savannah River Laboratory developed two alternatives to steam-jet circulation. One technique was density-driven circulation, which in bench tests dissolved salt at the same rate as a simulated steam circulation jet but at a lower temperature. The other technique was mechanical agitation, which dissolved the salt cake faster and required less fresh water than either density-driven circulation or the simulated steam circulation jet. Tests in an actual waste tank verified bench-scale results and demonstrated the superiority of mechanical agitation.

  16. Circulating Heat Shock Protein 60 Levels Are Elevated in HIV Patients and Are Reduced by Anti-Retroviral Therapy

    PubMed Central

    Anraku, Itaru; Rajasuriar, Reena; Dobbin, Caroline; Brown, Richard; Lewin, Sharon R.; Suhrbier, Andreas

    2012-01-01

    Circulating heat shock protein 60 (Hsp60) and heat shock protein 10 (Hsp10) have been associated with pro- and anti-inflammatory activity, respectively. To determine whether these heat shock proteins might be associated with the immune activation seen in HIV-infected patients, the plasma levels of Hsp60 and Hsp10 were determined in a cohort of 20 HIV-infected patients before and after effective combination anti-retroviral therapy (cART). We show for the first time that circulating Hsp60 levels are elevated in HIV-infected patients, with levels significantly reduced after cART, but still higher than those in HIV-negative individuals. Hsp60 levels correlated significantly with viral load, CD4 counts, and circulating soluble CD14 and lipopolysaccharide levels. No differences or correlations were seen for Hsp10 levels. Elevated circulating Hsp60 may contribute to the immune dysfunction and non-AIDS clinical events seen in HIV-infected patients. PMID:23028910

  17. Comparable low-level mosaicism in affected and non affected tissue of a complex CDH patient.

    PubMed

    Veenma, Danielle; Beurskens, Niels; Douben, Hannie; Eussen, Bert; Noomen, Petra; Govaerts, Lutgarde; Grijseels, Els; Lequin, Maarten; de Krijger, Ronald; Tibboel, Dick; de Klein, Annelies; Van Opstal, Dian

    2010-01-01

    In this paper we present the detailed clinical and cytogenetic analysis of a prenatally detected complex Congenital Diaphragmatic Hernia (CDH) patient with a mosaic unbalanced translocation (5;12). High-resolution whole genome SNP array confirmed a low-level mosaicism (20%) in uncultured cells, underlining the value of array technology for identification studies. Subsequently, targeted Fluorescence In-Situ Hybridization in postmortem collected tissues demonstrated a similar low-level mosaicism, independently of the affected status of the tissue. Thus, a higher incidence of the genetic aberration in affected organs as lung and diaphragm cannot explain the severe phenotype of this complex CDH patient. Comparison with other described chromosome 5p and 12p anomalies indicated that half of the features presented in our patient (including the diaphragm defect) could be attributed to both chromosomal areas. In contrast, a few features such as the palpebral downslant, the broad nasal bridge, the micrognathia, microcephaly, abnormal dermatoglyphics and IUGR better fitted the 5p associated syndromes only. This study underlines the fact that low-level mosaicism can be associated with severe birth defects including CDH. The contribution of mosaicism to human diseases and specifically to congenital anomalies and spontaneous abortions becomes more and more accepted, although its phenotypic consequences are poorly described phenomena leading to counseling issues. Therefore, thorough follow-up of mosaic aberrations such as presented here is indicated in order to provide genetic counselors a more evidence based prediction of fetal prognosis in the future. PMID:21203572

  18. Detection and adequacy evaluation of erythrocyte glutathione transferase on levels of circulating toxins in hemodialysis patients.

    PubMed

    Yin, Rui; Qiu, Hui; Zuo, Huaiyun; Cui, Min; Zhai, Nailiang; Zheng, Hongguang; Zhang, Dewei; Huo, Ping; Hong, Min

    2016-08-01

    To explore detection and adequacy evaluation of erythrocyte glutathione S transferase (GST) on levels of circulating toxins in hemodialysis patients in Qinhuangdao region in China, this study divided 84 cases of long-term, end-stage hemodialysis patients into 2 groups: one group of 33 cases of adequate hemodialysis (spKt/V ≥ 1.3) and another group of 51 cases of inadequate hemodialysis (spKt/V < 1.3), according to the urea index value of the unit chamber model (spKt/V). Another 50 cases of subjects found healthy by a physical examination were taken as the control group, and the differences in the related clinical and biochemical indexes of the 3 groups were compared and analyzed. The levels of GST, creatinine, high sensitivity C-reactive protein (hs-CRP), transferrin saturation (TSAT), parathyroid hormone (PTH), interleukin-2,6,8 (IL-2,6,8) and tumor necrosis factor-a (TNF-a) in the hemodialysis group were significantly higher than those in the control group (P < 0.05), and GST, IL-2, 6, 8, and TNF-a levels in the inadequate hemodialysis group were significantly higher than in the adequate hemodialysis group (P < 0.05). Pearson's relevant analysis showed that the levels of GST and spKt/V, IL-2, IL-6, IL-8, and TNF-a have a positive correlation (P < 0.05), and they have no correlation with levels of creatinine, hs-CRP, TSAT, and PHT (P > 0.05). There were 23 patients with levels of spKt/V ≥ 1.3 after adjusting the dialysis solution for 51 cases of inadequate hemodialysis patients, and the GST level after the adjustment was significantly lower than that before the adjustment, but still higher than that in the adequate dialysis group. This concludes that the maintenance of hemodialysis in patients has certain relevance on spKt/V and associated inflammatory factors. Through the study, it can be determined that GST can effectively respond to adequate hemodialysis, which has a guiding significance on adjusting the blood dialysis solution in clinical practice. PMID

  19. Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause and impact female reproductive health

    PubMed Central

    Ruth, Katherine S.; Beaumont, Robin N.; Tyrrell, Jessica; Jones, Samuel E.; Tuke, Marcus A.; Yaghootkar, Hanieh; Wood, Andrew R.; Freathy, Rachel M.; Weedon, Michael N.; Frayling, Timothy M.; Murray, Anna

    2016-01-01

    STUDY QUESTION How does a genetic variant in the FSHB promoter, known to alter FSH levels, impact female reproductive health? SUMMARY ANSWER The T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) results in longer menstrual cycles and later menopause and, while having detrimental effects on fertility, is protective against endometriosis. WHAT IS KNOWN ALREADY The FSHB promoter polymorphism (rs10835638; c.-211G>T) affects levels of FSHB transcription and, as a result, circulating levels of FSH. FSH is required for normal fertility and genetic variants at the FSHB locus are associated with age at menopause and polycystic ovary syndrome (PCOS). STUDY DESIGN, SIZE, DURATION We used cross-sectional data from the UK Biobank to look at associations between the FSHB promoter polymorphism and reproductive traits, and performed a genome-wide association study (GWAS) for length of menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS We included white British individuals aged 40–69 years in 2006–2010, in the May 2015 release of genetic data from UK Biobank. We tested the FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) for associations with 29, mainly female, reproductive phenotypes in up to 63 350 women and 56 608 men. We conducted a GWAS in 9534 individuals to identify genetic variants associated with length of menstrual cycle. MAIN RESULTS AND THE ROLE OF CHANCE The FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; MAF 0.16) was associated with longer menstrual cycles [0.16 SD (c. 1 day) per minor allele; 95% confidence interval (CI) 0.12–0.20; P = 6 × 10−16], later age at menopause (0.13 years per minor allele; 95% CI 0.04–0.22; P = 5.7 × 10−3), greater female nulliparity [odds ratio (OR) = 1.06; 95% CI 1.02–1.11; P = 4.8 × 10−3] and lower risk of endometriosis (OR = 0.79; 95% CI 0.69–0.90; P = 4.1 × 10−4). The FSH-lowering T allele was not associated with other female

  20. Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women.

    PubMed

    Chandler, Paulette D; Buring, Julie E; Manson, JoAnn E; Giovannucci, Edward L; Moorthy, M V; Zhang, Shumin; Lee, I-Min; Lin, Jennifer H

    2015-08-01

    Observational data on the association between circulating 25(OH)D and colorectal cancer risk are limited in women. To determine whether prediagnostic levels of 25(OH)D were associated with risk of incident colorectal cancer in the Women's Health Study (WHS), we conducted a nested case-control study using 274 colorectal cases and 274 controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Conditional logistic regression was used to estimate the OR and 95% confidence interval (CI) for colorectal cancer by 25(OH)D quartiles. Mean plasma 25(OH)D was lower in cases versus controls (21.9 vs. 23.9 ng/mL, P = 0.01). In multivariable-adjusted logistic regression models, plasma 25(OH)D was significantly and inversely associated with odds of colorectal cancer (quartile 4 [Q4] vs. quartile 1 [Q1]: OR, 0.45; 95% CI, 0.25-0.81; Ptrend 0.02). In addition, we observed a somewhat lower risk of colorectal cancer-related mortality after adjustment for matching variables, randomization treatment and other risk factors (Q4:Q1 OR, 0.40; 95% CI, 0.17-0.97; Ptrend 0.05). In this cohort of healthy women, we found a significant inverse association between prediagnostic 25(OH)D levels and risk of incident colorectal cancer, and a borderline significant inverse association between prediagnostic 25(OH)D levels and colorectal cancer-related mortality. These results support a possible association between plasma 25(OH)D and risk of colorectal cancer in women. PMID:25813525

  1. Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans

    PubMed Central

    Luo, Zhong-Cheng; Bilodeau, Jean-François; Monique Nuyt, Anne; Fraser, William D.; Julien, Pierre; Audibert, Francois; Xiao, Lin; Garofalo, Carole; Levy, Emile

    2015-01-01

    In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p < 0.0001). Adjusting for gestational age at blood sampling, cord plasma ghrelin concentrations were consistently negatively correlated to oxidative stress biomarkers in maternal (r = −0.32, p < 0.0001 for MDA; r = −0.31, p < 0.0001 for F2-isoprostanes) or cord plasma (r = −0.13, p = 0.04 for MDA; r = −0.32, p < 0.0001 for F2-isoprostanes). Other fetal metabolic health biomarkers were not correlated to oxidative stress. Adjusting for maternal and pregnancy characteristics, similar associations were observed. Our study provides the first preliminary evidence suggesting that oxidative stress may affect fetal ghrelin levels in humans. The implications in developmental “programming” the vulnerability to metabolic syndrome related disorders remain to be elucidated. PMID:26643495

  2. Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies

    PubMed Central

    Song, Ci; Nutile, Teresa; Vernon Smith, Albert; Concas, Maria Pina; Traglia, Michela; Barbieri, Caterina; Ndiaye, Ndeye Coumba; Stathopoulou, Maria G.; Lagou, Vasiliki; Maestrale, Giovanni Battista; Sala, Cinzia; Debette, Stephanie; Kovacs, Peter; Lind, Lars; Lamont, John; Fitzgerald, Peter; Tönjes, Anke; Gudnason, Vilmundur; Toniolo, Daniela; Pirastu, Mario; Bellenguez, Celine; Vasan, Ramachandran S.; Ingelsson, Erik; Leutenegger, Anne-Louise; Johnson, Andrew D.; DeStefano, Anita L.; Visvikis-Siest, Sophie; Seshadri, Sudha; Ciullo, Marina

    2016-01-01

    importance of this process in regulation of VEGF levels. This work also provided new insights into the involvement of genes implicated in various angiogenesis related pathologies in determining circulating VEGF levels. The understanding of the molecular mechanisms by which the identified genes affect circulating VEGF levels could be important in the development of novel VEGF-related therapies for such diseases. PMID:26910538

  3. Linking variations in large-scale climatic circulation and groundwater level in southern England

    NASA Astrophysics Data System (ADS)

    Lavers, D. A.; Hannah, D. M.; Bradley, C.

    2012-12-01

    Groundwater is a crucial water resource in many parts of the World. It can sustain river/ wetland ecosystems and human water needs during dry spells and droughts. In certain geological settings, periods of prolonged high rainfall can generate groundwater flooding while elevated water tables prime river basins for more rapid stormflow runoff. In a changing climate with projected increases in the frequency and intensity of hydrologic extremes, groundwater levels are also expected to change. In this study, we quantify the links between groundwater levels in the Lambourn river basin (a sub-catchment of the Thames basin) in southern England, which is underlain by a major permeable (Chalk) aquifer, and the large-scale climatic circulation to improve processes understanding of groundwater response to hydroclimatological drivers. Precipitation, river discharge and groundwater levels for borehole sites in the Lambourn basin over 1974-2010 are analysed as the target variables. We use two sources of monthly large-scale climate data: (1) Indices of the North Atlantic Oscillation (NAO) and the Scandinavian Pattern (SCP) from the Climate Prediction Center, and (2) gridded reanalysis data from the Twentieth Century Reanalysis Project (20CR). Firstly, links between groundwater levels (and precipitation / discharge) and the climate data are explored using monthly concurrent and lagged correlation analyses between the NAO and SCP, and groundwater (and precipitation / discharge). Secondly, gridded 20CR reanalysis data are used in a correlation analysis to determine whether the regions of strongest climate-groundwater association have more explanatory power than the static NAO/SCP indices. Results show that reasonably strong climate-groundwater connections exist in the Lambourn basin, with a several months lag; these lags are associated with the time taken for rainfall delivered to travel through the basin. The 20CR gridded product is shown to have stronger links than the NAO or SCP

  4. Precipitation trends in southeastern South America: relationship with ENSO phases and with low-level circulation

    NASA Astrophysics Data System (ADS)

    Barros, V. R.; Doyle, M. E.; Camilloni, I. A.

    2008-06-01

    Rainfall trends in subtropical South America east of the Andes during the period 1960 1999 were studied in connection with El Niño-Southern Oscillation (ENSO) phases. In addition, monthly mean sea level pressure (SLP) fields from the National Center for Environmental Prediction reanalysis were used to look at the connection between rainfall trends and the interannual variability of the low-level atmospheric circulation. South of 22° S, annual rainfall trends were positive everywhere, and statistically significant over part of western subtropical Argentina. Over most of the region, trends resulted mostly from the warm semester (October March) trends with little contribution from the cold semester (April September). Under certain conditions, linear precipitation trends of each ENSO phase add up to the total rainfall trend. In northeastern Argentina, southern Brazil and Paraguay, half of the annual rainfall trend came from El Niño phase with a minor contribution from La Niña and the neutral phase. However, in most of subtropical South America, east of the Andes, precipitation trends during the extreme phases of the ENSO constitute only a small part of the trends. A Principal Component Analysis (PCA) was applied to the monthly SLP fields of the austral warm semester. The mode that advects humid air from the Atlantic Ocean over most of Argentina and Uruguay has grown at the expense of the one that favors the flow from the tropical forest over the eastern part of the continent. South of 30° S, annual rainfall trends took place predominantly during the neutral phase of the ENSO, and were related to the trends of the first two SLP leading modes. On the other hand, the annual trends were negative in the continental part of the South Atlantic Convergence Zone (SACZ), but with contributions from all ENSO phases.

  5. Levels of maternal care in dogs affect adult offspring temperament.

    PubMed

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  6. Levels of maternal care in dogs affect adult offspring temperament

    PubMed Central

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  7. C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

    PubMed

    Ancelin, M-L; Farré, A; Carrière, I; Ritchie, K; Chaudieu, I; Ryan, J

    2015-01-01

    C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression. PMID:25603415

  8. Association of Circulating Orexin-A Level With Metabolic Risk Factors in North Indian Pre Menopausal Women.

    PubMed

    Gupta, Vani; Mishra, Sameeksha; Kumar, Sandeep; Mishra, Supriya

    2015-01-01

    The present study was designed to investigate the association between circulating Orexin-A level with metabolic risk factors in North Indian adult women. 342 women were enrolled for the case-control study, 172 women were with metabolic syndrome (mets) and 170 healthy control women were without metabolic syndrome, (womets) according to (NCEP ATP III criteria). Circulating Orexin-A level was determined by enzyme-linked immunosorbent assay. Observations indicated low levels of orexin-A (26.06 ± 6.09 ng/ml) in women with mets and other metabolic risk factors compared to women without metabolic syndrome (36.50 ± 10.42 ng/ml). Further, in women with metabolic syndrome, circulating Orexin A was significantly associated with waist circumference, triglyceride (negative correlation) and hyperdensity lipoprotein (positive correlation). Our study shows that circulating Orexin A was found to be significantly associated with hyperlipidemia, obesity and obesity-related disorders in North Indian premenopausal women. PMID:27530010

  9. Response of the South Pacific Convergence Zone to imposed circulation and moisture perturbations in an intermediate level complexity model

    NASA Astrophysics Data System (ADS)

    Niznik, M. J.; Lintner, B. R.

    2014-12-01

    Previous research has identified a connection between the strength of low-level trade wind inflow from the relatively dry southeastern Pacific basin and the position of the South Pacific Convergence Zone (SPCZ). This circulation-precipitation relationship has been noted in composite analysis applied to reanalysis data as well as to output from current generation climate models, although the causality is ambiguous. Additionally, given that prior studies exhibit deep vertical structures associated with changes to low-level inflow east of the SPCZ, the relationship between low-level inflow variability and the propagation of upper level mid-latitude synoptic disturbances into the SPCZ remains unclear. Thus, forcing models with prescribed circulation and moisture anomalies may be instructive for untangling the dynamic and thermodynamic contributions to such interactions, as well as their potential causality. To that end, we use the Quasi-equilibrium Tropical Circulation Model 2 (QTCM2), an intermediate complexity model with a separate boundary layer of fixed height imposed at the base of the free troposphere, to explore the response of the SPCZ, and more broadly convection across the South Pacific, to perturbed low- and upper-level circulation and moisture fields east of its climatological position. Preliminary results suggest a strong precipitation response to strengthened low-level trade wind inflow, hypothesized to be the result of increased convergence in the climatological SPCZ, with an associated decrease in Intertropical Convergence Zone (ITCZ) precipitation. Conversely, there is a limited precipitation response to weakened low-level trade wind inflow despite a notable (2-3 g kg-1) increase in specific humidity, suggesting the climatological low-level inflow is already associated with the necessary moisture threshold for deep convection. Ultimately, these results suggest dynamics play a stronger role than thermodynamics in the interaction as modeled by QTCM2.

  10. New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women

    PubMed Central

    2011-01-01

    Background Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines. Design We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m2] and 31 lean [BMI ≤ 25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR. Results Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue. Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls. Conclusions The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women. PMID:21526992

  11. Hfq affects mRNA levels independently of degradation

    PubMed Central

    2010-01-01

    Background The bacterial Lsm protein, Hfq, is an RNA chaperone involved in many reactions related to RNA metabolism, such as replication and stability, control of small RNA activity and polyadenylation. Despite this wide spectrum of known functions, the global role of Hfq is almost certainly undervalued; its capacity to bind DNA and to interact with many other proteins are only now beginning to be taken into account. Results The role of Hfq in the maturation and degradation of the rpsO mRNA of E. coli was investigated in vivo. The data revealed a decrease in rpsO mRNA abundance concomitant to an increase in its stability when Hfq is absent. This indicates that the change in mRNA levels in hfq mutants does not result from its modification of RNA stability. Moreover, a series of independent experiments have revealed that the decrease in mRNA level is not a consequence of a reduction of translation efficiency and that Hfq is not directly implicated in translational control of rpsO expression. Reduced steady-state mRNA levels in the absence of Hfq were also shown for rpsT, rpsB and rpsB-tsf, but not for lpp, pnp or tRNA transcripts. The abundance of chimeric transcripts rpsO-lacZ and rpsB-lacZ, whose expression was driven by rpsO and rpsB promoters, respectively, was also lower in the hfq null-mutants, while the β-galactosidase yield remained about the same as in the parent wild-type strain. Conclusions The data obtained suggest that alteration of rpsO, rpsT and rpsB-tsf transcript levels observed under conditions of Hfq deficiency is not caused by the post-transcriptional events, such as mRNA destabilization or changes in translation control, and may rather result from changes in transcriptional activity. So far, how Hfq affects transcription remains unclear. We propose that one of the likely mechanisms of Hfq-mediated modulation of transcription might operate early in the elongation step, when interaction of Hfq with a nascent transcript would help to overcome

  12. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    PubMed Central

    2011-01-01

    Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first

  13. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

    PubMed

    De Santis, S; Pace, A; Bove, L; Cognetti, F; Properzi, F; Fiore, M; Triaca, V; Savarese, A; Simone, M D; Jandolo, B; Manzione, L; Aloe, L

    2000-01-01

    The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds. PMID:10656436

  14. Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation – Description of a novel in vitro model

    SciTech Connect

    Ehnert, Sabrina; Freude, Thomas; Ihle, Christoph; Mayer, Larissa; Braun, Bianca; Graeser, Jessica; Flesch, Ingo; and others

    2015-03-15

    Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts' maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera. Between both control groups, no significant changes were observed. Proliferation was significantly increased (1.69-fold), while AP activity and matrix mineralization was significantly reduced in the T2DM group. Expression levels of osteogenic marker genes and transcription factors were altered, e.g. down-regulation of RUNX2 and SP-7 or up-regulation of STAT1, in the T2DM group. Active TGF-β levels were significantly increased (1.46-fold) in T2DM patients' sera. SCP-1 cells treated with these sera showed significantly increased TGF-β signaling (2.47-fold). Signaling inhibition effectively restored osteoblast maturation in the T2DM group. Summarizing our data, SCP-1 cells differentiated in the presence of T2DM patients' serum exhibit reduced osteoblast function. Thus, this model has a high physiological impact, as it can identify circulating factors in T2DM patients' blood that may affect bone function, e.g. TGF-β. - Highlights: • We present here a physiologically relevant in vitro model for diabetic osteopathy. • Blood of T2DM patients contains factors that affect osteoblasts' function. • The model developed here can be used to identify these factors, e.g. TGF-β. • Blocking TGF-β signaling partly rescues the osteoblasts' function in the T2DM group. • The model is useful to demonstrate the role of single factors in diabetic osteopathy.

  15. Association of Circulating Follistatin-Like 1 Levels with Inflammatory and Oxidative Stress Markers in Healthy Men

    PubMed Central

    Hayakawa, Satoko; Ohashi, Koji; Shibata, Rei; Takahashi, Ryotaro; Otaka, Naoya; Ogawa, Hayato; Ito, Masanori; Kanemura, Noriyoshi; Hiramatsu-Ito, Mizuho; Ikeda, Nobuo; Murohara, Toyoaki; Ouchi, Noriyuki

    2016-01-01

    Objectives Follistatin-like 1 (Fstl1) is a circulating glycoprotein that plays a crucial role in cardiovascular diseases and inflammation-related disorders. We have shown that Fstl1 acts as an anti-inflammatory factor that protects against ischemic heart disease and chronic kidney disease. Here we examined whether plasma level of Fstl1 associates with markers of inflammation and oxidative stress in apparently healthy Japanese men. Methods and Results Plasma Fstl1 levels were measured by enzyme-linked immunosorbent assay. Circulating Fstl1 concentrations positively correlated with levels of fasting immune-reactive insulin (FIRI), high-sensitive CRP (hsCRP) and derivatives of reactive oxidative metabolites (dROMs), an indicator of oxidative stress. The levels of hsCRP positively associated with Fstl1, body mass index (BMI), triglyceride, FIRI and dROMs levels. dROMs levels positively associated with Fstl1, Hemoglobin A1c and hsCRP levels. Multiple regression analysis with confounding factors revealed that Fstl1 levels, together with BMI and FIRI, correlated with hsCRP and that Fstl1 levels correlated with dROMs. Conclusion Our observations indicate that measurement of plasma Fstl1 levels can be valuable for assessment of pro-inflammatory and oxidative stress conditions. PMID:27145224

  16. Numerical simulations of a transverse indirect circulation and low-level jet in the exit region of an upper-level jet

    NASA Technical Reports Server (NTRS)

    Brill, K. F.; Uccellini, L. W.; Burkhart, R. P.; Warner, T. T.; Anthes, R. A.

    1985-01-01

    A numerical study was performed of a severe weather event (tornado) which occurred on May 10, 1973 in the Ohio region. The situation was modeled with a primitive equation mesoscale dynamic formulation. Account was taken of precipitation, the planetary boundary layer parameters as bulk quantities, the vertical pressure gradient, and lateral boundary conditions based on radiosonde data. Two 12-hr simulations, adiabatic and nondivergent, respectively, were analyzed for relationships between upper and lower level jets. In the adiabatic formulation, a transverse circulation with a low level jet formed at the exit region of the upper level jet. The nondivergent situation led to similar, but weaker, phenomena. Both forms suggest that indirect circulation in the exit zone of an upper level jet is strongly influenced by the initial structure of the jet.

  17. Type of Speech Material Affects Acceptable Noise Level Test Outcome.

    PubMed

    Koch, Xaver; Dingemanse, Gertjan; Goedegebure, André; Janse, Esther

    2016-01-01

    The acceptable noise level (ANL) test, in which individuals indicate what level of noise they are willing to put up with while following speech, has been used to guide hearing aid fitting decisions and has been found to relate to prospective hearing aid use. Unlike objective measures of speech perception ability, ANL outcome is not related to individual hearing loss or age, but rather reflects an individual's inherent acceptance of competing noise while listening to speech. As such, the measure may predict aspects of hearing aid success. Crucially, however, recent studies have questioned its repeatability (test-retest reliability). The first question for this study was whether the inconsistent results regarding the repeatability of the ANL test may be due to differences in speech material types used in previous studies. Second, it is unclear whether meaningfulness and semantic coherence of the speech modify ANL outcome. To investigate these questions, we compared ANLs obtained with three types of materials: the International Speech Test Signal (ISTS), which is non-meaningful and semantically non-coherent by definition, passages consisting of concatenated meaningful standard audiology sentences, and longer fragments taken from conversational speech. We included conversational speech as this type of speech material is most representative of everyday listening. Additionally, we investigated whether ANL outcomes, obtained with these three different speech materials, were associated with self-reported limitations due to hearing problems and listening effort in everyday life, as assessed by a questionnaire. ANL data were collected for 57 relatively good-hearing adult participants with an age range representative for hearing aid users. Results showed that meaningfulness, but not semantic coherence of the speech material affected ANL. Less noise was accepted for the non-meaningful ISTS signal than for the meaningful speech materials. ANL repeatability was comparable across

  18. Type of Speech Material Affects Acceptable Noise Level Test Outcome

    PubMed Central

    Koch, Xaver; Dingemanse, Gertjan; Goedegebure, André; Janse, Esther

    2016-01-01

    The acceptable noise level (ANL) test, in which individuals indicate what level of noise they are willing to put up with while following speech, has been used to guide hearing aid fitting decisions and has been found to relate to prospective hearing aid use. Unlike objective measures of speech perception ability, ANL outcome is not related to individual hearing loss or age, but rather reflects an individual’s inherent acceptance of competing noise while listening to speech. As such, the measure may predict aspects of hearing aid success. Crucially, however, recent studies have questioned its repeatability (test–retest reliability). The first question for this study was whether the inconsistent results regarding the repeatability of the ANL test may be due to differences in speech material types used in previous studies. Second, it is unclear whether meaningfulness and semantic coherence of the speech modify ANL outcome. To investigate these questions, we compared ANLs obtained with three types of materials: the International Speech Test Signal (ISTS), which is non-meaningful and semantically non-coherent by definition, passages consisting of concatenated meaningful standard audiology sentences, and longer fragments taken from conversational speech. We included conversational speech as this type of speech material is most representative of everyday listening. Additionally, we investigated whether ANL outcomes, obtained with these three different speech materials, were associated with self-reported limitations due to hearing problems and listening effort in everyday life, as assessed by a questionnaire. ANL data were collected for 57 relatively good-hearing adult participants with an age range representative for hearing aid users. Results showed that meaningfulness, but not semantic coherence of the speech material affected ANL. Less noise was accepted for the non-meaningful ISTS signal than for the meaningful speech materials. ANL repeatability was comparable

  19. Effects of electromagnetic fields on photophasic circulating melatonin levels in American kestrels.

    PubMed Central

    Fernie, K J; Bird, D M; Petitclerc, D

    1999-01-01

    Birds reproduce within electromagnetic fields (EMFs) from transmission lines. Melatonin influences physiologic and behavioral processes that are critical to survival, and melatonin has been equivocally suppressed by EMFs in mammalian species. We examined whether EMFs affect photophasic plasma melatonin in reproducing adult and fledgling American kestrels (Falco sparverius), and whether melatonin was correlated with body mass to explain previously reported results. Captive kestrel pairs were bred under control or EMF conditions for one (short-term) or two (long-term) breeding seasons. EMF exposure had an overall effect on plasma melatonin in male kestrels, with plasma levels suppressed at 42 days and elevated at 70 days of EMF exposure. The similarity in melatonin levels between EMF males at 42 days and controls at 70 days suggests a seasonal phase-shift of the melatonin profile caused by EMF exposure. Melatonin was also suppressed in long-term fledglings, but not in short-term fledglings or adult females. Melatonin levels in adult males were higher than in adult females, possibly explaining the sexually dimorphic response to EMFs. Melatonin and body mass were not associated in American kestrels. It is likely that the results are relevant to wild raptors nesting within EMFs. Images Figure 1 PMID:10544158

  20. Increased circulating heat shock protein 70 (HSPA1A) levels in gestational diabetes mellitus: a pilot study.

    PubMed

    Garamvölgyi, Zoltán; Prohászka, Zoltán; Rigó, János; Kecskeméti, András; Molvarec, Attila

    2015-07-01

    Recent data indicate that serum Hsp70 (HSPA1A) levels are increased in type 1 and 2 diabetes mellitus. However, there is no report in the literature on circulating Hsp70 levels in gestational diabetes mellitus. In this pilot study, we measured serum Hsp70 levels in 11 pregnant women with pregestational diabetes, 38 women with gestational diabetes, and 40 healthy pregnant women with ELISA. Plasma glucose levels, serum insulin concentrations, HbA1c values, and the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were also determined. According to our results, serum Hsp70 concentrations were significantly higher in women with pregestational and gestational diabetes mellitus than in healthy pregnant women. In addition, pregestational diabetic women had significantly higher Hsp70 levels than those with gestational diabetes. Furthermore, in the group of women with gestational diabetes mellitus, serum Hsp70 levels showed a significant positive correlation with HbA1c values. However, there was no other relationship between clinical features and metabolic parameters of the study subjects and their serum Hsp70 levels in either study group. In conclusion, we demonstrated for the first time in the literature that serum Hsp70 levels are increased and correlate with HbA1c values in women with gestational diabetes mellitus. Nevertheless, further studies are needed to determine whether circulating Hsp70 plays a causative role in the pathogenesis of gestational diabetes or elevated serum Hsp70 levels are only consequences of the disease. PMID:25720752

  1. Irisin mRNA and circulating levels in relation to other myokines in healthy and morbidly obese humans

    PubMed Central

    Vamvini, Maria T.; Aronis, Konstantinos N.; Panagiotou, Grigorios; Huh, Joo Young; Chamberland, John P.; Brinkoetter, Mary T.; Petrou, Michael; Christophi, Costas A.; Kales, Stefanos N.; Christiani, David C.; Mantzoros, Christos S.

    2013-01-01

    Objective Skeletal muscle is considered to be an endocrine organ that secretes a number of myokines including follistatin, myostatin, activin A and the newly identified irisin. Irisin’s biology and function exhibits similarities with the functions of the follistatin-myostatin-activin A axis. It remains unknown whether there is any interplay among these molecules. The aim of this study is to examine potential associations of irisin with the follistatin, myostatin and activin A axis. Material-methods Two observational studies were performed to evaluate the associations of irisin with the other three peptides. Study A included 150 healthy males aged 18.48 ±0.16 years with Body Mass Index (BMI) 23.18± 3.75 kg/m2. Fasting serum samples were used to measure the levels of the molecules of interest. Study B included 14 morbidly obese individuals, candidates for bariatric surgery, aged 53.14±8.93 years with BMI 50.18±10.63 kg/m2. Blood samples were obtained after an overnight fast. Eight out of the fourteen participants consented to an optional thigh biopsy during their bariatric surgery. Using the above blood and tissue samples, we measured circulating levels and muscle mRNA of irisin, follistatin, myostatin and activin A. Results We report that FNDC5 mRNA in muscle is positively correlated with follistatin mRNA expression in morbidly obese subjects (rho=0.93, p<0.001). We also found that circulating irisin is positively correlated with follistatin circulating levels among lean subjects (rho=0.17, p=0.05) while this association was suggestive among the obese (rho=0.56, p=0.07). Conclusion The newly identified myokine irisin may be positively associated with follistatin at both the mRNA and circulating protein level. PMID:24062354

  2. Comparison of TOPEX/Poseidon Sea Level Observations to Simulations by the Los Alamos Ocean General Circulation Mode

    NASA Technical Reports Server (NTRS)

    Fu, L.; Smith, R.

    1995-01-01

    The sea level observations from the TOPEX/Poseidon radar altimeter from October, 1992 to October, 1994 were used to study the circulation of the global oceans and their temporal changes. To provide a framework for interpreting the observations, the Parallel Ocean Program model of the Los Alamos National Laboratory was run for the same period of time for comparison. A report of that data is given.

  3. Quantitation of protein 3 content of circulating erythrocytes at the single-cell level

    SciTech Connect

    Jennings, L.K.; Brown, L.K.; Dockter, M.E.

    1985-05-01

    The density and size of human erythrocytes has been roughly correlated with cell age, with the denser and smaller cells being older. Observations of this type have led to a hypothesis that the membranes of circulating erythrocytes are dynamic with respect to composition and that material is lost from the membrane during cell maturation and circulation. In this study, flow cytofluorimetry was used to investigate the distribution of the human erythrocyte anion transport protein (protein 3) in heterogeneous samples of circulating red cells. We verified that protein 3 can be specifically and quantitatively labeled in intact human erythrocytes with eosin-5-maleimide, a luminescent probe. Individual cells were accordingly analyzed for size by forward light scattering and for protein 3 content by quantitation of eosin fluorescence. Initial results indicated that the smallest erythrocytes had a protein 3 content equal to that of the largest circulating erythrocytes. This result was independently verified by light scatter-activated cell sorting; direct measurement of cell diameters by microscopy verified that the cell sizes of erythrocytes showing the 10% greatest and 10% smallest light-scattering signal were indeed distinct. Independent analysis of the size-sorted erythrocytes for protein 3 content was accomplished by gel electrophoresis of stroma from 150,000 large and small erythrocytes. Quantitative scanning densitometry of silver-stained gels of prepared stroma showed that protein 3 content of each set of fractionated cells was equal and did not vary as a function of cell size. Taken in combination with the reported correlation between increasing red blood cell age and decreasing cell size, these results indicate that any loss of membranous material during the cell aging process is not random.

  4. Circulating levels of insulin-like growth factor-I (IGF-I) correlate with disease status in leprosy

    PubMed Central

    2011-01-01

    Background Caused by Mycobacterium leprae (ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocrine systems. Methods In the present retrospective study, we measured the serum levels of IGF-I and IGBP-3, its major binding protein. These measurements were taken at diagnosis in nonreactional borderline tuberculoid (NR BT), borderline lepromatous (NR BL), and lepromatous (NR LL) leprosy patients in addition to healthy controls (HC). LL and BL patients who developed reaction during the course of the disease were also included in the study. The serum levels of IGF-I, IGFBP-3 and tumor necrosis factor-alpha (TNF-α) were evaluated at diagnosis and during development of reversal (RR) or erythema nodosum leprosum (ENL) reaction by the solid phase, enzyme-labeled, chemiluminescent-immunometric method. Results The circulating IGF-I/IGFBP-3 levels showed significant differences according to disease status and occurrence of reactional episodes. At the time of leprosy diagnosis, significantly lower levels of circulating IGF-I/IGFBP-3 were found in NR BL and NR LL patients in contrast to NR BT patients and HCs. However, after treatment, serum IGF-I levels in BL/LL patients returned to normal. Notably, the levels of circulating IGF-I at diagnosis were low in 75% of patients who did not undergo ENL during treatment (NR LL patients) in opposition to the normal levels observed in those who suffered ENL during treatment (R LL patients). Nonetheless, during ENL episodes, the levels observed in RLL sera tended to decrease, attaining similar levels to those found in NR LL patients. Interestingly, IGF

  5. Exploring Secondary Students' Epistemological Features Depending on the Evaluation Levels of the Group Model on Blood Circulation

    NASA Astrophysics Data System (ADS)

    Lee, Shinyoung; Kim, Heui-Baik

    2014-05-01

    The purpose of this study is to identify the epistemological features and model qualities depending on model evaluation levels and to explore the reasoning process behind high-level evaluation through small group interaction about blood circulation. Nine groups of three to four students in the eighth grade participated in the modeling practice. Their group models, which were represented by discourse and blood circulation diagrams, were analyzed for the development of the framework that informed the model evaluation levels and epistemological features. The model evaluation levels were categorized into levels one to four based on the following evaluation criteria: no evaluation, authoritative sources, superficial criteria, and more comprehensive criteria. The qualities of group models varied with the criteria of model evaluation. While students who used authoritative sources for evaluating the group model appeared to have an absolutist epistemology, students who evaluated according to the superficial criteria and more comprehensive criteria appeared to have an evaluative epistemology. Furthermore, groups with Level four showed a chain reaction of cognitive reasoning during the modeling practice concerning practical epistemology. The findings have implications for science teachers and education researchers who want to understand the context for developing students' practical epistemologies.

  6. Full-Length mRNA-Seq from single cell levels of RNA and individual circulating tumor cells

    PubMed Central

    Ramsköld, Daniel; Luo, Shujun; Wang, Yu-Chieh; Li, Robin; Deng, Qiaolin; Faridani, Omid R.; Daniels, Gregory A.; Khrebtukova, Irina; Loring, Jeanne F.; Laurent, Louise C.; Schroth, Gary P.; Sandberg, Rickard

    2012-01-01

    In the last decade, genome-wide transcriptome analyses have been routinely used to monitor tissue-, disease- and cell type-specific gene expression, but it has been technically challenging to generate expression profiles from single cells. Here we describe a novel and robust mRNA-Seq protocol (Smart-Seq) that is applicable down to single cell levels. Compared with existing methods, Smart-Seq has improved read coverage across transcripts, which significantly enhances detailed analyses of alternative transcript isoforms and identification of SNPs. We have determined the sensitivity and quantitative accuracy of Smart-Seq for single-cell transcriptomics by evaluating it on total RNA dilution series. Applying Smart-Seq to circulating tumor cells from melanomas, we identified distinct gene expression patterns, including new candidate biomarkers for melanoma circulating tumor cells. Importantly, our protocol can easily be utilized for addressing fundamental biological problems requiring genome-wide transcriptome profiling in rare cells. PMID:22820318

  7. Affective Education in the Primary Grade Levels: A Pilot Program.

    ERIC Educational Resources Information Center

    Stilwell, William E.; Barclay, James R.

    This report describes a 12-week pilot phase of an affective education program in the Stuttgart School District, Arkansas. Participating in the program were 218 children, grades 2-4, and a team of nineteen teachers who were given 12 weeks of in-service training designed to facilitate their use of the DUSO, Focus on Self-Development Human…

  8. The relationship between typhoons' peripheral circulation and ground-level ozone concentrations in central Taiwan.

    PubMed

    Cheng, Wan-Li; Lai, Li-Wei; Den, Walter; Wu, Meng-Ting; Hsueh, Chao-An; Lin, Pay-Liam; Pai, Chueh-Ling; Yan, Yeou-Lih

    2014-02-01

    Surface data of meteorological parameters (wind speed, wind direction, and mixing height) and air pollutant concentrations (O3, NO, and NO2) were collected for a 92-day period associated with typhoon formation in 2005. The influence of typhoons on O3 concentration were defined by azimuth and distance from Taiwan, and Types A, B, and C correspond to typhoons less than 1,500 km from Taiwan and located between azimuths 45° and 135°, 135° and 225°, and 225° and 45°, respectively. Type D corresponds to typhoons more than 1,500 km from Taiwan. Titration reactions were conducted at three temporal phases: 2000-0700, 0800-1100, and 1200-1400 LST (Local Standard Time). The air pollution model (TAPM) was used to simulate wind fields and trajectories of air masses. It was determined that typhoon position affected O3 concentration, temporal and spatial patterns of O3 titration and vertical meteorological characteristics, which were not all at the statistically significant level. PMID:24105123

  9. Sustained elevated levels of circulating vasopressin selectively stimulate the proliferation of kidney tubular cells via the activation of V2 receptors.

    PubMed

    Alonso, Gérard; Galibert, Evelyne; Boulay, Véra; Guillou, Anne; Jean, Alexandra; Compan, Valérie; Guillon, Gilles

    2009-01-01

    The hypothalamic hormone vasopressin (AVP) has known mitogenic effects on various cell types. This study was designed to determine whether sustained elevated levels of circulating AVP could influence cell proliferation within adult tissues known to express different AVP receptors, including the pituitary, adrenal gland, liver, and kidney. Plasmatic AVP was chronically increased by submitting animals to prolonged hyperosmotic stimulation or implanting them with a AVP-containing osmotic minipump. After several days of either treatment, increased cell proliferation was detected only within the kidney. This kidney cell proliferation was not affected by the administration of selective V1a or V1b receptor antagonists but was either inhibited or mimicked by the administration of a selective V2 receptor antagonist or agonist, respectively. Kidney proliferative cells mostly concerned a subpopulation of differentiated tubular cells known to express the V2 receptors and were associated with the phosphorylation of ERK. These data indicate that in the adult rat, sustained elevated levels of circulating AVP stimulates the proliferation of a subpopulation of kidney tubular cells expressing the V2 receptor, providing the first illustration of a mitogenic effect of AVP via the activation of the V2 receptor subtype. PMID:18787031

  10. HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

    PubMed Central

    López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Mª; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R.

    2015-01-01

    Background and Objectives Obesity and HIV-1/HAART–associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. Methods This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student’s t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Results Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001–0.521, p = 0.027). Conclusions HALS is associated with decreased sTWEAK levels. PMID:26658801

  11. High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels

    PubMed Central

    Dong, Bin; Singh, Amar Bahadur; Azhar, Salman; Seidah, Nabil G.; Liu, Jingwen

    2015-01-01

    Background High fructose diet (HFD) induces dyslipidemia and insulin resistance in experimental animals and humans with incomplete mechanistic understanding. By utilizing mice and hamsters as in vivo models, we investigated whether high fructose consumption affects serum PCSK9 and liver LDL receptor (LDLR) protein levels. Results Feeding mice with a HFD increased serum cholesterol and reduced serum PCSK9 levels as compared with the mice fed a normal chow diet (NCD). In contrast to the inverse relationship in mice, serum PCSK9 and cholesterol levels were co-elevated in HFD-fed hamsters. Liver tissue analysis revealed that PCSK9 mRNA and protein levels were both reduced in mice and hamsters by HFD feeding, however, liver LDLR protein levels were markedly reduced by HFD in hamsters but not in mice. We further showed that circulating PCSK9 clearance rates were significantly lower in hamsters fed a HFD as compared with the hamsters fed NCD, providing additional evidence for the reduced hepatic LDLR function by HFD consumption. The majority of PCSK9 in hamster serum was detected as a 53 kDa N-terminus cleaved protein. By conducting in vitro studies, we demonstrate that this 53 kDa truncated hamster PCSK9 is functionally active in promoting hepatic LDLR degradation. Conclusion Our studies for the first time demonstrate that high fructose consumption increases serum PCSK9 concentrations and reduces liver LDLR protein levels in hyperlipidemic hamsters. The positive correlation between circulating cholesterol and PCSK9 and the reduction of liver LDLR protein in HFD-fed hamsters suggest that hamster is a better animal model than mouse to study the modulation of PCSK9/LDLR pathway by atherogenic diets. PMID:25682035

  12. Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background/Objectives: To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking. Subjects/Methods: A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Sub...

  13. Vocabulary Level; One Variable Affecting Learning from Audiovisual Media.

    ERIC Educational Resources Information Center

    Lewis, Richard F.

    Vocabulary level of 10 special students was determined and compared to their supposed level of proficiency on the Functional Basic Word List for Special Pupils (Tudyman and Groelle, 1958). Ss were five educable mentally retarded (EMR) students (CA 9-6 to 12-0, IQ 64-77, MA 6-6 to 9-7) and five matched emotionally disturbed students. Word sampling…

  14. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    PubMed

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors. PMID:26780604

  15. Nitrogen dioxide assimilation as affected by light level

    SciTech Connect

    Srivastava, H. ); Ormond, D.; Marie, B. )

    1989-04-01

    The air pollutant NO{sub 2} is absorbed and assimilated by plants to serve as a source of nitrogen but only to a limited extent. The objective of this research was to identify the constraints on NO{sub 2} assimilation. Differential light levels were used to manipulate carbohydrate metabolites available for nitrogen assimilation. Bean plants were grown at four light levels with or without nutrient nitrate and exposed to 0.25 ppm NO{sub 2} for 6h each day. Growth of roots and shoots was inhibited by NO{sub 2} in both the presence and absence of nutrient nitrate. The inhibition was most pronounced at the lowest light level. Light level similarly influenced the effect of nitrate and of NO{sub 2} on soluble protein, nitrate nitrogen and Kjeldahl nitrogen in the root and shoot tissues. Two experiments demonstrated that the injurious effects of NO{sub 2} are more pronounced at low light than at high light and that more NO{sub 2} is assimilated into soluble shoot protein at higher light levels.

  16. Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels.

    PubMed

    Pluchino, N; Genazzani, A D; Bernardi, F; Casarosa, E; Pieri, M; Palumbo, M; Picciarelli, G; Gabbanini, M; Luisi, M; Genazzani, A R

    2005-03-01

    The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the

  17. Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

    PubMed Central

    Szeto, Cheuk-Chun; Kwan, Bonnie Ching-Ha; Chow, Kai-Ming; Kwok, Jeffrey Sung-Shing; Lai, Ka-Bik; Cheng, Phyllis Mei-Shan; Pang, Wing-Fai; Ng, Jack Kit-Chung; Chan, Michael Ho-Ming; Lit, Lydia Choi-Wan; Leung, Chi-Bon; Li, Philip Kam-Tao

    2015-01-01

    Background Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients. Methods We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival. Results The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005). Conclusions Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients. PMID:26010741

  18. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    PubMed Central

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P.; Islas-Morris-Hernandez, A.; Borget, I.; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. Results ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24–55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7–11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. Conclusion We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged

  19. Affect and Digital Learning at the University Level

    ERIC Educational Resources Information Center

    Katz, Yaacov J.; Yablon, Yaacov B.

    2011-01-01

    Purpose: The purpose of the paper is to examine the efficiency of SMS based cell-phone vocabulary learning as compared to email vocabulary delivery and snail mail vocabulary delivery at the university level. Design/methodology/approach: A total of 241 first year university students studied English vocabulary in their mandatory English foundation…

  20. CAN FLUORIDATION AFFECT WATER LEAD LEVELS AND LEAD NEUROTOXICITY?

    EPA Science Inventory

    Recent reports have attempted to show that certain approaches to fluoridating potable water is linked to increased levels of lead(II) in the blood. We examine these claims in light of the established science and critically evaluate their significance. The completeness of nexafluo...

  1. HSF1-deficiency affects gait coordination and cerebellar calbindin levels.

    PubMed

    Ingenwerth, Marc; Estrada, Veronica; Stahr, Anna; Müller, Hans Werner; von Gall, Charlotte

    2016-09-01

    Heat shock proteins (HSPs) play an important role in cell homeostasis and protect against cell damage. They were previously identified as key players in different ataxia models. HSF1 is the main transcription factor for HSP activation. HSF1-deficient mice (HSF1-/-) are known to have deficiencies in motor control test. However, little is known about effects of HSF1-deficiency on locomotor, especially gait, coordination. Therefore, we compared HSF-deficient (HSF1-/-) mice and wildtype littermates using an automated gait analysis system for objective assessment of gait coordination. We found significant changes in gait parameters of HSF1-/- mice reminiscent of cerebellar ataxia. Immunohistochemical analyses of a cerebellum revealed co-localization of HSF1 and calbindin in Purkinje cells. Therefore, we tested the hypothesis of a potential interconnection between HSF1 and calbindin in Purkinje cells. Calbindin levels were analyzed qualitatively and quantitatively by immunohistochemistry and immunoblotting, respectively. While quantitative PCR revealed no differences in calbindin mRNA levels between HSF1+/+ and HSF1-/- mice, calbindin protein levels, however, were significantly decreased in a cerebellum of HSF1-/- mice. A pathway analysis supports the hypothesis of an interconnection between HSF1 and calbindin. In summary, the targeted deletion of HSF1 results in changes of locomotor function associated with changes in cerebellar calbindin protein levels. These findings suggest a role of HSF1 in regular Purkinje cell calcium homeostasis. PMID:27173427

  2. CHILDHOOD BLOOD LEAD LEVELS NOT AFFECTED BY HOUSING COMPLIANCE STATUS

    EPA Science Inventory

    In a secondary analysis of data from the Childhood Lead Poisoning Prevention Program of Philadelphia (July 1, 1999 through September 1, 2004), the authors evaluated the effect of housing compliance status and time to achieve compliance on changes in children's blood lead levels. ...

  3. Fruiting Branch K+ Level Affects Cotton Fiber Elongation Through Osmoregulation

    PubMed Central

    Yang, Jiashuo; Hu, Wei; Zhao, Wenqing; Chen, Binglin; Wang, Youhua; Zhou, Zhiguo; Meng, Yali

    2016-01-01

    Potassium (K) deficiency in cotton plants results in reduced fiber length. As one of the primary osmotica, K+ contributes to an increase in cell turgor pressure during fiber elongation. Therefore, it is hypothesized that fiber length is affected by K deficiency through an osmotic pathway, so in 2012 and 2013, an experiment was conducted to test this hypothesis by imposing three potassium supply regimes (0, 125, 250 kg K ha-1) on a low-K-sensitive cultivar, Siza 3, and a low-K-tolerant cultivar, Simian 3. We found that fibers were longer in the later season bolls than in the earlier ones in cotton plants grown under normal growth conditions, but later season bolls showed a greater sensitivity to low-K stress, especially the low-K sensitive genotype. We also found that the maximum velocity of fibre elongation (Vmax) is the parameter that best reflects the change in fiber elongation under K deficiency. This parameter mostly depends on cell turgor, so the content of the osmotically active solutes was analyzed accordingly. Statistical analysis showed that K+ was the major osmotic factor affecting fiber length, and malate was likely facilitating K+ accumulation into fibers, which enabled the low-K-tolerant genotype to cope with low-K stress. Moreover, the low-K-tolerant genotype tended to have greater K+ absorptive capacities in the upper fruiting branches. Based on our findings, we suggest a fertilization scheme for Gossypium hirsutum that adds extra potash fertilizer or distributes it during the development of late season bolls to mitigate K deficiency in the second half of the growth season and to enhance fiber length in late season bolls. PMID:26834777

  4. Fruiting Branch K(+) Level Affects Cotton Fiber Elongation Through Osmoregulation.

    PubMed

    Yang, Jiashuo; Hu, Wei; Zhao, Wenqing; Chen, Binglin; Wang, Youhua; Zhou, Zhiguo; Meng, Yali

    2016-01-01

    Potassium (K) deficiency in cotton plants results in reduced fiber length. As one of the primary osmotica, K(+) contributes to an increase in cell turgor pressure during fiber elongation. Therefore, it is hypothesized that fiber length is affected by K deficiency through an osmotic pathway, so in 2012 and 2013, an experiment was conducted to test this hypothesis by imposing three potassium supply regimes (0, 125, 250 kg K ha(-1)) on a low-K-sensitive cultivar, Siza 3, and a low-K-tolerant cultivar, Simian 3. We found that fibers were longer in the later season bolls than in the earlier ones in cotton plants grown under normal growth conditions, but later season bolls showed a greater sensitivity to low-K stress, especially the low-K sensitive genotype. We also found that the maximum velocity of fibre elongation (V max) is the parameter that best reflects the change in fiber elongation under K deficiency. This parameter mostly depends on cell turgor, so the content of the osmotically active solutes was analyzed accordingly. Statistical analysis showed that K(+) was the major osmotic factor affecting fiber length, and malate was likely facilitating K(+) accumulation into fibers, which enabled the low-K-tolerant genotype to cope with low-K stress. Moreover, the low-K-tolerant genotype tended to have greater K(+) absorptive capacities in the upper fruiting branches. Based on our findings, we suggest a fertilization scheme for Gossypium hirsutum that adds extra potash fertilizer or distributes it during the development of late season bolls to mitigate K deficiency in the second half of the growth season and to enhance fiber length in late season bolls. PMID:26834777

  5. High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects.

    PubMed

    Sesti, G; Andreozzi, F; Fiorentino, T V; Mannino, G C; Sciacqua, A; Marini, M A; Perticone, F

    2014-10-01

    Irisin, a novel myokine, was proposed to be able to regulate glucose homeostasis and obesity in mice. Whether irisin levels are associated with cardio-metabolic variables, insulin sensitivity, and vascular atherosclerosis in humans remain unsettled. To determine the associations between circulating irisin levels, cardio-metabolic variables, insulin sensitivity, and common carotid intima-media thickness (IMT), an indicator of vascular atherosclerosis, a cross-sectional evaluation of circulating irisin levels and cardio-metabolic variables in 192 White adults was conducted. Insulin sensitivity and insulin clearance were assessed by euglycemic-hyperinsulinemic clamp. Common carotid IMT was measured by ultrasound. After adjusting for age and gender, irisin levels were positively correlated with body fat mass (r = 0.12, P < 0.05), fasting (r = 0.17, P < 0.01), 2 h post-load insulin (r = 0.15, P < 0.02) levels, and IMT (r = 0.29, P < 0.0001) and were negatively correlated with insulin-stimulated glucose disposal (r = -0.18, P = 0.007), Matsuda index (r = -0.13, P < 0.04), disposition index (r = -0.278, P < 0.0001), and insulin clearance (r = -0.26, P < 0.0001). After adjusting for age, gender, and BMI, individuals in the highest tertile of irisin levels exhibited higher body fat mass (P < 0.01), fasting (P < 0.05), 2 h post-load (P < 0.01) insulin levels, carotid IMT (P < 0.001), lower insulin-stimulated glucose disposal (P < 0.001), Matsuda index (P < 0.01), disposition index (P < 0.01), and insulin clearance (P < 0.001) as compared with subjects in the lowest tertile of circulating irisin levels. Irisin is inversely associated with insulin sensitivity and positively associated with carotid IMT in humans, suggesting either increased release by adipose/muscle tissue in response to deterioration of insulin sensitivity or a compensatory increase in irisin to overcome an underlying irisin resistance. PMID:24619655

  6. Wind resource quality affected by high levels of renewables

    DOE PAGESBeta

    Diakov, Victor

    2015-06-17

    For solar photovoltaic (PV) and wind resources, the capacity factor is an important parameter describing the quality of the resource. As the share of variable renewable resources (such as PV and wind) on the electric system is increasing, so does curtailment (and the fraction of time when it cannot be avoided). At high levels of renewable generation, curtailments effectively change the practical measure of resource quality from capacity factor to the incremental capacity factor. The latter accounts only for generation during hours of no curtailment and is directly connected with the marginal capital cost of renewable generators for a givenmore » level of renewable generation during the year. The Western U.S. wind generation is analyzed hourly for a system with 75% of annual generation from wind, and it is found that the value for the system of resources with equal capacity factors can vary by a factor of 2, which highlights the importance of using the incremental capacity factor instead. Finally, the effect is expected to be more pronounced in smaller geographic areas (or when transmission limitations imposed) and less pronounced at lower levels of renewable energy in the system with less curtailment.« less

  7. Wind resource quality affected by high levels of renewables

    SciTech Connect

    Diakov, Victor

    2015-06-17

    For solar photovoltaic (PV) and wind resources, the capacity factor is an important parameter describing the quality of the resource. As the share of variable renewable resources (such as PV and wind) on the electric system is increasing, so does curtailment (and the fraction of time when it cannot be avoided). At high levels of renewable generation, curtailments effectively change the practical measure of resource quality from capacity factor to the incremental capacity factor. The latter accounts only for generation during hours of no curtailment and is directly connected with the marginal capital cost of renewable generators for a given level of renewable generation during the year. The Western U.S. wind generation is analyzed hourly for a system with 75% of annual generation from wind, and it is found that the value for the system of resources with equal capacity factors can vary by a factor of 2, which highlights the importance of using the incremental capacity factor instead. Finally, the effect is expected to be more pronounced in smaller geographic areas (or when transmission limitations imposed) and less pronounced at lower levels of renewable energy in the system with less curtailment.

  8. Sunlight and Other Determinants of Circulating 25-Hydroxyvitamin D Levels in Black and White Participants in a Nationwide US Study

    PubMed Central

    Freedman, D. Michal; Cahoon, Elizabeth K.; Rajaraman, Preetha; Major, Jacqueline M.; Doody, Michele M.; Alexander, Bruce H.; Hoffbeck, Richard W.; Kimlin, Michael G.; Graubard, Barry I.; Linet, Martha S.

    2013-01-01

    Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n = 842), blacks (n = 646), and people of other races/ethnicities (n = 12). Participants were recruited monthly (2008–2009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25% of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest. PMID:23292956

  9. Impact of Enhanced Low-level Stratus on Simulated SSTs, Precipitation and the Circulation in the Tropical Atlantic Sector

    NASA Astrophysics Data System (ADS)

    Bader, J.; Eichhorn, A.

    2015-12-01

    Most coupled atmosphere-ocean general circulation models (AOGCMs) show a substantial warm bias in sea-surface temperatures (SSTs) in the eastern tropical Atlantic. The impact of enhanced low-level clouds on SST, precipitation and the circulation in the tropical Atlantic sector is tested. Therefore, we have conducted sensitivity experiments with the atmospheric model ECHAM6 and the coupled version of it (MPI-ESM1) in which we enhance the formation of low-level stratus at the inversion layer in the low troposphere. The impact of enhanced low-level clouds is compared to the standard version of the models. There is a direct cloud impact by reducing the incoming solar radiation at the surface. The reduced incoming solar radiation leads to a cooling of SSTs in the eastern tropical Atlantic in the coupled atmosphere-ocean model. This in turn causes not only locally rainfall reductions in oceanic precipitation but also a remote precipitation enhancement over north east Brazil. These precipitation changes are associated with changes in the equatorial wind-stress forcing. The impact of the wind stress changes on the equatorial zonal SST-gradient and the seasonal cycle is also analysed.

  10. How Temperature and Water levels affect Polar Mesospheric Cloud Formation

    NASA Astrophysics Data System (ADS)

    Smith, L. L.; Randall, C. E.; Harvey, V.

    2012-12-01

    Using the Cloud Imaging and Particle Size (CIPS) instrument data, which is part of the Aeronomy in the Mesosphere (AIM) mission, we compare the albedo and ice water content measurements of CIPS with the Navy Operation Global Atmospheric Prediction System - Advanced Level Phyiscs and High Altitude (NOGAPS-ALPHA) temperature and water vapor data in order to derive a greater understanding of cloud formation and physics. We particularly focus on data from June 2007 and July 2007 in this case study because of particular cloud structures and formations during this time period for future studies.

  11. Circulating Annexin A5 Levels after Atrial Switch for Transposition of the Great Arteries: Relationship with Ventricular Deformation and Geometry

    PubMed Central

    Lai, Clare T. M.; Chow, Pak-cheong; Wong, Sophia J.; Chan, Koon-wing; Cheung, Yiu-fai

    2012-01-01

    Background Inflammatory cytokines, cardiomyocyte apoptosis, and altered collagen turnover may contribute to unfavourable ventricular remodeling. This unfavourable ventricular remodelling is well documented in patients after atrial switch operation for complete transposition of the great arteries. We therefore tested if levels of circulating markers of inflammation, apoptosis, collagen synthesis, and extracellular matrix degradation are altered in patients after atrial switch operation for transposition of the great arteries. Methods and Results Circulating tumour necrosis factor (TNF)-α, annexin A5 (AnxA5), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined in 27 patients aged 25.2±3.1 years and 20 controls. Ventricular myocardial deformation and left ventricular eccentricity index (EI) were determined by speckle tracking and two-dimensional echocardiography, respectively. Compared with controls, patients had significantly higher circulating AnxA5 (p<0.001) and TNF-α (p = 0.018) levels, but similar PICP, PIIINP, MMP-1 and TIMP-1 levels. For the whole cohort, plasma AnxA5 correlated with serum TNF-α (p = 0.002), systemic ventricular global longitudinal strain (GLS) and systolic and early diastolic strain rate (all p<0.001), and subpulmonary ventricular GLS and early diastolic strain rate (both p<0.001). In patients, plasma AnxA5 level correlated positively with subpulmonary ventricular EI (p = 0.027). Multiple linear regression analysis identified systemic ventricular GLS (β = −0.50, p<0.001) and serum TNF-α (β = 0.29, p = 0.022) as significant correlates of plasma AnxA5. Conclusions Elevated plasma AnxA5 level in patients after atrial switch operation is associated with impaired systemic myocardial deformation, increased subpulmonary ventricular

  12. On Evaluating circulation and temperature stratification under changing water levels in Lake Mead with a 3D hydrodynamic model

    NASA Astrophysics Data System (ADS)

    Li, Y.; Acharya, K.; Chen, D.; Stone, M.; Yu, Z.; Young, M.; Zhu, J.; Shafer, D. S.; Warwick, J. J.

    2009-12-01

    Sustained drought in the western United States since 2000 has led to a significant drop (about 35 meters) in the water level of Lake Mead, the largest reservoir by volume in United States. The drought combined with rapid urban development in southern Nevada and emergence of invasive species has threatened the water quality and ecological processes in Lake Mead. A three-dimensional hydrodynamic model, Environmental Fluid Dynamics Code (EFDC), was applied to investigate lake circulation and temperature stratification in parts of Lake Mead (Las Vegas Bay and Boulder Basin) under changing water levels. Besides the inflow from Las Vegas Wash and the Colorado River, the model considered atmospheric changes as well as the boundary conditions restricted by the operation of Hoover Dam. The model was calibrated and verified by using observed data including water level, velocity, and temperature from 2003 and 2005. The model was applied to study the hydrodynamic processes at water level 366.8 m (year 2000) and at water level 338.2 m (year 2008). The high-stage simulation described the pre-drought lake hydrodynamic processes while the low-stage simulation highlighted the drawdown impact on such processes. The results showed that both inflow and wind-driven mixing process played major roles in the thermal stratification and lake circulation in both cases. However, the atmospheric boundary played a more important role than inflow temperature on thermal stratification of Lake Mead during water level decline. Further, the thermal stratification regime and flow circulation pattern in shallow lake regions (e.g.., the Boulder Basin area) were most impacted. The temperature of the lake at the high-stage was more sensitive to inflow temperatures than at low-stage. Furthermore, flow velocities decreased with the decreasing water level due to reduction in wind impacts, particularly in shallow areas of the lake. Such changes in temperature and lake current due to present drought have a

  13. Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

    SciTech Connect

    Egloff, Caroline; Crump, Doug; Porter, Emily; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T.; Kennedy, Sean W.

    2014-09-15

    The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy

  14. Lipopolysaccharide differentially decreases plasma acyl and desacyl ghrelin levels in rats: potential role of the circulating ghrelin acylating enzyme GOAT

    PubMed Central

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Reeve, Joseph R.; Taché, Yvette; Lambrecht, Nils W.G.

    2014-01-01

    Bacterial lipopolysaccharide (LPS) in rodents is an established model for studying innate immune responses to gram-negative bacteria and mimicking symptoms of infections including reduced food intake associated with decreased circulating total ghrelin levels. The ghrelin-acylating enzyme, ghrelin-O-acyltransferase (GOAT) involved in the formation of acyl ghrelin (AG) was recently identified. We investigated changes in circulating AG, desacyl ghrelin (DG) and GOAT induced by intraperitoneal LPS (100μg/kg) and associated changes in food intake. Plasma AG and total ghrelin were assessed by radioimmunoassay, GOAT protein by Western blot and mRNA by RT-qPCR. DG was derived from total minus AG. Plasma AG and DG were decreased at 2h, 5h and 7h (p<0.01) post injection compared to vehicle and recovered at 24h. At 2h there was a significantly greater decrease of AG (-53%) than DG (-28%) resulting in a decreased AG/DG ratio (1:5, p <0.01), which thereafter returned to pre-injection values (1:3). This altered ratio was associated with a 38% decrease in plasma GOAT protein compared to vehicle (p <0.001), whereas gastric GOAT protein was slightly increased by 10% (p<0.05). GOAT mRNA expression was unchanged. Food intake was reduced by 58% measured during the 1.5-2h period post LPS injection. Decreased plasma AG and DG preceded the rise in rectal temperature and blood glucose that peaked at 7h. These data indicate that LPS induces a long-lasting reduction of AG and DG levels that may have a bearing with the decrease in food intake. The faster drop in AG than DG within 2h is associated with reduced circulating GOAT. PMID:20599577

  15. Patterns in atmospheric circulation affect emission sources contributing to nitrogen deposition in the Columbia River Gorge, Pacific Northwest USA

    NASA Astrophysics Data System (ADS)

    Anderson, S. M.; Chung, S. H.; Welker, J. M.; Harlow, B.; Evans, R. D.

    2014-12-01

    The Columbia River Gorge separating Oregon and Washington provides an ideal setting to investigate how atmospheric circulation patterns determine types of emission sources contributing to atmospheric deposition. Up-gorge and down-gorge atmospheric circulation patterns each provide a different suite of emission sources. Up-gorge airflow originates in the Portland-Vancouver metro area dominated by urban and industrial sources. Down-gorge patterns originate in the Columbia River basin, which is dominated by agricultural production. We tested the dependence of emission sources contributing to atmospheric deposition on circulation patterns by measuring the isotopic composition of nitrate (NO3-) in 2003-2004 precipitation samples from the WA98-Columbia River Gorge NADP & USNIP site. Circulation patterns were determined using back-trajectory analysis with the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model using the archived EDAS meteorological dataset. We observed a significant difference (P=0.01) between up-gorge and down-gorge patterns with mean δ15N-NO3- of +1.8 and -2.1‰ for up- and down-gorge, respectively. The differences observed between these two patterns is likely tied to the different emission sources of N found in these different geographic areas. The lower δ15N of down-gorge sources is due to the large amount of agricultural production in the Columbia River basin. Observed values for the up-gorge patterns likely result from industrial and fossil fuel emissions of NOx, the precursor of deposited NO3-, in the Portland-Vancouver area. The significantly greater amount of NO3- in precipitation from up-gorge patterns (0.72 mg/L) compared to down-gorge patterns (0.36 mg/L, P=0.01) supports the influence of urban sources rather than relatively clean marine air which characteristically has low amounts of NO3-. No significant differences are found in δ18Onitrate or Δ17Onitrate between the two patterns, suggesting that atmospheric chemistry

  16. Eighteen Insulin-like Growth Factor (IGF) pathway genes, circulating levels of IGF-1 and its binding protein (IGFBP-3), and risk of prostate and breast cancer

    PubMed Central

    Gu, Fangyi; Schumacher, Fredrick R.; Canzian, Federico; Allen, Naomi E.; Albanes, Demetrius; Berg, Christine D; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Chabbert-Buffet, Nathalie; Chanock, Stephen J.; Clavel-Chapelon, Françoise; Dumeaux, Vanessa; Gaziano, J. Michael; Giovannucci, Edward L.; Haiman, Christopher A.; Hankinson, Susan E.; Hayes, Richard B.; Henderson, Brian E.; Hunter, David J.; Hoover, Robert N.; Johansson, Mattias; Key, Timothy J.; Khaw, Kay-Tee; Kolonel, Laurence N.; Lagiou, Pagona; Lee, I-Min; LeMarchand, Loic; Lund, Eiliv; Ma, Jing; Onland-Moret, N. Charlotte; Overvad, Kim; Rodriguez, Laudina; Sacerdote, Carlotta; Sánchez, Maria-José; Stampfer, Meir J.; Stattin, Pär; Stram, Daniel O.; Thomas, Gilles; Thun, Michael J.; Tjønneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Virtamo, Jarmo; Weinstein, Stephanie J.; Willett, Walter C.; Yeager, Meredith; Zhang, Shumin M.; Kaaks, Rudolf; Riboli, Elio; Ziegler, Regina G.; Kraft, Peter

    2010-01-01

    Background Circulating levels of insulin-like growth factor I (IGF-1) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-1 and IGFBP-3 in studies of adult twins. Methods We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-1 and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNPs) were genotyped in over 5500 Caucasian men and 5500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium (BPC3). Results After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-1 (p<2.1×10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2=0.62% of the variation in circulating IGF-1 and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-1 or IGFBP-3 and risk of prostate or breast cancers. Conclusion Common genetic variation in the IGF1 and SSTR5 genes appears to influence circulating IGF-1 levels, and variation in IGFBP3 and IGFALS appears to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-1 and IGFBP-3 in Caucasian men and women. Impact Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes. PMID:20810604

  17. Prions are affected by evolution at two levels.

    PubMed

    Wickner, Reed B; Kelly, Amy C

    2016-03-01

    Prions, infectious proteins, can transmit diseases or be the basis of heritable traits (or both), mostly based on amyloid forms of the prion protein. A single protein sequence can be the basis for many prion strains/variants, with different biological properties based on different amyloid conformations, each rather stably propagating. Prions are unique in that evolution and selection work at both the level of the chromosomal gene encoding the protein, and on the prion itself selecting prion variants. Here, we summarize what is known about the evolution of prion proteins, both the genes and the prions themselves. We contrast the one known functional prion, [Het-s] of Podospora anserina, with the known disease prions, the yeast prions [PSI+] and [URE3] and the transmissible spongiform encephalopathies of mammals. PMID:26713322

  18. Euthanasia by CO₂ inhalation affects potassium levels in mice.

    PubMed

    Traslavina, Ryan P; King, Edward J; Loar, Andrew S; Riedel, Elyn R; Garvey, Michael S; Ricart-Arbona, Rodolfo; Wolf, Felix R; Couto, Suzana S

    2010-05-01

    We and others frequently have noted serum potassium levels of 8.0 +/- 0.85 mEq/L or greater in laboratory mice; this concentration has even been published as the upper limit of a 'normal' reference range. However, if bone fide, this potassium concentration would be incompatible with life in all species. We investigated conditions frequently encountered in the research setting to distinguish artifactual from true hyperkalemia. Variables evaluated included site of collection, time allowed for clot formation before serum separation, time elapsed between collection and analysis of samples collected in a serum separator tube, precollection method of anesthesia, and euthanasia technique. Serum potassium was measured from 75 C57BL/6NTac 10-wk-old female mice and divided into at least 5 mice per variable. Animals were euthanized by exsanguination immediately after terminal CO₂ or ketamine-xylazine (KX) administration. Mice euthanized with CO₂ had higher mean serum potassium (7.0 +/- 0.5 mEq/L) and range serum potassium (6.0 to 8.1 mEq/L) than did KX-treated mice. CO₂ inhalation resulted in significantly lower blood pH (6.9 +/- 0.1), higher pCO₂ (153.3 +/- 38.8 mm Hg), and higher lactate levels (3.9 +/- 0.9 mmol/L) than did KX anesthesia followed by exsanguination. These results suggest that antemortem respiratory acidosis from CO₂ administration causes artifactual hyperkalemia in mice. Therefore, blood collection under KX anesthesia is preferable over CO₂ inhalation to obtain accurate potassium values from mice. PMID:20587163

  19. Factors affecting levels of genetic diversity in natural populations.

    PubMed Central

    Amos, W; Harwood, J

    1998-01-01

    Genetic variability is the clay of evolution, providing the base material on which adaptation and speciation depend. It is often assumed that most interspecific differences in variability are due primarily to population size effects, with bottlenecked populations carrying less variability than those of stable size. However, we show that population bottlenecks are unlikely to be the only factor, even in classic case studies such as the northern elephant seal and the cheetah, where genetic polymorphism is virtually absent. Instead, we suggest that the low levels of variability observed in endangered populations are more likely to result from a combination of publication biases, which tend to inflate the level of variability which is considered 'normal', and inbreeding effects, which may hasten loss of variability due to drift. To account for species with large population sizes but low variability we advance three hypotheses. First, it is known that certain metapopulation structures can result in effective population sizes far below the census size. Second, there is increasing evidence that heterozygous sites mutate more frequently than equivalent homozygous sites, plausibly because mismatch repair between homologous chromosomes during meiosis provides extra opportunities to mutate. Such a mechanism would undermine the simple relationship between heterozygosity and effective population size. Third, the fact that related species that differ greatly in variability implies that large amounts of variability can be gained or lost rapidly. We argue that such cases are best explained by rapid loss through a genome-wide selective sweep, and suggest a mechanism by which this could come about, based on forced changes to a control gene inducing coevolution in the genes it controls. Our model, based on meiotic drive in mammals, but easily extended to other systems, would tend to facilitate population isolation by generating molecular incompatabilities. Circumstances can even be

  20. A short-term extremely low frequency electromagnetic field exposure increases circulating leukocyte numbers and affects HPA-axis signaling in mice.

    PubMed

    de Kleijn, Stan; Ferwerda, Gerben; Wiese, Michelle; Trentelman, Jos; Cuppen, Jan; Kozicz, Tamas; de Jager, Linda; Hermans, Peter W M; Verburg-van Kemenade, B M Lidy

    2016-10-01

    There is still uncertainty whether extremely low frequency electromagnetic fields (ELF-EMF) can induce health effects like immunomodulation. Despite evidence obtained in vitro, an unambiguous association has not yet been established in vivo. Here, mice were exposed to ELF-EMF for 1, 4, and 24 h/day in a short-term (1 week) and long-term (15 weeks) set-up to investigate whole body effects on the level of stress regulation and immune response. ELF-EMF signal contained multiple frequencies (20-5000 Hz) and a magnetic flux density of 10 μT. After exposure, blood was analyzed for leukocyte numbers (short-term and long-term) and adrenocorticotropic hormone concentration (short-term only). Furthermore, in the short-term experiment, stress-related parameters, corticotropin-releasing hormone, proopiomelanocortin (POMC) and CYP11A1 gene-expression, respectively, were determined in the hypothalamic paraventricular nucleus, pituitary, and adrenal glands. In the short-term but not long-term experiment, leukocyte counts were significantly higher in the 24 h-exposed group compared with controls, mainly represented by increased neutrophils and CD4 ± lymphocytes. POMC expression and plasma adrenocorticotropic hormone were significantly lower compared with unexposed control mice. In conclusion, short-term ELF-EMF exposure may affect hypothalamic-pituitary-adrenal axis activation in mice. Changes in stress hormone release may explain changes in circulating leukocyte numbers and composition. Bioelectromagnetics. 37:433-443, 2016. © 2016 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc. PMID:27553635

  1. C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.

    PubMed

    Nsaiba, Mohamed Jalloul; Lapointe, Marc; Mabrouk, Hajer; Douki, Wahiba; Gaha, Lotfi; Pérusse, Louis; Bouchard, Claude; Jrad, Besma Bel Hadj; Cianflone, Katherine

    2015-05-01

    Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences. PMID:25720829

  2. Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects.

    PubMed

    Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels. PMID:27312476

  3. Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects

    PubMed Central

    Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels. PMID:27312476

  4. Circulating IGF-I and IGFBP3 levels control human colonic stem cell function and are disrupted in diabetic enteropathy

    PubMed Central

    Maestroni, Anna; Jung, Peter; Orsenigo, Elena; Nasr, Moufida Ben; Tezza, Sara; Bassi, Roberto; Finzi, Giovanna; Marando, Alessandro; Vergani, Andrea; Frego, Roberto; Albarello, Luca; Andolfo, Annapaola; Manuguerra, Roberta; Viale, Edi; Staudacher, Carlo; Corradi, Domenico; Batlle, Eduard; Breault, David; Secchi, Antonio; Folli, Franco; Fiorina, Paolo

    2016-01-01

    Summary The role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy (DE), though its etiology is unknown. Here, we report T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (IGF-1) and its binding protein-3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an IGF-1-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating IGF-1/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral IGF-1/IGFBP3 control CoSCs and their dysfunction in DE. PMID:26431183

  5. Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.

    PubMed

    Landi, Abdolamir; Broadhurst, David; Vernon, Suzanne D; Tyrrell, D Lorne J; Houghton, Michael

    2016-02-01

    Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis. In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients. Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future. PMID:26615570

  6. Determinants affecting physical activity levels in animal models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C L.; Wade, Charles E.

    2002-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  7. Determinants Affecting Physical Activity Levels In Animal Models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C. L.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  8. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

    SciTech Connect

    Ali, Imran; Engström, Annette; Vahter, Marie; Skerfving, Staffan; Lundh, Thomas; Lidfeldt, Jonas; Samsioe, Göran; Halldin, Krister; Åkesson, Agneta

    2014-10-15

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.

  9. Maternal HIV status affects the infant hemoglobin level

    PubMed Central

    Feleke, Berhanu Elfu

    2016-01-01

    Abstract Children, especially infants, are highly vulnerable to iron-deficiency anemia because of their rapid growth of the brain and the rest of the body. The objectives of this study were to compare the prevalence of iron-deficiency anemia in infants born from HIV-positive mothers and HIV-negative mothers and to identify the determinants of iron-deficiency anemia in infants. A comparative cross-sectional study was conducted in Bahir Dar city. Simple random sampling technique was used to select the study participants. Mothers were interviewed; blood samples were collected from mothers and infants to measure the hemoglobin level and anthropometric indicators were obtained from the infants using world health organization standards. Descriptive statistics were used to estimate the prevalence of infantile anemia. Binary logistic regression and multiple linear regressions were used to identify the determinants of infant anemia. A total of 1459 infants born from HIV-positive and HIV-negative mothers were included. The prevalence of iron-deficiency anemia in infants born from HIV-positive and HIV-negative mothers was 41.9% (95% CI: 39–44). Infantile iron-deficiency anemia was associated with maternal HIV infection (adjusted odds ratio [AOR] 2.54 [95% CI: 1.65–3.9]), stunting (AOR 3.46 [95% CI: 2.41–4.97]), low income (AOR 2.72 [95% CI: 2–3.73]), maternal malaria during pregnancy (AOR 1.81 [95% CI: 1.33–2.47]), use of cow milk before 6 month (AOR 1.82 [95% CI: 1.35–2.45]), residence (AOR 0.09 [95% CI: 0.06–0.13]), history of cough or fever 7 days preceding the survey (AOR 2.71 [95% CI: 1.99–3.69]), maternal hemoglobin (B 0.65 [95% CI: 0.61–0.68]), educational status of mother (B 0.22 [95% CI: 0.2–0.23]), age of the mother (B –0.03 [95% CI: –0.03, –0.02]), and family size (B –0.14 [95% CI: –0.18,–0.11]). PMID:27495044

  10. A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels

    PubMed Central

    Bonnefond, Amélie; Bouatia-Naji, Nabila; Dechaume, Aurélie; Siest, Gérard; Herbeth, Bernard; Falchi, Mario; Bottolo, Leonardo; Guéant-Rodriguez, Rosa-Maria; Lecoeur, Cécile; Langlois, Michel R.; Labrune, Yann; Ruokonen, Aimo; El Shamieh, Said; Stathopoulou, Maria G.; Morandi, Anita; Maffeis, Claudio; Meyre, David; Delanghe, Joris R.; Jacobson, Peter; Sjöström, Lars; Carlsson, Lena M. S.; Walley, Andrew; Elliott, Paul; Jarvelin, Marjo-Riita; Dedoussis, George V.; Visvikis-Siest, Sophie

    2012-01-01

    Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far. We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (Poverall = 8.1×10−59), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23±0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (Ptotal cholesterol = 0.002 and PLDL = 0.0008). Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact. PMID:22403646

  11. Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Armengol, Sandra; Sabench, Fàtima; Ras, Rosa; Hernandez, Mercè; Aguilar, Carmen; Colom, Josep; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. Materials and Methods We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. Results We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis. Conclusion These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH. PMID:27123846

  12. Circulating memory B cells and plasmablasts are associated with the levels of serum immunoglobulin in patients with ulcerative colitis.

    PubMed

    Wang, Xinrui; Jiang, Yanfang; Zhu, Yonggang; Zhang, Manli; Li, Man; Wang, Hongjuan; Gao, Pujun

    2016-05-01

    Humoural immunity is crucial for the pathogenesis of ulcerative colitis (UC), but the precise perturbation of B cell immunity is poorly understood. This study is aimed at evaluating the numbers of different subsets of circulating memory B cells, plasmablasts, and the levels of serum immunoglobulin in UC patients. Total of 23 patients with active UC and 14 healthy controls (HC) were examined for the numbers of different subsets of circulating memory B cells and plasmablasts before and after treatment with mesalazine for 8-12 weeks by flow cytometry. Disease activity was evaluated by the Mayo clinic score. The levels of serum immunoglobulin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in individual subjects. In comparison with that in HC, significantly reduced numbers of IgG(+)  IgD(-)  CD27(+)  CD19(+) memory B cells, increased numbers of CD20(-)  CD19(+) plasmablast subsets, and higher serum IgG levels were detected in UC patients. The concentrations of serum IgG, the numbers of CD138(+)  CD38(+)  CD20(-)  CD19(+) , and IgG(+)  CD38(+)  CD20(-)  CD19(+) plasmablasts were negatively associated with the numbers of IgG(+)  IgD(-)  CD27(+)  CD19(+) memory B cells. Furthermore, the values of Mayo clinic score, CRP, or ESR in UC patients were negatively correlated with the numbers of IgG(+)  IgD(-)  CD27(+)  CD19(+) memory B cells, while positively correlated with the serum IgG levels and the numbers of plasmablast subsets. Following treatment with mesalazine, the numbers of circulating IgG(+)  IgD(-)  CD27(+)  CD19(+) memory B cells were significantly increased, while the numbers of CD138(+)  CD38(+)  CD20(-)  CD19(+) and IgG(+)  CD38(+)  CD20(-)  CD19(+) plasmablasts were reduced in UC patients. These decreased IgG(+)  IgD(-)  CD27(+)  CD19(+) memory B cells and increased plasmablasts may be involved in the pathogenic process of UC. PMID:26800315

  13. Circulating levels of plasminogen and oxidized phospholipids bound to plasminogen distinguish between atherothrombotic and non-atherothrombotic myocardial infarction.

    PubMed

    DeFilippis, Andrew P; Chernyavskiy, Ilya; Amraotkar, Alok R; Trainor, Patrick J; Kothari, Shalin; Ismail, Imtiaz; Hargis, Charles W; Korley, Frederick K; Leibundgut, Gregor; Tsimikas, Sotirios; Rai, Shesh N; Bhatnagar, Aruni

    2016-07-01

    Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to circulating plasminogen after myocardial infarction (MI), and their binding to plasminogen may accentuate fibrinolysis. We sought to assess whether circulating levels of plasminogen and OxPL bound to plasminogen (OxPL-PLG) increase following acute MI and whether this increase differs between atherothrombotic (Type 1) and non-atherothrombotic (Type 2) MI. We measured circulating levels of plasminogen and OxPL-PLG at 0, 6, 24, 48 h, and >3 months (stable state) following acute MI and following an angiogram for stable coronary artery disease (CAD). Forty-nine subjects met the criteria for acute MI, of whom 34 had clearly defined atherothrombotic (n = 22) or non-atherothrombotic (n = 12) MI; 15 patients met the criteria for stable CAD. Mean baseline levels of plasminogen and OxPL-PLG were lower in the acute MI group than in the stable CAD group (9.75 vs 20.2, p < 0.0001 for plasminogen and 165.5 vs 275.1, p = 0.0002 for OxPL-PLG) and did not change over time or between time points, including the 3-month follow-up. Mean baseline levels of plasminogen and OxPL-PLG were also lower in atherothrombotic (Type 1) than in non-atherothrombotic (Type 2) MI subjects (8.65 vs 12.1, p < 0.03 for plasminogen and 164.5 vs 245.7, p = 0.02 for OxPL-PLG), and this relationship did not change over time or between time points. Plasminogen and OxPL-PLG were lower in patients presenting with an acute MI than in those with stable CAD and also in those with atherothrombotic MI (Type 1) vs. those with non-atherothrombotic MI (Type 2). These findings persisted at a median follow-up of 3 months post-MI. The association of plasminogen and OxPL-PLG with acute MI, particularly atherothrombotic MI (Type 1), could reflect a reduced fibrinolytic capacity, associated with an increased risk of atherothrombotic events differentiating stable CAD from unstable CAD and atherothrombotic MI (Type 1

  14. FNDC5 expression and circulating irisin levels are modified by diet and hormonal conditions in hypothalamus, adipose tissue and muscle.

    PubMed

    Varela-Rodríguez, B M; Pena-Bello, L; Juiz-Valiña, P; Vidal-Bretal, B; Cordido, F; Sangiao-Alvarellos, S

    2016-01-01

    Irisin is processed from fibronectin type III domain-containing protein 5 (FNDC5). However, a controversy exists concerning irisin origin, regulation and function. To elucidate the relationship between serum irisin and FNDC5 mRNA expression levels, we evaluated plasma irisin levels and FNDC5 gene expression in the hypothalamus, gastrocnemius muscle and different depots of adipose tissue in models of altered metabolism. In normal rats, blood irisin levels diminished after 48-h fast and with leptin, insulin and alloxan treatments, and serum irisin concentrations increased in diabetic rats after insulin treatment and acute treatments of irisin increased blood insulin levels. No changes were observed during long-term experiments with different diets. We suggested that levels of circulating irisin are the result of the sum of the irisin produced by different depots of adipose tissue and skeletal muscle. This study shows for the first time that there are differences in FNDC5 expression depending on white adipose tissue depots. Moreover, a considerable decrease in visceral and epididymal adipose tissue depots correlated with increased FNDC5 mRNA expression levels, probably in an attempt to compensate the decrease that occurs in their mass. Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5/irisin expression and functions are different. PMID:27432282

  15. FNDC5 expression and circulating irisin levels are modified by diet and hormonal conditions in hypothalamus, adipose tissue and muscle

    PubMed Central

    Varela-Rodríguez, B. M.; Pena-Bello, L.; Juiz-Valiña, P.; Vidal-Bretal, B.; Cordido, F.; Sangiao-Alvarellos, S.

    2016-01-01

    Irisin is processed from fibronectin type III domain-containing protein 5 (FNDC5). However, a controversy exists concerning irisin origin, regulation and function. To elucidate the relationship between serum irisin and FNDC5 mRNA expression levels, we evaluated plasma irisin levels and FNDC5 gene expression in the hypothalamus, gastrocnemius muscle and different depots of adipose tissue in models of altered metabolism. In normal rats, blood irisin levels diminished after 48-h fast and with leptin, insulin and alloxan treatments, and serum irisin concentrations increased in diabetic rats after insulin treatment and acute treatments of irisin increased blood insulin levels. No changes were observed during long-term experiments with different diets. We suggested that levels of circulating irisin are the result of the sum of the irisin produced by different depots of adipose tissue and skeletal muscle. This study shows for the first time that there are differences in FNDC5 expression depending on white adipose tissue depots. Moreover, a considerable decrease in visceral and epididymal adipose tissue depots correlated with increased FNDC5 mRNA expression levels, probably in an attempt to compensate the decrease that occurs in their mass. Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5/irisin expression and functions are different. PMID:27432282

  16. Circulating levels of irisin is elevated in hypothyroidism, a case-control study.

    PubMed

    Ateş, İhsan; Altay, Mustafa; Topçuoğlu, Canan; Yılmaz, Fatma Meriç

    2016-04-01

    Objective Our objective in this study was to determine the relationship between irisin hormone, which has a similar effect with thyroid hormones on adipose tissue and the metabolism, and the thyroid functions and the obesity secondary to thyroid disease. Subjects and methods Seventy-four patients were included in the study, of the patients, 37 were newly diagnosed with Hashimoto's thyroiditis related hypothyroidism but not started on a treatment yet, and the remaining 37 were healthy volunteers without a known disease. Serum thyroid stimulating hormone (TSH), free thyroxin (fT4), anti-thyroglobulin and anti-thyroid peroxidase were measured and thyroid ultrasonography was performed in both groups. Serum irisin levels were measured using the commercially available ELISA kit. The hypothyroidism group had higher levels of irisin compared to the control group (2.77 ng/mL vs. 2.15 ng/mL respectively; p = 0.017). Results The hypothyroidism group had higher median levels of irisin in the obese patients than those in the control group (3.10 ng/mL vs. 2.10 ng/mL respectively; p = 0.013). Irisin level was negatively correlated with age in the whole population and patients with hypothyroidism (r = -0.255, p = 0.028; r = -0.346, p = 0.036 respectively). Irisin level was positively correlated with TSH (r = 0.247, p = 0.034) but negatively correlated with the fT4 (r = -0.316, p = 0.006) in the whole population. Obesity, fT4 and irisin levels were identified to be independent predictors in the diagnosis of hypothyroidism in the multivariable logistic regression analysis. Conclusion To the best of our knowledge, this study is the first in literature to identify that obesity, irisin level and fT4 level are independent risk factors for hypothyroidism. PMID:26201007

  17. Low-level circulations induced by an upper-level jet in a fine mesh numerical model

    NASA Technical Reports Server (NTRS)

    Burkhart, R. P.; Anthes, R. A.

    1981-01-01

    Attention is given to varying the initial conditions in the Penn State three-dimensional numerical model in the development of the low-level jet over the Ohio Valley during the 10 May 1973 severe weather event. The results of two forecasts are summarized: (1) the control forecast which interpolated the National Meteorological Center's operational analysis to the mesoscale model grid; and (2) modifying the control forecast by inserting artificial soundings and surface observations. Enhancements are made on the basis of subsynoptic scale analyses by Uccellini and surface data. The results indicate that the low-level jet was in part induced by pressure changes associated with deceleration and horizontal divergence of air in the exit region of the upper-level jet. The enhancement of the initial moisture field using surface reports of clouds and precipitation has a substantial effect on precipitation.

  18. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels.

    PubMed

    Goedeke, Leigh; Rotllan, Noemi; Canfrán-Duque, Alberto; Aranda, Juan F; Ramírez, Cristina M; Araldi, Elisa; Lin, Chin-Sheng; Anderson, Norma N; Wagschal, Alexandre; de Cabo, Rafael; Horton, Jay D; Lasunción, Miguel A; Näär, Anders M; Suárez, Yajaira; Fernández-Hernando, Carlos

    2015-11-01

    The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL cholesterol (LDL-C). Whereas the transcriptional regulation of LDLR is well characterized, the post-transcriptional mechanisms that govern LDLR expression are just beginning to emerge. Here we develop a high-throughput genome-wide screening assay to systematically identify microRNAs (miRNAs) that regulate LDLR activity in human hepatic cells. From this screen we identified and characterized miR-148a as a negative regulator of LDLR expression and activity and defined a sterol regulatory element-binding protein 1 (SREBP1)-mediated pathway through which miR-148a regulates LDL-C uptake. In mice, inhibition of miR-148a increased hepatic LDLR expression and decreased plasma LDL-C. Moreover, we found that miR-148a regulates hepatic expression of ATP-binding cassette, subfamily A, member 1 (ABCA1) and circulating high-density lipoprotein cholesterol (HDL-C) levels in vivo. These studies uncover a role for miR-148a as a key regulator of hepatic LDL-C clearance through direct modulation of LDLR expression and demonstrate the therapeutic potential of inhibiting miR-148a to ameliorate an elevated LDL-C/HDL-C ratio, a prominent risk factor for cardiovascular disease. PMID:26437365

  19. Antimicrobial activity of various immunomodulators: independence from normal levels of circulating monocytes and natural killer cells. Technical report

    SciTech Connect

    Morahan, P.S.; Dempsey, W.L.; Volkman, A.; Connor, J.

    1986-01-01

    The effects of /sup 89/Sr treatment on the natural host resistance of CD-1 mice and the enhancement of resistance by immunomodulators to infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) were determined. In the CD-1 mouse, single-dose treatment with /sup 89/Sr caused a profound decrease in the number of circulating monocytes (Mo), lymphocytes, and polymorphonuclear leukocytes (PMN) within 1 week. There was also marked functional impairment of the Mo inflammatory response, as well as markedly decreased spontaneous and activatable cytoxicity by splenic natural killer (NK) cells. Despite this profound cellular suppression, there was no significant change in natural resistance of CD-1 mice to L. monocytogenes of HSV-2 infection. Furthermore, prophylactic treatment of mice with the biologic immunomodulator Corynebacterium parvum or the synthetic immunomodulators maleic anhydride-divinyl ether or avridine in liposomes resulted in comparable enhancement of resistance in /sup 89/Sr-treated and normal mice. These data indicate that natural and immunomodulator-enhanced resistance of CD-1 mice to microbail infections do not depend on normal levels of Mo, PMN, or NK cells. The resistance enhancement may rely on activated tissue macrophages. In contrast to the early changes in circulating leukocytes, the residenet peritoneal cell populations were not markedly altered until after day 30. There then was a distinct decline in lymphocytes and a gradual decline in activated tissue macrophages.

  20. Radiative Heating of the ISCCP Upper Level Cloud Regimes and its Impact on the Large-scale Tropical Circulation

    SciTech Connect

    Li, Wei; Schumacher, Courtney; McFarlane, Sally A.

    2013-01-31

    Radiative heating profiles of the International Satellite Cloud Climatology Project (ISCCP) cloud regimes (or weather states) were estimated by matching ISCCP observations with radiative properties derived from cloud radar and lidar measurements from the Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) sites at Manus, Papua New Guinea, and Darwin, Australia. Focus was placed on the ISCCP cloud regimes containing the majority of upper level clouds in the tropics, i.e., mesoscale convective systems (MCSs), deep cumulonimbus with cirrus, mixed shallow and deep convection, and thin cirrus. At upper levels, these regimes have average maximum cloud occurrences ranging from 30% to 55% near 12 km with variations depending on the location and cloud regime. The resulting radiative heating profiles have maxima of approximately 1 K/day near 12 km, with equal heating contributions from the longwave and shortwave components. Upper level minima occur near 15 km, with the MCS regime showing the strongest cooling of 0.2 K/day and the thin cirrus showing no cooling. The gradient of upper level heating ranges from 0.2 to 0.4 K/(day∙km), with the most convectively active regimes (i.e., MCSs and deep cumulonimbus with cirrus) having the largest gradient. When the above heating profiles were applied to the 25-year ISCCP data set, the tropics-wide average profile has a radiative heating maximum of 0.45Kday-1 near 250 hPa. Column-integrated radiative heating of upper level cloud accounts for about 20% of the latent heating estimated by the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR). The ISCCP radiative heating of tropical upper level cloud only slightly modifies the response of an idealized primitive equation model forced with the tropics-wide TRMM PR latent heating, which suggests that the impact of upper level cloud is more important to large-scale tropical circulation variations because of convective feedbacks rather than direct forcing by

  1. Clinical evaluation of circulating microRNA-25 level change in sepsis and its potential relationship with oxidative stress

    PubMed Central

    Yao, Liqiong; Liu, Zhiwu; Zhu, Jinhong; Li, Bin; Chai, Chen; Tian, Yunlin

    2015-01-01

    Objective: to investigated the circulating microRNA expression profile in sepsis and its clinical evaluation. Methods: 70 patients with sepsis and 30 patients with SIRS were selected and their blood samples were collected. Using liquid bead array with 3 statistical analysis approaches analyzed the circulating microRNA expression profiles, for confirming the data of liquid bead array, qRT-PCR was performed. The prognostic value of the changed microRNA in sepsis was determined and compared with CRP and PCT by analyzing the receiver operating characteristic (ROC) curves. To reveal whether the selected microRNAs could predict the outcome of patients, 28 d survival rate were calculated using Kaplan-Meier curves. Furthermore, the level of malondialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma were detected and the relationship with the changed microRNA was determined. Results: By integrating data from liquid bead array, we ultimately identified 6 microRNAs that were consistently changed in both of 3 statistical analysis approaches, however, only the change of microRNA-25 was significant according to the qPCR’s result. The area under ROC curve showed that the clinical accuracy of microRNA-25 for sepsis diagnosis was better than CRP and PCT (AUG=0.806, 0.676 and 0.726, P<0.05).The decrease in level of microRNA-25 was correlated with the severity of sepsis, SOFA score, CRP and PCT level, meanwhile, microRNA-25 level can be used for predicting the prognosis of patients, the patients with microRNA-25 level ≤0.492 had a lower 28 d survival rate. Moreover, Decreased microRNA-25 level was related to the level of oxidative stress indicators in sepsis patients. Conclusions: microRNA-25 can be used as a biomarker for the diagnosis and assessment of sepsis. Meanwhile, microRNA-25 level may be associated with oxidative stress in patients with sepsis, and it is expected to become a target for anti-oxidation therapy. PMID

  2. Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients.

    PubMed

    Eichelser, Corinna; Stückrath, Isabel; Müller, Volkmar; Milde-Langosch, Karin; Wikman, Harriet; Pantel, Klaus; Schwarzenbach, Heidi

    2014-10-30

    In this study, we compared the blood serum levels of circulating cell-free and exosomal microRNAs, and their involvement in the molecular subtypes of breast cancer patients. Our analyses on cell-free miR-101, miR-372 and miR-373 were performed in preoperative blood serum of 168 patients with invasive breast cancer, 19 patients with benign breast diseases and 28 healthy women. MicroRNAs were additionally quantified in exosomes of 50 cancer patients and 12 healthy women from the same cohort. Relative concentrations were measured by quantitative TaqMan MicroRNA assays and correlated to clinicopathological risk factors. The concentrations of cell-free miR-101 (p=0.013) and miR-373 (p=0.024) were significantly different between patients with breast cancer and benign tumors. A prevalence of miR-101, miR-372 and miR-373 were found in exosomes. The levels of circulating exosomal (but not cell-free) miR-373 were higher in triple negative than luminal carcinomas (p=0.027). Also, estrogen-negative (p=0.021) and progesterone-negative (p=0.01) tumors displayed higher concentrations of exosomal miR-373 than patients with hormone-receptor positive tumors. Overexpression of miR-373 by transfection of MCF-7 cells showed downregulated protein expression of the estrogen receptor, and inhibition of apoptosis induced by camptothecin. Our data indicate that serum levels of exosomal miR-373 are linked to triple negative and more aggressive breast carcinomas. PMID:25333260

  3. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  4. Circulating Matrix Metalloproteinase Levels Following Ventricular Septal Defect Repair in Infants

    PubMed Central

    McQuinn, Tim C.; Deardorff, Rachael L.; Mukherjee, Rupak; Taylor, Anna Greta B.; Graham, Eric M.; Atz, Andrew M.; Forbus, Geoffrey A.; DeSantis, Stacia M.; Young, Jennifer B.; Stroud, Robert E.; Crawford, Fred A.; Bradley, Scott M.; Reeves, Scott T.; Spinale, Francis G.

    2010-01-01

    Background Congenital heart surgery initiates a complex inflammatory response that can influence the post-operative course. However, broad integration of the cytokine and proteolytic cascades (matrix metalloproteinases: MMPs), which may contribute to post-operative outcomes has not been performed. Methods/Results Using a low volume (50 – 60 μL), high sensitivity, multiplex approach a panel of cytokines (IL-2, -4, -6, -8, -10, TNFα, IL-1β, GM-CSF) and MMPs (MMP-2, -3, -7, -8, -9, -12, -13) were serially measured in patients (n=9) pre-operatively and post-VSD repair. Results were correlated with outcomes such as inotropic requirement, oxygenation, and fluid balance. Serial changes in peri-operative plasma levels of the cytokines and MMPs exhibited distinct temporal profiles. Plasma levels of IL-2, -8, -10, and MMP-9 peaked within 4 hours, while MMP-3 and MMP-8 levels remained elevated at 24 and 48 hours following cross-clamp removal. Area-under-the-curve analysis of early cytokine levels were associated with major clinical variables, including inverse correlations between early IL-10 levels and cumulative inotrope requirement at 48 hours (r: −0.85, p<0.005) and late MMP-7 levels and cumulative fluid balance (r: −0.90, p<0.001). Conclusions The unique findings of this study were that serial profiling a large array of cytokines and proteolytic enzymes following congenital heart surgery can provide insight into relationships between changes in bioactive molecules to early postoperative outcomes. Specific patterns of cytokine and MMP release may hold significance as biomarkers for predicting and managing the post-operative course following congenital heart surgery. PMID:20561637

  5. Measurement of circulating cell-free DNA levels by a new simple fluorescent test in patients with primary colorectal cancer.

    PubMed

    Czeiger, David; Shaked, Gad; Eini, Hadar; Vered, Ilan; Belochitski, Olga; Avriel, Avital; Ariad, Samuel; Douvdevani, Amos

    2011-02-01

    Elevated circulating cell-free DNA (CFD) levels were found in patients with cancer. The standard CFD assays are work-intensive and expensive. The aim was to evaluate in patients with cancer a new simple CFD assay. In mice inoculated with cancer cells, CFD levels correlated with tumor size. Compared with healthy subjects, 38 patients with colorectal cancer (CRC) had higher preoperative CFD levels (798 ± 409 vs 308 ± 256 ng/mL; P < .0001). Compared with patients free of disease at 1 year, CFD levels were elevated in patients who remained with disease or died (DD). CFD correlated with DD (P = .033), and a combined index of carcinoembryonic antigen × CFD exhibited a better correlation to DD than did pathologic staging (P = .0027 vs P = .0065). For patients with CRC, CFD levels were prognostic of death and disease. A large prospective study will need to be performed to truly evaluate the efficacy of this method for early detection, follow-up, and evaluation of patient response to treatment. PMID:21228367

  6. Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma.

    PubMed

    Wang, Wei; Li, Ping; Yang, Jiong

    2015-08-01

    Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate inflammatory and autoimmune diseases. The purpose of this study was to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma. IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qPCR). The frequencies of cytotoxic T cells (Tc)1, Tc2 and Tc17 cells were measured by flow cytometry. Plasma levels of IL-35, interferon (IFN)-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson's test. IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients and healthy controls. More importantly, plasma IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma. Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. PMID:26547705

  7. Population correlates of circulating mercury levels in Korean adults: the Korea National Health and Nutrition Examination Survey IV

    PubMed Central

    2014-01-01

    Background Prior studies focused on bioaccumulation of mercury (Hg) and on large, long-lived fish species as the major environmental source of Hg, but little is known about consumption of small-sized fish or about non-dietary determinants of circulating Hg levels. The purpose of this study was to evaluate whole blood mercury concentration (WBHg) and its major dietary and non-dietary correlates in Korean adults. Methods We analyzed cross-sectional data from 3,972 (male = 1,994; female = 1,978) participants who completed the Korean National Health and Nutrition Examination Survey IV, 2008 to 2009. Relevant factors included diet, geographic location of residence, demographics, and lifestyle. WBHg concentration was measured using cold-vapor atomic absorption spectrometry. Multivariable linear models assessed independent correlates of dietary and non-dietary factors for WBHg levels. Results Median levels of WBHg were 5.1 μg/L in men and 3.7 μg/L in women. Higher levels of fish/shellfish intake were associated with higher levels of WBHg. Higher consumption of small-sized fish was linked to higher levels of WBHg. Non-dietary predictors of higher WBHg were being male, greater alcohol consumption, higher income and education, overweight/obesity, increasing age, and living in the southeast region. Conclusions Both dietary and non-dietary factors were associated with WBHg levels in the Korean population. There is significant geographic variation in WBHg levels; residents living in the mid-south have higher WBHg levels. We speculate that uncontrolled geographic characteristics, such as local soil/water content and specific dietary habits are involved. PMID:24884916

  8. IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

    PubMed

    Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

    2016-09-01

    IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo. PMID:27388717

  9. Circulating T helper 9 cells and increased serum interleukin-9 levels in patients with knee osteoarthritis.

    PubMed

    Qi, Changlin; Shan, Yuxing; Wang, Jing; Ding, Fupeng; Zhao, Ding; Yang, Teng; Jiang, Yanfang

    2016-05-01

    The purpose of this study was to examine the roles of T helper 9 (Th9) cells and the serum interleukin (IL)-9 level in the pathogenesis of osteoarthritis (OA). The numbers of IL-9(+)  CD4(+)  CD8(-) T cells, interferon (IFN)-γ+ CD4(+)  CD8(-) T cells, IL-4(+) CD4(+)  CD8(-) T cells, and IL-17A(+ ) CD4(+ ) CD8(-) T cells in 25 OA patients and 13 healthy controls (HC) were examined by flow cytometry. The serum concentrations of IL-9, IL-4, IL-17A, and IFN-γ were also determined. The numbers of CD4(+) CD45RO(+) T cells, Th9 cells, Th1 cells, and Th17 cells in OA patients were significantly higher than those in HCs. Furthermore, serum IL-9, IL-17A, and IFN-γ levels in OA patients were higher than those in HCs. The number of Th9 cells was positively correlated with the number of Th17 cells in OA patients. Furthermore, greater numbers of Th9 cells were positively associated with elevated C-reactive protein, and both Th9 cells and IL-9 levels were positively correlated with the Western Ontario and McMaster Universities Osteoarthritis index in OA patients. Th9 cell numbers and IL-9 levels are correlated with OA patient symptoms and joint functionality and may be a marker of disease activity. PMID:26926842

  10. The Response of Circulating Leptin Levels to Exercise Stress Testing in Subjects Diagnosed with Metabolic Syndrome

    PubMed Central

    Pop, Dana; Dădârlat, Alexandra; Bodizs, Gyorgy; Stanca, Liana; Zdrenghea, Dumitru

    2014-01-01

    Aim. To assess the plasma leptin responses after exercise stress testing in patients with metabolic syndrome (MS). Material and Methods. We investigated 67 patients with MS, with mean age of 55 ± 7 years. They underwent exercise stress testing on cycloergometer. The lot was divided into three groups: group 1—10 patients with a true positive test, group 2—18 patients with a true negative test, and group 3—39 patients with a false negative test. Leptin levels were measured using the ELISA method. Results. Leptin levels decreased after effort in patients with MS (9.42 ± 11.08 ng/mL before and 8.18 ± 11.5 ng/mL after the exercise stress test, P = 0.0005, r = 0.874). In groups 1 (8.98 ± 9.09 at rest versus 5.98 ± 8.73 ng/mL after the exercise test, P = 0.002) and 3 (8.6 ± 10.53 at rest versus 6.91 ± 9.07 ng/mL, P = 0.0005), lower leptin levels were recorded immediately after exercise testing. Leptin levels were not significantly lower in group 2 before effort (9.49 ± 11.36 ng/ml) and after (9.46 ± 13.81 ng/mL). We found no correlation between leptinemia and exercise stress testing parameters, regardless of group. Conclusion. Our research showed that short-term exercise lowers leptin levels in coronary patients, without a relationship between its parameters and leptin values. PMID:24616817

  11. Skin fibrosis correlates with circulating thyrotropin levels in systemic sclerosis: translational association with Hashimoto's thyroiditis.

    PubMed

    Bagnato, Gian Luca; Roberts, William Neal; Fiorenza, Alessia; Arcuri, Chiara; Certo, Rosaria; Trimarchi, Francesco; Ruggeri, Rosaria Maddalena; Bagnato, Gian Filippo

    2016-02-01

    Systemic sclerosis (SSc) is a connective tissue disease, characterized by cutaneous and multi-organ fibrosis, and vascular abnormalities. Skin thickening is a characteristic feature of SSc and resembles myxedematous skin. Our aim was to correlate the degree of skin involvement in SSc patients with serum TSH levels, since TSH receptors are widely expressed in human tissues, including the skin. In this cross-sectional study, we enrolled 70 SSc patients, all females with a mean age of 47 ± 11 year. Thirty-five age- and sex-matched HT patients were recruited, as controls. Subjects under L-thyroxine therapy and/or with positive anti-TSH receptor antibodies were excluded. In all subjects, we measured serum TSH, FT4, and free tri-iodothyronine (FT3) levels. Skin thickness was evaluated using the modified Rodnan total skin score (mRSS). mRSS averaged 14 ± 9 for SSc and 4 ± 6 for HT patients. TSH levels positively correlated with skin scores in both SSc and HT patients groups. In SSc patients, FT3 and FT4 showed an inverse correlation with mRSS, while in HT only FT4 levels showed this inverse significance. When divided by cutaneous extent, SSc patients with diffuse disease form had higher TSH serum levels compared to those with the limited form; additionally, the correlations between TSH, FT4, and mRSS reached statistical significance. Our preliminary data clearly indicate that serum TSH is higher in SSc patients with more severe skin disease, and significantly correlate with the mRSS. Therefore, TSH could play a role in the development of cutaneous changes in SSc patients. PMID:25994300

  12. Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease.

    PubMed

    Polyzos, Stergios A; Anastasilakis, Athanasios D; Kountouras, Jannis; Makras, Polyzois; Papatheodorou, Athanasios; Kokkoris, Panagiotis; Sakellariou, Grigorios T; Terpos, Evangelos

    2016-07-01

    There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation. PMID:26056025

  13. Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status?

    PubMed Central

    Perfetto, F; Tarquini, R; Simonini, G; Bindi, G; Mancuso, F; Guiducci, S; Matucci-Cerinic, M; Falcini, F

    2005-01-01

    Objective: To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA. Methods: Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls. Results: Patients had significantly reduced body mass index (BMI) compared with controls (17.3 (3) v 19.1 (3) kg/m2; p<0.005). Leptin was significantly lower in patients than controls (8.1 (4.8) v 10.7 (7.3) ng/ml; p = 0.036), but leptin/BMI values were similar. Absolute (8.2 (4.8) v 8 (4.9); p>0.05) and normalised (0.45 (0.24) v 0.47 (0.24); p>0.05) leptin levels were not significantly different between patients with active and inactive disease and between patients with oligoarticular and polyarticular arthritis (7.8 (4.4) v 8.6 (5.3); p>0.05 and 0.45 (0.23) v 0.48 (0.26); p>0.05, respectively). Conclusions: Leptin production per unit of fat mass is similar in patients and controls. The hypothesis that high levels of proinflammatory cytokines that characterise JIA might induce an increase of adipocytes leptin production is not supported by the results. Leptin may be a marker of nutritional status of JIA. PMID:15608316

  14. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice

    PubMed Central

    Goedeke, Leigh; Salerno, Alessandro; Ramírez, Cristina M; Guo, Liang; Allen, Ryan M; Yin, Xiaoke; Langley, Sarah R; Esau, Christine; Wanschel, Amarylis; Fisher, Edward A; Suárez, Yajaira; Baldán, Angel; Mayr, Manuel; Fernández-Hernando, Carlos

    2014-01-01

    Plasma high-density lipoprotein (HDL) levels show a strong inverse correlation with atherosclerotic vascular disease. Previous studies have demonstrated that antagonism of miR-33 in vivo increases circulating HDL and reverse cholesterol transport (RCT), thereby reducing the progression and enhancing the regression of atherosclerosis. While the efficacy of short-term anti-miR-33 treatment has been previously studied, the long-term effect of miR-33 antagonism in vivo remains to be elucidated. Here, we show that long-term therapeutic silencing of miR-33 increases circulating triglyceride (TG) levels and lipid accumulation in the liver. These adverse effects were only found when mice were fed a high-fat diet (HFD). Mechanistically, we demonstrate that chronic inhibition of miR-33 increases the expression of genes involved in fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the livers of mice treated with miR-33 antisense oligonucleotides. We also report that anti-miR-33 therapy enhances the expression of nuclear transcription Y subunit gamma (NFYC), a transcriptional regulator required for DNA binding and full transcriptional activation of SREBP-responsive genes, including ACC and FAS. Taken together, these results suggest that persistent inhibition of miR-33 when mice are fed a high-fat diet (HFD) might cause deleterious effects such as moderate hepatic steatosis and hypertriglyceridemia. These unexpected findings highlight the importance of assessing the effect of chronic inhibition of miR-33 in non-human primates before we can translate this therapy to humans. PMID:25038053

  15. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo.

    PubMed

    Ferri, C; Pittoni, V; Piccoli, A; Laurenti, O; Cassone, M R; Bellini, C; Properzi, G; Valesini, G; De Mattia, G; Santucci, A

    1995-03-01

    Endothelin-1 (ET-1) is a potent vasoactive and mitogenic peptide produced by the vascular endothelium. In this study, we evaluated whether insulin stimulates ET-1 secretion by human endothelial cells derived from umbilical cord veins and by human permanent endothelial hybrid cells Ea.hy 926. Moreover, to provide evidence that insulin may stimulate ET-1 secretion in vivo, plasma ET-1 levels were evaluated in 7 type II diabetic normotensive males (mean age, 54.3 +/- 4.0 yr) during 2-h hyperinsulinemic euglycemic clamps (287 pmol insulin/m2.min-1) as well as in 12 obese hypertensive males (mean age, 44.2 +/- 4.6 yr) before and after a 12-week period of caloric restriction. Our results showed that insulin stimulated ET-1 release from cultured endothelial cells in a dose-dependent fashion. ET-1 release persisted for 24 h and was also observed at physiological insulin concentrations (10(-9) mol/L). The insulin-induced ET-1 secretion was inhibited by genistein, a tyrosine kinase inhibitor, and by cycloheximide, a protein synthesis inhibitor, suggesting that it requires de novo protein synthesis rather than ET-1 release from intracellular stores. In the in vivo experiments, plasma ET-1 levels rapidly increased during euglycemic hyperinsulinemic clamps (from 0.76 +/- 0.18 pg/mL at time zero to 1.65 +/- 0.21 pg/mL at 60 min; P < 0.05) and persisted elevated until the end of insulin infusion (1.37 +/- 0.37 pg/mL at 120 min; P < 0.05 vs. time zero). In obese hypertensives, plasma ET-1 levels significantly decreased after 12 weeks of caloric restriction (from 0.85 +/- 0.51 to 0.48 +/- 0.28 pg/mL; P < 0.04). The decrease in body weight induced by caloric restriction was accompanied by a significant reduction in fasting insulin levels (from 167.2 +/- 94.0 to 98.9 +/- 44.9 pmol/L; P < 0.05) which correlated with the reduction in plasma ET-1 levels (r = 0.78; P < 0.003). In conclusion, our data show that insulin stimulates both in vitro and in vivo ET-1 secretion. Such interaction

  16. Maternal circulating levels of some metabolic syndrome biomarkers in gestational diabetes mellitus.

    PubMed

    Khosrowbeygi, Ali; Shiamizadeh, Najmeh; Taghizadeh, Nima

    2016-02-01

    The aims of the present study were to explore serum levels of lipid profile, atherogenic indexes LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C, bilirubin, adiponectin, pseudocholinesterase, activities of gamma-glutamyltransferase (GGT), adenosine deaminase (ADA), and α-amylase, insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) formula, and assessment of correlations between them in gestational diabetes mellitus (GDM) compared with normal pregnancy. A cross-sectional study was designed. The patients consisted of 30 women with GDM. The normal group consisted of 30 healthy pregnant women. The Mann-Whitney U test and Spearman's correlation analysis were used for statistical analysis. A p value less than 0.05 was considered significant. Serum activities of enzymes GGT (p = 0.001) and ADA (p = 0.02) were significantly higher in GDM compared with normal pregnancy, while pseudocholinesterase were significantly decreased (p = 0.02). However, activity of enzyme α-amylase did not show significant difference between two groups (p = 0.75). Serum levels of both HDL-C and adiponectin were significantly decreased in GDM group (p = 0.001). The atherogenic indexes and the HOMA-IR index were significantly higher in GDM (p = 0.001). Serum activity of ADA showed positive correlation with total cholesterol (TC) (r = 0.46, p = 0.01) and CRP (r = 0.66, p = 0.001) in GDM group. Serum levels of total bilirubin correlated negatively with both ADA (r = -0.38, p = 0.04) and triglyceride (r = -0.45, p = 0.01) in women with GDM. Serum activity of GGT correlated positively with LDL-C (r = 0.48, p = 0.01) and TC (r = 0.52, p = 0.003) in GDM group. Increased atherogenic indexes, ADA, GGT, and decreased pseudocholinesterase might be risk factors for GDM. PMID:26219405

  17. Circulation within the primary system at TMI-2 with lowered coolant level and at atmospheric conditions

    SciTech Connect

    Baston, V.F.; Hofstetter, K.J.; Malinauskas, A.P.

    1985-06-01

    Experiments were performed with the Three Mile Island reactor coolant system open to the atmosphere and the coolant lowered to a level above the fuel (a condition required for defueling) to ascertain the extent of coolant mixing. A principal concern for coolant decontamination during defueling is the radionuclides released and their distribution within the primary system. Analyses of radionuclide, temperature, and dissolved oxygen data taken during these experiments confirm mixing in the primary system under forced coolant flow conditions with only minimal mixing occurring during static periods.

  18. Effectiveness of the GnRH agonist Deslorelin as a tool to decrease levels of circulating testosterone in zebra finches.

    PubMed

    Murphy, Karagh; Wilson, David A; Burton, Mark; Slaugh, Shayla; Dunning, Jeffery L; Prather, Jonathan F

    2015-10-01

    Songbirds are widely used in studies of the neurobiology underlying learning, memory and performance of the sounds used in vocal communication. Development and activity of neurons in many brain sites implicated in those behaviors are closely related to levels of circulating testosterone. Approaches to understand the effects of testosterone in songbirds are presently limited to testosterone implants, which elevate testosterone levels to supraphysiological values, or castration, which eliminates gonadal production of testosterone. Previous studies in mammals indicate that GnRH agonists may be an effective tool to reduce testosterone within that range of extremes and without invasive surgery. To evaluate the effectiveness of the GnRH agonist Deslorelin as a tool to modulate levels of testosterone in songbirds, we recorded the effects of Deslorelin in adult male zebra finches. We recorded songs, body mass and blood testosterone levels pre-treatment, then we gave each bird a small subcutaneous implant of Deslorelin. We measured blood plasma testosterone levels weekly and recorded song behavior and gross morphology of brain, testes and heart at the end of each experiment. Testosterone levels were reduced at the 5mg/kg dose, and the very slight song changes we observed at that dose were like those reported for castrated zebra finches. As expected, there were no changes in the number of cells in androgen-sensitive brain structures. Suppression of testosterone at the 5mg/kg dose was reversible through implant removal. Thus, Deslorelin is a new tool to transiently suppress testosterone levels without the invasiveness and undesirable aftereffects of surgical castration. PMID:26391838

  19. High levels of cell-free circulating nucleic acids in pancreatic cancer are associated with vascular encasement, metastasis and poor survival.

    PubMed

    Singh, Nidhi; Gupta, Surabhi; Pandey, R M; Chauhan, Shyam S; Saraya, Anoop

    2015-03-01

    Pancreatic cancer is a highly aggressive disease with rapid invasion and early encasement of blood vessels. Hence, levels of circulating nucleic acids and tumor-associated mutations in them may have clinical importance. We analyzed the levels of circulating tumor DNA and oncogenic k-ras mutation in plasma of patients with pancreatic cancer and correlated their levels with survival and clinicopathological parameters. Higher levels of plasma DNA (>62 ng/mL) was found to associate significantly with lower overall survival time (p=.002), presence of vascular encasement (p=.030) and metastasis (p=.001). However, k-ras mutation status did not correlate with any of the clinicopathological parameters or survival. We conclude that circulating DNA in plasma can be an important predictor of prognosis in pancreatic cancer. PMID:25647443

  20. Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis.

    PubMed

    Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U; Kegel, Johanna; Haller, Hermann; Haubitz, Marion; Kirsch, Torsten

    2015-11-01

    ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease. PMID:25788529

  1. Two seconds is all it takes: European starlings (Sturnus vulgaris) increase levels of circulating glucocorticoids after witnessing a brief raptor attack.

    PubMed

    Jones, Blake C; Smith, Adam D; Bebus, Sara E; Schoech, Stephan J

    2016-02-01

    Researchers typically study "acute" activation of the hypothalamic-pituitary-adrenal (HPA) axis by measuring levels of circulating glucocorticoids in animals that have been exposed to a predator or a cue from a predator (e.g., odor), or have experienced a standardized capture-and-restraint protocol, all of which are many minutes in duration. However, exposure to predators in the "wild", either as the subject of an attack or as a witness to an attack, is generally much shorter as most depredation attempts upon free-living animals last <5s. Yet, whether a stimulus lasting only seconds can activate the HPA axis is unknown. To determine if a stimulus of a few seconds triggers a glucocorticoid response, we measured levels of corticosterone (CORT; the primary avian glucocorticoid) in wild-caught European starlings (Sturnus vulgaris) after they witnessed a brief (<2-8s) raptor attack upon a conspecific, a human "attack" (i.e., a researcher handling a conspecific), and an undisturbed control. Witnesses of a raptor attack responded with CORT levels comparable to that induced by a standardized capture-and-restraint protocol. Glucocorticoid levels of individuals following the control treatment were similar to baseline levels, and those that witnessed a human "attack" had intermediate levels. Our results demonstrate that witnessing a predator attack of very brief duration triggers a profound adrenocortical stress response. Given the considerable evidence of a role for glucocorticoids in learning and memory, such a response may affect how individuals learn to recognize and appropriately react to predators. PMID:26522494

  2. High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice.

    PubMed Central

    Fukuchi, K.; Ho, L.; Younkin, S. G.; Kunkel, D. D.; Ogburn, C. E.; LeBoeuf, R. C.; Furlong, C. E.; Deeb, S. S.; Nochlin, D.; Wegiel, J.; Wisniewski, H. M.; Martin, G. M.

    1996-01-01

    We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human beta-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick beta-actin promoter. There were exceptionally high levels of beta-amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral beta-amyloidosis despite extremely high levels of circulating beta-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of beta-amyloid precursor protein may play a predominant role in cerebral beta-amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8686746

  3. Association between circulating galectin-3 levels and the immunological, inflammatory and nutritional parameters in patients with colorectal cancer

    PubMed Central

    Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Nakajima, Takahiro; Chida, Shun; Noda, Masaru; Suzuki, Satoshi; Nakamura, Izumi; Ohki, Shinji; Takenoshita, Seiichi

    2016-01-01

    Galectin-3, a β-galactoside-binding lectin, exhibits pleiotropic biological functions and has a role as one of the immunological modulators. However, the associations between circulating galectin-3 and immunological, inflammatory and nutritional parameters have not yet been fully elucidated. The serum concentration of galectin-3 was examined in association with interleukin-10 (IL-10), IL-12 and IL17 production, lymphocyte stimulation, neutrophil/lymphocyte ratio (NLR), white blood cell count (WBC), C-reactive protein (CRP) and rapid turnover proteins, including retinol-binding protein (RBP), prealbumin (PA) and transferrin (TF) in 50 patients with untreated colorectal cancers. Significant increases (P<0.05) were observed in the serum galectin-3 levels in patients with untreated colorectal cancer (9.6±4.5 ng/ml) compared with the normal controls (3.2±1.6 ng/ml). Higher serum galectin-3 concentrations were observed in patients with colon cancer (11.5±4.4 ng/ml) compared to in patients with rectal cancer (8.0±4.0 ng/ml) (P=0.005). The levels of circulating galectin-3 inversely correlated with the production of IL-10 (r=−0.59, P<0.001), and IL-12 (r=−0.69, P<0.001). Galectin-3 concentration also inversely correlated with the lymphocyte stimulation assay stimulation index (r=−0.42, P=0.021). However, the level of serum galectin-3 correlated with IL-17 production (r=0.67, P<0.001). Serum galectin-3 levels exhibited significant correlations with NLR (r=0.41, P=0.009), WBC (r=0.32, P=0.035), and CRP (r=0.63, P<0.001), and statistically significant inverse correlations with RBP (r=−0.45, P=0.002), PA (r=−0.46, P=0.001) and TF (r=−0.72, P<0.001). Galectin-3 may be one of the key factors in the regulation of immunological, inflammatory and nutritional conditions.

  4. Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

    PubMed Central

    Benz, Fabian; Tacke, Frank; Luedde, Mark; Trautwein, Christian; Luedde, Tom; Koch, Alexander; Roderburg, Christoph

    2015-01-01

    Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not

  5. Level of maternal winter supplement and feed restriction during postweaning development influences circulating concentrations of IGF-I in heifers during the peripartum and rebreeding period.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective of this research was to evaluate effects of 2 levels of supplemental feed provided to cows during late gestation and 2 levels of feed provided to their daughters during postweaning development on circulating concentrations of IGF-I in the daughters before calving, after calving and before ...

  6. Level of maternal winter supplement and feed restriction during postweaning development influence circulating concentrations of IGF-I in heifers during the peripartum and rebreeding period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective of this research was to evaluate effects of 2 levels of supplemental feed provided to cows during late gestation and 2 levels of feed provided to their daughters during postweaning development on circulating concentrations of IGF-I in the daughters before calving, after calving and before ...

  7. Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation

    PubMed Central

    Huang, Jie; Sabater-Lleal, Maria; Asselbergs, Folkert W.; Tregouet, David; Shin, So-Youn; Ding, Jingzhong; Baumert, Jens; Oudot-Mellakh, Tiphaine; Folkersen, Lasse; Johnson, Andrew D.; Smith, Nicholas L.; Williams, Scott M.; Ikram, Mohammad A.; Kleber, Marcus E.; Becker, Diane M.; Truong, Vinh; Mychaleckyj, Josyf C.; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; Moore, Jason H.; Williams, Frances M. K.; Dehghan, Abbas; Silbernagel, Günther; Schrijvers, Elisabeth M. C.; Smith, Shelly; Karakas, Mahir; Tofler, Geoffrey H.; Silveira, Angela; Navis, Gerjan J.; Lohman, Kurt; Chen, Ming-Huei; Peters, Annette; Goel, Anuj; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Lundmark, Per; Psaty, Bruce M.; Strawbridge, Rona J.; Boehm, Bernhard O.; Carter, Angela M.; Meisinger, Christa; Peden, John F.; Bis, Joshua C.; McKnight, Barbara; Öhrvik, John; Taylor, Kent; Franzosi, Maria Grazia; Seedorf, Udo; Collins, Rory; Franco-Cereceda, Anders; Syvänen, Ann-Christine; Goodall, Alison H.; Yanek, Lisa R.; Cushman, Mary; Müller-Nurasyid, Martina; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Kooner, Jaspal S.; Hofman, Albert; Danesh, John; Clarke, Robert; Meigs, James B.; Kathiresan, Sekar; Reilly, Muredach P.; Klopp, Norman; Harris, Tamara B.; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Watkins, Hugh; Spector, Timothy D.; Becker, Lewis C.; Tracy, Russell P.; März, Winfried; Uitterlinden, Andre G.; Eriksson, Per; Cambien, Francois; Morange, Pierre-Emmanuel; Koenig, Wolfgang; Soranzo, Nicole; van der Harst, Pim; Liu, Yongmei

    2012-01-01

    We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 × 10−8) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 × 10−10); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10−8); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 10−8). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1. PMID:22990020

  8. Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal Epithelial Cells and Circulating Level in Mice

    PubMed Central

    Jacouton, Elsa; Mach, Núria; Cadiou, Julie; Lapaque, Nicolas; Clément, Karine; Doré, Joël; van Hylckama Vlieg, Johan E. T.; Smokvina, Tamara; Blottière, Hervé M

    2015-01-01

    Background and Objectives Identification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms. Subjects and Methods Nineteen lactobacilli strains have been tested on HT–29 human intestinal epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analysed the whole genome transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow. Results We identified one strain (Lactobacillus rhamnosus CNCMI–4317) that modulated Fiaf expression in IECs. This regulation relied potentially on bacterial surface-exposed molecules and seemed to be PPAR-γ independent but PPAR-α dependent. Transcriptome functional analysis revealed that multiple pathways including cellular function and maintenance, lymphoid tissue structure and development, as well as lipid metabolism were regulated by this strain. The regulation of immune system and lipid and carbohydrate metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues (except a trend in distal small intestine). Conclusion We showed that Lactobacillus rhamnosus CNCMI–4317 induced Fiaf expression in human IECs, and increased circulating FIAF protein level in mice. Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro. PMID:26439630

  9. Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice.

    PubMed

    Bo, E; Farinetti, A; Marraudino, M; Sterchele, D; Eva, C; Gotti, S; Panzica, G

    2016-07-01

    Tributyltin (TBT), a pesticide used in antifouling paints, is toxic for aquatic invertebrates. In vertebrates, TBT may act in obesogen- inducing adipogenetic gene transcription for adipocyte differentiation. In a previous study, we demonstrated that acute administration of TBT induces c-fos expression in the arcuate nucleus. Therefore, in this study, we tested the hypothesis that adult exposure to TBT may alter a part of the nervous pathways controlling animal food intake. In particular, we investigated the expression of neuropeptide Y (NPY) immunoreactivity. This neuropeptide forms neural circuits dedicated to food assumption and its action is mediated by Y1 receptors that are widely expressed in the hypothalamic nuclei responsible for the regulation of food intake and energy homeostasis. To this purpose, TBT was orally administered at a dose of 0.025 mg/kg/day/body weight to adult animals [male and female C57BL/6 (Y1-LacZ transgenic mice] for 4 weeks. No differences were found in body weight and fat deposition, but we observed a significant increase in feed efficiency in TBT-treated male mice and a significant decrease in circulating leptin in both sexes. Computerized quantitative analysis of NPY immunoreactivity and Y1-related β-galactosidase activity demonstrated a statistically significant reduction in NPY and Y1 transgene expression in the hypothalamic circuit controlling food intake of treated male mice in comparison with controls. In conclusion, the present results indicate that adult exposure to TBT is profoundly interfering with the nervous circuits involved in the stimulation of food intake. PMID:27310180

  10. Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Scher, Howard I.; Heller, Glenn; Molina, Arturo; Attard, Gerhardt; Danila, Daniel C.; Jia, Xiaoyu; Peng, Weimin; Sandhu, Shahneen K.; Olmos, David; Riisnaes, Ruth; McCormack, Robert; Burzykowski, Tomasz; Kheoh, Thian; Fleisher, Martin; Buyse, Marc; de Bono, Johann S.

    2015-01-01

    Purpose Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure. Patients and Methods Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest. The Prentice criteria were applied to test candidate biomarkers as surrogates for overall survival at the individual-patient level. Results A biomarker panel using CTC count and lactate dehydrogenase (LDH) level was shown to satisfy the four Prentice criteria for individual-level surrogacy. Twelve-week surrogate biomarker data were available for 711 patients. The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference (P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival. Overall, 2-year survival of patients with CTCs < 5 (low risk) versus patients with CTCs ≥ 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively. Conclusion A biomarker panel containing CTC number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic CRPC. Additional trials are ongoing to validate the findings. PMID:25800753

  11. Associations between joint effusion in the knee and gene expression levels in the circulation: a meta-analysis

    PubMed Central

    Peters, Marjolein J.; Ramos, Yolande F.M.; den Hollander, Wouter; Schiphof, Dieuwke; Hofman, Albert; Uitterlinden, André G.; Oei, Edwin H.G.; Slagboom, P. Eline; Kloppenburg, Margreet; Bloem, Johan L.; Bierma-Zeinstra, Sita M.A.; Meulenbelt, Ingrid; van Meurs, Joyce B.J.

    2016-01-01

    Objective: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. Materials and Methods: Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools. Results: In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways. Conclusion: Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage. PMID:27134727

  12. Tamm-Horsfall Protein Regulates Circulating and Renal Cytokines by Affecting Glomerular Filtration Rate and Acting as a Urinary Cytokine Trap*

    PubMed Central

    Liu, Yan; El-Achkar, Tarek M.; Wu, Xue-Ru

    2012-01-01

    Although few organ systems play a more important role than the kidneys in cytokine catabolism, the mechanism(s) regulating this pivotal physiological function and how its deficiency affects systemic cytokine homeostasis remain unclear. Here we show that elimination of Tamm-Horsfall protein (THP) expression from mouse kidneys caused a marked elevation of circulating IFN-γ, IL1α, TNF-α, IL6, CXCL1, and IL13. Accompanying this were enlarged spleens with prominent white-pulp macrophage infiltration. Lipopolysaccharide (LPS) exacerbated the increase of serum cytokines without a corresponding increase in their urinary excretion in THP knock-out (KO) mice. This, along with the rise of serum cystatin C and the reduced inulin and creatinine clearance from the circulation, suggested that diminished glomerular filtration may contribute to reduced cytokine clearance in THP KO mice both at the baseline and under stress. Unlike wild-type mice where renal and urinary cytokines formed specific in vivo complexes with THP, this “trapping” effect was absent in THP KO mice, thus explaining why cytokine signaling pathways were activated in renal epithelial cells in such mice. Our study provides new evidence implicating an important role of THP in influencing cytokine clearance and acting as a decoy receptor for urinary cytokines. Based on these and other data, we present a unifying model that underscores the role of THP as a major regulator of renal and systemic immunity. PMID:22451664

  13. Effect of aerobic training and resistance training on circulating irisin level and their association with change of body composition in overweight/obese adults: a pilot study.

    PubMed

    Kim, H-J; Lee, H-J; So, B; Son, J S; Yoon, D; Song, W

    2016-06-20

    The novel myokine irisin has been reported as a therapeutic target for metabolic disease. The objective of this study is to reveal the effects of aerobic training (AT) and resistance training (RT) on circulating irisin levels and their associations with change of body composition in overweight/obese adults. Twenty eight overweight/obese adults (BMI>23 kg/m(2)) were included in this study and compared before and after 8 weeks of exercise program (60 min/day, 5 times in a week). The subjects, in both aerobic and resistance training, showed significant improvement in anthropometric parameters and exercise capacities including maximal oxygen uptake and muscle strength. Interestingly, the circulating irisin was significantly increased in resistance training group (p=0.002) but not in aerobic training (p=0.426) compared to control group. In addition, we found the positive correlation between change of the circulating irisin and muscle mass (r=0.432, p=0.022) and the negative correlation between change of the circulating irisin and fat mass (r=-0.407, p=0.031). In the present pilot study, we found that circulating irisin level was increased by 8 weeks of resistance training in overweight/obese adults, suggesting that resistance training could be the efficient exercise type in overweight/obese considering positive change of body composition concomitant with increase of irisin levels. PMID:26447516

  14. Circulating levels of IL-1B+IL-6 cause ER stress and dysfunction in islets from prediabetic male mice.

    PubMed

    O'Neill, Christina M; Lu, Christine; Corbin, Kathryn L; Sharma, Poonam R; Dula, Stacey B; Carter, Jeffrey D; Ramadan, James W; Xin, Wenjun; Lee, Jae K; Nunemaker, Craig S

    2013-09-01

    Elevated levels of circulating proinflammatory cytokines are associated with obesity and increased risk of type 2 diabetes, but the mechanism is unknown. We tested whether proinflammatory cytokines IL-1B+IL-6 at low picogram per milliliter concentrations (consistent with serum levels) could directly trigger pancreatic islet dysfunction. Overnight exposure to IL-1B+IL-6 in islets isolated from normal mice and humans disrupted glucose-stimulated intracellular calcium responses; cytokine-induced effects were more severe among islets from prediabetic db/db mice that otherwise showed no signs of dysfunction. IL-1B+IL-6 exposure reduced endoplasmic reticulum (ER) calcium storage, activated ER stress responses (Nos2, Bip, Atf4, and Ddit3 [CHOP]), impaired glucose-stimulated insulin secretion, and increased cell death only in islets from prediabetic db/db mice. Furthermore, we found increased serum levels of IL-1B and IL-6 in diabetes-prone mice at an age before hyperglycemia was exhibited, suggesting that low-grade systemic inflammation develops early in the disease process. In addition, we implanted normal outbred and inbred mice with subcutaneous osmotic mini-pumps containing IL-1B+IL-6 to mimic the serum increases found in prediabetic db/db mice. Both IL-1B and IL-6 were elevated in serum from cytokine-pump mice, but glucose tolerance and blood glucose levels did not differ from controls. However, when compared with controls, isolated islets from cytokine-pump mice showed deficiencies in calcium handling and insulin secretion that were similar to observations with islets exposed to cytokines in vitro. These findings provide proof of principle that low-grade systemic inflammation is present early in the development of type 2 diabetes and can trigger ER stress-mediated islet dysfunction that can lead to islet failure. PMID:23836031

  15. Directionality of affective priming: effects of trait anxiety and activation level.

    PubMed

    Maier, Markus A; Berner, Michael P; Pekrun, Reinhard

    2003-01-01

    Among the most influential models of automatic affective processing is the spreading activation account (Fazio, Sanbonmatsu, Powell, & Kardes, 1986). However, investigations of this model by different research groups using the pronunciation task in an affective priming paradigm yielded contradictory results. Whereas one research group reported congruency effects, another obtained reversed priming effects (contrast effects), and still another found null effects. In Experiment 1, we were able to show an influence of trait anxiety on the direction of the affective priming effect. By using a multiple priming paradigm in Experiment 2, we were able to link the occurrence of reversed priming effects to increased levels of activation of affective representations. We propose that this relation might underlie the influence of trait anxiety on the direction of affective priming effects. Both experiments indicate that automatic evaluation in an affective network is substantially moderated by personality traits and activation level. PMID:12693196

  16. How changes in pore pressure affect fluid circulation in volcanoes: three examples from Vulcano Island, Mt. Etna and Mt Vesuvius (Italy)

    NASA Astrophysics Data System (ADS)

    Federico, C.; Madonia, P.; Capasso, G.; D'Alessandro, W.; Bellomo, S.; Brusca, L.; Cusano, P.; Longo, M.; Paonita, A.; Petrosino, S.

    2013-05-01

    Fluids circulating in volcanic edifices are attracting increasing interest from scientists, mostly because their role in triggering flank instability, phreatic explosions, and eruptions has been documented in several cases worldwide [Newhall et al. 2001, Thomas et al. 2004]. Fluid pore pressure can change as an effect of either external (meteoric recharge, variation of the stress field), or endogenous causes (e.g. internal pressurization of magmatic volatiles and hydrothermal systems). The reciprocal roles of tectonics and magmatic/hydrothermal activity are still under investigation [Gottsman et al. 2007, Roeloffs et al. 2003]. We discuss the results of decennial data records collected in the aquifers of Mt Etna, Vulcano Island and Mt Vesuvius, and get insights on the role of tectonics and volcanic activity on the observed variations of water level and chemical composition. In Vulcano Island, the shallow thermal aquifer is deeply concerned by deep volcanic fluids. The most significant variations were observed during the 1988-96 crisis, due to the large input of steam and acidic gases from depth. In addition, the record of the water table elevation provided remarkable insights on the pressure of the volcano-hydrothermal system, which can be envisaged as the cause for the onset of the phase of higher vapor output in the fumarolic field in late 2004. On Mt. Vesuvius, the geochemical behavior of the aquifer appears strictly controlled by the input of volcanic gases and variations in the stress field. These latter, which were responsible for the seismic crisis of 1999, and the almost simultaneous increased input of CO2-rich vapor, significantly affected water chemistry and temperature, until 2006. The recent observations of low salinity, temperature, and dissolved carbon contents in groundwater provide strong evidence for reduced pressure in the volcano-hydrothermal system. The record of water chemistry available on Mt. Etna since 1994 shows coeval changes in almost all

  17. A Screening-Level Approach for Comparing Risks Affecting Aquatic Ecosystem Services over Socio-Environmental Gradients

    NASA Astrophysics Data System (ADS)

    Harmon, T. C.; Conde, D.; Villamizar, S. R.; Reid, B.; Escobar, J.; Rusak, J.; Hoyos, N.; Scordo, F.; Perillo, G. M.; Piccolo, M. C.; Zilio, M.; Velez, M.

    2015-12-01

    Assessing risks to aquatic ecosystems services (ES) is challenging and time-consuming, and effective strategies for prioritizing more detailed assessment efforts are needed. We propose a screening-level risk analysis (SRA) approach that scales ES risk using socioeconomic and environmental indices to capture anthropic and climatic pressures, as well as the capacity for institutional responses to those pressures. The method considers ES within a watershed context, and uses expert input to prioritize key services and the associated pressures that threaten them. The SRA approach focuses on estimating ES risk affect factors, which are the sum of the intensity factors for all hazards or pressures affecting the ES. We estimate the pressure intensity factors in a novel manner, basing them on the nation's (i) human development (proxied by Inequality-adjusted Human Development Index, IHDI), (ii) environmental regulatory and monitoring state (Environmental Performance Index, EPI) and (iii) the current level of water stress in the watershed (baseline water stress, BWS). Anthropic intensity factors for future conditions are derived from the baseline values based on the nation's 10-year trend in IHDI and EPI; ES risks in nations with stronger records of change are rewarded more/penalized less in estimates for good/poor future management scenarios. Future climatic intensity factors are tied to water stress estimates based on two general circulation model (GCM) outcomes. We demonstrate the method for an international array of six sites representing a wide range of socio-environmental settings. The outcomes illustrate novel consequences of the scaling scheme. Risk affect factors may be greater in a highly developed region under intense climatic pressure, or in less well-developed regions due to human factors (e.g., poor environmental records). As a screening-level tool, the SRA approach offers considerable promise for ES risk comparisons among watersheds and regions so that

  18. Dietary Sodium Reduction Does Not Affect Circulating Glucose Concentrations in Fasting Children or Adults: Findings from a Systematic Review and Meta-Analysis1234

    PubMed Central

    Patel, Sheena M; Cobb, Paul; Saydah, Sharon; Zhang, Xuanping; de Jesus, Janet M; Cogswell, Mary E

    2015-01-01

    Background: Although evidence shows that reduced sodium intake lowers blood pressure, some studies suggest that sodium reduction may adversely affect insulin resistance and glucose tolerance. Objectives: The objectives were to assess the effects of sodium reduction on glucose tolerance, evaluate strengths and weaknesses of the relevant scientific literature, and provide direction for future research. Methods: We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, and Web of Science through August 2014. Both randomized and nonrandomized intervention trials were included in our meta-analyses. The effects of sodium reduction on glucose tolerance were evaluated in 37 articles, but because of a lack of comparable data, 8 trials were excluded from the meta-analyses. Results: Participants were 10–79 y old, either primarily healthy or with hypertension. In meta-analyses of 20 randomized, crossover trials (n = 504 participants) and 9 nonrandomized crossover trials (n = 337), circulating glucose concentrations of fasting participants were not affected by reduction in sodium intake. In contrast, in meta-analyses of 19 of the 20 randomized, crossover trials (n = 494), fasting insulin concentrations were 9.53 pmol/L higher (95% CI: 5.04, 14.02 pmol/L higher) with sodium reduction. In 9 nonrandomized trials (n = 337), fasting insulin did not differ with reduced sodium intake. Results differed little when the analyses were restricted to studies with a low risk of bias and duration of ≥7 d. Conclusions: This meta-analysis revealed no evidence that, in trials with a short intervention and large reductions in sodium, circulating glucose concentrations differed between groups. Recommendations for future studies include extending intervention durations, ensuring comparability of groups at baseline through randomization, and assessing sodium intakes relevant to population sodium reduction. In addition, analyses on other metabolic variables were limited because of the number of

  19. A modeling study of the physical processes affecting the development of seasonal hypoxia over the inner Louisiana-Texas shelf: Circulation and stratification

    NASA Astrophysics Data System (ADS)

    Wang, Lixia; Justić, Dubravko

    2009-06-01

    The physical processes affecting the development of seasonal hypoxia over the Louisiana-Texas shelf were examined using a high-resolution, three-dimensional, unstructured-grid, Finite Volume Coastal Ocean Model (FVCOM). The model was forced with the observed freshwater fluxes from the Mississippi and Atchafalaya Rivers, surface winds, heat fluxes, tides and offshore conditions. The simulations were carried out over a six-month period, from April to September 2002, and the model performance was evaluated against several independent series of observations that included tidal gauge data, Acoustic Doppler Current Profiler (ADCP) data, shipboard measurements of temperature and salinity, vertical salinity and sigma-t profiles, and satellite imagery. The model accurately described the offshore circulation mode generated over the Louisiana-Texas shelf by the westerly winds during summer months, as well as the prevalent westward flow along the coast caused by the easterly winds during the rest of the study period. The seasonal cycle of stratification also was well represented by the model. During 2002, the stratification was initiated in early spring and subsequently enhanced by the intensity and phasing of riverine freshwater discharges. Strong stratification persisted throughout the summer and was finally broken down in September by tropical storms. The model simulations also revealed a quasi-permanent anticyclonic gyre in the Louisiana Bight region formed by the rotational transformation of the Mississippi River plume, whose existence during 2002 was supported by the satellite imagery and ADCP current measurements. Model simulations support the conclusion that local wind forcing and buoyancy flux resulting from riverine freshwater discharges were the dominant mechanisms affecting the circulation and stratification over the inner Louisiana-Texas shelf.

  20. Ecological concerns following Superstorm Sandy: stressor level and recreational activity levels affect perceptions of ecosystem

    PubMed Central

    2015-01-01

    Coastal habitats are vulnerable to storms, and with increasing urbanization, sea level rise, and storm frequency, some urban populations are at risk. This study examined perceptions of respondents in coastal and central New Jersey to Superstorm Sandy, including: 1) concerns about ecological resources and effects (open-ended question), 2) information sources for ecology of the coast (open-ended), and 3) ratings of a list of ecological services as a function of demographics, location (coastal, central Jersey), stressor level (power outages, high winds, flooding) and recreational rates. “Wildlife” and “fish” were the ecological concerns mentioned most often, while beaches and dunes were most often mentioned for environmental concerns. Television, radio, and web/internet were sources trusted for ecological information. The data indicate 1) stressor level was a better predictor of ratings of ecological services than geographical location, but days engaged in recreation contributed the most to variations in ratings, 2) ecological services were rated the highest by respondents with the highest stressor levels, and by those from the coast, compared to others, 3) Caucasians rated ecological services higher than all others, and 4) recreational rates were highest for coastal respondents, and ratings for ecological services increased with recreational rates. Only 20 % of respondents listed specific ecological services as one of their three most important environmental concerns. These data will be useful for increasing preparedness, enhancing educational strategies for shore protection, and providing managers and public policy makers with data essential to developing resiliency strategies. PMID:27011729

  1. Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

    NASA Astrophysics Data System (ADS)

    Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

    2015-11-01

    resistin but not the circulating levels of visfatin. In view of the recent evidences about the involvement of adiponectin and resistin in the pathogenesis and progression of OA, the decrease of these adipokines after mud-bath therapy may play a protective role in the course of the disease. However, it remains to be clarified which of the mechanisms of action of MBT may have determined the changes in serum levels of adiponectin and resistin that we observed.

  2. Circulating CD36 and oxLDL levels are associated with cardiovascular risk factors in young subjects

    PubMed Central

    2014-01-01

    Background Cardiovascular disease (CVD) results from a combination of abnormalities in lipoprotein metabolism, oxidative stress, chronic inflammation, and susceptibility to thrombosis. Atherosclerosis is the major cause of CVD. CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its capacity to bind and promote endocytosis of oxidized low-density lipoprotein (oxLDL) and is implicated in the formation of foam cells. The purpose of this research was to evaluate whether there is an association of sCD36 and oxLDL levels with cardiovascular risk factors in young subjects. Methods A total of 188 subjects, 18 to 25 years old, 133 normal-weight and 55 obese subjects from the state of Guerrero, Mexico were recruited in the study. The lipid profile and glucose levels were measured by enzymatic colorimetric assays. Enzyme-linked immunosorbant assays (ELISA) for oxLDL and sCD36 were performed. Statistical analyses of data were performed with Wilcoxon- Mann Whitney and chi-square tests as well as with multinomial regression. Results TC, LDL-C, TG, oxLDL and sCD36 levels were higher in obese subjects than in normal-weight controls, as well as, monocyte and platelet counts (P < 0.05). Obese subjects had 5.8 times higher risk of sCD36 in the third tertil (>97.8 ng/mL) than normal-weight controls (P = 0.014), and 7.4 times higher risk of oxLDL levels in third tertile (>48 U/L) than control group. The subjects with hypercholesterolemia, hypertriglyceridemia, fasting impaired LDL-C had a higher risk of oxLDL levels in the third tertile (>48 U/L) than the control group (P < 0.05). Conclusions Circulating CD36 and oxLDL levels are associated with cardiovascular risk factors in young subjects and may be potential early markers for cardiovascular disease (CVD). PMID:24766787

  3. A Python Implementation of an Intermediate-Level Tropical Circulation Model and Implications for How Modeling Science is Done

    NASA Astrophysics Data System (ADS)

    Lin, J. W. B.

    2015-12-01

    Historically, climate models have been developed incrementally and in compiled languages like Fortran. While the use of legacy compiledlanguages results in fast, time-tested code, the resulting model is limited in its modularity and cannot take advantage of functionalityavailable with modern computer languages. Here we describe an effort at using the open-source, object-oriented language Pythonto create more flexible climate models: the package qtcm, a Python implementation of the intermediate-level Neelin-Zeng Quasi-Equilibrium Tropical Circulation model (QTCM1) of the atmosphere. The qtcm package retains the core numerics of QTCM1, written in Fortran, to optimize model performance but uses Python structures and utilities to wrap the QTCM1 Fortran routines and manage model execution. The resulting "mixed language" modeling package allows order and choice of subroutine execution to be altered at run time, and model analysis and visualization to be integrated in interactively with model execution at run time. This flexibility facilitates more complex scientific analysis using less complex code than would be possible using traditional languages alone and provides tools to transform the traditional "formulate hypothesis → write and test code → run model → analyze results" sequence into a feedback loop that can be executed automatically by the computer.

  4. Circulating levels of prolactin and progesterone in a wild population of red kangaroos (Macropus rufus) Marsupialia: Macropodidae

    USGS Publications Warehouse

    Muths, E.; Hinds, L. A.

    1996-01-01

    Circulating progesterone and prolactin levels were measured in shot and live-caught wild red kangaroos using radioimmunoassays validated for the red kangaroo. The objective of the study was to correlate hormone profiles with reproductive status and determine if red kangaroos follow the general pattern elucidated for other macropodids. During Phase 2a lactation (<70 days) plasma progesterone concentrations were <189 pg/ml (n= 41). This value increased to >600 pg/ml (n= 32) during the transition to Phase 3 lactation (181 to 235 days) when the quiescent corpus luteum and embryo were reactivated. Progesterone concentrations then decreased to <300 pg/ml (n= 29) during dual lactation when females were suckling a neonate and a young at foot. Concentrations of prolactin during Phase 2a were <6 ng/ml (n= 17). Coincident with the period of reactivation of the diapausing blastocyst (181 to 235 days), plasma prolactin concentrations increased to 15 ng/ml (n= 32), then decreased and remained low through the subsequent stage of dual lactation. These results indicate that progesterone and prolactin profiles in wild red kangaroos follow patterns found previously in other macropodid species, the tammar and Bennett's wallabies.

  5. Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

    PubMed Central

    2012-01-01

    Background and aim We tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs), angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control. Methods 8-week-old C57BL/6J mice (n = 27) were equally divided into group 1 (fed with 22-week control diet), group 2 (22-week high fat diet), and group 3 (14-week high fat diet, followed by 8-week control diet). Critical limb ischemia (CLI) was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks. Results Heart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p < 0.001). The numbers of circulating EPCs (C-kit/CD31+, Sca-1/KDR + and CXCR4/CD34+) were lower in groups 1 and 2 than in group 3 at 18 h after CLI induction (p < 0.03). The numbers of differentiated EPCs (C-kit/CD31+, CXCR4/CD34+ and CD133+) from adipose tissue after 14-day cultivation were also lowest in group 2 (p < 0.001). Protein expressions of VCAM-1, oxidative index, Smad3, and TGF-β were higher, whereas the Smad1/5 and BMP-2, mitochondrial cytochrome-C SDF-1α and CXCR4 were lower in group 2 than in groups 1 and 3 (all p < 0.02). Immunofluorescent staining of CD31+ and vWF + cells, the number of small vessel (<15 μm), and blood flow through Laser Doppler scanning of ischemic area were lower in group 2 compared to groups 1 and 3 on day 14 after CLI induction (all p < 0.001). Conclusion Obesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control. PMID:22568992

  6. Levels of circulating homocysteine, vitamin B6, vitamin B12, and folate in different types of open-angle glaucoma

    PubMed Central

    Turgut, Burak; Kaya, Murat; Arslan, Sermal; Demir, Tamer; Güler, Mete; Kaya, Mehmet Kaan

    2010-01-01

    Objective: To compare the levels of plasma homocysteine (Hcy), vitamin B6 (vit-B6), serum vitamin B12 (vit-B12), and folate in healthy individuals and in patients with normal tension glaucoma (NTG), pseudoexfoliative glaucoma (PXG), or primary open-angle glaucoma (POAG). Study design: A prospective controlled trial. Participants and methods: Forty healthy subjects, 48 patients with NTG, 38 patients with PXG, and 34 patients with POAG were included in the study. Those who used vitamin supplements or medications affecting Hcy and vitamin levels were excluded from the study. The levels of Hcy and vit-B6 were measured by High Performance Liquid Chromatography (HPLC). The levels of serum vit-B12 and folic acid were measured by competitive chemiluminescent enzyme immunoassay (CEI). One-way analysis if variance (ANOVA), analysis of covariance (ANCOVA), and the Tukey honestly significant difference test were used for statistical analysis. Results: The mean Hcy level of the PXG group was 15.46 ± 9.27 μmol/L which was significantly higher (P = 0.03) than that of the control group. There were no statistical differences in serum vit-B12 and folate levels among control subjects and NTG, PXG and POAG groups (P > 0.05). It was found that the mean plasma vit-B6 level was significantly higher in subjects with NTG (P = 0.03) and POAG (P = 0.025) versus controls. Mean vit-B6 levels in NTG and POAG were 30.50 ± 11.29 μg/L and 30 ± 12.15 μg/L, respectively. Conclusions: The plasma level of Hcy was found to be increased only in PXG patients and the plasma levels of vit-B6 were found to increase in the NTG and POAG sample groups. Using homocysteine and vit-B6 levels as the determinants of hyperhomocysteinemia still needs further research. PMID:20458351

  7. The effects of graded levels of calorie restriction: II. Impact of short term calorie and protein restriction on circulating hormone levels, glucose homeostasis and oxidative stress in male C57BL/6 mice

    PubMed Central

    Mitchell, Sharon E.; Delville, Camille; Konstantopedos, Penelope; Hurst, Jane; Derous, Davina; Green, Cara; Chen, Luonan; Han, Jackie J.D.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Douglas, Alex; Speakman, John R.

    2015-01-01

    Limiting food intake attenuates many of the deleterious effects of aging, impacting upon healthspan and leading to an increased lifespan. Whether it is the overall restriction of calories (calorie restriction: CR) or the incidental reduction in macronutrients such as protein (protein restriction: PR) that mediate these effects is unclear. The impact of 3 month CR or PR, (10 to 40%), on C57BL/6 mice was compared to controls fed ad libitum. Reductions in circulating leptin, tumor necrosis factor-α and insulin-like growth factor-1 (IGF-1) were relative to the level of CR and individually associated with morphological changes but remained unchanged following PR. Glucose tolerance and insulin sensitivity were improved following CR but not affected by PR. There was no indication that CR had an effect on oxidative damage, however CR lowered antioxidant activity. No biomarkers of oxidative stress were altered by PR. CR significantly reduced levels of major urinary proteins suggesting lowered investment in reproduction. Results here support the idea that reduced adipokine levels, improved insulin/IGF-1 signaling and reduced reproductive investment play important roles in the beneficial effects of CR while, in the short-term, attenuation of oxidative damage is not applicable. None of the positive effects were replicated with PR. PMID:26061745

  8. Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression

    PubMed Central

    2011-01-01

    Background As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. Methods The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Results Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Conclusion Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression. PMID:21211028

  9. Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure☆

    PubMed Central

    Asselin, Caroline; Ducharme, Anique; Ntimbane, Thierry; Ruiz, Matthieu; Fortier, Annik; Guertin, Marie-Claude; Lavoie, Joël; Diaz, Ariel; Levy, Émile; Tardif, Jean-Claude; Des Rosiers, Christine

    2013-01-01

    Objective Measurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA). Methods and results Circulating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R2=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only. Conclusion Results from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts. PMID:24494189

  10. Low levels of circulating T-regulatory lymphocytes and short cervical length are associated with preterm labor.

    PubMed

    Koucký, Michal; Malíčková, Karin; Cindrová-Davies, Tereza; Germanová, Anna; Pařízek, Antonín; Kalousová, Marta; Hájek, Zdeněk; Zima, Tomáš

    2014-12-01

    Recent discoveries suggest that T-regulatory lymphocytes (Treg) might play an important role in the pathophysiology of preterm labor. The aim of this study was to assess the relationship among the levels of maternal circulating Treg cells, uterine cervical length, and the risk of preterm labor. Sixty women with regular contractions and/or cervical incompetence at 24-32 weeks' gestation were recruited into a prospective study. Each patient underwent transvaginal ultrasound examination of the cervical length, and regulatory T cells were quantified in peripheral blood samples by flow cytometry. Patients with cervical incompetence were prescribed vaginal progesterone until birth. Measurements of Treg levels and cervical length correlated with the timing of labor. The risk of preterm labor happening within 48 h of testing was demonstrated to be almost 35 times higher (OR=35.21, CI 13.3; 214, p<0.001) in the group with simultaneously low Treg values (<0.031 × 10(9)/L) and a shortened uterine cervix (<17.5mm), compared with the situation where both of these values were normal. Similar results were found in predicting preterm delivery before 34 weeks, or between 34 and 37 weeks. A statistically nonsignificant trend toward increased cervical length and increased Treg count was noted in the women on progesterone treatment. We show for the first time that the combined assessment of Treg cell count and cervical length is a much better predictor of preterm delivery than either parameter used on its own. This combined approach may offer clinical application in patients who present with risk factors for preterm labor. PMID:24855050

  11. Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study

    PubMed Central

    Guo, Ming-ming; Duan, Xue-ning; Cui, Shu-de; Tian, Fu-guo; Cao, Xu-chen; Geng, Cui-zhi; Fan, Zhi-min; Wang, Xiang; Wang, Shu; Jiang, Hong-chuan; Zhang, Jian-guo; Jin, Feng; Tang, Jin-hai; Liang, Hong; Yang, Zhen-lin; Wang, Hai-bo; Wang, Qi-tang; Li, Guo-lou; Li, Liang; Zhu, Shi-guang; Zuo, Wen-shu; Liu, Li-yuan; Wang, Lu; Ma, Dan-dan; Liu, Shu-chen; Xiang, Yu-juan; Liu, Lu; Ye, Chun-miao; Zhou, Wen-zhong; Wang, Fei; Yu, Li-xiang; Ma, Zhong-bing; Yu, Zhi-gang

    2015-01-01

    The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed. PMID:26070203

  12. Exploring Factors Affecting Girls' Education at Secondary Level: A Case of Karak District, Pakistan

    ERIC Educational Resources Information Center

    Suleman, Qaiser; Aslam, Hassan Danial; Habib, Muhammad Badar; Yasmeen, Kausar; Jalalian, Mehrdad; Akhtar, Zaitoon; Akhtar, Basreen

    2015-01-01

    The study examined the factors that affect girls' education at secondary school level in Karak District, Khyber Pakhtunkhwa (Pakistan). All the female heads, teachers and students serving and studying at secondary school level in Karak District constituted the population of the study. The study was delimited to only 30 girls' secondary schools in…

  13. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance

    PubMed Central

    Sayers, Sophie R.; Reimann, Frank; Gribble, Fiona M.; Parker, Helen; Zac-Varghese, Sagen; Bloom, Stephen R.; Foretz, Marc; Viollet, Benoit; Rutter, Guy A.

    2016-01-01

    Background Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1) in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK) in these cells. Method Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre) to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay. Results Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01) in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01) and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01) GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01). Conclusion AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes. PMID:27010458

  14. The Reduction in Circulating Melatonin Level May Contribute to the Pathogenesis of Ovarian Cancer: A Retrospective Study

    PubMed Central

    Zhao, Min; Wan, Jiayi; Zeng, Ke; Tong, Mancy; Lee, Arier C; Ding, Jinxin; Chen, Qi

    2016-01-01

    Ovarian cancer is the third most common gynaecological malignancy. Changes in circadian rhythms such as bright light exposure may affect female reproductive physiology. Night shift work is associated with higher risks of developing gynaecological cancers. In addition, the season of birth is also suggested as an important environmental risk factor for developing gynaecological cancers. Melatonin may play an important role in this association as a marker of circadian rhythms. Serum from 96 women with ovarian cancer and 40 healthy women were collected and the level of melatonin was measured. In addition 277 women with ovarian cancer and 1076 controls were retrospectively collected for season of birth analysis over seven years. The serum levels of melatonin were significantly lower in women with ovarian cancer compared with healthy women (p<0.05). However there was no difference in melatonin levels in perimenopausal and postmenopausal patients. In addition, there is no statistically significant difference in seasonal distribution of birth between ovarian cancer patients and the control group. The melatonin levels in ovarian cancer patients and controls were not associated with the season of birth. Our results demonstrate the lower serum levels of melatonin in ovarian cancer patients which may contribute to the pathogenesis of ovarian cancer. The incidence of ovarian cancer was not associated with the season of birth. The serum levels of melatonin do not appear to be associated with season of birth in ovarian cancer patients. PMID:27162542

  15. The Reduction in Circulating Melatonin Level May Contribute to the Pathogenesis of Ovarian Cancer: A Retrospective Study.

    PubMed

    Zhao, Min; Wan, Jiayi; Zeng, Ke; Tong, Mancy; Lee, Arier C; Ding, Jinxin; Chen, Qi

    2016-01-01

    Ovarian cancer is the third most common gynaecological malignancy. Changes in circadian rhythms such as bright light exposure may affect female reproductive physiology. Night shift work is associated with higher risks of developing gynaecological cancers. In addition, the season of birth is also suggested as an important environmental risk factor for developing gynaecological cancers. Melatonin may play an important role in this association as a marker of circadian rhythms. Serum from 96 women with ovarian cancer and 40 healthy women were collected and the level of melatonin was measured. In addition 277 women with ovarian cancer and 1076 controls were retrospectively collected for season of birth analysis over seven years. The serum levels of melatonin were significantly lower in women with ovarian cancer compared with healthy women (p<0.05). However there was no difference in melatonin levels in perimenopausal and postmenopausal patients. In addition, there is no statistically significant difference in seasonal distribution of birth between ovarian cancer patients and the control group. The melatonin levels in ovarian cancer patients and controls were not associated with the season of birth. Our results demonstrate the lower serum levels of melatonin in ovarian cancer patients which may contribute to the pathogenesis of ovarian cancer. The incidence of ovarian cancer was not associated with the season of birth. The serum levels of melatonin do not appear to be associated with season of birth in ovarian cancer patients. PMID:27162542

  16. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD.

    PubMed

    Rabinovich, Roberto A; Miller, Bruce E; Wrobel, Karolina; Ranjit, Kareshma; Williams, Michelle C; Drost, Ellen; Edwards, Lisa D; Lomas, David A; Rennard, Stephen I; Agustí, Alvar; Tal-Singer, Ruth; Vestbo, Jørgen; Wouters, Emiel F M; John, Michelle; van Beek, Edwin J R; Murchison, John T; Bolton, Charlotte E; MacNee, William; Huang, Jeffrey T J

    2016-05-01

    Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD. PMID:27009168

  17. Relation between ticagrelor response and levels of circulating reticulated platelets in patients with non-ST elevation acute coronary syndromes.

    PubMed

    Vaduganathan, Muthiah; Zemer-Wassercug, Noa; Rechavia, Eldad; Lerman-Shivek, Hila; Perl, Leor; Leshem-Lev, Dorit; Orvin, Katia; Kornowski, Ran; Lev, Eli I

    2015-08-01

    Antiplatelet responses to clopidogrel and prasugrel are highly variable and subject to significant rates of high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI). The proportion of circulating young reticulated platelets (RPs) inversely correlates with responsiveness to both agents. We aimed to determine the relationship between RPs and on-treatment platelet reactivity in ticagrelor-treated patients. Patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI and ticagrelor were tested for platelet reactivity using the VerifyNow P2Y12 assay and multiplate aggregometry. RPs levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2-4 and 30 days post-PCI. Fifty three patients were included (mean age 62.6 ± 9.8 years, 18.9 % women, 35.8 % diabetes), of which 41 patients (77 %) completed follow-up. Variability in response to ticagrelor was very low according to both assays with no identified cases of HTPR at either time-point. In addition, there were no differences in platelet reactivity, as analyzed by the VerifyNow P2Y12 assay, or in the proportion of RPs between the two time points (p > 0.5). With the multiplate assay, platelet reactivity increased between the two time-points (8.6 ± 6.0 vs. 15.5 ± 11 AU*min; p = 0.0007). There was no significant correlation between RPs and platelet reactivity at both time-points and using both assays (p > 0.5). There were no cases of HTPR up to 30-days post-PCI in patients with NSTE-ACS treated with ticagrelor. In this cohort, no correlation between % RPs and platelet reactivity was observed. Attenuation of RP-induced platelet reactivity as a novel mechanism for ticagrelor's benefit requires further investigation. PMID:25631351

  18. Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-β and TNF-α.

    PubMed

    Lemini, María; Ruiz-Herrera, Xarubet; Ledesma-Colunga, María G; Díaz-Lezama, Nundehui; De Los Ríos, Ericka A; López-Barrera, Fernando; Méndez, Isabel; Martínez de la Escalera, Gonzalo; Macotela, Yazmín; Clapp, Carmen

    2015-05-01

    The levels of the hormone prolactin (PRL) are reduced in the circulation of patients with Type 2 diabetes and in obese children, and lower systemic PRL levels correlate with an increased prevalence of diabetes and a higher risk of metabolic syndrome. The secretion of anterior pituitary (AP) PRL in metabolic diseases may be influenced by the interplay between transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α), which inhibit and can stimulate AP PRL synthesis, respectively, and are known contributors to insulin resistance and metabolic complications. Here, we show that TGF-β and TNF-α antagonize the effect of each other on the expression and release of PRL by the GH4C1 lactotrope cell line. The levels of AP mRNA and circulating PRL decrease in high-fat diet-induced obese rats in parallel with increased and reduced AP levels of TGF-β and TNF-α mRNA, respectively. Likewise, AP expression and circulating levels of PRL are reduced in streptozotocin-induced diabetic rats and are associated with higher AP expression and protein levels of TGF-β and TNF-α. The opposing effects of the two cytokines on cultured AP cells, together with their altered expression in the AP of obese and diabetic rats suggest they are linked to the reduced PRL production and secretion characteristics of metabolic diseases. PMID:25715833

  19. The effect of non-starch polysaccharide supplementation on circulating bile acids, hormone and metabolite levels following a fat meal in human subjects.

    PubMed

    Morgan, L M; Tredger, J A; Shavila, Y; Travis, J S; Wright, J

    1993-09-01

    The effects of guar gum, sugar-beet fibre (SBF) and wheat bran supplementation of a high-fat test meal were compared with an NSP-free control meal and a meal containing an equivalent amount of the ion-exchange resin cholestyramine in healthy non-obese human volunteers. Their effects on gastric emptying, postprandial circulating bile acids, triacylglycerols and gastrointestinal hormone levels were studied. The in vitro binding of NSP and cholestyramine to [1-14C]glycocholic acid was measured and compared with their in vivo effect. Guar gum and cholestyramine supplementation significantly lowered circulating postprandial bile acid, triacylglycerol and gastric inhibitory polypeptide concentrations, but sugar-beet fibre and wheat bran were without effect. Liquid gastric emptying, as assessed by circulating paracetamol levels, was slightly accelerated in the guar gum-supplemented meal. Glycocholic acid bound strongly to the insoluble fraction of cholestyramine and the soluble fraction of guar gum. The insoluble fractions of SBF and wheat bran bound only small quantities of glycocholate; no bile acid binding was detected in the soluble fractions of these NSP. The study demonstrates that measurement of postprandial bile acids enables an indirect measurement to be made of bile acid binding to NSP in vivo. The results support the hypothesis that the hypocholesterolaemic action of guar gum is largely mediated via interruption of the enterohepatic bile acid circulation, but indicate that the hypocholesterolaemic action of SBF is mediated by another mechanism. PMID:8260476

  20. Pre-pubertal stress exposure affects adult behavioral response in association with changes in circulating corticosterone and brain-derived neurotrophic factor.

    PubMed

    Bazak, Noam; Kozlovsky, Nitsan; Kaplan, Zeev; Matar, Michael; Golan, Hava; Zohar, Joseph; Richter-Levin, Gal; Cohen, Hagit

    2009-07-01

    Early-life stress produces a cascade of neurobiological events that cause enduring changes in neural plasticity and synaptic efficacy that appear to play pivotal roles in the pathophysiology of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has been implicated in the neurobiological mechanisms of these changes, in interaction with components of the stress response, such as corticosterone. This study examined the consequences of juvenile stress for behavior during adulthood in association with circulating corticosterone levels and BDNF expression. The experiments examined single exposure to predator scent stress (soiled cat litter for 10 min) as compared to repeated exposure, early in life and later on. Behavioral responses were assessed in the elevated plus maze and the acoustic startle response paradigms at 28, 60 and 90 days of age. Plasma corticosterone was measured and brain areas analyzed for BDNF levels. The results show that juvenile stress exposure increased anxiety-like behavior and startle amplitude and decreased plasma corticosterone. This response was seen immediately after exposure and also long term. Adult stress exposure increased anxiety-like behavior, startle amplitude and plasma corticosterone. Exposure to both early and later life trauma elicited reduced levels of corticosterone following the initial exposure, which were not raised by re-exposure, and elicited significant downregulation of BDNF mRNA and protein levels in the hippocampus CA1 subregion. The consequences of adult stress exposure were more severe in rats were exposed to the same stressor as juveniles, indicated increased vulnerability. The results suggest that juvenile stress has resounding effects in adulthood reflected in behavioral responses. The concomitant changes in BDNF and corticosterone levels may mediate the changes in neural plasticity and synaptic functioning underlying clinical manifestations of PTSD. PMID:19181453

  1. Developmental coexposure to polychlorinated biphenyls and polybrominated diphenyl ethers has additive effects on circulating thyroxine levels in rats.

    PubMed

    Miller, Veronica M; Sanchez-Morrissey, Susana; Brosch, Karl O; Seegal, Richard F

    2012-05-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widespread environmental contaminants found in seafood and dairy products. PCBs and PBDEs are structurally similar chemicals and affect thyroid hormone function and behavior in children and laboratory rodents. Although coexposure frequently exists, the in vivo developmental effects of combined exposure to PCBs and PBDEs on thyroxine (T4) levels are unknown. We examined the effects of PCB and PBDE coexposure from gestational day 6 through postnatal day (p) 21, alone and in combination, on T4 levels in rat offspring. In males, exposure to PCBs and PBDEs at 1.7, 5, 10, 20, 40, and 60 μmol/kg/day induced equivalent and dose-dependent reductions in T4 from p 7 to p 21. Exposure to equimolar mixtures of PCBs and PBDEs at 3.4, 10, 20, 40, and 80 μmol/kg/day additively reduced T4 from p 7 to p 21 in males. In a second series of experiments, we determined sex effects on the mixture exposures and found that coexposure to PCBs and PBDEs had similar additive effects on T4 levels in male and female offspring. This study demonstrates that equimolar exposure to PCBs and PBDEs induces similar reductions in T4 levels and that coexposure to a mixture of PCBs and PBDEs has additive effects on T4 levels. These thyroid hormone effects of coexposure to PCBs and PBDEs are important when considering the cumulative effects of coexposure to multiple environmental thyroid hormone-disrupting agents in risk assessment for developmental disorders. PMID:22345314

  2. Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients

    PubMed Central

    Cattin, Sarah; Fellay, Benoît; Pradervand, Sylvain; Trojan, Andreas; Ruhstaller, Thomas

    2016-01-01

    Background Whether bevacizumab exerts its anti-tumor properties through systemic effects beyond local inhibition of angiogenesis and how these effects can be monitored in patients, remain largely elusive. To address these questions, we investigated bone marrow-derived cells and cytokines in the peripheral blood of metastatic breast cancer patients undergoing therapy with bevacizumab. Methods Circulating endothelial cells (CEC), circulating endothelial progenitor (CEP) and circulating CD11b+ cells in metastatic breast cancer patients before and during therapy with paclitaxel alone (n = 11) or in combination with bevacizumab (n = 10) were characterized using flow cytometry, real time PCR and RNASeq. Circulating factors were measured by ELISA. Aged-matched healthy donors were used as baseline controls (n = 12). Results Breast cancer patients had elevated frequencies of CEC, CEP, TIE2+CD11b+ and KIT+CD11b+ cell subsets. CEC decreased during therapy, irrespective of bevacizumab, while TIE2+CD11b+ remained unchanged. KIT+CD11b+ cells decreased in response to paclitaxel with bevacizumab, but not paclitaxel alone. Cancer patients expressed higher mRNA levels of the M2 polarization markers CD163, ARG1 and IL-10 in CD11b+ cells and increased levels of the M2 cytokines IL-10 and CCL20 in plasma. M1 activation markers and cytokines were low or equally expressed in cancer patients compared to healthy donors. Chemotherapy with paclitaxel and bevacizumab, but not with paclitaxel alone, significantly decreased IL-10 mRNA in CD11b+ cells and IL-10 protein in plasma. Conclusions This pilot study provides evidence of systemic immunomodulatory effects of bevacizumab and identified circulating KIT+CD11b+ cells and IL-10 as candidate biomarkers of bevacizumab activity in metastatic breast cancer patients. PMID:26840567

  3. Basic Factors that Affect General Academic Motivation Levels of Candidate Preschool Teachers

    ERIC Educational Resources Information Center

    Celikoz, Nadir

    2010-01-01

    The purpose of this study is to investigate some personal and familial factors that affect overall academic motivation levels of candidate preschool teachers. The study group of this research consists of 285 students attending the child development and preschool education department at Selcuk University Faculty of Vocational Education in the…

  4. Affective, Normative, and Continuance Commitment Levels across Cultures: A Meta-Analysis

    ERIC Educational Resources Information Center

    Meyer, John P.; Stanley, David J.; Jackson, Timothy A.; McInnis, Kate J.; Maltin, Elyse R.; Sheppard, Leah

    2012-01-01

    With increasing globalization of business and diversity within the workplace, there has been growing interest in cultural differences in employee commitment. We used meta-analysis to compute mean levels of affective (AC; K=966, N=433,129), continuance (CC; K=428, N=199,831), and normative (NC; K=336, N=133,277) organizational commitment for as…

  5. Neutral models as a way to evaluate the Sea Level Affecting Marshes Model (SLAMM)

    EPA Science Inventory

    A commonly used landscape model to simulate wetland change – the Sea Level Affecting Marshes Model(SLAMM) – has rarely been explicitly assessed for its prediction accuracy. Here, we evaluated this model using recently proposed neutral models – including the random constraint matc...

  6. Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome.

    PubMed

    Berezin, Alexander E; Kremzer, Alexander A; Berezina, Tatyana A; Martovitskaya, Yulia V; Gronenko, Elena A

    2016-09-01

    Metabolic syndrome (MetS) is defined as cluster of multiple metabolic and cardiovascular (CV) abnormalities included abdominal obesity, high-normal blood pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has a growing prevalence worldwide. We investigated whether an elevated level of osteoprotegerin (OPG) predicts imbalance between different phenotypes of circulating endothelial (EPCs) and mononuclear (MPCs) progenitor cells in MetS patients. We have analyzed data regarding dysmetabolic disorder subjects without known CV disease), as well as with known type two diabetes mellitus. All patients have given their informed written consent for participation in the study. This article contains data on the independent predictors of depletion in numerous of circulating EPCs and MPCs in MetS patients. The data are supplemental to our original research article describing detailed associations of elevated OPG level in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk factors. PMID:27508223

  7. Common-Mode Circulating Current Control of Paralleled Interleaved Three-Phase Two-Level Voltage-Source Converters With Discontinuous Space-Vector Modulation

    SciTech Connect

    Zhang, Di; Wang, Fei; Burgos, Rolando; Boroyevich, Dushan

    2011-01-01

    This paper presents a control method to limit the common-mode (CM) circulating current between paralleled three-phase two-level voltage-source converters (VSCs) with discontinuous space-vector pulsewidth modulation (DPWM) and interleaved switching cycles. This CM circulating current can be separated into two separate components based on their frequency; the high-frequency component, close to the switching frequency, can be effectively limited by means of passive components; the low-frequency component, close to the fundamental frequency, embodies the jumping CM circulating current observed in parallel VSCs. This is the main reason why it is usually recommended not to implement discontinuous and interleaving PWM together. The origin of this low-frequency circulating current is analyzed in detail, and based on this, a method to eliminate its presence is proposed by impeding the simultaneous use of different zero vectors between the converters. This control method only requires six additional switching actions per line cycle, presenting a minimum impact on the converter thermal design. The analysis and the feasibility of the control method are verified by simulation and experimental results.

  8. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes

    PubMed Central

    Liao, Xin; Wang, Xuemei; Li, Haopeng; Li, Ling; Zhang, Guohao; Yang, Mengliu; Yuan, Lei; Liu, Hua; Yang, Gangyi; Gao, Lin

    2016-01-01

    ZAG has recently been characterized as a potent metabolic regulator, but the effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162 subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight, FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C was significantly increased. Importantly, circulating ZAG and ADI levels in these patients were also significantly increased after DAPA therapy. Basal ZAG levels were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post-treatment, whereas basal ADI levels were associated with changes in FAT%, TC, HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression and secretion in HepG2 cells. When combined with a PPAR-γinhibitor GW9662, the effect of DAPA on ZAG was abrogated. These findings suggest that circulating ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of ZAG in the liver via the activation of PPAR-γ. The changes in ZAG induced by DAPA may play a physiologic role in enhancing insulin sensitivity. PMID:27611858

  9. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes.

    PubMed

    Liao, Xin; Wang, Xuemei; Li, Haopeng; Li, Ling; Zhang, Guohao; Yang, Mengliu; Yuan, Lei; Liu, Hua; Yang, Gangyi; Gao, Lin

    2016-01-01

    ZAG has recently been characterized as a potent metabolic regulator, but the effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162 subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight, FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C was significantly increased. Importantly, circulating ZAG and ADI levels in these patients were also significantly increased after DAPA therapy. Basal ZAG levels were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post-treatment, whereas basal ADI levels were associated with changes in FAT%, TC, HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression and secretion in HepG2 cells. When combined with a PPAR-γinhibitor GW9662, the effect of DAPA on ZAG was abrogated. These findings suggest that circulating ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of ZAG in the liver via the activation of PPAR-γ. The changes in ZAG induced by DAPA may play a physiologic role in enhancing insulin sensitivity. PMID:27611858

  10. Changes in Dietary Fat Content Rapidly Alters the Mouse Plasma Coagulation Profile without Affecting Relative Transcript Levels of Coagulation Factors

    PubMed Central

    van Diepen, Janna A.; Verhoef, Daniël; Voshol, Peter J.; Reitsma, Pieter H.; van Vlijmen, Bart J. M.

    2015-01-01

    Background Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events. Objective Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of coagulation factors as well as its relation to changes in metabolic and inflammatory parameters. Methods Male C57BL/6J mice were fed a low fat (10% kcal as fat; LFD) or high fat diet (45% kcal as fat; HFD) for 2, 4, 8 or 16 weeks. To study the effects of weight loss, mice were fed the HFD for 16 weeks and switched to the LFD for 1, 2 or 4 weeks. For each time point analyses of plasma and hepatic mRNA levels of coagulation factors were performed after overnight fasting, as well as measurements of circulating metabolic and inflammatory parameters. Furthermore, in vivo clearance rates of human factor (F) VII, FVIII and FIX proteins were determined after 2 weeks of HFD-feeding. Results HFD feeding gradually increased the body and liver weight, which was accompanied by a significant increase in plasma glucose levels from 8 weeks onwards, while insulin levels were affected after 16 weeks. Besides a transient rise in cytokine levels at 2 weeks after starting the HFD, no significant effect on inflammation markers was present. Increased plasma levels of fibrinogen, FII, FVII, FVIII, FIX, FXI and FXII were observed in mice on a HFD for 2 weeks, which in general persisted throughout the 16 weeks of HFD-feeding. Interestingly, with the exception of FXI the effects on plasma coagulation levels were not paralleled by changes in relative transcript levels in the liver, nor by decreased clearance rates. Switching from HFD to LFD reversed the HFD-induced procoagulant shift in plasma, again not coinciding with transcriptional modulation. Conclusions Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby

  11. Effect of fasting during Ramadan on serum lithium level and mental state in bipolar affective disorder.

    PubMed

    Farooq, Saeed; Nazar, Zahid; Akhtar, Javaid; Akhter, Javed; Irfan, Muhammad; Irafn, Mohammad; Subhan, Fazal; Ahmed, Zia; Khan, Ejaz Hassan; Khatak, Ijaz Hassan; Naeem, Farooq

    2010-11-01

    The Muslims fast every year during the month of Ramadan. A fasting day can last 12-17 h. The effects of fasting on serum lithium levels and the mood changes in patients suffering from bipolar affective disorder during Ramadan are not well studied. We aimed to compare the serum lithium levels, side effects, toxicity and mental state in patients suffering from bipolar affective disorder and on prophylactic lithium therapy before, during and after Ramadan. Sixty-two patients meeting the International Classification of Diseases, Tenth Revision, Research Diagnostic Criteria of bipolar affective disorder receiving lithium treatment for prophylaxis were recruited in a tertiary care teaching hospital in Peshawar, Pakistan. Serum lithium, electrolytes, Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were assessed at three points, 1 week before Ramadan, midRamadan and 1 week after Ramadan. The side effects and toxicity were measured by a symptoms and signs checklist. There was no significant difference in mean serum lithium levels at three time points (preRamadan=0.45±0.21, midRamadan=0.51±0.20 and postRamadan=0.44±0.23 milli equivalents/litre, P=0.116). The scores on HDRS and YMRS showed significant decrease during Ramadan (F=34.12, P=0.00, for HDRS and F=15.6, P=0.000 for YMRS). The side effects and toxicity also did not differ significantly at three points. In conclusion, the patients who have stable mental state and lithium levels before Ramadan can be maintained on lithium during Ramadan. Fasting in an average temperature of 28°C for up to 12 h per day did not result in elevated serum lithium levels or more side effects and did not have adverse effects on mental state of patients suffering from bipolar affective disorder. PMID:20827213

  12. The role of particular tick developmental stages in the circulation of tick-borne pathogens affecting humans in Central Europe. 1. The general pattern.

    PubMed

    Karbowiak, Grzegorz; Biernat, Beata; Szewczyk, Tomasz; Sytykiewicz, Hubert

    2015-01-01

    Tick-borne pathogens are common in the natural environment, but their occurrence has a focal character. They occur in the natural environment in the form of the enzootic sources of infection. The general components include the animal reservoir, amplifiers and the efficient vector. However, the particular role of components can differ depending on the pathogen, the host range and possible transmission routes. Animal reservoir of pathogen are vertebrate animals, being the hosts of pathogens. In Europe these are small or medium-sized mammals and sometimes birds that feed on the ground. The competence of an animal reservoir is determined by the ability to communicate the infection; long-term persistence of the pathogen in the host; long-duration of infectivity of the animal for ticks; a sufficient number of animals in the endemic region. Amplifiers for ticks are artiodactyls. They are hosts for nymphs and adult ticks, thereby making it possible for ticks to propagate and maintain the proper size of their population. Efficient vector for pathogen are ticks. The first characteristic feature of efficient vectors is feeding duration exceeding 24 hours; the high density of the tick population. The conditions necessary to consider ticks as efficient vectors are met in Central Europe by the Ixodes ricinus, Dermacentor reticulatus and D. marginatus ticks. There are the general differences in biology between Ixodes persulcatus complex ticks and Dermacentor ticks, affecting their different role and ability in pathogens spreading - the range of hosts; the ability to inhabiting of various environments and resistance to unfavourable conditions; the duration of larvae and nymphs activity. The combination of tick's biology, pathogen ability to transmission, and mammal hosts' competence, determines the particular role of larvae, nymphs and adults in pathogen circulation in the natural environment, as well as transmission to new hosts. PMID:26878618

  13. Data on the circulating levels of endothelial microparticles are elevated in patients with bicuspid aortic valve and are related to aortic dilation.

    PubMed

    Alegret, Josep M; Martínez-Micaelo, Neus; Aragonès, Gerard; Beltrán-Debón, Raúl

    2016-09-01

    The data included here support the research article "Circulating endothelial microparticles are elevated in bicuspid aortic valve (BAV) disease and related to aortic dilation" (Alegret et al., 2016 [1]) where circulating levels of platelet endothelial cell adhesion molecule (PECAM(+)) endothelial microparticles (EMPs) were identified as a biological variable related to aortic dilation in patients with BAV disease. The data presented in this article are composed by four tables and one figure containing the clinical and echocardiographic characteristics of the patients (Alegret et al., 2016 [1]) included in this study, and summarize the results of multivariate linear analyses. Furthermore, is also included a figure showing a representative flow cytometry dot plots and histograms used in PECAM(+) EMPs quantification is also included. PMID:27453924

  14. Hypocalcemic focal seizures in a one-month-old infant of a mother with a low circulating level of vitamin D.

    PubMed

    Oki, J; Takedatsu, M; Itoh, J; Yano, K; Cho, K; Okuno, A

    1991-01-01

    We present a case of a one-month-old infant with hypocalcemia and rickets, with symptoms of focal seizures. The ictal EEG showed left occipital spikes spreading over all of the left hemisphere. From the laboratory studies, we concluded that a low maternal circulating level of vitamin D would cause infantile hypocalcemia and rickets, while immature renal response to parathyroid hormone and transient hypoparathyroidism in infancy would induce hyperphosphatemia. Hypocalcemia may be an important factor in the cause of focal seizures which start even after the age of one month. Further, investigation of maternal vitamin D levels should be done in infantile hypocalcemia. PMID:1892219

  15. The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood.

    PubMed

    Bosch-Panadero, Enrique; Mas, Sebastian; Sanchez-Ospina, Didier; Camarero, Vanesa; Pérez-Gómez, Maria V; Saez-Calero, Isabel; Abaigar, Pedro; Ortiz, Alberto; Egido, Jesus; González-Parra, Emilio

    2016-05-01

    Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/10(6) cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/10(6) cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis. PMID:26432902

  16. Analysis of factors affecting satisfaction level on problem based learning approach using structural equation modeling

    NASA Astrophysics Data System (ADS)

    Hussain, Nur Farahin Mee; Zahid, Zalina

    2014-12-01

    Nowadays, in the job market demand, graduates are expected not only to have higher performance in academic but they must also be excellent in soft skill. Problem-Based Learning (PBL) has a number of distinct advantages as a learning method as it can deliver graduates that will be highly prized by industry. This study attempts to determine the satisfaction level of engineering students on the PBL Approach and to evaluate their determinant factors. The Structural Equation Modeling (SEM) was used to investigate how the factors of Good Teaching Scale, Clear Goals, Student Assessment and Levels of Workload affected the student satisfaction towards PBL approach.

  17. Environmental noise levels affect the activity budget of the Florida manatee

    NASA Astrophysics Data System (ADS)

    Miksis-Olds, Jennifer L.; Donaghay, Percy L.; Miller, James H.; Tyack, Peter L.

    2005-09-01

    Manatees inhabit coastal bays, lagoons, and estuaries because they are dependent on the aquatic vegetation that grows in shallow waters. Food requirements force manatees to occupy the same areas in which human activities are the greatest. Noise produced from human activities has the potential to affect these animals by eliciting responses ranging from mild behavioral changes to extreme aversion. This study quantifies the behavioral responses of manatees to both changing levels of ambient noise and transient noise sources. Results indicate that elevated environmental noise levels do affect the overall activity budget of this species. The proportion of time manatees spend feeding, milling, and traveling in critical habitats changed as a function of noise level. More time was spent in the directed, goal-oriented behaviors of feeding and traveling, while less time was spent milling when noise levels were highest. The animals also responded to the transient noise of approaching vessels with changes in behavioral state and movements out of the geographical area. This suggests that manatees detect and respond to changes in environmental noise levels. Whether these changes legally constitute harassment and produce biologically significant effects need to be addressed with hypothesis-driven experiments and long-term monitoring. [For Animal Bioacoustics Best Student Paper Award.

  18. Sensitivity analysis of hydrogeological parameters affecting groundwater storage change caused by sea level rise

    NASA Astrophysics Data System (ADS)

    Shin, J.; Kim, K.-H.; Lee, K.-K.

    2012-04-01

    Sea level rise, which is one of the representative phenomena of climate changes caused by global warming, can affect groundwater system. The rising trend of the sea level caused by the global warming is reported to be about 3 mm/year for the most recent 10 year average (IPCC, 2007). The rate of sea level rise around the Korean peninsula is reported to be 2.30±2.22 mm/yr during the 1960-1999 period (Cho, 2002) and 2.16±1.77 mm/yr (Kim et al., 2009) during the 1968-2007 period. Both of these rates are faster than the 1.8±0.5 mm/yr global average for the similar 1961-2003 period (IPCC, 2007). In this study, we analyzed changes in the groundwater environment affected by the sea level rise by using an analytical methodology. We tried to find the most effective parameters of groundwater amount change in order to estimate the change in fresh water amount in coastal groundwater. A hypothetical island model of a cylindrical shape in considered. The groundwater storage change is bi-directional as the sea level rises according to the natural and hydrogeological conditions. Analysis of the computation results shows that topographic slope and hydraulic conductivity are the most sensitive factors. The contributions of the groundwater recharge rate and the thickness of aquifer below sea level are relatively less effective. In the island with steep seashore slopes larger than 1~2 degrees or so, the storage amount of fresh water in a coastal area increases as sea level rises. On the other hand, when sea level drops, the storage amount decreases. This is because the groundwater level also rises with the rising sea level in steep seashores. For relatively flat seashores, where the slope is smaller than around 1-2 degrees, the storage amount of coastal fresh water decreases when the sea level rises because the area flooded by the rising sea water is increased. The volume of aquifer fresh water in this circumstance is greatly reduced in proportion to the flooded area with the sea

  19. Waste and cost reduction using dual wall reverse circulation drilling with multi-level groundwater sampling for contaminant plume delineation

    SciTech Connect

    Smuin, D.R.

    1995-12-01

    This paper describes the drilling and sampling methods used to delineate a groundwater contaminant plume at the Paducah Gaseous Diffusion Plant (PGDP) during the Groundwater Monitoring IV characterization. The project was unique in that it relied upon dual wall reverse circulation drilling instead of the traditional hollow stem auger method. The Groundwater Monitoring program sought to characterize the boundaries, both vertically and horizontally, of the northeast plume which contains both {sup 99}Tc and trichloroethene. This paper discusses the strengths and weaknesses of the drilling method used by investigators.

  20. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

    PubMed Central

    Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

    2015-01-01

    Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001; n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis. PMID:26174087

  1. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

    NASA Astrophysics Data System (ADS)

    Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

    2015-07-01

    Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001 n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.

  2. Patterns of orographic uplift in the Sierra Nevada and their relationship to upper-level atmospheric circulation

    USGS Publications Warehouse

    Aguado, Edward; Cayan, Daniel R.; Reece, Brian D.; Riddle, Larry

    1993-01-01

    We examine monthly and seasonal patterns of precipitation across various elevations of the eastern Central Valley of California and the Sierra Nevada. A measure of the strength of the orographic effect called the “precipitation ratio” is calculated, and we separate months into four groups based on being wet or dry and having low or high precipitation ratios. Using monthly maps of mean 700-mb height anomalies, we describe the northern hemisphere mid-tropospheric circulation patterns associated with each of the four groups. Wet months are associated with negative height anomalies over the eastern Pacific, as expected. However, the orientation of the trough is different for years with high and low precipitation ratios. Wet months with high ratios typically have circulation patterns factoring a west-southwest to east-northeast storm track from around the Hawaiian Islands to the Pacific Northwest of the United States. Wet months with low precipitation ratios are associated with a trough centered near the Aleutians and a northwest to southeast storm track. Dry months are marked by anticyclones in the Pacific, but this feature is more localized to the eastern Pacific for months with low precipitation ratios than for those with high ratios. Using precipitation gauge and snow course data from the American River and Truckee-Tahoe basins, we determined that the strength of the orographic effect on a seasonal basis is spatially coherent at low and high elevations and on opposite sides of the Sierra Nevada crestline.

  3. Hemoglobin levels and circulating blasts are two easily evaluable diagnostic parameters highly predictive of leukemic transformation in primary myelofibrosis.

    PubMed

    Rago, Angela; Latagliata, Roberto; Montanaro, Marco; Montefusco, Enrico; Andriani, Alessandro; Crescenzi, Sabrina Leonetti; Mecarocci, Sergio; Spirito, Francesca; Spadea, Antonio; Recine, Umberto; Cicconi, Laura; Avvisati, Giuseppe; Cedrone, Michele; Breccia, Massimo; Porrini, Raffaele; Villivà, Nicoletta; De Gregoris, Cinzia; Alimena, Giuliana; D'Arcangelo, Enzo; Guglielmelli, Paola; Lo-Coco, Francesco; Vannucchi, Alessandro; Cimino, Giuseppe

    2015-03-01

    To predict leukemic transformation (LT), we evaluated easily detectable diagnostic parameters in 338 patients with primary myelofibrosis (PMF) followed in the Latium region (Italy) between 1981 and 2010. Forty patients (11.8%) progressed to leukemia, with a resulting 10-year leukemia-free survival (LFS) rates of 72%. Hb (<10g/dL), and circulating blasts (≥1%) were the only two independent prognostic for LT at the multivariate analysis. Two hundred-fifty patients with both the two parameters available were grouped as follows: low risk (none or one factor)=216 patients; high risk (both factors)=31 patients. The median LFS times were 269 and 45 months for the low and high-risk groups, respectively (P<.0001). The LT predictive power of these two parameters was confirmed in an external series of 270 PMF patients from Tuscany, in whom the median LFS was not reached and 61 months for the low and high risk groups, respectively (P<.0001). These results establish anemia and circulating blasts, two easily and universally available parameters, as strong predictors of LT in PMF and may help to improve prognostic stratification of these patients particularly in countries with low resources where more sophisticated molecular testing is unavailable. PMID:25636356

  4. Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

    PubMed Central

    2010-01-01

    Background The administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasis is on the penultimate step of the process, i.e. L-3-hydroxybutyryl-CoA dehydrogenase activity. We determined changes in enzyme activity and in circulating ketone body levels in the MPTP mouse model of Parkinson's disease. Since the active moiety of CoA is pantetheine, mice were treated with pantethine, its naturally-occurring form. Pantethine has the advantage of being known as an anti-inflammatory and hypolipidemic agent with very few side effects. Results We found that dehydrogenase activity and circulating ketone body levels were drastically reduced by the neurotoxin MPTP, whereas treatment with pantethine overcame these adverse effects. Pantethine prevented dopaminergic neuron loss and motility disorders. In vivo and in vitro experiments showed that the protection was associated with enhancement of glutathione (GSH) production as well as restoration of respiratory chain complex I activity and mitochondrial ATP levels. Remarkably, pantethine treatment boosted the circulating ketone body levels in MPTP-intoxicated mice, but not in normal animals. Conclusions These finding demonstrate the feasibility of the enhancement of endogenous ketone body production and provide a promising therapeutic approach to Parkinson's disease as well as, conceivably, to other neurodegenerative disorders. PMID:20416081

  5. Anticipatory and consummatory effects of (hedonic) chocolate intake are associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults

    PubMed Central

    Rigamonti, Antonello E.; Piscitelli, Fabiana; Aveta, Teresa; Agosti, Fiorenza; De Col, Alessandra; Bini, Silvia; Cella, Silvano G.; Di Marzo, Vincenzo; Sartorio, Alessandro

    2015-01-01

    Background Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown. Methods To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale. Results The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one. Conclusions When motivation to eat is generated by exposure to, and consumption of, chocolate a peripheral activation of specific endogenous rewarding chemical signals, including ghrelin, AEA, and 2-AG, is observed in obese subjects. Although preliminary, these findings predict the effectiveness of ghrelin and endocannabinoid antagonists in the treatment of obesity. PMID:26546790

  6. Do Amplitudes of Water Level Fluctuations Affect the Growth and Community Structure of Submerged Macrophytes?

    PubMed Central

    Wang, Mo-Zhu; Liu, Zheng-Yuan; Luo, Fang-Li; Lei, Guang-Chun; Li, Hong-Li

    2016-01-01

    Submerged macrophytes are subjected to potential mechanical stresses associated with fluctuating water levels in natural conditions. However, few experimental studies have been conducted to further understand the effects of water level fluctuating amplitude on submerged macrophyte species and their assemblages or communities. We designed a controlled experiment to investigate the responses of three submerged macrophyte species (Hydrilla verticillata, Ceratophyllum demersum and Elodea nuttallii) and their combinations in communities to three amplitudes (static, ± 30 cm, ± 60 cm) of water level fluctuations. Results showed that water level fluctuating amplitude had little effects on the community performance and the three tested species responded differently. H. verticillata exhibited more growth in static water and it was negatively affected by either of the water level fluctuations amplitude, however, growth parameters of H. verticillata in two fluctuating water level treatments (i.e., ± 30 cm, ± 60 cm) were not significantly different. On the other hand, the growth of C. demersum was not significantly correlated with different amplitude treatments. However, it became more abundant when water levels fluctuated. E. nuttallii was inhibited by the two fluctuating water level treatments, and was less in growth parameters compared to the other species especially in water level fluctuating conditions. The inherent differences in the adaptive capabilities of the tested species indicate that C. demersum or other species with similar responses may be dominant species to restore submerged macrophyte communities with great fluctuating water levels. Otherwise, H. verticillata, E. nuttallii or other species with similar responses could be considered for constructing the community in static water conditions. PMID:26735689

  7. Ultra-high-density 3D DNA arrays within nanoporous biocompatible membranes for single-molecule-level detection and purification of circulating nucleic acids.

    PubMed

    Aramesh, M; Shimoni, O; Fox, K; Karle, T J; Lohrmann, A; Ostrikov, K; Prawer, S; Cervenka, J

    2015-04-14

    Extracellular nucleic acids freely circulating in blood and other physiologic fluids are important biomarkers for non-invasive diagnostics and early detection of cancer and other diseases, yet difficult to detect because they exist in very low concentrations and large volumes. Here we demonstrate a new broad-range sensor platform for ultrasensitive and selective detection of circulating DNA down to the single-molecule level. The biosensor is based on a chemically functionalized nanoporous diamond-like carbon (DLC) coated alumina membrane. The few nanometer-thick, yet perfect and continuous DLC-coating confers the chemical stability and biocompatibility of the sensor, allowing its direct application in biological conditions. The selective detection is based on complementary hybridization of a fluorescently-tagged circulating cancer oncomarker (a 21-mer nucleic acid) with covalently immobilized DNA on the surface of the membrane. The captured DNAs are detected in the nanoporous structure of the sensor using confocal scanning laser microscopy. The flow-through membrane sensor demonstrates broad-range sensitivity, spanning from 10(15) molecules per cm(2) down to single molecules, which is several orders of magnitude improvement compared to the flat DNA microarrays. Our study suggests that these flow-through type nanoporous sensors represent a new powerful platform for large volume sampling and ultrasensitive detection of different chemical biomarkers. PMID:25744416

  8. Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans.

    PubMed

    Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla; Lee, Tammy C; Morgan, Timothy M; Nicklas, Barbara J; Mathias, Rasika A; Chilton, Floyd H

    2016-01-28

    Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk. PMID:26615716

  9. Elevated atmospheric CO2 levels affect community structure of rice root-associated bacteria

    PubMed Central

    Okubo, Takashi; Liu, Dongyan; Tsurumaru, Hirohito; Ikeda, Seishi; Asakawa, Susumu; Tokida, Takeshi; Tago, Kanako; Hayatsu, Masahito; Aoki, Naohiro; Ishimaru, Ken; Ujiie, Kazuhiro; Usui, Yasuhiro; Nakamura, Hirofumi; Sakai, Hidemitsu; Hayashi, Kentaro; Hasegawa, Toshihiro; Minamisawa, Kiwamu

    2015-01-01

    A number of studies have shown that elevated atmospheric CO2 ([CO2]) affects rice yields and grain quality. However, the responses of root-associated bacteria to [CO2] elevation have not been characterized in a large-scale field study. We conducted a free-air CO2 enrichment (FACE) experiment (ambient + 200 μmol.mol−1) using three rice cultivars (Akita 63, Takanari, and Koshihikari) and two experimental lines of Koshihikari [chromosome segment substitution and near-isogenic lines (NILs)] to determine the effects of [CO2] elevation on the community structure of rice root-associated bacteria. Microbial DNA was extracted from rice roots at the panicle formation stage and analyzed by pyrosequencing the bacterial 16S rRNA gene to characterize the members of the bacterial community. Principal coordinate analysis of a weighted UniFrac distance matrix revealed that the community structure was clearly affected by elevated [CO2]. The predominant community members at class level were Alpha-, Beta-, and Gamma-proteobacteria in the control (ambient) and FACE plots. The relative abundance of Methylocystaceae, the major methane-oxidizing bacteria in rice roots, tended to decrease with increasing [CO2] levels. Quantitative PCR revealed a decreased copy number of the methane monooxygenase (pmoA) gene and increased methyl coenzyme M reductase (mcrA) in elevated [CO2]. These results suggest elevated [CO2] suppresses methane oxidation and promotes methanogenesis in rice roots; this process affects the carbon cycle in rice paddy fields. PMID:25750640

  10. Homocysteine levels in schizophrenia and affective disorders—focus on cognition

    PubMed Central

    Moustafa, Ahmed A.; Hewedi, Doaa H.; Eissa, Abeer M.; Frydecka, Dorota; Misiak, Błażej

    2014-01-01

    Although homocysteine (Hcy) has been widely implicated in the etiology of various physical health impairments, especially cardiovascular diseases, overwhelming evidence indicates that Hcy is also involved in the pathophysiology of schizophrenia and affective disorders. There are several mechanisms linking Hcy to biological underpinnings of psychiatric disorders. It has been found that Hcy interacts with NMDA receptors, initiates oxidative stress, induces apoptosis, triggers mitochondrial dysfunction and leads to vascular damage. Elevated Hcy levels might also contribute to cognitive impairment that is widely observed among patients with affective disorders and schizophrenia. Supplementation of vitamins B and folic acid has been proved to be effective in lowering Hcy levels. There are also studies showing that this supplementation strategy might be beneficial for schizophrenia patients with respect to alleviating negative symptoms. However, there are no studies addressing the influence of add-on therapies with folate and vitamins B on cognitive performance of patients with schizophrenia and affective disorders. In this article, we provide an overview of Hcy metabolism in psychiatric disorders focusing on cognitive correlates and indicating future directions and perspectives. PMID:25339876

  11. Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

    PubMed Central

    Upadhyay, Swapna; Stoeger, Tobias; Harder, Volkar; Thomas, Ronald F; Schladweiler, Mette C; Semmler-Behnke, Manuela; Takenaka, Shinji; Karg, Erwin; Reitmeir, Peter; Bader, Michael; Stampfl, Andreas; Kodavanti, Urmila P; Schulz, Holger

    2008-01-01

    Background Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY). Methods Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF). Results Increased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma. Conclusion Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by

  12. Increased Levels of Circulating and Tissue mRNAs of Oct-4, Sox-2, Bmi-1 and Nanog is ESCC Patients: Potential Tool for Minimally Invasive Cancer Diagnosis

    PubMed Central

    Bahl, Kriti; Saraya, Anoop; Sharma, Rinu

    2012-01-01

    Background Early stages of esophageal cancer lack a specific symptom, a reliable biomarker and accurate non-invasive diagnostic modalities prompting the pressing need for identification of a marker for early diagnosis of this disease. Methods In the present study we investigated the levels of circulating and tissue mRNAs of Oct-3/4, Sox-2, Nanog and Bmi-1 in esophageal cancer patients using Reverse-Transcription Polymerase Chain Reaction (RT-PCR) with the aim of evaluating their potential as minimally invasive diagnostic markers. Result Increased transcript levels of Oct-4, Sox-2, Bmi-1 and Nanog were detected in (92%), (95%), (75%) and (67%) of the esophageal cancer tissues, respectively as compared with the matched distant normals. Conclusion Interestingly, most of the preneoplastic tissues exhibited increased transcript levels of these stemness markers suggesting their role in early stages of esophageal tumorigenesis. Furthermore, the detection of elevated levels of circulating mRNAs of Oct-4 and Nanog in sera of esophageal cancer patients emphasizes their potential as minimally invasive diagnostic markers for esophageal cancer. PMID:22493560

  13. Zonal winds near Venus' cloud top level - A model study of the interaction between the zonal mean circulation and the semidiurnal tide

    NASA Astrophysics Data System (ADS)

    Baker, N. L.; Leovy, C. B.

    1987-02-01

    A primitive equation wave-mean flow interaction model, designed by J. R. Holton and used originally to study Earth's middle atmosphere, has been adapted to Venus in order to clarify the understanding of the interaction between the semidiurnal tide and the thermally driven mean meridional circulation near the cloud top level. With or without the tide the model produces midlatitude jets whose structure is insensitive to vertical shear of the background angular velocity above and below the cloud top level, but it is sensitive to background angular velocity at the cloud top level. Agreement between the model tide and the observed tide, or the tide determined in the more detailed calculations of Pechmann and Ingersoll, is best when the background angular velocity at the jet level is about 30% larger than that observed.

  14. Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk.

    PubMed

    Papp, Audrey C; Pinsonneault, Julia K; Wang, Danxin; Newman, Leslie C; Gong, Yan; Johnson, Julie A; Pepine, Carl J; Kumari, Meena; Hingorani, Aroon D; Talmud, Philippa J; Shah, Sonia; Humphries, Steve E; Sadee, Wolfgang

    2012-01-01

    Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5-7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4 × 10(-5), allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8 × 10(-10)) and intron 8 polymorphism rs9930761-T>C (5.6 × 10(-8)) (in high linkage disequilibrium with allele frequencies 6-7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9.The effect of these polymorphisms was evaluated in two clinical studies. In the Whitehall II study of 4745 subjects, both rs247616 and rs5883T/rs9930761C were independently associated with increased HDL-C levels in males with similar effect size (rs247616 p = 9.6 × 10(-28) and rs5883 p = 8.6 × 10(-10), adjusted for rs247616). In an independent multiethnic US cohort of hypertensive subjects with CAD (INVEST-GENE), rs5883T/rs9930761C alone were significantly associated with increased incidence of MI, stroke, and all-cause mortality in males (rs5883: OR 2.36 (CI 1.29-4.30), p = 0.005, n = 866). These variants did not reach significance in females in either study. Similar to earlier results linking low CETP activity with poor outcomes in males, our results suggest genetic, sex

  15. Lung Circulation.

    PubMed

    Suresh, Karthik; Shimoda, Larissa A

    2016-01-01

    The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. © 2016 American Physiological Society. Compr Physiol 6:897-943, 2016. PMID:27065170

  16. Ecological and physiological factors affecting brood patch area and prolactin levels in arctic-nesting geese

    USGS Publications Warehouse

    Jonsson, J.E.; Afton, A.D.; Alisauskas, R.T.; Bluhm, C.K.; El Halawani, M.E.

    2006-01-01

    We investigated effects of ecological and physiological factors on brood patch area and prolactin levels in free-ranging Lesser Snow Geese (Chen caerulescens caerulescens; hereafter "Snow Geese") and Ross's Geese (C. rossii). On the basis of the body-size hypothesis, we predicted that the relationships between prolactin levels, brood patch area, and body condition would be stronger in Ross's Geese than in the larger Snow Geese. We found that brood patch area was positively related to clutch volume and inversely related to prolactin levels in Ross's Geese, but not in Snow Geese. Nest size, nest habitat, and first egg date did not affect brood patch area in either species. Prolactin levels increased as incubation progressed in female Snow Geese, but this relationship was not significant in Ross's Geese. Prolactin levels and body condition (as indexed by size-adjusted body mass) were inversely related in Ross's Geese, but not in Snow Geese. Our findings are consistent with the prediction that relationships between prolactin levels, brood patch area, and body condition are relatively stronger in Ross's Geese, because they mobilize endogenous reserves at faster rates than Snow Geese. ?? The American Ornithologists' Union, 2006. Printed in USA.

  17. Performance level affects the dietary supplement intake of both individual and team sports athletes.

    PubMed

    Giannopoulou, Ifigenia; Noutsos, Kostantinos; Apostolidis, Nikolaos; Bayios, Ioannis; Nassis, George P

    2013-01-01

    Dietary supplement (DS) intake is high in elite level athletes, however few studies have investigated the impact that the performance level of the athletes has on supplementation intake in individual and team sports. The purpose of the study was to determine and compare the DS intake among individual and team sport athletes of various performance levels. A total of 2845 participants (athletes: 2783, controls: 62) between the ages of 11 and 44 years old participated in the study. A 3-page questionnaire was developed to assess the intake of DS. Athletes were categorized based on participation in individual (n = 775) and team sports (n = 2008). To assess the effect of performance level in supplementation intake, athletes were categorized based on training volume, participation in the national team, and winning at least one medal in provincial, national, international or Olympic games. Overall, 37% of all athletes of various performance levels reported taking at least one DS in the last month. A higher prevalence of DS intake was reported in individual (44%) compared to team sport athletes (35%) (p < 0.001). Athletes of high performance level reported greater DS intake compared to lower performance athletes. Males reported a significantly greater prevalence of DS intake compared to females. The most popular supplement reported was amino acid preparation with the main reason of supplementation being endurance improvements. In conclusion, performance level and type of sport appear to impact the DS practices of male and female athletes. These findings should be validated in other populations. Key points37% of Mediterranean athletes of various sports and levels have reported taking dietary supplements.The performance level of the athletes affects the dietary supplementation intake.Athletes in individual sports appear to have a higher DS intake compared to team sport athletes.Male athletes appear to take more dietary supplements compared to female athletes. PMID:24149744

  18. Elevated Progesterone Levels on the Day of Oocyte Maturation May Affect Top Quality Embryo IVF Cycles

    PubMed Central

    Huang, Bo; Ren, Xinling; Wu, Li; Zhu, Lixia; Xu, Bei; Li, Yufeng; Ai, Jihui; Jin, Lei

    2016-01-01

    In contrast to the impact of elevated progesterone on endometrial receptivity, the data on whether increased progesterone levels affects the quality of embryos is still limited. This study retrospectively enrolled 4,236 fresh in vitro fertilization (IVF) cycles and sought to determine whether increased progesterone is associated with adverse outcomes with regard to top quality embryos (TQE). The results showed that the TQE rate significantly correlated with progesterone levels on the day of human chorionic gonadotropin (hCG) trigger (P = 0.009). Multivariate linear regression analysis of factors related to the TQE rate, in conventional IVF cycles, showed that the TQE rate was negatively associated with progesterone concentration on the day of hCG (OR was -1.658, 95% CI: -2.806 to -0.510, P = 0.005). When the serum progesterone level was within the interval 2.0–2.5 ng/ml, the TQE rate was significantly lower (P <0.05) than when the progesterone level was < 1.0 ng/ml; similar results were obtained for serum progesterone levels >2.5 ng/ml. Then, we choose a progesterone level at 1.5ng/ml, 2.0 ng/ml and 2.5 ng/ml as cut-off points to verify this result. We found that the TQE rate was significantly different (P <0.05) between serum progesterone levels < 2.0 ng/ml and >2.0 ng/ml. In conclusion, the results of this study clearly demonstrated a negative effect of elevated progesterone levels on the day of hCG trigger, on TQE rate, regardless of the basal FSH, the total gonadotropin, the age of the woman, or the time of ovarian stimulation. These data demonstrate that elevated progesterone levels (>2.0 ng/ml) before oocyte maturation were consistently detrimental to the oocyte. PMID:26745711

  19. Energized by love: thinking about romantic relationships increases positive affect and blood glucose levels.

    PubMed

    Stanton, Sarah C E; Campbell, Lorne; Loving, Timothy J

    2014-10-01

    We assessed the impact of thinking of a current romantic partner on acute blood glucose responses and positive affect over a short period of time. Participants in romantic relationships were randomly assigned to reflect on their partner, an opposite-sex friend, or their morning routine. Blood glucose levels were assessed prior to reflection, as well as at 10 and 25 min postreflection. Results revealed that individuals in the routine and friend conditions exhibited a decline in glucose over time, whereas individuals in the partner condition did not exhibit this decline (rather, a slight increase) in glucose over time. Reported positive affect following reflection was positively associated with increases in glucose, but only for individuals who reflected on their partner, suggesting this physiological response reflects eustress. These findings add to the literature on eustress in relationships and have implications for relationship processes. PMID:24924647

  20. Factors Affecting Parent's Perception on Air Quality-From the Individual to the Community Level.

    PubMed

    Guo, Yulin; Liu, Fengfeng; Lu, Yuanan; Mao, Zongfu; Lu, Hanson; Wu, Yanyan; Chu, Yuanyuan; Yu, Lichen; Liu, Yisi; Ren, Meng; Li, Na; Chen, Xi; Xiang, Hao

    2016-01-01

    The perception of air quality significantly affects the acceptance of the public of the government's environmental policies. The aim of this research is to explore the relationship between the perception of the air quality of parents and scientific monitoring data and to analyze the factors that affect parents' perceptions. Scientific data of air quality were obtained from Wuhan's environmental condition reports. One thousand parents were investigated for their knowledge and perception of air quality. Scientific data show that the air quality of Wuhan follows an improving trend in general, while most participants believed that the air quality of Wuhan has deteriorated, which indicates a significant difference between public perception and reality. On the individual level, respondents with an age of 40 or above (40 or above: OR = 3.252; 95% CI: 1.170-9.040), a higher educational level (college and above: OR = 7.598; 95% CI: 2.244-25.732) or children with poor healthy conditions (poor: OR = 6.864; 95% CI: 2.212-21.302) have much more negative perception of air quality. On the community level, industrial facilities, vehicles and city construction have major effects on parents' perception of air quality. Our investigation provides baseline information for environmental policy researchers and makers regarding the public's perception and expectation of air quality and the benefits to the environmental policy completing and enforcing. PMID:27187432

  1. Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

    PubMed Central

    Farace, F; Gross-Goupil, M; Tournay, E; Taylor, M; Vimond, N; Jacques, N; Billiot, F; Mauguen, A; Hill, C; Escudier, B

    2011-01-01

    Background: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45−CD31+CD146+7-amino-actinomycin (7AAD)− cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45dimCD34+VEGFR2+7AAD− progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45dimCD34+VEGFR2+7AAD− progenitor cells, plasma factors, as well as day 1–day 14 changes in CEC, CD45dimCD34+VEGFR2+7AAD− progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined. Results: No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45dimCD34+VEGFR2+7AAD− progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007). Conclusion: Monitoring CD45dimCD34+VEGFR2+ progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome. PMID:21386843

  2. Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation.

    PubMed

    Becker-Merok, A; Østli-Eilersten, G; Lester, S; Nossent, Jc

    2013-02-01

    Mutations in interferon (IFN) regulatory factor genes and the biological activity of type I IFN on expression of specific genes that are induced by IFN have been associated with various aspects of systemic lupus erythematosus (SLE). Circulating levels of IFN-α in SLE has not been extensively studied because of limited sensitivity of available ELISA assays. We performed a cross-sectional case-control study where circulating levels of IFN-α2 were measured by a highly sensitive, solution phase multiplex magnetized bead assay and investigated the relation of IFN-α2 with autoantibody profiles, clinical disease activity and levels of inflammatory cytokines in SLE patients (n = 87). Cytokine levels were determined on stored sera aliquots with cut-off levels determined by the geometric mean + 2SD in healthy controls (n = 27). IFN-α2 levels were increased in 64% of SLE patients, who displayed more renal disease and higher disease activity (p = 0.06) and had a significantly higher sum of activated cytokines (median 4.5, range 7) compared to patients with normal IFN-α2 (median one, range 3; p < 0.001). Solution phase micro-bead assay thus identified increased IFN-α2 levels in two-thirds of SLE patients with longstanding disease. The association with clinical disease and activation of multiple inflammatory cytokines supports a role for IFN-α2 in disease perpetuation in a large subset of SLE patients. PMID:23213068

  3. Effect of High-Flux Dialysis on Circulating FGF-23 Levels in End-Stage Renal Disease Patients: Results from a Randomized Trial

    PubMed Central

    Schneider, Andreas; Schneider, Markus P.; Krieter, Detlef H.; Genser, Bernd; Scharnagl, Hubert; Stojakovic, Tatjana; Wanner, Christoph; Drechsler, Christiane

    2015-01-01

    Background In patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. Interventional strategies aiming to reduce levels of FGF-23 in HD patients are of particular interest. The purpose of the current study was to compare the impact of high-flux versus low-flux HD on circulating FGF-23 levels. Methods We conducted a post-hoc analysis of the MINOXIS study, including 127 dialysis patients randomized to low-flux (n = 62) and high-flux (n = 65) HD for 52 weeks. Patients with valid measures for FGF-23 investigated baseline and after 52 weeks were included. Results Compared to baseline, a significant increase in FGF-23 levels after one year of low-flux HD was observed (Delta plasma FGF-23: +4026 RU/ml; p < 0.001). In contrast, FGF-23 levels remained stable in the high flux group (Delta plasma FGF-23: +373 RU/ml, p = 0.70). The adjusted difference of the absolute change in FGF-23 levels between the two treatment groups was statistically significant (p < 0.01). Conclusions Over a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23. However, the implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in specifically designed clinical trials. Trial Registration German Clinical Trials Register (DRKS) DRKS00007612. PMID:26024521

  4. Prenatal Thyroxine Treatment Disparately Affects Peripheral and Amygdala Thyroid Hormone Levels

    PubMed Central

    Shukla, Pradeep K.; Sittig, Laura J.; Andrus, Brian M.; Schaffer, Daniel J.; Batra, Kanchi K.; Redei, Eva E.

    2009-01-01

    Summary A prenatal hypothyroid state is associated with behavioral abnormalities in adulthood. Wistar–Kyoto (WKY) rats exhibit hypothyroidism and increased depressive and anxiety-like behaviors. Thus, the WKY could illuminate the mechanisms by which the reversal of developmental hypothyroidism in humans and animals results in adult behavioral improvement. We examined the outcome of maternal thyroxine (T4) treatment on thyroid hormone-regulated functions and adult behavior of the WKY offspring. Pregnant WKY dams completed gestation with and without T4 administration and their adult male offspring were tested. Measures included depressive and anxiety-like behaviors, and thyroid hormone (TH) concentrations in both plasma and specific brain regions. In addition, the expression of two proteins affecting thyroid hormone trafficking and metabolism, monocarboxylate transporter 8 (MCT-8) and iodothyronine deiodinase type III (Dio3), and of several behavior-altering molecules, glucocorticoid receptor (GR), prepro-thyrotropin releasing hormone (prepro-TRH) and corticotrophin releasing hormone (CRH), were determined in the hippocampus and amygdala of the offspring. Prenatal T4 treatment of WKYs did not affect adult depressive behavior but increased anxiety-like behavior and decreased plasma levels of THs. In the hippocampus of males treated with T4 in utero, Dio3 and MCT-8 protein levels were increased, while in the amygdala, there were increases of free T4, MCT-8, GR, prepro-TRH protein and CRH mRNA levels. These results show that T4 administration in utero programs adult peripheral and amygdalar thyroid hormone levels divergently, and that the resulting upregulation of anxiety-related genes in the amygdala could be responsible for the exacerbated anxiety-like behavior seen in WKYs after prenatal T4 treatment. PMID:20005050

  5. Maternal vitamin levels in pregnancies affected by congenital malformations other than neural tube defects

    PubMed Central

    Sutton, Marie; Mills, James L.; Molloy, Anne M.; Troendle, James F.; Brody, Lawrence C.; Conley, Mary; Mc Donnell, Robert; Scott, John M.; Kirke, Peadar N.

    2012-01-01

    Background Periconceptional use of folic acid prevents most neural tube defects (NTDs). Whether folic acid and/or multivitamins can prevent other congenital anomalies is not clear. This study tested whether maternal blood levels of folate and vitamin B12 in pregnancies affected by congenital malformations excluding NTDs are lower when compared to non-affected pregnancies. Methods We measured pregnancy red cell folate (RCF), vitamin B12, and homocysteine (tHcy) concentrations in blood samples taken at the first antenatal clinic in Dublin maternity hospitals in 1986–1990 when vitamin supplementation was rare. The cases were mothers who delivered a baby with a congenital malformation other than NTD identified by the Dublin EUROCAT Registry; controls were a systematic sample of mothers of offspring without congenital malformations from the same hospitals in the same time period. Results The median maternal levels of RCF and tHcy did not differ significantly between cases and controls for any of the congenital malformation groups examined (RCF: all malformations 275.9 ug/L v controls 271.2; p=0.77; tHcy: all malformations 7.5 umol/L v controls 7.6; p=0.57). In an unadjusted analysis vitamin B12 was significantly higher in case-mothers whose babies had cleft palate only (p=0.006), musculoskeletal malformations (p=0.034) and midline defects (p=0.039) but not after adjustment for multiple testing. Conclusions Our data suggest that low maternal folate and B12 levels or high tHcy levels in early pregnancy are not associated with all congenital malformations excluding NTDs. Fortification with folic acid or B12 may not have a beneficial effect in the prevention of these anomalies. PMID:21591245

  6. Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4+ T cell recovery after the initiation of antiretroviral therapy for HIV disease

    PubMed Central

    2014-01-01

    The level (or frequency) of circulating monocyte subpopulations such as classical (CD14hiCD16-) and non-classical (CD14dimCD16+) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4+ T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4+ T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14hiCD16-) and decreased levels of non-classical monocyte populations (CD14dimCD16+). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14+ monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14+ monocytes were significantly associated with the degree of CD4+ T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4+ T cell recovery after the initiation of ART. PMID:25180041

  7. The relationship between mesoscale circulation and cloud morphology at the upper cloud level of Venus from VMC/Venus Express

    NASA Astrophysics Data System (ADS)

    Patsaeva, M. V.; Khatuntsev, I. V.; Patsaev, D. V.; Titov, D. V.; Ignatiev, N. I.; Markiewicz, W. J.; Rodin, A. V.

    2015-08-01

    The Venus Monitoring Camera (VMC) acquired a set of ultraviolet (UV) images during the Venus Express mission unprecedented in its duration from May 2006 to September 2013. Here we present the results of digital tracking of the cloud features in the upper cloud layer at latitudes 25-75°S using images from 257 orbits with the best spatial coverage. The method relies on analysis of correlations between pairs of UV images separated in time. The bulk of data processed allows us to clarify the reasons why the mid-latitude jet is not always present in latitudinal wind profiles. Comparing VMC images with wind velocity fields we found a relationship between cloud morphology at middle latitudes and the circulation. The vector field in middle latitudes depends on the presence of a contrast global streak in the cloud morphology tilted with respect to latitude circles. The angle of the flow deflection (the angle between the wind velocity and latitudinal circles) and the difference of the zonal velocity on the opposite sides of the streak are in direct relationship to the angle between the streak and latitude circles. During such orbits the jet bulge does not appear in the latitudinal profile of the zonal wind component. Otherwise a zonal flow with small changes of the meridional velocity dominates in middle latitudes and manifests itself as a jet bulge. The relationship between the cloud cover morphology and circulation peculiarities can be attributed to the motion of global cloud features, like the Y-feature. We prepared plots of zonal and meridional velocities averaged with respect to the entire observation period. The average zonal velocity has a diurnal maximum at 15:00 local solar time and at 40°S. The meridional velocity reaches its maximum between 13:00 and 16:00 and at 50°S. The velocities obtained by the digital method are in good agreement with results of the visual method in the middle latitudes published earlier by Khatuntsev et al. (2013).

  8. Tadpole swimming performance and activity affected by acute exposure to sublethal levels of carbaryl

    USGS Publications Warehouse

    Bridges, C.M.

    1997-01-01

    General activity and swimming performance (i.e., sprint speed and distance) of plains leopard frog tadpoles (Rana blairi) were examined after acute exposure to three sublethal concentrations of carbaryl (3.5, 5.0, and 7.2 mg/L). Both swimming performance and spontaneous swimming activity are important for carrying out life history functions (e.g., growth and development) and for escaping from predators. Measured tadpole activity diminished by nearly 90% at 3.5 mg/L carbaryl and completely ceased at 7.2 mg/L. Sprint speed and sprint distance also decreased significantly following exposure. Carbaryl affected both swimming performance and activity after just 24 h, suggesting that 24 h may be an adequate length of exposure to determine behavioral effects on tadpoles. Slight recovery of activity levels was noted at 24 and 48 h post-exposure; no recovery of swimming performance was observed. Reduction in activity and swimming performance may result in increased predation rates and, because activity is closely associated with feeding, may result in slowed growth leading to a failure to emerge before pond drying or an indirect reduction in adult fitness. Acute exposure to sublethal toxicants such as carbaryl may not only affect immediate survival of tadpoles but also impact critical life history functions and generate changes at the local population level.

  9. A preliminary study of pamidronic acid downregulation of angiogenic factors IGF-1/PECAM-1 expression in circulating level in bone metastatic breast cancer patients

    PubMed Central

    Wang, Zeng; Lei, Lei; Cai, Xin-jun; Chen, Ling Ya; Yuan, Meiqin; Yang, Guonong; Huang, Ping; Wang, Xiaojia

    2016-01-01

    Objective To evaluate the expressions of circulating angiogenic factors affected by pamidronic acid (PA) intravenous infusion in bone metastatic breast cancer patients and the impact on their prognosis. Methods Peripheral blood of ten bone metastatic breast cancer patients was collected for serum insulin-like growth factor-1 (IGF-1) and platelet endothelial cell adhesion molecule-1 expression detection just before and 2 days after PA infusion. Results Both IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations decreased after PA treatment for 48 hours (P<0.05). Modification was defined as >20% decrease recorded 2 days after PA administration. The decrease of IGF-1 was more significant in breast cancer patients who had received previous hormonotherapy. Moreover, the progression-free survival of first-line chemotherapy treatment of IGF-1 modified patients was longer than that of IGF-1 unmodified patients (P=0.009). Conclusion PA treatment could suppress circulating serum IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations; moreover, the prognosis of patients in IGF-1 unmodified group was relatively poor. PMID:27307756

  10. An evaluation of supervised classifiers for indirectly detecting salt-affected areas at irrigation scheme level

    NASA Astrophysics Data System (ADS)

    Muller, Sybrand Jacobus; van Niekerk, Adriaan

    2016-07-01

    Soil salinity often leads to reduced crop yield and quality and can render soils barren. Irrigated areas are particularly at risk due to intensive cultivation and secondary salinization caused by waterlogging. Regular monitoring of salt accumulation in irrigation schemes is needed to keep its negative effects under control. The dynamic spatial and temporal characteristics of remote sensing can provide a cost-effective solution for monitoring salt accumulation at irrigation scheme level. This study evaluated a range of pan-fused SPOT-5 derived features (spectral bands, vegetation indices, image textures and image transformations) for classifying salt-affected areas in two distinctly different irrigation schemes in South Africa, namely Vaalharts and Breede River. The relationship between the input features and electro conductivity measurements were investigated using regression modelling (stepwise linear regression, partial least squares regression, curve fit regression modelling) and supervised classification (maximum likelihood, nearest neighbour, decision tree analysis, support vector machine and random forests). Classification and regression trees and random forest were used to select the most important features for differentiating salt-affected and unaffected areas. The results showed that the regression analyses produced weak models (<0.4 R squared). Better results were achieved using the supervised classifiers, but the algorithms tend to over-estimate salt-affected areas. A key finding was that none of the feature sets or classification algorithms stood out as being superior for monitoring salt accumulation at irrigation scheme level. This was attributed to the large variations in the spectral responses of different crops types at different growing stages, coupled with their individual tolerances to saline conditions.

  11. Natural Disaster Induced Losses at Household Level: A Study on the Disaster Affected Migrants

    NASA Astrophysics Data System (ADS)

    Ishtiaque, A.; Nazem, N. I.; Jerin, T.

    2015-12-01

    Given its geographical location Bangladesh frequently confronts natural disasters. Disaster induced losses often obligate socio-economic dislocation from rural areas to large urban centers. After incurring what type/amount of losses people migrate is still unknown. In this paper we focus on migrants who migrated due to natural disasters. Thus, the objectives of this paper are, first, ascertaining the proportion of disaster migrants in Dhaka city; second, determining types of natural disasters which compel rural out-migration; third, assessing the resource and economic losses stem from these disasters at household level. Using the slum database (N = 4966), we select eight slums randomly with a purpose to include migrants from maximum districts available. In order to identify the proportion of disaster affected migrants a census is conducted in 407 households of those 8 slums and the result demonstrates that 18.43% of the migrants are disaster affected, which was only 5% in 1993. Out of all hydro-meteorological disasters, river bank erosion (RBE), followed by flood, drives most people out of their abode. However, unlike RBE migrants, migrants affected by flood usually return to their origin after certain period. In-depth interviews on the disaster migrants reveal that RBE claims total loss of homestead land & agricultural land while flood causes 20% and 23% loss respectively. Agricultural income decreases 96% because of RBE whereas flood victims encounter 98% decrease. People also incur 79% & 69% loss in livestock owing to RBE and flood severally. These disasters cause more than eighty percent reduction in total monthly income. Albeit RBE appears more vigorous but total economic loss is greater in flood- on average each household experiences a loss of BDT 350,555 due to flood and BDT 300,000 on account of RBE. Receiving no substantial support from community or government the affected people are compelled to migrate.

  12. Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

    NASA Astrophysics Data System (ADS)

    Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

    2010-04-01

    This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

  13. Social competition affects electric signal plasticity and steroid levels in the gymnotiform fish Brachyhypopomus gauderio

    PubMed Central

    Salazar, Vielka L.; Stoddard, Philip K.

    2009-01-01

    Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. Steroid regulation of these signals can render them as reliable indicators of a male's physiological state. We investigated how plasticity in electrocommunication signals is driven by social competition for mates, mediated by steroid hormones, and subject to the effects of past social experience. We measured the electric waveform's amplitude and duration and steroid hormone levels of male gymnotiform electric fish (Brachyhypopomus gauderio) following week-long periods of social isolation, and low or high social competition. To quantify the effect of social history on the modulation of the electric signal, six groups of six males experienced all the above three social conditions but in different order. We found that males differentially modulate their electric signals depending on the order they experienced these conditions. Thus, past social interactions affect both present and future social electric signals. Cortisol levels and the amplitude of the electric signal appeared to track the intensity of competition, while androgen levels and the duration of the electric signal only responded to the presence (low and high competition) or absence (isolation) of a social environment (low and high androgens respectively). In addition, cortisol levels were related to the body size of the males at high social competition. Taken together, these findings suggest that the capacity of males to modulate their signals in response to social competition is regulated by steroids. PMID:19647742

  14. Host tree phenology affects vascular epiphytes at the physiological, demographic and community level

    PubMed Central

    Einzmann, Helena J. R.; Beyschlag, Joachim; Hofhansl, Florian; Wanek, Wolfgang; Zotz, Gerhard

    2015-01-01

    The processes that govern diverse tropical plant communities have rarely been studied in life forms other than trees. Structurally dependent vascular epiphytes, a major part of tropical biodiversity, grow in a three-dimensional matrix defined by their hosts, but trees differ in their architecture, bark structure/chemistry and leaf phenology. We hypothesized that the resulting seasonal differences in microclimatic conditions in evergreen vs. deciduous trees would affect epiphytes at different levels, from organ physiology to community structure. We studied the influence of tree leaf phenology on vascular epiphytes on the Island of Barro Colorado, Panama. Five tree species were selected, which were deciduous, semi-deciduous or evergreen. The crowns of drought-deciduous trees, characterized by sunnier and drier microclimates, hosted fewer individuals and less diverse epiphyte assemblages. Differences were also observed at a functional level, e.g. epiphyte assemblages in deciduous trees had larger proportions of Crassulacean acid metabolism species and individuals. At the population level a drier microclimate was associated with lower individual growth and survival in a xerophytic fern. Some species also showed, as expected, lower specific leaf area and higher δ13C values when growing in deciduous trees compared with evergreen trees. As hypothesized, host tree leaf phenology influences vascular epiphytes at different levels. Our results suggest a cascading effect of tree composition and associated differences in tree phenology on the diversity and functioning of epiphyte communities in tropical lowland forests. PMID:25392188

  15. Muscular activity level during pedalling is not affected by crank inertial load.

    PubMed

    Duc, S; Villerius, V; Bertucci, W; Pernin, J N; Grappe, F

    2005-10-01

    The aim of the present study was to investigate the influence of gear ratio (GR) and thus crank inertial load (CIL), on the activity levels of lower limb muscles. Twelve competitive cyclists performed three randomised trials with their own bicycle equipped with a SRM crankset and mounted on an Axiom ergometer. The power output ( approximately 80% of maximal aerobic power) and the pedalling cadence were kept constant for each subject across all trials but three different GR (low, medium and high) were indirectly obtained for each trial by altering the electromagnetic brake of the ergometer. The low, medium and high GR (mean +/- SD) resulted in CIL of 44 +/- 3.7, 84 +/- 6.5 and 152 +/- 17.9 kg.m(2), respectively. Muscular activity levels of the gluteus maximus (GM), the vastus medialis (VM), the vastus lateralis (VL), the rectus femoris (RF), the medial hamstrings (MHAM), the gastrocnemius (GAS) and the soleus (SOL) muscles were quantified and analysed by mean root mean square (RMS(mean)). The muscular activity levels of the measured lower limb muscles were not significantly affected when the CIL was increased approximately four fold. This suggests that muscular activity levels measured on different cycling ergometers (with different GR and flywheel inertia) can be compared among each other, as they are not influenced by CIL. PMID:16032416

  16. Beneficial effect of combination therapy using an angiotensin-converting enzyme inhibitor plus verapamil on circulating resistin levels in hypertensive patients with type 2 diabetes

    PubMed Central

    Rubio-Guerra, Alberto F; Vargas-Robles, Hilda; Lozano Nuevo, Jose J; Elizalde-Barrera, Cesar I; Huerta-Ramirez, Saul; Escalante-Acosta, Bruno A

    2012-01-01

    BACKGROUND: Resistin levels are strongly correlated with insulin resistance and vascular inflammation. Type 2 diabetic and hypertensive patients have higher circulating levels of resistin, which is associated with endothelial dysfunction. OBJECTIVE: To compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on resistin levels in hypertensive, type-2 diabetic patients. METHODS: Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group received FDTV 2 mg/180 mg once per day; the other group received T 2 mg once per day. Study drugs were administered for three months in both groups. Resistin levels were measured using ELISA at the beginning of the study and at study end. Patients were evaluated monthly for blood pressure, fasting serum glucose levels and adverse events. Statistical analysis was performed using ANOVA. RESULTS: All patients experienced a significant reduction in blood pressure. Both therapeutic regimens reduced resistin levels; however, FDTV treatment resulted in a greater decrease in resistin levels (mean [± SD] 25.5±13 ng/mL to 17.2±10 ng/mL) when compared with T treatment (22.4±12 ng/mL to 18.5±8 ng/mL) (P<0.05). None of the patients experienced an adverse event. CONCLUSION: Results showed that FDTV resulted in a greater reduction in resistin levels than T treatment alone. PMID:23592936

  17. Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

    PubMed Central

    Calandra, Sebastiano; Tarugi, Patrizia; Speedy, Helen E.; Dean, Andrew F.; Bertolini, Stefano; Shoulders, Carol C.

    2011-01-01

    This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means. PMID:21862702

  18. Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk.

    PubMed

    Calandra, Sebastiano; Tarugi, Patrizia; Speedy, Helen E; Dean, Andrew F; Bertolini, Stefano; Shoulders, Carol C

    2011-11-01

    This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means. PMID:21862702

  19. Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys.

    PubMed

    Elsworth, John D; Jentsch, James D; Groman, Stephanie M; Roth, Robert H; Redmond, Eugene D; Leranth, Csaba

    2015-06-01

    Bisphenol-A (BPA) is widely used in the manufacture of plastics, epoxy resins, and certain paper products. A majority of the population in the developed world is routinely exposed to BPA from multiple sources and has significant circulating levels of BPA. Although BPA is categorized as an endocrine disruptor with a growing literature on adverse effects, it is uncertain whether cognitive dysfunction is induced in humans by exposure to BPA. The present study examined the impact of BPA in primate brain by exposing adult male vervet monkeys for 4 weeks continuously to circulating levels of BPA that were in the range measured in studies of humans environmentally exposed to BPA. This regimen of exposure to BPA decreased both working memory accuracy and the number of excitatory synaptic inputs on dendritic spines of pyramidal neurons in two brain regions that are necessary for working memory (prefrontal cortex and hippocampus). These observed behavioral and synaptic effects were ameliorated following withdrawal from BPA. As Old World monkeys (e.g., vervets) and humans share some uniquely primate morphological, endocrine, and cognitive traits, this study indicates the potential for significant cognitive disruption following exposure of humans to BPA. PMID:25557059

  20. Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys

    PubMed Central

    Elsworth, John D; Jentsch, James D; Groman, Stephanie M; Roth, Robert H; Redmond, D. Eugene; Leranth, Csaba

    2015-01-01

    Bisphenol-A (BPA) is widely used in the manufacture of plastics, epoxy resins and certain paper products. A majority of the population in the developed world is routinely exposed to BPA from multiple sources and has significant circulating levels of BPA. Although BPA is categorized as an endocrine disruptor with a growing literature on adverse effects, it is uncertain whether cognitive dysfunction is induced in humans by exposure to BPA. The present study examined the impact of BPA in primate brain by exposing adult male vervet monkeys for 4 weeks continuously to circulating levels of BPA that were in the range measured in studies of humans environmentally exposed to BPA. This regimen of exposure to BPA decreased both working memory accuracy and the number of excitatory synaptic inputs on dendritic spines of pyramidal neurons in two brain regions that are necessary for working memory (prefrontal cortex and hippocampus). These observed behavioral and synaptic effects ameliorated following withdrawal from BPA. As Old world monkeys (e.g., vervets) and humans share some uniquely primate morphological, endocrine and cognitive traits, this study indicates the potential for significant cognitive disruption following exposure of humans to BPA. PMID:25557059

  1. A Fasting Insulin–Raising Allele at IGF1 Locus Is Associated with Circulating Levels of IGF-1 and Insulin Sensitivity

    PubMed Central

    Mannino, Gaia Chiara; Greco, Annalisa; De Lorenzo, Carlo; Andreozzi, Francesco; Marini, Maria A.; Perticone, Francesco; Sesti, Giorgio

    2013-01-01

    Background A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance. Methodology/Principal Findings Two samples of adult nondiabetic white Europeans were studied. In sample 1 (n=569), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (190±77 vs. 218±97 ng/ml, respectively; P=0.007 after adjusting for age, gender, and BMI). Insulin sensitivity assessed by euglycaemic-hyperinsulinemic clamp was lower in GG genotype carriers compared with A allele carriers (8.9±4.1 vs. 10.1±5.1 mg x Kg-1 free fat mass x min-1, respectively; P=0.03 after adjusting for age, gender, and BMI). The rs35767 polymorphism did not show significant association with insulin clearance. In sample 2 (n=859), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (155±60 vs. 164±63 ng/ml, respectively; P=0.02 after adjusting for age, gender, and BMI). Insulin sensitivity, as estimated by the HOMA index, was lower in GG genotype carriers compared with A allele carriers (2.8±2.2 vs. 2.5±1.3, respectively; P=0.03 after adjusting for age, gender, and BMI). Conclusion/Significance The rs35767 polymorphism near IGF1 was associated with circulating IGF-1 levels, and insulin sensitivity with carriers of the GG genotype exhibiting lower IGF-1 concentrations and insulin sensitivity as compared with subjects carrying the A allele. PMID:24392014

  2. Fibrillin levels in a severely affected Marfan syndrome patient with a null allele

    SciTech Connect

    Boxer, M.; Withers, A.P.; Al-Ghaban, Z. |

    1994-09-01

    Marfan syndrome is an autosomal dominantly inherited connective tissue disorder characterized by defects in the cardiovascular, skeletal and ocular systems. A patient was first examined in 1992 having survived an acute sortic dissection with subsequent composite repair and insertion of a prosthetic aortic valve. Clinical examination revealed arachnodactyly, narrow, high arched palate with dental crowding, an arm span exceeding her height by 10.5 cm, joint laxity and bilateral lens subluxation. Analysis of the family showed affected members in three generations and the fibrillin gene, FBN1, was shown to segregate with the disease when using polymorphic markers including an RsaI polymorphism in the 3{prime}-untranslated region of the gene. Analysis of patient mRNA for this RsaI polymorphism by RT-PCR (reverse transcriptase-PCR) amplification and restriction enzyme digestion of the PCR products showed that the copy of the gene segregating with the disease was not transcribed. No low level expression of this allele was observed despite RT-PCR amplification incorporating radioactively labelled dCTP, thus revealing a null allele phenotype. Western blotting analysis of fibrillin secreted by the patient`s dermal fibroblasts using fibrillin-specific antibodies showed only normal sized fibrillin protein. However, immunohistochemical studies of the patient`s tissue and fibroblasts showed markedly lowered levels in staining of microfibrillar structures compared with age-matched controls. This low level of expression of the protein affected in Marfan syndrome in a patient with such severe clinical manifestations is surprising since current understanding would suggest that this molecular phenotype should lead to a mild clinical disorder.

  3. Sediment size distribution and composition in a reservoir affected by severe water level fluctuations.

    PubMed

    López, Pilar; López-Tarazón, José A; Casas-Ruiz, Joan P; Pompeo, Marcelo; Ordoñez, Jaime; Muñoz, Isabel

    2016-01-01

    The reservoir sediments are important sinks for organic carbon (OC), the OC burial being dependent on two opposite processes, deposition and mineralization. Hence factors such as severe water level fluctuations are expected to influence the rate of OC accumulation as they may affect both deposition and mineralization. The Barasona Reservoir has been historically threatened by siltation, whilst the use of water for irrigation involves a drastic decrease of the water level. In this context, we have studied the physical and chemical characteristics (grain size, major and minor elemental compositions, organic and inorganic carbon, and nitrogen) of the recent sediments of the Barasona Reservoir and the relationships among them in order to: a) elucidate the main processes governing OC accumulation, b) evaluate the rate of OC mineralization and c) approach the effect of drought on the sediment characteristics in this system. Our results indicated that Barasona sediments were dominated by fine silts (>60%) and clays (>20%), the mean particle size decreasing from tail to dam. Desiccation increased particle sorting and size distribution became bimodal, but no effect on average size was observed. Attending to the composition, Barasona sediments were very homogeneous with low concentrations of nitrogen (TN) and phosphorus (<1.2 g kg(-1) dw and <0.6 g kg(-1) dw, respectively) and high concentration of OC (≈36 g kg(-1) dw). TN was negatively related to dry weight. Sediment mixing due to drastic changes in water level may have favoured the observed homogeneity of Barasona sediments affecting carbon, major ions and grain size. The high amount of OC deposited in Barasona sediment suggested that the adsorption of OC onto fine particles was more important than in boreal lakes. The rate of oxygen consumption by wet sediment ranged from 2.26 to 3.15 mg O2 m(-2) day(-1), values close to those compiled for Mediterranean running waters. PMID:26105704

  4. Ultra-high-density 3D DNA arrays within nanoporous biocompatible membranes for single-molecule-level detection and purification of circulating nucleic acids

    NASA Astrophysics Data System (ADS)

    Aramesh, M.; Shimoni, O.; Fox, K.; Karle, T. J.; Lohrmann, A.; Ostrikov, K.; Prawer, S.; Cervenka, J.

    2015-03-01

    Extracellular nucleic acids freely circulating in blood and other physiologic fluids are important biomarkers for non-invasive diagnostics and early detection of cancer and other diseases, yet difficult to detect because they exist in very low concentrations and large volumes. Here we demonstrate a new broad-range sensor platform for ultrasensitive and selective detection of circulating DNA down to the single-molecule level. The biosensor is based on a chemically functionalized nanoporous diamond-like carbon (DLC) coated alumina membrane. The few nanometer-thick, yet perfect and continuous DLC-coating confers the chemical stability and biocompatibility of the sensor, allowing its direct application in biological conditions. The selective detection is based on complementary hybridization of a fluorescently-tagged circulating cancer oncomarker (a 21-mer nucleic acid) with covalently immobilized DNA on the surface of the membrane. The captured DNAs are detected in the nanoporous structure of the sensor using confocal scanning laser microscopy. The flow-through membrane sensor demonstrates broad-range sensitivity, spanning from 1015 molecules per cm2 down to single molecules, which is several orders of magnitude improvement compared to the flat DNA microarrays. Our study suggests that these flow-through type nanoporous sensors represent a new powerful platform for large volume sampling and ultrasensitive detection of different chemical biomarkers.Extracellular nucleic acids freely circulating in blood and other physiologic fluids are important biomarkers for non-invasive diagnostics and early detection of cancer and other diseases, yet difficult to detect because they exist in very low concentrations and large volumes. Here we demonstrate a new broad-range sensor platform for ultrasensitive and selective detection of circulating DNA down to the single-molecule level. The biosensor is based on a chemically functionalized nanoporous diamond-like carbon (DLC) coated

  5. Protein level affects the relative lysine requirement of growing rainbow trout (Oncorhynchus mykiss) fry.

    PubMed

    Bodin, Noelie; Govaerts, Bernadette; Abboudi, Tarik; Detavernier, Christel; De Saeger, Sarah; Larondelle, Yvan; Rollin, Xavier

    2009-07-01

    The effect of two digestible protein levels (310 and 469 g/kg DM) on the relative lysine (Lys; g Lys/kg DM or g Lys/100 g protein) and the absolute Lys (g Lys intake/kg 0.75 per d) requirements was studied in rainbow trout fry using a dose-response trial. At each protein level, sixteen isoenergetic (22-23 MJ digestible energy/kg DM) diets were tested, involving a full range (2-70 g/kg DM) of sixteen Lys levels. Each diet was given to one group of sixty rainbow trout fry (mean initial body weight 0.78 g) reared at 15 degrees C for 31 feeding d. The Lys requirements were estimated based on the relationships between weight, protein, and Lys gains (g/kg 0.75 per d) and Lys concentration (g/kg DM or g/100 g protein) or Lys intake (g/kg 0.75 per d), using the broken-line model (BLM) and the non-linear four-parameter saturation kinetics model (SKM-4). Both the model and the response criterion chosen markedly impacted the relative Lys requirement. The relative Lys requirement for Lys gain of rainbow trout estimated with the BLM (and SKM-4 at 90 % of the maximum response) increased from 16.8 (19.6) g/kg DM at a low protein level to 23.4 (24.5) g/kg DM at a high protein level. However, the dietary protein content affected neither the absolute Lys requirement nor the relative Lys requirement expressed as g Lys/100 g protein nor the Lys requirement for maintenance (21 mg Lys/kg 0.75 per d). PMID:19138439

  6. How much do tides affect the circulation of the Mediterranean Sea? From local processes in the Strait of Gibraltar to basin-scale effects

    NASA Astrophysics Data System (ADS)

    Naranjo, C.; Garcia-Lafuente, J.; Sannino, G.; Sanchez-Garrido, J. C.

    2014-09-01

    The effects of tidal forcing on the exchange flow through the Strait of Gibraltar and the circulation in the near-field region are revisited with a regional numerical model. Also a basin-scale model run is conducted in a first attempt to assess the impact of these local processes on the Western Mediterranean thermohaline circulation. In the Strait of Gibraltar, tides are found to (1) increase the exchange flow volume transport, (2) modify the hydrological properties of Atlantic inflowing waters through the enhancement of mixing, and (3) facilitate the drainage of Mediterranean deep water. In the far-field, the model reveals that these local processes can favor deep convection in the Gulf of Lion. Some thoughts are provided offering possible explanations.

  7. Diminished FoxP2 levels affect dopaminergic modulation of corticostriatal signaling important to song variability.

    PubMed

    Murugan, Malavika; Harward, Stephen; Scharff, Constance; Mooney, Richard

    2013-12-18

    Mutations of the FOXP2 gene impair speech and language development in humans and shRNA-mediated suppression of the avian ortholog FoxP2 disrupts song learning in juvenile zebra finches. How diminished FoxP2 levels affect vocal control and alter the function of neural circuits important to learned vocalizations remains unclear. Here we show that FoxP2 knockdown in the songbird striatum disrupts developmental and social modulation of song variability. Recordings in anesthetized birds show that FoxP2 knockdown interferes with D1R-dependent modulation of activity propagation in a corticostriatal pathway important to song variability, an effect that may be partly attributable to reduced D1R and DARPP-32 protein levels. Furthermore, recordings in singing birds reveal that FoxP2 knockdown prevents social modulation of singing-related activity in this pathway. These findings show that reduced FoxP2 levels interfere with the dopaminergic modulation of vocal variability, which may impede song and speech development by disrupting reinforcement learning mechanisms. PMID:24268418

  8. Low-level lasers affect Escherichia coli cultures in hyperosmotic stress

    NASA Astrophysics Data System (ADS)

    Pinheiro, C. C.; Barboza, L. L.; Paoli, F.; Fonseca, A. S.

    2015-08-01

    Physical characteristics and practical properties have made lasers of interest for biomedical applications. Effects of low-level lasers on biological tissues could occur or be measurable depending on cell type, presence of a pathologic process or whether the cells are in an adverse environment. The objective of this work was to evaluate the survival, morphology and filamentation of E. coli cells proficient and deficient in the repair of oxidative DNA lesions exposed low-level red and infrared lasers submitted to hyperosmotic stress. Wild type and endonuclease VIII deficient E. coli cells in exponential and stationary growth phase were exposed to red and infrared lasers and submitted to hyperosmotic stress. Cell viability, filamentation phenotype and cell morphology were evaluated. Cell viability was not significantly altered but previous laser exposure induced filamentation and an altered area of stressed cells depending on physiologic condition and presence of the DNA repair. Results suggest that previous exposure to low-level red and infrared lasers could not affect viability but induced morphologic changes in cells submitted to hyperosmotic stress depending on physiologic conditions and repair of oxidative DNA lesions.

  9. Circulating Vitamin D Correlates with Serum Anti-Mullerian Hormone Levels in Late Reproductive-Aged Women: Women’s Interagency HIV Study

    PubMed Central

    Merhi, Zaher O.; Seifer, David B.; Weedon, Jeremy; Adeyemi, Oluwatoyin; Holman, Susan; Anastos, Kathryn; Golub, Elizabeth T.; Young, Mary; Karim, Roksana; Greenblatt, Ruth; Minkoff, Howard

    2012-01-01

    Objective To study the correlation between circulating 25 hydroxy-vitamin D (25OH-D) levels and serum AMH in women enrolled in the Women’s Interagency HIV Study (WIHS). Design A cross-sectional study. Setting WIHS, a multicenter prospective study. Patient(s) All premenopausal women (n=388) with regular menstrual cycles were included and subdivided into three groups: group 1 with age <35 (N=128), group 2 with age 35 to 39 (N=119), and group 3 with age ≥ 40 (N=141). Intervention(s) Serum for 25OH-D, AMH, fasting glucose and insulin, and creatinine levels. Main Outcome Measure(s) Correlation between 25OH-D and AMH before and after adjusting for HIV status, BMI, race, smoking, illicit drug use, glucose and insulin levels, estimated glomerular filtration rate and geographic site of participation. Result(s) After adjusting for all covariates, the regression slope in all participants for total 25OH-D predicting log10AMH for 25-year-olds (youngest participant) was −0.001 (SE=0.008, p=0.847); and for 45-year-olds (oldest participant), the corresponding slope was +0.011 (SE=0.005, p=0.021). Fasting insulin level was negatively correlated with serum AMH (p=0.016). The regression slope for the correlation between 25OH-D and AMH in group 1 was +0.002 (SE=0.006, p=0.764); in group 2 was +0.006 (SE=0.005, p=0.269); and in group 3 was +0.011 (SE=0.005, p=0.022). There was no association between HIV and AMH. Conclusion(s) A novel relationship is reported between circulating 25OH-D and AMH in women aged = 40 suggesting that 25OH-D deficiency might be associated with lower ovarian reserve in late reproductive-aged women. PMID:22494925

  10. The role of particular tick developmental stages in the circulation of tick-borne pathogens affecting humans in Central Europe. 2. Tick-borne encephalitis virus.

    PubMed

    Karbowiak, Grzegorz; Biernat, Beata

    2016-01-01

    Hard-bodied ticks transmit various pathogens, such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia spp., Babesia spp., and carry numerous other microorganisms with an unknown pathogenic potential. Among them, tick-borne encephalitis virus has great importance. In Central European conditions all developmental stages of ticks participate in the zoonotic cycle of the TBE virus. According to pathogen and tick biology, the roles of larvae, nymphs and adults are different. Larvae and nymphs of Ixodes ricinus ticks are responsible for circulation in rodents and medium sized mammals; adults transfer the infection to ruminants and to next generations via transovarial transmission. All active developmental stages of I. ricinus can play role of the bridge vector, transmitting the infection to humans apart males which don't feed. The late summer peak of human infectivity is caused by the summer peak of I. ricinus nymphs' activity. The Dermacentor reticulatus tick attacks humans infrequently, but does participate in the circulation of the virus in the zoonotic foci; larvae and nymphs of the D. reticulatus ticks are responsible for circulation in rodents, mainly Microtinae, while adults transmit the infection to ruminants. PMID:27262951

  11. Connecting large-scale atmospheric circulation, river flow and groundwater levels in a chalk catchment in southern England

    NASA Astrophysics Data System (ADS)

    Lavers, David A.; Hannah, David M.; Bradley, Chris

    2015-04-01

    Groundwater is an important water resource and globally it represents the largest distributed store of freshwater. In southern England, groundwater is a major source for public water supply, and many aquifers have recently experienced both extreme low and high groundwater levels. In this paper, we use observations of precipitation, river discharge and groundwater levels (1964-2010) and an atmospheric reanalysis to explore the large-scale climate patterns preceding the nine highest and lowest March river discharge and groundwater levels in the chalk catchment of the River Lambourn (Berkshire Downs, southern England). Peak monthly precipitation is shown to occur from October to January, while the highest river discharge and groundwater levels are found from February to April. For high discharge/groundwater levels, composite anomaly patterns of the mean sea level pressure show a stronger than average pressure gradient across the North Atlantic Ocean, with enhanced water vapour transport across southern England. For the lowest discharge/groundwater levels, a blocking high pressure system is found across the British Isles deflecting storms and precipitation to the north. Significantly, the intra-composite variability suggests that different sequences of atmospheric states may lead to high and low discharge/groundwater events.

  12. An experimental survey of the factors that affect leaching from low-level radioactive waste forms

    SciTech Connect

    Dougherty, D.R.; Pietrzak, R.F.; Fuhrmann, M.; Colombo, P.

    1988-09-01

    This report represents the results of an experimental survey of the factors that affect leaching from several types of solidified low-level radioactive waste forms. The goal of these investigations was to determine those factors that accelerate leaching without changing its mechanism(s). Typically, although not in every case,the accelerating factors include: increased temperature, increased waste loading (i.e., increased waste to binder ratio), and decreased size (i.e., decreased waste form volume to surface area ratio). Additional factors that were studied were: increased leachant volume to waste form surface area ratio, pH, leachant composition (groundwaters, natural and synthetic chelating agents), leachant flow rate or replacement frequency and waste form porosity and surface condition. Other potential factors, including the radiation environment and pressure, were omitted based on a survey of the literature. 82 refs., 236 figs., 13 tabs.

  13. [Reading poems to oneself affects emotional state and level of distraction].

    PubMed

    Morita, Haruka; Sugamura, Genji

    2014-12-01

    Bibliotherapy has occasionally been used as a counseling technique. However, most reports are basically single-case studies and the psychological effect of this approach remains unclear. Two experiments using 96 healthy college volunteers were conducted to determine how the reading of emotionally positive, negative, or neutral passages affect one's mood and level of distraction. Study 1 revealed that participants felt more relaxed after reading positive poems with either personal or social content than after reading negativie ones, and they felt least refreshed and calm after reading negative poems with personal content. Study 2 showed that participants reported less depressed feelings, both after reading an excerpt from an explanatory leaflet and after a controlled rest period. These results were discussed in terms of the mood congruence effect. Future research may evaluate the effects of reading novels, manga, and life teachings on self-narratives and views of life in normal and clinical populations. PMID:25639026

  14. Telomere protein RAP1 levels are affected by cellular aging and oxidative stress

    PubMed Central

    Swanson, Mark J.; Baribault, Michelle E.; Israel, Joanna N.; Bae, Nancy S.

    2016-01-01

    Telomeres are important for maintaining the integrity of the genome through the action of the shelterin complex. Previous studies indicted that the length of the telomere did not have an effect on the amount of the shelterin subunits; however, those experiments were performed using immortalized cells with stable telomere lengths. The interest of the present study was to observe how decreasing telomere lengths over successive generations would affect the shelterin subunits. As neonatal human dermal fibroblasts aged and their telomeres became shorter, the levels of the telomere-binding protein telomeric repeat factor 2 (TRF2) decreased significantly. By contrast, the levels of one of its binding partners, repressor/activator protein 1 (RAP1), decreased to a lesser extent than would be expected from the decrease in TRF2. Other subunits, TERF1-interacting nuclear factor 2 and protection of telomeres protein 1, remained stable. The decrease in RAP1 in the older cells occurred in the nuclear and cytoplasmic fractions. Hydrogen peroxide (H2O2) stress was used as an artificial means of aging in the cells, and this resulted in RAP1 levels decreasing, but the effect was only observed in the nuclear portion. Similar results were obtained using U251 glioblastoma cells treated with H2O2 or grown in serum-depleted medium. The present findings indicate that TRF2 and RAP1 levels decrease as fibroblasts naturally age. RAP1 remains more stable compared to TRF2. RAP1 also responds to oxidative stress, but the response is different to that observed in aging. PMID:27446538

  15. High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

    PubMed Central

    Hoda, Mir Alireza; Rozsas, Anita; Lang, Elisabeth; Klikovits, Thomas; Lohinai, Zoltan; Torok, Szilvia; Berta, Judit; Bendek, Matyas; Berger, Walter; Hegedus, Balazs; Klepetko, Walter; Renyi-Vamos, Ferenc; Grusch, Michael; Dome, Balazs; Laszlo, Viktoria

    2016-01-01

    Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p=0.015). ActA levels also correlated with more advanced disease stage (p<0.0001) and T (p=0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients (p<0.001). High serum ActA level was associated with poor overall survival (p<0.0001) and was confirmed as an independent prognostic factor (p=0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases. PMID:26950277

  16. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis.

    PubMed

    Jin, Junhua; Niu, Xiaojuan; Zou, Lihui; Li, Lin; Li, Shugang; Han, Jingli; Zhang, Peiying; Song, Jinghai; Xiao, Fei

    2016-08-01

    Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis. PMID:27160647

  17. Circulating Stromal Cell-Derived Factor 1α Levels in Heart Failure: A Matter of Proper Sampling

    PubMed Central

    Baerts, Lesley; Waumans, Yannick; Brandt, Inger; Jungraithmayr, Wolfgang; Van der Veken, Pieter; Vanderheyden, Marc; De Meester, Ingrid

    2015-01-01

    Background The chemokine Stromal cell-derived factor 1α (SDF1α, CXCL12) is currently under investigation as a biomarker for various cardiac diseases. The correct interpretation of SDF1α levels is complicated by the occurrence of truncated forms that possess an altered biological activity. Methodology We studied the immunoreactivities of SDF1α forms and evaluated the effect of adding a DPP4 inhibitor in sampling tubes on measured SDF1α levels. Using optimized sampling, we measured DPP4 activity and SDF1α levels in patients with varying degrees of heart failure. Results The immunoreactivities of SDF1α and its degradation products were determined with three immunoassays. A one hour incubation of SDF1α with DPP4 at 37°C resulted in 2/3 loss of immunoreactivity in each of the assays. Incubation with serum gave a similar result. Using appropriate sampling, SDF1α levels were found to be significantly higher in those heart failure patients with a severe loss of left ventricular function. DPP4 activity in serum was not altered in the heart failure population. However, the DPP4 activity was found to be significantly decreased in patients with high SDF1α levels Conclusions We propose that all samples for SDF1α analysis should be collected in the presence of at least a DPP4 inhibitor. In doing so, we found higher SDF1α levels in subgroups of patients with heart failure. Our work supports the need for further research on the clinical relevance of SDF1α levels in cardiac disease. PMID:26544044

  18. Intense exercise increases circulating endocannabinoid and BDNF levels in humans--possible implications for reward and depression.

    PubMed

    Heyman, E; Gamelin, F-X; Goekint, M; Piscitelli, F; Roelands, B; Leclair, E; Di Marzo, V; Meeusen, R

    2012-06-01

    The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise. Here we investigated, in 11 healthy trained male cyclists, the effects of an intense exercise (60 min at 55% followed by 30 min at 75% W(max)) on plasma levels of endocannabinoids (anandamide, AEA and 2-arachidonoylglycerol, 2-AG) and their possible link with serum BDNF. AEA levels increased during exercise and the 15 min recovery (P<0.001), whereas 2-AG concentrations remained stable. BDNF levels increased significantly during exercise and then decreased during the 15 min of recovery (P<0.01). Noteworthy, AEA and BDNF concentrations were positively correlated at the end of exercise and after the 15 min recovery (r>0.66, P<0.05), suggesting that AEA increment during exercise might be one of the factors involved in exercise-induced increase in peripheral BDNF levels and that AEA high levels during recovery might delay the return of BDNF to basal levels. AEA production during exercise might be triggered by cortisol since we found positive correlations between these two compounds and because corticosteroids are known to stimulate endocannabinoid biosynthesis. These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise. PMID:22029953

  19. Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2

    PubMed Central

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Shaikh, Almaas; Lambrecht, Nils W. G.; Rivier, Jean

    2011-01-01

    Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst2) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone for 10 min, P < 0.05). Levels were partly recovered at 7 h and fully restored at 24 h. The percentage of acyl ghrelin reduction was significantly higher than that of desacyl ghrelin at 2 h postsurgery and not at any other time point. This was associated with a 48 and 23% decrease in gastric and plasma ghrelin-O-acyltransferase protein concentrations, respectively (P < 0.001). Ghrelin-positive cells in the oxyntic mucosa expressed sst2a receptor and the sst2 agonist S-346-011 inhibited fasting acyl ghrelin levels by 64 and 77% at 0.5 and 2 h, respectively. The sst2 antagonist S-406-028 prevented the abdominal surgery-induced decreased circulating acyl ghrelin but not the delayed gastric emptying assessed 0.5 h postinjection. These data show that activation of sst2 receptor located on gastric X/A-like cells plays a key role in the rapid inhibition of circulating acyl ghrelin induced by abdominal surgery while not being primarily involved in the early phase of postoperative gastric ileus. PMID:21636529

  20. Endogenous Levels of Circulating Androgens and Risk of Crohn's Disease and Ulcerative Colitis Among Women: A Nested Case–Control Study from the Nurses' Health Study Cohorts

    PubMed Central

    Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Higuchi, Leslie M.; Fuchs, Charles S.; Richter, James M.; Tworoger, Shelley S.; Hankinson, Susan E.; Chan, Andrew T.

    2015-01-01

    Background: Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a nested case–control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone–binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. Results: Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39–1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21–1.15) for the third quartile, 0.22 (0.08–0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16–0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone–binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). Conclusions: Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted. PMID:25844961

  1. DNA topoisomerase III localizes to centromeres and affects centromeric CENP-A levels in fission yeast.

    PubMed

    Norman-Axelsson, Ulrika; Durand-Dubief, Mickaël; Prasad, Punit; Ekwall, Karl

    2013-01-01

    Centromeres are specialized chromatin regions marked by the presence of nucleosomes containing the centromere-specific histone H3 variant CENP-A, which is essential for chromosome segregation. Assembly and disassembly of nucleosomes is intimately linked to DNA topology, and DNA topoisomerases have previously been implicated in the dynamics of canonical H3 nucleosomes. Here we show that Schizosaccharomyces pombe Top3 and its partner Rqh1 are involved in controlling the levels of CENP-A(Cnp1) at centromeres. Both top3 and rqh1 mutants display defects in chromosome segregation. Using chromatin immunoprecipitation and tiling microarrays, we show that Top3, unlike Top1 and Top2, is highly enriched at centromeric central domains, demonstrating that Top3 is the major topoisomerase in this region. Moreover, centromeric Top3 occupancy positively correlates with CENP-A(Cnp1) occupancy. Intriguingly, both top3 and rqh1 mutants display increased relative enrichment of CENP-A(Cnp1) at centromeric central domains. Thus, Top3 and Rqh1 normally limit the levels of CENP-A(Cnp1) in this region. This new role is independent of the established function of Top3 and Rqh1 in homologous recombination downstream of Rad51. Therefore, we hypothesize that the Top3-Rqh1 complex has an important role in controlling centromere DNA topology, which in turn affects the dynamics of CENP-A(Cnp1) nucleosomes. PMID:23516381

  2. DNA Topoisomerase III Localizes to Centromeres and Affects Centromeric CENP-A Levels in Fission Yeast

    PubMed Central

    Norman-Axelsson, Ulrika; Durand-Dubief, Mickaël; Prasad, Punit; Ekwall, Karl

    2013-01-01

    Centromeres are specialized chromatin regions marked by the presence of nucleosomes containing the centromere-specific histone H3 variant CENP-A, which is essential for chromosome segregation. Assembly and disassembly of nucleosomes is intimately linked to DNA topology, and DNA topoisomerases have previously been implicated in the dynamics of canonical H3 nucleosomes. Here we show that Schizosaccharomyces pombe Top3 and its partner Rqh1 are involved in controlling the levels of CENP-ACnp1 at centromeres. Both top3 and rqh1 mutants display defects in chromosome segregation. Using chromatin immunoprecipitation and tiling microarrays, we show that Top3, unlike Top1 and Top2, is highly enriched at centromeric central domains, demonstrating that Top3 is the major topoisomerase in this region. Moreover, centromeric Top3 occupancy positively correlates with CENP-ACnp1 occupancy. Intriguingly, both top3 and rqh1 mutants display increased relative enrichment of CENP-ACnp1 at centromeric central domains. Thus, Top3 and Rqh1 normally limit the levels of CENP-ACnp1 in this region. This new role is independent of the established function of Top3 and Rqh1 in homologous recombination downstream of Rad51. Therefore, we hypothesize that the Top3-Rqh1 complex has an important role in controlling centromere DNA topology, which in turn affects the dynamics of CENP-ACnp1 nucleosomes. PMID:23516381

  3. How the initial level of visibility and limited resource affect the evolution of cooperation

    PubMed Central

    Han, Dun; Li, Dandan; Sun, Mei

    2016-01-01

    This work sheds important light on how the initial level of visibility and limited resource might affect the evolution of the players’ strategies under different network structure. We perform the prisoner’s dilemma game in the lattice network and the scale-free network, the simulation results indicate that the average density of death in lattice network decreases with the increases of the initial proportion of visibility. However, the contrary phenomenon is observed in the scale-free network. Further results reflect that the individuals’ payoff in lattice network is significantly larger than the one in the scale-free network. In the lattice network, the visibility individuals could earn much more than the invisibility one. However, the difference is not apparent in the scale-free network. We also find that a high Successful-Defection-Payoff (SDB) and a rich natural environment have relatively larger deleterious cooperation effects. A high SDB is beneficial to raising the level of visibility in the heterogeneous network, however, that has adverse visibility consequences in homogeneous network. Our result reveals that players are more likely to cooperate voluntarily under homogeneous network structure. PMID:27250335

  4. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe*

    PubMed Central

    Di, Guo-qing; Zhou, Bing; Li, Zheng-guang; Lin, Qi-li

    2011-01-01

    In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L WECPN) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals. After 29 d of airport noise exposure, the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe. PMID:22135145

  5. Lead level in seminal plasma may affect semen quality for men without occupational exposure to lead

    PubMed Central

    2012-01-01

    Background Infertility affects approximately 10–15% of reproductive-age couples. Poor semen quality contributes to about 25% of infertile cases. Resulting from the direct effect on testicular function or hormonal alterations, heavy metals exposure has been related to impaired semen quality. The objective of this study was to assess the level of lead in the seminal plasma in men without occupational exposure to lead, and to determine the relationship between semen quality and lead concentration in the semen. Methods This is a prospective and nonrandomized clinical study conducted in University infertility clinic and academic research laboratory. Three hundred and forty-one male partners of infertile couples undergoing infertility evaluation and management were recruited to the study. Semen samples collected for the analyses of semen quality were also used for the measurement of lead concentrations. Semen samples were evaluated according to the WHO standards. Results All subjects were married and from infertile couples without occupational exposure to lead. There is a significant inverse correlation between the lead concentration in seminal plasma and sperm count. A higher semen lead concentration was correlated with lower sperm count, but not with semen volume, sperm motility or sperm morphology as assessed by simple linear regression. Conclusions We found that semen lead concentration was significantly higher among the patients with lower sperm count. To our knowledge, this is the first study to demonstrate that a high level of lead accumulation in semen may reduce the sperm count contributing to infertility of men without occupational exposure to lead. PMID:23137356

  6. Ethanol exposure affects gene expression in the embryonic organizer and reduces retinoic acid levels.

    PubMed

    Yelin, Ronit; Schyr, Racheli Ben-Haroush; Kot, Hadas; Zins, Sharon; Frumkin, Ayala; Pillemer, Graciela; Fainsod, Abraham

    2005-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is a set of developmental malformations caused by alcohol consumption during pregnancy. Fetal Alcohol Syndrome (FAS), the strongest manifestation of FASD, results in short stature, microcephally and facial dysmorphogenesis including microphthalmia. Using Xenopus embryos as a model developmental system, we show that ethanol exposure recapitulates many aspects of FAS, including a shortened rostro-caudal axis, microcephally and microphthalmia. Temporal analysis revealed that Xenopus embryos are most sensitive to ethanol exposure between late blastula and early/mid gastrula stages. This window of sensitivity overlaps with the formation and early function of the embryonic organizer, Spemann's organizer. Molecular analysis revealed that ethanol exposure of embryos induces changes in the domains and levels of organizer-specific gene expression, identifying Spemann's organizer as an early target of ethanol. Ethanol also induces a defect in convergent extension movements that delays gastrulation movements and may affect the overall length. We show that mechanistically, ethanol is antagonistic to retinol (Vitamin A) and retinal conversion to retinoic acid, and that the organizer is active in retinoic acid signaling during early gastrulation. The model suggests that FASD is induced in part by an ethanol-dependent reduction in retinoic acid levels that are necessary for the normal function of Spemann's organizer. PMID:15708568

  7. How the initial level of visibility and limited resource affect the evolution of cooperation.

    PubMed

    Han, Dun; Li, Dandan; Sun, Mei

    2016-01-01

    This work sheds important light on how the initial level of visibility and limited resource might affect the evolution of the players' strategies under different network structure. We perform the prisoner's dilemma game in the lattice network and the scale-free network, the simulation results indicate that the average density of death in lattice network decreases with the increases of the initial proportion of visibility. However, the contrary phenomenon is observed in the scale-free network. Further results reflect that the individuals' payoff in lattice network is significantly larger than the one in the scale-free network. In the lattice network, the visibility individuals could earn much more than the invisibility one. However, the difference is not apparent in the scale-free network. We also find that a high Successful-Defection-Payoff (SDB) and a rich natural environment have relatively larger deleterious cooperation effects. A high SDB is beneficial to raising the level of visibility in the heterogeneous network, however, that has adverse visibility consequences in homogeneous network. Our result reveals that players are more likely to cooperate voluntarily under homogeneous network structure. PMID:27250335

  8. Plant volatiles induced by herbivore egg deposition affect insects of different trophic levels.

    PubMed

    Fatouros, Nina E; Lucas-Barbosa, Dani; Weldegergis, Berhane T; Pashalidou, Foteini G; van Loon, Joop J A; Dicke, Marcel; Harvey, Jeffrey A; Gols, Rieta; Huigens, Martinus E

    2012-01-01

    Plants release volatiles induced by herbivore feeding that may affect the diversity and composition of plant-associated arthropod communities. However, the specificity and role of plant volatiles induced during the early phase of attack, i.e. egg deposition by herbivorous insects, and their consequences on insects of different trophic levels remain poorly explored. In olfactometer and wind tunnel set-ups, we investigated behavioural responses of a specialist cabbage butterfly (Pieris brassicae) and two of its parasitic wasps (Trichogramma brassicae and Cotesia glomerata) to volatiles of a wild crucifer (Brassica nigra) induced by oviposition of the specialist butterfly and an additional generalist moth (Mamestra brassicae). Gravid butterflies were repelled by volatiles from plants induced by cabbage white butterfly eggs, probably as a means of avoiding competition, whereas both parasitic wasp species were attracted. In contrast, volatiles from plants induced by eggs of the generalist moth did neither repel nor attract any of the tested community members. Analysis of the plant's volatile metabolomic profile by gas chromatography-mass spectrometry and the structure of the plant-egg interface by scanning electron microscopy confirmed that the plant responds differently to egg deposition by the two lepidopteran species. Our findings imply that prior to actual feeding damage, egg deposition can induce specific plant responses that significantly influence various members of higher trophic levels. PMID:22912893

  9. LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor Localization

    PubMed Central

    Spissu, Ylenia; Sanna, Giovanna; Xiong, Yulan; Dawson, Ted M.; Dawson, Valina L.; Galioto, Manuela; Rocchitta, Gaia; Biosa, Alice; Serra, Pier Andrea; Carri, Maria Teresa; Crosio, Claudia; Iaccarino, Ciro

    2013-01-01

    The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson’s disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2G2019S pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2G2019S shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells. PMID:24167564

  10. How the initial level of visibility and limited resource affect the evolution of cooperation

    NASA Astrophysics Data System (ADS)

    Han, Dun; Li, Dandan; Sun, Mei

    2016-06-01

    This work sheds important light on how the initial level of visibility and limited resource might affect the evolution of the players’ strategies under different network structure. We perform the prisoner’s dilemma game in the lattice network and the scale-free network, the simulation results indicate that the average density of death in lattice network decreases with the increases of the initial proportion of visibility. However, the contrary phenomenon is observed in the scale-free network. Further results reflect that the individuals’ payoff in lattice network is significantly larger than the one in the scale-free network. In the lattice network, the visibility individuals could earn much more than the invisibility one. However, the difference is not apparent in the scale-free network. We also find that a high Successful-Defection-Payoff (SDB) and a rich natural environment have relatively larger deleterious cooperation effects. A high SDB is beneficial to raising the level of visibility in the heterogeneous network, however, that has adverse visibility consequences in homogeneous network. Our result reveals that players are more likely to cooperate voluntarily under homogeneous network structure.

  11. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe.

    PubMed

    Di, Guo-Qing; Zhou, Bing; Li, Zheng-Guang; Lin, Qi-Li

    2011-12-01

    In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L(WECPN)) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals. After 29 d of airport noise exposure, the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe. PMID:22135145

  12. Plant Volatiles Induced by Herbivore Egg Deposition Affect Insects of Different Trophic Levels

    PubMed Central

    Fatouros, Nina E.; Lucas-Barbosa, Dani; Weldegergis, Berhane T.; Pashalidou, Foteini G.; van Loon, Joop J. A.; Dicke, Marcel; Harvey, Jeffrey A.; Gols, Rieta; Huigens, Martinus E.

    2012-01-01

    Plants release volatiles induced by herbivore feeding that may affect the diversity and composition of plant-associated arthropod communities. However, the specificity and role of plant volatiles induced during the early phase of attack, i.e. egg deposition by herbivorous insects, and their consequences on insects of different trophic levels remain poorly explored. In olfactometer and wind tunnel set-ups, we investigated behavioural responses of a specialist cabbage butterfly (Pieris brassicae) and two of its parasitic wasps (Trichogramma brassicae and Cotesia glomerata) to volatiles of a wild crucifer (Brassica nigra) induced by oviposition of the specialist butterfly and an additional generalist moth (Mamestra brassicae). Gravid butterflies were repelled by volatiles from plants induced by cabbage white butterfly eggs, probably as a means of avoiding competition, whereas both parasitic wasp species were attracted. In contrast, volatiles from plants induced by eggs of the generalist moth did neither repel nor attract any of the tested community members. Analysis of the plant’s volatile metabolomic profile by gas chromatography-mass spectrometry and the structure of the plant-egg interface by scanning electron microscopy confirmed that the plant responds differently to egg deposition by the two lepidopteran species. Our findings imply that prior to actual feeding damage, egg deposition can induce specific plant responses that significantly influence various members of higher trophic levels. PMID:22912893

  13. Circulating Levels of Betatrophin and Irisin Are Not Associated with Pancreatic β-Cell Function in Previously Diagnosed Type 2 Diabetes Mellitus Patients

    PubMed Central

    Wang, Lingshu; Song, Jun; Wang, Chuan; Lin, Peng; Liang, Kai; Sun, Yu; He, Tianyi; Li, Wenjuan; Zhao, Ruxing; Qin, Jun; Lu, Yiran; Liu, Jinbo; Liu, Fuqiang; Hou, Xinguo; Chen, Li

    2016-01-01

    Betatrophin and irisin are two recently identified hormones which may participate in regulating pancreatic β-cell function. However, the associations of these two hormones with β-cell function remain unclear. The present study aims to demonstrate the associations of circulating betatrophin and irisin levels with β-cell function, assessed by the area under the curve (AUC) of C-peptide, and the possible correlation between these two hormones in previously diagnosed type 2 diabetes mellitus (T2DM) patients. In total, 20 age-, sex-, and body mass index- (BMI-) matched normal glucose tolerance (NGT) subjects and 120 previously diagnosed T2DM patients were included in this study. Partial correlation analysis was used to evaluate the relationships between these two hormones and indexes of β-cell function and insulin resistance. Our results showed that betatrophin levels were significantly elevated, while irisin levels were significantly decreased, in patients with T2DM compared with NGT subjects. However, partial correlation analysis showed that betatrophin levels did not correlate with β-cell function-related variables or insulin resistance-related variables before or after controlling multiple covariates, while irisin correlated positively with insulin sensitivity but is not associated with β-cell function-related variables. Besides, no correlation was observed between betatrophin and irisin levels. Hence we concluded that betatrophin and irisin were not associated with β-cell function in previously diagnosed T2DM patients. PMID:26649318

  14. A pilot trial to examine the association between circulating endothelial cell levels and vascular injury in patients with diabetes and chronic kidney disease

    PubMed Central

    Shirazian, Shayan; Grant, Candace; Rambhujun, Vikash; Sharma, Ritika; Patel, Ronak; Islam, Shahidul; Mattana, Joseph

    2016-01-01

    Objective While albuminuria is a marker for progressive chronic kidney disease (CKD) in patients with type 2 diabetes (T2DM), both albuminuric and normoalbuminuric patients appear prone to vascular injury. This pilot study examines the association between circulating endothelial cell (CEC) levels and vascular injury in patients with T2DM and CKD. Methods In this cross-sectional study, eligible adult patients had T2DM, and stage 3 CKD (estimated glomerular filtration rate between 30 and 60 mL/min/1.73m 2). CEC levels were tested by Janssen Diagnostics, LLC using an immuno-magnetic bead-based assay. CEC levels were compared to levels in a previously tested normal population. Correlations between CEC levels and other vascular injury markers (urine albumin, von-Willebrand factor antigen, hs-CRP, uric acid) were performed. Results Patients included 40 adults of which nineteen were normoalbuminuric.  Mean CEC levels (38.7, SD 38.1 cells) were significantly higher than the normal population (M = 21±18 cells, p<0.001; N = 249), including in the normoalbuminuric subgroup (M = 42.9±42.5 cells, p<0.001). CEC levels were significantly correlated with uric acid levels (r=0.33, p=0.039). Conclusions CEC levels in patients with T2DM and CKD, both albuminuric and normoalbuminuric, are significantly higher than a normal population, suggesting the presence of vascular injury in both groups. Future studies are needed to evaluate the role of CECs as a biomarker to predict outcomes in normoalbuminuric patients with CKD. PMID:27303625

  15. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    NASA Technical Reports Server (NTRS)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

    1998-01-01

    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  16. Prenatal exposure to perfluorinated compounds affects thyroid hormone levels in newborn girls.

    PubMed

    Shah-Kulkarni, Surabhi; Kim, Byung-Mi; Hong, Yun-Chul; Kim, Hae Soon; Kwon, Eun Jin; Park, Hyesook; Kim, Young Ju; Ha, Eun-Hee

    2016-09-01

    Perfluorinated compounds (PFCs) are ubiquitous in the environment and have been detected in humans and wildlife. Exposure to PFCs has decreased in the United States recently, while exposure to PFCs continues in Asian countries, which represents a public health concern. Various mechanisms by which PFCs affect fetal growth have been proposed, such as activation of peroxisome proliferators, disruption of thyroid hormones and changes in lipid metabolism. However, the overall evidence for an association with thyroid hormones is not strong. Therefore, we examined the effect of various prenatal PFCs on cord blood thyroid hormones: triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) levels, and explored the endocrine disrupting effect of these PFCs on thyroid hormone levels in children according to gender. Two hundred and seventy-nine study participants were selected from among the enrolled participants in the Ewha Birth & Growth Retrospective Cohort, a retrospective birth cohort study conducted at Ewha Womans University Hospital, Seoul, Korea between 2006 and 2010. A generalized linear model was constructed to explore the association of PFCs and thyroid hormones. Further, an analysis stratified by gender was conducted. Our study shows that cord blood perfluoro n-pentanoic acid (PFPeA) was positively associated with cord blood T4 (p=0.01) level. Gender-specific analysis showed that prenatal PFCs: PFPeA and Perfluorohexane sulfonic acid (PFHxS) exposure significantly increased T4 (p<0.01) and T3 (p=0.03), respectively, while perfluorononanoic acid (PFNA) decreased TSH (p=0.04) concentration in newborn girls. Thus, prenatal PFC exposure may disrupt thyroid hormone homeostasis. Thyroid hormones play a crucial role in fetal development and may have gender specific action. Hence, these results are of utmost importance in high-risk groups, such as pregnant women and children. PMID:27395336

  17. Chronic Exposure to Ambient Levels of Urban Particles Affects Mouse Lung Development

    PubMed Central

    Mauad, Thais; Rivero, Dolores Helena Rodriguez Ferreira; de Oliveira, Regiani Carvalho; de Faria Coimbra Lichtenfels, Ana Julia; Guimarães, Eliane Tigre; de Andre, Paulo Afonso; Kasahara, David Itiro; de Siqueira Bueno, Heloisa Maria; Saldiva, Paulo Hilário Nascimento

    2008-01-01

    Rationale: Chronic exposure to air pollution has been associated with adverse effects on children's lung growth. Objectives: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development. Methods: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in São Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM2.5 inside the filtered chamber (filtered = 2.9 ± 3.0 μg/m3, nonfiltered = 16.8 ± 8.3 μg/m3; P = 0.001). At this exposure site, vehicular sources are the major components of PM2.5 (PM ≤ 2.5μm). Exposure of the parental generation in the two chambers occurred from the 10th to the 120th days of life. After mating and birth of offspring, a crossover of mothers and pups occurred within the chambers, resulting in four groups of pups: nonexposed, prenatal, postnatal, and pre+postnatal. Offspring were killed at the age of 15 (n = 42) and 90 (n = 35) days; lungs were analyzed by morphometry for surface to volume ratio (as an estimator of alveolization). Pressure–volume curves were performed in the older groups, using a 20-ml plethysmograph. Measurements and Main Results: Mice exposed to PM2.5 pre+postnatally presented a smaller surface to volume ratio when compared with nonexposed animals (P = 0.036). The pre+postnatal group presented reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure (P = 0.001). There were no differences among prenatal and postnatal exposure and nonexposed animals. Conclusions: Our data provide anatomical and functional support to the concept that chronic exposure to urban PM affects lung growth. PMID:18596224

  18. Levels of Schistosoma mansoni Circulating Antigen in Chronic Hepatitis C Patients with Different Stages of Liver Fibrosis.

    PubMed

    Attallah, Abdelfattah M; El-Far, Mohamed; Omran, Mohamed M; Farid, Khaled; Attallah, Ahmed A; Abd-Elaziz, Dalal; El-Bendary, Mohamed S; El-Dosoky, Ibrahim; Ismail, Hisham

    2016-01-01

    The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (μg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 μg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease. PMID:26745203

  19. An evaluation of circulating bovine diarrhea virus type 2 maternal antibody level and response to vaccination in Angus calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination against viruses has been shown to help prevent bovine respiratory disease in cattle. However, both passively acquired maternal antibody level and calf age have been shown to impact the ability of a calf’s immune system to respond to vaccination. The objectives of this study were to ident...

  20. Effects of niacin, statin, and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 levels in patients with dyslipidemia.

    PubMed

    Khera, Amit V; Qamar, Arman; Reilly, Muredach P; Dunbar, Richard L; Rader, Daniel J

    2015-01-15

    Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 (PCSK9). Although statins and fibrates have been reported to increase plasma PCSK9 levels, the effect of niacin on PCSK9 is unknown. We investigated the impact of niacin, atorvastatin, and fenofibrate on PCSK9 levels in 3 distinct studies. A statin-only study randomized 74 hypercholesterolemic patients to placebo, atorvastatin 10 mg/day, or atorvastatin 80 mg/day for 16 weeks. A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean +27% (95% confidence interval [CI] +12 to +42), confirming the effect of statin therapy on raising PCSK9. A second study randomized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day, simvastatin 80 mg/day, or simvastatin 20 mg/extended-release (ER) niacin 2 g/day. PCSK9 levels were increased with statin therapy, but decreased with the simvastatin 20 mg/ER niacin combination (mean -13%, CI -3 to -23). A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day. Fenofibric acid led to a +23% (CI +10 to +36, p = 0.001) increase in PCSK9; the addition of niacin resulted in a subsequent -17% decrease (CI -19 to -5, p = 0.004). A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels (r = 0.62, p = 0.006) with the addition of niacin. In conclusion, niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy. A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9. PMID:25432415

  1. Higher circulating levels of chemokines CXCL10, CCL20 and CCL22 in patients with ischemic heart disease.

    PubMed

    Safa, A; Rashidinejad, H R; Khalili, M; Dabiri, S; Nemati, M; Mohammadi, M M; Jafarzadeh, A

    2016-07-01

    Recruitment of leukocytes is one of the earliest events in the pathogenesis of ischemic heart disease (IHD) and chemokines play an important role in the migration of these cells into the inflammation sites. The aim of this study was to evaluate the CXCL10, CCL20 and CCL22 levels and the single nucleotide polymorphisms (SNPs) rs4508917, rs6749704 and rs4359426 in chemokine genes in patients with IHD to clarify any association. A total of 300 patients with IHD as having acute myocardial infarction (AMI; n=100), stable angina (SA; n=100) or unstable angina (UA; n=100) and 100 healthy subjects as a control group were enrolled to study. Serum samples from all participants were tested for the CXCL10, CCL20 and CCL22 levels by using ELISA. The SNPs were determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method. The mean serum concentrations of CXCL10, CCL20 and CCL22 in AMI patients (395.97±21.20Pg/mL, 108.38±10.31Pg/mL and 1852.58±205.77Pg/mL), SA patients (405.48±27.36Pg/mL, 90.20±7.69Pg/mL and 2322.04±231.23Pg/mL) and UA patients (396.69±22.79Pg/mL, 141.87±18.10Pg/mL and 2754.89±211.70Pg/mL) were significantly higher than in the healthy group (179.38±8.85Pg/mL, 51.92±4.62Pg/mL and 451.82±23.76Pg/mL, respectively; P<0.001). Similarly, the serum levels of CXCL10, CCL20 and CCL22 in total IHD patients (399.38±13.77Pg/mL, 113.49±7.48Pg/mL and 2309.84±126.39Pg/mL, respectively) were also significantly higher as compared with healthy subjects (P<0.001). The serum levels of CCL20 and CCL22 in UA patients were significantly higher than those in SA and AMI patients, respectively (P<0.01 and P<0.003, respectively). The serum levels of CXCL10 and CCL20 in diabetic patients were significantly higher in comparison to non-diabetic patients (P<0.05 and P<0.02, respectively). The serum levels of CCL22 in dyslipidemic- and obese patients were also significantly higher in comparison with non-dyslipidemic- and non-obese patients

  2. Gravitoinertial force background level affects adaptation to coriolis force perturbations of reaching movements

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; Dizio, P.

    1998-01-01

    We evaluated the combined effects on reaching movements of the transient, movement-dependent Coriolis forces and the static centrifugal forces generated in a rotating environment. Specifically, we assessed the effects of comparable Coriolis force perturbations in different static force backgrounds. Two groups of subjects made reaching movements toward a just-extinguished visual target before rotation began, during 10 rpm counterclockwise rotation, and after rotation ceased. One group was seated on the axis of rotation, the other 2.23 m away. The resultant of gravity and centrifugal force on the hand was 1.0 g for the on-center group during 10 rpm rotation, and 1.031 g for the off-center group because of the 0.25 g centrifugal force present. For both groups, rightward Coriolis forces, approximately 0.2 g peak, were generated during voluntary arm movements. The endpoints and paths of the initial per-rotation movements were deviated rightward for both groups by comparable amounts. Within 10 subsequent reaches, the on-center group regained baseline accuracy and straight-line paths; however, even after 40 movements the off-center group had not resumed baseline endpoint accuracy. Mirror-image aftereffects occurred when rotation stopped. These findings demonstrate that manual control is disrupted by transient Coriolis force perturbations and that adaptation can occur even in the absence of visual feedback. An increase, even a small one, in background force level above normal gravity does not affect the size of the reaching errors induced by Coriolis forces nor does it affect the rate of reacquiring straight reaching paths; however, it does hinder restoration of reaching accuracy.

  3. Prenatal and lactation nicotine exposure affects Sertoli cell and gonadotropin levels in rats.

    PubMed

    Paccola, C C; Miraglia, S M

    2016-02-01

    Nicotine is largely consumed in the world as a component of cigarettes. It can cross the placenta and reach the milk of smoking mothers. This drug induces apoptosis, affects sex hormone secretion, and leads to male infertility. To investigate the exposure to nicotine during the whole intrauterine and lactation phases in Sertoli cells, pregnant rats received nicotine (2 mg/kg per day) through osmotic minipumps. Male offsprings (30, 60, and 90 days old) had blood collected for hormonal analysis (FSH and LH) and their testes submitted for histophatological study, analysis of the frequency of the stages of seminiferous epithelium cycle, immunolabeling of apoptotic epithelial cells (TUNEL and Fas/FasL), analysis of the function and structure of Sertoli cells (respectively using transferrin and vimentin immunolabeling), and analysis of Sertoli-germ cell junctional molecule (β-catenin immunolabeling). The exposure to nicotine increased the FSH and LH plasmatic levels in adult rats. Although nicotine had not changed the number of apoptotic cells, neither in Fas nor FasL expression, it provoked an intense sloughing of epithelial cells and also altered the frequency of some stages of the seminiferous epithelium cycle. Transferrin and β-catenin expressions were not changed, but vimentin was significantly reduced in the early stages of the seminiferous cycle of the nicotine-exposed adult rats. Thus, we concluded that nicotine exposure during all gestational and lactation periods affects the structure of Sertoli cells by events causing intense germ cell sloughing observed in the tubular lumen and can compromise the fertility of the offspring. PMID:26556892

  4. The balance of kinetic and total energy simulated by the OSU two-level atmospheric general circulation model for January and July

    NASA Technical Reports Server (NTRS)

    Wang, J.-T.; Gates, W. L.; Kim, J.-W.

    1984-01-01

    A three-year simulation which prescribes seasonally varying solar radiation and sea surface temperature is the basis of the present study of the horizontal structure of the balances of kinetic and total energy simulated by Oregon State University's two-level atmospheric general circulation model. Mechanisms responsible for the local energy changes are identified, and the energy balance requirement's fulfilment is examined. In January, the vertical integral of the total energy shows large amounts of external heating over the North Pacific and Atlantic, together with cooling over most of the land area of the Northern Hemisphere. In July, an overall seasonal reversal is found. Both seasons are also characterized by strong energy flux divergence in the tropics, in association with the poleward transport of heat and momentum.

  5. Reduced circulating levels of angiotensin‐(1–7) in systemic sclerosis: a new pathway in the dysregulation of endothelial‐dependent vascular tone control

    PubMed Central

    Pignone, Alberto; Del Rosso, Angela; Brosnihan, K Bridget; Perfetto, Federico; Livi, Riccardo; Fiori, Ginevra; Guiducci, Serena; Cinelli, Marina; Rogai, Veronica; Tempestini, Alessio; Bartoli, Francesca; Generini, Sergio; Ferrario, Carlos M; Cerinic, Marco Matucci

    2007-01-01

    Objective Systemic sclerosis (SSc) impairs endothelium‐dependent vasodilatation. Among angiotensin I (Ang I)‐derived compounds, vasoconstrictor angiotensin II (Ang II) and vasodilator angiotensin‐(1–7) (Ang‐(1–7)), cleaved from ACE and neutral endopeptidase (NEP) 24.11, respectively, play an important role in vascular tone regulation. Ang‐(1–7) may act independently or by activating other vasodilating molecules, such as nitric oxide (NO) or prostaglandin I2 (PGI2). Our aim was to assess, in patients with SSc, circulating levels of Ang I, Ang II and Ang‐(1–7), with their metabolising enzymes ACE and NEP, and levels of NO and PGI2, and to correlate them to the main characteristics of SSc. Methods Levels of Ang I, Ang II, Ang‐(1–7), NEP, ACE, NO and PGI2 were measured in 32 patients with SSc, who were also assessed for humoral and clinical characteristics, and 55 controls. Results Plasma Ang I, Ang II and Ang‐(1–7) levels were lower in patients with SSc than in controls (p<0.001in all cases). When Ang II and Ang‐(1–7) levels were expressed as a function of the available Ang I, lower Ang‐(1–7) levels in patients with SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In patients with SSc, the Ang II/Ang‐(1–7) ratio indicated a prevalence of Ang II over Ang‐(1–7), while in controls Ang‐(1–7) was prevalent (p<0.001). Levels of ACE, NEP, NO and PGI2 were lower in patients with SSc than in controls (p<0.05 in all cases). Conclusion In patients with SSc, prevalence of the vasoconstricting Ang II over the vasodilator Ang‐(1–7) suggests a dysfunction of the angiotensin‐derived cascade that may contribute to dysregulation of vascular tone. PMID:17360781

  6. Parental care, loss of paternity and circulating levels of testosterone and corticosterone in a socially monogamous song bird

    PubMed Central

    2014-01-01

    Introduction In biparental birds testosterone levels of males are typically high during the mating phase and decrease during the parental phase. Testosterone implants may enhance mating behaviors, increase the likelihood of males to engage in extra-pair mating behavior and may reduce paternal care. Thus, sex steroids such as testosterone influence reproductive behaviors. Little is known, however, as to whether the more subtle differences in physiological concentrations of testosterone that occur between individuals are related to differences in paternal care, extra-pair behavior, and genetic paternity between those males. Here, we investigate these relationships in the male black redstart (Phoenicurus ochruros), a socially monogamous songbird with a low breeding synchrony. We used nestling provisioning as a proxy for parental care behavior and genetic paternity loss as a proxy for the efficiency of mate-guarding. Results There was no relationship between nestling provisioning and paternity loss of males. Baseline and gonadotropin releasing hormone (GnRH)-induced levels of testosterone, but not baseline corticosterone, were significantly higher during the mating than during the provisioning phase. Males fed more often when temperatures decreased and fed less when they sang more, but we found no correlation between parental behavior and baseline or GnRH-induced testosterone, and baseline corticosterone – both measured during either the mating or the parental phase. However, males that experienced loss of paternity had lower levels of testosterone during the provisioning phase than males that did not lose paternity. Further, males that lost paternity also expressed higher baseline levels of corticosterone. Conclusions Physiological differences in testosterone or baseline corticosterone were not related to differences in parental care, suggesting that the variation of testosterone within a physiological range may not relate to the degree of paternal care in this

  7. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.

    PubMed

    Bonilla, Carolina; Lewis, Sarah J; Rowlands, Mari-Anne; Gaunt, Tom R; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lathrop, Mark; Martin, Richard M; Holly, Jeff M P

    2016-10-01

    Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. PMID:27225428

  8. Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up

    PubMed Central

    Domanico, Daniela; Fragiotta, Serena; Cutini, Alessandro; Carnevale, Carmela; Zompatori, Luigi; Vingolo, Enzo Maria

    2015-01-01

    Aims: The aim was to evaluate circulating levels of reactive oxygen species (ROS) and changes in central macular thickness (CMT) in patients with nonproliferative diabetic retinopathy (NPDR) after antioxidant supplementation. Materials and Methods: A total of 68 patients (68 eyes) with NPDR were enrolled. Patients were randomly divided into two groups: Treated with antioxidant supplement (Group A) and untreated control group (Group B). Each tablet, for oral administration, containing pycnogenol 50 mg, Vitamin E 30 mg and coenzyme Q10 20 mg. CMT and free oxygen radical test (FORT) were analyzed at baseline (T0), 3 (T1) and 6 (T2) months in both groups. Results: In Group A, FORT levels and CMT were significantly reduced over time (P < 0.001 for both). In Group B, FORT levels were increased (P < 0.001) and CMT did not vary significantly (P = 0.81) over 3 time points. Conclusions: This is the first study showing the reduction of ROS levels in patients with NPDR thanks to antioxidant therapy. Moreover, our findings have suggested also an influence on retinal thickness. PMID:25686055

  9. Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-Care Test Strip and a Portable Spectrodensitometer.

    PubMed

    Chesnais, Cédric B; Vlaminck, Johnny; Kunyu-Shako, Billy; Pion, Sébastien D; Awaca-Uvon, Naomi-Pitchouna; Weil, Gary J; Mumba, Dieudonné; Boussinesq, Michel

    2016-06-01

    The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements were highly correlated with vFTS scores (ρ = 0.94; P < 0.001) and with plasma CFA levels (ρ = 0.91; P < 0.001). Thus, qFTS assessment is a convenient method for quantifying W. bancrofti CFA levels in human blood, which are correlated with adult worm burdens. This tool may be useful for assessing the impact of treatment on adult filarial worms in individuals and communities. PMID:27114288

  10. Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-Care Test Strip and a Portable Spectrodensitometer

    PubMed Central

    Chesnais, Cédric B.; Vlaminck, Johnny; Kunyu-Shako, Billy; Pion, Sébastien D.; Awaca-Uvon, Naomi-Pitchouna; Weil, Gary J.; Mumba, Dieudonné; Boussinesq, Michel

    2016-01-01

    The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements were highly correlated with vFTS scores (ρ = 0.94; P < 0.001) and with plasma CFA levels (ρ = 0.91; P < 0.001). Thus, qFTS assessment is a convenient method for quantifying W. bancrofti CFA levels in human blood, which are correlated with adult worm burdens. This tool may be useful for assessing the impact of treatment on adult filarial worms in individuals and communities. PMID:27114288

  11. Circulating myosin light chain I levels after coronary reperfusion: a comparison with myocardial necrosis evaluated from single photon emission computed tomography with pyrophosphate.

    PubMed

    Yoshida, H; Mochizuki, M; Sakata, K; Takezawa, M; Matsumoto, Y; Yoshimura, M; Mori, N; Yokoyama, S; Hoshino, T; Kaburagi, T

    1992-02-01

    This study was performed to assess the influence of coronary reperfusion on the serial serum myosin light chain (LC)I levels and to evaluate the relationship between the peak LCI level and the infarct size calculated from single photon emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m PYP) in 11 patients who underwent coronary reperfusion. Blood was drawn before reperfusion, immediately after reperfusion, and once a day for 14 days, to estimate the time course of serum LCI release. The infarct size estimated by Tc-99m PYP ranged from 7.3 to 62.4 ml. The LCI levels obtained before reperfusion were less than 2.5 ng/ml but those obtained immediately after reperfusion were much higher. The value ranged from 2.7 to 9.7 ng/ml and that expressed as a percentage of peak LCI (% peak LCI) ranged from 19 to 83%. Collateral circulation, reperfusion arrhythmia and the degree of residual stenosis had no influence upon the % peak LCI. The correlation between peak LCI levels and SPECT-determined infarct size was good, with a correlation of 0.76 (p less than 0.01, regression line by least squares method y = 3.31 + 1.53x). Early serum LCI might be influenced by coronary reperfusion but the peak LCI value reflected acute myocardial necrosis in patients who underwent coronary reperfusion. PMID:1387796

  12. LPS alters pattern of sickness behavior but does not affect glutathione level in aged male rats.

    PubMed

    Wrotek, Sylwia; Jędrzejewski, Tomasz; Nowakowska, Anna; Kozak, Wiesław

    2016-08-01

    Behavioral symptoms of sickness, such as fever and motor activity are a coordinated set of changes that develop during infection. The aim of study was to compare the sickness behaviour (SB) in healthy old and young rats treated with pyrogenic dose of endotoxin and to check their glutathione level. Before experimentation male Wistar rats were selected according to standard body mass, motor activity, and white blood cells count. Intraperitoneal injection of lipopolysaccharide (LPS) from E. coli was used to provoke SB. The level of liver glutathione, interleukin (IL) -6, deep body temperature (Tb) and motor activity were measured. Glutathione level in old and young rats did not differ significantly. In both young and old rats LPS administration provoked fever (the mean value of Tb was 38.06 ± 0.01 °C in old rats, and 38.19 ± 0.06 °C in young rats). LPS injection affected night-time activity in both groups (12 h averages were 1.56 ± 0.40 counts in old LPS-treated rats vs 2.74 ± 0.53 counts in not-treated old rats and 3.44 ± 0.60 counts for young LPS-treated vs 4.28 ± 0.57 counts for young not-treated rats). The injection of LPS provoked an elevation of plasma IL-6 concentration (from values below the lowest detectable standard in not-treated groups of animals to 6322.82 ± 537.00 pg/mL in old LPS-treated rats and 7415.62 ± 451.88 pg/mL in young LPS-treated rats). Based on these data, we conclude that good health of aged rats prevents decrease in the glutathione level. Old rats are still able to develop SB in response to pyrogenic dose of LPS, although its components have changed pattern compared to young animals. PMID:26829940

  13. Circulating S100A12 Levels Are Associated with Progression of Abdominal Aortic Calcification in Hemodialysis Patients

    PubMed Central

    Jung, Eul Sik; Kim, Ae Jin; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Jung, Ji Yong

    2016-01-01

    Vascular calcification is an important factor associated with mortality in dialysis patients. Recently, soluble receptor for advanced glycation end product (sRAGE) and extracellular RAGE binding protein S100A12 (EN-RAGE) have been reported to be involved in the process of vascular calcification. Therefore, we investigated whether sRAGE and S100A12 are useful indicators of progression of abdominal aortic calcification in hemodialysis (HD) patients. We analyzed annual changes in vascular calcification score (VCS) for up to 4 years, compared to clinical and biological parameters in 149 HD patients. VCS was assessed annually using plain X-ray images of the lateral lumbar spine. The progression group was defined as patients with an increase in VCS more than 1 point each year on average during the observation period. Time-averaged concentrations were also evaluated to examine the association between biological parameters and changes in VCS. The patients had a mean age of 58.59 ± 12.93 years; 53.7% were male, and 45% were diabetic. The VCS increased in 55 patients; the mean increase was 1.60 ± 2.91 points. In a stepwise multivariate logistic analysis, we found that higher levels of S100A12 were significantly associated with progression of VCS (odds ratio [OR], 2.622; 95% confidence interval [CI], 1.371–5.016; P = 0.004). The relationship between sRAGE and VCS was not statistically significant (OR, 0.644; 95% CI, 0.302–1.374; P = 0.255). Our findings suggest that serum levels of S100A12 are associated with progression of abdominal aortic calcification in HD patients, independent of sRAGE level. PMID:26914918

  14. Association Between Circulating Levels of Sex Steroid Hormones and Barrett's Esophagus in Men: a Case–Control Analysis

    PubMed Central

    Cook, Michael B.; Wood, Shannon N.; Cash, Brooks D.; Young, Patrick; Acosta, Ruben D.; Falk, Roni T.; Pfeiffer, Ruth M.; Hu, Nan; Su, Hua; Wang, Lemin; Wang, Chaoyu; Gherman, Barbara; Giffen, Carol; Dykes, Cathy; Turcotte, Veronique; Caron, Patrick; Guillemette, Chantal; Dawsey, Sanford M.; Abnet, Christian C.; Hyland, Paula L.; Taylor, Philip R.

    2014-01-01

    Background & Aims Esophageal adenocarcinoma is believed to result from the progression of gastroesophageal reflux disease to erosive esophagitis and re-epithelialization of the esophagus with a columnar cell population termed Barrett's esophagus (BE). Men develop BE and esophageal adenocarcinoma more frequently than women, and the ratio is increasing; approximately 7 men are diagnosed with malignancy for every woman, yet little is known about the mechanisms of this difference. We assessed whether sex steroid hormones were associated with BE in a male population. Methods We analyzed data from the Barrett's Esophagus Early Detection Case Control Study, based at the Walter Reed National Military Medical Center. Blood samples were collected from 173 men with BE and 213 men without BE (controls, based on endoscopic analysis); 13 sex steroid hormones were measured by mass spectrometry and sex hormone binding globulin was measured by ELISA. We also calculated free estradiol, free testosterone and free dihydrotestosterone (DHT). We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, race, smoking status, alcohol consumption, body mass index (BMI; kg/m2), heartburn, regurgitation, and gastroesophageal symptom score (excluding heartburn and regurgitation). Results Levels of free testosterone and free DHT were positively associated with BE risk; patients in the highest quartile for these hormones were most likely to have BE (for free testosterone, OR=5.36; 95% CI, 2.21–13.03; P=0.0002 and for free DHT, OR=4.25, 95% CI, 1.87–9.66; P=.001). Level of estrone sulfate was inversely associated with BE risk (P for trend=.02). No other hormone was associated with BE risk. Relationships were not modified by age or BMI. Conclusions In an analysis of men, levels of free testosterone and free DHT were significantly associated with risk of BE. PMID:25158929

  15. Reduction in DNA topoisomerase I level affects growth, phenotype and nucleoid architecture of Mycobacterium smegmatis.

    PubMed

    Ahmed, Wareed; Menon, Shruti; Karthik, Pullela V; Nagaraja, Valakunja

    2015-02-01

    The steady-state negative supercoiling of eubacterial genomes is maintained by the action of DNA topoisomerases. Topoisomerase distribution varies in different species of mycobacteria. While Mycobacterium tuberculosis (Mtb) contains a single type I (TopoI) and a single type II (Gyrase) enzyme, Mycobacterium smegmatis (Msm) and other members harbour additional relaxases. TopoI is essential for Mtb survival. However, the necessity of TopoI or other relaxases in Msm has not been investigated. To recognize the importance of TopoI for growth, physiology and gene expression of Msm, we have developed a conditional knock-down strain of TopoI in Msm. The TopoI-depleted strain exhibited extremely slow growth and drastic changes in phenotypic characteristics. The cessation of growth indicates the essential requirement of the enzyme for the organism in spite of having additional DNA relaxation enzymes in the cell. Notably, the imbalance in TopoI level led to the altered expression of topology modulatory proteins, resulting in a diffused nucleoid architecture. Proteomic and transcript analysis of the mutant indicated reduced expression of the genes involved in central metabolic pathways and core DNA transaction processes. RNA polymerase (RNAP) distribution on the transcription units was affected in the TopoI-depleted cells, suggesting global alteration in transcription. The study thus highlights the essential requirement of TopoI in the maintenance of cellular phenotype, growth characteristics and gene expression in mycobacteria. A decrease in TopoI level led to altered RNAP occupancy and impaired transcription elongation, causing severe downstream effects. PMID:25516959

  16. Changes in serum calcium, phosphorus, and magnesium levels in captive ruminants affected by diet manipulation.

    PubMed

    Miller, Michele; Weber, Martha; Valdes, Eduardo V; Neiffer, Donald; Fontenot, Diedre; Fleming, Gregory; Stetter, Mark

    2010-09-01

    A combination of low serum calcium (Ca), high serum phosphorus (P), and low serum magnesium (Mg) has been observed in individual captive ruminants, primarily affecting kudu (Tragelaphus strepsiceros), eland (Taurotragus oryx), nyala (Tragelaphus angasii), bongo (Tragelaphus eurycerus), and giraffe (Giraffa camelopardalis). These mineral abnormalities have been associated with chronic laminitis, acute tetany, seizures, and death. Underlying rumen disease secondary to feeding highly fermentable carbohydrates was suspected to be contributing to the mineral deficiencies, and diet changes that decreased the amount of starch fed were implemented in 2003. Serum chemistry values from before and after the diet change were compared. The most notable improvement after the diet change was a decrease in mean serum P. Statistically significant decreases in mean serum P were observed for the kudu (102.1-66.4 ppm), eland (73.3-58.4 ppm), and bongo (92.1-64.2 ppm; P < 0.05). Although not statistically significant, mean serum P levels also decreased for nyala (99.3-86.8 ppm) and giraffe (82.6-68.7 ppm). Significant increases in mean serum Mg were also observed for kudu (15.9-17.9 ppm) and eland (17.1-19.7 ppm). A trend toward increased serum Mg was also observed in nyala, bongo, and giraffe after the diet change. No significant changes in mean serum Ca were observed in any of the five species evaluated, and Ca was within normal ranges for domestic ruminants. The mean Ca:P ratio increased to greater than one in every species after the diet change, with kudu, eland, and bongo showing a statistically significant change. The results of this study indicate that the diet change had a generally positive effect on serum P and Mg levels. PMID:20945636

  17. Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample

    SciTech Connect

    Lind, Lars; Penell, Johanna; Syvänen, Anne-Christine; Axelsson, Tomas; Ingelsson, Erik; Morris, Andrew P.; Lindgren, Cecilia; Salihovic, Samira; Bavel, Bert van; Lind, P. Monica

    2014-08-15

    Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures >80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003–0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005–0.05 range. Very few associations with p<0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs. - Highlights: • We studied the relationship between PCBs and the genetic variation in the CYP genes. • Cross sectional data from a cohort of elderly were analysed. • The PCB levels were evaluated versus 21 SNPs in three CYP genes. • PCB 118 was related to variation in the CYP1A1 gene.

  18. Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.

    PubMed Central

    Nemoto, E; Nakamura, M; Shoji, S; Horiuchi, H

    1997-01-01

    Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP. PMID:9284170

  19. Assessment of Gravity Field and Steady State Ocean Circulation Explorer (GOCE) geoid model using GPS levelling over Sabah and Sarawak

    NASA Astrophysics Data System (ADS)

    Othman, A. H.; Omar, K. M.; Din, A. H. M.; Som, Z. A. M.; Yahaya, N. A. Z.; Pa'suya, M. F.

    2016-06-01

    The GOCE satellite mission has significantly contributed to various applications such as solid earth physics, oceanography and geodesy. Some substantial applications of geodesy are to improve the gravity field knowledge and the precise geoid modelling towards realising global height unification. This paper aims to evaluate GOCE geoid model based on the recent GOCE Global Geopotential Model (GGM), as well as EGM2008, using GPS levelling data over East Malaysia, i.e. Sabah and Sarawak. The satellite GGMs selected in this study are the GOCE GGM models which include GOCE04S, TIM_R5 and SPW_R4, and the EGM2008 model. To assess these models, the geoid heights from these GGMs are compared to the local geometric geoid height. The GGM geoid heights was derived using EGMLAB1 software and the geometric geoid height was computed by available GPS levelling information obtained from the Department Survey and Mapping Malaysia. Generally, the GOCE models performed better than EGM2008 over East Malaysia and the best fit GOCE model for this region is the TIM_R5 model. The TIM_R5 GOCE model demonstrated the lowest R.M.S. of ± 16.5 cm over Sarawak, comparatively. For further improvement, this model should be combined with the local gravity data for optimum geoid modelling over East Malaysia.

  20. Circulating levels of the innate and humoral immune regulators CD14 and CD23 are associated with adult glioma

    PubMed Central

    Zhou, Mi; Wiemels, Joseph L.; Bracci, Paige; Wrensch, Margaret R.; Mccoy, Lucie; Rice, Terri; Sison, Jennette; Patoka, Joseph; Wiencke, John K.

    2012-01-01

    Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1079 glioma patients post diagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 (highest vs. lowest quartile OR = 3.94 (95% CI: 2.98-5.21) and low sCD23 (lowest vs. highest quartile OR=2.5 (95% CI: 1.89-3.23)). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. While temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, and in particular immunoregulatory proteins, in gliomagenesis. PMID:20719886

  1. Circulating levels of the innate and humoral immune regulators CD14 and CD23 are associated with adult glioma.

    PubMed

    Zhou, Mi; Wiemels, Joseph L; Bracci, Paige M; Wrensch, Margaret R; McCoy, Lucie S; Rice, Terri; Sison, Jennette D; Patoka, Joseph S; Wiencke, John K

    2010-10-01

    Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1,079 glioma patients postdiagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 [highest versus lowest quartile odds ratio (OR), 3.94; 95% confidence interval (95% CI), 2.98-5.21] and low sCD23 (lowest versus highest quartile OR, 2.5; 95% CI, 1.89-3.23). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. Whereas temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long-observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, in particular immunoregulatory proteins, in gliomagenesis. PMID:20719886

  2. Attention to local and global levels of hierarchical Navon figures affects rapid scene categorization.

    PubMed

    Brand, John; Johnson, Aaron P

    2014-01-01

    In four experiments, we investigated how attention to local and global levels of hierarchical Navon figures affected the selection of diagnostic spatial scale information used in scene categorization. We explored this issue by asking observers to classify hybrid images (i.e., images that contain low spatial frequency (LSF) content of one image, and high spatial frequency (HSF) content from a second image) immediately following global and local Navon tasks. Hybrid images can be classified according to either their LSF, or HSF content; thus, making them ideal for investigating diagnostic spatial scale preference. Although observers were sensitive to both spatial scales (Experiment 1), they overwhelmingly preferred to classify hybrids based on LSF content (Experiment 2). In Experiment 3, we demonstrated that LSF based hybrid categorization was faster following global Navon tasks, suggesting that LSF processing associated with global Navon tasks primed the selection of LSFs in hybrid images. In Experiment 4, replicating Experiment 3 but suppressing the LSF information in Navon letters by contrast balancing the stimuli examined this hypothesis. Similar to Experiment 3, observers preferred to classify hybrids based on LSF content; however and in contrast, LSF based hybrid categorization was slower following global than local Navon tasks. PMID:25520675

  3. Using photovoice to examine community level barriers affecting maternal health in rural Wakiso district, Uganda.

    PubMed

    Musoke, David; Ekirapa-Kiracho, Elizabeth; Ndejjo, Rawlance; George, Asha

    2015-05-01

    Uganda continues to have poor maternal health indicators including a high maternal mortality ratio. This paper explores community level barriers affecting maternal health in rural Wakiso district, Uganda. Using photovoice, a community-based participatory research approach, over a five-month period, ten young community members aged 18-29 years took photographs and analysed them, developing an understanding of the emerging issues and engaging in community dialogue on them. From the study, known health systems problems including inadequate transport, long distance to health facilities, long waiting times at facilities and poor quality of care were confirmed, but other aspects that needed to be addressed were also established. These included key gender-related determinants of maternal health, such as domestic violence, low contraceptive use and early teenage pregnancy, as well as problems of unclean water, poor sanitation and women's lack of income. Community members appreciated learning about the research findings precisely hence designing and implementing appropriate solutions to the problems identified because they could see photographs from their own local area. Photovoice's strength is in generating evidence by community members in ways that articulate their perspectives, support local action and allow direct communication with stakeholders. PMID:26278841

  4. Neuroleptics Affect Neuropeptide S and NPSR mRNA Levels in the Rat Brain.

    PubMed

    Pałasz, Artur; Rojczyk, Ewa

    2015-11-01

    Neuropeptide S (NPS) has a multidirectional regulatory activity, especially when considered as a potent endogenous anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signaling in various brain structures. However, there is no information regarding the influence of treatment with antipsychotics on brain NPS expression. In the current study, we assessed the NPS and NPS receptor (NPSR) mRNA levels in the brains of rats shortly and chronically treated with chlorpromazine and olanzapine using quantitative real-time PCR. Both single-dose and long-term (4 months) olanzapine treatment led to the upregulation of NPS expression in the rat hypothalamus. It supports the hypothesis that NPS is involved in the dopamine-dependent anxiolytic actions of selected neuroleptics and possibly also in the pathophysiology of mental disorders. On the other hand, NPSR expression decreased after single-dose and chronic chlorpromazine administration in the hypothalamus, as well as after chronic olanzapine and chlorpromazine administration in the striatum and hippocampus. These results cast a new light on the pharmacology of antipsychotics and contribute to a better understanding of the mechanisms responsible for their action. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications. PMID:26227793

  5. CXC chemokine CXCL12 tissue expression and circulating levels in peptic ulcer patients with Helicobacter pylori infection.

    PubMed

    Bagheri, Vahid; Hassanshahi, Gholamhossein; Mirzaee, Vahid; Khorramdelazad, Hossein

    2016-09-01

    Helicobacter pylori (H. pylori) infection is among the most prevalent human infections. CXCL12 is a well-known CXC chemokine involved in inflammation and play major roles in angiogenesis. There is currently very limited data on the role of CXCL12 in peptic ulcer disease. Hence, we aimed to explore whether CXCL12 is involved in the pathogenesis of peptic ulcer induced by H. pylori. In this study, we enrolled 102 H. pylori-infected patients, including 51 with active ulcer (GA) and 51 with healing ulcer (GH). We also recruited 50 healthy subjects as control, which did not show any sign or symptoms of chronic inflammatory diseases, infection, or immune-related disorders. Endoscopy was performed to determine the stage of the disease. ELISA was used for detection of H. pylori infection and CXCL12 measurement. We also employed western blotting to detect CXCL12 in ulcerative lesions of H. pylori. Demographic data were also collected by questionnaire. Our results demonstrated that CXCL12 serum levels in GA group (151.8±18.31pg/mL) were significantly higher than those in GH (36.89±6.78pg/mL) and control groups (33.77±9.12pg/mL) (P<0.0001). However, we did not observe a significant difference between GH and control groups. Moreover, overexpression of CXCL12 in gastric lesions of patients in GA group was confirmed by Western blot analysis. According to the result of the present study, it could be concluded that CXCL12 is involved in the pathogenesis and healing of H. pylori-induced peptic ulcer. CXCL12 serum levels may also be used to distinguish between GA and GH phases of the disease. PMID:27269177

  6. Exposure to Palladium Nanoparticles Affects Serum Levels of Cytokines in Female Wistar Rats

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Corbi, Maddalena; Leso, Veruscka; Marinaccio, Alessandro; Leopold, Kerstin; Schindl, Roland; Sgambato, Alessandro

    2015-01-01

    Background Information currently available on the impact of palladium on the immune system mainly derives from studies assessing the biological effects of palladium salts. However, in the last years, there has been a notable increase in occupational and environmental levels of fine and ultrafine palladium particles released from automobile catalytic converters, which may play a role in palladium sensitization. In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential. Aim Therefore, the aim of this study was to investigate the effects of Pd-NPs on the immune system of female Wistar rats exposed to this xenobiotic for 14 days, by assessing possible quantitative changes in a number of cytokines: IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, GM-CSF, INF-γ and TNF-α. Methods Twenty rats were randomly divided into four exposure groups and one of control. Animals were given a single tail vein injection of vehicle (control group) and different concentrations of Pd-NPs (0.012, 0.12, 1.2 and 12 μg/kg). A multiplex biometric enzyme linked immunosorbent assay was used to evaluate cytokine serum levels. Results The mean serum concentrations of all cytokines decreased after the administration of 0.012 μg/kg of Pd-NPs, whereas exceeded the control levels at higher exposure doses. The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls. Discussion and Conclusions These results demonstrated that Pd-NP exposure can affect the immune response of rats inducing a stimulatory action that becomes significant at the highest administered dose. Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the

  7. The levels and composition of persistent organic pollutants in alluvial agriculture soils affected by flooding.

    PubMed

    Maliszewska-Kordybach, Barbara; Smreczak, Bozena; Klimkowicz-Pawlas, Agnieszka

    2013-12-01

    The concentrations and composition of persistent organic pollutants (POPs) were determined in alluvial soils subjected to heavy flooding in a rural region of Poland. Soil samples (n = 30) were collected from the upper soil layer from a 70-km(2) area. Chemical determinations included basic physicochemical properties and the contents of polychlorinated biphenyls (PCBs), hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs) and polycyclic aromatic hydrocarbons (PAHs, 16 compounds). The median concentrations of Σ7PCB (PCB28 + PCB52 + PCB101 + PCB118 + PCB138 + PCB153 + PCB180), Σ3HCH (α-HCH + β-HCH + γ-HCH) and Σ3pp'(DDT + DDE + DDD) were 1.60 ± 1.03, 0.22 ± 0.13 and 25.18 ± 82.70 μg kg(-1), respectively. The median concentrations of the most abundant PAHs, phenanthrene, fluoranthene, pyrene, benzo[b]fluoranthene and benzo[a]pyrene were 50 ± 37, 38 ± 27, 29 ± 30, 45 ± 36 and 24 ± 22 μg kg(-1), respectively. Compared with elsewhere in the world, the overall level of contamination with POPs was low and similar to the levels in agricultural soils from neighbouring countries, except for benzo[a]pyrene and DDT. There was no evidence that flooding affected the levels of POPs in the studied soils. The patterns observed for PAHs and PCBs indicate that atmospheric deposition is the most important long-term source of these contaminants. DDTs were the dominant organochlorine pesticides (up to 99%), and the contribution of the parent pp' isomer was up to 50 % of the ΣDDT, which indicates the advantage of aged contamination. A high pp'DDE/pp'DDD ratio suggests the prevalence of aerobic transformations of parent DDT. Dominance of the γ isomer in the HCHs implies historical use of lindane in the area. The effect of soil properties on the POP concentrations was rather weak, although statistically significant links with the content of the <0.02-mm fraction, Ctotal or Ntotal were observed for some individual compounds in the PCB group. PMID:23877573

  8. Different circulating progesterone concentrations during synchronization of ovulation protocol did not affect ovarian follicular and pregnancy responses in seasonal anestrous buffalo cows.

    PubMed

    Carvalho, N A T; Soares, J G; Souza, D C; Vannucci, F S; Amaral, R; Maio, J R G; Sales, J N S; Sá Filho, M F; Baruselli, P S

    2014-02-01

    Three experiments were designed to evaluate the effect of different circulating progesterone (P4) concentrations during synchronization of ovulation protocol for timed artificial insemination of seasonal anestrous buffalo cows. In the first trial, ovariectomized cows were randomly allocated into one of three groups: using new P4 devices (G-New; n = 8), using devices previously used for 9 days (G-Used1x; n = 8), and using devices previously used for 18 days (G-Used2x; n = 8). The P4 device was maintained for 9 days, and the circulating P4 concentration was measured daily. The circulating P4 concentrations during the P4 device treatment were the lowest for G-Used2x (1.10 ± 0.04 ng/mL), intermediate for G-Used1x (1.52 ± 0.05 ng/mL), and the highest for G-New (2.47 ± 0.07 ng/mL; P = 0.001). In the second trial, 31 anestrous cows had their ovarian follicular dynamics evaluated after receiving the treatments described previously (G-New [n = 10], G-Used1x [n = 11], and G-Used2x [n = 10]). At insertion of the P4 device, cows were administered 2.0 mg of estradiol benzoate. Nine days later, the P4 device was removed and cows were administered 0.53 mg of cloprostenol sodium plus 400 IU of eCG. Forty-eight hours after P4 device removal, 10 μg of buserelin acetate was administered. There were no differences among the groups (G-New vs. G-Used1x vs. G-Used2x) in diameter of the largest follicle at P4 device removal (9.0 ± 0.8 vs. 10.1 ± 0.9 vs. 8.6 ± 0.8 mm; P = 0.35), in interval from P4 device removal to ovulation (77.1 ± 4.5 vs. 76.5 ± 4.7 vs. 74.0 ± 4.4 hours; P = 0.31), or in ovulation rate (80.0% vs. 81.8% vs. 60.0%; P = 0.51). In experiment 3, 350 anestrous cows were randomly assigned into one of the three treatments described previously (G-New, n = 111; G-Used1x, n = 121; G-Used2x, n = 118) and received a timed artificial insemination for 16 hours after buserelin treatment. The 30-day pregnancy rates did not differ among groups (55.9% vs. 55.4% vs. 48.3%; P = 0

  9. The effect of chronic peripheral nesfatin-1 application on blood pressure in normal and chronic restraint stressed rats: related with circulating level of blood pressure regulators.

    PubMed

    Ayada, Ceylan; Turgut, Günfer; Turgut, Sebahat; Güçlü, Zuhal

    2015-01-01

    Nesfatin is a peptide secreted by peripheral tissues, central and peripheral nervous system. It is involved in the regulation of homeostasis. Although the effects of nesfatin-1 on nutrition have been studied widely in the literature, the mechanisms of nesfatin-1 action and also relations with other physiological parameters are still not clarified well. We aimed to investigate the effect of peripheral chronic nesfatin-1 application on blood pressure regulation in normal and in rats exposed to restraint immobilization stress. In our study, three month-old male Wistar rats were used. Rats were divided into 4 groups as Control, Stress, Control+Nesfatin-1, Nesfatin-1+Stress. Angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone, cortisol, nesfatin-1 levels were determined in plasma samples by ELISA. Our results have shown that chronic peripheral nesfatin-1 administration increases blood pressure in normal and in rats exposed to chronic restraint stress. Effect of nesfatin-1 on circulating level of angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone and cortisol has been identified. We can conclude that elevated high blood pressure after chronic peripheral nesfatin-1 administration in rats exposed to chronic restraint stress may be related to decreased plasma level of endothelial nitric oxide synthase concentration. PMID:25504061

  10. Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals

    PubMed Central

    Shaviya, Nathan; Budambula, Valentine; Webale, Mark K.; Were, Tom

    2016-01-01

    Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon-gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n = 13) and controls (n = 14) from Kenya. Interferon-gamma levels (P < 0.0001) and interferon-gamma to interleukin-10 (P < 0.001) and interferon-gamma to adiponectin (P = 0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (ρ = −0.849; P < 0.0001), body mass index (ρ = 0.664; P = 0.013), hip girth (ρ = −0.579; P = 0.038), and plateletcrit (ρ = 0.605; P = 0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (ρ = −0.729; P = 0.005); and interferon-gamma to adiponectin ratio with body weight (ρ = −0.560; P = 0.047), body mass index (ρ = −0.604; P = 0.029), and plateletcrit (ρ = 0.793; P = 0.001). Taken together, our results suggest mild-inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients. PMID:26880909

  11. PDE4 inhibitors augment levels of glucocorticoid receptor in B cell chronic lymphocytic leukemia but not in normal circulating hematopoietic cells

    PubMed Central

    Meyers, John A.; Taverna, Josephine; Chaves, Jorge; Makkinje, Anthony; Lerner, Adam

    2009-01-01

    Purpose Type 4 cAMP phosphodiesterase (PDE4) inhibitors, compounds that activate cAMP-mediated signaling by inhibiting cAMP catabolism, potentiate glucocorticoid-mediated apoptosis in chronic lymphocytic leukemia (CLL) cells but the mechanism by which this occurs is unknown. In this study, we sought to address whether PDE4 inhibitors alter expression of glucocorticoid receptor (GRα) in CLL cells. Experimental Design CLL cells or normal hematopoietic cells were treated with PDE4 inhibitors followed by analysis of GRα transcript and protein by real-time PCR and Western analysis. Results PDE4 inhibitors up-regulate glucocorticoid receptor transcript levels in CLL cells but not normal circulating T cells, B cells, monocytes or neutrophils. As GRα transcript half-life does not vary in CLL cells treated with the prototypic PDE4 inhibitor rolipram, the four-fold increase in GRα mRNA levels observed within four hours of rolipram treatment appears to result from an increase in transcription. Rolipram treatment increases levels of transcripts derived from the 1A3 promoter to a greater extent than the 1B promoter. Treatment of CLL cells with cilomilast and roflumilast, two PDE4 inhibitors previously studied in clinical trials also augments GRα transcript levels and glucocorticoid-mediated apoptosis. Washout studies demonstrate that simultaneous treatment with both drug classes irreversibly augments apoptosis over the same time frame that glucocorticoid receptor up-regulation occurs. While treatment of CLL cells with glucocorticoids reduces basal GRα transcript levels in a dose-related manner, co-treatment with rolipram maintained GRα transcript levels above baseline. Conclusion Our results suggest that PDE4 inhibitors may sensitize CLL cells to glucocorticoid-induced apoptosis by augmenting GRα expression. PMID:17699872

  12. Assessing the role of insulin‐like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

    PubMed Central

    Bonilla, Carolina; Lewis, Sarah J.; Rowlands, Mari‐Anne; Gaunt, Tom R.; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L.; Hamdy, Freddie C.; Neal, David E.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev; Lathrop, Mark; Holly, Jeff M. P.

    2016-01-01

    Circulating insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome‐wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF‐II and IGFBP‐3, less so for IGF‐I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF‐II/IGFBP‐3 level‐raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF‐II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. PMID:27225428

  13. Assimilation of Cloud- and Land-Affected TOVS/ATOVS Level 1B Radiances in DAO's Next Generation Finite-Volume Data Assimilation System

    NASA Technical Reports Server (NTRS)

    Joiner, J.; daSilva, A.; Einaudi, Franco (Technical Monitor)

    2001-01-01

    The Physical-space/Finite-volume Data Assimilation System (fvDAS) is the next generation global atmospheric data assimilation system in development at the Data Assimilation Office (DAO) at NASA's Goddard Space Flight Center. It is based on a new finite-volume general circulation model jointly developed by NASA and NCAR, and on the Physical-Space Statistical Analysis System (PSAS) developed at the DAO. In this talk we will focus on the assimilation of data from the (Advanced) TIROS Operational Vertical Sounder (ATOVS), with emphasis on the impact of cloud- and land-affected level 1B radiances. Recently, it has been shown that the use of observations from satellite-borne microwave and infrared radiometers in data assimilation systems consistently increases forecast skill. Considerable effort has been expended over the past two decades, particularly with the (Advanced) TIROS Operational Vertical Sounder (ATOVS), to achieve this result. The positive impact on forecast skill has resulted from improvements in quality control algorithms, systematic error correction schemes, and more sophisticated data assimilation algorithms. Despite these advances, there are still many issues regarding the use of satellite data in data assimilation systems that remain unresolved. In particular, most operational centers still do not assimilate cloud- and land-affected TOVS data. In this study, we evaluate the impact of assimilating cloud-and land-affected TOVS/ATOVS level 1B data in DAO's next generation fvDAS, using a 1D variational scheme. We will discuss the impact of these data on both tropospheric and stratospheric forecasts, as well as on the general aspects of the earth climate system.

  14. Population dynamics of dechlorinators and factors affecting the level and products of PCB dechlorination in sediments

    SciTech Connect

    Kim, J.S.; Sokol, R.C.; Liu, X.; Bethoney, C.M.; Rhee, G.Y.

    1996-12-31

    Microbial dechlorination of polychlorinated biphenyls (PCBs) often stops although a significant number of removable chlorines remain. To determine the reason for the cessation, we investigated the limitation of organic carbon, PCB bioavailability, and inhibition by metabolic products. Enrichment with carbon sources did not induce additional chlorination, indicating the plateau was not due to depletion of organic carbon. The bioavailability was not limiting, since a subcritical micelle concentration of the surfactant, which enhanced desorption without inhibiting dechlorinating microorganisms, failed to lower the plateau. Neither was it due to accumulation of metabolites, since no additional dechlorination was detected when plateau sediments were incubated with fresh medium. Similarly, dechlorination was not inhibited in freshly spiked sediment slurries. Dechlorination ended up at the same level with nearly identical congener profiles, regardless of treatment. These results indicate that cessation of dechlorination was due to the accumulation of daughter congeners, which cannot be used as electron acceptors by microbes. To determine whether the decreasing availability affected the microorganisms, we determined the population dynamics of dechlorinators using the most probable number technique. The growth dynamics of the dechlorinators mirrored the time course of dechlorination. It started when the population increased by two orders of magnitude. Once dechlorination stopped the dechlorinating population also began to decrease. When dechlorinators were inoculated into PCB-free sediments, the population decreased over time. The decrease of the population as dechlorination ceased confirms that the diminishing availability of congeners was the reason for the incomplete dechlorination. Recent findings have shown that a second phase of dechlorination of certain congeners can occur after a long lag. 45 refs., 8 figs.

  15. Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels.

    PubMed

    Hudmon, A; Davenport, G; Coleman, E S; Sartin, J L

    2009-10-01

    Estradiol increases basal growth hormone (GH) concentrations in sheep and cattle. This study sought to determine the effects of estradiol on GH-releasing hormone (GRH)-stimulated GH release in sheep. Growth hormone secretory characteristics, the GH response to GRH, and steady-state GH mRNA concentrations were determined in castrated male lambs treated with 2 different doses of estradiol 17-beta for a 28-d experimental period. Although no differences between treatments in mean GH, basal GH, or GH pulse number were observed after 28 d of estradiol treatment, GH pulse amplitude was greater (P < 0.05) in the 2.00-cm implant-treated animals than in the control and 0.75-cm implant group. The effect of estradiol treatment on GRH-stimulated GH release revealed differences between the control and estradiol-treated animals (P < 0.05). The 15-min GH responses to 0.075 microg/kg hGRH in the control, 0.75-cm, and 2.00-cm implant groups, respectively, were 76 +/- 10, 22.6 +/- 2.1, and 43.6 +/- 15.0 ng/mL. Growth hormone mRNA content was determined for pituitary glands from the different treatment groups, and no differences in steady-state GH mRNA levels were observed. There were no differences in the mean plasma concentrations of IGF-I, cortisol, T(3), or T(4) from weekly samples. Growth hormone release from cultured ovine pituitary cells from control sheep was not affected by estradiol after 72 h or in a subsequent 3-h incubation with estradiol combined with GRH. These data suggest that estradiol has differing actions on basal and GRH-stimulated GH concentrations in plasma, but the increase in pulse amplitude does not represent an increased pituitary sensitivity to GRH. PMID:19616401

  16. The Development and Application of Affective Assessment in an Upper-Level Cell Biology Course

    ERIC Educational Resources Information Center

    Kitchen, Elizabeth; Reeve, Suzanne; Bell, John D.; Sudweeks, Richard R.; Bradshaw, William S.

    2007-01-01

    This study exemplifies how faculty members can develop instruments to assess affective responses of students to the specific features of the courses they teach. Means for assessing three types of affective responses are demonstrated: (a) student attitudes towards courses with differing instructional objectives and methodologies, (b) student…

  17. Successful Antiparasitic Treatment for Cysticercosis is Associated with a Fast and Marked Reduction of Circulating Antigen Levels in a Naturally Infected Pig Model.

    PubMed

    Gonzalez, Armando E; Bustos, Javier A; Garcia, Hector H; Rodriguez, Silvia; Zimic, Mirko; Castillo, Yesenia; Praet, Nicolas; Gabriël, Sarah; Gilman, Robert H; Dorny, Pierre

    2015-12-01

    Taenia solium cysticercosis is a common parasitic infection of humans and pigs. We evaluated the posttreatment evolution of circulating parasite-specific antigen titers in 693 consecutive blood samples from 50 naturally infected cysticercotic pigs, which received different regimes of antiparasitic drugs (N = 39, 7 groups), prednisone (N = 5), or controls (N = 6). Samples were collected from baseline to week 10 after treatment, when pigs were euthanized and carefully dissected at necropsy. Antigen levels decreased proportionally to the efficacy of treatment and correlated with the remaining viable cysts at necropsy (Pearson's p = 0.67, P = 0.000). A decrease of 5 times in antigen levels (logarithmic scale) compared with baseline was found in 20/26 pigs free of cysts at necropsy, compared with 1/24 of those who had persisting viable cysts (odds ratio [OR] = 76.7, 95% confidence interval [CI] = 8.1-3308.6, P < 0.001). Antigen monitoring reflects the course of infection in the pig. If a similar correlation exists in infected humans, this assay may provide a minimally invasive and easy monitoring assay to assess disease evolution and efficacy of antiparasitic treatment in human neurocysticercosis. PMID:26392159

  18. Technical note: The role of circulating low-density lipoprotein levels as a phenotypic marker for Holstein cholesterol deficiency in dairy cattle.

    PubMed

    Saleem, S; Heuer, C; Sun, C; Kendall, D; Moreno, J; Vishwanath, R

    2016-07-01

    With the recent discovery of a Holstein cholesterol deficiency (HCD) haplotype, the USDA has labeled many dairy animals as HCD carriers based on haplotype and pedigree analysis. We set out to investigate the effect of HCD status on various cholesterol transport molecules, namely low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides in both males and females. A genome-wide association study was also conducted to narrow down the genomic region correlated with varying LDL-C levels. In the study, 34 HCD carrier animals showed significantly lower cholesterol and LDL-C levels compared with their 34 closely related, non-HCD controls. The genome-wide association study based on 73 animals using 56,198 SNP markers revealed an association with chromosome 11 in the region of 66,218,925 to 66,946,746 bp. We also tested the effect of HCD status on sperm quality traits using fresh ejaculates and frozen-thawed semen samples, but did not find any discriminating effects. Our study has demonstrated the use of LDL-C as a key phenotypic marker for determining HCD status in dairy cattle and this is the first study that clearly shows a cause-effect relationship of the HCD haplotype on circulating LDL-C. PMID:27108167

  19. Unaltered ratio of circulating levels of growth hormone/GH isoforms in adults with Prader-Willi syndrome after GHRH plus arginine administration.

    PubMed

    Rigamonti, A E; Grugni, G; Marazzi, N; Bini, S; Bidlingmaier, M; Sartorio, A

    2015-08-01

    Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms, the most abundant being 22 kDa- and 20 kDa-GH. The availability of analytical methods to measure these GH isoforms might represent a valuable diagnostic tool to investigate GH hyposecretory states, including Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity. The aim of the present study was to measure circulating levels of 22 kDa- and 20 kDa-GH in PWS adults (n=14; M/F: 5/9; genotype DEL15/UPD15: 12/2; age: 19.0±3.7 years; BMI: 29.9±8.7 kg/m2) after combined GH releasing hormone (GHRH) plus arginine (ARG) administration. The results were analysed subdividing the study population in obese vs. nonobese (6/8) and GH deficient vs. nonGH deficient (GHD) (6/8) subjects, according to appropriate BMI-related diagnostic cut-off limits of GH peak response to the provocative test. Circulating levels of 22 kDa-GH were measured by a chemiluminescent method based on a detection monoclonal antibody targeting an epitope in the loop connecting helix 1 and 2 of GH, which is missing in 20 kDa-GH; the 20 kDa-GH was measured using a time resolved fluorescence assay based on two monoclonal antibodies with no cross-reactivity to 22-kDa GH. GHRH plus ARG significantly stimulated the secretions of 22 kDa- and 20 kDa-GH in nonobese (at 30, 45, 60 and 90 min and at 45, 60, 90 and 120 min vs. 0 min, p<0.05, with GH peaks of 15.8±10.3 ng/ml and 2.7±1.2 ng/ml, respectively) and in nonGHD PWS (at 30, 45 and 60 min and at 45, 60 and 90 min vs 0 min, p<0.05, with GH peaks of 12.5±9.0 ng/ml and 2.0±1.8 ng/ml, respectively). No significant GHRH plus ARG-induced changes in 22 kDa- and 20 kDa-GH were observed in obese or GHD PWS patients, the only exception being the increase of 22 kDa-GH (p<0.05) 60 min after the stimulus administration in GHD group (with GH peaks of 6.9±4.7 ng/ml and 0.8±0.6 ng/ml in obese subjects and 8.5±6.0 ng/ml and 1.2±1.0 ng/ml in GHD subjects

  20. Return of spontaneous Circulation Is Not Affected by Different Chest Compression Rates Superimposed with Sustained Inflations during Cardiopulmonary Resuscitation in Newborn Piglets

    PubMed Central

    Li, Elliott S.; Cheung, Po-Yin; Lee, Tze-Fun; Lu, Min; O'Reilly, Megan

    2016-01-01

    Objective Recently, sustained inflations (SI) during chest compression (CC) have been suggested as an alternative to the current approach during neonatal resuscitation. However, the optimal rate of CC during SI has not yet been established. Our aim was to determine whether different CC rates during SI reduce time to return of spontaneous circulation (ROSC) and improve hemodynamic recovery in newborn piglets with asphyxia-induced bradycardia. Intervention and measurements Term newborn piglets were anesthetized, intubated, instrumented and exposed to 45-min normocapnic hypoxia followed by asphyxia. Resuscitation was initiated when heart rate decreased to 25% of baseline. Piglets were randomized into three groups: CC superimposed by SI at a rate of 90 CC per minute (SI+CC 90, n = 8), CC superimposed by SI at a rate of 120 CC per minute (SI+CC 120, n = 8), or a sham group (n = 6). Cardiac function, carotid blood flow, cerebral oxygenation and respiratory parameters were continuously recorded throughout the experiment. Main results Both treatment groups had similar time of ROSC, survival rates, hemodynamic and respiratory parameters during cardiopulmonary resuscitation. The hemodynamic recovery in the subsequent 4h was similar in both groups and was only slightly lower than sham-operated piglets at the end of experiment. Conclusion Newborn piglets resuscitated by SI+CC 120 did not show a significant advantage in ROSC, survival, and hemodynamic recovery as compared to those piglets resuscitated by SI+CC 90. PMID:27304210

  1. Longitudinal measures of circulating leptin and ghrelin concentrations are associated with the growth of young Peruvian children but are not affected by zinc supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Leptin, ghrelin and insulin are hormonal regulators of energy balance and, therefore, may be related to growth during infancy. Zinc is essential for growth and may have an effect on growth through these hormones. Objectives: To determine whether supplemental zinc affects plasma leptin an...

  2. Vitamin D-Binding Protein Influences Total Circulating Levels of 1,25-Dihydroxyvitamin D3 but Does Not Directly Modulate the Bioactive Levels of the Hormone in Vivo

    PubMed Central

    Zella, Lee A.; Shevde, Nirupama K.; Hollis, Bruce W.; Cooke, Nancy E.; Pike, J. Wesley

    2008-01-01

    Mice deficient in the expression of vitamin D-binding protein (DBP) are normocalcemic despite undetectable levels of circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We used this in vivo mouse model together with cells in culture to explore the impact of DBP on the biological activity of 1,25(OH)2D3. Modest changes in the basal expression of genes involved in 1,25(OH)2D3 metabolism and calcium homeostasis were observed in vivo; however, these changes seemed unlikely to explain the normal calcium balance seen in DBP-null mice. Further investigation revealed that despite the reduced blood levels of 1,25(OH)2D3 in these mice, tissue concentrations were equivalent to those measured in wild-type counterparts. Thus, the presence of DBP has limited impact on the extracellular pool of 1,25(OH)2D3 that is biologically active and that accumulates within target tissues. In cell culture, in contrast, the biological activity of 1,25(OH)2D3 is significantly impacted by DBP. Here, although DBP deficiency had no effect on the activation profile itself, the absence of DBP strongly reduced the concentration of exogenous 1,25(OH)2D3 necessary for transactivation. Surprisingly, analogous studies in wild-type and DBP-null mice, wherein we explored the activity of exogenous 1,25(OH)2D3, produced strikingly different results as compared with those in vitro. Here, the carrier protein had virtually no impact on the distribution, uptake, activation profile, or biological potency of the hormone. Collectively, these experiments suggest that whereas DBP is important to total circulating 1,25(OH)2D3 and sequesters extracellular levels of this hormone both in vivo and in vitro, the binding protein does not influence the hormone’s biologically active pool. PMID:18372326

  3. Joint Analysis of Individual Participants’ Data from 17 Studies on the Association of the IL6 Variant -174G>C with Circulating Glucose Levels, Interleukin-6 Levels, and Body-Mass Index

    PubMed Central

    Huth, Cornelia; Illig, Thomas; Herder, Christian; Gieger, Christian; Grallert, Harald; Vollmert, Caren; Rathmann, Wolfgang; Hamid, Yasmin H.; Pedersen, Oluf; Hansen, Torben; Thorand, Barbara; Meisinger, Christa; Döring, Angela; Klopp, Norman; Gohlke, Henning; Lieb, Wolfgang; Hengstenberg, Christian; Lyssenko, Valeriya; Groop, Leif; Ireland, Helen; Stephens, Jeffrey W.; Asterholm, Ingrid Wernstedt; Jansson, John-Olov; Boeing, Heiner; Möhlig, Matthias; Stringham, Heather M.; Boehnke, Michael; Tuomilehto, Jaakko; Fernandez-Real, Jose-Manuel; Lopez-Bermejo, Abel; Gallart, Luis; Vendrell, Joan; Humphries, Steve E.; Kronenberg, Florian; Wichmann, H.-Erich; Heid, Iris M.

    2013-01-01

    Background Several studies have investigated associations between the -174G>C polymorphism (rs1800795) of the IL6-gene, but presented inconsistent results. Aims This joint analysis aimed to clarify whether IL6 -174G>C was associated with type 2 diabetes mellitus (T2DM) related quantitative phenotypes. Methods Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected. As study-specific estimates did not show heterogeneity (P>0.1), they were combined by using the inverse-variance fixed-effect model. Results The main analysis included 9440, 7398, 24,117, or 5659 nondiabetic and manifest T2DM subjects for fasting glucose, 2-hour glucose, BMI or circulating interleukin-6 levels, respectively. IL6 -174 C-allele carriers had significantly lower fasting glucose (−0.091mmol/L, P=0.014). There was no evidence for association between IL6 -174G>C and BMI or interleukin-6. In an additional analysis of 641 subjects known to develop T2DM later on, the IL6 -174 CC-genotype was associated with higher baseline interleukin-6 (+0.75pg/mL, P=0.004), which was consistent with higher interleukin-6 in the 966 manifest T2DM subjects (+0.50pg/mL, P=0.044). Conclusions Our data suggest association between IL6 -174G>C and quantitative glucose, and exploratory analysis indicated modulated interleukin-6 levels in pre-diabetic subjects, being in-line with this SNP’s previously reported T2DM association and a role of circulating interleukin-6 as intermediate phenotype. PMID:18752089

  4. Adverse childhood experiences associate to reduced glutamate levels in the hippocampus of patients affected by mood disorders.

    PubMed

    Poletti, Sara; Locatelli, Clara; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

    2016-11-01

    Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls. Exposure to stress during early life could lead to a hypofunctionality of the glutamatergic system in the hippocampus of depressed patients. Abnormalities of glutamatergic signaling could then possibly underpin the structural and functional abnormalities observed in patients affected by mood disorders. PMID:27449360

  5. Differences in affective behaviors and hippocampal allopregnanolone levels in adult rats of lines selectively bred for infantile vocalizations.

    PubMed

    Zimmerberg, Betty; Brunelli, Susan A; Fluty, Alyssa J; Frye, Cheryl A

    2005-04-30

    Allopregnanolone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP), a progesterone metabolite, is an endogenous neurosteroid mediating affective behaviors via its positive modulation of GABA(A) receptors. In order to better understand the role of this neurosteroid in individual differences in affective behavior, we used an animal model based on selective breeding for an infantile affective trait, ultrasonic vocalizations (USV). Adult male and female (in either proestrus or diestrus) rats that had been bred for low (low line) or high (high line) rates of USV after maternal separation were tested in a series of affective behavioral tests: open field, emergence, social interaction, defensive freezing, and the Porsolt forced swim task. Concentrations of allopregnanolone in combined hippocampus and amygdala tissue were then measured. low line subjects showed significantly lower anxiety and depression responses in the emergence, open field, and Porsolt forced swim tasks than did high line subjects. Proestrus females exhibited less affective behaviors than diestrus females or males. Allopregnanolone levels in hippocampus/amygdala were significantly higher in low line subjects compared to high line subjects, and in proestrus females compared to diestrus females and males. These data indicate that: (1) affective behaviors in lines selectively bred for an infantile anxiety trait exhibit selection persistence into adulthood; and (2) levels of allopregnanolone in the limbic system parallel selected disparities in affective behavior, suggesting a selection for alterations in the neurosteroid/GABA(A) receptor system in these lines. PMID:15817193

  6. Assimilation of Cloud- and Land-affected TOVS/ATOVS Level 1b data at DAO

    NASA Technical Reports Server (NTRS)

    Joiner, Joanna; Frank, Donald; daSilva, Arlindo; Bosilovich, Mike; Radacovich, Jon; Atlas, Robert (Technical Monitor)

    2002-01-01

    Despite significant advances in the assimilation of TIROS Operational Vertical Sounder/Advanced TIROS Operational Vertical Sounder (TOVS)/(ATOVS) data over the last decade, there are still many unresolved issues. For example, at several centers, cloud-and land-affected TOVS data are not assimilated. In this study, we show positive impact from the use of cloud cleared and land-affected TOVS data in the NASA Data Assimilation Office's (DAO) Finite Volume Data Assimilation System (fv-DAS). We will discuss how treatment of TOVS data affects the stratosphere and tropopause in the fvDAS. We will also describe the use of TOVS data for land-surface analysis and assimilation and other developments regarding the use of TOVS data at the DAO.

  7. Imbalanced Hemolymph Lipid Levels Affect Feeding Motivation in the Two-Spotted Cricket, Gryllus bimaculatus

    PubMed Central

    Konuma, Takahiro; Tsukamoto, Yusuke; Nagasawa, Hiromichi; Nagata, Shinji

    2016-01-01

    Insect feeding behavior is regulated by many intrinsic factors, including hemolymph nutrient levels. Adipokinetic hormone (AKH) is a peptide factor that modulates hemolymph nutrient levels and regulates the nutritional state of insects by triggering the transfer of lipids into the hemolymph. We recently demonstrated that RNA interference (RNAi)-mediated knockdown of the AKH receptor (AKHR) reduces hemolymph lipid levels, causing an increase in the feeding frequency of the two-spotted cricket, Gryllus bimaculatus. This result indicated that reduced hemolymph lipid levels might motivate crickets to feed. In the present study, to elucidate whether hemolymph lipid levels contribute to insect feeding behavior, we attempted to manipulate hemolymph lipid levels via the lipophorin (Lp)-mediated lipid transferring system in G. bimaculatus. Of the constituent proteins in Lp, we focused on apolipophorin-III (GrybiApoLp-III) because of its possible role in facilitating lipid mobilization. First, we used RNAi to reduce the expression of GrybiApoLp-III. RNAi-mediated knockdown of GrybiApoLp-III had little effect on basal hemolymph lipid levels and the amount of food intake. In addition, hemolymph lipid levels remained static even after injecting AKH into GrybiApoLp-IIIRNAi crickets. These observations indicated that ApoLp-III does not maintain basal hemolymph lipid levels in crickets fed ad libitum, but is necessary for mobilizing lipid transfer into the hemolymph following AKH stimulation. Second, Lp (containing lipids) was injected into the hemolymph to induce a temporary increase in hemolymph lipid levels. Consequently, the initiation of feeding was delayed in a dose-dependent manner, indicating that increased hemolymph lipid levels reduced the motivation to feed. Taken together, these data validate the importance of basal hemolymph lipid levels in the control of energy homeostasis and for regulating feeding behavior in crickets. PMID:27144650

  8. Imbalanced Hemolymph Lipid Levels Affect Feeding Motivation in the Two-Spotted Cricket, Gryllus bimaculatus.

    PubMed

    Konuma, Takahiro; Tsukamoto, Yusuke; Nagasawa, Hiromichi; Nagata, Shinji

    2016-01-01

    Insect feeding behavior is regulated by many intrinsic factors, including hemolymph nutrient levels. Adipokinetic hormone (AKH) is a peptide factor that modulates hemolymph nutrient levels and regulates the nutritional state of insects by triggering the transfer of lipids into the hemolymph. We recently demonstrated that RNA interference (RNAi)-mediated knockdown of the AKH receptor (AKHR) reduces hemolymph lipid levels, causing an increase in the feeding frequency of the two-spotted cricket, Gryllus bimaculatus. This result indicated that reduced hemolymph lipid levels might motivate crickets to feed. In the present study, to elucidate whether hemolymph lipid levels contribute to insect feeding behavior, we attempted to manipulate hemolymph lipid levels via the lipophorin (Lp)-mediated lipid transferring system in G. bimaculatus. Of the constituent proteins in Lp, we focused on apolipophorin-III (GrybiApoLp-III) because of its possible role in facilitating lipid mobilization. First, we used RNAi to reduce the expression of GrybiApoLp-III. RNAi-mediated knockdown of GrybiApoLp-III had little effect on basal hemolymph lipid levels and the amount of food intake. In addition, hemolymph lipid levels remained static even after injecting AKH into GrybiApoLp-IIIRNAi crickets. These observations indicated that ApoLp-III does not maintain basal hemolymph lipid levels in crickets fed ad libitum, but is necessary for mobilizing lipid transfer into the hemolymph following AKH stimulation. Second, Lp (containing lipids) was injected into the hemolymph to induce a temporary increase in hemolymph lipid levels. Consequently, the initiation of feeding was delayed in a dose-dependent manner, indicating that increased hemolymph lipid levels reduced the motivation to feed. Taken together, these data validate the importance of basal hemolymph lipid levels in the control of energy homeostasis and for regulating feeding behavior in crickets. PMID:27144650

  9. Student Cognitive and Affective Development in the Context of Classroom-Level Curriculum Development

    ERIC Educational Resources Information Center

    Shawer, Saad Fathy; Gilmore, Deanna; Banks-Joseph, Susan Rae

    2008-01-01

    This qualitative study examined the impact of teacher curriculum approaches (curriculum-transmitter/curriculum-developer/curriculum-maker) on student cognitive change (reading, writing, speaking, and listening abilities) and their affective change (motivation and interests). This study's conceptual framework was grounded in teacher curriculum…

  10. Dispositional Empathic Concern, Gender, Level of Experience, Teacher Efficacy, Attributions of Controllability and Teacher Affect

    ERIC Educational Resources Information Center

    Panik, Meredith Anne

    2010-01-01

    Teachers' pity and anger responses to students who fail often are interpreted by the students as indicative of the teachers' attributions for the cause behind the student failure. Students' interpretations of these emotional responses can affect their self-esteem and expectations for future success. The present study explored variables that may…

  11. Project BEST-PAL (Basic Education Skills Through-Parenting Affective Learning): Level II Modules.

    ERIC Educational Resources Information Center

    Brevard Community Coll., Cocoa, FL.

    These eight learning modules were prepared for parents participating in Brevard Community College's Project BEST-PAL (Basic Education Skills Through-Parenting Affective Learning), which was designed for low socioeconomic parents who are in need of an opportunity to explore effective parenting. First, materials for the BEST-PAL volunteer sponsors…

  12. Project BEST-PAL (Basic Education Skills Through-Parenting Affective Learning): Level I Modules.

    ERIC Educational Resources Information Center

    Brevard Community Coll., Cocoa, FL.

    These eight learning m