Imel, Erik A.; DiMeglio, Linda A.; Hui, Siu L.; Carpenter, Thomas O.; Econs, Michael J.
2010-01-01
Context: X-Linked hypophosphatemia (XLH) is characterized by renal phosphate wasting, with inappropriately low or normal serum 1,25-dihydroxyvitamin D concentrations causing rickets and osteomalacia. Mutations in PHEX result in increased fibroblast growth factor 23 (FGF23) expression, elevating circulating FGF23 concentrations. Treating XLH with phosphate and calcitriol may further increase FGF23 concentrations, based on in vitro and in vivo models. Objective: The aim of the study was to investigate whether current standard XLH therapies increase circulating FGF23 concentrations. Design and Setting: We conducted a prospective observational study of XLH subjects during routine clinical management at two tertiary referral centers. Patients: The study included 10 XLH patients (seven children, three adults; age, 2–30 yr) initiating therapy and five XLH patients (age, 18–41 yr) electing not to undergo therapy. Intervention(s): Oral calcitriol and phosphate were administered. Main Outcome Measures: We measured circulating intact FGF23 concentrations. Results: Baseline circulating FGF23 concentrations were elevated in 14 of 15 subjects, increasing after treatment in most subjects. Follow-up was 14.4 ± 11.7 months (treatment cohort) and 25 ± 32 months (nontreatment cohort). FGF23 concentrations increased 132.7 ± 202.4% from pretreatment to peak during therapy but did not change significantly over time in the nontreatment cohort. FGF23 concentrations were related to phosphate doses (P = 0.04) and nonsignificantly to calcitriol doses (P = 0.06). Conclusions: Treating XLH with phosphate and calcitriol was associated with concurrent increases in circulating FGF23 concentrations, which may diminish therapeutic effect or contribute to complications of therapy. Because it is unknown whether the degree of FGF23 elevation correlates with disease severity in XLH, further study is needed to determine whether adjusting therapy to minimize effects on FGF23 concentration is warranted. PMID:20157195
USDA-ARS?s Scientific Manuscript database
Previous reports suggest increased circulating concentrations of estradiol prior to GnRH induced ovulation improved conception rates and pregnancy maintenance in beef cattle, and cultured granulosa cells from animals with high antral follicle numbers produced more estradiol and had increased express...
USDA-ARS?s Scientific Manuscript database
Cows with greater circulating concentrations of estradiol during the preovulatory period (HighE2) have increased pregnancy success following a fixed-time AI protocol. Furthermore, these animals have an enhanced ability to produce estradiol as indicated by increased expression of CYP19A1 and LHR wit...
Abdel Aziz, R L; Khalil, A A Y; Abdel-Wahab, A; Hassan, N Y; Abdel-Hamied, E; Kasimanickam, R K
2017-09-15
The objectives of this study were 1. to determine the associations among circulating anti-Mullerian hormone (AMH), insulin like growth factor 1 (IGF1) and cadmium (Cd) concentrations of lactating Holstein cows at the time of superovulation and 2. to determine the effect of circulating AMH, IGF1 and Cd concentrations on the superovulatory response in Holstein dairy cows. Holstein cows (n = 30) were milked thrice daily and housed and fed in free stall barn as a separate group. All animals were synchronized for superovulation and flushed. Three blood samples for AMH, IGF1 and Cd analysis were collected prior to superovulation, at estrus and at the time of embryo collection. The concentrations of blood makers prior to superovulation were highly correlated to superovulatory response. Circulating concentrations of AMH, IGF1 prior to superovulation were negatively correlated to Cd concentrations (P < 0.05). There was no correlation between circulating concentrations of AMH and IGF1. The number of corpus luteum (r = 0.71), total embryo (r = 0.67), total transferable embryo (r = 0.51) and total grade 1 embryo (r = 0.5) were positively correlated to AMH concentrations (P < 0.05). There was a trend for negative correlation found between circulating cadmium concentrations and total grade 1 embryo yield (P < 0.1). When cows were classified into quartiles (Q) of circulating AMH concentration, number of corpus luteum, and total embryos, total transferable embryos and total grade 1 embryos yield was significantly different for AMH quartiles. The superovulatory response parameters evaluated were increased with increased AMH concentrations; particularly we observed a >2-fold difference between first and fourth AMH quartiles in total transferable embryo yield and total grade 1 embryo yield. In conclusion, circulating AMH concentration was strongly associated with superovulatory response. Measuring AMH before enrolling cows in superovulation programs will likely allow practitioners to improve numbers of embryos produced and, thereby, reduce costs per embryo produced. Published by Elsevier Inc.
Larmo, Petra S; Yang, Baoru; Hurme, Saija A M; Alin, Jouni A; Kallio, Heikki P; Salminen, Eeva K; Tahvonen, Raija L
2009-08-01
Epidemiological studies indicate beneficial effects of flavonoids on cardiovascular disease (CVD) risk. To study the effect of flavonoid-rich sea buckthorn berry (SBB) on circulating lipid markers associated with CVD risk and plasma flavonol concentration. Also investigated was whether changes in the circulating flavonol concentrations correlate with the SBB induced changes in C-reactive protein (CRP) concentration observed previously. In all 229 healthy participants completed the randomized double-blind study and consumed daily 28 g of SBB or placebo for 3 months. Fasting blood samples for the analysis of lipid markers and flavonols were obtained at the beginning and end of the study. Compared to the placebo, the consumption of SBB increased the plasma concentration of the flavonols quercetin and isorhamnetin significantly [treatment differences 3.0 ng/ml (P = 0.03) and 3.9 ng/ml (P < 0.01), respectively]. The increase of kaempferol concentration was not significant [treatment difference 0.7 ng/ml (P = 0.08)]. SBB did not affect the serum total, HDL, LDL cholesterol, or the serum triacylglycerol concentrations. There was no correlation between the changes in flavonol and CRP concentrations of participants. The consumption of SBB significantly increased the fasting plasma concentration of quercetin and isorhamnetin indicating that it is a good dietary source of flavonols. However, this did not convert to affecting the circulating concentrations of lipid markers in healthy, normolipidemic adults having healthy diets.
Swarbrick, Michael M.
2008-01-01
Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans. PMID:18510434
Plasma enteroglucagon and CCK levels and cell proliferation in defunctioned small bowel in the rat.
Gornacz, G E; Ghatei, M A; Al-Mukhtar, M Y; Yeats, J C; Adrian, T E; Wright, N A; Bloom, S R
1984-11-01
Luminal nutrients exert a powerful trophic effect on small bowel mucosa. Recent evidence suggests that a circulating factor, possibly enteroglucagon, is also growth-promoting. In order to study the isolated effect of nonluminal influences on bowel mucosa, Thiry-Vella fistulae (TVF) were constructed in rats. Circulating enteric hormone concentrations were manipulated by resecting different lengths of remaining gut. Thirty-two male Wistar rats had either 25%, 50%, 75%, or 90% proximal small bowel resection. In each animal the first 25% of resected bowel was exteriorized as a Thiry-Vella fistula. Seven control rats underwent jejunal transection. Twelve days postoperatively the fasted animals were killed, and circulating and tissue concentrations of enteroglucagon and CCK were estimated by radioimmunoassay. Crypt-cell production rate was used as an index of cellular proliferation in the Thiry-Vella fistulae. Proximal small bowel defunctioned in the Thirty-Vella fistulae had a significantly lower crypt-cell production rate and enteroglucagon and CCK content than the equivalent segment in transected rats. Further small bowel resection produced a subsequent increase in circulating enteroglucagon and CCK concentrations, an increase in the Thiry-Vella fistula content of these hormones, and a doubling of the crypt-cell production rate in the Thiry-Vella fistulae. These results show that circulating enteroglucagon and CCK concentrations match closely with enterocyte production even when luminal influences are excluded. It is suggested that circulating factors may play a major role in postresectional ileal hyperplasia. This hyperplasia apparently affects endocrine cells as well as enterocytes.
Alberro, Ainhoa; Sáenz-Cuesta, Matías; Muñoz-Culla, Maider; Mateo-Abad, Maider; Gonzalez, Esperanza; Carrasco-Garcia, Estefania; Araúzo-Bravo, Marcos J.; Matheu, Ander; Vergara, Itziar; Otaegui, David
2016-01-01
In the last decades extracellular vesicles (EVs) have emerged as key players for intercellular communication. In the case of inflammation, several studies have reported that EV levels are increased in circulation during inflammatory episodes. Based on this, we investigated whether aging results in elevated EV number, as a basal proinflammatory status termed “inflammaging” has been described in aged individuals. Moreover, we also hypothesized that frailty and dependence conditions of the elderly could affect EV concentration in plasma. Results showed that inflammaging, frailty or dependence status do not result in EV increase, at least in the total number of EVs in circulation. These results open a new perspective for investigating the role of EVs in human aging and in the inflammaging process. PMID:27447627
Alberro, Ainhoa; Sáenz-Cuesta, Matías; Muñoz-Culla, Maider; Mateo-Abad, Maider; Gonzalez, Esperanza; Carrasco-Garcia, Estefania; Araúzo-Bravo, Marcos J; Matheu, Ander; Vergara, Itziar; Otaegui, David
2016-07-20
In the last decades extracellular vesicles (EVs) have emerged as key players for intercellular communication. In the case of inflammation, several studies have reported that EV levels are increased in circulation during inflammatory episodes. Based on this, we investigated whether aging results in elevated EV number, as a basal proinflammatory status termed "inflammaging" has been described in aged individuals. Moreover, we also hypothesized that frailty and dependence conditions of the elderly could affect EV concentration in plasma. Results showed that inflammaging, frailty or dependence status do not result in EV increase, at least in the total number of EVs in circulation. These results open a new perspective for investigating the role of EVs in human aging and in the inflammaging process.
Future changes in tropospheric ozone under Representative Concentration Pathways (RCPs)
NASA Astrophysics Data System (ADS)
Kawase, Hiroaki; Nagashima, Tatsuya; Sudo, Kengo; Nozawa, Toru
2011-03-01
We consider future changes in tropospheric ozone based on the Representative Concentration Pathways (RCPs), which are new emission and concentration scenarios for the 5th coupled model intercomparison project. In contrast to the SRES scenarios, all the RCP scenarios assume an emission reduction of NOx by the late 21st Century that has the potential to achieve tropospheric ozone reduction. However, increasing radiative forcing (RF) due to greenhouse gases and changes in CH4 concentration also contribute to differences in the tropospheric ozone distribution among RCP scenarios. In the RCP4.5 and RCP6.0, assuming the stabilization of RF, the increase in tropospheric ozone due to enhanced residual circulation is cancelled out by the ozone reduction due to ozone precursor reductions. In contrast, in the RCP8.5, assuming increasing RF even after 2100, further enhanced residual circulation and significant increase in CH4 cause a dramatic increase in tropospheric ozone.
Gamarra, G; Ponsart, C; Lacaze, S; Le Guienne, B; Humblot, P; Deloche, M-C; Monniaux, D; Ponter, A A
2015-11-01
Rapid genetic improvement in cattle requires the production of high numbers of embryos of excellent quality. Increasing circulating insulin and/or glucose concentrations improves ovarian follicular growth, which may improve the response to superovulation. The measurement of anti-Müllerian hormone (AMH) can help predict an animal's response to superovulation treatment. The aim of the present study was to investigate whether increasing circulating insulin concentrations, through propylene glycol (PG) drenches, could improve in vitro embryo production in oestrus-synchronised superovulated heifers with different AMH profiles. Holstein heifers were grouped according to pre-experimental AMH concentrations as low (L) or high (H). The PG drench increased circulating insulin and glucose concentrations and reduced β-hydroxybutyrate and urea concentrations compared with the control group. AMH was a good predictor of follicle and oocyte numbers at ovum pick-up (OPU), and of oocyte and embryo quality (AMH H>AMH L). PG in the AMH H group increased the number of follicles and blastocyst quality above that in the control group, but did not improve these parameters in the AMH L group. These results indicate that short-term oral PG supplementation modifies an animal's metabolic milieu and is effective in improving in vitro embryo production, after superovulation-OPU, more markedly in heifers with high rather than low AMH concentrations.
McMillen, I C; Muhlhausler, B S; Duffield, J A; Yuen, B S J
2004-08-01
Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.
Jeon, Jin Hee; Kim, Sang Done; Lim, Tak Hyoung; Lee, Dong Hyun
2005-08-01
The effects of initial trichloroethylene (TCE) concentration, recirculating liquid flow rate and gas velocity on photodegradation of TCE have been determined in an internally circulating slurry bubble column reactor (0.15m-ID x 0.85 m-high). Titanium dioxide (TiO2) powder was employed as a photocatalyst and the optimum loading of TiO2 in the present system is found to be approximately 0.2 wt%. The stripping fraction of TCE by air flow increases but photodegradation fraction of TCE decreases with increasing the initial TCE concentration, recirculating liquid flow rate and gas velocity. The average removal efficiency of TCE is found to be approximately 97% in an internally circulating slurry bubble column reactor.
2009-04-01
Shelf, and into the Gulf of Mexico, empirically derived chl ; increases were observed in the Tortugas Gyre circulation feature, and in adjacent...Mexico, empirically derived chl a increases were observed in the Tortugas Gyre circulation feature, and in adjacent waters. Analy- sis of the...hurricane interaction also influenced the Tortugas Gyre, a recognized circulation feature in the southern Gulf of Mexico induced by the flow of the
Emanueli, Costanza; Shearn, Andrew I U; Laftah, Abas; Fiorentino, Francesca; Reeves, Barnaby C; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D
2016-01-01
Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage. The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs. The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.
Emanueli, Costanza; Fiorentino, Francesca; Reeves, Barnaby C.; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D.
2016-01-01
Introduction Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current “gold standard” surrogate biomarker of myocardial damage. Methods and Results The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs. Conclusions The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients. PMID:27128471
Pastor, Antoni; Fernández-Aranda, Fernando; Fitó, Montserrat; Jiménez-Murcia, Susana; Botella, Cristina; Fernández-Real, Jose M; Frühbeck, Gema; Tinahones, Francisco J; Fagundo, Ana B; Rodriguez, Joan; Agüera, Zaida; Langohr, Klaus; Casanueva, Felipe F; de la Torre, Rafael
2016-01-01
The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.
Transient Atmospheric Circulation Changes in a Grand ensemble of Idealized CO2 Increase Experiments
NASA Astrophysics Data System (ADS)
Karpechko, A.; Manzini, E.; Kornblueh, L.
2017-12-01
The yearly evolution with increasing forcing of the large-scale atmospheric circulation is examined in a 68-member ensemble of 1pctCO2 scenario experiments performed with the MPI-ESM model. Each member of the experiment ensemble is integrated for 155 years, from initial conditions taken from a 2000-yr long pre-industrial control climate experiment. The 1pctCO2 scenario experiments are conducted following the protocol of including as external forcing only a CO2 concentration increase at 1%/year, till quadrupling of CO2 concentrations. MPI-ESM is the Max-Planck-Institute Earth System Model (including coupling between the atmosphere, ocean and seaice). By averaging over the 68 members (ensemble mean), atmospheric variability is greatly reduced. Thus, it is possible to investigate the sensitivity to the climate state of the atmospheric response to CO2 doubling. Indicators of global change show the expected monotonic evolution with increasing CO2 and a weak dependence of the thermodynamical response to CO2 doubling on the climate state. The surface climate response of the atmospheric circulation, diagnosed for instance by the pressure at sea level, and the eddy-driven jet response show instead a marked dependence to the climate state, for the Northern winter season. We find that as the CO2 concentration increases above doubling, Northern winter trends in some indicators of atmospheric circulation changes decrease or even reverse, posing the question on what are the causes of this nonlinear behavior. The investigation of the role of stationary waves, the meridional overturning circulation, the decrease in Arctic sea ice and the stratospheric vortex points to the latter as a plausible cause of such nonlinear response.
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.
Passive heat stress reduces circulating endothelial and platelet microparticles.
Bain, Anthony R; Ainslie, Philip N; Bammert, Tyler D; Hijmans, Jamie G; Sekhon, Mypinder; Hoiland, Ryan L; Flück, Daniela; Donnelly, Joseph; DeSouza, Christopher A
2017-06-01
What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23 ± 3 years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean ± SD oesophageal temperature in normothermia was 37.2 ± 0.1°C and in hyperthermia 39.1 ± 0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean ± SD; from 61 ± 8 to 43 ± 7 microparticles μl -1 ; P < 0.05) and apoptosis-derived EMPs by ∼45% (from 46 ± 7 to 23 ± 3 microparticles μl -1 ; P < 0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia (from 256 ± 43 to 62 ± 14 microparticles μl -1 ). These beneficial reductions in circulating EMPs and PMPs in response to a 2°C increase in core temperature might partly underlie the reported vascular improvements following therapeutic bouts of physiological hyperthermia. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.
Kasperska-Zając, Alicja; Damasiewicz-Bodzek, Aleksandra; Grzanka, Ryszard; Skrzypulec-Frankel, Agnieszka; Bieniek, Katarzyna; Sikora-Żydek, Agnieszka; Jochem, Jerzy
2018-01-01
LIGHT (homologous to lymphotoxins, exhibiting inducible expression, and competing with herpes simplex virus (HSV) glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) has been involved in various autoimmune and inflammatory disorders. LIGHT induces the expression of interleukin-8 (IL-8), which is up-regulated in chronic spontaneous urticaria (CSU). To determine circulating soluble LIGHT concentration and its relationship with IL-8 concentration in patients with CSU. Concentrations of LIGHT, IL-8, and C-reactive protein (CRP) were determined in plasma or serum of CSU patients by an enzyme-linked immunosorbent assay. LIGHT plasma concentration was significantly higher in moderate-severe CSU patients as compared with the healthy subjects, but not with mild CSU patients. There were significant correlations between increased LIGHT and IL-8 concentrations, but not with increased CRP in CSU patients. Enhanced plasma concentrations of soluble LIGHT and its association with IL-8 concentration suggest the role of LIGHT in systemic inflammatory activation in CSU patients. We hypothesize that LIGHT-mediated immune-inflammatory response plays a role in severe phenotypes of the disease.
USDA-ARS?s Scientific Manuscript database
The synthetic met-enkephalin syndyphalin-33 (SD-33) increases feed intake in sheep and transiently increases circulating growth hormone (GH) concentrations in sheep, rats, and pigs. Two experiments were performed to evaluate the effects of SD-33 on recently-weaned pigs. In a preliminary experiment, ...
Locher, L; Häussler, S; Laubenthal, L; Singh, S P; Winkler, J; Kinoshita, A; Kenéz, Á; Rehage, J; Huber, K; Sauerwein, H; Dänicke, S
2015-02-01
In response to negative energy balance, overconditioned cows mobilize more body fat than thin cows and subsequently are prone to develop metabolic disorders. Changes in adipose tissue (AT) metabolism are barely investigated in overconditioned cows. Therefore, the objective was to investigate the effect of increasing body condition on key regulator proteins of fat metabolism in subcutaneous AT and circulation of dairy cows. Nonlactating, nonpregnant dairy cows (n=8) investigated in the current study served as a model to elucidate the changes in the course of overcondition independent from physiological changes related to gestation, parturition, and lactation. Cows were fed diets with increasing portions of concentrate during the first 6wk of the experiment until 60% were reached, which was maintained for 9wk. Biopsy samples from AT of the subcutaneous tailhead region were collected every 8wk, whereas blood was sampled monthly. Within the experimental period cows had an average BW gain of 243±33.3 kg. Leptin and insulin concentrations were increased until wk 12. Based on serum concentrations of glucose, insulin, and nonesterified fatty acids, the surrogate indices for insulin sensitivity were calculated. High-concentrate feeding led to decreased quantitative insulin sensitivity check index and homeostasis model assessment due to high insulin and glucose concentrations indicating decreased insulin sensitivity. Adiponectin, an adipokine-promoting insulin sensitivity, decreased in subcutaneous AT, but remained unchanged in the circulation. The high-concentrate diet affected key enzymes reflecting AT metabolism such as AMP-activated protein kinase and hormone-sensitive lipase, both represented as the proportion of the phosphorylated protein to total protein, as well as fatty acid synthase. The extent of phosphorylation of AMP-activated protein kinase and the protein expression of fatty acid synthase were inversely regulated throughout the experimental period, whereas the extent of phosphorylation of hormone-sensitive lipase was consistently decreasing by the high-concentrate diet. Overcondition in nonpregnant, nonlactating dairy cows changed the expression of key regulator proteins of AT metabolism and circulation accompanied by impaired insulin sensitivity, which might increase the risk for metabolic disorders. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Pizon, M T; Gburek, T; Pizon, M; Sztefko, K
2006-12-01
Heat shock protein HSP-70 is known as protective chaperone molecule synthetized in response following ischemia and stress agents. It is detected in the myocardium and endothelium as well as in the circulation. Damaged as well as viable but exposed to stress cells contribute to the release of HSP-70 into the circulation. The aim of the study was to investigate if cardiopulmonary bypss (CPB) leads to more circulating HSP-70, on the basis of comparison dynamics of plasma concentration HSP-70 in 8 men undergoing procedures with the use of CPB (coronary artery bypass grafting, CABG group) and 8 men undergoing off-pump surgery (OPCAB group). Blood samples were taken preoperatively, twice intraoperatively, immediately after surgical procedure (1 h) and 24-hours thereafter. The concentration of plasma HSP-70 was measured by means of immunoassay. The derived results were compared statistically with the frequency of incidence postoperative atrial fibrillation (AF). In CABG group was observed continuous gradual increase of plasma HSP-70 concentration during the operation with the peak 1 h after surgery (P<0.01), in striking contrast to OPCAB group, in which was detected small, but non statistically significant increase of HSP-70 1 h after operation. Significantly more of circulating HSP-70 it was detected in CABG group during the operation and 1 h after surgery (CABG vs OPCAB, respectively P<0.015 and P<0.028). In both groups among patients witch AF it was found higher postoperative values of circulating HSP-70 compared with the non-AF group (P=0.0415). The use of CPB leads to significant more release of HSP-70 into the circulation. According to our findings high plasma concentration of HSP-70 may be the measure of operative cellular stress, ischemia or injury and may be related with greater onset of postoperative AF. High circulating HSP-70 levels is connected with higher incidence of postoperative AF after open heart surgery.
How the sauna affects the endocrine system.
Kukkonen-Harjula, K; Kauppinen, K
1988-01-01
The sauna induces changes in the secretion of hormones, some similar to changes induced in any other stress situation and others characteristic of exposure to the sauna. Noradrenaline is usually the only catecholamine raised by the sauna in people accustomed to it. The secretion of the antidiuretic hormone is increased and the renin-angiotensin-aldosterone system is activated. The concentrations of the growth hormone and prolactin, in particular, secreted from the anterior pituitary are increased in the circulation. The concentration of the immunoreactive beta-endorphin in blood may also increase which may reflect the feeling of pleasure or, on the other hand, discomfort induced by the sauna. The views on the effects of the sauna on the secretion of the ACTH and cortisol are partly contradictory, probably due to differing ways of taking the sauna bath. In Finnish sauna takers the concentration of cortisol in blood is not usually increased. The changes induced by the sauna in various hormone concentrations in the circulation are, however, normalized within a couple of hours after the heat stress.
Boutry, Claire; Matsumoto, Hideki; Bos, Cécile; Moinard, Christophe; Cynober, Luc; Yin, Yulong; Tomé, Daniel; Blachier, François
2012-10-01
Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg(-1) lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-α. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.
Moreno-Navarrete, J M; Manco, M; Ibáñez, J; García-Fuentes, E; Ortega, F; Gorostiaga, E; Vendrell, J; Izquierdo, M; Martínez, C; Nolfe, G; Ricart, W; Mingrone, G; Tinahones, F; Fernández-Real, J M
2010-02-01
Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.
Damoiseaux, C; Merveille, A-C; Krafft, E; Da Costa, A M; Gomart, S; Jespers, P; Michaux, C; Clercx, C; Verhoeven, C; Mc Entee, K
2014-01-01
In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis. To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM). One hundred and fourteen client-owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège. We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine-specific sandwich ELISA kit. An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014). Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome. Copyright © 2014 by the American College of Veterinary Internal Medicine.
Roble, N D; Ogbonna, J C; Tanaka, H
2003-02-01
A circulating loop bioreactor (CLB) with cells immobilized in loofa sponge was constructed for simultaneous aerobic and anaerobic processes. The CLB consists of an aerated riser and a non-aerated downcomer column connected at the top and bottom by cylindrical pipes. Ethanol production from raw cassava starch was investigated in the CLB. Aspergillus awamori IAM 2389 and Saccharomyces cerevisiae IR2 immobilized on loofa sponge were placed, respectively, in the aerated riser column and non-aerated downcomer column. Both alpha-amylase and glucoamylase activities increased as the aeration rate was increased. Ethanol yield and productivity increased with an increase in the aeration rate up to 0.5 vvm, but decreased at higher aeration rates. The CLB was operated at an aeration rate of 0.5 vvm for more than 600 h, resulting in an average ethanol productivity and yield from raw cassava starch of 0.5 g-ethanol l(-1) x h(-1) and 0.45 g ethanol/g starch, respectively. In order to increase ethanol productivity, it was necessary to increase the dissolved oxygen (DO) concentration in the riser column and decrease the DO concentration in the downcomer column. However, increasing the aeration rate resulted in increases in the DO concentration in both the riser and the downcomer columns. At high aeration rate, there was no significant difference in the DO concentration in the riser and downcomer columns. The aeration rate was therefore uncoupled from the liquid circulation by attaching a time-controlled valve in the upper connecting pipe. By optimizing the time and frequency of valve opening, and operation at high aeration rate, it was possible to maintain a very high DO concentration in the riser column and a low DO concentration in the downcomer column. Under these conditions, ethanol productivity increased by more than 100%, to 1.17 g l(-1) x h(-1).
NASA Astrophysics Data System (ADS)
Frisbee, Marty D.; Tolley, Douglas G.; Wilson, John L.
2017-04-01
Estimates of groundwater circulation depths based on field data are lacking. These data are critical to inform and refine hydrogeologic models of mountainous watersheds, and to quantify depth and time dependencies of weathering processes in watersheds. Here we test two competing hypotheses on the role of geology and geologic setting in deep groundwater circulation and the role of deep groundwater in the geochemical evolution of streams and springs. We test these hypotheses in two mountainous watersheds that have distinctly different geologic settings (one crystalline, metamorphic bedrock and the other volcanic bedrock). Estimated circulation depths for springs in both watersheds range from 0.6 to 1.6 km and may be as great as 2.5 km. These estimated groundwater circulation depths are much deeper than commonly modeled depths suggesting that we may be forcing groundwater flow paths too shallow in models. In addition, the spatial relationships of groundwater circulation depths are different between the two watersheds. Groundwater circulation depths in the crystalline bedrock watershed increase with decreasing elevation indicative of topography-driven groundwater flow. This relationship is not present in the volcanic bedrock watershed suggesting that both the source of fracturing (tectonic versus volcanic) and increased primary porosity in the volcanic bedrock play a role in deep groundwater circulation. The results from the crystalline bedrock watershed also indicate that relatively deep groundwater circulation can occur at local scales in headwater drainages less than 9.0 km2 and at larger fractions than commonly perceived. Deep groundwater is a primary control on streamflow processes and solute concentrations in both watersheds.
Microplasmin-Induced Posterior Vitreous Detachment Affects Vitreous Oxygen Levels
Quiram, Polly A.; Leverenz, Victor R.; Baker, Robert M.; Dang, Loan; Giblin, Frauk J.; Trese, Michael T.
2009-01-01
Purpose To determine if enzymatic induction of a posterior vitreous detachment (PVD) and/or vitreous liquefaction affects O2 concentration in the vitreous cavity in animals with vascularized and avascular retinal circulations. Methods Either microplasmin or hyaluronidase was injected intravitreally into guinea pigs (avascular retinal circulation), brown Norway rats (vascularized retinal circulation without fovea), or cats (vascularized retinal circulation with fovea) with the contralateral eye used as a control. One to 2 weeks post injection, vitreal oxygen concentration was measured using a highly sensitive, platinum-based fluorophore O2 sensor. In addition, control and microplasmin-injected rats, guinea pigs, and cats were exposed to 100% oxygen and vitreal O2 levels were measured over time. Scanning electron microscopy (SEM) was used to evaluate the vitreoretinal interface for the presence of a PVD. Results In animals with a vascularized retinal circulation (brown Norway rats and cats), intravitreal injection of microplasmin with induction of a PVD significantly increased baseline O2 concentration in the vitreous cavity compared to hyaluronidase injected eyes and controls in rats (35, 25, and 23 mm Hg, P < 0.001 and P < 0.001, respectively) and cats (26, 18, and 16 mm Hg, P < 0.01 and P < 0.001, respectively). Interestingly, intravitreal injection of hyaluronidase (vitreous liquefaction without induction of a PVD) did not significantly increase vitreal O2 levels in any of the animal species (P > 0.1). Upon exposure to 100% oxygen by facemask, microplasmin injected animals showed a rapid increase in vitreal oxygen levels compared to hyaluronidase injected animals and controls, indicating that the presence of a PVD allows rapid O2 exchange within the vitreous cavity. Similarly, once O2 was discontinued, the O2 concentration decreased in a similarly rapid rate. SEM showed smooth retinal surfaces in microplasmin-injected cat eyes, indicating the presence of a PVD which was not present in hyaluronidase injected or control eyes. Conclusion The results suggest that enzymatic-assisted PVD with microplasmin increases vitreal O2 levels and increases the rate of O2 exchange within the vitreous cavity. PMID:18040251
Briana, Despina D; Boutsikou, Maria; Baka, Stavroula; Hassiakos, Demetrios; Gourgiotis, Demetrios; Malamitsi-Puchner, Ariadne
2009-01-01
Intrauterine growth restriction (IUGR) has been associated with low bone mass in infancy and increased risk for osteoporosis development in adult life. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are main determinants of bone resorption. To investigate OPG and soluble RANKL (sRANKL) concentrations in maternal, fetal and neonatal serum of IUGR patients and appropriate for gestational age (AGA) pregnancies. Additionally, plasma intact parathormone (PTH) concentrations were evaluated. Circulating OPG, sRANKL and PTH concentrations were measured in 40 mothers and their singleton full-term fetuses-neonates (AGA: n = 20, and IUGR: n =20) on postnatal days 1 (N1) and 4 (N4). No significant differences in OPG, sRANKL or PTH concentrations were observed between AGA and IUGR groups. In both groups, maternal OPG concentrations were elevated compared with fetal, and N1 and N4 concentrations (p < or = 0.045 in all cases). N4 sRANKL concentrations were elevated compared with maternal, fetal and N1 ones (p < or = 0.01 in all cases). Fetal and N1 sRANKL concentrations correlated positively with PTH levels (r = 0.642, p = 0.024 and r = 0.584, p = 0.046, respectively). The lack of a difference in circulating OPG, sRANKL or PTH concentrations between IUGR cases and AGA controls suggests that the low bone mass of IUGR infants may not be related to higher bone resorption rates. The increased maternal, compared with fetal/neonatal, OPG concentrations may suggest their placental origin. The lower OPG and higher sRANKL concentrations in fetuses and neonates could represent high bone resorption rates. Copyright 2009 S. Karger AG, Basel.
McCormack, S E; Shaham, O; McCarthy, M A; Deik, A A; Wang, T J; Gerszten, R E; Clish, C B; Mootha, V K; Grinspoon, S K; Fleischman, A
2013-02-01
What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.
Preston, D M; Adrian, T E; Christofides, N D; Lennard-Jones, J E; Bloom, S R
1985-01-01
Motilin, pancreatic polypeptide and gastrin blood concentrations in response to drinking water have been studied in 40 patients with functional bowel disease and compared with results in two groups of healthy control subjects. Patients with slow transit constipation and idiopathic megacolon showed impaired motilin release. Pancreatic polypeptide release was reduced in patients with slow transit constipation, but increased in those with functional diarrhoea. Gastrin release was impaired in all groups complaining of chronic constipation. Circulating motilin, pancreatic polypeptide and gastrin concentrations appear to bear some relationship to intestinal transit time in patients with functional bowel disorders. PMID:4054704
Preston, D M; Adrian, T E; Christofides, N D; Lennard-Jones, J E; Bloom, S R
1985-10-01
Motilin, pancreatic polypeptide and gastrin blood concentrations in response to drinking water have been studied in 40 patients with functional bowel disease and compared with results in two groups of healthy control subjects. Patients with slow transit constipation and idiopathic megacolon showed impaired motilin release. Pancreatic polypeptide release was reduced in patients with slow transit constipation, but increased in those with functional diarrhoea. Gastrin release was impaired in all groups complaining of chronic constipation. Circulating motilin, pancreatic polypeptide and gastrin concentrations appear to bear some relationship to intestinal transit time in patients with functional bowel disorders.
Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J
2014-07-03
Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.
Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Izaguirre, Maitane; Hernández-Lizoain, José Luis; Baixauli, Jorge; Martí, Pablo; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Salvador, Javier; Frühbeck, Gema
2016-01-01
Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics. PMID:27612200
Cloud Coverage Enhancement and Nocturnal Drizzle Suppression in Stratocumulus by Aerosols
NASA Technical Reports Server (NTRS)
Ackerman, Andrew S.; Toon, Owen B.; Stevens, David E.; Coakley, James A., Jr.; Gore, Warren J. (Technical Monitor)
2002-01-01
Recent satellite observations of ship tracks surprisingly indicate that cloud water decreases with increasing droplet concentrations. However, we find by analyzing detailed simulations of stratocumulus that the reported trend is likely an artifact of sampling, only overcast clouds. The simulations instead show cloud coverage increasing with droplet concentrations, accounting for 25% of cloud albedo increase at moderate droplet concentrations. Our simulations also show that increases in cloud water from drizzle suppression (by increasing droplet concentrations) are favored only at night or at extremely low droplet concentrations, suggesting that the indirect aerosol forcing is overestimated in climate change projections by many general circulation models.
Koh, Gar Yee; Derscheid, Rachel; Fuller, Kelly N Z; Valentine, Rudy J; Leow, Shu En; Reed, Leah; Wisecup, Emily; Schalinske, Kevin L; Rowling, Matthew J
2016-04-01
We previously reported that dietary resistant starch (RS) type 2 prevented proteinuria and promoted vitamin D balance in type 2 diabetic (T2D) rats. Here, our primary objective was to identify potential mechanisms that could explain our earlier observations. We hypothesized that RS could promote adiponectin secretion and regulate the renin-angiotensin system activity in the kidney. Lean Zucker rats (n = 5) were fed control diet; Zucker diabetic fatty rats (n = 5/group) were fed either an AIN-93G control diet (DC) or AIN-93G diet containing either 10% RS or 20% RS (HRS) for 6 weeks. Resistant starch had no impact on blood glucose concentrations and hemoglobin A1c percentage, yet circulating adiponectin was 77% higher in HRS-fed rats, compared to DC rats. Adiponectin concentrations strongly correlated with serum 25-hydroxycholecalciferol (r = 0.815; P < .001) and urinary creatinine concentrations (r = 0.818; P < .001) and inversely correlated with proteinuria (r = -0.583; P = .02). Serum angiotensin II concentrations were 44% lower, and expression of the angiotensin II receptor, type 1, was attenuated in RS-fed rats. Moreover, we observed a 14-fold increase in messenger RNA expression of nephrin, which is required for functioning of the renal filtration barrier, in HRS rats. The HRS, but not 10% RS diet, increased circulating 25-hydroxycholecalciferol concentrations and attenuated urinary loss of vitamin D metabolites in Zucker diabetic fatty rats. Taken together, we provide evidence that vitamin D balance in the presence of hyperglycemia is strongly associated with serum adiponectin levels and reduced renal renin-angiotensin system signaling. Copyright © 2016 Elsevier Inc. All rights reserved.
Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.
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. © 2016 British Society for Neuroendocrinology.
Collection and use of circulating hematopoietic progenitor cells.
Lee, J H; Klein, H G
1995-02-01
Although lymphocytes and monocytes are becoming increasingly important in transfusion therapy, peripheral stem cells have been responsible for the recent explosive interest in harvesting mononuclear cells from the peripheral circulation. Despite their low concentration in peripheral blood and the consequent difficulty in cell collection, circulating hematopoietic progenitor cells are collected and used almost routinely. These mononuclear cells, possessing the capacity for hematopoietic reconstitution and the potential for definitive therapy of a variety of disorders, have been the focus of recent intense interest in transfusion medicine.
Adhikari, Dinesh; Jiang, Tianyi; Kawagoe, Taiki; Kai, Takamitsu; Kubota, Kenzo; Araki, Kiwako S; Kubo, Motoki
2017-12-04
Improvement of phosphorus circulation in the soil is necessary to enhance phosphorus availability to plants. Phosphorus circulation activity is an index of soil's ability to supply soluble phosphorus from organic phosphorus in the soil solution. To understand the relationship among phosphorus circulation activity; bacterial biomass; pH; and Fe, Al, and Ca concentrations (described as mineral concentration in this paper) in agricultural soil, 232 soil samples from various agricultural fields were collected and analyzed. A weak relationship between phosphorus circulation activity and bacterial biomass was observed in all soil samples ( R ² = 0.25), and this relationship became significantly stronger at near-neutral pH (6.0-7.3; R ² = 0.67). No relationship between phosphorus circulation activity and bacterial biomass was observed at acidic (pH < 6.0) or alkaline (pH > 7.3) pH. A negative correlation between Fe and Al concentrations and phosphorus circulation activity was observed at acidic pH ( R ² = 0.72 and 0.73, respectively), as well as for Ca at alkaline pH ( R ² = 0.64). Therefore, bacterial biomass, pH, and mineral concentration should be considered together for activation of phosphorus circulation activity in the soil. A relationship model was proposed based on the effects of bacterial biomass and mineral concentration on phosphorus circulation activity. The suitable conditions of bacterial biomass, pH, and mineral concentration for phosphorus circulation activity could be estimated from the relationship model.
Nass, Ralf; Liu, Jianhua; Patrie, James; Pezzoli, Suzan S; Farhy, Leon S; Gaylinn, Bruce D; Thorner, Michael O
2014-09-01
Ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin is found in the circulation in two forms: acyl- and desacyl-ghrelin. Acyl- and desacyl-ghrelin concentrations increase at night, when cortisol concentrations are low. Acute ghrelin administration increases ACTH and cortisol concentrations and a feedback loop between the ghrelin and ACTH-cortisol axis has been postulated. A previous study showed that exogenously induced hypercortisolism for 5 days decreased plasma ghrelin concentrations. The objective of the study was to determine whether a 4-hour infusion of hydrocortisone given at a time of low endogenous cortisol concentrations (11:00 pm to 3:00 am) acutely suppresses acyl- and desacyl-ghrelin. Eight healthy young men aged (mean ± SD) 21.5 ± 2.7 years with a body mass index of 22.4 ± 2.5 kg/m(2) were studied in a single-blind, placebo-controlled study during two separate overnight admissions on the Clinical Research Unit. The volunteers received either a 4-hour (11:00 pm to 3:00 am) infusion of hydrocortisone or a saline infusion. The hydrocortisone infusion rate was 0.3 mg/kg·h for the initial 3 minutes, 0.24 mg/kg·h for 9 minutes, and then 0.135 mg/kg·h until the end of the infusion. Plasma acyl- and desacyl-ghrelin concentrations (in-house two site sandwich assay) and ACTH, cortisol, insulin, GH, and glucose levels were measured every 10 minutes for 16 hours (5:00 pm to 9:00 am). The mean differences (lower 95% limit; upper 95% limit) between the saline infusion and hydrocortisone infusion for acyl- and desacyl-ghrelin concentrations were not significantly different from zero. The infusion period (11:00 pm to 3:00 am) was as follows: acyl-ghrelin, 0.22 (-7.39; 7.83) (P = 1.00); desacyl-ghrelin, -3.36 (-17.66; 10.95) (P = 1.00). The postinfusion period (3:00-7:00 am) was as follows: acyl-ghrelin, 8.68 (1.07; 16.28); (P = .056); desacyl-ghrelin, 8.75 (-5.56; 23.05) (P = .403). A short-term increase in circulating cortisol concentrations by exogenous hydrocortisone infusion does not suppress circulating nocturnal acyl- or desacyl-ghrelin concentrations. Thus, it is likely that the diurnal pattern of ghrelin secretion is under circadian control and not directly regulated by cortisol.
Liu, Jianhua; Patrie, James; Pezzoli, Suzan S.; Farhy, Leon S.; Gaylinn, Bruce D.; Thorner, Michael O.
2014-01-01
Background: Ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin is found in the circulation in two forms: acyl- and desacyl-ghrelin. Acyl- and desacyl-ghrelin concentrations increase at night, when cortisol concentrations are low. Acute ghrelin administration increases ACTH and cortisol concentrations and a feedback loop between the ghrelin and ACTH-cortisol axis has been postulated. A previous study showed that exogenously induced hypercortisolism for 5 days decreased plasma ghrelin concentrations. Objective: The objective of the study was to determine whether a 4-hour infusion of hydrocortisone given at a time of low endogenous cortisol concentrations (11:00 pm to 3:00 am) acutely suppresses acyl- and desacyl-ghrelin. Methods: Eight healthy young men aged (mean ± SD) 21.5 ± 2.7 years with a body mass index of 22.4 ± 2.5 kg/m2 were studied in a single-blind, placebo-controlled study during two separate overnight admissions on the Clinical Research Unit. The volunteers received either a 4-hour (11:00 pm to 3:00 am) infusion of hydrocortisone or a saline infusion. The hydrocortisone infusion rate was 0.3 mg/kg·h for the initial 3 minutes, 0.24 mg/kg·h for 9 minutes, and then 0.135 mg/kg·h until the end of the infusion. Plasma acyl- and desacyl-ghrelin concentrations (in-house two site sandwich assay) and ACTH, cortisol, insulin, GH, and glucose levels were measured every 10 minutes for 16 hours (5:00 pm to 9:00 am). Results: The mean differences (lower 95% limit; upper 95% limit) between the saline infusion and hydrocortisone infusion for acyl- and desacyl-ghrelin concentrations were not significantly different from zero. The infusion period (11:00 pm to 3:00 am) was as follows: acyl-ghrelin, 0.22 (−7.39; 7.83) (P = 1.00); desacyl-ghrelin, −3.36 (−17.66; 10.95) (P = 1.00). The postinfusion period (3:00–7:00 am) was as follows: acyl-ghrelin, 8.68 (1.07; 16.28); (P = .056); desacyl-ghrelin, 8.75 (−5.56; 23.05) (P = .403). Conclusions: A short-term increase in circulating cortisol concentrations by exogenous hydrocortisone infusion does not suppress circulating nocturnal acyl- or desacyl-ghrelin concentrations. Thus, it is likely that the diurnal pattern of ghrelin secretion is under circadian control and not directly regulated by cortisol. PMID:24963646
Maule, A.G.; Schrock, R.M.; Slater, C.; Fitzpatrick, M.S.; Schreck, C. B.
1996-01-01
The immune –endocrine responses in spring chinook salmon (Oncorhynchus tshawytscha) were examined during their freshwater migration and final maturation. In 1990, migrating fish had high plasma cortisol titres (means 200 ng ml−1) and generated relatively few antibody-producing cells (APC) from peripheral blood leukocytes (PBL) (100 –200 per culture). After three weeks acclimation in constant environmental conditions, plasma cortisol was reduced and APC increased. There were no changes in number or affinity of glucocorticoid receptors. Concentrations of several sex steroids correlated with APC in females, but there were no such correlations in males. In 1993, fish in a hatchery had significantly greater cortisol concentrations in primary circulation than in secondary circulation, but sex steroid concentrations did not differ between circulations. Mean lysozyme activity in the primary and secondary circulation did not differ in June. In August, activity in the primary circulation was significantly less than that of the secondary, perhaps the result of acute stress associated with sampling. While some sex steroids correlated with lysozyme activity, the fact that in both years all endocrine and immune variables that correlated with each other also correlated with the date of sample, raises the question as to whether or not these are cause-and-effect relations.
NASA Astrophysics Data System (ADS)
Kracher, D.; Manzini, E.; Reick, C. H.; Schultz, M. G.; Stein, O.
2014-12-01
Greenhouse gas induced climate change will modify the physical conditions of the atmosphere. One of the projected changes is an acceleration of the Brewer-Dobson circulation in the stratosphere, as it has been shown in many model studies. This change in the stratospheric circulation consequently bears an effect on the transport and distribution of atmospheric components such as N2O. Since N2O is involved in ozone destruction, a modified distribution of N2O can be of importance for ozone chemistry. N2O is inert in the troposphere and decays only in the stratosphere. Thus, changes in the exchange between troposphere and stratosphere can also affect the stratospheric sink of N2O, and consequently its atmospheric lifetime. N2O is a potent greenhouse gas with a global warming potential of currently approximately 300 CO2-equivalents in a 100-year perspective. A faster decay in atmospheric N2O mixing ratios, i.e. a decreased atmospheric lifetime of N2O, will also reduce its global warming potential. In order to assess the impact of climate change on atmospheric circulation and implied effects on the distribution and lifetime of atmospheric N2O, we apply the Max Planck Institute Earth System Model, MPI-ESM. MPI-ESM consists of the atmospheric general circulation model ECHAM, the land surface model JSBACH, and MPIOM/HAMOCC representing ocean circulation and ocean biogeochemistry. Prognostic atmospheric N2O concentrations in MPI-ESM are determined by land N2O emissions, ocean-atmosphere N2O exchange and atmospheric tracer transport. As stratospheric chemistry is not explicitly represented in MPI-ESM, stratospheric decay rates of N2O are prescribed from a MACC MOZART simulation. Increasing surface temperatures and CO2 concentrations in the stratosphere impact atmospheric circulation differently. Thus, we conduct a series of transient runs with the atmospheric model of MPI-ESM to isolate different factors governing a shift in atmospheric circulation. From those transient simulations we diagnose decreasing tropospheric N2O concentrations, increased transport of N2O from the troposphere to the stratosphere, and increasing stratospheric decay of N2O leading to a reduction in atmospheric lifetime of N2O, in dependency to climate change evolution.
Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J
2015-10-05
Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.
Tobolowsky, F A; Wada, N; Martinez-Maza, O; Magpantay, L; Koletar, S L; Palella, F J; Brown, T T; Lake, J E
2018-01-01
Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants. HIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA. Median pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01). Higher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART.
Wada, N.; Martinez-Maza, O.; Magpantay, L.; Koletar, S. L.; Palella, F. J.; Brown, T. T.; Lake, J. E.
2018-01-01
Introduction Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants. Methods HIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA. Results Median pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01). Conclusions Higher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART. PMID:29381717
USDA-ARS?s Scientific Manuscript database
GnRH-induced ovulation of small dominant follicles resulted in increased late embryonic/fetal mortality. The objective of this study was to examine the relationship between ovulatory follicle size, embryo/fetal survival, and circulating concentrations of bPAGs (detects presence of an embryo/fetus a...
Uncertainties in Carbon Dioxide Radiative Forcing in Atmospheric General Circulation Models
NASA Technical Reports Server (NTRS)
Cess, R. D.; Zhang, M.-H.; Potter, G. L.; Gates, W. L.; Taylor, K. E.; Barker, H. W.; Colman, R. A.; Fraser, J. R.; McAvaney, B. J.; Dazlich, D. A.;
1993-01-01
Global warming, caused by an increase in the concentrations of greenhouse gases, is the direct result of greenhouse gas-induced radiative forcing. When a doubling of atmospheric carbon dioxide is considered, this forcing differed substantially among 15 atmospheric general circulation models. Although there are several potential causes, the largest contributor was the carbon dioxide radiation parameterizations of the models.
Fair, Patricia A; Montie, Eric; Balthis, Len; Reif, John S; Bossart, Gregory D
2011-11-01
Thyroid hormones (TH) are key regulators of metabolism and development, yet our understanding of the variability in serum TH concentrations in free-ranging marine mammals is limited. Thus, we examined the interrelationships between TH and age, sex, reproductive status, geographic location, and ocean temperatures in wild bottlenose dolphins (Tursiops truncatus). Circulating concentrations of TH (total thyroxine (tT(4)), free T(4) (fT(4)), and total triiodothyronine (tT(3))) were determined in a total of 195 dolphins; 80 from the coastal waters of Charleston, South Carolina (CHS) and 115 from the Indian River Lagoon, Florida (IRL). Age had the most influence on circulating TH concentrations in dolphins at both sites with decreasing concentrations (p<0.0001) observed with increasing age for all TH. No significant differences were found between males and non-reproductive females. Geographic location significantly influenced tT(4) and tT(3) concentrations; CHS dolphins had higher concentrations than IRL animals. These TH differences between CHS and IRL dolphins may be attributed to the colder year-round water temperature that CHS dolphins inhabit compared to IRL dolphins and could constitute an adaptive response to their colder environment. Results from this study highlight the importance of establishing reference values for dolphins in different geographic locations to support valid comparisons. This initial assessment provides a foundation of how biological and environmental variables could affect circulating TH in dolphins, which will help to elucidate the impacts of disease, pollution, and climate change on the thyroid hormone system of aquatic mammals. Published by Elsevier Inc.
Oil Palm Empty Fruit Bunch (OPEFB) Fiber as Lost Circulation Material (LCM) in Water Based Mud (WBM)
NASA Astrophysics Data System (ADS)
Ghazali, N. A.; Sauki, A.; Abu Bakar, N. F.; Mohamed, S.
2018-05-01
Lost Circulation Material (LCM) is an additive used to prevent lost of mud to the formation as a results from natural or induced fractured during drilling operation. Losses of mud could give great impact to the oil industry as it increases mud cost and rig time. The objective of this research was to investigate the effect of size and concentration of Oil Palm Empty Fruit Bunch (OPEFB) as LCM in water based mud (WBM). Several important properties of WBM rheology after adding the OPEFB namely plastic viscosity, apparent viscosity, yield point and gel strength were characterized. The sizes of OPEFB added into the WBM were 150μm, 250μm, 500μm and 1000μm while the concentration of OPEFB used were 5g, 10g, 15g and 20g in 350 mL of WBM. Results indicated that the plastic viscosity and apparent viscosity increased with increasing of the OPEFB concentrations. On the other hand, the plastic viscosity and apparent viscosity decreased with increasing sizes of OPEFB. Yield point increased as the concentration and size of OPEFB increases. This study indicated that OPEFB was effective to be used as LCM for size of 150μm and concentration of 15g whereby it produced least amount of filtrate volume as well as good control in mud rheology.
Quantification of free circulating tumor DNA as a diagnostic marker for breast cancer.
Catarino, Raquel; Ferreira, Maria M; Rodrigues, Helena; Coelho, Ana; Nogal, Ana; Sousa, Abreu; Medeiros, Rui
2008-08-01
To determine whether the amounts of circulating DNA could discriminate between breast cancer patients and healthy individuals by using real-time PCR quantification methodology. Our standard protocol for quantification of cell-free plasma DNA involved 175 consecutive patients with breast cancer and 80 healthy controls. We found increased levels of circulating DNA in breast cancer patients compared to control individuals (105.2 vs. 77.06 ng/mL, p < 0.001). We also found statistically significant differences in circulating DNA amounts in patients before and after breast surgery (105.2 vs. 59.0 ng/mL, p = 0.001). Increased plasma cell-free DNA concentration was a strong risk factor for breast cancer, conferring an increased risk for the presence of this disease (OR, 12.32; 95% CI, 2.09-52.28; p < 0.001). Quantification of circulating DNA by real-time PCR may be a good and simple tool for detection of breast cancer with a potential to clinical applicability together with other current methods used for monitoring the disease.
Nyberg, Michael; Blackwell, James R; Damsgaard, Rasmus; Jones, Andrew M; Hellsten, Ylva; Mortensen, Stefan P
2012-01-01
Ageing has been proposed to be associated with increased levels of reactive oxygen species (ROS) that scavenge nitric oxide (NO). In eight young sedentary (23 ± 1 years; Y), eight older lifelong sedentary (66 ± 2 years; OS) and eight older lifelong physically active subjects (62 ± 2 years; OA), we studied the effect of ROS on systemic and skeletal muscle NO bioavailability and leg blood flow by infusion of the antioxidant N-acetylcysteine (NAC). Infusion of NAC increased the bioavailability of NO in OS, as evidenced by an increased concentration of stable metabolites of NO (NOx) in the arterial and venous circulation and in the muscle interstitium. In OA, infusion of NAC only increased NOx concentrations in venous plasma whereas in Y, infusion of NAC did not affect NOx concentrations. Skeletal muscle protein levels of endothelial and neuronal NO synthase were 32% and 24% higher, respectively, in OA than in OS. Exercise at 12 W elicited a lower leg blood flow response that was associated with a lower leg oxygen uptake in OS than in Y. The improved bioavailability of NO in OS did not increase blood flow during exercise. These data demonstrate that NO bioavailability is compromised in the systemic circulation and in the musculature of sedentary ageing humans due to increased oxidative stress. Lifelong physical activity opposes this effect within the trained musculature and in the arterial circulation. The lower blood flow response to leg exercise in ageing humans is not associated with a reduced NO bioavailability. PMID:22890714
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xiaolin Wei; Yang Wang; Dianfu Liu
2009-03-15
An internally circulating fluidized bed (ICFB) was applied to investigate the behavior of chlorine and sulfur during cofiring RDF and coal. The pollutant emissions in the flue gas were measured by Fourier transform infrared (FTIR) spectrometry (Gasmet DX-3000). In the tests, the concentrations of the species CO, CO{sub 2}, HCl, and SO{sub 2} were measured online. Results indicated when cofiring RDF and char, due to the higher content of chlorine in RDF, the formation of HCl significantly increases. The concentration of SO{sub 2} is relatively low because alkaline metal in the fuel ash can absorb SO{sub 2}. The concentration ofmore » CO emission during firing pure RDF is relatively higher and fluctuates sharply. With the CaO addition, the sulfur absorption by calcium quickly increases, and the desulfurization ratio is bigger than the dechlorination ratio. The chemical equilibrium method is applied to predict the behavior of chlorine. Results show that gaseous HCl emission increases with increasing RDF fraction, and gaseous KCl and NaCl formation might occur. 35 refs., 18 figs., 2 tabs.« less
Ketosis and appetite-mediating nutrients and hormones after weight loss.
Sumithran, P; Prendergast, L A; Delbridge, E; Purcell, K; Shulkes, A; Kriketos, A; Proietto, J
2013-07-01
Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss. Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding. During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding. The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.
Vila, Greisa; Hopfgartner, Judith; Grimm, Gabriele; Baumgartner-Parzer, Sabina M; Kautzky-Willer, Alexandra; Clodi, Martin; Luger, Anton
2015-10-28
Breast-feeding is associated with maternal hormonal and metabolic changes ensuring adequate milk production. In this study, we investigate the impact of breast-feeding on the profile of changes in maternal appetite-regulating hormones 3-6 months postpartum. Study participants were age- and BMI-matched lactating mothers (n 10), non-lactating mothers (n 9) and women without any history of pregnancy or breast-feeding in the previous 12 months (control group, n 10). During study sessions, young mothers breast-fed or bottle-fed their babies, and maternal blood samples were collected at five time points during 90 min: before, during and after feeding the babies. Outcome parameters were plasma concentrations of ghrelin, peptide YY (PYY), leptin, adiponectin, prolactin, cortisol, insulin, glucose and lipid values. At baseline, circulating PYY concentrations were significantly increased in lactating mothers (100·3 (se 6·7) pg/ml) v. non-lactating mothers (73·6 (se 4·9) pg/ml, P=0·008) and v. the control group (70·2 (se 9) pg/ml, P=0·021). We found no differences in ghrelin, leptin and adiponectin values. Baseline prolactin concentrations were over 4-fold higher in lactating mothers (P<0·001). Lactating women had reduced TAG levels and LDL-cholesterol:HDL-cholesterol ratio, but increased waist circumference, when compared with non-lactating women. Breast-feeding sessions further elevated circulating prolactin (P<0·001), but induced no acute effects on appetite-regulating hormones. In summary, one single breast-feeding session did not acutely modulate circulating appetite-regulating hormones, but increased baseline PYY concentrations are associated with prolonged lactation. PYY might play a role in the coordination of energy balance during lactation, increasing fat mobilisation from maternal depots and ensuring adequate milk production for the demands of the growing infant.
Shetty, Greeshma K; Matarese, Giuseppe; Magkos, Faidon; Moon, Hyun-Seuk; Liu, Xiaowen; Brennan, Aoife M; Mylvaganam, Geetha; Sykoutri, Despina; Depaoli, Alex M; Mantzoros, Christos S
2011-08-01
Short-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic-pituitary-peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified. In this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5-38.0 kg/m(2)) were prescribed a hypocaloric diet (-500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months. Metreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (P<0.001) and led to the generation of anti-leptin antibodies. Despite free leptin concentration (P for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups. Leptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.
Rosol, T J; Nagode, L A; Couto, C G; Hammer, A S; Chew, D J; Peterson, J L; Ayl, R D; Steinmeyer, C L; Capen, C C
1992-09-01
Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.9 +/- 27 pM), lymphoma (8.3 +/- 4.4 pM), and miscellaneous carcinomas (13.3 +/- 11.4 pM). The PTHrP concentration decreased in dogs with lymphoma and anal sac adenocarcinomas after successful treatment of CAH. The PTHrP concentration had a significant linear correlation with total serum calcium in dogs with anal sac adenocarcinomas and hypercalcemia, but not in dogs with lymphoma and hypercalcemia. Serum N-terminal PTH concentrations were usually in the normal range (12-34 pg/ml) for all groups of dogs except dogs with parathyroid adenomas (83 +/- 38 pg/ml). The serum PTH concentration increased after successful treatment of CAH. Serum 1,25-(OH)2D concentrations were decreased, normal, or increased in dogs with CAH, and 1,25-(OH)2D levels decreased after treatment of CAH. In summary, circulating concentrations of PTHrP are consistently increased in dogs with CAH, and PTHrP appears to play an important role in the induction of hypercalcemia.
Petrick, Jessica L; Hyland, Paula L; Caron, Patrick; Falk, Roni T; Pfeiffer, Ruth M; Dawsey, Sanford M; Abnet, Christian C; Taylor, Philip R; Weinstein, Stephanie J; Albanes, Demetrius; Freedman, Neal D; Gapstur, Susan M; Bradwin, Gary; Guillemette, Chantal; Campbell, Peter T; Cook, Michael B
2018-05-17
Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case-control study drawn from participants in three prospective cohort studies. Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.
Boosalis, M G; Snowdon, D A; Tully, C L; Gross, M D
1996-01-01
This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.
2013-01-01
BACKGROUND Although pregnancies associated with hyperinsulinemia and altered placental angiogenic and inflammatory factors are at increased risk for developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental factors and blood pressure regulation during pregnancy are unclear. We hypothesized that chronic hyperinsulinemia results in increased placental soluble fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor α (TNF- α) levels and hypertension in pregnant rats. METHODS On gestational day (GD) 14, Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin. Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of 1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and heart rate (HR) were assessed in conscious rats by indwelling carotid catheters, followed by collections of blood, placentas, and fetuses. In addition to pl acental sFlt-1 and TNF-α levels, circulating insulin, glucose, leptin, cholesterol, triglyceride, and free fatty acid concentrations were measured. RESULTS MAP was higher in pregnant + insulin vs. normal pregnant rats; however, HR was similar between groups. Although litter size and placental weight were comparable, fetuses from pregnant + insulin rats were heavier. Importantly, circulating insulin concentration was elevated in the pregnant + insulin group, with no change in glucose level. Moreover, circulating leptin, cholesterol, triglyceride, and free fatty acid concentrations were increased in the pregnant + insulin group. There were no differences in placental sFlt-1 and TNF-α concentrations between groups. CONCLUSIONS In summary, sustained euglycemic hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise blood pressure in pregnancy independent of recognized placental factors associated with preeclampsia. PMID:23955606
Circulating DNA: a potential marker of sickle cell crisis.
Vasavda, Nisha; Ulug, Pinar; Kondaveeti, Sheila; Ramasamy, Karthik; Sugai, Taku; Cheung, Gordon; Rees, David C; Awogbade, Moji; Bannister, Sybil; Cunningham, Juliette; Menzel, Stephan; Thein, Swee Lay
2007-10-01
Free circulating DNA is present in the plasma of healthy subjects, and is elevated in conditions characterized by increased cell death, such as cancer and physical trauma. Analysis of circulating DNA in plasma could provide a useful biomarker in sickle cell disease (SCD) in view of the increased cell turnover through chronic ongoing haemolysis, recurrent vaso-occlusion and inflammation. Plasma DNA was determined by real-time quantitative polymerase chain reaction (PCR) amplification of the beta-globin gene (HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/beta(0) thalassaemia] and 53 ethnically matched controls. Blood samples were obtained from all patients in steady state; 21 of the 154 patients were also sampled during admission to hospital for acute pain. Median concentration of circulating plasma DNA in acute pain was more than 10-fold that in steady state and in controls - 10070 vs. 841 and 10070 vs. 933 genome equivalents/ml respectively (P < 0.0001, in both cases). During steady state, patients had plasma DNA levels similar to controls. Plasma DNA levels in SCD correlated with C-reactive protein levels (P < 0.005) and total white cell counts (P < 0.05) in steady state. The study shows that plasma DNA concentration may have potential as a biomarker in sickle cell patients.
Vitamin D, secondary hyperparathyroidism, and preeclampsia123
Scholl, Theresa O; Chen, Xinhua; Stein, T Peter
2013-01-01
Background: Secondary hyperparathyroidism, which is defined by a high concentration of intact parathyroid hormone when circulating 25-hydroxyvitamin D [25(OH)D] is low, is a functional indicator of vitamin D insufficiency and a sign of impaired calcium metabolism. Two large randomized controlled trials examined effects of calcium supplementation on preeclampsia but did not consider the vitamin D status of mothers. Objective: We examined the association of secondary hyperparathyroidism with risk of preeclampsia. Design: Circulating maternal 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone were measured at entry to care (mean ± SD: 13.7 ± 5.7 wk) using prospective data from a cohort of 1141 low-income and minority gravidae. Results: Secondary hyperparathyroidism occurred in 6.3% of the cohort and 18.4% of women whose 25(OH)D concentrations were <20 ng/mL. Risk of preeclampsia was increased 2.86-fold (95% CI: 1.28-, 6.41-fold) early in gestation in these women. Gravidae with 25(OH)D concentrations <20 ng/mL who did not also have high parathyroid hormone and women with high parathyroid hormone whose 25(OH)D concentrations were >20 ng/mL were not at increased risk. Intact parathyroid hormone was related to higher systolic and diastolic blood pressures and arterial pressure at week 20 before clinical recognition of preeclampsia. Energy-adjusted intakes of total calcium and lactose and circulating 25(OH)D were correlated inversely with systolic blood pressure or arterial pressure and with parathyroid hormone. Conclusion: Some women who are vitamin D insufficient develop secondary hyperparathyroidism, which is associated with increased risk of preeclampsia. PMID:23885046
Machado, Paola; Caris, Aline; Santos, Samile; Silva, Edgar; Oyama, Lila; Tufik, Sergio; Santos, Ronaldo
2017-01-01
Hypoxia and high altitudes affect various organs, which impairs important physiological functions, such as a disruption of the intestinal barrier mediated by increased translocation of bacteria and increased circulating endotoxin levels. Physical exercise can alter endotoxin concentration in normoxia. The aim of this study is to evaluate the effects of moderate exercise on endotoxin concentration in normobaric hypoxia. Nine healthy male volunteers exercised on a treadmill for 60 minutes at an intensity of 50% VO2peak in normoxic or hypoxic conditions (4200 m). Blood was collected at rest, immediately after exercise and 1 hour after exercise to evaluate serum endotoxin levels. Under hypoxic exercise conditions, SaO2% saturation was lower after exercise compared with resting levels (P < 0.05) and returned to the resting level during recovery in normoxia (P < 0.05). Endotoxin concentration increased after exercise in hypoxia (P < 0.05); it remained high 1 hour after exercise in hypoxia compared with normoxia (P < 0.05) and was higher after exercise and recovery compared with resting levels (P < 0.05). HR was higher during exercise in relation basal in both conditions (P < 0.05) and RPR increase after 60 minutes in comparison to 20 minutes in hypoxia (P < 0.05). Moderate exercise performed in hypoxia equivalent to 4200 m increased endotoxin plasma concentration after exercise. One hour of rest in normoxic conditions was insufficient for the recovery of circulating endotoxins.
Kovilakam, Mahesh; Mahajan, Salil
2016-06-28
While black carbon aerosols (BC) are believed to modulate the Indian monsoons, the radiative forcing estimate of BC suffers from large uncertainties globally. In this paper, we analyze a suite of idealized experiments forced with a range of BC concentrations that span a large swath of the latest estimates of its global radiative forcing. Within those bounds of uncertainty, summer precipitation over the Indian region increases nearly linearly with the increase in BC burden. The linearity holds even as the BC concentration is increased to levels resembling those hypothesized in nuclear winter scenarios, despite large surface cooling over India andmore » adjoining regions. The enhanced monsoonal circulation is associated with a linear increase in the large-scale meridional tropospheric temperature gradient. The precipitable water over the region also increases linearly with an increase in BC burden, due to increased moisture transport from the Arabian sea to the land areas. The wide range of Indian monsoon response elicited in these experiments emphasizes the need to reduce the uncertainty in BC estimates to accurately quantify their role in modulating the Indian monsoons. Finally, the increase in monsoonal circulation in response to large BC concentrations contrasts earlier findings that the Indian summer monsoon may break down following a nuclear war.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kovilakam, Mahesh; Mahajan, Salil
While black carbon aerosols (BC) are believed to modulate the Indian monsoons, the radiative forcing estimate of BC suffers from large uncertainties globally. In this paper, we analyze a suite of idealized experiments forced with a range of BC concentrations that span a large swath of the latest estimates of its global radiative forcing. Within those bounds of uncertainty, summer precipitation over the Indian region increases nearly linearly with the increase in BC burden. The linearity holds even as the BC concentration is increased to levels resembling those hypothesized in nuclear winter scenarios, despite large surface cooling over India andmore » adjoining regions. The enhanced monsoonal circulation is associated with a linear increase in the large-scale meridional tropospheric temperature gradient. The precipitable water over the region also increases linearly with an increase in BC burden, due to increased moisture transport from the Arabian sea to the land areas. The wide range of Indian monsoon response elicited in these experiments emphasizes the need to reduce the uncertainty in BC estimates to accurately quantify their role in modulating the Indian monsoons. Finally, the increase in monsoonal circulation in response to large BC concentrations contrasts earlier findings that the Indian summer monsoon may break down following a nuclear war.« less
USDA-ARS?s Scientific Manuscript database
Ghrelin is a gut peptide that when acylated is thought to stimulate appetite. Circulating ghrelin concentrations could potentially be used as a predictor of DMI in cattle. The objective of this experiment was to determine the association of circulating ghrelin concentrations with DMI and other produ...
Mechanisms and detectability of oxygen depletion in the North Atlantic
NASA Astrophysics Data System (ADS)
Tjiputra, J. F.; Goris, N.; Lauvset, S. K.; Schwinger, J.
2016-12-01
Dissolved oxygen is a key tracer in models used to represent the tight interaction between ocean biogeochemical cycle and circulation. Future ocean warming and stratification are projected, leading to a reduced oxygen concentration. Reduction in export production, in contrast, is projected to increase subsurface concentration by lowering the oxygen consumption during organic matter remineralization. In this exercise, we use a suite of CMIP5 models to study the oxygen evolution under the RCP8.5 scenario focusing on the North Atlantic, a region of rapid and steady circulation change. Most models agree with a large reduction in the deep North Atlantic (north of 40N), whereas an increase is projected in the upper subtropical ocean region. We attribute the former to weakening of the net primary production due to stronger stratification and the latter to less air-sea oxygen flux owing to less ventilation. The models also show that interior oxygen could provide earlier indicator of climate change than surface tracers. Sustained observation of oxygen is therefore crucial to reaffirm the ongoing circulation change due to global warming.
Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates.
Lundsgaard, Anne-Marie; Fritzen, Andreas M; Sjøberg, Kim A; Myrmel, Lene S; Madsen, Lise; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente
2017-01-01
Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml -1 , p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser 660 phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n-7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.
Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J
2000-01-01
Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. PMID:11133399
USDA-ARS?s Scientific Manuscript database
We previously reported that temperamental cattle have greater non-esterified fatty acid (NEFA) concentrations and an altered innate immune response compared to calm cattle. Therefore, this trial was designed to determine if increasing energy availability via a lipid infusion or bolus dextrose inject...
Marina, Michela; Ceda, Gian Paolo; Aloe, Rosalia; Gnocchi, Cecilia; Ceresini, Graziano
2017-01-16
Liquid levothyroxine (LT4) given at breakfast normalizes TSH in hypothyroid patients. However, a few studies are available on circulating free thyroxine (FT4) concentrations after liquid vs solid LT4 preparations. During an "ad interim" analysis on serum FT4 after 200 mcg liquid LT4 consumption while fasting in thyroidectomized thyroid cancer patients, we found that seven subjects fortuitously took liquid LT4 at breakfast. As established in the original protocol, serum FT4 was measured both at baseline as well as at 3 and 4 hours after solid or liquid LT4 consumption. We compared serum profile of FT4 in these subjects with those obtained in other subjects participating in the same study who took liquid LT4 (n. 7 subjects) or solid LT4 (n. 7 subjects) while fasting. The percentage increase of circulating FT4 was calculated at the above reported peak-times over the baseline values. Circulating FT4 increased of about 40% in each group of subjects at both the 3rd and the 4th hour with no difference between these two time points in either group. The maximum FT4 % increase, irrespective of the time point, was 44.62 ± 3.05 (Mean ± SE), 44.84 ± 5.43, and 43.83 ± 1.30 after fasting solid, fasting liquid, and breakfast liquid LT4 consumption, respectively, with no differences among the three groups. Circulating FT4 obtained after 3 and 4 hours from the ingestion of 200 mcg liquid LT4 is not influenced by meal and is comparable with that observed after solid LT4 preparations ingested while fasting.
Ingelsson, Erik; Larson, Martin G; Yin, Xiaoyan; Wang, Thomas J; Meigs, James B; Lipinska, Izabella; Benjamin, Emelia J; Keaney, John F; Vasan, Ramachandran S
2008-08-01
The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured. Ghrelin and leptin concentrations were significantly higher in women (P < 0.0001). In multivariable models, ghrelin was inversely associated with age and systolic blood pressure, and leptin was positively related to body mass index and WC. sOB-R was positively associated with age, total cholesterol, and fasting glucose and inversely with WC and high-density lipoprotein cholesterol. Ghrelin and sOB-R concentrations were significantly lower with number of MetS components (P for trend = 0.022 and < 0.0001, respectively), whereas leptin concentrations were higher (P for trend = 0.0001). Relating all adipokines to MetS conjointly, higher ghrelin and leptin concentrations were associated with decreased and increased odds of MetS (odds ratio 0.55, P < 0.0001; odds ratio 4.44, P = 0.0002, per 1 sd increase of respective log adipokine). In our community-based sample, we observed a sexual dimorphism in circulating ghrelin and leptin concentrations. Ghrelin, leptin, and sOB-R were associated with number of MetS components cross-sectionally, consistent with the hypothesis that these adipokines may have a central role in cardiometabolic risk.
USDA-ARS?s Scientific Manuscript database
Previously, Melengestrol Acetate (MGA) fed for 14 d (0.5mg/cow/d; < 1 ng/ml P4) resulted in persistent follicles with increased size, decreased number of GC/follicular fluid (FF) volume, and less fertile oocytes. An experiment was conducted to determine effects of circulating P4 on amount of mRNA fo...
NASA Technical Reports Server (NTRS)
Schneider, Hans R.; Ko, Malcolm K. W.; Shia, Run-Lie; Sze, Nien-Dak
1993-01-01
The impact of increased levels of carbon dioxide (CO2), chlorofluorocarbons (CFCs), and other trace gases on stratospheric ozone is investigated with an interactive, two-dimensional model of gas phase chemistry, dynamics, and radiation. The scenarios considered are (1) a doubling of the CO2 concentration, (2) increases of CFCs, (3) CFC increases combined with increases of nitrous oxide (N2O) and methane CH4, and (4) the simultaneous increase of CO2, CFCs, N2O, and CH4. The radiative feedback and the effect of temperature and circulation changes are studied for each scenario. For the double CO2 calculations the tropospheric warming was specified. The CO2 doubling leads to a 3.1% increase in the global ozone content. Doubling of the CO2 concentrations would lead to a maximum cooling of about 12 C at 45 km if the ozone concentration were held fixed. The cooling of the stratosphere leads to an ozone increase with an associated increase in solar heating, reducing the maximum temperature drop by about 3 C. The CFC increase from continuous emissions at 1985 rate causes a 4.5% loss of ozone. For the combined perturbations a net loss of 1.3% is calculated. The structure of the perturbations shows a north-south asymmetry. Ozone losses (when expressed in terms of percent changes) are generally larger in the high latitudes of the southern hemisphere as a result of the eddy mixing being smaller than in the northern hemisphere. Increase of chlorine leads to ozone losses above 30 km altitude where the radiative feedback results in a cooler temperature and an ozone recovery of about one quarter of the losses predicted with a noninteractive model. In all the cases, changes in circulation are small. In the chlorine case, circulation changes reduce the calculated column depletion by about one tenth compared to offline calculations.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kelly, Patrick; Kravitz, Ben; Lu, Jian
Here we demonstrate that changes of the North Atlantic subtropical high (NASH) and its regional rainfall pattern during mid-Holocene precessional changes and idealized 4xCO2 increase can both be understood as a remote response to changes in the African and Indian monsoon systems. Despite different sources and patterns of radiative forcing (increase in CO2 concentration vs. changes in orbital parameters), we find that the pattern of energy, circulation, and rainfall responses in the Northern Hemisphere summer subtropics are very similar in the two forcing scenarios because both are dominated by the same land-sea heating contrast in response to the forcing. Anmore » increase in energy input over land drives a westward displacement of the coupled NASH-monsoon circulation, consistent with increased precipitation in the Afro-Asia region and decreased precipitation in the America-Atlantic region. Ultimately, this study underscores the importance of land heating in dictating remote drying through zonal shifts of the subtropical circulation.« less
Roth, Carina; Pantel, Klaus; Müller, Volkmar; Rack, Brigitte; Kasimir-Bauer, Sabine; Janni, Wolfgang; Schwarzenbach, Heidi
2011-01-06
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. 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. 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). 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.
NASA Astrophysics Data System (ADS)
Bellomo, K.; Polvani, L. M.
2017-12-01
It is widely believed that the Walker Circulation will weaken in response to increasing greenhouse gases (GHG) by the end of the 21st century. But over the 20th century, the existence of a statistical significant weakening trends in the observations remains unclear. We here present new modelling evidence showing that Ozone Depleting Substances (ODS) may have significantly contributed to the weakening of the Walker Circulation over the years 1955-2005. While the primary impact of increasing ODS has been the formation of the ozone hole, it is perhaps not as widely appreciated that ODS are also powerful greenhouse gases. Using an ensemble of integrations with the the Whole Atmosphere Chemistry Climate Model, we show that the surface warming caused by increasing ODS over the second half of the 20th century causes a statistically significant weakening of the Walker Circulation in the model. In fact, we find that the increase of the other well-mixed GHG alone leads to a strengthening, not a weakening of the Walker Circulation, over that period in our model. When ODS concentrations are held fixed at 1950's levels, the effect of the other GHG is not sufficient, and a warming delay in the eastern tropical Pacific SST leads to an increase in the east-west SST gradient which is accompanied by a strengthening of the Walker Circulation. But, when the forcing from ODS is added in, the additional radiative forcing causes the eastern Pacific to warm faster, and the trend in the Walker Circulation reverses sign and becomes negative over the second half of the 20th century.
Butler, Andrew A.; St-Onge, Marie-Pierre; Siebert, Emily A.; Medici, Valentina; Stanhope, Kimber L.; Havel, Peter J.
2015-01-01
Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060
Circulating microparticle levels are reduced in patients with ARDS.
Shaver, Ciara M; Woods, Justin; Clune, Jennifer K; Grove, Brandon S; Wickersham, Nancy E; McNeil, J Brennan; Shemancik, Gregory; Ware, Lorraine B; Bastarache, Julie A
2017-05-25
It is unclear how to identify which patients at risk for acute respiratory distress syndrome (ARDS) will develop this condition during critical illness. Elevated microparticle (MP) concentrations in the airspace during ARDS are associated with activation of coagulation and in vitro studies have demonstrated that MPs contribute to acute lung injury, but the significance of MPs in the circulation during ARDS has not been well studied. The goal of the present study was to test the hypothesis that elevated levels of circulating MPs could prospectively identify critically ill patients who will develop ARDS and that elevated circulating MPs are associated with poor clinical outcomes. A total of 280 patients with platelet-poor plasma samples from the prospective Validating Acute Lung Injury biomarkers for Diagnosis (VALID) cohort study were selected for this analysis. Demographics and clinical data were obtained by chart review. MP concentrations in plasma were measured at study enrollment on intensive care unit (ICU) day 2 and on ICU day 4 by MP capture assay. Activation of coagulation was measured by plasma recalcification (clot) times. ARDS developed in 90 of 280 patients (32%) in the study. Elevated plasma MP concentrations were associated with reduced risk of developing ARDS (odds ratio (OR) 0.70 per 10 μM increase in MP concentration, 95% CI 0.50-0.98, p = 0.042), but had no significant effect on hospital mortality. MP concentration was greatest in patients with sepsis, pneumonia, or aspiration as compared with those with trauma or receiving multiple blood transfusions. MP levels did not significantly change over time. The inverse association of MP levels with ARDS development was most striking in patients with sepsis. After controlling for age, presence of sepsis, and severity of illness, higher MP concentrations were independently associated with a reduced risk of developing ARDS (OR 0.69, 95% CI 0.49-0.98, p = 0.038). MP concentration was associated with reduced plasma recalcification time. Elevated levels of circulating MPs are independently associated with a reduced risk of ARDS in critically ill patients. Whether this is due to MP effects on systemic coagulation warrants further investigation.
Gustavson, Lisa; Ciesielski, Tomasz M; Bytingsvik, Jenny; Styrishave, Bjarne; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M
2015-04-01
As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause-effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears. Copyright © 2015 Elsevier Inc. All rights reserved.
Fernández-Real, José Manuel; Moreno, José María; Ricart, Wifredo
2008-01-01
OBJECTIVES—The mechanisms behind the association between retinol-binding protein-4 (RBP4) and insulin resistance are not well understood. An interaction between iron and vitamin A status, of which RBP4 is a surrogate, has long been recognized. We hypothesized that iron-associated insulin resistance could be behind the impaired insulin action caused by RBP4. RESEARCH DESIGN AND METHODS—Serum ferritin and RBP4 concentration and insulin resistance were evaluated in a sample of middle-aged men (n = 132) and in a replication independent study. Serum RBP4 was also studied before and after iron depletion in patients with type 2 diabetes. Finally, the effect of iron on RBP4 release was evaluated in vitro in adipose tissue. RESULTS—A positive correlation between circulating RBP4 and log serum ferritin (r = 0.35 and r = 0.61, respectively; P < 0.0001) was observed in both independent studies. Serum RBP4 concentration was higher in men than women in parallel to increased ferritin levels. On multiple regression analyses to predict serum RBP4, log serum ferritin contributed significantly to RBP4 variance after controlling for BMI, age, and homeostasis model assessment value. Serum RBP4 concentration decreased after iron depletion in type 2 diabetic patients (percent mean difference −13.7 [95% CI −25.4 to −2.04]; P = 0.024). The iron donor lactoferrin led to increased dose-dependent adipose tissue release of RBP4 (2.4-fold, P = 0.005) and increased RBP4 expression, while apotransferrin and deferoxamine led to decreased RBP4 release. CONCLUSIONS—The relationship between circulating RBP4 and iron stores, both cross-sectional and after iron depletion, and in vitro findings suggest that iron could play a role in the RBP4–insulin resistance relationship. PMID:18426863
Zhang, Lei; Chen, Chao; Zhou, Nan; Fu, Yuming; Cheng, Xingbo
2017-11-03
Asprosin has been identified as a novel hormone enriched in white adipose tissue and is pathologically increased in insulin-resistant mice and humans. However, information regarding the role of asprosin in type 2 diabetes mellitus (T2DM) remains unavailable. Via conducting a hospital-based study, we purposed to ascertain the potential relationship between circulating asprosin concentrations and T2DM. The study recruited 84 adults with T2DM and 86 controls with normal glucose tolerance. They matched in age, body mass index (BMI), and sex. Serum asprosin concentrations were measured via ELISA method. Compared to the controls, serum asprosin concentrations were significantly increased in the T2DM adults (P<0.001). As asprosin concentrations increased across its tertiles, the percentage of T2DM increased (39.28, 37.50, and 70.68%; P value for trend <0.001). Multivariate logistic regression models demonstrated that compared with the 1st tertile of asprosin, the odds ratio of T2DM was 3.278(95% CI 1.053-10.200, P=0.040) for the 3rd tertile after adjustment for potential confounders. Area under ROC curve of asprosin (sex and age adjusted) for predicting the presence of T2DM was 0.707[95% CI 0.628-0.786]. Finally, multiple stepwise regression analysis indicated that fasting glucose and triglyceride were independently associated with serum asprosin in T2DM. Asprosin concentrations are increased in adults with T2DM. The results suggest that asprosin might serve as a risk factor associated with the pathogenesis of T2DM, but not an ideal biomarker for predicting T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Staten, Paul; Reichler, Thomas; Lu, Jian
Tropospheric circulation shifts have strong potential to impact surface climate. But the magnitude of these shifts in a changing climate, and the attending regional hydrological changes, are difficult to project. Part of this difficulty arises from our lack of understanding of the physical mechanisms behind the circulation shifts themselves. In order to better delineate circulation shifts and their respective causes, we decompose the circulation response into (1) the "direct" response to radiative forcings themselves, and (2) the "indirect" response to changing sea surface temperatures. Using ensembles of 90-day climate model simulations with immediate switch-on forcings, including perturbed greenhouse gas concentrations,more » stratospheric ozone concentrations, and sea surface temperatures, we document the direct and indirect transient responses of the zonal mean general circulation, and investigate the roles of previously proposed mechanisms in shifting the midlatitude jet. We find that both the direct and indirect wind responses often begin in the lower stratosphere. Changes in midlatitude eddies are ubiquitous and synchronous with the midlatitude zonal wind response. Shifts in the critical latitude of wave absorption on either flank of the jet are not indicted as primary factors for the poleward shifting jet, although we see some evidence for increasing equatorward wave reflection over the southern hemisphere in response to sea surface warming. Mechanisms for the northern hemisphere jet shift are less clear.« less
Hyysalo, Jenni; Gopalacharyulu, Peddinti; Bian, Hua; Hyötyläinen, Tuulia; Leivonen, Marja; Jaser, Nabil; Juuti, Anne; Honka, Miikka-Juhani; Nuutila, Pirjo; Olkkonen, Vesa M; Oresic, Matej; Yki-Järvinen, Hannele
2014-01-01
We examined whether relative concentrations of circulating triacylglycerols (TAGs) between carriers compared with noncarriers of PNPLA3(I148M) gene variant display deficiency of TAGs, which accumulate in the liver because of defective lipase activity. We also analyzed the effects of obesity-associated nonalcoholic fatty liver disease (NAFLD) independent of genotype, and of NAFLD due to either PNPLA3(I148M) gene variant or obesity on circulating TAGs. A total of 372 subjects were divided into groups based on PNPLA3 genotype or obesity. Absolute and relative deficiency of distinct circulating TAGs was observed in the PNPLA3(148MM/148MI) compared with the PNPLA3(148II) group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulin-resistant. Liver fat was similarly increased in obese and PNPLA3(148MM/148MI) groups. Relative concentrations of TAGs in the obese subjects versus nonobese displayed multiple changes. These closely resembled those between obese subjects with NAFLD but without PNPLA3(I148M) versus those with the I148M variant and NAFLD. The etiology of NAFLD influences circulating TAG profiles. 'PNPLA3 NAFLD' is associated with a relative deficiency of TAGs, supporting the idea that the I148M variant impedes intrahepatocellular lipolysis rather than stimulates TAG synthesis. 'Obese NAFLD' is associated with multiple changes in TAGs, which can be attributed to obesity/insulin resistance rather than increased liver fat content per se.
Rijks, Jesse M; Plat, Jogchum; Dorenbos, Elke; Penders, Bas; Gerver, Willem-Jan M; Vreugdenhil, Anita C E
2017-06-01
Overweight and obese children have an increased risk to develop cardiovascular diseases (CVDs) in which thyroid-stimulating hormone (TSH) has been suggested as an intermediary factor. However, results of cross-sectional studies are inconclusive, and intervention studies investigating changes in TSH concentrations in association with changes in cardiovascular risk parameters in overweight and obese children are scarce. To gain insight in associations of circulating TSH concentrations and cardiovascular risk parameters in overweight and obese children. Nonrandomized lifestyle intervention. Centre for Overweight Adolescent and Children's Healthcare. Three hundred thirty euthyroid overweight and obese children. Long-term lifestyle intervention. TSH concentrations, pituitary TSH release in response to thyrotropin-releasing hormone (TRH), and cardiovascular risk parameters. At baseline, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), and monocyte chemotactic protein 1 concentrations were significantly associated with serum TSH concentrations. TSH release by the pituitary in response to exogenous TRH was not associated with cardiovascular risk parameters. During lifestyle intervention, several cardiovascular risk parameters significantly improved. In children whose body mass index z score improved, changes in TSH concentrations were significantly associated with changes in TC, LDL-C, and TAG concentrations. In euthyroid overweight and obese children, circulating TSH concentrations are positively associated with markers representing increased CVD risk. Changes in TSH concentrations are also associated with changes in lipid concentrations in children with successful weight loss, which is consistent with TSH being an intermediary factor in modulating lipid and lipoprotein metabolism. Copyright © 2017 Endocrine Society
Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes
Kanikarla-Marie, Preeti; Jain, Sushil K.
2016-01-01
Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body’s energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate (AA), 3-β-hydroxybutyrate (BHB), and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increasing the risk of morbidity and mortality in patients. PMID:27036365
Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.
Kanikarla-Marie, Preeti; Jain, Sushil K
2016-06-01
Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients. Copyright © 2016 Elsevier Inc. All rights reserved.
Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Fernández-Real, José Manuel; Salvador, Javier; Frühbeck, Gema
2011-01-01
Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage–related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity-associated comorbidities. PMID:21738950
Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.
Cook, Michael B; Stanczyk, Frank Z; Wood, Shannon N; Pfeiffer, Ruth M; Hafi, Muhannad; Veneroso, Carmela C; Lynch, Barlow; Falk, Roni T; Zhou, Cindy Ke; Niwa, Shelley; Emanuel, Eric; Gao, Yu-Tang; Hemstreet, George P; Zolfghari, Ladan; Carroll, Peter R; Manyak, Michael J; Sesterhann, Isabell A; Levine, Paul H; Hsing, Ann W
2017-11-01
Background: Sex hormones have been implicated in prostate carcinogenesis, yet epidemiologic studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically verified benign prostate tissue from prostate cancer cases. Methods: Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race, and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race, and age were assessed as potential effect modifiers. Results: Circulating sex steroid hormone concentrations had low-to-moderate correlations with, and explained small proportions of variations in, intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r 2 = 0.21), followed by serum testosterone and tissue dihydrotestosterone ( r 2 = 0.10), and then serum estrone and tissue estrone ( r 2 = 0.09). There was no effect modification by Gleason score, race, or age. Conclusions: Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu. Impact: The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(11); 1660-6. ©2017 AACR . ©2017 American Association for Cancer Research.
Adrian, T E; Sagor, G R; Savage, A P; Bacarese-Hamilton, A J; Hall, G M; Bloom, S R
1986-10-01
Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kelly, Patrick; Kravitz, Ben; Lu, Jian
In this study, we demonstrate that changes of the North Atlantic subtropical high and its regional rainfall pattern during mid-Holocene precessional changes and idealized 4xCO 2 increase can both be understood as a remote response to increased land heating near North Africa. Despite different sources and patterns of radiative forcing (increase in CO 2 concentration versus changes in orbital parameters), we find that the pattern of energy, circulation, and rainfall responses in the Northern Hemisphere summer subtropics are remarkably similar in the two forcing scenarios because both are dominated by the same land-sea heating contrast in response to the forcing.more » An increase in energy input over arid land drives a westward displacement of the coupled North Atlantic subtropical high-monsoon circulation, consistent with increased precipitation in the Afro-Asia region and decreased precipitation in the America-Atlantic region. This study underscores the importance of land heating in dictating remote drying through zonal shifts of the subtropical circulation.« less
Kelly, Patrick; Kravitz, Ben; Lu, Jian; ...
2018-04-16
In this study, we demonstrate that changes of the North Atlantic subtropical high and its regional rainfall pattern during mid-Holocene precessional changes and idealized 4xCO 2 increase can both be understood as a remote response to increased land heating near North Africa. Despite different sources and patterns of radiative forcing (increase in CO 2 concentration versus changes in orbital parameters), we find that the pattern of energy, circulation, and rainfall responses in the Northern Hemisphere summer subtropics are remarkably similar in the two forcing scenarios because both are dominated by the same land-sea heating contrast in response to the forcing.more » An increase in energy input over arid land drives a westward displacement of the coupled North Atlantic subtropical high-monsoon circulation, consistent with increased precipitation in the Afro-Asia region and decreased precipitation in the America-Atlantic region. This study underscores the importance of land heating in dictating remote drying through zonal shifts of the subtropical circulation.« less
NASA Astrophysics Data System (ADS)
Michelet-Habchi, C.; Barberet, Ph.; Dutta, R. K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph.
2003-09-01
Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K + and Ca 2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K + channels, K Ca) and of high concentration of K + (which blocks the voltage-sensitive K + channels, K df). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K + medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K + medium, a significant increase in Cl and K concentration. These results indicated the importance of K df, K Ca and K ATP channels in the regulation of K + intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Egloff, Caroline; Crump, Doug, E-mail: doug.crump@ec.gc.ca; Porter, Emily
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 highestmore » 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. • TEP elicited more adverse molecular and phenotypic effects than TBOEP.« less
Treatment and therapeutic monitoring of canine hypothyroidism.
Dixon, R M; Reid, S W J; Mooney, C T
2002-08-01
Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.
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.
Takahashi, Masato; Sawada, Yoshisuke; Aoyagi, Hideki
2017-08-23
Monitoring the environmental factors during shake-flask culture of microorganisms can help to optimise the initial steps of bioprocess development. Herein, we developed a circulation direct monitoring and sampling system (CDMSS) that can monitor the behaviour of CO 2 and O 2 in the gas-liquid phases and obtain a sample without interrupting the shaking of the culture in Erlenmeyer flasks capped with breathable culture plugs. Shake-flask culturing of Escherichia coli using this set-up indicated that a high concentration of CO 2 accumulated not only in the headspace (maximum ~100 mg/L) but also in the culture broth (maximum ~85 mg/L) during the logarithmic phase (4.5-9.0 h). By packing a CO 2 absorbent in the gas circulation unit of CDMSS, a specialised shake-flask culture was developed to remove CO 2 from the headspace. It was posited that removing CO 2 from the headspace would suppress increases in the dissolved CO 2 concentration in the culture broth (maximum ~15 mg/L). Furthermore, the logarithmic growth phase (4.5-12.0 h) was extended, the U.O.D. 580 and pH value increased, and acetic acid concentration was reduced, compared with the control. To our knowledge, this is the first report of a method aimed at improving the growth of E. coli cells without changing the composition of the medium, temperature, and shaking conditions.
Cherel, Yves; Durant, Joël M; Lacroix, André
2004-05-01
Plasma concentrations of thyroid hormones (TH) were investigated during the extended posthatching developmental period (approximately 11 months) of a semi-altricial bird species, the king penguin (Aptenodytes patagonicus). The first period of growth in summer was marked by a progressive rise in plasma T4 concentration that paralleled rapid increases in body mass and in structural and down growth. By contrast, plasma T3 concentration had already reached adult levels in newly hatched chicks and did not change thereafter. Circulating TH of king penguin chicks thus follow an original pattern when comparing to altricial and precocial species. During the austral winter, the long period of undernutrition of king penguin chicks was characterized by a decrease in circulating TH that can be related to a seasonal stop in growth and energy saving mechanisms. Plasma TH concentrations increased again during the second growth phase in spring, and they reached their highest levels at the end of the fledging period, slightly before juveniles initiated their first foraging trip at sea. As expected, plasma T4 levels were elevated when chicks moulted, developing a true-adult type waterproof plumage. The data also suggest that T4 plays a major role in skeletal development and pectoral muscle maturation in anticipation of marine life. Plasma T3 was at its highest during the period when juveniles improved resistance to cold waters by going back and forth to the sea, suggesting a role for circulating T3 in cold acclimatization occurring at that time.
Escobar-Morreale, Héctor F; Martínez-García, M Ángeles; Montes-Nieto, Rafael; Fernández-Durán, Elena; Temprano-Carazo, Sara; Luque-Ramírez, Manuel
2017-04-01
Low-grade chronic inflammation is involved in the pathophysiology of obesity. However, little is known about the influence of sex and sex hormones on surrogate inflammatory markers and mediators, particularly after glucose ingestion. Observational study. We measured the circulating concentrations of interleukin-6, interleukin-18, macrophage migration inhibitory factor, matrix metallopeptidase-9, monocyte chemotactic protein-1 and pentraxin-3, in the fasting state and during a 75 g oral glucose tolerance test, in 24 women and 25 men. Eleven men and 11 women were lean whereas 14 men and 13 women had weight excess. Anti-inflammatory cytokines (interleukin-6 and interleukin-18) were increased in the fasting state and/or decreased in some women during the oral glucose tolerance test, as opposed to inflammatory mediators such as macrophage migration inhibitory factor and matrix metallopeptidase-9 that increased during the oral glucose tolerance test especially in subjects with weight excess. Body mass index and waist circumference were the main determinants of these changes. Fasting pentraxin-3 levels were especially increased in lean women in parallel to a decrease in free testosterone levels, and decreased during the oral glucose tolerance test as opposed to the increase in insulin concentrations. The circulating concentrations of markers of low-grade chronic inflammation in young healthy adults are not only influenced by obesity but also by abdominal adiposity, fasting and glucose ingestion and, in some cases, by sex and sex hormones. These influences should be considered when these markers are used as surrogate markers of the inflammatory milieu associated with obesity. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Giuffrida, María J; Valero, Nereida; Mosquera, Jesús; Alvarez de Mon, Melchor; Chacín, Betulio; Espina, Luz Marina; Gotera, Jennifer; Bermudez, John; Mavarez, Alibeth
2014-01-01
Background Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. Objectives The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. Patients/Methods Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. Results Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. Conclusions Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections. PMID:23962134
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 endocannabinoid 2-arachidonoylglycerol. SLEEP 2016;39(3):653–664. PMID:26612385
NASA Astrophysics Data System (ADS)
Yamamoto, M.; Nam, S. I.; Polyak, L.; Kobayashi, D.; Suzuki, K.; Irino, T.; Shimada, K.
2017-12-01
The Bering Strait inflow (BSI) is an important element of the Arctic Ocean circulation system. We report records of the chlorite/illite ratios in three sediment cores from the northern Chukchi Sea providing insights into the long-term dynamics of the BSI during the Holocene. The BSI approximation by the chlorite/illite record, despite a considerable geographic variability, consistently shows intensified flow from the Bering Sea to the Arctic during the middle Holocene, which is attributed primarily to the effect of higher atmospheric pressure over the Aleutian Basin. The intensified BSI was associated with decrease in sea-ice concentrations and increase in marine production, as indicated by biomarker concentrations, suggesting a major influence of the BSI on sea-ice and biological conditions in the Chukchi Sea. Multi-century to millennial fluctuations, presumably controlled by solar activity, were also identified. This middle Holocene strengthening of the BSI was coeval with intense subpolar gyre circulation in the North Atlantic. We propose that the BSI is linked with the North Atlantic circulation via an atmospheric teleconnection between the Aleutian and Icelandic Lows.
Optimization of Progressive Freeze Concentration on Apple Juice via Response Surface Methodology
NASA Astrophysics Data System (ADS)
Samsuri, S.; Amran, N. A.; Jusoh, M.
2018-05-01
In this work, a progressive freeze concentration (PFC) system was developed to concentrate apple juice and was optimized by response surface methodology (RSM). The effects of various operating conditions such as coolant temperature, circulation flowrate, circulation time and shaking speed to effective partition constant (K) were investigated. Five different level of central composite design (CCD) was employed to search for optimal concentration of concentrated apple juice. A full quadratic model for K was established by using method of least squares. A coefficient of determination (R2) of this model was found to be 0.7792. The optimum conditions were found to be coolant temperature = -10.59 °C, circulation flowrate = 3030.23 mL/min, circulation time = 67.35 minutes and shaking speed = 30.96 ohm. A validation experiment was performed to evaluate the accuracy of the optimization procedure and the best K value of 0.17 was achieved under the optimized conditions.
Melanin-concentrating hormone in peripheral circulation in the human.
Naufahu, J; Alzaid, F; Fiuza Brito, M; Doslikova, B; Valencia, T; Cunliffe, A; Murray, J F
2017-03-01
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role. © 2017 Society for Endocrinology.
Samavat, Hamed; Newman, April R; Wang, Renwei; Yuan, Jian-Min; Wu, Anna H; Kurzer, Mindy S
2016-01-01
Background: Green tea has been suggested to improve cardiovascular disease risk factors, including circulating lipid variables. However, current evidence is predominantly based on small, short-term randomized controlled trials conducted in diverse populations. Objective: The aim of this study was to examine the efficacy and impact of green tea extract (GTE) supplementation high in epigallocatechin gallate (EGCG) on blood lipids in healthy postmenopausal women. Design: This was an ancillary study of a double-blind, randomized, placebo-controlled, parallel-arm trial investigating the effects of a GTE supplement containing 1315 mg catechins (843 mg EGCG) on biomarkers of breast cancer risk. Participants were randomly assigned to receive GTE (n = 538) or placebo (n = 537) and were stratified by catechol-O-methyltransferase (COMT) genotype activity (high COMT compared with low or intermediate COMT genotype activity). They consumed either 4 GTE or identical placebo capsules daily for 12 mo. A total of 936 women completed this substudy. Circulating lipid panels including total cholesterol (TC), HDL cholesterol, and triglycerides were measured at baseline and at months 6 and 12. Results: Compared with placebo, 1-y supplementation with GTE capsules resulted in a significant reduction in circulating TC (−2.1% compared with 0.7%; P = 0.0004), LDL cholesterol (−4.1% compared with 0.9%; P < 0.0001) and non-HDL cholesterol (−3.1% compared with 0.4%; P = 0.0032). There was no change in HDL-cholesterol concentration, but triglyceride concentrations increased by 3.6% in the GTE group, whereas they decreased by 2.5% in the placebo group (P = 0.046). A significant reduction in TC was observed only among women with high (i.e., ≥200 mg/dL) baseline TC concentrations (P-interaction = 0.01) who consumed GTE capsules. The effect of GTE on the increase in triglycerides was mainly observed among obese women and statin users (P-interaction = 0.06). Conclusion: Supplementation with GTE significantly reduced circulating TC and LDL-cholesterol concentrations, especially in those with elevated baseline TC concentrations. This trial was registered at clinicaltrials.gov as NCT00917735. PMID:27806972
Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes
Hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations in rodents. PB induction of hepatic xenobiotic metabolizing enzymes increases thyroid hormones catabolism and biliary elimination. This study examines the catabolism and cl...
The Effect of Climate Change on Ozone Depletion through Changes in Stratospheric Water Vapour
NASA Technical Reports Server (NTRS)
Kirk-Davidoff, Daniel B.; Hintsa, Eric J.; Anderson, James G.; Keith, David W.
1999-01-01
Several studies have predicted substantial increases in Arctic ozone depletion due to the stratospheric cooling induced by increasing atmospheric CO2 concentrations. But climate change may additionally influence Arctic ozone depletion through changes in the water vapor cycle. Here we investigate this possibility by combining predictions of tropical tropopause temperatures from a general circulation model with results from a one-dimensional radiative convective model, recent progress in understanding the stratospheric water vapor budget, modelling of heterogeneous reaction rates and the results of a general circulation model on the radiative effect of increased water vapor. Whereas most of the stratosphere will cool as greenhouse-gas concentrations increase, the tropical tropopause may become warmer, resulting in an increase of the mean saturation mixing ratio of water vapor and hence an increased transport of water vapor from the troposphere to the stratosphere. Stratospheric water vapor concentration in the polar regions determines both the critical temperature below which heterogeneous reactions on cold aerosols become important (the mechanism driving enhanced ozone depletion) and the temperature of the Arctic vortex itself. Our results indicate that ozone loss in the later winter and spring Arctic vortex depends critically on water vapor variations which are forced by sea surface temperature changes in the tropics. This potentially important effect has not been taken into account in previous scenarios of Arctic ozone loss under climate change conditions.
Effect of strenuous physical exercise on circulating cell-derived microparticles.
Chaar, Vicky; Romana, Marc; Tripette, Julien; Broquere, Cédric; Huisse, Marie-Geneviève; Hue, Olivier; Hardy-Dessources, Marie-Dominique; Connes, Philippe
2011-01-01
Strenuous exercise is associated with an inflammatory response involving the activation of several types of blood cells. In order to document the specific activation of these cell types, we studied the effect of three maximal exercise tests conducted to exhaustion on the quantitative and qualitative pattern of circulating cell-derived microparticles and inflammatory molecules in healthy subjects. This study mainly indicated that the plasma concentration of microparticles from platelets and polymorphonuclear neutrophils (PMN) was increased immediately after the strenuous exercise. In addition, the increase in plasma concentration of microparticles from PMN and platelets was still observed after 2 hours of recovery. A similar pattern was observed for the IL-6 plasma level. In contrast, no change was observed for either soluble selectins or plasma concentration of microparticles from red blood cells, monocytes and endothelial cells. In agreement, sVCAM-1 and sICAM-1 levels were not changed by the exercise. We conclude that a strenuous exercise is accompanied by platelet- and PMN-derived microparticle production that probably reflects the activation of these two cell types.
Global warming preceded by increasing carbon dioxide concentrations during the last deglaciation.
Shakun, Jeremy D; Clark, Peter U; He, Feng; Marcott, Shaun A; Mix, Alan C; Liu, Zhengyu; Otto-Bliesner, Bette; Schmittner, Andreas; Bard, Edouard
2012-04-04
The covariation of carbon dioxide (CO(2)) concentration and temperature in Antarctic ice-core records suggests a close link between CO(2) and climate during the Pleistocene ice ages. The role and relative importance of CO(2) in producing these climate changes remains unclear, however, in part because the ice-core deuterium record reflects local rather than global temperature. Here we construct a record of global surface temperature from 80 proxy records and show that temperature is correlated with and generally lags CO(2) during the last (that is, the most recent) deglaciation. Differences between the respective temperature changes of the Northern Hemisphere and Southern Hemisphere parallel variations in the strength of the Atlantic meridional overturning circulation recorded in marine sediments. These observations, together with transient global climate model simulations, support the conclusion that an antiphased hemispheric temperature response to ocean circulation changes superimposed on globally in-phase warming driven by increasing CO(2) concentrations is an explanation for much of the temperature change at the end of the most recent ice age.
Breakfast frequency and quality may affect glycemia and appetite in adults and children
USDA-ARS?s Scientific Manuscript database
Substantial evidence relates increased sex hormone concentrations with increased breast cancer risk. Varying omega-3 fatty acid (n-3) intake may lead to alterations in eicosanoid balance and subsequent changes in circulating sex hormones that reduce risk. To clarify effects of dietary fat and n-3 i...
Increased erythropoietin concentration after repeated apneas in humans.
de Bruijn, Robert; Richardson, Matt; Schagatay, Erika
2008-03-01
Hypoxia-induced increases in red blood cell production have been found in both altitude-adapted populations and acclimatized lowlanders. This process is mediated by erythropoietin (EPO) released mainly by the hypoxic kidney. We have previously observed high hemoglobin concentrations in elite breath-hold divers and our aim was to investigate whether apnea-induced hypoxia could increase EPO concentration. Ten healthy volunteers performed 15 maximal duration apneas, divided into three series of five apneas, each series separated by 10 min of rest. Apneas within series were separated by 2 min and preceded by 1 min of hyperventilation to increase apnea duration and arterial oxygen desaturation. When EPO concentration after serial apneas was compared to baseline values, an average maximum increase of 24% was found (P < 0.01). No changes in EPO concentration were observed during a control day without apnea, eliminating possible effects of a diurnal rhythm or blood loss. We therefore conclude that serial apneas increase circulating EPO concentration in humans.
Young, Lindsay R; Kurzer, Mindy S; Thomas, William; Redmon, J Bruce; Raatz, Susan K
2013-07-01
The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P < .001) and IGFBP-3 (P = .01) and the LF diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals. Published by Elsevier Inc.
Microgravity Diode Laser Spectroscopy Measurements in a Reacting Vortex Ring
NASA Technical Reports Server (NTRS)
Chen, Shin-Juh; Dahm, Werner J. A.; Silver, Joel A.; Piltch, Nancy D.; VanderWal, R. (Technical Monitor)
2001-01-01
The technique of Diode Laser Spectroscopy (DLS) with wavelength modulation is utilized to measure the concentration of methane in reacting vortex rings under microgravity conditions. From the measured concentration of methane, other major species such as water, carbon dioxide, nitrogen, and oxygen can be easily computed under the assumption of equilibrium chemistry with an iterative method called ITAC (Iterative Temperature with Assumed Chemistry). The conserved scalar approach in modelling the coupling between fluid dynamics and combustion is utilized to represent the unknown variables in terms of the mixture fraction and scalar dissipation rate in conjunction with ITAC. Post-processing of the DLS and the method used to compute the species concentration are discussed. From the flame luminosity results, ring circulation appears to increase the fuel consumption rate inside the reacting vortex ring and the flame height for cases with similar fuel volumes but different ring circulations. The concentrations of methane, water, and carbon dioxide agree well with available results from numerical simulations.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bianchetti, Lorenza, E-mail: lbianchetti@avail-research.com; Laboratory of Cytopathology and Cytogenetics, Italian ABR Operative Unit, Milan; Marini, Maurizio A., E-mail: mam.marini@yahoo.com
2012-09-14
Highlights: Black-Right-Pointing-Pointer IL-33 is considered a new therapeutic target for reducing inflammation in asthma. Black-Right-Pointing-Pointer This study shows that IL-33 is a potent chemoattractant for fibrocytes in asthma. Black-Right-Pointing-Pointer IL-33 also promotes fibrocyte proliferation without reducing collagen production. Black-Right-Pointing-Pointer The study uncovers a novel non-inflammatory, profibrotic function of IL-33. -- Abstract: The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthmamore » by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in asthma.« less
Seibert, Julia; Hysek, Cédric M; Penno, Carlos A; Schmid, Yasmin; Kratschmar, Denise V; Liechti, Matthias E; Odermatt, Alex
2014-01-01
3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors. © 2014 S. Karger AG, Basel.
Examining the transplacental passage of apixaban using the dually perfused human placenta.
Bapat, P; Pinto, L S R; Lubetsky, A; Aleksa, K; Berger, H; Koren, G; Ito, S
2016-07-01
Essentials Apixaban is a novel oral anticoagulant that has not been studied in pregnant patients. Our objective was to determine the rate and extent of the placental transfer of apixaban. Apixaban rapidly crosses the ex vivo term human placenta from maternal to fetal circulation. Fetal apixaban levels in vivo are estimated to be 35-90% of the corresponding maternal levels. Background Apixaban is a novel oral anticoagulant that is increasingly being prescribed to women of reproductive age. However, information regarding its placental transfer is non-existent. Objective To determine the rate and extent of placental transfer of apixaban, using the human placenta ex vivo. Methods Placentae collected after Caesarean or vaginal delivery of healthy term infants were perfused in the respective maternal and fetal circulation. At the start of the experiment, apixaban was added to the maternal circulation at a concentration of 150 ng mL(-1) , and samples from maternal and fetal reservoirs were collected over 3 h. Results There was a rapid decline of apixaban in the maternal compartment, followed by emergence in the fetal compartment with a median fetal-to-maternal drug concentration ratio of 0.77 (interquartile range [IQR], 0.76-0.81) and fetal concentration of 39.0 ng mL(-1) (IQR, 36.8-40.6) after 3 h (n = 5). The perfusion results were subsequently adjusted to account for differences in the concentration of plasma proteins in maternal and fetal blood, as apixaban remains highly bound to albumin and alpha-1 acid glycoprotein. After the adjustment, the predicted fetal-to-maternal ratio of total (bound plus unbound) apixaban concentrations in vivo ranged from 0.35 to 0.90. Conclusions We conclude that unbound apixaban rapidly crosses from the maternal to fetal circulation. We further predict that total apixaban concentrations in cord blood in vivo are 35-90% of the corresponding maternal levels, suggesting that apixaban could have a possible adverse effect on fetal and neonatal coagulation. © 2016 International Society on Thrombosis and Haemostasis.
Bradbury, Kathryn E; Balkwill, Angela; Tipper, Sarah J; Crowe, Francesca L; Reeves, Gillian K; Green, Jane; Beral, Valerie; Key, Timothy J
2015-04-01
Higher circulating concentrations of insulin like growth factor (IGF-I) are associated with an increased risk of breast cancer. The objective of this study was to investigate associations between circulating IGF-I concentrations and dietary factors (intakes of protein, dairy protein, and alcohol), lifestyle factors (smoking and HT use), anthropometric indices (height and adiposity) and factors in early life (birth weight, having been breastfed, body size at age 10, and at age 20) in postmenopausal women in the UK. An analysis of plasma IGF-I concentrations (measured by immunoassay) in 1883 postmenopausal women. Multivariate analysis was used to examine correlates of plasma IGF-I concentrations. Women in the highest quintile of total protein and dairy protein intakes had, respectively, 7.6% and 5.5% higher plasma IGF-I concentrations than women in the lowest quintile (p trend <0.05 for both). Other factors significantly (p<0.05) associated with reduced IGF-I concentrations were: consuming 14 or more vs 3-7 alcoholic drinks per week (8.8% lower IGF-I); current vs non-current HT users (9.9% lower IGF-I); current use of oestrogen alone vs oestrogen+progestagen (16.9% lower IGF-I); obese vs overweight (6.8% lower IGF-I); and women who reported wearing larger vs smaller clothes sizes at age 20 (4.9% lower IGF-I). This study in post-menopausal women identified several potentially modifiable determinants of circulating IGF-I concentrations. There is now strong evidence from this and other studies that IGF-I concentrations are associated with dietary protein intakes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Lozano-Bartolomé, J; Llauradó, G; Rodriguez, M M; Fernandez-Real, J M; Garcia-Fontgivell, J F; Puig, J; Maymó-Masip, E; Vendrell, J; Chacón, M R
2016-09-01
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD. We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation.Design setting and patients:This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation. We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression of cluster of differentiation 36 (CD36) and perilipin 1 and 2 (PLIN1 and PLIN2) genes. Decreased sTWEAK concentrations are independently associated with the presence of NAFLD. This is concordant with the observation that TWEAK reduces lipid accumulation in human liver cells.
USDA-ARS?s Scientific Manuscript database
Scope: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated i...
Garlan, Fanny; Blanchet, Benoit; Kramkimel, Nora; Puszkiel, Alicja; Golmard, Jean-Louis; Noe, Gaelle; Dupin, Nicolas; Laurent-Puig, Pierre; Vidal, Michel; Taly, Valerie; Thomas-Schoemann, Audrey
2017-06-01
Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman ® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences. At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04-6.56; p = 0.04). This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.
Zhang, Zhongzhi; Song, Shaofu; Huang, Jie; Ji, Lin; Wu, Fangyun
2003-01-01
The corrosion rate of steel plate using single-factor, multifactor, and complex water systems was investigated via refinery wastewater effluents used as circulating cooling water. The results show that the primary corrosion factors of steel depend on the characteristics of the ions, the formation of the oxidized coating, the diffusion of dissolved oxygen, and other complex factors, although ions such as chloride, calcium, and carbonate play an important role. The corrosion rate of carbon steel exhibits two trends: The corrosion rate is high at low conductivity, increases to a maximum, and then decreases and becomes stable with increasing conductivity, as is the case with chloride, sulfate, nitrate and calcium ions. On the other hand, the corrosion rate is highest at low conductivity and then decreases and becomes stable with increasing conductivity, as is the case with carbonate, silicate, and sodium nitrate ions. Research results indicate that the anticorrosive ability is minimal at low conductivity; but is excellent at high conductivity. Pretreatment of low-conductivity water using air flotation and clarification to decrease the concentrations of chloride, calcium, and carbonate ions to a suitable level to satisfy the anticorrosion requirements is required. However, it is not necessary to significantly reduce the salt concentration or conductivity of the water by osmosis or ion exchange to obtain an anticorrosion effect when reusing wastewater effluents as circulating cooling water.
Chen, Tianbao; Wu, Bing; Lin, Rong
2017-01-01
It is well established that apelin-APLNR (apelin receptor) pathway plays a central role in cardiovascular system. In this meta-analysis, we summarized published results on circulating apelin concentration in association with coronary artery disease (CAD), apelin and APLNR genetic polymorphism(s) in predisposition to CAD risk and circulating apelin changes after surgical treatment for CAD. The results from 15 articles were pooled. Two authors independently took charge of literature search, article selection and information collection. Overall, circulating apelin concentration was significantly lower in CAD patients (N=1021) than in controls (N=654) (weighted mean difference [WMD]: -1.285 ng/mL, 95% confidence interval [CI]: -1.790 to -0.780, P<0001), with significant heterogeneity (I2=99.3%) but without publication bias. For the association of APLNR gene rs9943582 polymorphism with CAD (patients/controls: 5975/4717), the mutant T allele was associated with a 5.2% increased risk relative to the wild C allele (odds ratio: 1.052, 95% CI: 0.990 to 1.117, P=0.100), without heterogeneity (I2=0.0%) or publication bias. Circulating apelin was increased significantly after surgical treatment for CAD (N=202) (WMD: 2.011 ng/mL, 95% CI: 0.541 to 3.481, P=0.007), with significant heterogeneity (I2=98.0%). Stratified analyses showed that circulating apelin was significantly reduced in studies with age- and sex-matched patients and controls (WMD: -1.881 ng/mL, 95% CI: -2.457 to -1.304, P<0.001) and with total sample size ≥125 (WMD: -1.657 ng/mL, 95% CI: -2.378 to -0.936, P<0.001), relative to studies without matching reports and with total sample size <125. In brief, our results suggested that circulating apelin was a prominent athero-protective marker against the development of CAD. PMID:28915675
Maillo, V; Duffy, P; O'Hara, L; de Frutos, C; Kelly, A K; Lonergan, P; Rizos, D
2014-03-01
This study examined the effect of a single administration of human chorionic gonadotrophin (hCG) on Day 1 to 4 after oestrus on corpus luteum (CL) development and circulating progesterone (P4). Oestrus-synchronized heifers (n=43) were administered a single intramuscular injection of saline on Day 1 (control) or 3000IU hCG on Day 1, 2, 3 or 4 after oestrus. Administration of hCG on Day 1 had no effect on CL area, on Day 2 increased CL area from Day 6 to 12 (P<0.05), on Day 3 increased CL area from Day 9 to 11, while on Day 4 increased CL size on Days 9 and 10 (P<0.05). Administration of hCG on Day 4 induced the formation of an accessory CL in 89% of heifers, resulting in a significant increase in total luteal tissue area on the ovaries compared with all other groups. Consistent with the effects on the CL, hCG on Day 1 did not affect P4 concentrations, on Day 2 significantly increased P4 compared with the control from Day 6 to 11 (P<0.05), on Day 3 resulted in a non-significant increase in P4 while hCG on Day 4 increased P4 from Day 8 to 13 compared with the control (P<0.05). In conclusion, administration of hCG as early as Day 2 after oestrus results in increased P4 in circulation from Day 6, which should have beneficial downstream effects in terms of uterine receptivity and conceptus elongation.
Environmental contaminants can act as stressors, inducing elevated circulating concentrations of stress hormones such as corticosterone and cortisol. Development in contaminated eggs has been reported to modify circulating sex steroid hormone concentrations in alligators (Alligat...
Conahey, George R.; Power, Gordon G.; Hopper, Andrew O.; Terry, Michael H.; Kirby, Laura S.; Blood, Arlin B.
2009-01-01
Inhaled nitric oxide (iNO) has many extrapulmonary effects. As the half-life of NO in blood is orders of magnitude less than the circulation time from lungs to the brain, the mediator of systemic effects of iNO is unknown. We hypothesized that concentrations of nitrite, a circulating byproduct of NO with demonstrated NO bioactivity, would increase in blood and cerebrospinal fluid (CSF) during iNO therapy. iNO (80ppm) was given to six newborn lambs and results compared to six control lambs. Blood and CSF nitrite concentrations increased two-fold in response to iNO. cGMP increased in blood but not CSF suggesting brain guanylate cyclase activity was not increased. When sodium nitrite was infused intravenously blood and CSF nitrite levels increased within 10 min and reached similar levels of 14.6±1.5 µM after 40 min. The reactivity of nitrite in hemoglobin-free brain homogenates was investigated, with the findings that nitrite did not disappear nor did measurable amounts of s-nitroso, n-nitroso, or iron-nitrosyl-species appear. We conclude that although nitrite diffuses freely between blood and CSF, due to its lack of reactivity in the brain, nitrite’s putative role as the mediator of the systemic effects of iNO is limited to intravascular reactions. PMID:18535482
A comparison of two- and three-dimensional tracer transport within a stratospheric circulation model
NASA Technical Reports Server (NTRS)
Schneider, H.-R.; Geller, M. A.
1985-01-01
Use of the residual circulation for stratospheric tracer transport has been compared to a fully three-dimensional calculation. The wind fields used in this study were obtained from a global, semispectral, primitive equation model, extending from 10 to 100 km in altitude. Comparisons were done with a passive tracer and an ozone-like substance over a two-month period corresponding to a Northern Hemisphere winter. It was found that the use of the residual circulation can lead to errors in the tracer concentrations of about a factor of 2. The error is made up of two components. One is fluctuating with a period of approximately one month and reflects directly the wave transience that occurs on that time-scale. The second part is increasing steadily over the integration period and results from an overestimate of the vertical transport by the residual circulation. Furthermore, the equatorward and upward mixing that occurs with transport by the three-dimensional circulation at low latitudes is not well reproduced when the residual circulation is used.
NASA Astrophysics Data System (ADS)
Haskell, Brian J.; Johnson, Thomas C.
1993-01-01
Two transects of box core, hydrographic and photographic stations were made along the Blake Outer Ridge on the southeastern U.S. continental rise to study how circulation patterns affect surface sediment properties. Circulation is strongest at 4200 m on the flanks of the ridge and is reflected in the suspended particulate distribution. A second turbidity maximum at 3600 m suggests that there may be a second axis of circulation at this depth. The intense circulation on the flanks of the ridge has resulted in winnowing of the sediment revealed by coarsening and flattening of the grain size distribution in the detrital silt fraction, and concentration of carbonate by the formation of a foraminiferal lag deposit. The mean grain size of the detrital silt fraction on the crest of the ridge decreases southeastwards with increasing distance from upstream sediment sources. Shifts in the position and strength of the Western Boundary Undercurrent affect the distance that relatively coarse silt is transported. Downcore changes in grain size can therefore be used as paleoceanographic proxy for changes in deepwater circulation.
Windsor, Mark T.; Bailey, Tom G.; Perissiou, Maria; Meital, Lara; Golledge, Jonathan; Russell, Fraser D.; Askew, Christopher D.
2018-01-01
Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6]) and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]). However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α) and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg−1.min−1) and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg−1.min−1) completed three 24 min experimental protocols in a randomized order: (1) moderate-intensity continuous exercise (40% of peak power output [PPO]); (2) higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO); or (3) non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02), with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01). However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control) protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6 were elevated in older individuals with higher levels of cardiorespiratory fitness. However, changes in plasma cytokine concentrations after exercise were not different to changes after non-exercise control in both the lower- and higher-fit groups. PMID:29599722
B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.
Vila, Greisa; Grimm, Gabriele; Resl, Michael; Heinisch, Birgit; Einwallner, Elisa; Esterbauer, Harald; Dieplinger, Benjamin; Mueller, Thomas; Luger, Anton; Clodi, Martin
2012-10-01
Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.
Mian, Rubina; Shelton-Rayner, Graham; Harkin, Brendan; Williams, Paul
2003-03-01
The aim of this study was to assess the effect of watching a psychological stressful event on the activation of leukocytes in healthy human volunteers. Blood samples were obtained from 32 healthy male and female subjects aged between 20 and 26 years before, during and after either watching an 83-minute horror film that none of the subjects had previously seen (The Texas Chainsaw Massacre, 1974) or by sitting quietly in a room (control group). Total differential cell counts, leukocyte activation as measured by the nitroblue tetrazolium (NBT) test, heart rate and blood pressure (BP) measurements were taken at defined time points. There were significant increases in peripheral circulating leukocytes, the number of activated circulating leukocytes, haemoglobin (Hb) concentration and haematocrit (Hct) in response to the stressor. These were accompanied by significant increases in heart rate, systolic and diastolic BP (P<0.05 from baseline). This is the first reported study on the effects of observing a psychologically stressful, albeit fictitious event on circulating leukocyte numbers and the state of leukocyte activation as determined by the nitrotetrazolium test.
Ejarque, Miriam; Borlaug, Marianne; Vilarrasa, Nuria; Martinez-Perez, Bruno; Llauradó, Gemma; Megía, Ana; Helland, Thomas; Gutierrez, Cristina; Serena, Carolina; Folkestad, Oddry; Nuñez-Roa, Catalina; Roche, Kelly; Casajoana, Ana; Fradera, Rosa; González-Clemente, José Miguel; López, Miguel; Mohn, Arne C; Nedrebø, Bjørn G; Nogueiras, Ruben; Mellgren, Gunnar; Fernø, Johan; Fernández-Veledo, Sonia; Vendrell, Joan
2017-06-01
This work aimed to explore the link between angiopoietin-like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross-sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow-up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.
MEAN-FIELD SOLAR DYNAMO MODELS WITH A STRONG MERIDIONAL FLOW AT THE BOTTOM OF THE CONVECTION ZONE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pipin, V. V.; Kosovichev, A. G.
2011-09-01
This paper presents a study of kinematic axisymmetric mean-field dynamo models for the case of meridional circulation with a deep-seated stagnation point and a strong return flow at the bottom of the convection zone. This kind of circulation follows from mean-field models of the angular momentum balance in the solar convection zone. The dynamo models include turbulent sources of the large-scale poloidal magnetic field production due to kinetic helicity and a combined effect due to the Coriolis force and large-scale electric current. In these models the toroidal magnetic field, which is responsible for sunspot production, is concentrated at the bottommore » of the convection zone and is transported to low-latitude regions by a meridional flow. The meridional component of the poloidal field is also concentrated at the bottom of the convection zone, while the radial component is concentrated in near-polar regions. We show that it is possible for this type of meridional circulation to construct kinematic dynamo models that resemble in some aspects the sunspot magnetic activity cycle. However, in the near-equatorial regions the phase relation between the toroidal and poloidal components disagrees with observations. We also show that the period of the magnetic cycle may not always monotonically decrease with the increase of the meridional flow speed. Thus, for further progress it is important to determine the structure of the meridional circulation, which is one of the critical properties, from helioseismology observations.« less
Barker, Tyler; Henriksen, Vanessa T; Rogers, Victoria E; Momberger, Nathan G; Rasmussen, G Lynn; Trawick, Roy H
2016-12-01
The purpose of this study was to identify if circulating interleukin (IL)-6 and γ-tocopherol (γT) fluctuate with vitamin D status in subjects with an underlying knee joint injury or disease. We hypothesized that low vitamin D associates with an increase in plasma γT while serum IL-6 remains unchanged in subjects with an underlying knee joint trauma or disease. Fifty-four subjects scheduled to undergo primary, unilateral anterior cruciate ligament reconstructive surgery (ACL; n=27) or total knee arthroplasty (TKA; n=27) were studied. Circulating γT, α-tocopherol (αT), lipids (cholesterol and triglycerides), IL-6, and 25-hydroxyvitamin D (25(OH)D) were measured in fasting blood samples obtained prior to surgery. Subjects were classified as vitamin D deficient, insufficient, or sufficient if they had a serum 25(OH)D concentration <50, 50-75, or >75nM, respectively. The majority (57%) of the subjects possessed a serum 25(OH)D less than 50nM. Circulating cholesterol, triglycerides, and IL-6 were not significantly (all p>0.05) different between vitamin D status groups. However, lipid corrected αT was significantly (p<0.05) decreased and both lipid- and non-lipid-corrected plasma γT concentrations were significantly (both p<0.05) increased with low serum 25(OH)D (i.e., <50nM). A significant (p<0.05) multi-variate analysis revealed that an increase in plasma γT per lipids was significantly (p<0.05) predicted by a decrease in serum 25(OH)D but not by a decrease in plasma αT per lipids. We conclude that low vitamin D associates with an increase in plasma γT but not IL-6 in subjects with an underlying joint injury or disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
Rotor Wake Development During the First Revolution
NASA Technical Reports Server (NTRS)
McAlister, Kenneth W.
2003-01-01
The wake behind a two-bladed model rotor in light climb was measured using particle image velocimetry, with particular emphasis on the development of the trailing vortex during the first revolution of the rotor. The distribution of vorticity was distinguished from the slightly elliptical swirl pattern. Peculiar dynamics within the void region may explain why the peak vorticity appeared to shift away from the center as the vortex aged, suggesting the onset of instability. The swirl and axial velocities (which reached 44 and 12 percent of the rotor-tip speed, respectively) were found to be asymmetric relative to the vortex center. In particular, the axial flow was composed of two concentrated zones moving in opposite directions. The radial distribution of the circulation rapidly increased in magnitude until reaching a point just beyond the core radius, after which the rate of growth decreased significantly. The core-radius circulation increased slightly with wake age, but the large-radius circulation appeared to remain relatively constant. The radial distributions of swirl velocity and vorticity exhibit self-similar behaviors, especially within the core. The diameter of the vortex core was initially about 10 percent of the rotor-blade chord, but more than doubled its size after one revolution of the rotor. According to vortex models that approximate the measured data, the core-radius circulation was about 79 percent of the large-radius circulation, and the large-radius circulation was about 67 percent of the maximum bound circulation on the rotor blade. On average, about 53 percent of the maximum bound circulation resides within the vortex core during the first revolution of the rotor.
Zhang, Fengbo; Pang, Nannan; Zhu, Yuejie; Zhou, Dexian; Zhao, Hui; Hu, Jinwei; Ma, Xiumin; Li, Jun; Wen, Hao; Samten, Buka; Fan, Haining; Ding, Jianbing
2015-10-26
In our study, we investigated whether circulating T follicular helper (Tfh) and the related cytokines are involved in human cystic echinococcosis (CE). A total of 64 patients with CE and 30 healthy controls were enrolled in this study. Percentages of CCR7(lo)PD-1(hi) cells within CXCR5(+) CD4(+) T cells (circulating Tfh cells) were detected by flow cytometry. Levels of IL-21 and IL-4 in peripheral blood were detected by cytometric bead array. The mRNA expression of IL-21, IL-4, Bcl-6, and Blimp-1 in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR. Levels of IgG1, IgG2, IgG3, and IgG4 in the patients' sera were measured using enzyme-linked immunosorbent assay. Percentages of circulating Tfh cells were significantly increased in the CE1, CE2, and CE3 groups (p < 0.05). The concentrations of IL-21 and IL-4 in the serum were significantly increased in CE1, CE2, and CE3 groups (p < 0.05). IL-21 was positively correlated with circulating Tfh cells in CE3 group (r = 0.779, p < 0.05). The mRNA levels of IL-21, IL-4, and Bcl-6 were increased in CE1, CE2, and CE3 groups. Levels of IgG1 and IgG4 in patients' sera were increased in CE1, CE2, and CE3 groups. Levels of IgG2 and IgG3 were increased in CE4-5 group. Additionally, after stimulation with hydatid fluid in vitro, the levels of circulating Tfh cells, IL-21 and IL-4 in PBMCs isolated from CE patients were significantly increased (p < 0.05). The levels of circulating Tfh and related cytokines were significantly increased in CE patients, suggesting that they are involved in human CE.
Noninvasive Measurement of Steroid Hormones in Zebrafish Holding-Water
Félix, Ana S.; Faustino, Ana I.; Cabral, Eduarda M.
2013-01-01
Abstract Zebrafish (Danio rerio) has recently emerged as a new animal model in neuroendocrinology and behavior (e.g., stress physiology and ecotoxicology studies). In these areas, the concentrations of steroid hormones in the blood are often used to study the endocrinological status of individuals. However, due to the small body size of zebrafish, blood sampling is difficult to perform and the amount of plasma obtained per sample for assaying hormones is very small (ca. 1–5 μL), and therefore most studies have been using whole-body hormone concentrations, which implies sacrificing the individuals and hampers sequential sampling of the same individual. Here a noninvasive method to assay steroid hormones from zebrafish holding-water, based on the fact that steroids are released into the fish holding-water through the gills by passive diffusion, is validated. Cortisol and the androgen 11-ketotestosterone (KT) were measured in water samples and compared to plasma levels in the same individuals. Cortisol released to holding-water correlates positively with plasma concentrations, but there was a lack of correlation between KT water and circulating levels. However, KT levels showed a highly significant sex difference that can be used to noninvasively sex individuals. An ACTH challenge test demonstrated that an induced increase in circulating cortisol concentration can be reliably detected in holding-water levels, hence attesting the responsiveness of holding-water levels to fluctuations in circulating levels. PMID:23445429
Alexandre, Daniel; Ozório, Renata A; Derner, Roberto B; Fracalossi, Débora M; Oliveira, Gabriel B; Samuels, Richard I; Terra, Walter R; Silva, Carlos P
2014-01-01
The effect of dietary protein concentration on the spatial distribution of digestive proteinases in the shrimp Litopenaeus vannamei indicates the existence of endo-ectoperitrophic enzyme circulation in this species. Samples recovered from the midgut gland tissues, stomach contents, three different portions of the midgut and feces were used for quantitative and qualitative analyses of the composition and distribution of the digestive proteinases. Animals were divided into three different groups: (1) animals (controls) fed with a commercial 35% protein diet, (2) animals fed with a commercial diet supplemented with ovalbumin to a final protein concentration of 60%; (3) animals fed with an 80% protein diet. Quantitative determinations using different substrates and zymograms showed that increasing protein concentration in the diet alters the distribution of proteinases along the digestive tract. Composition of proteinases in the midgut gland, stomach contents, midgut sections and feces were similar, but not identical. Chymotrypsin and trypsin paralogues were identified in all enzyme sources in a concentration gradient along the midgut in the control shrimp, the expected distribution supporting the existence of a recycling mechanism. The occurrence of a peritrophic membrane in other Decapoda suggests that endo-ectoperitrophic circulation of digestive enzymes and nutrients may also occur in other crustaceans and also extends beyond the Insecta. Copyright © 2014 Elsevier Inc. All rights reserved.
Ibrahim, Yomna I; Ninnis, Janet R; Hopper, Andrew O; Deming, Douglas D; Zhang, Amy X; Herring, Jason L; Sowers, Lawrence C; McMahon, Timothy J; Power, Gordon G; Blood, Arlin B
2012-02-01
To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs. Copyright © 2012 Mosby, Inc. All rights reserved.
Ibrahim, Yomna I.; Ninnis, Janet R.; Hopper, Andrew O.; Deming, Douglas D.; Zhang, Amy X.; Herring, Jason L.; Sowers, Lawrence C.; McMahon, Timothy J.; Power, Gordon G.; Blood, Arlin B.
2011-01-01
Objective To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity following inhaled NO therapy in infants with pulmonary hypertension. Study design In this single center study five sequential blood samples were collected from infants with pulmonary hypertension before, during and after therapy with iNO (n=17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n=16) and from healthy adults for comparison (n=12). Results After beginning iNO (20 ppm) whole blood nitrite increased about two-fold within two hours (P<0.01). Whole blood nitrate increased to four-fold higher than baseline during treatment with 20ppm iNO (P<0.01). S-nitrosohemoglobin (SNO-Hb) increased measurably after beginning iNO (P<0.01) whereas iron nitrosyl hemoglobin and total Hb-bound NO-species compounds did not change. Conclusion Treatment of pulmonary hypertensive infants with iNO results in increases in nitrite, nitrate, and SNO-Hb in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart and other organs. PMID:21907348
Kocić, Gordana; Radenkovic, Sonja; Cvetkovic, Tatjana; Cencic, Avrelija; Carluccio, Francesco; Musovic, Dijana; Nikolić, Goran; Jevtović-Stoimenov, Tatjana; Sokolović, Dusan; Milojkovic, Boban; Basic, Jelena; Veljkovic, Andrej; Stojanović, Svetlana
2010-05-01
Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV-V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-kappaB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.
Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.
Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L
2006-04-01
The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.
Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows.
Caixeta, Luciano S; Giesy, Sarah L; Krumm, Christopher S; Perfield, James W; Butterfield, Anthony; Schoenberg, Katie M; Beitz, Donald C; Boisclair, Yves R
2017-11-01
Modern dairy cows meet the energy demand of early lactation by calling on hormonally driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and nonesterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy-sufficient, nonpregnant, nonlactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over a 72-h period. GCG increased hepatic FGF21 mRNA by an average of fivefold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with Intralipid and injected with saline, or infused with Intralipid and injected with GCG. Infusions and injections were administered intravenously over 16 h and subcutaneously every 8 h, respectively. Intralipid infusion increased plasma NEFA from 92 to 550 µM within 3 h and increased plasma FGF21 from 1.3 to >11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the Intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA, or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation. Copyright © 2017 the American Physiological Society.
Hughes, David J; Duarte-Salles, Talita; Hybsier, Sandra; Trichopoulou, Antonia; Stepien, Magdalena; Aleksandrova, Krasimira; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Affret, Aurélie; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verena; Kaaks, Rudolf; Boeing, Heiner; Bamia, Christina; Lagiou, Pagona; Peppa, Eleni; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, Hendrik Bastiaan; Peeters, Petra H; Engeset, Dagrun; Weiderpass, Elisabete; Lasheras, Cristina; Agudo, Antonio; Sánchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Hemmingsson, Oskar; Wareham, Nicholas J; Khaw, Kay-Tee; Bradbury, Kathryn E; Cross, Amanda J; Gunter, Marc; Riboli, Elio; Romieu, Isabelle; Schomburg, Lutz; Jenab, Mazda
2016-08-01
Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-μg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. © 2016 American Society for Nutrition.
Circulating GLP-1 in infants born small-for-gestational-age: breast-feeding versus formula-feeding.
Díaz, M; Bassols, J; Sebastiani, G; López-Bermejo, A; Ibáñez, L; de Zegher, F
2015-10-01
Prenatal growth restraint associates with the risk for later diabetes, particularly if such restraint is followed by postnatal formula-feeding (FOF) rather than breast-feeding (BRF). Circulating incretins can influence the neonatal programming of hypothalamic setpoints for appetite and energy expenditure, and are thus candidate mediators of the long-term effects exerted by early nutrition. We have tested this concept by measuring (at birth and at age 4 months) the circulating concentrations of glucagon-like peptide-1 (GLP-1) in BRF infants born appropriate-for-gestational-age (AGA; n=63) and in small-for-gestational-age (SGA) infants receiving either BRF (n=28) or FOF (n=26). At birth, concentrations of GLP-1 were similar in AGA and SGA infants. At 4 months, pre-feeding GLP-1 concentrations were higher than at birth; SGA-BRF infants had GLP-1 concentrations similar to those in AGA-BRF infants but SGA-FOF infants had higher concentrations. In conclusion, nutrition appears to influence the circulating GLP-1 concentrations in SGA infants and may thereby modulate long-term diabetes risk.
Stewart, Laura K.; Soileau, Jeff L.; Ribnicky, David; Wang, Zhong Q.; Raskin, Ilya; Poulev, Alexander; Majewski, Martin; Cefalu, William T.; Gettys, Thomas W.
2008-01-01
Quercetin, a polyphenolic compound and a major bioflavonoid in the human diet, has anti-inflammatory properties and has been postulated to enhance energy expenditure (EE). We sought to determine whether quercetin alters body weight, body composition, EE, and circulating markers of inflammation. At 6 weeks (W) of age, 2 cohorts of C57BL/6J mice (N = 80) were placed on one of 2 diets for 3W or 8W: (1) high fat (HF) (45% kcal fat) or (2) high fat + quercetin (HF + Q) (45% kcal fat + 0.8% quercetin). Quercetin concentrations in the diet and plasma were evaluated using mass spectrometry. Body weight, composition (nuclear magnetic resonance), and food consumption were measured weekly. Energy expenditure was measured by indirect calorimetry at 3 and 8W, and inflammatory markers were measured in plasma obtained at 8W. The presence of quercetin in the HF diet did not alter food consumption over time in the HF + Q group and did not differ from the HF group at any time point. However, circulating plasma quercetin concentrations declined between 3 and 8W. At 3W, EE was higher during both day and night phases (P < .0001) in the HF + Q group compared with the HF group; but this difference was not detected at 8W and did not translate into significant differences between the HF + Q and HF groups with respect to body weight or body composition. During the night phase, concentrations of the inflammatory markers (interferon-γ, interleukin-1α, and interleukin-4) were significantly lower when compared with HF treatment group (P < .05). Dietary supplementation with quercetin produces transient (3W) increases in EE that are not detected after 8W on the diet. A corresponding decrease in circulating quercetin between 3 and 8W suggests that metabolic adaptation may have diminished the impact of quercetin's early effect on EE and diminished its overall effect on nutrient partitioning and adiposity. However, quercetin at the levels provided was effective in reducing circulating markers of inflammation observed in animals on an HF diet at 8W. PMID:18555853
Montenegro, Marcelo F; Sundqvist, Michaela L; Nihlén, Carina; Hezel, Michael; Carlström, Mattias; Weitzberg, Eddie; Lundberg, Jon O
2016-12-01
In humans dietary circulating nitrate accumulates rapidly in saliva through active transport in the salivary glands. By this mechanism resulting salivary nitrate concentrations are 10-20 times higher than in plasma. In the oral cavity nitrate is reduced by commensal bacteria to nitrite, which is subsequently swallowed and further metabolized to nitric oxide (NO) and other bioactive nitrogen oxides in blood and tissues. This entero-salivary circulation of nitrate is central in the various NO-like effects observed after ingestion of inorganic nitrate. The very same system has also been the focus of toxicologists studying potential carcinogenic effects of nitrite-dependent nitrosamine formation. Whether active transport of nitrate and accumulation in saliva occurs also in rodents is not entirely clear. Here we measured salivary and plasma levels of nitrate and nitrite in humans, rats and mice after administration of a standardized dose of nitrate. After oral (humans) or intraperitoneal (rodents) sodium nitrate administration (0.1mmol/kg), plasma nitrate levels increased markedly reaching ~300µM in all three species. In humans ingestion of nitrate was followed by a rapid increase in salivary nitrate to >6000µM, ie 20 times higher than those found in plasma. In contrast, in rats and mice salivary nitrate concentrations never exceeded the levels in plasma. Nitrite levels in saliva and plasma followed a similar pattern, ie marked increases in humans but modest elevations in rodents. In mice there was also no accumulation of nitrate in the salivary glands as measured directly in whole glands obtained after acute administration of nitrate. This study suggests that in contrast to humans, rats and mice do not actively concentrate circulating nitrate in saliva. These apparent species differences should be taken into consideration when studying the nitrate-nitrite-nitric oxide pathway in rodents, when calculating doses, exploring physiological, therapeutic and toxicological effects and comparing with human data. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Role of smooth muscle cells on endothelial cell cytosolic free calcium in porcine coronary arteries.
Budel, S; Schuster, A; Stergiopoulos, N; Meister, J J; Bény, J L
2001-09-01
We tested the hypothesis that the cytosolic free calcium concentration in endothelial cells is under the influence of the smooth muscle cells in the coronary circulation. In the left descending branch of porcine coronary arteries, cytosolic free calcium concentration ([Ca(2+)](i)) was estimated by determining the fluorescence ratio of two calcium probes, fluo 4 and fura red, in smooth muscle and endothelial cells using confocal microscopy. Acetylcholine and potassium, which act directly on smooth muscle cells to increase [Ca(2+)](i), were found to indirectly elevate [Ca(2+)](i) in endothelial cells; in primary cultures of endothelial cells, neither stimulus affected [Ca(2+)](i), yet substance P increased the fluorescence ratio twofold. In response to acetylcholine and potassium, isometric tension developed by arterial strips with intact endothelium was attenuated by up to 22% (P < 0.05) compared with strips without endothelium. These findings suggest that stimuli that increase smooth muscle [Ca(2+)](i) can indirectly influence endothelial cell function in porcine coronary arteries. Such a pathway for negative feedback can moderate vasoconstriction and diminish the potential for vasospasm in the coronary circulation.
NASA Astrophysics Data System (ADS)
Weitnauer, C.; Beck, C.; Jacobeit, J.
2013-12-01
In the last decades the critical increase of the emission of air pollutants like nitrogen dioxide, sulfur oxides and particulate matter especially in urban areas has become a problem for the environment as well as human health. Several studies confirm a risk of high concentration episodes of particulate matter with an aerodynamic diameter < 10 μm (PM10) for the respiratory tract or cardiovascular diseases. Furthermore it is known that local meteorological and large scale atmospheric conditions are important influencing factors on local PM10 concentrations. With climate changing rapidly, these connections need to be better understood in order to provide estimates of climate change related consequences for air quality management purposes. For quantifying the link between large-scale atmospheric conditions and local PM10 concentrations circulation- and weather type classifications are used in a number of studies by using different statistical approaches. Thus far only few systematic attempts have been made to modify consisting or to develop new weather- and circulation type classifications in order to improve their ability to resolve local PM10 concentrations. In this contribution existing weather- and circulation type classifications, performed on daily 2.5 x 2.5 gridded parameters of the NCEP/NCAR reanalysis data set, are optimized with regard to their discriminative power for local PM10 concentrations at 49 Bavarian measurement sites for the period 1980 to 2011. Most of the PM10 stations are situated in urban areas covering urban background, traffic and industry related pollution regimes. The range of regimes is extended by a few rural background stations. To characterize the correspondence between the PM10 measurements of the different stations by spatial patterns, a regionalization by an s-mode principal component analysis is realized on the high-pass filtered data. The optimization of the circulation- and weather types is implemented using two representative classification approaches, a k-means cluster analysis and an objective version of the Grosswetter types. They have been run with varying spatial and temporal settings as well as modified numbers of classes. As an evaluation metric for their performance several skill scores are used. Taking into account the outcome further attempts towards the optimization of circulation type classifications are made. These are varying meteorological input parameters (e.g. geopotential height, zonal and meridional wind, specific humidity, temperature) on several pressure levels (1000, 850 and 500 hPa) and combinations of these variables. All classification variants are again evaluated. Based on these analyses it is further intended to develop robust downscaling models for estimating possible future - climate change induced - variations of local PM10 concentrations in Bavaria from scenario runs of global CMIP5 climate models.
The Effect of Particle Size on the Biodistribution of Low-modulus Hydrogel PRINT Particles
Merkel, Timothy J.; Chen, Kai; Jones, Stephen W.; Pandya, Ashish A.; Tian, Shaomin; Napier, Mary E.; Zamboni, William E.; DeSimone, Joseph M.
2012-01-01
There is a growing recognition that the deformability of particles used for drug delivery plays a significant role on their biodistribution and circulation profile. Understanding these effects would provide a crucial tool for the rational design of drug delivery systems. While particles resembling red blood cells (RBCs) in size, shape and deformability have extended circulation times and altered biodistribution profiles compared to rigid, but otherwise similar particles, the in vivo behavior of such highly deformable particles of varied size has not been explored. We report the fabrication of a series of discoid, monodisperse, low-modulus hydrogel particles with diameters ranging from 0.8 to 8.9 μm, spanning sizes smaller than and larger than RBCs. We injected these particles into healthy mice, and tracked their concentration in the blood and their distribution into major organs. These deformable particles all demonstrated some hold up in filtration tissues like the lungs and spleen, followed by release back into the circulation, characterized by decreases in particles in these tissues with concomitant increases in particle concentration in blood. Particles similar to red blood cells in size demonstrated longer circulation times, suggesting that this size and shape of deformable particle is uniquely suited to avoid clearance. PMID:22705460
NASA Astrophysics Data System (ADS)
McNeeley, Kathleen M.; Annapragada, Ananth; Bellamkonda, Ravi V.
2007-09-01
Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas.
Serial hepatic gene expression profiling in Angus steers during feed restriction and realimentation
USDA-ARS?s Scientific Manuscript database
Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentration...
Subclinical thyroid disease in elderly subjects.
Ceresini, Graziano; Morganti, Simonetta; Maggio, Marcello; Usberti, Elisa; Fiorino, Ilaria; Artoni, Andrea; Teresi, Giulio; Belli, Serena; Ridolfi, Valentina; Valenti, Giorgio; Ceda, Gian Paolo
2010-01-01
Subclinical thyroid disease (STD) is defined as circulating concentrations of free T4 and free T3 within their respective reference ranges in the presence of abnormal circulating concentrations of TSH. SCD is being diagnosed more frequently in clinical practice and is reported to be more prevalent in elderly as compared to young or adult subjects. The clinical impact of subclinical thyroid dysfunction is still a matter of debate, although it has been associated with various negative clinical outcomes, such as increased cardiovascular risk, reduction in bone density, decline in cognitive function, and increased risk of overt thyroid dysfunction. The treatment of STD is controversial and there is no consensus on the TSH cutoff values which can be used as indicators for treatment, especially in elderly subjects. In the present review, we report data on the prevalence of STD and on the potential clinical consequences of these disorders. Also, data of the Literature regarding the issue of the treatment of STD in relation to the age of the patient are reported.
NASA Astrophysics Data System (ADS)
Zhu, Jianlei; Liao, Hong; Li, Jianping
2012-05-01
China has been experiencing increased concentrations of aerosols, commonly attributed to the large increases in emissions associated with the rapid economic development. We show by using a chemical transport model driven by the assimilated meteorological fields that the observed decadal-scale weakening of the East Asian summer monsoon also contributed to the increases in aerosols in China. We find that the simulated aerosol concentrations have strong negative correlations with the strength of the East Asian Summer monsoon. Accounting for sulfate, nitrate, ammonium, black carbon, and organic carbon aerosols, the summer surface-layer PM2.5 concentration averaged over eastern China (110°-125°E, 20°-45°N) can be 17.7% higher in the weakest monsoon years than in the strongest monsoon years. The weakening of the East Asian Summer monsoon increases aerosol concentrations mainly by the changes in atmospheric circulation (the convergence of air pollutants) in eastern China.
Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment.
Català, Raquel; Cabré, Anna; Hernández-Flix, Salvador; Ferré, Raimón; Sangenís, Sandra; Plana, Núria; Texidó, Anna; Masana, Lluís
2013-12-01
To evaluate circulating adipocyte and epidermal fatty acid-binding protein (FABP4 and FABP5) concentrations in patients with obstructive sleep apnea (OSA), as well as the effects of continuous positive airway pressure (CPAP) treatment. Our cross-sectional study included 125 patients. After polysomnography, 58 participants met the criteria for CPAP treatment and were included in a closed cohort study of 8 weeks of CPAP treatment. General anthropometric and biochemical data and circulating FABP4 and FABP5 levels were determined in all patients at baseline and after CPAP treatment in those receiving this therapy. Circulating FABP4 but not FABP5 levels were higher in patients with OSA (P = 0.003). FABP4 but not FABP5 values were associated with parameters of OSA severity independently of age, gender, adiposity and insulin resistance (P < 0.05). FABP4 but not FABP5 concentrations were determinants of OSA presence (OR: 1.11, P = 0.010) and severity (OR: 1.06, P = 0.020). After CPAP treatment, FABP4 levels decreased in the more severe patients (P = 0.019), while FABP5 levels increased in all patients (P < 0.001). FABP4 is directly associated with obstructive sleep apnea severity and did not change with continuous positive airway pressure treatment, while FABP5 was not associated with obstructive sleep apnea severity and increased with continuous positive airway pressure treatment. FABP4 and FABP5 have different associations with obstructive sleep apnea. FABP4 but not FABP5 could be considered a marker of metabolic alterations in obstructive sleep apnea patients.
NASA Astrophysics Data System (ADS)
Pausata, F.; Pozzoli, L.; Van Dingenen, R.; Vignati, E.; Cavalli, F.; Dentener, F. J.
2013-12-01
Ozone pollution and particulate matter (PM) represent a serious health and environmental problem. While ozone pollution is mostly produced by photochemistry in summer, PM is of main concern during winter. Both pollutants can be influenced nt only by local scale processes but also by long range transport driven by the atmospheric circulation and stratospheric ozone intrusions. We analyze the role of large scale atmospheric circulation variability in the North Atlantic basin in determining surface ozone and PM concentrations over Europe. Here, we show, using ground station measurements and a coupled atmosphere-chemistry model simulation for the period 1980-2005, that with regard to ozone the North Atlantic Oscillation (NAO) does affect surface ozone concentrations - on a monthly timescale, over 10 ppbv in southwestern, central and northern Europe - during all seasons except fall. We find that the first Principal Component, computed from the time variation of the sea level pressure (SLP) field, detects the atmosphere circulation/ozone relationship not only in winter and spring but also during summer, when the atmospheric circulation weakens and regional photochemical processes peak. Given the NAO forecasting skill at intraseasonal time scale, the first Principal Component of the SLP field could be used as an indicator to identify areas more exposed to forthcoming ozone pollution events. Finally, our results suggest that the increasing baseline ozone in western and northern Europe during the 1990s could be related to the prevailing positive phase of the NAO in that period. With regard to PM, our study shows that in winter the NAO modulates surface PM concentrations accounting in average up to 30% of the total PM variability. During positive NAO phases, positive PM anomalies occur over southern Europe, and negative anomalies in central-northern Europe. A positve shift of the NAO mean states, hence, leads to an increase in cardiac and resipratory morbidity related to PM exposure in the Mediterranean countries with up to over 5000 more deaths per 20 million people for a 2000 emission inventory.
Complement factor H is expressed in adipose tissue in association with insulin resistance.
Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel
2010-01-01
Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances.
Reappearance of beriberi heart disease in Japan. A study of 23 cases.
Kawai, C; Wakabayashi, A; Matsumura, T; Yui, Y
1980-09-01
Twenty-three Japanese patients with beriberi heart disease, 17 of them teenagers, were studied. The recent tendency for teenagers to take excessive sweet carbonated soft drinks, instant noodles and powermill-polished rice readily induces relative thiamine deficiency. A sudden increase in thiamine requirements due to strenuous exercise can result in overt beriberi heart disease. Alcohol had nothing to do with the development of the disease. Characteristic features commonly seen in teenage patients include peripheral edema, low peripheral vascular resistance, increased venous pressure enlarged heart, T wave abnormalities, hyperkinetic circulatory state and increased circulating blood volume. Thiamine deficiency was confirmed by a decrease in blood thiamine concentration, a decrease in erythrocyte transketolase activity and an increase in thiamine pyrophosphate (TPP) effect. Improvement was rapidly achieved with thiamine administration, balanced nutrition and rest, especially in the teenage patients. Increased circulating blood volume was useful in differentiating beriberi heart disease from hyperthyroidism.
Ibaraki, Masanobu; Shinohara, Yuki; Nakamura, Kazuhiro; Miura, Shuichi; Kinoshita, Fumiko; Kinoshita, Toshibumi
2010-07-01
Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with (15)O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C(a)O(2)), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO(2)) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO(2) was independent of Hb concentration. Oxygen delivery defined as a product of C(a)O(2) and CBF (C(a)O(2) CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO(2). The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the (15)O PET data in clinical practice.
NASA Astrophysics Data System (ADS)
Frouin, Robert; Ueyoshi, Kyozo; Kampel, Milton
2007-09-01
Numerical experiments conducted with an ocean general ocean circulation model reveal the potential influence of solar radiation absorbed by phytoplankton on the thermal structure and currents of the Tropical Atlantic Ocean. In the model, solar radiation penetration is parameterized explicitly as a function of chlorophyll-a concentration, the major variable affecting water turbidity in the open ocean. Two types of runs are performed, a clear water (control) run with a constant minimum chlorophyll-a concentration of 0.02 mgm -3, and a turbid water (chlorophyll) run with space- and time-varying chlorophyll-a concentration from satellite data. The difference between results from the two runs yields the biological effects. In the chlorophyll run, nutrients and biology production are implicitly taken into account, even though biogeochemical processes are not explicitly included, since phytoplankton distribution, prescribed from observations, is the result of those processes. Due to phytoplankton-radiation forcing, the surface temperature is higher by 1-2 K on average annually in the region of the North Equatorial current, the Northern part of the South Equatorial current, and the Caribbean system, and by 3-4 K in the region of the Guinea current. In this region, upwelling is reduced, and heat trapped in the surface layers by phytoplankton is not easily removed. The surface temperature is lower by 1 K in the Northern region of the Benguela current, due to increased upwelling. At depth, the equatorial Atlantic is generally cooler, as well as the eastern part of the tropical basin (excluding the region of the sub-tropical gyres). The North and South equatorial currents, as well as the Equatorial undercurrent, are enhanced by as much as 3-4 cms -1, and the circulation of the subtropical gyres is increased. Pole-ward heat transport is slightly reduced North of 35°N, suggesting that phytoplankton, by increasing the horizontal return flow in the subtropical region, may exert a cooling influence on higher latitude regions. The findings indicate that biology-induced buoyancy plays a significant role, in an indirect if not direct way, in the variability of the Tropical Atlantic Ocean, with consequences on atmospheric circulation and climate.
Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel
2017-11-27
Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.
Laurent, Michaël R.; Hammond, Geoffrey L.; Blokland, Marco; Jardí, Ferran; Antonio, Leen; Dubois, Vanessa; Khalil, Rougin; Sterk, Saskia S.; Gielen, Evelien; Decallonne, Brigitte; Carmeliet, Geert; Kaufman, Jean-Marc; Fiers, Tom; Huhtaniemi, Ilpo T.; Vanderschueren, Dirk; Claessens, Frank
2016-01-01
Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology. PMID:27748448
Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan
2016-06-01
Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Cho, Clara E; Taesuwan, Siraphat; Malysheva, Olga V; Bender, Erica; Tulchinsky, Nathan F; Yan, Jian; Sutter, Jessica L; Caudill, Marie A
2017-01-01
Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome. A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control. Fish yielded higher circulating and urinary concentrations of TMAO (46-62 times; p < 0.0001), trimethylamine (8-14 times; p < 0.0001), and dimethylamine (4-6-times; P<0.0001) than eggs, beef, or the fruit control. Circulating TMAO concentrations were increased within 15 min of fish consumption, suggesting that dietary TMAO can be absorbed without processing by gut microbes. Analysis of 16S rRNA genes indicated that high-TMAO producers (≥20% increase in urinary TMAO in response to eggs and beef) had more Firmicutes than Bacteroidetes (p = 0.04) and less gut microbiota diversity (p = 0.03). Consumption of fish yielded substantially greater increases in circulating TMAO than eggs or beef. The higher Firmicutes to Bacteroidetes enrichment among men exhibiting a greater response to dietary TMAO precursor intake indicates that TMAO production is a function of individual differences in the gut microbiome. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
Pasternak, K; Dabrowski, W; Wyciszczok, T; Korycińska, A; Dobija, J; Biernacka, J; Rzecki, Z
2005-12-01
The effects of procedures with extracorporeal circulation on the disturbance of relationships between blood magnesium (Mg), epinephrine, and norepinephrine levels have not been explicitly explained. It is assumed that both hypomagnesemia and increased concentration of the above mentioned hormones exert adverse effects on the myocardium often causing life threatening disorders. This problem is particularly important in cases of stunned myocardium, observed after extracorporeal circulation procedures. The complex nature of the procedures and the intraoperative normovolemic hemodilution (NH) employed are likely to alter Mg, epinephrine, and norepinephrine concentrations, as well as the above mentioned relations. The aim of the study was to evaluate the changes in blood Mg, epinephrine and norepinephrine concentrations in patients undergoing extracorporeal circulation and normovolemic hemodilution. The study encompassed 16 men operated on for stable coronary disease (I or II degrees according to the Canadian Scale). The patients were divided into two groups according to body weight: A) patients weighing less than 75 kg and B) patients weighing more than 75 kg. The degree of NH caused by constant volume of priming (1800 mL) was determined on the basis of hematocrit measurements and in relation to body weight. The examinations were conducted in 5 stages: 1) after radial artery cannulation before anaesthesia and surgery, 2) during hemodilution and deepest hypothermia, 3) after surgery before sending the patient to Intensive Postoperative care Unit, 4) in the first postoperative day, 5) in the second postoperative day. The observations showed an increase in epinephrine levels in group A in the second stage and of norepinephrine levels in stage 4. Decreased blood Mg levels were noted in all the patients in the second stage, however in group A significantly lower values were also observed in stage 3. Moreover, the correlation between Mg level changes and blood epinephrine and norepinephrine levels were observed. The study revealed significant effects of extracorporeal circulation procedures on adrenergic reactions as well as blood magnesium concentrations. It seems that the degree of NH is the main factor determining blood levels of Mg, epinephrine and norepinephrine during the use of a heart-lung apparatus, which may be particularly relevant in patients with impaired heart function and low body weight.
Hypolipidemic effect of hemicellulose component of coconut fiber.
Sindhurani, J A; Rajamohan, T
1998-08-01
The neutral detergent fiber (NDF) isolated from coconut kernel was digested with cellulase and hemicellulase and the residual fiber rich in hemicellulose (without cellulose) and cellulose (with out hemicellulose) were fed to rats and compared with a fiber free group. The results indicate that hemicellulose rich fiber showed decreased concentration of total cholesterol, LDL + VLDL cholesterol and increased HDL cholesterol, while cellulose rich fiber showed no significant alteration. There was increased HMG CoA reductase activity and increased incorporation of labeled acetate into free cholesterol. Rats fed hemicellulose rich coconut fiber produced lower concentration of triglycerides and phospholipids and lower release of lipoproteins into circulation. There was increased concentration of hepatic bile acids and increased excretion of faecal sterols and bile acids. These results indicate that the hemicellulose component of coconut fiber was responsible for the observed hypolipidemic effect.
Effects of an iodine-restricted food on client-owned cats with hyperthyroidism.
van der Kooij, Marieke; Bečvářová, Iveta; Meyer, Hein P; Teske, Erik; Kooistra, Hans S
2014-06-01
The objective of this prospective, multicentre, non-controlled, open-label study was to evaluate the effects of an iodine-restricted food on circulating total thyroxine (TT4) concentrations and clinical parameters in client-owned cats with hyperthyroidism. Two hundred and twenty-five cats were enrolled in the study and adapted to the iodine-restricted food. Data from physical examinations, questionnaires completed by veterinarians and owners, and circulating concentrations of TT4, urea and creatinine were recorded at weeks 0, 4 and 8. The study group included 136 female and 89 male cats (median age 15 years, range 4-21 years). Group 1 (n = 113) had been on previous anti-thyroid medication, while group 2 (n = 112) consisted of newly diagnosed cats. No differences were found between the two groups at any time point. Circulating TT4 concentrations had decreased (P <0.0001) at week 4 and did not change significantly from week 4 to week 8. Circulating TT4 concentration was within the reference range in 56/88 cats at week 4 and in 51/68 cats at week 8. Clinical parameters (vomiting, polyuria, polydipsia, hyperactivity, polyphagia, weight loss, hair coat quality, and quality of life) had improved (P <0.0001) by week 4. Circulating creatinine concentration decreased (P = 0.001) from week 0 to week 4. Side effects associated with feeding the iodine-restricted food were not observed. In conclusion, in client-owned cats with hyperthyroidism an iodine-restricted food is a valuable management option to normalise circulating TT4 concentrations, and improve clinical signs of hyperthyroidism within 4 weeks. This applies to newly diagnosed cats, as well as to previously diagnosed cats receiving anti-thyroid drugs. © ISFM and AAFP 2013.
Rinaldi, Sabina; Biessy, Carine; de la Luz Hernandez, Maria; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle
2015-03-01
Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.
MOORE, BRANDON C.; KOHNO, SATOMI; COOK, ROBERT W.; ALVERS, ASHLEY L.; HAMLIN, HEATHER J.; WOODRUFF, TERESA K.; GUILLETTE, LOUIS J.
2014-01-01
Activins and estrogens participate in regulating the breakdown of ovarian germ cell nests and follicle assembly in mammals. In 1994, our group reported elevated frequencies of abnormal, multioocytic ovarian follicles in 6 month old, environmental contaminant-exposed female alligators after gonadotropin challenge. Here, we investigated if maternal contribution of endocrine disrupting contaminants to the egg subsequently alters estrogen/inhibin/activin signaling in hatchling female offspring, putatively predisposing an increased frequency of multioocytic follicle formation. We quantified basal and exogenous gonadotropin-stimulated concentrations of circulating plasma steroid hormones and ovarian activin signaling factor mRNA abundance in hatchling alligators from the same contaminated (Lake Apopka) and reference (Lake Woodruff) Florida lakes, as examined in 1994. Basal circulating plasma estradiol and testosterone concentrations were greater in alligators from the contaminated environment, whereas activin/inhibin βA subunit and follistatin mRNA abundances were lower than values measured in ovaries from reference lake animals. Challenged, contaminant-exposed animals showed a more robust increase in plasma estradiol concentration following an acute follicle stimulating hormone (FSH) challenge compared with reference site alligators. Aromatase and follistatin mRNA levels increased in response to an extended FSH challenge in the reference site animals, but not in the contaminant-exposed animals. In hatchling alligators, ovarian follicles have not yet formed; therefore, these endocrine differences are likely to affect subsequent ovarian development, including ovarian follicle assembly. PMID:20166196
Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings
DOE Office of Scientific and Technical Information (OSTI.GOV)
Garcia, J.F.; Ebbe, S.N.; Hollander, L.
1982-05-01
Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay 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 showmore » a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or 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 RA in the hematology clinic, which will most certainly be expanded with its more extensive use.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Juarez de Ku, L.M.
1992-01-01
Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than ormore » in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.« less
Moro, H
1992-01-01
Renal hemodynamics during IABP-assisted pulsatile flow extracorporeal circulation was assessed in terms of measurement values for intraoperative renal blood flow obtained by the local thermodilution method in human clinical patients. In addition, the effect of IABP on renal hemodynamics was investigated in an animal model of renal denervation in a study undertaken to elucidate the action mechanism of IABP. Eighteen patients with acquired heart disease were involved in the study and measured for the renal blood flow (RBF), cardiac output (CO), renal-systemic partition coefficient for blood flow (RBF/CO), renal vascular resistance (RVR) and perfusion pressure. In the pulsatile flow group, the RBF/CO increased as the number of pump runs increased, whole the RVR was conversely reduced with increasing pump runs. The experimental study without extracorporeal circulation was conducted on 19 mongrel dogs. During IABP runs RBF/CO increased, while the RVR decreased. After renal denervation, no noticeable influence of IABP upon renal hemodynamics was observed. Following a loading dose of noradrenaline (Norad), the RVR increased in a Norad concentration-dependent fashion, independently of IABP and renal denervation. These results indicate that IABP reduces the RVR and thereby exerts a favorable action on renal hemodynamics during pump times. The study thus warrants us to surmise that a mechanism involving the renal sympathetic nerves might play an important role in the production of favorable renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation.
Exocrine and endocrine release of kallikrein after reflex-induced salivary secretion.
Berg, T; Johansen, L; Poulsen, K
1990-05-01
Exocrine and endocrine release of rat submandibular gland kallikrein has been shown to be low after parasympathetic and beta-adrenergic stimulation but greatly increased after alpha-adrenergic stimulation. In the present study, release of glandular kallikrein was investigated under conditions known to give a reflex-induced salivary gland response. Heat stress induced a rich flow of saliva originating in the submandibular glands. Salivary kallikrein secretory rate was higher than after parasympathetic stimulation but lower than after sympathetic stimulation (P less than 0.005). Only heat stress increased circulating glandular kallikrein (12.7 +/- 0.8 ng ml-1 before heat exposure and 53.3 +/- 14.1 ng ml-1 40 min afterwards, P less than 0.005). There were no indications that the endocrine release of kallikrein was due to non-specific leakage. Atropine abolished heat-induced salivation and endocrine kallikrein secretion, possibly through interference with central pathways (P less than 0.05). However, phentolamine did not, which may indicate as an yet unidentified mediator of endogenous kallikrein release. The salivary gland response to acid and ether was comparable to that observed after parasympathetic nerve stimulation and was abolished by atropine (P less than 0.005). Stimuli known to influence other salivary gland ductal cells, such as aggression and starvation followed by drinking, also did not increase the plasma concentration of glandular kallikrein. The fact that various conditions which induce salivation did not increase circulating glandular kallikrein, coupled with the fact that kallikrein concentration was the highest in animals that died from heat stress, may suggest that the increase in circulating glandular kallikrein seen after heat stress may be pathological and could contribute to the development of heat shock.
Li, Junjie; Zhang, Weixia; Chung, Ting-Fung; Slipchenko, Mikhail N; Chen, Yong P; Cheng, Ji-Xin; Yang, Chen
2015-07-23
We report a transient absorption (TA) imaging method for fast visualization and quantitative layer analysis of graphene and GO. Forward and backward imaging of graphene on various substrates under ambient condition was imaged with a speed of 2 μs per pixel. The TA intensity linearly increased with the layer number of graphene. Real-time TA imaging of GO in vitro with capability of quantitative analysis of intracellular concentration and ex vivo in circulating blood were demonstrated. These results suggest that TA microscopy is a valid tool for the study of graphene based materials.
Mesoscale simulations of atmospheric flow and tracer transport in Phoenix, Arizona
NASA Astrophysics Data System (ADS)
Wang, Ge; Ostoja-Starzewski, Martin
2006-09-01
Large urban centres located within confining rugged or complex terrain can frequently experience episodes of high concentrations of lower atmospheric pollution. Metropolitan Phoenix, Arizona (United States), is a good example, as the general population is occasionally subjected to high levels of lower atmospheric ozone, carbon monoxide and suspended particulate matter. As a result of dramatic but continuous increase in population, the accompanying environmental stresses and the local atmospheric circulation that dominates the background flow, an accurate simulation of the mesoscale pollutant transport across Phoenix and similar urban areas is becoming increasingly important. This is particularly the case in an airshed, such as that of Phoenix, where the local atmospheric circulation is complicated by the complex terrain of the area.
The Impact of Carbon Dioxide on Climate.
ERIC Educational Resources Information Center
MacDonald, Gordon J.
1979-01-01
Examines the relationship between climatic change and carbon dioxide from the historical perspective; details the contributions of carbon-based fuels to increasing carbon dioxide concentrations; and using global circulation models, discusses the future impact of the heavy reliance of our society on carbon-based fuels on climatic change. (BT)
USDA-ARS?s Scientific Manuscript database
Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentration...
Alterations in the response of pigs to Salmonella typhimurium when provided Enterobacter cloacae
USDA-ARS?s Scientific Manuscript database
Weanling pigs are at risk of succumbing to illness due to an immature immune system and insufficient supply of available energy at the time of weaning. Recent evidence has suggested that providing pigs with Enterobacter cloacae can increase the concentration of circulating triglycerides (TAGs) and t...
Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.
Yende, Sachin; D'Angelo, Gina; Kellum, John A; Weissfeld, Lisa; Fine, Jonathan; Welch, Robert D; Kong, Lan; Carter, Melinda; Angus, Derek C
2008-06-01
Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown. To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes. Prospective cohort study at 28 sites. We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008). Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.
Increased plasma ghrelin suppresses insulin release in wethers fed with a high-protein diet.
Takahashi, T; Sato, K; Kato, S; Yonezawa, T; Kobayashi, Y; Ohtani, Y; Ohwada, S; Aso, H; Yamaguchi, T; Roh, S G; Katoh, K
2014-06-01
Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein (HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet. © 2014 Society for Endocrinology.
Anti-Müllerian Hormone (AMH) and fertility management in agricultural species.
Mossa, F; Jimenez-Krassel, F; Scheetz, D; Weber-Nielsen, M; Evans, A C O; Ireland, J J
2017-07-01
A reliable, easy to assess marker for fertility in agricultural species would be highly desirable and Anti-Müllerian Hormone (AMH) is a promising candidate. This review summarizes recent findings concerning AMH and its role in fertility management, mainly in cattle. It focuses on (1) alterations in circulating AMH concentrations from birth to puberty and during estrous cycles; (2) correlation of circulating AMH concentrations with ovarian follicle numbers and ovarian reserve; (3) factors that impact circulating AMH concentrations; (4) use of AMH as a predictor of fertility. Circulating AMH concentrations can be easily and reliably measured with a single blood sample in adult cattle because AMH varies minimally during the estrous cycle and is repeatable across multiple cycles. Circulating AMH concentrations are positively associated with several measures of fertility. Dairy heifers with low compared with higher AMH concentrations subsequently had lower pregnancy rates, higher probability of being culled after birth of their first calf and shorter herd longevity. Also, AMH is predictive of response to superovulation in cattle and sheep. Several factors contribute to the variability in AMH concentrations among individuals; for example, beef cattle have higher AMH than dairy cattle. Nutritional imbalances, disease and endocrine disruptors during fetal life may negatively program the size of the ovarian reserve and consequently serum AMH concentrations and potential fertility in adulthood. We conclude that AMH may be a predictor of fertility and herd longevity in cattle, whereas in sheep and other farm species, the potential association between AMH and reproductive performance remains largely unexplored.Free Italian abstract: An Italian translation of this abstract is freely available at http://www.reproduction-online.org/content/154/1/R1/suppl/DC1. © 2017 Society for Reproduction and Fertility.
ERIC Educational Resources Information Center
Weiss, Craig; Sametsky, Evgeny; Sasse, Astrid; Spiess, Joachim; Disterhoft, John F.
2005-01-01
The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned…
Jones, G.D.; Whitaker, F.F.; Smart, P.L.; Sanford, W.E.
2004-01-01
Density-driven seawater circulation may occur in carbonate platforms due to geothermal heating and / or reflux of water of elevated salinity. In geothermal circulation lateral contrasts in temperature between seawater and platform groundwaters warmed by the geothermal heat flux result in upward convective flow, with colder seawater drawn into the platform at depth. With reflux circulation, platform-top waters concentrated by evaporation flow downward, displacing less dense underlying groundwaters. We have used a variable density groundwater flow model to examine the pattern, magnitude and interaction of these two different circulation mechanisms, for mesosaline platform-top waters (50???) and brines concentrated up to saturation with respect to gypsum (150???) and halite (246???). Geothermal circulation, most active around the platform margin, becomes restricted and eventually shut-off by reflux of brines from the platform interior towards the margin. The persistence of geothermal circulation is dependent on the rate of brine reflux, which is proportional to the concentration of platform-top brines and also critically dependent on the magnitude and distribution of permeability. Low permeability evaporites can severely restrict reflux whereas high permeability units in hydraulic continuity enhance brine transport. Reduction in permeability with depth and anisotropy of permeability (kv < < kh) focuses flow laterally in the shallow subsurface (<1 km), resulting in a horizontally elongated brine plume. Aquifer porosity and dispersivity are relatively minor controls on reflux. Platform brines can entrain surficial seawater when brine generating conditions cease but the platform-top remains submerged, a variant of reflux we term "latent reflux". Brines concentrated up to gypsum saturation have relatively long residence times of at least 100 times the duration of the reflux event. They thus represent a long-term control on post-reflux groundwater circulation, and consequently on the rates and spatial patterns of shallow burial diagenesis, such as dolomitization.
Ortega, Francisco J; Cardona-Alvarado, Mónica I; Mercader, Josep M; Moreno-Navarrete, José M; Moreno, María; Sabater, Mònica; Fuentes-Batllevell, Núria; Ramírez-Chávez, Enrique; Ricart, Wifredo; Molina-Torres, Jorge; Pérez-Luque, Elva L; Fernández-Real, José M
2015-10-01
Consumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). The profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 (P=.01) and ω-6 (P=.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased (P=.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b (r=0.58, P=.003) and miR-221 (r=0.46, P=.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides (r=-0.44, P=.019) and increased adiponectin (r=0.43, P=.026). Dietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet. Copyright © 2015. Published by Elsevier Inc.
Circulating FABP4 and FABP5 Levels Are Differently Linked to OSA Severity and Treatment
Català, Raquel; Cabré, Anna; Hernández-Flix, Salvador; Ferré, Raimón; Sangenís, Sandra; Plana, Núria; Texidó, Anna; Masana, Lluís
2013-01-01
Objective: To evaluate circulating adipocyte and epidermal fatty acid-binding protein (FABP4 and FABP5) concentrations in patients with obstructive sleep apnea (OSA), as well as the effects of continuous positive airway pressure (CPAP) treatment. Methods: Our cross-sectional study included 125 patients. After polysomnography, 58 participants met the criteria for CPAP treatment and were included in a closed cohort study of 8 weeks of CPAP treatment. General anthropometric and biochemical data and circulating FABP4 and FABP5 levels were determined in all patients at baseline and after CPAP treatment in those receiving this therapy. Results Circulating FABP4 but not FABP5 levels were higher in patients with OSA (P = 0.003). FABP4 but not FABP5 values were associated with parameters of OSA severity independently of age, gender, adiposity and insulin resistance (P < 0.05). FABP4 but not FABP5 concentrations were determinants of OSA presence (OR: 1.11, P = 0.010) and severity (OR: 1.06, P = 0.020). After CPAP treatment, FABP4 levels decreased in the more severe patients (P = 0.019), while FABP5 levels increased in all patients (P < 0.001). Conclusions FABP4 is directly associated with obstructive sleep apnea severity and did not change with continuous positive airway pressure treatment, while FABP5 was not associated with obstructive sleep apnea severity and increased with continuous positive airway pressure treatment. FABP4 and FABP5 have different associations with obstructive sleep apnea. FABP4 but not FABP5 could be considered a marker of metabolic alterations in obstructive sleep apnea patients. Citation: Català R; Cabré A; Hernández-Flix S; Ferré R; Sangenís S; Plana N; Texidó A; Masana L. Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment. SLEEP 2013;36(12):1831-1837. PMID:24293757
Saande, Cassondra J; Jones, Samantha K; Hahn, Kaylee E; Reed, Carter H; Rowling, Matthew J; Schalinske, Kevin L
2017-09-01
Background: Type 2 diabetes (T2D) is characterized by vitamin D insufficiency owing to excessive urinary loss of 25-hydroxycholecalciferol [25(OH)D]. We previously reported that a diet containing dried whole egg, a rich source of vitamin D, was effective at maintaining circulating 25(OH)D concentrations in rats with T2D. Furthermore, whole egg consumption reduced body weight gain in rats with T2D. Objective: This study was conducted to compare whole egg consumption with supplemental cholecalciferol with respect to vitamin D balance, weight gain, and body composition in rats with T2D. Methods: Male Zucker diabetic fatty (ZDF) rats ( n = 24) and their lean controls ( n = 24) were obtained at 5 wk of age and randomly assigned to 3 treatment groups: a casein-based diet (CAS), a dried whole egg-based diet (WE), or a casein-based diet containing supplemental cholecalciferol (CAS+D) at the same amount of cholecalciferol provided by WE (37.6 μg/kg diet). Rats were fed their respective diets for 8 wk. Weight gain and food intake were measured daily, circulating 25(OH)D concentrations were measured by ELISA, and body composition was analyzed by dual X-ray absorptiometry. Results: Weight gain and percentage of body fat were reduced by ∼20% and 11%, respectively, in ZDF rats fed WE compared with ZDF rats fed CAS or CAS+D. ZDF rats fed CAS had 21% lower serum 25(OH)D concentrations than lean rats fed CAS. In ZDF rats, WE consumption increased serum 25(OH)D concentrations 130% compared with CAS, whereas consumption of CAS+D increased serum 25(OH)D concentrations 35% compared with CAS. Conclusions: Our data suggest that dietary consumption of whole eggs is more effective than supplemental cholecalciferol in maintaining circulating 25(OH)D concentrations in rats with T2D. Moreover, whole egg consumption attenuated weight gain and reduced percentage of body fat in ZDF rats. These data may support new dietary recommendations targeting the prevention of vitamin D insufficiency in T2D. © 2017 American Society for Nutrition.
Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer
Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L.; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N.
2010-01-01
Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974–2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50–<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (≥100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185
Ceriello, A; Giugliano, D; Quatraro, A; Marchi, E; Barbanti, M; Lefebvre, P
1990-04-01
In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.
Burks, Scott R.; Legenzov, Eric A.; Rosen, Gerald M.
2011-01-01
Electron paramagnetic resonance (EPR) imaging using nitroxides as molecular probes is potentially a powerful tool for the detection and physiological characterization of micrometastatic lesions. Encapsulating nitroxides in anti-HER2 immunoliposomes at high concentrations to take advantage of the “self-quenching” phenomenon of nitroxides allows generation of robust EPR signals in HER2-overexpressing breast tumor cells with minimal background from indifferent tissues or circulating liposomes. We investigated the in vivo pharmacological properties of nitroxides encapsulated in sterically stabilized liposomes designed for long circulation times. We show that circulation times of nitroxides can be extended from hours to days; this increases the proportion of liposomes in circulation to enhance tumor targeting. Furthermore, nitroxides encapsulated in sterically stabilized anti-HER2 immunoliposomes can be delivered to HER2-overexpressing tumors at micromolar concentrations, which should be imageable by EPR. Lastly, after in vivo administration, liposomally encapsulated nitroxide signal also appears in the liver, spleen, and kidneys. Although these organs are spatially distinct and would not hinder tumor imaging in our model, understanding nitroxide signal retention in these organs is essential for further improvements in EPR imaging contrast between tumors and other tissues. These results lay the foundation to use liposomally delivered nitroxides and EPR imaging to visualize tumor cells in vivo. PMID:21737567
Garg, Mayur; Burrell, Louise M; Velkoska, Elena; Griggs, Karen; Angus, Peter W; Gibson, Peter R; Lubel, John S
2015-09-01
The relationship between intestinal inflammation and circulating components of the renin-angiotensin system (RAS) is poorly understood. Demographic and clinical data were obtained from healthy controls and patients with inflammatory bowel disease (IBD). Plasma concentrations of the classical RAS components (angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)) and alternative RAS components (ACE2 and angiotensin (1-7) (Ang (1-7))) were analysed by radioimmuno- and enzymatic assays. Systemic inflammation was assessed using serum C-reactive protein (CRP), white cell count, platelet count and albumin, and intestinal inflammation by faecal calprotectin. Nineteen healthy controls (11 female; mean age 38 years, range 23-68), 19 patients with Crohn's disease (11 female; aged 45 years, range 23-76) and 15 patients with ulcerative colitis (6 female; aged 42 years, 26-64) were studied. Circulating classical RAS component levels were similar across the three groups, whereas ACE2 activity and Ang (1-7) concentrations were higher in patients with IBD compared to controls (ACE2: 21.5 vs 13.3 pmol/ml/min, p<0.05; Ang (1-7): 22.8 vs 14.1 pg/ml, p<0.001). Ang (1-7) correlated weakly with platelet and white cell counts, but not calprotectin or CRP, in patients with IBD. Circulating components of the alternative RAS are increased in patients with IBD. © The Author(s) 2014.
Whole-Body Vibrations Do Not Elevate the Angiogenic Stimulus when Applied during Resistance Exercise
Beijer, Åsa; Rosenberger, André; Bölck, Birgit; Suhr, Frank; Rittweger, Jörn; Bloch, Wilhelm
2013-01-01
Knowledge about biological factors involved in exercise-induced angiogenesis is to date still scanty. The present study aimed to investigate the angiogenic stimulus of resistance exercise with and without superimposed whole-body vibrations. Responses to the exercise regimen before and after a 6-week training intervention were investigated in twenty-six healthy male subjects. Serum was collected at the initial and final exercise sessions and circulating levels of matrix metalloproteinases (MMP) -2 and -9, Vascular Endothelial Growth Factor (VEGF) and endostatin were determined via ELISA. Furthermore, we studied the proliferative effect of serum-treated human umbilical vein endothelial cells in vitro via BrdU-incorporation assay. It was found that circulating MMP-2, MMP-9, VEGF and endostatin levels were significantly elevated (P<0.001) from resting levels after both exercise interventions, with higher post-exercise VEGF concentrations in the resistance exercise (RE) group compared to the resistive vibration exercise (RVE) group. Moreover, RE provoked increased endothelial cell proliferation in vitro and higher post-exercise circulating endostatin concentrations after 6 weeks of training. These effects were elusive in the RVE group. The present findings suggest that resistance exercise leads to a transient rise in circulating angiogenic factors and superimposing vibrations to this exercise type might not further trigger a potential signaling of angiogenic stimulation in skeletal muscle. PMID:24260349
NASA Astrophysics Data System (ADS)
Lee, B. Y.; Lee, C. H.; KIm, K. T.
2016-02-01
Since 2012 to present, the Tidal Power Plant (TPP) has been operated in Shihwa Coastal Reservoir (SCR) to improve the water quality. The tidal mixing volume increased about 5 times from 0.03 to 0.16 billion ton/day which represents about 50% of the SCR water volume. Water quality monitoring data showed that it break a strong stratification and hypoxia (≤3 mg/L Dissolved Oxygen) during summer season in main tidal channel. In addition, Total Phosphorus (TP), Total Nitrogen (TN) and Chemical Oxygen Demand concentrations in the main tidal channel reached to similar level with outside SCR concentrations. However, inner area with limited tidal mixing has not experienced improvement in TN and TP concentrations after the TPP operation. Trophic State Index (TSI) which was composite index of trophic condition also kept high score (>50) and remained in eutrophic state especially in summer season. Overall, an increase of seawater circulation has a positive effect on water quality in main tidal channel but not in inner area because of limited seawater mixing and effects of stormwater runoff. The stormwater runoff should be properly managed in this case because most point source pollution load is discharged outside of SCR. Acknowledgement : This research was a part of the project titled 'Development of integrated estuarine management system', funded by the Ministry of Oceans and Fisheries, Korea
Induction of the 72 kDa heat shock protein by glucose ingestion in black pregnant women.
Jaffe, Shirlee; Doulaveris, Georgios; Orfanelli, Theofano; Arantes, Mariana; Damasceno, Débora; Calderon, Iracema; Rudge, Marilza V C; Witkin, Steven S
2013-07-01
Obese Black women are at increased risk for development of gestational diabetes mellitus and have worse perinatal outcomes than do obese women of other ethnicities. Since hsp72 has been associated with the regulation of obesity-induced insulin resistance, we evaluated associations between glucose ingestion, hsp72 release and insulin production in Black pregnant women. Specifically, the effect of a 50-g glucose challenge test (GCT) on heat shock protein and insulin levels in the circulation 1 h later was evaluated. Hsp27 and hsp60 levels remained unchanged. In contrast, serum levels of hsp72 markedly increased after glucose ingestion (p = 0.0054). Further analysis revealed that this increase was limited to women who were not obese (body mass index <30). Insulin levels pre-GCT were positively correlated with body mass index (p = 0.0189). Median insulin concentrations also increased post GCT in non-obese women but remained almost unchanged in obese women. Post-GCT serum hsp72 concentrations were inversely correlated with post GCT insulin concentrations (p = 0.0111). These observations suggest that glucose intake during gestation in Black women rapidly leads to an elevation in circulating hsp72 only in non-obese Black women. The release of hsp72 may regulate the extent of insulin production in response to a glucose challenge and, thereby, protect the mother and/or fetus from development of hyperglycemia, hyperinsulinemia, and/or immune system alterations.
Gomes-Santos, Igor Lucas; Fernandes, Tiago; Couto, Gisele Kruger; Ferreira-Filho, Julio César Ayres; Salemi, Vera Maria Cury; Fernandes, Fernanda Barrinha; Casarini, Dulce Elena; Brum, Patricia Chakur; Rossoni, Luciana Venturini; de Oliveira, Edilamar Menezes; Negrao, Carlos Eduardo
2014-01-01
Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.
[Circulating endothelial progenitor cell levels in treated hypertensive patients].
Maroun-Eid, C; Ortega-Hernández, A; Abad, M; García-Donaire, J A; Barbero, A; Reinares, L; Martell-Claros, N; Gómez-Garre, D
2015-01-01
Most optimally treated hypertensive patients still have an around 50% increased risk of any cardiovascular event, suggesting the possible existence of unidentified risk factors. In the last years there has been evidence of the essential role of circulating endothelial progenitor cells (EPCs) in the maintenance of endothelial integrity and function, increasing the interest in their involvement in cardiovascular disease. In this study, the circulating levels of EPCs and vascular endothelial growth factor (VEGF) are investigated in treated hypertensive patients with adequate control of blood pressure (BP). Blood samples were collected from treated hypertensive patients with controlled BP. Plasma levels of EPCs CD34+/KDR+ and CD34+/VE-cadherin+ were quantified by flow cytometry. Plasma concentration of VEGF was determined by ELISA. A group of healthy subjects without cardiovascular risk factors was included as controls. A total of 108 hypertensive patients were included (61±12 years, 47.2% men) of which 82.4% showed BP<140/90 mmHg, 91.7% and 81.5% controlled diabetes (HbA1c <7%) and cLDL (<130 or 100 mg/dL), respectively, and 85.2% were non-smokers. Around 45% of them were obese. Although patients had cardiovascular parameters within normal ranges, they showed significantly lower levels of CD34+/KDR+ and CD34+/VE-cadherin+ compared with healthy control group, although plasma VEGF concentration was higher in patients than in controls. Despite an optimal treatment, hypertensive patients show a decreased number of circulating EPCs that could be, at least in part, responsible for their residual cardiovascular risk, suggesting that these cells could be a therapeutic target. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.
The Acid-Secreting Parietal Cell as an Endocrine Source of Sonic Hedgehog During Gastric Repair
Engevik, Amy C.; Feng, Rui; Yang, Li
2013-01-01
Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Despite its known function in tissue regeneration, the role of Shh secreted from the gastric epithelium during tissue repair in the stomach remains unknown. Here we tested the hypothesis that Shh secreted from the acid-secreting parietal cell is a fundamental circulating factor that drives gastric repair. A mouse model expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated using animals bearing loxP sites flanking exon 2 of the Shh gene (Shhflx/flx) and mice expressing a Cre transgene under the control of the H+,K+-ATPase β-subunit promoter. Shhflx/flx, the H+,K+-ATPase β-subunit promoter, and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury. At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood samples were collected. Parabiosis experiments were used to establish the effect of circulating Shh on ulcer repair. Control mice exhibited an increased expression of Shh in the gastric tissue and plasma that correlated with the repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis experiment whereby a control mouse was paired with a PC-ShhKO littermate and both animals subjected to gastric injury, a significant increase in the circulating Shh was measured in both parabionts. Elevated circulating Shh concentrations correlated with the repair of gastric ulcers in the PC-ShhKO parabionts. Therefore, the acid-secreting parietal cell within the stomach acts as an endocrine source of Shh during repair. PMID:24092639
Complement Factor H Is Expressed in Adipose Tissue in Association With Insulin Resistance
Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel
2010-01-01
OBJECTIVE Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. RESEARCH DESIGN AND METHODS Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. RESULTS Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. CONCLUSIONS Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances. PMID:19833879
Lu, Wei-Qun; Qiu, Ji-Liang; Huang, Zhi-Liang; Liu, Hai-Ying
2016-12-20
The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67-2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43-1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08-2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01-2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03-4.65) and 49% (95% CI: 1.01-6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.
Insulin regulates the novel adipokine adipolin/CTRP12: in vivo and ex vivo effects.
Tan, Bee K; Lewandowski, Krzysztof C; O'Hare, Joseph Paul; Randeva, Harpal S
2014-04-01
There has been intense interest in the adipokines of the C1q complement/TNF-related protein (CTRP) superfamily. Adipolin (CTRP12) has been described as a novel adipokine, abundantly expressed in adipose tissue with insulin-sensitising and anti-inflammatory effects. We wanted to investigate the effects of acute and chronic hyperinsulinaemia on circulating adipolin concentrations (ELISA) via a prolonged insulin-glucose infusion in humans. We also examined the effects of insulin and the insulin sensitiser, rosiglitazone, on adipolin concentrations (western blotting) in human adipose tissue explants. We found that hyperinsulinaemic induction in healthy lean human subjects significantly increased circulating levels of adipolin (P<0.05 and P<0.01). Furthermore, in subcutaneous adipose tissue explants, insulin significantly increased adipolin protein expression and secretion (P<0.05 and P<0.01). This effect was attenuated by the phosphatidylinositol 3-kinase inhibitor, LY294002 (P<0.05). Moreover, the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) agonist, rosiglitazone, significantly increased adipolin protein expression and secretion in subcutaneous adipose tissue explants (P<0.05 and P<0.01). This effect was inhibited by the PPARγ antagonist, GW9662 (P<0.05). Our data provide novel insights into adipolin physiology in human subjects.
de Moura, R; Lopes, M A
1995-01-01
1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485
Olszanecka-Glinianowicz, Magdalena; Owczarek, Aleksander; Bożentowicz-Wikarek, Maria; Brzozowska, Aniceta; Mossakowska, Małgorzata; Zdrojewski, Tomasz; Grodzicki, Tomasz; Więcek, Andrzej; Chudek, Jerzy
2014-11-01
Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.
Interference among viruses circulating and administered in Hungary from 1931 to 2008.
Berencsi, Gy; Kapusinszky, Beatrix; Rigó, Zita; Szomor, Katalin
2010-06-01
Viral interference was discovered about 60 years ago. Molecular epidemiology revealed that this phenomenon possesses important biological implications, it can reduce the epidemic spread of certain viruses from time to time (influenza and enteroviruses) and the efficiency of live vaccination can be impaired, too. Phenomena observed during the last 80 years in Hungary are analyzed. It is suggested to concentrate the distribution of MMR vaccines to seasons of limited influenza and enterovirus circulation. Interference seems to impair the progress of wild poliovirus eradication in the endemic tropical countries. It is recommended to enhance enterovirus surveillance in the region of European countries, since the exchange of the oral poliovirus vaccine to the enhanced inactivated polio vaccine might result in enhanced circulation of non-polio enteroviruses leading to the increase in the number of type I (juvenile) diabetes patients.
Stress hormone levels in a freshwater turtle from sites differing in human activity.
Polich, Rebecca L
2016-01-01
Glucocorticoids, such as corticosterone (CORT), commonly serve as a measure of stress levels in vertebrate populations. These hormones have been implicated in regulation of feeding behaviour, locomotor activity, body mass, lipid metabolism and other crucial behaviours and physiological processes. Thus, understanding how glucocorticoids fluctuate seasonally and in response to specific stressors can yield insight into organismal health and the overall health of populations. I compared circulating CORT concentrations between two similar populations of painted turtle, Chrysemys picta, which differed primarily in the level of exposure to human recreational activities. I measured basal CORT concentrations as well as the CORT stress response and did not find any substantive difference between the two populations. This similarity may indicate that painted turtles are not stressed by the presence of humans during the nesting season. The results of this study contribute to our understanding of CORT concentrations in freshwater reptiles, a group that is historically under-represented in studies of circulating hormone concentrations; specifically, studies that seek to use circulating concentrations of stress hormones, such as CORT, as a measure of the effect of human activities on wild populations. They also give insight into how these species as a whole may respond to human recreational activities during crucial life-history stages, such as the nesting season. Although there was no discernable difference between circulating CORT concentrations between the urban and rural populations studied, I did find a significant difference in circulating CORT concentrations between male and female C. picta. This important finding provides better understanding of the sex differences between male and female painted turtles and adds to our understanding of this species and other species of freshwater turtle.
Bielohuby, Maximilian; Popp, Sarah; Bidlingmaier, Martin
2012-01-01
Researchers analyse hormones to draw conclusions from changes in hormone concentrations observed under specific physiological conditions and to elucidate mechanisms underlying their biological variability. It is, however, frequently overlooked that also circumstances occurring after collection of biological samples can significantly affect the hormone concentrations measured, owing to analytical and pre-analytical variability. Whereas the awareness for such potential confounders is increasing in human laboratory medicine, there is sometimes limited consensus about the control of these factors in rodent studies. In this guide, we demonstrate how such factors can affect reliability and consequent interpretation of the data from immunoassay measurements of circulating metabolic hormones in rodent studies. We also compare the knowledge about such factors in rodent studies to recent recommendations established for biomarker studies in humans and give specific practical recommendations for the control of pre-analytical conditions in metabolic studies in rodents. PMID:24024118
Charcoal deposition and redeposition in Elk Lake, Minnesota, USA
Platt, Bradbury J.
1996-01-01
Sedimentary charcoal, diatom and phytolith records of the past 1500 years at Elk Lake, Minnesota, in combination with sediment trap studies and a transect of surface sediment samples, document the mechanisms by which previously deposited charcoal is redeposited and finally buried in this lake. The frequent correspondence of high diatom concentrations and peaks of phytolith and charcoal fragments suggest that currents and turbulence related to lake circulation are responsible for winnowing charcoal and phytoliths from shallow water depositional sites to deeper areas of the lake. High diatom concentrations in the record relate to increased nutrient fluxes also supplied by circulation. Despite the fact that the watershed and area around Elk Lake has not been burned since AD 1922, charcoal continues to reach the profundal zone from littoral source areas in Elk Lake. The variable redeposition of within-lake charcoal requires evaluation before fire-history records can be related to global, regional or even local fire events.
Internal flow inside droplets within a concentrated emulsion during droplet rearrangement
NASA Astrophysics Data System (ADS)
Leong, Chia Min; Gai, Ya; Tang, Sindy K. Y.
2018-03-01
Droplet microfluidics, in which each droplet serves as a micro-reactor, has found widespread use in high-throughput biochemical screening applications. These droplets are often concentrated at various steps to form a concentrated emulsion. As part of a serial interrogation and sorting process, such concentrated emulsions are typically injected into a tapered channel leading to a constriction that fits one drop at a time for the probing of droplet content in a serial manner. The flow physics inside the droplets under these flow conditions are not well understood but are critical for predicting and controlling the mixing of reagents inside the droplets as reactors. Here we investigate the flow field inside droplets of a concentrated emulsion flowing through a tapered microchannel using micro-particle image velocimetry. The confining geometry of the channel forces the number of rows of drops to reduce by one at specific and uniformly spaced streamwise locations, which are referred to as droplet rearrangement zones. Within each rearrangement zone, the phase-averaged velocity results show that the motion of the droplets involved in the rearrangement process, also known as a T1 event, creates vortical structures inside themselves and their adjacent droplets. These flow structures increase the circulation inside droplets up to 2.5 times the circulation in droplets at the constriction. The structures weaken outside of the rearrangement zones suggesting that the flow patterns created by the T1 process are transient. The time scale of circulation is approximately the same as the time scale of a T1 event. Outside of the rearrangement zones, flow patterns in the droplets are determined by the relative velocity between the continuous and disperse phases.
Parikh, Samip; Guo, De-huang; Pollock, Norman K.; Petty, Karen; Bhagatwala, Jigar; Gutin, Bernard; Houk, Chris; Zhu, Haidong; Dong, Yanbin
2012-01-01
OBJECTIVE Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population. RESEARCH DESIGN AND METHODS 25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14–18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP). RESULTS Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = −0.32, P < 0.01), fibrinogen (r = −0.05, P = 0.03), glucose (r = −0.16, P = 0.02), HOMA-IR (r = −0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = −0.10, P = 0.02), and diastolic BP (r = −0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates. CONCLUSIONS Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions. PMID:22410810
NASA Astrophysics Data System (ADS)
Bae, Sung Eun
Mares susceptible to persistent mating-induced endometritis (PMIE) accumulate intrauterine fluid after mating. One of the factors causing delayed uterine clearance is thought to be impaired uterine contractility. Oxytocin is central in controlling myometrial contractility. The objective of the present study was to describe peripheral oxytocin release during estrus and in the early postovulatory period in reproductively-normal mares and to compare the baseline circulating oxytocin concentrations in reproductively-normal mares and mares with PMIE. Blood samples were collected from reproductively-normal mares (n=5) from day -5 of estrus to day 2 postovulation and every 5 min for 30 min from reproductively-normal mares (n=5) and mares with PMIE (n=5) on day 3 of estrus. Pulsatile secretion of oxytocin was observed in all mares. Mean plasma oxytocin concentrations were significantly higher (P<0.05) in estrus (day -5 to day -2) than on the day of ovulation (day 0). After ovulation, plasma oxytocin concentrations tended to increase. On day 3 of estrus, plasma oxytocin concentrations were significantly higher (P<0.01) in reproductively-normal mares than in mares with PMIE. The results showed there is a significant difference in plasma oxytocin concentrations between mares to PMIE. The low plasma oxytocin concentrations in mares with PMIE may contribute to predisposing factors in their poor uterine clearance in these mares.
and of patients with sickle cell crisis were examined. It was found that patients with sickle cell anemia show a relative increase of phospholipids in...the ghosts which are enhanced in patients with sickle cell crisis . During sickle cell crisis the concentration of phosphatidylglycerol of blood
[Cardio-thyrotoxicosis with arrhythmia disclosed by an embolic cerebrovascular accident].
Caroff, P; Paris, A; Genco, G; Le Guern, G; Dumas, P
1996-01-01
We report a case of thyroid cardiomyopathy from an iodine overload in a patient admitted for a cerebrovascular accident. The diagnosis was suggested by a hyperkinetic circulatory status and confirmed by the increased circulating thyroid hormone concentrations. Treatment improved the haemodynamic status, however the patient died from a cerebral herniation.
USDA-ARS?s Scientific Manuscript database
During the postnatal feeding period, formula-fed infants have higher cholesterol synthesis rates, and lower circulating cholesterol concentrations as compared to their breastfed counterparts. Although this disparity has been attributed to the uniformly low dietary cholesterol content of typical inf...
Jellyman, Juanita K.; De Blasio, Miles J.; Johnson, Emma; Giussani, Dino A.; Broughton Pipkin, Fiona; Fowden, Abigail L.
2015-01-01
Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155
Zhenyukh, Olha; Civantos, Esther; Ruiz-Ortega, Marta; Sánchez, Maria Soledad; Vázquez, Clotilde; Peiró, Concepción; Egido, Jesús; Mas, Sebastián
2017-03-01
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. In cultured PBMCs, 10mmol/L BCAA increased the production of reactive oxygen species (ROS) via both NADPH oxidase and the mitochondria, and activated Akt-mTOR signalling. By using several inhibitors and activators of these molecular pathways we have described that mTOR activation by BCAA is linked to ROS production and mitochondrial dysfunction. BCAA stimulated the activation of the redox-sensitive transcription factor NF-κB, which resulted in the release of pro-inflammatory molecules, such as interleukin-6, tumor necrosis factor-α, intracellular adhesion molecule-1 or CD40L, and the migration of PBMCs. In conclusion, elevated BCAA blood levels can promote the activation of circulating PBMCs, by a mechanism that involving ROS production and NF-κB pathway activation. These data suggest that high concentrations of BCAA could exert deleterious effects on circulating blood cells and therefore contribute to the pro-inflammatory and oxidative status observed in several pathophysiological conditions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Koestel, Zoe L; Backus, Robert C; Tsuruta, Kaoru; Spollen, William G; Johnson, Sarah A; Javurek, Angela B; Ellersieck, Mark R; Wiedmeyer, Charles E; Kannan, Kurunthachalam; Xue, Jingchuan; Bivens, Nathan J; Givan, Scott A; Rosenfeld, Cheryl S
2017-02-01
Bisphenol A (BPA) is a widely present endocrine disruptor chemical found in many household items. Moreover, this chemical can bioaccumulate in various terrestrial and aquatic sources; thereby ensuring continual exposure of animals and humans. For most species, including humans, diet is considered the primary route of exposure. However, there has been little investigation whether commercial-brands of dog foods contain BPA and potential health ramifications of BPA-dietary exposure in dogs. We sought to determine BPA content within dog food, whether short-term consumption of these diets increases serum concentrations of BPA, and potential health consequences, as assessed by potential hematological, serum chemistry, cortisol, DNA methylation, and gut microbiome changes, in dogs associated with short-term dietary exposure to BPA. Fourteen healthy privately-owned dogs were used in this study. Blood and fecal samples were collected prior to dogs being placed for two-weeks on one of two diets (with one considered to be BPA-free), and blood and fecal samples were collected again. Serum/plasma samples were analyzed for chemistry and hematology profiles, cortisol concentrations, 5-methylcytosine in lymphocytes, and total BPA concentrations. Fecal samples were used for microbiome assessments. Both diets contained BPA, and after two-weeks of being on either diet, dogs had a significant increase in circulating BPA concentrations (pre-samples=0.7±0.15ng/mL, post-samples=2.2±0.15ng/mL, p<0.0001). Elevated BPA concentrations positively correlated with increased plasma bicarbonate concentrations and associated with fecal microbiome alterations. Short-term feeding of canned dog food increased circulating BPA concentrations in dogs comparable to amounts detected in humans, and greater BPA concentrations were associated with serum chemistry and microbiome changes. Dogs, who share our internal and external environments with us, are likely excellent indicators of potential human health concerns to BPA and other environmental chemicals. These findings may also have relevance to aquatic and terrestrial wildlife. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Technical Reports Server (NTRS)
Jenkins, Gregory S.
1993-01-01
Solar energy at the top of the atmosphere (solar constant), rotation rate, and carbon dioxide (CO2) may have varied significantly over Earth's history, especially during the earliest times. The sensitivity of a general circulation model to faster rotation, enhanced CO2 concentration, and reduced solar constant is presented. The control simulation of this study has a solar constant reduced by 10% the present amount, zero land fraction using a swamp ocean surface, CO2 concentrations of 330 ppmv, present-day rotation rate, and is integrated under mean diurnal and seasonal solar forcing. Four sensitivity test are performed under zero land fraction and reduced solar constant conditions by varying the earth's rotation rate atmospheric CO2 concentration and solar constant. The global mean sea surface temperatures (SSTs) compared to the control simulation: were 6.6 K to 12 K higher than the control's global mean temperature of 264.7 K. Sea ice is confined to higher latitudes in each experiment compared to the control, with ice-free areas equatorward of the subtropics. The warm SSTs are associated with a 20% reduction in clouds for the rotation rate experiments and higher CO2 concentrations in the other experiments. These results are in contrast to previous studies that have used energy balance and radiative convective models. Previous studies required a much larger atmospheric CO2 increase to prevent an ice-covered Earth. The results of the study, suggest that because of its possible feedback with clouds, the general circulation of the atmosphere should be taken into account in understanding the climate of early Earth. While higher CO2 concentrations are likely in view of the results, very large atmospheric CO2 concentrations may not be necessary to counterbalance the lower solar constant that existed early in Earth's history.
Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony
2015-09-03
The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.
Hanlon, Erin C; Tasali, Esra; Leproult, Rachel; Stuhr, Kara L; Doncheck, Elizabeth; de Wit, Harriet; Hillard, Cecilia J; Van Cauter, Eve
2016-03-01
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. 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. 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. 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. A commentary on this article appears in this issue on page 495. © 2016 Associated Professional Sleep Societies, LLC.
Bauchart-Thevret, Caroline; Stoll, Barbara; Benight, Nancy M.; Olutoye, Oluyinka; Lazar, David; Burrin, Douglas G.
2013-01-01
Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg−1·d−1) from d 4 to 8 of life (n = 5–8). Whole-body respiratory calorimetry and 13C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (∼500 μmol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath 13CO2 enrichments, 13CO2 production, percentage of 13CO2 recovery/h, and cumulative percentage recovery of 13C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2. PMID:23446960
Bauchart-Thevret, Caroline; Stoll, Barbara; Benight, Nancy M; Olutoye, Oluyinka; Lazar, David; Burrin, Douglas G
2013-05-01
Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg(-1)·d(-1)) from d 4 to 8 of life (n = 5-8). Whole-body respiratory calorimetry and (13)C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (∼500 μmol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath (13)CO2 enrichments, (13)CO2 production, percentage of (13)CO2 recovery/h, and cumulative percentage recovery of (13)C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2.
Anuradha; Krishna, Amitabh
2018-06-01
The aim of the present study was to evaluate the mechanism by which embryonic development in Cynopterus sphinx is impaired during the period of increased accumulation of white adipose tissue during winter scarcity of food. The change in the mass of white adipose tissue during adipogenesis showed significant positive correlation with the circulating glucose level. But increase in circulating glucose level during the adipogenesis showed negative correlation with circulating progesterone and adiponectin levels. The in vivo study showed increased glucose uptake by the adipose tissue during adipogenesis due to increased expression of insulin receptor (IR) and glucose transporter (GLUT) 4 proteins. This study showed decline in the adiponectin level during fat accumulation. In the in vitro study, ovary treated with high doses of glucose showed impaired progesterone synthesis. This is due to decreased glucose uptake mediated decrease in the expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein, IR, GLUT4 and AdipoR1 proteins. But the ovary treated with adiponectin either alone or with higher concentration of glucose showed improvement in progesterone synthesis due to increased expression of IR, GLUT4 and AdipoR1 mediated increased glucose uptake. In conclusion, increased circulating glucose level prior to winter dormancy preferably transported to white adipose tissue for fat accumulation diverting glucose away from the ovary. Consequently the decreased availability of adiponectin and glucose to the ovary and utero-embryonic unit may be responsible for impaired progesterone synthesis and delayed embryonic development. The delayed embryonic development in Cynopterus sphinx may have evolved, in part, as a mechanism to prevent pregnancy loss during the period of decreased energy availability. Copyright © 2018 Elsevier Inc. All rights reserved.
Madrigal-Matute, Julio; Lindholt, Jes Sandal; Fernandez-Garcia, Carlos Ernesto; Benito-Martin, Alberto; Burillo, Elena; Zalba, Guillermo; Beloqui, Oscar; Llamas-Granda, Patricia; Ortiz, Alberto; Egido, Jesus; Blanco-Colio, Luis Miguel; Martin-Ventura, Jose Luis
2014-08-05
Galectin-3 (Gal-3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal-3 in cardiovascular (CV) diseases. The role of Gal-3 as a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown. Because Gal-3 is involved in monocyte-to-macrophage transition, we used fresh isolated monocytes and the in vitro model of macrophage differentiation of THP-1 cells stimulated with phorbol myristate acetate (PMA). Gal-3 release is increased by PMA in human monocytes and macrophages, a process involving exosomes and regulated by reactive oxygen species/NADPH oxidase activity. In asymptomatic subjects (n=199), Gal-3 plasma levels are correlated with NADPH oxidase activity in peripheral blood mononuclear cells (r=0.476; P<0.001) and carotid intima-media thickness (r=0.438; P<0.001), a surrogate marker of atherosclerosis. Accordingly, Gal-3 plasma concentrations are increased in patients with carotid atherosclerosis (n=158), compared to control subjects (n=115; 14.3 [10.7 to 16.9] vs. 10.4 [8.6 to 12.5] ng/mL; P<0.001). Finally, on a 5-year follow-up study in patients with peripheral artery disease, Gal-3 concentrations are significantly and independently associated with an increased risk for CV mortality (hazard ratio=2.24, 95% confidence interval: 1.06 to 4.73, P<0.05). Gal-3 extracellular levels could reflect key underlying mechanisms involved in atherosclerosis etiology, development, and plaque rupture, such as inflammation, infiltration of circulating cells and oxidative stress. Moreover, circulating Gal-3 concentrations are associated with clinical outcomes in patients with atherothrombosis. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Li, Junjie; Zhang, Weixia; Chung, Ting-Fung; Slipchenko, Mikhail N.; Chen, Yong P.; Cheng, Ji-Xin; Yang, Chen
2015-01-01
We report a transient absorption (TA) imaging method for fast visualization and quantitative layer analysis of graphene and GO. Forward and backward imaging of graphene on various substrates under ambient condition was imaged with a speed of 2 μs per pixel. The TA intensity linearly increased with the layer number of graphene. Real-time TA imaging of GO in vitro with capability of quantitative analysis of intracellular concentration and ex vivo in circulating blood were demonstrated. These results suggest that TA microscopy is a valid tool for the study of graphene based materials. PMID:26202216
Anderson, D C
1974-01-01
A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the cells. Sex-hormone-binding globulin (SHBG) binds to both the main circulating steroid T and E2 but changes in SHBG concentrations exert significant results. Increased SHBG levels increase estrogen production and decreases T activity; whereas, increased androgens increase T action and inhibit SHBG production. These disturbances in hormone maintenance may lead to abnormal adult sex differentiation such as hirsutism and forms of hynaecomastia. By developing SHBG concentration measurement methods-responses of hirsutism to glucocorticoid or estrogem may be assessed. In addition, the effect of thyroid hormones on SHBG may also have therapeutic implications in endocrine disease.
Willis, G R; Connolly, K; Ladell, K; Davies, T S; Guschina, I A; Ramji, D; Miners, K; Price, D A; Clayton, A; James, P E; Rees, D A
2014-12-01
Are circulating microparticles (MPs) altered in young women with polycystic ovary syndrome (PCOS)? Women with PCOS have elevated concentrations of circulating platelet-derived MPs, which exhibit increased annexin V binding and altered microRNA (miR) profiles compared with healthy volunteers. Some studies have shown that cardiovascular risk is increased in young women with PCOS but the mechanisms by which this occurs are uncertain. Circulating MPs are elevated in patients with cardiovascular disease but the characteristics of MPs in patients with PCOS are unclear. Case-control study comprising 17 women with PCOS (mean ± SD; age 31 ± 7 years, BMI 29 ± 6 kg/m(2)) and 18 healthy volunteers (age 31 ± 6 years, BMI 30 ± 6 kg/m(2)). The study was conducted in a University hospital. Nanoparticle tracking analysis (NTA) and flow cytometry (CD41 platelet, CD11b monocyte, CD144 endothelial) were used to determine MP size, concentration, cellular origin and annexin V positivity (reflecting phosphatidylserine exposure). Fatty acid analysis was performed by gas chromatography and MP miR expression profiles were compared by microarray. PCOS subjects showed increased MP concentrations compared with healthy volunteers (mean ± SD; 11.5 ± 5 × 10(12)/ml versus 10.0 ± 4 × 10(12)/ml, respectively; P = 0.03), which correlated with the homeostasis model of insulin resistance (r = 0.53, P = 0.03). This difference was predominantly seen in MPs whose size was in the small exosomal range (<150 nm in diameter, P< 0.05). PCOS patients showed a greater percentage of annexin V(+) MPs compared with healthy volunteers (84 ± 18 versus 74 ± 24%, respectively, P = 0.05) but the cellular origin of MPs, which were predominantly platelet-derived (PCOS: 99 ± 0.9%; controls: 99 ± 2.5%), did not differ. MP fatty acid concentration and composition was similar between groups but 16 miRs were differentially expressed (P < 0.05). Patients with PCOS were classified by the Rotterdam criteria, which describes a less severe metabolic phenotype than other definitions of the syndrome. Our findings may thus not be generalizable to all patients with PCOS. MicroRNA expression analysis was only undertaken in an exploratory subset of the overall study population hence, validation of our findings in a larger cohort is mandatory. Furthermore, miR levels were unaltered for the highly expressed miRs and it is unclear whether differences in the lowly expressed miRs carries pathological relevance. This study suggests that women with PCOS have an altered MP profile but further studies are needed to confirm this, to explore the mechanisms by which these alterations develop and to establish whether therapies that improve insulin sensitivity are able to reduce circulating MP concentrations. The study was funded by grants from the Wales Heart Research Institute and Mrs John Nixon Scholarship. The authors have no conflicts of interest to declare. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging.
Yang, Shanshan; Gerow, Kenneth G; Huber, Hillary F; Considine, McKenna M; Li, Cun; Mattern, Vicki; Comuzzie, Anthony G; Ford, Stephen P; Nathanielsz, Peter W
2017-05-09
Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.
Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito
2016-01-01
Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.
Rahimlou, Mehran; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash
2016-01-01
Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Preparation, pharmacokinetics and tumour-suppressive activity of berberine liposomes.
Wang, Xinghui; Wang, Qiong; Liu, Zhihui; Zheng, Xiao
2017-06-01
Berberine (BBR) has shown promising antitumour effects in vitro. However, intravenous administration of BBR solution is complicated by lethal adverse cardiovascular effects. The aim of this study was to prepare common and polyethylene glycol (PEG)-modified long-circulating BBR liposomes and evaluate their efficacy and safety as potential antitumour agents. Physiochemical properties of common and long-circulating BBR liposomes were characterized including particle size, Zeta potential and thermal stability. Pharmacokinetic and tissue distribution study of liposomal BBR was performed in rats and tumour-bearing nude mice, respectively. Antitumour efficacy and safety were observed in SGC-7901 tumour-xenografted mice. Berberine liposomes showed homogenous morphology, storage stability and sustained-releasing behaviour in vitro. BBR liposomes led to significantly increased circulation retention of BBR in comparison with BBR solution. In tumour-bearing mice, BBR liposomes selectively increased BBR concentrations in the liver, spleen, lung and tumour, while conferred lower distribution to the heart and kidney. Importantly, chronic administration of BBR liposomes proved effective and safe in suppressing the tumour growth in nude mice, especially the PEG-modified long-circulating liposomes. Our study suggested that BBR liposomes may provide a safe form of intravenous drug therapy for strengthening the antitumour effects of BBR. © 2017 Royal Pharmaceutical Society.
Madsen, Søren Møller; Thorup, Anne Cathrine; Bjerre, Mette; Jeppesen, Per Bendix
2015-01-01
In the present study, the effects of 8 weeks of low volume high intensity interval training (HIIT) was investigated on circulating diabetes-related cytokines and free fatty acids (FFA) in adults with type 2 diabetes (T2D) and matched controls (CON). Participants exercised for 8 weeks (3 weekly sessions: 10 × 60 sec HIIT) on a cycle ergometer supervised by medical staff. Prior to the intervention and after the last HIIT session, venous blood samples were collected. Circulating omentin-1 concentrations increased significantly in both the CON-group (p = 0.003) and in the T2D-group (p = 0.002). Pentraxin-3 (p = 0.010) and IL-1ra (p = 0.031) levels increased significantly in the CON-group. Plasma FFA in the T2D-group was significantly reduced after 60 min (p = 0.011). Post HIIT area under curve of circulating FFAs was reduced by -17.73 ± 6.99% (p = 0.041) in the T2D-group. We observed only modest exercise-induced improvements of multiple diabetes-related cytokines. Circulating levels of FFAs were significantly lowered in the T2D-group.
Wilson, J X; Sawai, H; Kikuchi, M; Kubokawa, K; Ishii, S
1995-06-01
We investigated the relationship between catecholamine neurohormones and glucose during seasonal reproductive activity in Japanese toads (Bufo japonicus). Field studies found that plasma epinephrine concentration increased as toads migrated to their breeding ponds, where amplexus most frequently took place. Blood glucose concentration also increased as toads arrived at the ponds, even though these animals did not eat during the breeding season, and there was a positive correlation between epinephrine and glucose levels. Blood glucose concentration was higher in amplectic than in solitary males, whereas this relationship did not occur in females. For both males and females, plasma epinephrine concentration was elevated during amplexus. The plasma concentration of norepinephrine was lower than that of epinephrine and did not correlate with either the proximity of the animal to the breeding ponds or the blood glucose concentration. Laboratory experiments showed that systemic injection of [Trp7,Leu8]gonadotropin-releasing hormone (sGnRH) increased plasma epinephrine to levels characteristic of amplectic feral toads. These results suggest that a physiological role of GnRH-like peptides may be to stimulate epinephrine secretion and consequently to increase glucose production in toads under the starvation conditions associated with the breeding migration.
Hamlin, Heather J; Edwards, Thea M; McCoy, Jessica; Cruze, Lori; Guillette, Louis J
2016-11-01
Anthropogenic nitrogen is a ubiquitous environmental contaminant that is contributing to the degradation of freshwater, estuarine, and coastal ecosystems worldwide. The effects of environmental nitrate, a principal form of nitrogen, on the health of aquatic life is of increasing concern. We exposed female American alligators to three concentrations of nitrate (0.7, 10 and 100mg/L NO 3 -N) for a duration of five weeks and five months from hatch. We assessed growth, plasma sex steroid and thyroid hormone concentrations, and transcription levels of key genes involved in steroidogenesis (StAR, 3β-HSD, and P450 scc ) and hepatic clearance (Cyp1a, Cyp3a). Exposure to 100mg/L NO 3 -N for both five weeks and five months resulted in significantly increased plasma testosterone (T) concentrations compared with alligators in the reference treatment. No differences in 17β-estradiol, progesterone, or thyroid hormones were observed, nor were there differences in alligator weight or the mRNA abundance of steroidogenic or hepatic genes. Plasma and urinary nitrate concentrations increased with increasing nitrate treatment levels, although relative plasma concentrations of nitrate were significantly lower in five month, versus five week old animals, possibly due to improved kidney function in older animals. These results indicate that environmentally relevant concentrations of nitrate can increase circulating concentrations of T in young female alligators. Copyright © 2016 Elsevier Inc. All rights reserved.
Walker circulation in a transient climate
NASA Astrophysics Data System (ADS)
Plesca, Elina; Grützun, Verena; Buehler, Stefan A.
2016-04-01
The tropical overturning circulations modulate the heat exchange across the tropics and between the tropics and the poles. The anthropogenic influence on the climate system will affect these circulations, impacting the dynamics of the Earth system. In this work we focus on the Walker circulation. We investigate its temporal and spatial dynamical changes and their link to other climate features, such as surface and sea-surface temperature patterns, El-Niño Southern Oscillation (ENSO), and ocean heat-uptake, both at global and regional scale. In order to determine the impact of anthropogenic climate change on the tropical circulation, we analyze the outputs of 28 general circulation models (GCMs) from the CMIP5 project. We use the experiment with 1% year-1 increase in CO2 concentration from pre-industrial levels to quadrupling of the concentration. Consistent with previous studies (ex. Ma and Xie 2013), we find that for this experiment most GCMs associate a weakening Walker circulation to a warming transient climate. Due to the role of the Walker Pacific cell in the meridional heat and moisture transport across the tropical Pacific and also the connection to ENSO, we find that a weakened Walker circulation correlates with more extreme El-Niño events, although without a change in their frequency. The spatial analysis of the Pacific Walker cell suggests an eastward displacement of the ascending branch, which is consistent with positive SST anomalies over the tropical Pacific and the link of the Pacific Walker cell to ENSO. Recent studies (ex. England et al. 2014) have linked a strengthened Walker circulation to stronger ocean heat uptake, especially in the western Pacific. The inter-model comparison of the correlation between Walker circulation intensity and ocean heat uptake does not convey a robust response for the investigated experiment. However, there is some evidence that a stronger weakening of the Walker circulation is linked to a higher transient climate response (temperature change by the time of CO2 doubling), which in turn might be related to a decreased ocean heat uptake. This uncertainty across the models we attribute to the multitude of factors controlling ocean and atmosphere heat exchange, both at global and regional scales, as well as to the present capabilities of GCMs in simulating this exchange. References: England, M. H., McGregor, S., Spence, P., Meehl, G. A., Timmermann, A., Cai, W., Gupta, A. S., McPhaden, M. J., Purich, A., and Santoso, A., 2014. Recent intensification of wind-driven circulation in the Pacific and the ongoing warming hiatus. Nature Climate Change 4 (3): 222-227. Ma, J., and Xie, S. P., 2013. Regional Patterns of Sea Surface Temperature Change: A Source of Uncertainty in Future Projections of Precipitation and Atmospheric Circulation*. Journal of Climate, 26 (8): 2482-2501
USDA-ARS?s Scientific Manuscript database
These studies were conducted to evaluate causes for differences in circulating concentrations of estradiol prior to a GnRH-induced ovulation and to determine if exogenous GnRH administration could alter LH secretion and subsequent follicular estradiol production. Beef cows (Experiment 1; n = 32, Ex...
NASA Astrophysics Data System (ADS)
Kiro, Yael; Weinstein, Yishai; Starinsky, Abraham; Yechieli, Yoseph
2013-04-01
Saline lakes act as base level for both surface water and groundwater. Thus, a change in lake levels is expected to result in changes in the hydrogeological system in its vicinity, exhibited in groundwater levels, location of the fresh-saline water interface, sub-lacustrine groundwater discharge (SGD) and saline water circulation. All these processes were observed in the declining Dead Sea system, whose water level dropped by ~35 meters in the last 50 years. This work focuses mainly on the effect of circulation of Dead Sea water in the aquifer, which continues even in this very rapid base level drop. In general, seawater circulation in coastal aquifers is now recognized as a major process affecting trace element mass balances in coastal areas. Estimates of submarine groundwater discharge (SGD) vary over several orders of magnitude (1-1000000 m3/yr per meter shoreline). These estimates are sensitive to fresh-saline SGD ratios and to the temporal and spatial scales of the circulation. The Dead Sea system is an excellent natural field lab for studying seawater-groundwater interaction and large-scale circulation due to the absence of tides and to the minor role played by waves. During Dead Sea water circulation in the aquifer several geochemical reactions occur, ranging from short-term adsorption-desorption reactions and up to long-term precipitation and dissolution reactions. These processes affect the trace element distribution in the saline groundwater. Barite and celestine, which are supersaturated in the lake water, precipitate during circulation in the aquifer, reducing barium (from 5 to 1.5 mg/L), strontium (from 350 to 300 mg/L) and the long-lived 226Ra (from 145 to 60 dpm/L) in the saline groundwater. Redox-controlled reactions cause a decrease in uranium from 2.4 to 0.1 μg/L, and an increase in iron from 1 to 13 mg/L. 228Ra (t1/2=5.75 yr) activity in the Dead Sea is ~1 dpm/L and increase gradually as the saline water flows further inland until reaching steady-state activities (~27 dpm/L) with the aquifer sediments. The decrease in 226Ra and increase in 228Ra in the circulation process provide a robust method for calculating the amount of Dead Sea water circulating in the aquifer. This process can affect trace element concentrations in the Dead Sea and emphasize the potential of long-term seawater circulation in mass balances of saline water bodies.
Rodriguez, A; García-Esteban, R; Basterretxea, M; Lertxundi, A; Rodríguez-Bernal, C; Iñiguez, C; Rodriguez-Dehli, C; Tardón, A; Espada, M; Sunyer, J; Morales, E
2015-11-01
To investigate the association of maternal circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes. Prospective cohort study. Four geographical areas of Spain, 2003-2008. Of 2382 mother-child pairs participating in the INfancia y Medio Ambiente (INMA) Project. Maternal circulating 25(OH)D3 concentration was measured in pregnancy (mean [SD] 13.5 [2.2] weeks of gestation). We tested associations of maternal 25(OH)D3 concentration with pregnancy and birth outcomes. Gestational diabetes mellitus (GDM), preterm delivery, caesarean section, fetal growth restriction (FGR) and small-for-gestational age (SGA), anthropometric birth outcomes including weight, length and head circumference (HC). Overall, 31.8% and 19.7% of women had vitamin D insufficiency [25(OH)D3 20-29.99 ng/ml] and deficiency [25(OH)D3 < 20 ng/ml], respectively. After adjustment, there was no association between maternal 25(OH)D3 concentration and risk of GDM or preterm delivery. Women with sufficient vitamin D [25(OH)D3 ≥ 30 ng/ml] had a decreased risk of caesarean section by obstructed labour compared with women with vitamin D deficiency [relative risk (RR) = 0.60, 95% CI 0.37, 0.97). Offspring of mothers with higher circulating 25(OH)D3 concentration tended to have smaller HC [coefficient (SE) per doubling concentration of 25(OH)D3, -0.10 (0.05), P = 0.038]. No significant associations were found for other birth outcomes. This study did not find any evidence of an association between vitamin D status in pregnancy and GDM, preterm delivery, FGR, SGA and anthropometric birth outcomes. Results suggest that sufficient circulating vitamin D concentration [25(OH)D3 ≥ 30 ng/ml] in pregnancy may reduce the risk of caesarean section by obstructed labour. © 2014 Royal College of Obstetricians and Gynaecologists.
Asferg, Camilla L; Andersen, Ulrik B; Linneberg, Allan; Goetze, Jens P; Jeppesen, Jørgen L
2018-05-07
Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations. On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size. We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m2). All men were healthy, medication free, with normal left ventricular ejection fraction. We measured blood pressure using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hour ABP ≥ 130/80 mm Hg, and normotension was defined as 24-hour ABP < 130/80 mm Hg. We determined left atrial size using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP). Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean normotensive men (23.5 ± 4.5 ml/m2) and the obese normotensive men (22.7 ± 5.1 ml/m2), P < 0.01. Nevertheless, despite evidence of pressure-induced greater left atrial size, the obese hypertensive men had lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0-64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3-82.9] pmol/l), P < 0.01, whereas the obese normotensive men had serum MR-proANP concentrations in between the 2 other groups (54.1 [43.6-62.9] pmol/l). Despite greater left atrial size, obese hypertensive men have lower circulating MR-proANP concentrations compared with lean normotensive men.
Increased Levels of Circulating Anti-ANXA1 IgG Antibody in Patients with Non-Small Cell Lung Cancer.
Liang, Tingting; Han, Zhifeng; Zhao, Huan; Zhang, Xuan; Wang, Yao
2018-06-01
Our previous studies revealed that concentrations of circulating antibodies to annexin A1 (ANXA1) were increased in non-small lung cancer (NSCLC). This study was thus designed to replicate this initial finding with an independent sample set. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to examine plasma antiANXA1 IgG levels in 220 patients with NSCLC and 200 control subjects. Mann-Whitney U test showed that patients with NSCLC had significantly higher anti-ANXA1 IgG levels than control subjects (Z = -4.02, p < 0.001); male patients appeared to mainly contribute to the increased antibody level (Z = -3.09, p = 0.002). Receiver operating characteristic (ROC) curve analysis showed an overall area under the ROC curve (AUC) of 0.61 (95% CI: 0.56 - 0.67), with sensitivity of 8% against a specificity of 95.0%. Spearman's correlation analysis failed to show a significant correlation between the anti-ANXA1 IgG levels and the expression of three tumor-associated antigens including p53 (r = 0.156, p = 0.027), Ki67 (r = -0.048, p = 0.489), and EGFR (r = 0.02, p = 0.782). Increased levels of circulating anti-ANXA1 IgG antibody may have a prognostic value for NSCLC.
Body composition changes in men and women after 2-3 weeks of bed rest
NASA Technical Reports Server (NTRS)
Pace, N.; Kodama, A. M.; Grunbaum, B. W.; Rahlmann, D. F.; Price, D. C.; Newsom, B. D.
1976-01-01
Several parameters of body composition were measured in eight men before and after 14 days of continuous recumbency, and in eight women before and after 17 days of recumbency. The parameters measured included body weight, body water, body potassium, plasma volume, and plasma protein concentrations. From these, values were derived for body fat content, lean body mass, body mass, and circulating plasma proteins. In general, the men and women responded similarly to continuous recumbency. Characteristically, there was significant reduction of plasma volume and body potassium in both groups. The women showed a significant reduction in circulating plasma protein, entirely in the albumin fraction; a similar change was observed in the men. The women, but not the men, showed a significant increase in circulating fibrinogen. Both men and women lost body cell mass, while body fat content remained the same or tended to increase slightly. It is expected that similar changes would occur in weightlessness. It is further concluded that women should tolerate the weightlessness of space flight physiologically as well as men.
Xi, Wenyan; Yang, Yongkang; Mao, Hui; Zhao, Xiuhua; Liu, Ming; Fu, Shengyu
2016-02-11
To investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. This prospective cohort observational study included 81 anovulatory women with PCOS who underwent 213 cycles of CC ovarian stimulation. Serum AMH concentrations were measured on cycle day 3 before the commencement of CC in the first cycle, which were compared between responders and CC-resistant anovulation (CRA). Logistic regression analysis was applied to study the value of serum AMH for the prediction of ovarian responsiveness to CC stimulation. The receiver-operating characteristic (ROC) curve was used to evaluate the prognostic value of circulating AMH. Serum AMH levels. Women who ovulated after CC therapy had a significantly lower AMH compared with the CRA (5.34 ± 1.97 vs.7.81 ± 3.49, P < 0.001). There was a significant gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation (P < 0.05). In multivariate logistic regression analysis, AMH was an independent predictor of ovulation induction by CC in PCOS patients. ROC curve analysis showed AMH to be a useful predictor of ovulation induction by CC in PCOS patients, having 92 % specificity and 65 % sensitivity when the threshold AMH concentration was 7.77 ng/ml. Serum AMH may be clinically useful to predict which PCOS women are more likely to respond to CC treatment and thus to direct the selection of protocols of ovulation induction.
Frey, Helena; Moreth, Kristin; Hsieh, Louise Tzung-Harn; Zeng-Brouwers, Jinyang; Rathkolb, Birgit; Fuchs, Helmut; Gailus-Durner, Valérie; Iozzo, Renato V; de Angelis, Martin Hrabě; Schaefer, Liliana
2017-06-01
Secondary polycythemia, a disease characterized by a selective increase in circulating mature erythrocytes, is caused by enhanced erythropoietin (Epo) concentrations triggered by hypoxia-inducible factor-2α (HIF-2α). While mechanisms of hypoxia-dependent stabilization of HIF-2α protein are well established, data regarding oxygen-independent regulation of HIF-2α are sparse. In this study, we generated a novel transgenic mouse model, in which biglycan was constitutively overexpressed and secreted by hepatocytes (BGN Tg ), thereby providing a constant source of biglycan released into the blood stream. We discovered that although the mice were apparently normal, they harbored an increase in mature circulating erythrocytes. In addition to erythrocytosis, the BGN Tg mice showed elevated hemoglobin concentrations, hematocrit values and enhanced total iron binding capacity, revealing a clinical picture of polycythemia. In BGN Tg mice markedly enhanced Epo mRNA expression was observed in the liver and kidney, while elevated Epo protein levels were found in liver, kidney and blood. Mechanistically, we showed that the transgenic animals had an abundance of HIF-2α protein in the liver and kidney. Finally, by transiently overexpressing circulating biglycan in mice deficient in various Toll-like receptors (TLRs), we determined that this novel function of biglycan to promote Epo synthesis was specifically mediated by a selective interaction with TLR2. Thus, we discovered a novel biological pathway of soluble biglycan inducing HIF-2α protein stabilization and Epo production presumably in an oxygen-independent manner, ultimately giving rise to secondary polycythemia.
Stokhof, A A; Overduin, L M; Mol, J A; Rijnberk, A
1994-04-01
Factors regulating the secretion of atrial natriuretic hormone (ANH) and arginine vasopressin (AVP) have not been elucidated fully. In several studies the release of these peptides has been studied by inducing both increased atrial pressure and atrial distension. A few studies employ cardiac tamponade, allowing the effect of atrial pressure and atrial stretch to be studied separately. In eleven dogs with spontaneous cardiac tamponade the effect of pericardiocentesis on circulating concentrations of ANP and AVP was studied. Pericardiocentesis was followed by a prompt rise in (non-elevated) plasma ANH concentrations from 21.6 +/- 7.3 to 65.4 +/- 17.1 pmol/l (mean +/- SEM). The initially slightly elevated AVP concentration of 5.5 +/- 1.5 pmol/l declined following pericardiocentesis to 2.1 +/- 0.5 pmol/l. In three dogs the systolic arterial pressure was measured indirectly and the central venous pressure was measured with a fluid-filled catheter. Before and after pericardiocentesis arterial pressure readings did not change significantly. Central venous pressure values showed an immediate very steep significant decrease after centesis. It is concluded that ANH release is primarily regulated by stretch and not by atrial pressure, that plasma AVP concentrations are moderately elevated in cardiac tamponade and that in cardiac tamponade pericardiocentesis causes a rapid decline in plasma AVP concentration.
Surface water subduction during a downwelling event in a semienclosed bay
NASA Astrophysics Data System (ADS)
Barton, E. D.; Torres, R.; Figueiras, F. G.; Gilcoto, M.; Largier, J.
2016-09-01
The Ría de Vigo is a bay strongly influenced by upwelling-downwelling cycles along the adjacent coast of NW Iberia. Moored and ship-board observations during September 2006 showed that subduction, initially associated with an estuarine circulation, strengthened when a strong downwelling circulation, resulting from northward wind over the coastal ocean, was generated in the outer Ría causing ambient waters to be advected outward in the lower layer. Incoming surface waters confined the estuarine circulation to the shallow interior and displaced isopleths downward through the water column at ˜10 m d-1. As the estuarine circulation retreated inward, strong flow convergence developed between middle and inner ria in the layer above 15 m, while divergence developed beneath. The convergence increased through the period of downwelling-favorable wind at a rate consistent with the observed isopleth displacement velocities. The coefficient of turbulent diffusion Kt, from a microstructure profiler, indicated that mixing was strong in the estuarine circulation and subsequently in the downwelling zone, where localized instabilities and temperature-salinity inversions were observed. During the downwelling, concentrations of phytoplankton, including potentially harmful species, increased, especially in the middle and inner ria, as a result of inward advection, subduction, and the ability of the dinoflagellates to maintain their position in the water column by swimming. In the course of the 5 day event, the water mass of all but the innermost Ría was flushed completely and replaced by waters originating in the coastally trapped poleward flow along the Atlantic coastline.
Vigneron, Nicolas; Meryet-Figuière, Matthieu; Guttin, Audrey; Issartel, Jean-Paul; Lambert, Bernard; Briand, Mélanie; Louis, Marie-Hélène; Vernon, Mégane; Lebailly, Pierre; Lecluse, Yannick; Joly, Florence; Krieger, Sophie; Lheureux, Stéphanie; Clarisse, Bénédicte; Leconte, Alexandra; Gauduchon, Pascal; Poulain, Laurent; Denoyelle, Christophe
2016-08-01
Circulating miRNAs are promising biomarkers in oncology but have not yet been implemented in the clinic given the lack of concordance across studies. In order to increase the cross-studies reliability, we attempted to reduce and to control the circulating miRNA expression variability between patients. First, to maximize profiling signals and to reduce miRNA expression variability, three isolation kits were compared and the NucleoSpin(®) kit provided higher miRNA concentrations than the other widely used kits. Second, to control inter-sample variability during the profiling step, the exogenous miRNAs normalization method commonly used for RT-qPCR validation step was adapted to microarray experiments. Importantly, exogenous miRNAs presented two-fold lower inter-sample variability than the widely used endogenous miR-16-5p reflecting that the latter is subject to both biological and technical variability. Although Caenorhabditis elegans miRNAs isolation yields were heterogeneous, they correlated to each other and to their geometrical mean across samples. The normalization based on the geometrical mean of three exogenous miRNAs increased the correlation up-to 0.97 between the microarrays and individual RT-qPCR steps of circulating miRNAs expression. Overall, this new strategy open new avenue to identify reliable circulating miRNA signatures for translation into clinical practice. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Jiménez, Itzel Uribe; Díaz-Díaz, Eulises; Castro, Jorge Salmerón; Ramos, Julia Pérez; León, Mario Cárdenas; Alvarado Ríos, José Antonio; Auriostigue Bautista, Juan Carlos; Correa-Rotter, Ricardo; Aguilar Salinas, Carlos Alberto; Larrea, Fernando
2017-05-01
Diabetes Mellitus (DM) is characterized by the production and accumulation of advanced glycation end products (AGEs), which are one of the key mechanisms in the development of its chronic complications. To assess the serum AGEs concentration by a radioimmunoassay (RIA) developed in our laboratory, to establish reference values in healthy population and to evaluate the diagnostic potential of measuring longitudinal changes in circulating AGEs concentrations to predict the development of DM. Clinical and metabolic parameters were obtained from a cohort of 781 Mexican people, initially and then seven years later. AGEs were quantified by a specific RIA. Associations of the changes in circulating levels of AGEs with the appearance of impaired fasting glucose (IFG), and the development of DM were evaluated. Diabetic subjects had higher circulating levels of AGEs than normoglycemic subjects or individuals with IFG in both samples studied (471 vs. 246 and 342 μU/mL, p <0.001; and 912 vs. 428 and 519 μU/mL, p <0.001; respectively). A multinomial logistic regression analysis showed that subjects who had AGEs concentration ≥400 μU/mL in the baseline sample had a relative risk ratio of 1.98 to develop IFG seven years later (p = 0.003). While the subjects who had AGEs concentration ≥450 μU/mL in the baseline sample had a relative risk ratio of 10.7 to develop DM seven years later (p <0.001). Circulating AGEs concentration is a good early marker to predict risk of developing DM. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.
2011-01-01
Dairy cows are often fed high grain diets to meet the energy demand for high milk production or simply due to a lack of forages at times. As a result, ruminal acidosis, especially subacute ruminal acidosis (SARA), occurs frequently in practical dairy production. When SARA occurs, bacterial endotoxin (or lipopolysaccharide, LPS) is released in the rumen and the large intestine in a large amount. Many other bacterial immunogens may also be released in the digestive tract following feeding dairy cows diets containing high proportions of grain. LPS can be translocated into the bloodstream across the epithelium of the digestive tract, especially the lower tract, due to possible alterations of permeability and injuries of the epithelial tissue. As a result, the concentration of blood LPS increases. Immune responses are subsequently caused by circulating LPS, and the systemic effects include increases in concentrations of neutrophils and the acute phase proteins such as serum amyloid-A (SAA), haptoglobin (Hp), LPS binding protein (LBP), and C-reactive protein (CRP) in blood. Entry of LPS into blood can also result in metabolic alterations. Blood glucose and nonesterified fatty acid concentrations are enhanced accompanying an increase of blood LPS after increasing the amount of grain in the diet, which adversely affects feed intake of dairy cows. As the proportions of grain in the diet increase, patterns of plasma β-hydoxybutyric acid, cholesterol, and minerals (Ca, Fe, and Zn) are also perturbed. The bacterial immunogens can also lead to reduced supply of nutrients for synthesis of milk components and depressed functions of the epithelial cells in the mammary gland. The immune responses and metabolic alterations caused by circulating bacterial immunogens will exert an effect on milk production. It has been demonstrated that increases in concentrations of ruminal LPS and plasma acute phase proteins (CRP, SAA, and LBP) are associated with declines in milk fat content, milk fat yield, 3.5% fat-corrected milk yield, as well as milk energy efficiency. PMID:21824438
Beltrán, Luis M.; García Morillo, José S.; Egido, Jesús; Noval, Manuel Leal; Ferrando-Martinez, Sara; Blanco-Colio, Luis M.; Genebat, Miguel; Villar, José R.; Moreno-Luna, Rafael; Moreno, Juan Antonio
2014-01-01
Background Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART. PMID:24594990
Leung, Angela M
2017-01-01
Myxedema coma and thyroid storm are thyroid emergencies associated with increased mortality. Prompt recognition of these states—which represent the severe, life-threatening conditions of extremely reduced or elevated circulating thyroid hormone concentrations, respectively—is necessary to initiate treatment. Management of myxedema coma and thyroid storm requires both medical and supportive therapies and should be treated in an intensive care unit setting. PMID:27598067
USDA-ARS?s Scientific Manuscript database
APOA5 is one of the strongest regulators of plasma TG concentrations; nevertheless, its mechanisms of action are poorly characterized. Genetic variability at the APOA5 locus has also been associated with increased cardiovascular disease risk; however, this predisposition could be attenuated in the c...
Circulating androgens in women: exercise-induced changes.
Enea, Carina; Boisseau, Nathalie; Fargeas-Gluck, Marie Agnès; Diaz, Véronique; Dugué, Benoit
2011-01-01
Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance.
ERTS imagery applied to Alaskan coastal problems. [surface water circulation
NASA Technical Reports Server (NTRS)
Wright, F. F.; Sharma, G. D.; Burbank, D. C.; Burns, J. J.
1974-01-01
Along the Alaska coast, surface water circulation is relatively easy to study with ERTS imagery. Highly turbid river water, sea ice, and fluvial ice have proven to be excellent tracers of the surface waters. Sea truth studies in the Gulf of Alaska, Cook Inlet, Bristol Bay, and the Bering Strait area have established the reliability of these tracers. ERTS imagery in the MSS 4 and 5 bands is particularly useful for observing lower concentrations of suspended sediment, while MSS 6 data is best for the most concentrated plumes. Ice features are most clearly seen on MSS 7 imagery; fracture patterns and the movement of specific floes can be used to map circulation in the winter when runoff is restricted, if appropriate allowance is made for wind influence. Current patterns interpreted from satellite data are only two-dimensional, but since most biological activity and pollution are concentrated near the surface, the information developed can be of direct utility. Details of Alaska inshore circulation of importance to coastal engineering, navigation, pollution studies, and fisheries development have been clarified with satellite data. ERTS has made possible the analysis of circulation in many parts of the Alaskan coast.
Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N
2010-07-01
Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.
Arkoosh, Mary R; Van Gaest, Ahna L; Strickland, Stacy A; Hutchinson, Greg P; Krupkin, Alex B; Dietrich, Joseph P
2017-03-01
Polybrominated diphenyl ethers (PBDEs) have been used as flame-retardants in consumer products and are currently detected in salmon globally. The two most predominant PBDE congeners found in salmon are BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) and BDE-99 (2,2',4,4',5-pentabromodiphenyl ether). In the present study, groups of juvenile Pacific Chinook salmon were fed five environmentally relevant concentrations of either BDE-47 (0.3-552 ng total PBDEs/g food), BDE-99 (0.3-580 ng total PBDEs/g food), or nearly equal mixtures of both congeners (0.7-690 ng total PBDEs/g food) for 39-40 days. The concentrations of circulating total thyroid hormones, thyroxine (T 4 ) and 3,5,3'-triiodothyronine (T 3 ), were measured using a hormone-specific time-resolved fluoroimmunoassay to determine if PBDE exposure disrupts the hypothalamic-pituitary-thyroid endocrine axis. The concentrations of both circulating T 4 and T 3 were altered in juvenile salmon by dietary uptake of BDE-99. Exposure to BDE-47 did not alter either T 3 or T 4 circulating hormone concentrations. However, exposure to a mixture of BDE-47 and BDE-99 reduced T 3 in fish with lower concentrations of total whole body PBDEs than with either congener alone at equivalent PBDE whole body concentrations. Accordingly, the disruption of PBDEs on circulating thyroid hormone concentrations has the potential to impact a number of critical functions in juvenile salmon including growth, parr-smolt transformation, and immunological processes. Published by Elsevier Ltd.
Andersson, Maria; Egli, Ines; Foman, Jasmin Tajeri; Zeder, Christophe; Westerman, Mark E; Hurrell, Richard F
2014-01-01
Background: After the oral administration of iron, the production of circulating non–transferrin-bound iron may contribute to an increased risk of illness in malaria-endemic areas that lack effective medical services. Objective: In healthy women with a range of body iron stores, we aimed to determine effects on the production of circulating non–transferrin-bound iron resulting from the oral administration of 1) a supplemental dose of iron (60 mg) with water, 2) a supplemental dose of iron (60 mg) with a standard test meal, and 3) a fortification dose of iron (6 mg) with a standard test meal. Design: With the use of serum ferritin as the indicator, healthy women with replete iron stores (ferritin concentration >25 μg/L; n = 16) and reduced iron stores (ferritin concentration ≤25 μg/L; n = 16) were enrolled in a prospective, randomized, crossover study. After the oral administration of aqueous solutions of ferrous sulfate isotopically labeled with 54Fe, 57Fe, or 58Fe, blood samples were collected for 8 h, and iron absorption was estimated by erythrocyte incorporation at 14 d. Results: At 4 h, serum non–transferrin-bound iron reached peaks with geometric mean (95% CI) concentrations of 0.81 μmol/L (0.56, 1.1 μmol/L) for 60 mg Fe with water and 0.26 μmol/L (0.15, 0.38 μmol/L) for 60 mg Fe with food but was at assay limits of detection (0.1 μmol Fe/L) for 6 mg Fe with food. For the 60 mg Fe without food, the area under the curve over 8 h for serum non–transferrin-bound iron was positively correlated with the amount of iron absorbed (R = 0.49, P < 0.01) and negatively correlated with serum ferritin (R = −0.39, P < 0.05). Conclusions: In healthy women, the production of circulating non–transferrin-bound iron is determined by the rate and amount of iron absorbed. The highest concentrations of non–transferrin-bound iron resulted from the administration of supplemental doses of iron without food. Little or no circulating non–transferrin-bound iron resulted from the consumption of a meal with a fortification dose of iron. This trial was registered at clinicaltrials.gov as NCT01404533. PMID:25057155
Brittenham, Gary M; Andersson, Maria; Egli, Ines; Foman, Jasmin Tajeri; Zeder, Christophe; Westerman, Mark E; Hurrell, Richard F
2014-09-01
After the oral administration of iron, the production of circulating non-transferrin-bound iron may contribute to an increased risk of illness in malaria-endemic areas that lack effective medical services. In healthy women with a range of body iron stores, we aimed to determine effects on the production of circulating non-transferrin-bound iron resulting from the oral administration of 1) a supplemental dose of iron (60 mg) with water, 2) a supplemental dose of iron (60 mg) with a standard test meal, and 3) a fortification dose of iron (6 mg) with a standard test meal. With the use of serum ferritin as the indicator, healthy women with replete iron stores (ferritin concentration >25 μg/L; n = 16) and reduced iron stores (ferritin concentration ≤25 μg/L; n = 16) were enrolled in a prospective, randomized, crossover study. After the oral administration of aqueous solutions of ferrous sulfate isotopically labeled with ⁵⁴Fe, ⁵⁷Fe, or ⁵⁸Fe, blood samples were collected for 8 h, and iron absorption was estimated by erythrocyte incorporation at 14 d. At 4 h, serum non-transferrin-bound iron reached peaks with geometric mean (95% CI) concentrations of 0.81 μmol/L (0.56, 1.1 μmol/L) for 60 mg Fe with water and 0.26 μmol/L (0.15, 0.38 μmol/L) for 60 mg Fe with food but was at assay limits of detection (0.1 μmol Fe/L) for 6 mg Fe with food. For the 60 mg Fe without food, the area under the curve over 8 h for serum non-transferrin-bound iron was positively correlated with the amount of iron absorbed (R = 0.49, P < 0.01) and negatively correlated with serum ferritin (R = -0.39, P < 0.05). In healthy women, the production of circulating non-transferrin-bound iron is determined by the rate and amount of iron absorbed. The highest concentrations of non-transferrin-bound iron resulted from the administration of supplemental doses of iron without food. Little or no circulating non-transferrin-bound iron resulted from the consumption of a meal with a fortification dose of iron. © 2014 American Society for Nutrition.
Knight, Bridget Ann; Shields, Beverley M; Brook, Adam; Hill, Anita; Bhat, Dattatray S; Hattersley, Andrew T; Yajnik, Chittaranjan S
2015-01-01
Vitamin B12 and folate are critical micronutrients needed to support the increased metabolic demands of pregnancy. Recent studies from India have suggested that low vitamin B12 and folate concentrations in pregnancy are associated with increased obesity; however differences in diet, antenatal vitamin supplementation, and socioeconomic status may limit the generalisability of these findings. We aimed to explore the cross-sectional relationship of circulating serum vitamin B12 and folate at 28 weeks' gestation with maternal adiposity and related biochemical markers in a white non diabetic UK obstetric cohort. Anthropometry and biochemistry data was available on 995 women recruited at 28 weeks gestation to the Exeter Family Study of Childhood Health. Associations between B12 and folate with maternal BMI and other obesity-related biochemical factors (HOMA-R, fasting glucose, triglycerides, HDL and AST) were explored using regression analysis, adjusting for potential confounders (socioeconomic status, vegetarian diet, vitamin supplementation, parity, haemodilution (haematocrit)). Higher 28 week BMI was associated with lower circulating vitamin B12 (r = -0.25; P<0.001) and folate (r = -0.15; P<0.001). In multiple regression analysis higher 28 week BMI remained an independent predictor of lower circulating B12 (β (95% CI) = -0.59 (-0.74, -0.44) i.e. for every 1% increase in BMI there was a 0.6% decrease in circulating B12). Other markers of adiposity/body fat metabolism (HOMA-R, triglycerides and AST) were also independently associated with circulating B12. In a similar multiple regression AST was the only independent obesity-related marker associated with serum folate (β (95% CI) = 0.16 (0.21, 0.51)). In conclusion, our study has replicated the previous Indian findings of associations between lower serum B12 and higher obesity and insulin resistance during pregnancy in a non-diabetic White British population. These findings may have important implications for fetal and maternal health in obese pregnancies.
NASA Astrophysics Data System (ADS)
Kracher, Daniela; Manzini, Elisa; Reick, Christian H.; Schultz, Martin; Stein, Olaf
2014-05-01
Climate change is driven by an increasing release of anthropogenic greenhouse gases (GHGs) such as carbon dioxide and nitrous oxide (N2O). Besides fossil fuel burning, also land use change and land management are anthropogenic sources of GHGs. Especially inputs of reactive nitrogen via fertilizer and deposition lead to enhanced emissions of N2O. One effect of a drastic future increase in surface temperature is a modification of atmospheric circulation, e.g. an accelerated Brewer Dobson circulation affecting the exchange between troposphere and stratosphere. N2O is inert in the troposphere and decayed only in the stratosphere. Thus, changes in atmospheric circulation, especially changes in the exchange between troposphere and stratosphere, will affect the atmospheric transport, decay, and distribution of N2O. In our study we assess the impact of global warming on atmospheric circulation and implied effects on the distribution and lifetime of atmospheric N2O. As terrestrial N2O emissions are highly determined by inputs of reactive nitrogen - the location of which being determined by human choice - we examine in particular the importance of latitudinal source regions of N2O for its global distribution. For this purpose we apply the Max Planck Institute Earth System Model, MPI-ESM. MPI-ESM consists of the atmospheric general circulation model ECHAM, the land surface model JSBACH, and MPIOM/HAMOCC representing ocean circulation and ocean biogeochemistry. Prognostic atmospheric N2O concentrations in MPI-ESM are determined by land N2O emissions, ocean N2O exchange and atmospheric tracer transport. As stratospheric chemistry is not explicitly represented in MPI-ESM, stratospheric decay rates of N2O are prescribed from a MACC MOZART simulation.
Effects and mechanisms of action of sildenafil citrate in human chorionic arteries
Maharaj, Chrisen H; O'Toole, Daniel; Lynch, Tadhg; Carney, John; Jarman, James; Higgins, Brendan D; Morrison, John J; Laffey, John G
2009-01-01
Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO. PMID:19389232
Duchaine, Caroline S.; Diorio, Caroline
2014-01-01
Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OH)D concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OH)D levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1–3 and >3 servings/week, respectively; r = −0.11 (p = 0.004)). A correlation was observed between intake of other carbonated beverages and 25(OH)D concentrations but was not statistically significant (r = −0.06 (p = 0.10)). No association was observed between intake of sweet fruit drinks and 25(OH)D concentrations. This study suggests that high intake of colas may decrease 25(OH)D levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation. PMID:25072269
Duchaine, Caroline S; Diorio, Caroline
2014-07-28
Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OH)D concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OH)D levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1-3 and >3 servings/week, respectively; r = -0.11 (p = 0.004)). A correlation was observed between intake of other carbonated beverages and 25(OH)D concentrations but was not statistically significant (r = -0.06 (p = 0.10)). No association was observed between intake of sweet fruit drinks and 25(OH)D concentrations. This study suggests that high intake of colas may decrease 25(OH)D levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation.
Berezin, Alexander E.; Kremzer, Alexander A.; Martovitskaya, Yulia V.; Samura, Tatyana A.; Berezina, Tatyana A.
2015-01-01
Background: Subclinical hypothyroidism (SH) is diagnosed biochemically by the presence of normal serum free thyroxine concentration, in conjunction with an elevated serum thyroid-stimulating hormone level. Recent studies have demonstrated the frequent association between SH and cardiovascular diseases and risk factors. Objectives: To evaluate the impact of SH on patterns of circulating endothelial-derived microparticles, (EMPs) among chronic heart failure (CHF) patients Patients and Methods: This is a retrospective study involving a cohort of 388 patients with CHF. Fifty-three CHF subjects had SH and 335 patients were free from thyroid dysfunction. Circulating levels of N-terminal-pro brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), thyroid-stimulating hormone (TSH), total and free thyroxine (T4), and triiodothyronine (T3), and endothelial apoptotic microparticles (EMPs), were measured at baseline. SH was defined, according to contemporary clinical guidelines, as a biochemical state associated with an elevated serum TSH level of greater 10 μU/L and normal basal free T3 and T4 concentrations. Results: Circulating CD31+/annexin V+ EMPs were higher in patients with SH compared to those without SH. In contrast, activated CD62E+ EMP numbers were not significantly different between both patient cohorts. Using uni (bi) variate and multivariate age- and gender-adjusted regression analysis, we found several predictors that affected the increase of the CD31+/annexin V+ to CD62E+ ratio in the patient study population. The independent impact of TSH per 6.5 μU/L (odds ratio [OR] = 1.23, P = 0.001), SH (OR = 1.22, P = 0.001), NT-proBNP (OR = 1.19, P = 0.001), NYHA class (OR = 1.09, P = 0.001), hs-CRP per 4.50 mg/L (OR = 1.05, P = 0.001), dyslipidemia (OR = 1.06, P = 0.001), serum uric acid per 9.5 mmol/L (OR = 1.04, P = 0.022) on the increase in the CD31+/annexin V+ to CD62E+ ratio, was determined. Conclusions: We believe that the SH state in CHF patients may be associated with the impaired pattern of circulating EMPs, with the predominantly increased number of apoptotic-derived microparticles. PMID:26528453
The Dynamics of Hadley Circulation Variability and Change
NASA Astrophysics Data System (ADS)
Davis, Nicholas Alexander
The Hadley circulation exerts a dominant control on the surface climate of earth's tropical belt. Its converging surface winds fuel the tropical rains, while subsidence in the subtropics dries and stabilizes the atmosphere, creating deserts on land and stratocumulus decks over the oceans. Because of the strong meridional gradients in temperature and precipitation in the subtropics, any shift in the Hadley circulation edge could project as major changes in surface climate. While climate model simulations predict an expansion of the Hadley cells in response to greenhouse gas forcings, the mechanisms remain elusive. An analysis of the climatology, variability, and response of the Hadley circulation to radiative forcings in climate models and reanalyses illuminates the broader landscape in which Hadley cell expansion is realized. The expansion is a fundamental response of the atmosphere to increasing greenhouse gas concentrations as it scales with other key climate system changes, including polar amplification, increasing static stability, stratospheric cooling, and increasing global-mean surface temperatures. Multiple measures of the Hadley circulation edge latitudes co-vary with the latitudes of the eddy-driven jets on all timescales, and both exhibit a robust poleward shift in response to forcings. Further, across models there is a robust coupling between the eddy-driving on the Hadley cells and their width. On the other hand, the subtropical jet and tropopause break latitudes, two common observational proxies for the tropical belt edges, lack a strong statistical relationship with the Hadley cell edges and have no coherent response to forcings. This undermines theories for the Hadley cell width predicated on angular momentum conservation and calls for a new framework for understanding Hadley cell expansion. A numerical framework is developed within an idealized general circulation model to isolate the mean flow and eddy responses of the global atmosphere to radiative forcings. It is found that it is primarily the eddy response to greenhouse-gas-like forcings that causes Hadley cell expansion. However, the mean flow changes in the Hadley circulation itself crucially mediate this eddy response such that the full response comes about due to eddy-mean flow interactions. A theoretical scaling for the Hadley cell width based on moist static energy is developed to provide an improved framework to understand climate change responses of the general circulation. The scaling predicts that expansion is driven by increases in the surface latent heat flux and the width of the rising branch of the circulation and opposed by increases in tropospheric radiative cooling. A reduction in subtropical moist static energy flux divergence by the eddies is key, as it tilts the energetic balance in favor of expansion.
Understanding Thiel Embalming in Pig Kidneys to Develop a New Circulation Model
Willaert, Wouter; De Vos, Marie; Van Hoof, Tom; Delrue, Louke; Pattyn, Piet; D’Herde, Katharina
2015-01-01
The quality of tissue preservation in Thiel embalmed bodies varies. Research on the administered embalming volume and its vascular distribution may elucidate one of the mechanisms of tissue preservation and allow for new applications of Thiel embalming. Vascular embalming with (group 1, n = 15) or without (group 2, n = 20) contrast agent was initiated in pig kidneys. The distribution of Thiel embalming solution in group 1 was visualized using computed tomography. The kidneys in both groups were then immersed in concentrated salt solutions to reduce their weight and volume. Afterwards, to mimic a lifelike circulation in the vessels, group 2 underwent pump-driven reperfusion for 120 minutes with either paraffinum perliquidum or diluted polyethylene glycol. The circulation was imaged with computed tomography. All of the kidneys were adequately preserved. The embalming solution spread diffusely in the kidney, but fluid accumulation was present. Subsequent immersion in concentrated salt solutions reduced weight (P < 0.01) and volume (P < 0.01). Reperfusion for 120 minutes was established in group 2. Paraffinum perliquidum filled both major vessels and renal tissue, whereas diluted polyethylene glycol spread widely in the kidney. There were no increases in weight (P = 0.26) and volume (P = 0.79); and pressure further decreased (P = 0.032) after more than 60 minutes of reperfusion with paraffinum perliquidum, whereas there were increases in weight (P = 0.005), volume (P = 0.032) and pressure (P < 0.0001) after reperfusion with diluted polyethylene glycol. Arterial embalming of kidneys results in successful preservation due to complete parenchymatous spreading. More research is needed to determine whether other factors affect embalming quality. Dehydration is an effective method to regain the organs’ initial status. Prolonged vascular reperfusion with paraffinum perliquidum can be established in this model without increases in weight, volume and pressure. PMID:25806527
NASA Technical Reports Server (NTRS)
Tegen, Ina; Rind, David
2000-01-01
To investigate the effects of changes in the latitudinal temperature gradient and the global mean temperature on dust concentration in the Northern Hemisphere, experiments with the Goddard Institute for Space Studies General Circulation Model (GISS GCM) are performed. The dust concentration over Greenland is calculated from sources in central and eastern Asia, which are integrated on-line in the model. The results show that an increase in the latitudinal temperature gradient increases both the Asian dust source strength and the concentration over Greenland. The source increase is the result of increased surface winds, and to a minor extent, the increase in Greenland dust is also associated with increased northward transport. Cooling the climate in addition to this increased gradient leads to a decrease in precipitation scavenging, which helps produce a further (slight) increase in Greenland dust in this experiment. Reducing the latitudinal gradient reduces the surface wind and hence the dust source, with a subsequent reduction in Greenland dust concentrations. Warming the climate in addition to this reduced gradient leads to a further reduction in Greenland dust due to enhanced precipitation scavenging. These results can be used to evaluate the relationship of Greenland ice core temperature changes to changes in the latitudinal and global temperatures.
Friend, Andrew D; Lucht, Wolfgang; Rademacher, Tim T; Keribin, Rozenn; Betts, Richard; Cadule, Patricia; Ciais, Philippe; Clark, Douglas B; Dankers, Rutger; Falloon, Pete D; Ito, Akihiko; Kahana, Ron; Kleidon, Axel; Lomas, Mark R; Nishina, Kazuya; Ostberg, Sebastian; Pavlick, Ryan; Peylin, Philippe; Schaphoff, Sibyll; Vuichard, Nicolas; Warszawski, Lila; Wiltshire, Andy; Woodward, F Ian
2014-03-04
Future climate change and increasing atmospheric CO2 are expected to cause major changes in vegetation structure and function over large fractions of the global land surface. Seven global vegetation models are used to analyze possible responses to future climate simulated by a range of general circulation models run under all four representative concentration pathway scenarios of changing concentrations of greenhouse gases. All 110 simulations predict an increase in global vegetation carbon to 2100, but with substantial variation between vegetation models. For example, at 4 °C of global land surface warming (510-758 ppm of CO2), vegetation carbon increases by 52-477 Pg C (224 Pg C mean), mainly due to CO2 fertilization of photosynthesis. Simulations agree on large regional increases across much of the boreal forest, western Amazonia, central Africa, western China, and southeast Asia, with reductions across southwestern North America, central South America, southern Mediterranean areas, southwestern Africa, and southwestern Australia. Four vegetation models display discontinuities across 4 °C of warming, indicating global thresholds in the balance of positive and negative influences on productivity and biomass. In contrast to previous global vegetation model studies, we emphasize the importance of uncertainties in projected changes in carbon residence times. We find, when all seven models are considered for one representative concentration pathway × general circulation model combination, such uncertainties explain 30% more variation in modeled vegetation carbon change than responses of net primary productivity alone, increasing to 151% for non-HYBRID4 models. A change in research priorities away from production and toward structural dynamics and demographic processes is recommended.
Friend, Andrew D.; Lucht, Wolfgang; Rademacher, Tim T.; Keribin, Rozenn; Betts, Richard; Cadule, Patricia; Ciais, Philippe; Clark, Douglas B.; Dankers, Rutger; Falloon, Pete D.; Ito, Akihiko; Kahana, Ron; Kleidon, Axel; Lomas, Mark R.; Nishina, Kazuya; Ostberg, Sebastian; Pavlick, Ryan; Peylin, Philippe; Schaphoff, Sibyll; Vuichard, Nicolas; Warszawski, Lila; Wiltshire, Andy; Woodward, F. Ian
2014-01-01
Future climate change and increasing atmospheric CO2 are expected to cause major changes in vegetation structure and function over large fractions of the global land surface. Seven global vegetation models are used to analyze possible responses to future climate simulated by a range of general circulation models run under all four representative concentration pathway scenarios of changing concentrations of greenhouse gases. All 110 simulations predict an increase in global vegetation carbon to 2100, but with substantial variation between vegetation models. For example, at 4 °C of global land surface warming (510–758 ppm of CO2), vegetation carbon increases by 52–477 Pg C (224 Pg C mean), mainly due to CO2 fertilization of photosynthesis. Simulations agree on large regional increases across much of the boreal forest, western Amazonia, central Africa, western China, and southeast Asia, with reductions across southwestern North America, central South America, southern Mediterranean areas, southwestern Africa, and southwestern Australia. Four vegetation models display discontinuities across 4 °C of warming, indicating global thresholds in the balance of positive and negative influences on productivity and biomass. In contrast to previous global vegetation model studies, we emphasize the importance of uncertainties in projected changes in carbon residence times. We find, when all seven models are considered for one representative concentration pathway × general circulation model combination, such uncertainties explain 30% more variation in modeled vegetation carbon change than responses of net primary productivity alone, increasing to 151% for non-HYBRID4 models. A change in research priorities away from production and toward structural dynamics and demographic processes is recommended. PMID:24344265
Pedersen, Henrik D; Falk, Torkel; Häggström, Jens; Tarnow, Inge; Olsen, Lisbeth H; Kvart, Clarence; Nielsen, Mette O
2005-01-01
Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF-1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated congestive HF had similar serum IGF-1 concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11 control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was 16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2 +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The studies document that circulating IGF-1 concentrations are not altered before development of congestive HF in dogs with naturally occurring MR, but decrease by approximately 20% with the development of untreated HE In treated HF, circulating IGF-1 concentrations apparently return to within the reference range.
NASA Astrophysics Data System (ADS)
Rotstayn, L. D.; Jeffrey, S. J.; Collier, M. A.; Dravitzki, S. M.; Hirst, A. C.; Syktus, J. I.; Wong, K. K.
2012-07-01
We use a coupled atmosphere-ocean global climate model (CSIRO-Mk3.6) to investigate the drivers of trends in summer rainfall and circulation in the vicinity of northern Australia. As part of the Coupled Model Intercomparison Project Phase 5 (CMIP5), we perform a 10-member 21st century ensemble driven by Representative Concentration Pathway 4.5 (RCP4.5). To investigate the roles of different forcing agents, we also perform multiple 10-member ensembles of historical climate change, which are analysed for the period 1951-2010. The historical runs include ensembles driven by "all forcings" (HIST), all forcings except anthropogenic aerosols (NO_AA) and forcing only from long-lived greenhouse gases (GHGAS). Anthropogenic aerosol-induced effects in a warming climate are calculated from the difference of HIST minus NO_AA. CSIRO-Mk3.6 simulates a strong summer rainfall decrease over north-western Australia (NWA) in RCP4.5, whereas simulated trends in HIST are weakly positive (but insignificant) during 1951-2010. The weak rainfall trends in HIST are due to compensating effects of different forcing agents: there is a significant decrease in GHGAS, offset by an aerosol-induced increase. Observations show a significant increase of summer rainfall over NWA during the last few decades. The large magnitude of the observed NWA rainfall trend is not captured by 440 unforced 60-yr trends calculated from a 500-yr pre-industrial control run, even though the model's decadal variability appears to be realistic. This suggests that the observed trend includes a forced component, despite the fact that the model does not simulate the magnitude of the observed rainfall increase in response to "all forcings" (HIST). We investigate the mechanism of simulated and observed NWA rainfall changes by exploring changes in circulation over the Indo-Pacific region. The key circulation feature associated with the rainfall increase in reanalyses is a lower-tropospheric cyclonic circulation trend off the coast of NWA, which enhances the monsoonal flow. The model shows an aerosol-induced cyclonic circulation trend off the coast of NWA in HIST minus NO_AA, whereas GHGAS shows an anticyclonic circulation trend. This explains why the aerosol-induced effect is an increase of rainfall over NWA, and the greenhouse gas-induced effect is of opposite sign. Possible explanations for the cyclonic (anticyclonic) circulation trend in HIST minus NO_AA (GHGAS) involve changes in the Walker circulation or the local Hadley circulation. In either case, a plausible atmospheric mechanism is that the circulation anomaly is a Rossby wave response to convective heating anomalies south of the Equator. We also discuss the possible role of air-sea interactions, e.g. an increase (decrease) of sea-surface temperatures off the coast of NWA in HIST minus NO_AA (GHGAS). Further research is needed to better understand the mechanisms and the extent to which these are model-dependent. In summary, our results suggest that anthropogenic aerosols may have "masked" greenhouse gas-induced changes in rainfall over NWA and in circulation over the wider Indo-Pacific region. Due to the opposing effects of greenhouse gases and anthropogenic aerosols, future trends may be very different from trends observed over the last few decades.
Troisi, Rebecca; Braekke, Kristin; Harsem, Nina Kittelsen; Hyer, Marianne; Hoover, Robert N.; Staff, Anne Cathrine
2008-01-01
Objective The objective of the study was to determine whether blood pressure increases are associated with maternal angiogenic factors in uncomplicated and preeclamptic pregnancies. Study Design Associations of blood pressure increases from mid- to late pregnancy with maternal serum concentrations of soluble fms-like tyrosine kinase receptor (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) at delivery were analyzed in 43 uncomplicated and 44 preeclamptic pregnancies. Results In uncomplicated pregnancies, increases in diastolic and mean arterial pressure were inversely associated with PlGF at delivery and positively associated with sEng and sFlt1/PlGF ratio. There were no significant associations between blood pressure increases and angiogenic factor concentrations in preeclampsia. Conclusion These data suggest that angiogenic factors are involved in blood pressure modulation in normotensive pregnancy and are consistent with the hypothesis that angiogenic balance plays a role in maternal breast cancer risk reduction associated with mid- to late blood pressure increases in uncomplicated pregnancies. PMID:18722574
O'Hara, L; Forde, N; Duffy, P; Randi, F; Kelly, A K; Valenza, A; Rodriguez, P; Lonergan, P
2016-03-01
The aim was to examine the effect of a single intramuscular (i.m.) injection of equine chorionic gonadotrophin (eCG) on Day 3 after oestrus on corpus luteum (CL) development, circulating progesterone and conceptus development in cross-bred beef heifers. In Experiment 1, heifers received: (1) saline, or a single i.m. injection of eCG on Day 3 at (2) 250IU (3) 500IU (4) 750IU or (5) 1000IU. Administration of eCG resulted in increased luteal tissue area and progesterone and oestradiol concentrations compared with controls. In Experiment 2, heifers received (1) a progesterone-releasing intravaginal device (PRID Delta) from Day 3 to 5 or (2) a PRID Delta from Day 3 to 5 plus a single injection of 750IU eCG on Day 3. In vitro-produced blastocysts (n=10 per recipient) were transferred on Day 7 and heifers were slaughtered on Day 14 to assess conceptus development. Administration of eCG reduced the number of short cycles (6.3% vs 31.3%) and increased mean luteal tissue weight (P=0.02). Insertion of a PRID Delta on Day 3 resulted in an elevation (P<0.05) in serum progesterone until removal on Day 5. Administration of eCG at the time of PRID Delta insertion resulted in higher progesterone levels (P<0.05) from Day 10 onwards. Conceptus dimensions were not affected. In conclusion, a single injection of eCG on Day 3 increased CL size and progesterone concentrations and, when given in conjunction with a progesterone-releasing device, appeared to reduce the number of short cycles, presumably due to its luteotrophic nature. The implications of the elevated oestradiol concentrations for embryo quality require further study.
Cheng, Zhangrui; Oguejiofor, Chike F; Swangchan-Uthai, Theerawat; Carr, Susan; Wathes, D Claire
2015-08-14
Both high and low circulating urea concentrations, a product of protein metabolism, are associated with decreased fertility in dairy cows through poorly defined mechanisms. The rate of involution and the endometrial ability to mount an adequate innate immune response after calving are both critical for subsequent fertility. Study 1 used microarray analysis to identify genes whose endometrial expression 2 weeks postpartum correlated significantly with the mean plasma urea per cow, ranging from 3.2 to 6.6 mmol/L. The biological functions of 781 mapped genes were analysed using Ingenuity Pathway Analysis. These were predominantly associated with tissue turnover (e.g., BRINP1, FOXG1), immune function (e.g., IL17RB, CRISPLD2), inflammation (e.g., C3, SERPINF1, SERPINF2) and lipid metabolism (e.g., SCAP, ACBD5, SLC10A). Study 2 investigated the relationship between urea concentration and expression of 6 candidate genes (S100A8, HSP5A, IGF1R, IL17RB, BRINP1, CRISPLD2) in bovine endometrial cell culture. These were treated with 0, 2.5, 5.0 or 7.5 mmol/L urea, equivalent to low, medium and high circulating values with or without challenge by bacterial lipopolysaccharide (LPS). LPS increased S100A8 expression as expected but urea treatment had no effect on expression of any tested gene. Examination of the genes/pathways involved suggests that plasma urea levels may reflect variations in lipid metabolism. Our results suggest that it is the effects of lipid metabolism rather than the urea concentration which probably alter the rate of involution and innate immune response, in turn influencing subsequent fertility.
Youn, Byung-Soo; Bang, Sa-Ik; Klöting, Nora; Park, Ji Woo; Lee, Namseok; Oh, Ji-Eun; Pi, Kyung-Bae; Lee, Tae Hee; Ruschke, Karen; Fasshauer, Mathias; Stumvoll, Michael; Blüher, Matthias
2009-01-01
OBJECTIVE—Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown. RESEARCH DESIGN AND METHODS—For the measurement of progranulin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1–based cell migration assays. RESULTS—Progranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of Gα. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels. CONCLUSIONS—Elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes. PMID:19056610
Luan, Jingde; Li, Aimin; Su, Tong; Li, Xuan
2009-07-30
Oil shale and fly ash collected from two thermal power plants located in Huadian, the northeast city of China were subjected to fraction distribution, translocation regularity and toxicity assessment to provide preliminary assessment of suitability for land application. By Tessier sequential extraction, the results showed that Ni, Cr, Pb and Zn were mostly bounded with iron-manganese and organic bound in oil shale, but Cu and Cd were mostly associated with iron-manganese bound and residue fraction. Through circulated fluidized-bed combustion, high concentration of heavy metals (Cu, Cd, Ni, Cr, Pb, and Zn) was found in iron-manganese bound and residue fraction in fly ash. There was accumulation of all studied metals except Ni and Cr in fly ash and translocation mass of metals were as follows: Pb>Zn>Cu>Cd during circulated fluidized-bed combustion. Fly ash was contaminated with Cd higher than the pollution concentration limits listed in GB15168-1995, China. This work demonstrated that it was unadvisable way to carry out landfill without any treatment. By means of STI model, toxicity assessment of heavy metals was carried out to show that there was notable increase in toxicity from oil shale to fly ash.
Hyperthyroidism in four guinea pigs: clinical manifestations, diagnosis, and treatment.
Künzel, F; Hierlmeier, B; Christian, M; Reifinger, M
2013-12-01
Hyperthyroidism was diagnosed in four guinea pigs by demonstration of an increased serum total thyroxine concentration. The main clinical signs were comparable with those observed in feline hyperthyroidism and included weight loss despite maintenance of appetite and a palpable mass in the ventral cervical region. Three animals were treated successfully with methimazole for between 13 and 28 months. Clinical signs and regular measurement of circulating total thyroxine concentrations appear to be convenient parameters for monitoring response to medical therapy. © 2013 British Small Animal Veterinary Association.
The disinfection by-product dibromoacetic acid (DBA) has been found in female rats to increase circulating concentrations of both estradiol (E2) and estrone (E1). This effect is apparently due, at least in part, to a suppression in hepatic catabolism. The present study investigat...
Fiber Type-Specific Effects of Dietary Nitrate.
Jones, Andrew M; Ferguson, Scott K; Bailey, Stephen J; Vanhatalo, Anni; Poole, David C
2016-04-01
Dietary nitrate supplementation increases circulating nitrite concentration, and the subsequent reduction of nitrite to nitric oxide is promoted in hypoxic environments. Given that PO2 is lower in Type II compared with Type I muscle, this article examines the hypothesis that the ergogenicity of nitrate supplementation is linked to specific effects on vascular, metabolic, and contractile function in Type II muscle.
USDA-ARS?s Scientific Manuscript database
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 ...
Suzuki, Miwa; Tomoshige, Mika; Ito, Miki; Koga, Sotaro; Yanagisawa, Makio; Bungo, Takashi; Makiguchi, Yuya
2017-07-01
In cetaceans, diving behavior immediately induces a change in blood circulation to favor flow to the brain and heart; this is achieved by intense vasoconstriction of the blood vessels that serve other organs. This blood circulation response is allied to a decrease in heart rate in order to optimize oxygen usage during diving. Vasoconstrictors are present in all mammals and stimulate the contraction of the smooth muscle in the walls of blood vessels. The most important of these vasoconstrictors are the hormones adrenaline (A), noradrenaline (NA), and angiotensin II (ANG II). At present, the contribution of these hormones to vasoconstriction during diving in cetaceans is unclear. To elucidate their possible roles, changes in serum levels of A, NA and ANG II were monitored together with heart rate in the Indo-Pacific bottlenose dolphin Tursiops aduncus during 90 and 180s dives. Both brief diving periods induced an increase in serum NA concentration and a decrease in heart rate; however, no changes were detected in serum levels of A or ANG II. These data indicate that NA may play a role in diving-induced vasoconstriction. Copyright © 2017 Elsevier Inc. All rights reserved.
Laporta, J; Peters, T L; Weaver, S R; Merriman, K E; Hernandez, L L
2013-05-01
An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0.048). These results show that increasing 5-HT biosynthesis during the transition from pregnancy to lactation could be a potential therapeutic target to explore for prevention of subclinical and clinical hypocalcemia. Copyright © 2013 Elsevier Inc. All rights reserved.
A Method for Electrochemical Detection of Brain Derived Neurotrophic Factor (BDNF) in plasma.
Bockaj, Marina; Fung, Barnabas; Tsoulis, Michael; Foster, Lauren Warren; Soleymani, Leyla
2018-06-22
Currently, a blood test for the diagnosis of endometriosis, a common estrogen-dependent gynecological disease, does not exist. Recent studies suggest that circulating concentrations of brain derived neurotrophic factor (BDNF) have potential for the diagnosis of endometriosis. However, at present BDNF can only be measured by ELISA which requires a clinic visit, a routine blood sample, and laboratory testing. Therefore, we developed a point-of-care device (EndoChip) for use with small blood volumes that can be collected through a finger prick. Specifically, the presented device is a polymer-based chip with a wrinkled nanoporous gold film acting as the electrode/sensing layer, allowing for the electrochemical detection of BDNF in plasma. Increasing concentrations of BDNF (0.25 - 2.0 ng/ml) induced significant differences in redox current. The biosensor produces a signal readout in a matter of seconds, and is ideal for realizing multiplexing. Blood samples were collected from women (n=20) with chronic pelvic pain undergoing a diagnostic laparoscopy. Plasma BDNF concentrations measured by commercial ELISA were positively correlated (r2=0.8216; p<0.001) with results from the EndoChip. Our results demonstrate a quick and reliable method for point-of-care quantification of circulating concentrations of BDNF and a promising diagnostic tool for endometriosis.
Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development.
Morales, Eva; Guxens, Mònica; Llop, Sabrina; Rodríguez-Bernal, Clara L; Tardón, Adonina; Riaño, Isolina; Ibarluzea, Jesús; Lertxundi, Nerea; Espada, Mercedes; Rodriguez, Agueda; Sunyer, Jordi
2012-10-01
To investigate whether circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration in pregnancy is associated with neuropsychological development in infants. The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D(3) concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5 ± 2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11-23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D(3) were calculated by using linear regression analysis. The median plasma value of 25(OH)D(3) in pregnancy was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D(3) concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D(3) concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63-4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36-4.28) in comparison with those of mothers with 25(OH)D(3) concentrations <20 ng/mL. Higher circulating concentration of maternal 25(OH)D(3) in pregnancy was associated with improved mental and psychomotor development in infants.
Marchand, Geneviève B; Carreau, Anne-Marie; Weisnagel, S John; Bergeron, Jean; Labrie, Fernand; Lemieux, Simone; Tchernof, André
2018-05-01
The relationship between circulating estrogen levels and cardiometabolic risk factors such as insulin resistance is unclear in postmenopausal women. High estradiol (E 2 ) levels have been reported to predict increased risk of type 2 diabetes in this population. We aimed to examine associations among estrogen levels, adiposity measurements, and cardiometabolic risk variables including insulin resistance in postmenopausal women. One hundred-one healthy participants (mean ± SD: age 57 ± 4 yr, BMI 27.9 ± 4.8 kg/m 2 ) were included in the analysis. Fifteen plasma steroids or metabolites were measured by liquid chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were determined with hydrostatic weighing and computed tomography, respectively. Blood lipids and circulating cytokines were also measured. Circulating E 2 was positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001) except waist-to-hip ratio. E 2 was positively correlated with VLDL-cholesterol, plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL-cholesterol, adiponectin, and insulin sensitivity ( r = -0.36 to -0.20, P < 0.02). With adjustments for percent body fat, correlations between E 2 and metabolic risk variables were no longer significant. Similar results were observed for circulating estrone (E 1 ) and estrone-sulfate (E 1 -S) levels. In conclusion, circulating estrogen concentrations are proportional to adipose mass in postmenopausal women, although they remain in the low range. Insulin resistance as well as altered blood lipids and cytokines are observed when circulating estrogen levels are high within that range, but these differences are explained by concomitant variation in total adiposity.
Rosoff, J D; Soltow, L O; Vocelka, C R; Schmer, G; Chandler, W L; Cochran, R P; Kunzelman, K S; Spiess, B D
1998-08-01
To examine whether a second-generation perfluorocarbon (PFC) blood substitute added to the cardiopulmonary bypass (CPB) prime influences complement production. A prospective, randomized, single-blinded, ex vivo model. A university hospital, laboratory, and clinics. Ten healthy adult consented volunteer blood donors (five men, five women). Ex vivo closed-loop extracorporeal circuit including membrane oxygenator, tubing, and filter primed with crystalloid or crystalloid plus PFC was circulated for 1 hour with the addition of 500 mL of heparinized fresh human whole blood. Laboratory specimens were drawn from the circuit at 10-minute intervals for 1 hour and measured for complement (C3a, Bb fragment) concentrations, blood gases, fibrinogen concentration, platelet count, and hematocrit. In the PFC group, C3a and Bb fragments were equal to or less than those in the group that received crystalloid alone. The second-generation PFC added to the prime of a CPB circuit does not independently increase complement production.
The transfer of 6-mercaptopurine in the dually perfused human placenta.
Hutson, J R; Lubetsky, A; Walfisch, A; Ballios, B G; Garcia-Bournissen, F; Koren, G
2011-11-01
The immunosuppressant azathioprine is increasingly being used in pregnancy. The human placenta is considered a relative barrier to the major metabolite, 6-mercaptopurine (6-MP), and likely explains the lack of proven teratogenicity in humans. The aim of this study was to determine how the human placenta restricts 6-MP transfer using the human placental perfusion model. After addition of 50 ng/ml (n=4) and 500 ng/ml (n=3) 6-MP into the maternal circulation, there was a biphasic decline in its concentration and a delay in fetal circulation appearance. Under equilibrative conditions, the fetal-to-maternal concentration ratio was >1.0 as a result of ion trapping. Binding to placental tissue and maternal pharmacokinetic parameters are the main factors that restrict placental transfer of 6-MP. Active transport is unlikely to play a significant role and drug interactions involving, or polymorphisms in, placental drug efflux transporters are not likely to put the fetus at risk of higher 6-MP exposure. Copyright © 2011 Elsevier Inc. All rights reserved.
Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes.
Yamada, Hodaka; Saito, Tomoyuki; Aoki, Atsushi; Asano, Tomoko; Yoshida, Masashi; Ikoma, Aki; Kusaka, Ikuyo; Toyoshima, Hideo; Kakei, Masafumi; Ishikawa, San-E
2015-01-01
There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.
Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito
2016-01-01
Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671
Bai, Jing; Zhao, Yong-Sheng; Sun, Chao; Qin, Chuan-Yu; Yu, Ling
2014-10-01
A two-dimension simulated sand box was set up to investigate the influencing factors, such as the initial groundwater level, aeration rate and the initial groundwater rate, that affect groundwater circulation well (GCW) by determining the intensity of groundwater circulation which was characterized by the variation of groundwater level before and after aeration. The optimal operating parameters were used to remediate nitrobenzene contaminated aquifer. The results demonstrated that: GCW could be well operated under the conditions of 45 cm groundwater level, 0.7 m3 · h(-1) aeration rate. The effects of groundwater velocity less than 1.0 m · d(-1) could be ignored. The lateral mobility rate of nitrobenzene was faster than that of longitudinal. The average concentration of nitrobenzene was 246.97 mg · L(-1) on day 50 of leakage. During the remediation of circulation well, an efficient organics remediation region was gradually formed around the circulation well. The organics in this region was removed preferentially, and the concentration decreased continuously. Besides the efficient remediation region, there was a transient region, where the concentration of organics was influenced by the combined effects of adsorption/desorption and migration potential of organics. During the whole remediation process, the concentration of nitrobenzene went through three stages described as rapid removal, slow removal. After 14h aeration, the nitrobenzene average concentration was reduced to 71.19 mg L(-1). The residual nitrobenzene was distributed in regions far away from GCW. Therefore, nitrobenzene contaminated aquifer could be well remediated by GCW, and there were optimal operation conditions and appropriate remediation time which guaranteed the best remediation effect.
Progranulin is increased in human and murine lipodystrophy.
Miehle, Konstanze; Ebert, Thomas; Kralisch, Susan; Hoffmann, Annett; Kratzsch, Jürgen; Schlögl, Haiko; Stumvoll, Michael; Fasshauer, Mathias
2016-10-01
Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far. Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD. Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation. Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Zicker, S C; Vivrette, S; Rogers, Q R
1994-06-01
Concentrations of 16 of 24 amino acids in plasma of foetuses were significantly higher, while four of 24 were lower, than their concentration in maternal plasma. The higher foetal concentrations of amino acids in plasma are similar to other species, with some exceptions, and suggest that equine placenta actively transports and concentrates amino acids into the umbilical circulation. Concentrations of nine of 24 amino acids were significantly lower in plasma from the umbilical artery compared to plasma from the umbilical vein, while no significant differences were present between maternal artery and vein plasma. The umbilical venous-arterial difference in concentrations of amino acids in plasma suggests the foetus extracts amino acids from the umbilical circulation for catabolism or protein synthesis, as in other species.
Grotevendt, A; Wallaschofski, H; Reincke, M; Adolf, C; Quinkler, M; Nauck, M; Hoffmann, W; Rettig, R; Hannemann, A
2017-08-01
Chronic inflammation is an age-independent and body mass index-independent contributor to the development of multi-morbidity. Alterations of the renin-angiotensin-aldosterone system are observed within the context of proinflammatory states. We assessed circulating aldosterone, renin, and inflammatory biomarker concentrations in healthy, normotensive subjects and patients with primary aldosteronism. We included 1177 normotensive individuals from the population-based Study of Health in Pomerania (first follow-up, Study of Health in Pomerania-1) and 103 primary aldosteronism patients from the German Conn's Registry. A 1:1 matching for sex, age, body mass index, smoking status, diabetes mellitus, and the estimated glomerular filtration rate was performed to determine whether primary aldosteronism patients exhibit higher inflammatory biomarker concentrations than normotensive controls. The associations of plasma aldosterone concentration or plasma renin concentration with circulating fibrinogen concentrations, white blood cell count, and high sensitive C-reactive protein concentrations in the normotensive sample were determined with multivariable linear and logistic regression analyses. 1:1 matched primary aldosteronism patients demonstrated significantly (p < 0.01) higher plasma aldosterone concentration (198 vs. 47 ng/l), lower plasma renin concentration (3.1 vs. 7.7 ng/l) and higher high sensitive C-reactive protein concentrations (1.5 vs. 1.0 mg/l) than normotensive controls. Within the normotensive cohort, plasma renin concentration but not plasma aldosterone concentration was positively associated with fibrinogen concentrations and white blood cell count. Further, a J-shaped association between plasma renin concentration and high sensitive C-reactive protein concentrations was detected. High plasma aldosterone concentration in a primary aldosteronism cohort and high plasma renin concentration in normotensive subjects are associated with increased concentrations of inflammatory biomarkers. This suggests a link between the renin-angiotensin-aldosterone system and inflammatory processes in patients with primary aldosteronism and even in normotensive subjects.
Hazell, Tom J; Islam, Hashim; Townsend, Logan K; Schmale, Matt S; Copeland, Jennifer L
2016-03-01
The physiological control of appetite regulation involves circulating hormones with orexigenic (appetite-stimulating) and anorexigenic (appetite-inhibiting) properties that induce alterations in energy intake via perceptions of hunger and satiety. As the effectiveness of exercise to induce weight loss is a controversial topic, there is considerable interest in the effect of exercise on the appetite-regulating hormones such as acylated ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and pancreatic polypeptide (PP). Research to date suggests short-term appetite regulation following a single exercise session is likely affected by decreases in acylated ghrelin and increases in PYY, GLP-1, and PP. Further, this exercise-induced response may be intensity-dependent. In an effort to guide future research, it is important to consider how exercise alters the circulating concentrations of these appetite-regulating hormones. Potential mechanisms include blood redistribution, sympathetic nervous system activity, gastrointestinal motility, cytokine release, free fatty acid concentrations, lactate production, and changes in plasma glucose and insulin concentrations. This review of relevant research suggests blood redistribution during exercise may be important for suppressing ghrelin, while other mechanisms involving cytokine release, changes in plasma glucose and insulin concentrations, SNS activity, and muscle metabolism likely mediate changes in the anorexigenic signals PYY and GLP-1. Overall, changes in appetite-regulating hormones following acute exercise appear to be intensity-dependent, with increasing intensity leading to a greater suppression of orexigenic signals and greater stimulation of anorexigenic signals. However, there is less research on how exercise-induced responses in appetite-regulating hormones differ between sexes or different age groups. A better understanding of how exercise intensity and workload affect appetite across the sexes and life stages will be a powerful tool in developing more successful strategies for managing weight. Copyright © 2015 Elsevier Ltd. All rights reserved.
Role of Activin A and myostatin in human cancer cachexia.
Loumaye, Audrey; de Barsy, Marie; Nachit, Maxime; Lause, Pascale; Frateur, Lena; van Maanen, Aline; Trefois, Pierre; Gruson, Damien; Thissen, Jean-Paul
2015-05-01
Cachexia is a multifactorial syndrome, characterized by the loss of skeletal muscle mass and not fully reversible by nutritional support. Recent animal observations suggest that production of Activin A (ActA) and Myostatin (Mstn) by some tumors might contribute to cancer cachexia. Our goal was to investigate the role of ActA and Mstn in the development of the human cancer cachexia. The ACTICA study is a cross-sectional study, which prospectively enrolled patients from a tertiary-care center between January 2012 and March 2014. Subjects/Outcome Measures: One hundred fifty two patients with colorectal or lung cancer had clinical, nutritional and functional assessment. Body composition was measured by CT-scan, anthropometry, and bioimpedance. Plasma concentrations of ActA, Mstn, and Follistatin were determined. Cachexia was associated with reduced lean and fat mass (p < .01 and p < .001), reduced physical function, lower quality of life, and increased symptoms (QLQC30; p < .001). Anorexia (SNAQ score < 14) was more common in cachectic patients (CC) than in noncachectic patients (CNC) (p < .001). ActA concentrations in CC patients were higher than in CNC patients (+40%; p < .001) and were correlated positively with weight loss (R = 0.323; p < .001) and negatively with the SNAQ score (R = -0.225; p < .01). In contrast, Mstn concentrations were decreased in CC patients compared to CNC patients (-35%; p < .001). These results demonstrate an association between circulating concentrations of ActA and the presence of the anorexia/cachexia syndrome in cancer patients. Given the known muscle atrophic effects of ActA, our study suggests that increased circulating concentrations of ActA may contribute to the development of cachexia in cancer patients.
Kiefte-de Jong, Jessica C; Timmermans, Sarah; Jaddoe, Vincent W V; Hofman, Albert; Tiemeier, Henning; Steegers, Eric A; de Jongste, Johan C; Moll, Henriette A
2012-04-01
Recent studies suggest that in utero exposure of methyl donors influences programming of the fetal immune system in favor of development of allergic disease. The aim of this study was to assess whether the MTHFR C677T polymorphism, folic acid supplementation, and circulating folate and vitamin B-12 concentrations during pregnancy were associated with wheezing, shortness of breath, and atopic dermatitis in offspring. The study was a population-based birth cohort from fetal life until 48 mo (n = 8742). The use of folic acid supplementation during pregnancy was assessed by questionnaire. Plasma folate and serum vitamin B-12 concentrations and the MTHFR C677T polymorphism were available from blood collected in early pregnancy. Atopic dermatitis, wheezing, and shortness of breath in the offspring were assessed by parental-derived questionnaires at 12, 24, 36, and 48 mo. Maternal folate >16.2 nmol/L and vitamin B-12 >178 pmol/L were positively associated with the development of atopic dermatitis [adjusted OR: 1.18 (95% CI: 1.05-1.33) and adjusted OR: 1.30 (95% CI: 1.06-1.60) for the highest quartiles of folate and vitamin B-12 concentrations, respectively] but not with wheezing and shortness of breath. Maternal MTHFR C677T polymorphism and folic acid supplementation were not associated with wheezing, shortness of breath, and atopic dermatitis. No interactions were found by age, family history of atopy, folic acid supplementation, MTHFR C677T polymorphism, or maternal smoking (P-interaction > 0.10). High folate and vitamin B-12 levels during pregnancy are associated with increased prevalence of atopic dermatitis in the offspring. Potential risks of high folate and vitamin B-12 concentrations on allergic outcomes should be evaluated when discussing mandatory fortification programs.
Gatford, K L; Quinn, K J; Walton, P E; Grant, P A; Hosking, B J; Egan, A R; Owens, P C
1997-10-01
The ontogeny of the IGF endocrine system was investigated in 15 young lambs before and after weaning at 62 days of age. Before weaning, plasma IGF-I concentrations were higher in rams than ewes, and plasma concentrations of IGF-II and IGF-binding protein-3 (IGFBP-3) also tended to be higher in rams than in ewes. Feed intake of ewes and rams was restricted after weaning to remove sex differences in feed intake. Plasma concentrations of IGF-I and IGFBP-3 did not differ between rams and ewes at 100 days of age, but plasma IGF-II was higher in rams than in ewes at this time. Since circulating concentrations of GH were higher in rams than in ewes at 100 days of age, this implies that the restricted feed intake blocked the IGF-I and IGFBP-3 responses to GH. We conclude that sex differences in circulating IGF-I and IGFBP-3 concentrations in the growing lamb alter with age, and are not present when nutrition is restricted.
Atrial natriuretic factor in two kidney--two clip renovascular hypertension in the rat.
Puyo, A M; Vega, G W; Pellegrino de Iraldi, A; Albornoz, L E; Rosón, M I; Scaglia, P; Celentano, M M; Corazza, J P; Palumbo, E L; Fernández, B E; de la Riva, I J
1998-01-01
Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.
Most, Jasper; van Can, Judith G P; van Dijk, Jan-Willem; Goossens, Gijs H.; Jocken, Johan; Hospers, Jeannette J.; Bendik, Igor; Blaak, Ellen E.
2015-01-01
Green tea, particularly epigallocatechin-3-gallate (EGCG), may affect body weight and composition, possibly by enhancing fat oxidation. The aim of this double-blind, randomized placebo-controlled cross-over study was to investigate whether 3-day supplementation with EGCG (282mg/day) stimulates fat oxidation and lipolysis in 24 overweight subjects (age = 30 ± 2yrs, BMI = 27.7 ± 0.3 kg/m2). Energy expenditure, substrate metabolism and circulating metabolites were determined during fasting and postprandial conditions. After 6 h, a fat biopsy was collected to examine gene expression. In 12 subjects, skeletal muscle glycerol, glucose and lactate concentrations were determined using microdialysis. EGCG-supplementation did not alter energy expenditure and substrate oxidation compared to placebo. Although EGCG reduced postprandial circulating glycerol concentrations (P = 0.015), no difference in skeletal muscle lipolysis was observed. Fasting (P = 0.001) and postprandial (P = 0.003) skeletal muscle lactate concentrations were reduced after EGCG-supplementation compared to placebo, despite similar tissue blood flow. Adipose tissue leptin (P = 0.05) and FAT/CD36 expression (P = 0.08) were increased after EGCG compared to placebo. In conclusion, 3-day EGCG-supplementation decreased postprandial plasma glycerol concentrations, but had no significant effects on skeletal muscle lipolysis and whole-body fat oxidation in overweight individuals. Furthermore, EGCG decreased skeletal muscle lactate concentrations, which suggest a shift towards a more oxidative muscle phenotype. PMID:26647963
Cooley-Andrade, O; Connor, D E; Ma, D D F; Weisel, J W; Parsi, K
2016-04-01
To investigate morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants sodium tetradecyl sulfate and polidocanol. Samples of whole blood, isolated leukocytes, platelets, endothelial cells, and fibroblasts were incubated with varying concentrations of sclerosants. Whole blood smears were stained with Giemsa and examined by light and bright field microscopy. Phalloidin and Hoechst stains were used to analyze cytoplasmic and nuclear morphology by fluorescence microscopy. Endothelial cell and fibroblasts were analyzed by live cell imaging. Higher concentrations of sclerosants induced cell lysis. Morphological changes in intact cells were observed at sublytic concentrations of detergents. Low concentration sodium tetradecyl sulfate induced erythrocyte acanthocytosis and macrocytosis, while polidocanol induced Rouleaux formation and increased the population of target cells and stomatocytes. Leukocytes showed swelling, blebbing, vacuolation, and nuclear degradation following exposure to sodium tetradecyl sulfate, while polidocanol induced pseudopodia formation, chromatin condensation, and fragmentation. Platelets exhibited pseudopodia with sodium tetradecyl sulfate and a "fried egg" appearance with polidocanol. Exposure to sodium tetradecyl sulfate resulted in size shrinkage in both endothelial cell and fibroblasts, while endothelial cell developed distinct spindle morphology. Polidocanol induced cytoplasmic microfilament bundles in both endothelial cell and fibroblasts. Patchy chromatin condensation was observed following exposure of fibroblasts to either agent. Detergent sclerosants are biologically active at sublytic concentrations. The observed morphological changes are consistent with cell activation, apoptosis, and oncosis. The cellular response is concentration dependent, cell-specific, and sclerosant specific. © The Author(s) 2015.
Jasnic, Nebojsa; Djordjevic, Jelena; Vujovic, Predrag; Lakic, Iva; Djurasevic, Sinisa; Cvijic, Gordana
2013-06-15
Thermal stressors such as low and high ambient temperature elicit an abundance of neuroendocrine responses including activation of the hypothalamo-pituitary-adrenal (HPA) axis and arginine vasopressin (AVP) release. The exposure to heat is a particularly interesting model for studying AVP action because this kind of stressor represents not only an unpleasant experience but also a threat to osmotic homeostasis. As AVP has long been recognized as a hormone involved in the modulation of HPA axis activity, the aim of this study was to elucidate the role of AVP in acutely heat-exposed rats using Nelivaptan, a selective vasopressin 1b receptor (V1bR) antagonist. Rats were exposed to high ambient temperature (38°C) for 60 min. The circulating hormones were determined by ELISA or chemiluminescence, and intrapituitary adrenocorticotropic hormone (ACTH) and V1bR level were determined by western blot. The results obtained show that V1bR blockade negatively affected the increase in blood ACTH caused by heat exposure. This treatment alone, or in combination with Nelivaptan, decreased intrapituitary V1bR levels while circulating AVP concentration was increased under the same conditions. Furthermore, a strong correlation was observed between blood ACTH and corticosterone concentration. In conclusion, our results directly confirm the positive role of AVP in the regulation of ACTH secretion from the pituitary in animals exposed to heat. Moreover, the results suggest that AVP from the general circulation influences pituitary V1bR.
Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer.
Bellassai, Noemi; Spoto, Giuseppe
2016-10-01
The detection of cancer biomarkers freely circulating in blood offers new opportunities for cancer early diagnosis, patient follow-up, and therapy efficacy assessment based on liquid biopsy. In particular, circulating cell-free nucleic acids released from tumor cells have recently attracted great attention also because they become detectable in blood before the appearance of other circulating biomarkers, such as circulating tumor cells. The detection of circulating nucleic acids poses several technical challenges that arise from their low concentration and relatively small size. Here, possibilities offered by innovative biosensing approaches for the detection of circulating DNA in peripheral blood and blood-derived products such as plasma and serum blood are discussed. Different transduction principles are used to detect circulating DNAs and great advantages are derived from the combined use of nanostructured materials.
Impacts of fine particulate matter on premature mortality under future climate change
NASA Astrophysics Data System (ADS)
Park, S.; Allen, R.; Lim, C. H.
2016-12-01
Climate change modulates concentration of fine particulate matter (PM2.5) via modifying atmospheric circulation and the hydrological cycle. Furthermore, surface PM2.5 is significantly associated with respiratory diseases and premature mortality. In this study, we assess the response of PM2.5 concentration to climate change in the future (end of 21st century) and its effects on year of life lost (YLL) and premature mortality. We use outputs from five models participating in the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP) to evaluate climate change effects on PM2.5: for present climate with current aerosol emissions and greenhouse gas concentrations, and for future climate, also with present-day aerosol emissions, but with end-of-the century greenhouse gas concentrations, sea surface temperatures and sea-ice. The results show that climate change is associated with an increase in PM2.5 concentration. Combined with global future population data from the United Nation (UN), we also find an increase in premature mortality and YLL.
Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D
2003-08-01
Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.
NASA Astrophysics Data System (ADS)
Polvani, Lorenzo M.; Abalos, Marta; Garcia, Rolando; Kinnison, Doug; Randel, William J.
2018-01-01
It is well established that increasing greenhouse gases, notably CO2, will cause an acceleration of the stratospheric Brewer-Dobson circulation (BDC) by the end of this century. We here present compelling new evidence that ozone depleting substances are also key drivers of BDC trends. We do so by analyzing and contrasting small ensembles of "single-forcing" integrations with a stratosphere resolving atmospheric model with interactive chemistry, coupled to fully interactive ocean, land, and sea ice components. First, confirming previous work, we show that increasing concentrations of ozone depleting substances have contributed a large fraction of the BDC trends in the late twentieth century. Second, we show that the phasing out of ozone depleting substances in coming decades—as a consequence of the Montreal Protocol—will cause a considerable reduction in BDC trends until the ozone hole is completely healed, toward the end of the 21st century.
Doskocz, R; Adamiec, R; Kwiatkowska, W; Alexewicz, P; Doskocz, W; Adamiec, J
1999-11-01
Systemic lupus erythematodes is a disease commonly associated with peripheric circulation disturbances. The goal of the study was the evaluation of the role of the following nuclear antibodies: anti-Ro (SS-A), anti-La (SS-B) and anti-Sm in the endothelium damage process in the SLE patients with symptoms of microcirculation disturbances. The concentration of plasma thrombomodulin was used as a marker of the endothelium destructive changes intensity. Twenty-four patients with SLE (22 women and 2 man) aged of 18-57 (the average age 40.50 +/- 9.72 years) in which occurred: the Raynauds symptom (16 patients), fingers cyanosis (5 patients) and fingers and/or toes necrosis (3 patients) were investigated. Antinuclear antibodies and thrombomodulin level was estimated with the ELISA method. In all patients, the concentration of anticardiolipin antibodies in serum was determined (ELISA-method, cardiolipin was used as an antigenes, Sigma USA). Higher titers of ANA antibodies in 83%, anti-SM antibodies in 30%, anti-Ro in 42% and anti-La in 42%, examined patients and higher titer of anti-Ro and anti-La antibodies together in 29% of examined patients were stated. Statistical significant correlation between the increased level of thrombomodulin and anti-La antibodies concentrations in serum of patients with the disease lasting over 6 years was found out. The significant statistical correlation of thrombomodulin concentration increasing and anti-La antibodies in serum was proved. The dynamism of limbs circulation disorders depends on the disease duration.
Nascimento, Regina A; Mendes, Gabryella; Possomato-Vieira, Jose S; Gonçalves-Rizzi, Victor Hugo; Kushima, Hélio; Delella, Flavia K; Dias-Junior, Carlos A
2015-06-01
Intoxication with lead (Pb) results in increased blood pressure by mechanisms involving matrix metalloproteinases (MMPs). Recent findings have revealed that MMP type two (MMP-2) seems to cleave vasoactive peptides. This study examined whether MMP-2 and MMP-9 levels/activities increase after acute intoxication with low lead concentrations and whether these changes were associated with increases in blood pressure and circulating endothelin-1 or with reductions in circulating adrenomedullin and calcitonin gene-related peptide (CGRP). Here, we expand previous findings and examine whether doxycycline (a MMPs inhibitor) affects these alterations. Wistar rats received intraperitoneally (i.p.) 1st dose 8 μg/100 g of lead (or sodium) acetate, a subsequent dose of 0.1 μg/100 g to cover daily loss and treatment with doxycycline (30 mg/kg/day) or water by gavage for 7 days. Similar whole-blood lead levels (9 μg/dL) were found in lead-exposed rats treated with either doxycycline or water. Lead-induced increases in systolic blood pressure (from 143 ± 2 to 167 ± 3 mmHg) and gelatin zymography of plasma samples showed that lead increased MMP-9 (but not MMP-2) levels. Both lead-induced increased MMP-9 activity and hypertension were blunted by doxycycline. Doxycycline also prevented lead-induced reductions in circulating adrenomedullin. No significant changes in plasma levels of endothelin-1 or CGRP were found. Lead-induced decreases in nitric oxide markers and antioxidant status were not prevented by doxycycline. In conclusion, acute lead exposure increases blood pressure and MMP-9 activity, which were blunted by doxycycline. These findings suggest that MMP-9 may contribute with lead-induced hypertension by cleaving the vasodilatory peptide adrenomedullin, thereby inhibiting adrenomedullin-dependent lowering of blood pressure. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Teubner, Brett J. W.
2013-01-01
Circulating concentrations of the stomach-derived “hunger-peptide” ghrelin increase in direct proportion to the time since the last meal. Exogenous ghrelin also increases food intake in rodents and humans, suggesting ghrelin may increase post-fast ingestive behaviors. Food intake after food deprivation is increased by laboratory rats and mice, but not by humans (despite dogma to the contrary) or by Siberian hamsters; instead, humans and Siberian hamsters increase food hoarding, suggesting the latter as a model of fasting-induced changes in human ingestive behavior. Exogenous ghrelin markedly increases food hoarding by ad libitum-fed Siberian hamsters similarly to that after food deprivation, indicating sufficiency. Here, we tested the necessity of ghrelin to increase food foraging, food hoarding, and food intake, and neural activation [c-Fos immunoreactivity (c-Fos-ir)] using anti-ghrelin Spiegelmer NOX-B11–2 (SPM), an l-oligonucleotide that specifically binds active ghrelin, inhibiting peptide-receptor interaction. SPM blocked exogenous ghrelin-induced increases in food hoarding the first 2 days after injection, and foraging and food intake at 1–2 h and 2–4 h, respectively, and inhibited hypothalamic c-Fos-ir. SPM given every 24 h across 48-h food deprivation inconsistently inhibited food hoarding after refeeding and c-Fos-ir, similarly to inabilities to do so in laboratory rats and mice. These results suggest that ghrelin may not be necessary for food deprivation-induced foraging and hoarding and neural activation. A possible compensatory response, however, may underlie these findings because SPM treatment led to marked increases in circulating ghrelin concentrations. Collectively, these results show that SPM can block exogenous ghrelin-induced ingestive behaviors, but the necessity of ghrelin for food deprivation-induced ingestive behaviors remains unclear. PMID:23804279
Circulating Endocannabinoid Concentrations and Sexual Arousal in Women
Klein, Carolin; Hill, Matthew N.; Chang, Sabrina C.H.; Hillard, Cecilia J.; Gorzalka, Boris B.
2013-01-01
Introduction Several lines of evidence point to the potential role of the endocannabinoid system in female sexual functioning. These include results from studies describing the subjective effects of exogenous cannabinoids on sexual functioning in humans and the observable effects of exogenous cannabinoids on sexual functioning in other species, as well as results from studies investigating the location of cannabinoid receptors in the brain and periphery, and the effects of cannabinoid receptor activation on neurotransmitters implicated in sexual functioning. While these lines of research suggest a role for the endocannabinoid system in female sexual functioning, no studies investigating the relationship between concentrations of endogenous cannabinoids (i.e., arachidonoylethanolamide [AEA] and 2-arachidonoylglycerol [2-AG]) and sexual functioning have been conducted in any species. Aim To measure circulating endocannabinoid concentrations in relation to subjective and physiological indices of sexual arousal in women (n = 21). Methods Serum endocannabinoid (AEA and 2-AG) concentrations were measured immediately prior to, and immediately following, viewing of neutral (control) and erotic (experimental) film stimuli in a repeated measures design. Physiological sexual arousal was measured via vaginal photoplethysmography. Subjective sexual arousal was measured both continuously and non-continuously. Pearson’s correlations were used to investigate the relationships between endocannabinoid concentrations and sexual arousal. Main Outcome Measures Changes in AEA and 2-AG concentrations from pre- to post-film and in relation to physiological and subjective indices of sexual arousal. Results Results revealed a significant relationship between endocannabinoid concentrations and female sexual arousal, whereby increases in both physiological and subjective indices of sexual arousal were significantly associated with decreases in AEA, and increases in subjective indices of sexual arousal were significantly associated with decreases in 2-AG. Conclusions These findings support the hypothesis that the endocannabinoid system is involved in female sexual functioning, with implications for furthering understanding of the biological mechanisms underlying female sexual functioning. PMID:22462722
Reimann, M J; Ljungvall, I; Hillström, A; Møller, J E; Hagman, R; Falk, T; Höglund, K; Häggström, J; Olsen, L H
2016-03-01
Cardiovascular disease in humans and dogs is associated with mildly increased circulating concentrations of C-reactive protein (CRP). Few studies have evaluated associations between circulating CRP and canine myxomatous mitral valve disease (MMVD) and the results reported have been divergent. The aim of this study was to investigate whether serum concentrations of CRP, determined using a novel automated canine-specific high-sensitivity CRP assay (Gentian hsCRP), were associated with severity of MMVD and selected clinical variables in dogs. The study included 188 client-owned dogs with different severities of MMVD. Dogs were classified based on ACVIM consensus statement guidelines (group A, n = 58; group B1, n = 56; group B2, n = 38; group C, n = 36). Data were analysed using descriptive statistics and multiple regression analysis. Dogs with congestive heart failure (CHF; group C) had significantly higher CRP concentrations (median, 2.65 mg/L; quartile 1-quartile 3, 1.09-5.09) compared to dogs in groups A (median, 0.97 mg/L; quartile 1-quartile 3, <0.50-1.97; P = 0.001), B1 (median, 0.78 mg/L; quartile 1-quartile 3, <0.50-1.73, P <0.0001) and B2 (median, 0.60 mg/L; quartile 1-quartile 3, <0.50-1.23; P <0.0001). Other variables reflecting disease severity, including left atrial to aortic root ratio (P = 0.0002, adjusted r(2) = 0.07) and left ventricular end-diastolic diameter normalised for bodyweight (P = 0.0005, adjusted r(2) = 0.06), were positively associated with CRP concentration, but the association disappeared if dogs with CHF were excluded from analysis. In conclusion, slightly higher CRP concentrations were found in dogs with CHF whereas severity of asymptomatic MMVD showed no association with CRP concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.
Mondul, Alison; Mancina, Rosellina M; Merlo, Andrea; Dongiovanni, Paola; Rametta, Raffaela; Montalcini, Tiziana; Valenti, Luca; Albanes, Demetrius; Romeo, Stefano
2015-08-01
Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2)) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations. © 2015 American Society for Nutrition.
von Jeinsen, Beatrice; Short, Meghan I; Xanthakis, Vanessa; Carneiro, Herman; Cheng, Susan; Mitchell, Gary F; Vasan, Ramachandran S
2018-06-21
Adipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity-associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community-based sample. We evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid-binding protein 4, retinol-binding protein 4, fetuin-A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e'. In multivariable-adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid-binding protein 4 concentrations but positively related to retinol-binding protein 4 and leptin receptor levels ( P ≤0.002 for all). Left atrial end-systolic dimension was inversely related to leptin but positively related to retinol-binding protein 4 concentrations ( P ≤0.0001). E/e' was inversely related to leptin receptor levels ( P =0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid-binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P <0.05 for interactions). Fractional shortening was not associated with any of the adipokines. No echocardiographic trait was associated with fetuin-A or adiponectin concentrations. In our cross-sectional study of a large, young to middle-aged, relatively healthy community-based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of prohypertrophic and antihypertrophic adipokines in a context-specific manner. These observations may offer insights into the pathogenesis of the cardiomyopathy of obesity. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
NASA Astrophysics Data System (ADS)
Yasunari, Teppei J.; Shiraiwa, Takayuki; Kanamori, Syosaku; Fujii, Yoshiyuki; Igarashi, Makoto; Yamazaki, Koji; Benson, Carl S.; Hondoh, Takeo
2007-05-01
The North Pacific is subject to various seasonal climate phenomena and material circulations. Therefore intra-annual ice core data are necessary for an assessment of the climate variations. To assess past variations, a 50-m ice core was drilled at the summit of Mount Wrangell Volcano, Alaska. The dust number, tritium concentrations, and stable hydrogen isotope were analyzed. The period covered was from 1992 to 2002. We found that the concentrations of both fine dust (0.52-1.00 μm), an indicator of long-range transport, and coarse dust (1.00-8.00 μm) increased together every spring. Moreover, their concentrations increased drastically after 2000, corresponding to the recent increase in Asian dust outbreaks in spring. Additionally, an increase in the spring of 2001 corresponded to the largest dust storm recorded in east Asia since 1979. Therefore our findings imply that Asian dust strongly polluted Mount Wrangell every spring. The stratospheric tracer, tritium, had late spring maxima almost every year, and we found this useful for ice core dating to identify late spring in the North Pacific region. We also found that a high positive annual correlation existed between the calculated tritium and fine dust fluxes from late spring to summer. We propose that an annual relationship between the stratosphere-troposphere exchange and Asian dust storm are most closely connected in late spring because their activities are weak in summer. The Mount Wrangell ice core is important and useful for assessing the dust and tritium circulation in the distant past around the North Pacific with probable intra-annual timescale information.
Truong, Ha H; Chrystal, Peter V; Moss, Amy F; Selle, Peter H; Liu, Sonia Yun
2017-12-01
A foundation diet, an intermediate blend and a summit diet were formulated with different levels of soyabean meal, casein and crystalline amino acids to compare 'slow' and 'rapid' protein diets. The diets were offered to male Ross 308 chicks from 7 to 28 d post-hatch and assessed parameters included growth performance, nutrient utilisation, apparent digestibility coefficients and disappearance rates of starch and protein (N) in four small intestinal segments. Digestibility coefficients and disappearance rates of sixteen amino acids in three small intestinal segments and amino acid concentrations in plasma from portal and systemic circulations from the foundation and summit diets were determined. The dietary transition significantly accelerated protein (N) disappearance rates in the distal jejunum and ileum. The transition from foundation to summit diets significantly increased starch digestibility coefficients in the ileum and disappearance rates in all four small intestinal segments. These starch responses were associated with significant enhancements in nutrient utilisation. The dietary transition linearly increased digestibility coefficients and disappearance rates of amino acids in the majority of cases. The summit diet increased plasma concentrations of five amino acids but decreased those of four amino acids relative to the foundation diet to significant extents. Plasma concentrations of free amino acids were higher in the portal than systemic circulations. Rapid protein disappearance rates advantaged poultry performance and influenced post-enteral availability of amino acids. If the underlying mechanisms are to be identified, further research into the impact of protein digestive dynamics on broiler performance is required but appears justified.
Measurements of the Early Development of Trailing Vorticity from a Rotor
NASA Technical Reports Server (NTRS)
McAlister, Kenneth W.; Heineck, James T.
2002-01-01
The wake behind a two-bladed model rotor in light climb was measured using particle image velocimetry, with particular emphasis on the development of the trailing vortex during the first revolution of the rotor. The distribution of vorticity was distinguished from the slightly elliptical swirl pattern. Peculiar dynamics within the "void" region may explain why the peak vorticity appeared to shift away from the center as the vortex aged, suggesting the onset of instability. The swirl and axial velocities (which reached 44% and 12% of the rotor tip speed, respectively) were found to be asymmetric relative to the vortex center. In particular, the axial flow was composed of two concentrated zones moving in opposite directions. The radial distribution of the circulation rapidly increased in magnitude until reaching a point just beyond the core radius, after which the rate of growth decreased significantly. The core-radius circulation increased slightly with wake age, but the large-radius circulation appeared to remain relatively constant. The radial distributions of swirl velocity and vorticity exhibit self-similar behaviors, especially within the core. The diameter of the vortex core was initially about 10% of the rotor-blade chord, but more than doubled its size after one revolution of the rotor.
NASA Technical Reports Server (NTRS)
Wilcox, E. M.; Sud, Y. C.; Walker, G.
2009-01-01
Aerosol perturbations over selected land regions are imposed in Version-4 of the Goddard Earth Observing System (GEOS-4) general circulation model (GCM) to assess the influence of increasing aerosol concentrations on regional circulation patterns and precipitation in four selected regions: India, Africa, and North and South America. Part 1 of this paper addresses the responses to aerosol perturbations in India and Africa. This paper presents the same for aerosol perturbations over the Americas. GEOS-4 is forced with prescribed aerosols based on climatological data, which interact with clouds using a prognostic scheme for cloud microphysics including aerosol nucleation of water and ice cloud hydrometeors. In clear-sky conditions the aerosols interact with radiation. Thus the model includes comprehensive physics describing the aerosol direct and indirect effects on climate (hereafter ADE and AIE respectively). Each simulation is started from analyzed initial conditions for 1 May and was integrated through June-July-August of each of the six years: 1982 1987 to provide a 6-ensemble set. Results are presented for the difference between simulations with double the climatological aerosol concentration and one-half the climatological aerosol concentration for three experiments: two where the ADE and AIE are applied separately and one in which both the ADE and AIE are applied. The ADE and AIE both yield reductions in net radiation at the top of the atmosphere and surface while the direct absorption of shortwave radiation contributes a net radiative heating in the atmosphere. A large net heating of the atmosphere is also apparent over the subtropical North Atlantic Ocean that is attributable to the large aerosol perturbation imposed over Africa. This atmospheric warming and the depression of the surface pressure over North America contribute to a northward shift of the inter-Tropical Convergence Zone over northern America, an increase in precipitation over Central America and the Caribbean, and an enhancement of convergence in the North American monsoon region.
Cesium-137 concentrations in marine macroalgae from different biotopes in the Aegean Sea (Greece).
Sawidis, Thomas; Heinrich, Gerorg; Brown, Murray-T
2003-03-01
The commonest species of red, brown, and green macroalgae were sampled from a range of biotopes in the Aegean Sea during 1998 for their 137Cs content. Significant differences in 137Cs concentrations were found among different species growing under similar environmental conditions, suggesting that uptake does not follow physical levels but is influenced by allometric parameters and physiological mechanisms. 137Cs content in collected seaweeds were in the descending order: Ulva lactuca>Enteromorpha linza>Gracilaria verrucosa>Ceramium rubrum>Cystoseira barbata. A comparison of the stations studied indicated that the degree of accumulation is also dependent on the geomorphology of the specific area. The west side of Thermaikos Gulf, where the rivers Axios, Aliakmon, and Pinios flow, was highly contaminated as was the Strymonicos Gulf where the river Strymon flows. High cesium concentrations were also observed in algae from Lemnos Island near the mouth of the Dardanelles Channel, most likely due to the horizontal circulation of water masses from the Marmaras Sea to the Aegean Sea resulting in the discharge of 137Cs during the purification process in the Black Sea through the Dardanelles Straits. It is concluded that the general dispersion of 137Cs results from the water circulation regime within the Aegean Sea. Higher levels are present in the northern part of the basin due to current circulation originating from the Black Sea and from outflow of rivers. Levels decrease to the south and east, but increase again to the west of Crete where the Black Sea water mass can be periodically traced.
NASA Astrophysics Data System (ADS)
Nakanowatari, Takuya; Nakamura, Tomohiro; Uchimoto, Keisuke; Nishioka, Jun; Mitsudera, Humio; Wakatsuchi, Masaaki
2017-05-01
Iron (Fe) is an essential nutrient for marine phytoplankton and it constitutes an important element in the marine carbon cycle in the ocean. This study examined the mechanisms controlling seasonal variation of dissolved Fe (dFe) in the western subarctic North Pacific (WSNP), using an ocean general circulation model coupled with a simple biogeochemical model incorporating a dFe cycle fed by two major sources (atmospheric dust and continental shelf sediment). The model reproduced the seasonal cycle of observed concentrations of dFe and macronutrients at the surface in the Oyashio region with maxima in winter (February-March) and minima in summer (July-September), although the simulated seasonal amplitudes are a half of the observed values. Analysis of the mixed-layer dFe budget indicated that both local vertical entrainment and lateral advection are primary contributors to the wintertime increase in dFe concentration. In early winter, strengthened northwesterly winds excite southward Ekman transport and Ekman upwelling over the western subarctic gyre, transporting dFe-rich water southward. In mid to late winter, the southward western boundary current of the subarctic gyre and the outflow from the Sea of Okhotsk also bring dFe-rich water to the Oyashio region. The contribution of atmospheric dust to the dFe budget is several times smaller than these ocean transport processes in winter. These results suggest that the westerly wind-induced Ekman transport and gyre circulation systematically influence the seasonal cycle of WSNP surface dFe concentration.
Coulson, J; Bagley, L; Barnouin, Y; Bradburn, S; Butler-Browne, G; Gapeyeva, H; Hogrel, J-Y; Maden-Wilkinson, T; Maier, A B; Meskers, C; Murgatroyd, C; Narici, M; Pääsuke, M; Sassano, L; Sipilä, S; Al-Shanti, N; Stenroth, L; Jones, D A; McPhee, J S
2017-09-01
Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.
Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome
TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA
2013-01-01
Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the controls (median, 8.6%; range, 0–27.7% vs. median, 17.6%; range, 2.8–49.6%), suggesting an increased CD34+ cell survival. The functional evaluation of circulating hematopoietic progenitors showed specific patterns in NS and NS/MPD. These tests are a reliable integrative tool that, together with clinical data and other hematological parameters, could help detect NS patients with a high risk for a myeloproliferative evolution. PMID:23756559
Effect of Weight Reduction on Cardiovascular Risk Factors and CD34-positive Cells in Circulation
Mikirova, Nina A; Casciari, Joseph J; Hunninghake, Ronald E; Beezley, Margaret M
2011-01-01
Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis. In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body composition, lipid profile and CD34-positive cells in circulation. During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting. The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers. As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation. PMID:21850193
Effect of weight reduction on cardiovascular risk factors and CD34-positive cells in circulation.
Mikirova, Nina A; Casciari, Joseph J; Hunninghake, Ronald E; Beezley, Margaret M
2011-01-01
Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis. In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body composition, lipid profile and CD34-positive cells in circulation. During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting. The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers. As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation.
ERTS-1 observations of sea surface circulation and sediment transport, Cook Inlet, Alaska
NASA Technical Reports Server (NTRS)
Wright, F. F.; Sharma, G. D.; Burbank, D. C.
1973-01-01
Cook Inlet is a large tide-dominated estuary in southern Alaska. Highly turbid streams enter the upper inlet, providing an excellent tracer for circulation in the lower inlet. MSS 4 and 5 images both can be used in this area to plot sediment and pollutant trajectories, areas of (probable) commercial fish concentration, and the entire circulation regime.
Atmospheric conditions during high ragweed pollen concentrations in Zagreb, Croatia.
Prtenjak, Maja Telišman; Srnec, Lidija; Peternel, Renata; Madžarević, Valentina; Hrga, Ivana; Stjepanović, Barbara
2012-11-01
We examined the atmospheric conditions favourable to the occurrence of maximum concentrations of ragweed pollen with an extremely high risk of producing allergy. Over the 2002-2009 period, daily pollen data collected in Zagreb were used to identify two periods of high pollen concentration (> 600 grains/m(3)) for our analysis: period A (3-4 September 2002) and period B (6-7 September 2003). Synoptic conditions in both periods were very similar: Croatia was under the influence of a lower sector high pressure system moving slowly eastward over Eastern Europe. During the 2002-2009 period, this type of weather pattern (on ~ 70% of days), in conjunction with almost non-gradient surface pressure conditions in the area (on ~ 30% of days) characterised days when the daily pollen concentrations were higher than 400 grains/m(3). Numerical experiments using a mesoscale model at fine resolution showed successful multi-day simulations reproducing the local topographic influence on wind flow and in reasonable agreement with available observations. According to the model, the relatively weak synoptic flow (predominantly from the eastern direction) allowed local thermal circulations to develop over Zagreb during both high pollen episodes. Two-hour pollen concentrations and 48-h back-trajectories indicated that regional-range transport of pollen grains from the central Pannonian Plain was the cause of the high pollen concentrations during period A. During period B, the north-westward regional-range transport in Zagreb was supplemented significantly by pronounced horizontal recirculation of pollen grains. This recirculation happened within the diurnal local circulation over the city, causing a late-evening increase in pollen concentration.
Atmospheric conditions during high ragweed pollen concentrations in Zagreb, Croatia
NASA Astrophysics Data System (ADS)
Prtenjak, Maja Telišman; Srnec, Lidija; Peternel, Renata; Madžarević, Valentina; Hrga, Ivana; Stjepanović, Barbara
2012-11-01
We examined the atmospheric conditions favourable to the occurrence of maximum concentrations of ragweed pollen with an extremely high risk of producing allergy. Over the 2002-2009 period, daily pollen data collected in Zagreb were used to identify two periods of high pollen concentration (> 600 grains/m3) for our analysis: period A (3-4 September 2002) and period B (6-7 September 2003). Synoptic conditions in both periods were very similar: Croatia was under the influence of a lower sector high pressure system moving slowly eastward over Eastern Europe. During the 2002-2009 period, this type of weather pattern (on ~ 70% of days), in conjunction with almost non-gradient surface pressure conditions in the area (on ~ 30% of days) characterised days when the daily pollen concentrations were higher than 400 grains/m3. Numerical experiments using a mesoscale model at fine resolution showed successful multi-day simulations reproducing the local topographic influence on wind flow and in reasonable agreement with available observations. According to the model, the relatively weak synoptic flow (predominantly from the eastern direction) allowed local thermal circulations to develop over Zagreb during both high pollen episodes. Two-hour pollen concentrations and 48-h back-trajectories indicated that regional-range transport of pollen grains from the central Pannonian Plain was the cause of the high pollen concentrations during period A. During period B, the north-westward regional-range transport in Zagreb was supplemented significantly by pronounced horizontal recirculation of pollen grains. This recirculation happened within the diurnal local circulation over the city, causing a late-evening increase in pollen concentration.
Kang, Eun Seok; Magkos, Faidon; Sienkiewicz, Elizabeth; Mantzoros, Christos S
2011-06-01
Animal and in vitro studies indicate that leptin alleviates starvation-induced reduction in circulating vaspin and stimulates the production of visfatin. We thus examined whether vaspin and visfatin are affected by short- and long-term energy deprivation and leptin administration in human subjects in vivo. We measured circulating levels of vaspin and visfatin i) before and after 72 h of starvation (leading to severe hypoleptinemia) with or without leptin administration in replacement doses in 13 normal-weight subjects, ii) before and after 72 h of starvation with leptin administration in pharmacological doses in 13 lean and obese subjects, iii) during chronic energy deficiency in eight women with hypothalamic amenorrhea on leptin replacement for 3 months, and iv) during chronic energy deficiency in 18 women with hypothalamic amenorrhea on leptin replacement or placebo for 3 months. Acute starvation decreased serum leptin to 21% of baseline values, (P=0.002) but had no significant effect on vaspin and visfatin concentrations (P>0.05). Nor did normalization of leptin levels affect the concentrations of these two adipokines (P>0.9). Leptin replacement in women with hypothalamic amenorrhea did not significantly alter vaspin and visfatin concentrations, whether relative to baseline or placebo administration (P>0.25). Pharmacological doses of leptin did not affect circulating vaspin and visfatin concentrations (P>0.9). Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency leading to hypoleptinemia and are not regulated by leptin in human subjects, indicating that these adipocyte-secreted hormonal regulators of metabolism are independently regulated in humans.
Interpretation of snow-climate feedback as produced by 17 general circulation models
NASA Technical Reports Server (NTRS)
Cess, R. D.; Zhang, M.-H.; Potter, G. L.; Blanchet, J.-P.; Chalita, S.; Colman, R.; Dazlich, D. A.; Del Genio, A. D.; Lacis, A. A.; Dymnikov, V.
1991-01-01
Snow feedback is expected to amplify global warming caused by increasing concentrations of atmospheric greenhouse gases. The conventional explanation is that a warmer earth will have less snow cover, resulting in a darker planet that absorbs more solar radiation. An intercomparison of 17 general circulation models, for which perturbations of sea surface temperature were used as a surrogate climate change, suggests that this explanation is overly simplistic. The results instead indicate that additional amplification or moderation may be caused both by cloud interactions and longwave radiation. One measure of this net effect of snow feedback was found to differ markedly among the 17 climate models, ranging from weak negative feedback in some models to strong positive feedback in others.
Increased Circulating Levels of Vitamin D Binding Protein in MS Patients
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
Experimental Myocardial Infarction Upregulates Circulating Fibroblast Growth Factor-23.
Andrukhova, Olena; Slavic, Svetlana; Odörfer, Kathrin I; Erben, Reinhold G
2015-10-01
Myocardial infarction (MI) is a major cause of death worldwide. Epidemiological studies have linked vitamin D deficiency to MI incidence. Because fibroblast growth factor-23 (FGF23) is a master regulator of vitamin D hormone production and has been shown to be associated with cardiac hypertrophy per se, we explored the hypothesis that FGF23 may be a previously unrecognized pathophysiological factor causally linked to progression of cardiac dysfunction post-MI. Here, we show that circulating intact Fgf23 was profoundly elevated, whereas serum vitamin D hormone levels were suppressed, after induction of experimental MI in rat and mouse models, independent of changes in serum soluble Klotho or serum parathyroid hormone. Both skeletal and cardiac expression of Fgf23 was increased after MI. Although the molecular link between the cardiac lesion and circulating Fgf23 concentrations remains to be identified, our study has uncovered a novel heart-bone-kidney axis that may have important clinical implications and may inaugurate the new field of cardio-osteology. © 2015 American Society for Bone and Mineral Research.
NASA Astrophysics Data System (ADS)
Powley, Helen R.; Krom, Michael D.; Van Cappellen, Philippe
2018-03-01
Human activities have significantly modified the inputs of land-derived phosphorus (P) and nitrogen (N) to the Mediterranean Sea (MS). Here, we reconstruct the external inputs of reactive P and N to the Western Mediterranean Sea (WMS) and Eastern Mediterranean Sea (EMS) over the period 1950-2030. We estimate that during this period the land derived P and N loads increased by factors of 3 and 2 to the WMS and EMS, respectively, with reactive P inputs peaking in the 1980s but reactive N inputs increasing continuously from 1950 to 2030. The temporal variations in reactive P and N inputs are imposed in a coupled P and N mass balance model of the MS to simulate the accompanying changes in water column nutrient distributions and primary production with time. The key question we address is whether these changes are large enough to be distinguishable from variations caused by confounding factors, specifically the relatively large inter-annual variability in thermohaline circulation (THC) of the MS. Our analysis indicates that for the intermediate and deep water masses of the MS the magnitudes of changes in reactive P concentrations due to changes in anthropogenic inputs are relatively small and likely difficult to diagnose because of the noise created by the natural circulation variability. Anthropogenic N enrichment should be more readily detectable in time series concentration data for dissolved organic N (DON) after the 1970s, and for nitrate (NO3) after the 1990s. The DON concentrations in the EMS are predicted to exhibit the largest anthropogenic enrichment signature. Temporal variations in annual primary production over the 1950-2030 period are dominated by variations in deep-water formation rates, followed by changes in riverine P inputs for the WMS and atmospheric P deposition for the EMS. Overall, our analysis indicates that the detection of basin-wide anthropogenic nutrient concentration trends in the MS is rendered difficult due to: (1) the Atlantic Ocean contributing the largest reactive P and N inputs to the MS, hence diluting the anthropogenic nutrient signatures, (2) the anti-estuarine circulation removing at least 45% of the anthropogenic nutrients inputs added to both basins of the MS between 1950 and 2030, and (3) variations in intermediate and deep water formation rates that add high natural noise to the P and N concentration trajectories.
NASA Astrophysics Data System (ADS)
Yamamoto, Tatsumi; Kawasaki, Hiroyuki; Mori, Hidetoshi
2017-11-01
Loop type bubble columns have good performance of liquid circulation and mass transfer by airlift effect, where the liquid circulation time is an important measurable characteristic parameter. This parameter is affected by the column construction, the aspect ratio of the column, the cross-sectional area ratio of down comer to riser (R), and the superficial gas velocity in the riser (UGR). In this work, the mean gas holdup and the liquid circulation time (TC) have been measured in four types of loop airlift type bubble column: concentric tube internal loop airlift type, rectangular internal loop airlift type, external loop airlift type, external loop airlift with separator. Air and tap water were used as gas and liquid phase, respectively. The results have demonstrated that the mean gas holdup in riser increases in proportion to UGR, and that it in downcomer changes according to the geometric parameters of each bubble column. TC has been found to conform to an empirical equation which depends on UGR and the length of draft tube or division plate in the region of 0.33 < R < 1.
Hennings, Anna; Hannemann, Anke; Rettig, Rainer; Dörr, Marcus; Nauck, Matthias; Völzke, Henry; Lerch, Markus M.; Lieb, Wolfgang; Friedrich, Nele
2016-01-01
Background An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population. Methods Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated. Results In both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed. Conclusion Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected. PMID:27893762
Hennings, Anna; Hannemann, Anke; Rettig, Rainer; Dörr, Marcus; Nauck, Matthias; Völzke, Henry; Lerch, Markus M; Lieb, Wolfgang; Friedrich, Nele
2016-01-01
An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population. Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated. In both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed. Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected.
Rezvani, Reza; Cianflone, Katherine; McGahan, John P.; Berglund, Lars; Bremer, Andrew A.; Keim, Nancy L.; Griffen, Steven C.; Havel, Peter J.; Stanhope, Kimber L.
2013-01-01
Objective We determined the effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity. Design and Methods 32 overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8 and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks. Results Fasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels. Conclusions The consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption. PMID:23512943
Soliman, Ashraf T; Omar, Magdi; Assem, Hala M; Nasr, Ibrahim S; Rizk, Mohamed M; El Matary, Wael; El Alaily, Rania K
2002-03-01
Although obesity is a frequent feature of type 2 diabetes mellitus (DM), many patients with type 1 DM are prone to high body mass index (BMI). We measured serum leptin concentrations in a cohort of children (n = 55) with type 1 diabetes mellitus (DM), as well as their anthropometric parameters including BMI, skin fold thickness at multiple sites, and midarm circumference. Glycemic control was assessed by blood glucose (BG) monitoring before meals, and measurement of glycated hemoglobin (HbA1c) and insulin dose/kg/d was recorded. Dietary evaluation and assessment of caloric intake (kg/d) was performed by an expert dietitian. In the newly diagnosed children (n = 10) before initiation of insulin therapy, circulating leptin concentration was significantly lower (1.1 +/- 0.8 ng/dL) versus 5 days after insulin therapy (1.45 +/- 0.7 ng/dL). The decreased leptin level appears to be related to insulinopenia in these patients. In 45 children with type 1 DM on conventional therapy (2 doses of insulin mixture (NPH and regular) subcutaneous (SC) before breakfast and dinner for more than 2 years), serum leptin concentration was significantly higher (2.15 +/- 1 ng/dL) compared with age-matched normal children (1.3 +/- 1 ng/dL). Diabetic children were further divided into 2 groups according to their HbA1c level: group 1 with HbA1C less than 7.5% (less than 2 SD above the mean for normal population) (n = 29) and group 2 with HbA1c greater than 7.5%. (greater than 2 SD above the mean for normal population) (n = 16). Patients with a higher HbA1c level (group 2) had a higher leptin concentration (2.3 +/- 0.8 ng/dL), higher BMI (17.8 +/- 1.7), and were receiving higher insulin dose/kg (0.92 +/- 0.2 U/kg/d) compared with group 1 (lower HbA1c) (1.78 +/- 0.8 ng/dL, 16.7 +/- 1.5, and 0.59 +/- 0.2 U/kg/d, respectively). Group 2 patients had a higher incidence of late morning hypoglycemia (9/29) versus group 1 patients (2/16). Analysis of dietary intake showed that patients with a higher HbA1c (group 2) consumed more calories (73.5 +/- 10.5 kcal/kg/d) versus patients with lower HbA1c (64.2 +/- 8.7 kcal/kg/d). These findings pointed to the unphysiologic nature of injecting a mixture of insulin twice daily. To cover the relatively big lunch meal (40% to 50% of the total caloric intake in the Arab countries) and prevent afternoon hyperglycemia, there is a great tendency to increase NPH dose before breakfast. This, in turn, induces late-morning hypoglycemia and increases appetite and food intake at that time. Multiple regression analysis showed that circulating leptin concentrations (the dependent variable) were best correlated with the mean skinfold thickness (SFT), BMI, and caloric intake/kg/d (together they explained 65% of the variability in leptin concentrations). It appears that oversubstitution by insulin and increased food intake stimulate fat synthesis and subsequently BMI. Increased appetite and BMI contribute to increased leptin secretion and explains the higher leptin levels in undercontrolled diabetic children (higher circulating HbA1c concentrations) who were oversubstituted by insulin. Copyright 2002 by W.B. Saunders Company
NASA Astrophysics Data System (ADS)
Coria-Monter, Erik; Monreal-Gómez, María Adela; Salas de León, David Alberto; Durán-Campos, Elizabeth; Merino-Ibarra, Martín
2017-09-01
Nutrient and chlorophyll-a distributions in the Bay of La Paz, Gulf of California, Mexico were analyzed during the late spring of 2004 to assess their relations to hydrography and circulation patterns. The results show the presence of both Gulf of California Water and Subtropical Subsurface Water. Water circulation was dominated by wind stress driven cyclonic circulation along f / H contours (f is planetary vorticity and H is depth), and upwelling resulting from the divergence shows a vertical velocity of ∼0.4 m d-1. Nutrient concentrations were higher in the center of the cyclonic pattern, where a rise in the nutricline contributed nutrients to the euphotic layer as a result of Ekman pumping. The vertical section showed the presence of a chlorophyll-a maximum at the thermocline shoaling to a depth of only 12 m. Along the surface, two peaks of chlorophyll-a were observed, one at Boca Grande and another off San Juan de la Costa, associated with upwelling and mixing derived from current interactions with abrupt topographies. The chlorophyll-a maximum increased from 0.8 mg m-3 in the external part of the cyclonic pattern to 2.0 mg m-3 in its center. The vertically integrated chlorophyll-a concentrations followed a similar pattern, rising from 10 to 20 mg m-2 and reaching their highest values in the center of the cyclonic circulation pattern. A schematic model was developed to describe processes that occur in late spring: the wind stress driven cyclonic structure promotes upward nutrient flux, which in turn drives an enhancement of chlorophyll-a. Upwelling was found to be the main mechanism of fertilization responsible for the enhancement of productivity levels by means of nutrient transport into the euphotic zone during spring. Other chlorophyll enhancement areas point to the occurrence of additional fertilization processes that may derive from interactions between cyclonic circulation patterns and the topography off of San Juan de la Costa, where phosphate mining occurs.
Deglacial diatom production in the tropical North Atlantic driven by enhanced silicic acid supply
NASA Astrophysics Data System (ADS)
Hendry, Katharine R.; Gong, Xun; Knorr, Gregor; Pike, Jennifer; Hall, Ian R.
2016-03-01
Major shifts in ocean circulation are thought to be responsible for abrupt changes in temperature and atmospheric CO2 during the last deglaciation, linked to variability in meridional heat transport and deep ocean carbon storage. There is also widespread evidence for shifts in biological production during these times of deglacial CO2 rise, including enhanced diatom production in regions such as the tropical Atlantic. However, it remains unclear as to whether this diatom production was driven by enhanced wind-driven upwelling or density-driven vertical mixing, or by elevated thermocline concentrations of silicic acid supplied to the surface at a constant rate. Here, we demonstrate that silicic acid supply at depth in the NE Atlantic was enhanced during the abrupt climate events of the deglaciation. We use marine sediment archives to show that an increase in diatom production during abrupt climate shifts could only occur in regions of the NE Atlantic where the deep supply of silicic acid could reach the surface. The associated changes are indicative of enhanced regional wind-driven upwelling and/or weakened stratification due to circulation changes during phases of weakened Atlantic meridional overturning. Globally near-synchronous pulses of diatom production and enhanced thermocline concentrations of silicic acid suggest that widespread deglacial surface-driven breakdown of stratification, linked to changes in atmospheric circulation, had major consequences for biological productivity and carbon cycling.
Park, Heyjun; Wood, Madeleine R; Malysheva, Olga V; Jones, Sara; Mehta, Saurabh; Brannon, Patsy M; Caudill, Marie A
2017-12-01
Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P < 0.001) with 24,25-dihydroxyvitamin D 3 Moreover, these placental metabolites were strongly correlated ( r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations ( P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 ( LRP2 , also known as megalin) with 25(OH)D 3 and the C3 epimer of 25(OH)D 3 [3-epi-25(OH)D 3 ]; cubilin ( CUBN ) with 25(OH)D 3 ; 25-hydroxylase ( CYP2R1 ) with 3-epi-25(OH)D 3 ; 24-hydroxylase ( CYP24A1 ) with 25(OH)D 3 , 3-epi-25(OH)D 3 , and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]; and 1α-hydroxylase [( CYP27B1 ) with 3-epi-25(OH)D 3 and 1,25(OH) 2 D 3 ]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D 3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment. Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1 -associated increase in 1,25(OH) 2 D 3 ] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D 3 , suggest that the placenta may play an active role in modulating the vitamin D metabolite profile in maternal circulation in human pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867. © 2017 American Society for Nutrition.
Placental passage of antiepileptic drugs at delivery and neonatal outcomes
Bank, Anna M.; Stowe, Zachary N.; Newport, D. Jeffrey; Ritchie, James C.; Pennell, Page B.
2017-01-01
Summary Children of women treated with antiepileptic drugs (AEDs) are at increased risk for adverse outcomes detectable in the neonatal period, which may be associated with the amount of AED in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical to maternal ratios for AEDs, and to determine whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother-newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical to maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical to maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical to maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications. PMID:28387929
Cell-Free circulating DNA: a new biomarker for the acute coronary syndrome.
Cui, Ming; Fan, Mengkang; Jing, Rongrong; Wang, Huimin; Qin, Jingfeng; Sheng, Hongzhuan; Wang, Yueguo; Wu, Xinhua; Zhang, Lurong; Zhu, Jianhua; Ju, Shaoqing
2013-01-01
In recent studies, concentrations of cell-free circulating DNA (cf-DNA) have been correlated with clinical characteristics and prognosis in several diseases. The relationship between cf-DNA concentrations and the acute coronary syndrome (ACS) remains unknown. Moreover, no data are available for the detection cf-DNA in ACS by a branched DNA (bDNA)-based Alu assay. The aim of the present study was to investigate cf-DNA concentrations in ACS and their relationship with clinical features. Plasma cf-DNA concentrations of 137 ACS patients at diagnosis, of 60 healthy individuals and of 13 patients with stable angina (SA) were determined using a bDNA-based Alu assay. ACS patients (median 2,285.0, interquartile range 916.4-4,857.3 ng/ml), especially in ST-segment elevation myocardial infarction patients (median 5,745.4, interquartile range 4,013.5-8,643.9 ng/ml), showed a significant increase in plasma cf-DNA concentrations compared with controls (healthy controls: median 118.3, interquartile range 81.1-221.1 ng/ml; SA patients: median 202.3, interquartile range 112.7-256.1 ng/ml) using a bDNA-based Alu assay. Moreover, we found positive correlations between cf-DNA and Gensini scoring and GRACE (Global Registry of Acute Coronary Events) scoring in ACS. cf-DNA may be a valuable marker for diagnosing and predicting the severity of coronary artery lesions and risk stratification in ACS. Copyright © 2013 S. Karger AG, Basel.
Varela, Lourdes M; Ortega, Almudena; Bermudez, Beatriz; Lopez, Sergio; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G
2011-05-01
The postprandial metabolism of dietary fats results in the production of apolipoprotein B-48 (apoB48)-containing triglyceride-rich lipoproteins (TRLs), which cause rapid receptor-mediated macrophage lipid engorgement via the apoB48 cell surface receptor (apoB48R). Monocytes circulate together with apoB48-containing TRLs in the postprandial bloodstream and may start accumulating lipids even before their migration to tissues and differentiation to macrophages. We sought to determine whether circulating monocytes are equipped with apoB48R and whether, in the postprandial state, circulating monocytes accumulate lipids and modulate apoB48R transcriptional activity after intake of a high-fat meal. In a crossover design, we studied the effect of a high-fat meal on fasting and postprandial concentrations of triglycerides, free fatty acids, cholesterol, and insulin in 12 healthy men. TRLs and monocytes were freshly isolated at fasting, hourly until the postprandial peak, and at the late postprandial phase. TRLs were subjected to triglycerides, apoB48, and apolipoprotein B-100 analyses; and lipid accumulation and apoB48R mRNA expression levels were measured in monocytes. Monocytes showed a time-dependent lipid accumulation in response to the high-fat meal, which was paralleled by an increase in apoB48R mRNA expression levels. These effects were coincident only with an increase in apoB48-containing TRLs in the postprandial phase and were also observed ex vivo in freshly isolated monocytes incubated with apoB48-containing TRLs. In a setting of abundant plasma apoB48-containing TRLs, these findings highlight the role of dietary fat in inducing lipid accumulation and apoB48R gene transcription in circulating monocytes.
Jia, Yanjun; Luo, Xiaohe; Ji, Ying; Xie, Jingwen; Jiang, Han; Fu, Mao; Li, Xiaoqiang
2017-09-01
C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown to promote lipid metabolism, enhance insulin sensitivity and protect against cardiovascular disease. However, previous studies in humans have produced controversial results regarding the association between CTRP9 and insulin resistance. The objective of this study was to evaluate the relationships between CTRP9 and insulin resistance in Chinese population. Subjects with normal glucose tolerance (NGT, n=108), impaired glucose tolerance (IGT, n=92), and newly diagnosed type 2 diabetes mellitus (nT2DM, n=106) were recruited to determining the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent assay. Anthropometric and biochemical measurements related to insulin resistance, adiposity and lipid profile were examined for all participants. Oral glucose tolerance test was performed in healthy subjects (17 male and 17 female). Circulating CTRP9 level was significantly higher in both IGT and nT2DM than in individuals with NGT. Overweight/obese subjects had much higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. In addition, circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance, including body mass index, fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin resistance and low-density lipoprotein-cholesterol, while was inversely correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover, hyperglycemia during an oral glucose challenge increased circulating CTRP9 concentrations. We conclude that CTRP9 was strongly associated with insulin resistance, suggesting that CTRP9 might be important in the development of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.
Investigating the Climatic Impacts of Globally Shifted Anthropogenic Emissions
NASA Astrophysics Data System (ADS)
Wang, Y.; Jiang, J. H.; Su, H.
2014-12-01
With a quasi-exponential growth in industrialization since the mid-1990s, Asia has undergone a dramatic increase in anthropogenic emissions of aerosol and precursor gases to the atmosphere. Meanwhile, such emissions have been stabilized or reduced over North America and Europe. This geographical shift of global emission sources could potentially perturb the regional and global climate due to impact of aerosols on cloud properties, precipitation, and large-scale circulation. We use an atmospheric general circulation model (AGCM) with different aerosol scenarios to investigate the radiative and microphysical effects of anthropogenic aerosols on the large-scale circulation and regional climate over the globe. We conduct experiments to simulate the continental shift of aerosol distribution by contrasting two simulations using 1970 and 2010 anthropogenic emission sources. We found the elevation of aerosol concentrations in East and South Asia results in regional surface temperature cooling of -0.10° to -0.17°C, respectively, due to the enhanced solar extinction by aerosols and cloud reflectivity. The reduction of the local aerosol loadings in Europe causes a significant warming of +0.4°C. However, despite recent decreasing in aerosol emission, North America shows a cooling of -0.13°C, likely caused by increasing of cloudiness under the influence of modulated general circulation. These aerosol induced temperature changes are consistent with the observed temperature trends from 1980 to 2013 in the reanalysis data. Our study also predicts weaker East/South Asia summer monsoons due to strong regional aerosol forcing. Moreover, the ascending motion in the northern tropics is found to be weakened by asymmetrical aerosol forcing, resulting in the cross-equatorial shift of Hadley Circulation.
Sahebkar, Amirhossein; Simental-Mendía, Luis E; Pirro, Matteo; Montecucco, Fabrizio; Carbone, Federico; Banach, Maciej; Barreto, George E; Butler, Alexandra E
2018-06-29
To assess the effect of fibrates on circulating cystatin C levels. Clinical studies evaluating the effect of a fibrate on circulating cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A random-effect model and generic inverse variance method were used for quantitative data synthesis, sensitivity analysis conducted using the leave-one-out method, and weighted random-effects meta-regression performed to evaluate potential confounders on cystatin C levels. This meta-analysis of data from 9 published studies (16 treatment arms) involved a total of 2195 subjects. In a single-arm analysis of clinical trials (without control group; 8 studies comprising 14 treatment arms), fibrate therapy increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04, 0.10, p <0.001; I 2 = 82.66%). When the analysis was restricted to randomized controlled trials (4 studies comprising 6 treatment arms), again elevation of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03, 0.09, p <0.001; I 2 = 42.98%). Elevated cystatin C levels were only seen with fenofibrate, not other fibrates. The results suggest that fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.
NASA Astrophysics Data System (ADS)
Suzuki, Takashi; Otosaka, Shigeyoshi; Togawa, Orihiko
2013-01-01
To investigate the migration of anthropogenic 129I in the environment, we measured 129I concentrations at both subarctic (above 40oN) and subtropical (below 40oN) circulations in the surface seawater of the Japan Sea. The averaged concentrations of stations 193, 194, 201, 206 and 210 above 200 m were (2.1 ± 0.3) × 1010 atoms/m3, (2.0 ± 0.2) × 1010 atoms/m3, (1.6 ± 0.3) × 1010 atoms/m3, (1.4 ± 0.3) × 1010 atoms/m3 and (1.7 ± 0.3) × 1010 atoms/m3, respectively. The averaged concentration at the subarctic circulation in the Japan Sea above 200 m (1.9 × 1010 atoms/m3) was higher than that in the subtropical circulation (1.5 × 1010 atoms/m3). This latitudinal distribution pattern of 129I is not consistent with those of bomb-derived radionuclides such as 14C, 90Sr and 137Cs. Taking into account latitudinal location and the total amount of releases from reprocessing plants, this discriminating latitudinal distribution of 129I in the Japan Sea would indicate that a significant amount of 129I originating from active reprocessing plants in Europe is supplied to the surface of the Japan Sea.
Iso, Tatsuya; Sunaga, Hiroaki; Matsui, Hiroki; Kasama, Shu; Oshima, Naomi; Haruyama, Hikari; Furukawa, Nozomi; Nakajima, Kiyomi; Machida, Tetsuo; Murakami, Masami; Yokoyama, Tomoyuki; Kurabayashi, Masahiko
2017-11-01
Lipolysis is stimulated by activation of adrenergic inputs to adipose tissues. Our recent study showed that serum concentrations of fatty acid binding protein 4 (FABP4) are robustly elevated in patients with acute myocardial infarction and ventricular tachyarrhythmia, that display a marked activation of the sympathetic nervous system (SNS). However, it remains unknown whether circulating FABP4 concentrations are associated with exercise-induced SNS activation. Thirty one healthy volunteers underwent cardiopulmonary exercise testing on a cycle ergometer up to the workload levels below and above anaerobic threshold, low- and high-intensity exercise, respectively. Serial blood samplings were performed before and after exercise. High-intensity exercise significantly increased serum concentrations of FABP4 and catecholamines, and their concentrations declined fast thereafter in a similar fashion. These changes were accompanied by little, if any, changes in other metabolic markers. Regardless of adiposity, percent change from baseline to peak FABP4 levels (%FABP4) was comparable in all subjects. Stepwise regression analysis revealed that %FABP4 was highly correlated with that in norepinephrine. Our study reveals the significant correlation between circulating FABP4 and norepinephrine levels during exercise testing. Together with the fact that FABP4 is secreted from adipocytes via β-adrenergic-mediated lipolytic mechanisms, this study suggests FABP4 as a potential biomarker for adrenergic overdrive. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
de Boer, Ian H.; Sachs, Michael C.; Chonchol, Michel; Himmelfarb, Jonathan; Hoofnagle, Andrew N.; Ix, Joachim H.; Kremsdorf, Robin A.; Lin, Yvonne S.; Mehrotra, Rajnish; Robinson-Cohen, Cassianne; Siscovick, David S.; Steffes, Michael W.; Thummel, Kenneth E.; Tracy, Russell P.; Wang, Zhican; Kestenbaum, Bryan
2014-01-01
Background Decreased glomerular filtration rate (GFR) leads to reduced production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 (25(OH)D3). Effects of low GFR on vitamin D catabolism are less well understood. We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFR. Study Design Cross-sectional study. Setting & Participants 9596 participants in 5 cohort studies and clinical trials: the Diabetes Control and Complications Trial (N=1193), Multi-Ethnic Study of Atherosclerosis (N=6470), Cardiovascular Health Study (N=932), Seattle Kidney Study (N=289), and Hemodialysis Study (N=712). Predictor eGFR. Outcome Circulating 24,25(OH)2D3 concentration. Measurements GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry. Results Circulating 24,25(OH)2D3 concentration was correlated with circulating 25(OH)D3 concentration (Pearson r range, 0.64–0.88). This correlation was weaker with lower eGFR. Moreover, the increment in 24,25(OH)2D3 associated with higher 25(OH)D3 (“slope”) was lower with lower eGFR: 2.06 (95% CI, 2.01–2.10), 1.77 (95% CI, 1.74–1.81), 1.55 (95% CI, 1.48–1.62), 1.17 (95% CI, 1.05–1.29), 0.92 (95% CI, 0.74–1.10), 0.61 (95% CI, 0.22–1.00), and 0.37 (95% CI, 0.35–0.39) ng/mL 24,25(OH)2D3 per 10 ng/mL 25(OH)D3 for eGFR ≥90, 60–89, 45–59, 30–44, 15–29, and <15 mL/min/1.73 m2 and ESRD treated with hemodialysis, respectively. As a result, at a 25(OH)D3 concentration of 20 ng/mL, mean 24,25(OH)2D3 concentration was 2.92 (95% CI, 2.87–2.96), 2.68 (95% CI, 2.64–2.72), 2.35 (95% CI, 2.26–2.45), 1.92 (95% CI, 1.74–2.10), 1.69 (95% CI, 1.43–1.95), 1.14 (95% CI, 0.62–1.66), and 1.04 (95% CI,1.02–1.07) ng/mL for each category, respectively. This interaction was independent of other relevant clinical characteristics. Race, diabetes, urine albumin excretion, and the circulating concentrations of parathyroid hormone and fibroblast growth factor 23 more modestly modified the association of 24,25(OH)2D3 with 25(OH)D3. Limitations Lack of direct pharmacokinetic measurements of vitamin D catabolism. Conclusions Lower eGFR is strongly associated with reduced vitamin D catabolism as measured by circulating 24,25(OH)2D3 concentration. PMID:24703961
Effects of a Model Inducer, Phenobarbital, on Thyroid Hormone Glucuronidation in Rat Hepatocytes
In vivo, hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations. This decrease in circulating TH occurs in part through extrathyroidal mechanisms. Specifically, through the induction of hepatic xenobiotic metabolizing enzymes...
USDA-ARS?s Scientific Manuscript database
Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anti-cancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and c...
NASA Astrophysics Data System (ADS)
Anber, U.; Wang, S.; Gentine, P.; Jensen, M. P.
2017-12-01
A framework is introduced to investigate the indirect impact of aerosol loading on tropical deep convection using 3-dimentional idealized cloud-system resolving simulations with coupled large-scale circulation. The large scale dynamics is parameterized using a spectral weak temperature gradient approximation that utilizes the dominant balance in the tropics between adiabatic cooling and diabatic heating. Aerosol loading effect is examined by varying the number concentration of nuclei (CCN) to form cloud droplets in the bulk microphysics scheme over a wide range from 30 to 5000 without including any radiative effect as the radiative cooling is prescribed at a constant rate, to isolate the microphysical effect. Increasing aerosol number concentration causes mean precipitation to decrease monotonically, despite the increase in cloud condensates. Such reduction in precipitation efficiency is attributed to reduction in the surface enthalpy fluxes, and not to the divergent circulation, as the gross moist stability remains unchanged. We drive a simple scaling argument based on the moist static energy budget, that enables a direct estimation of changes in precipitation given known changes in surfaces enthalpy fluxes and the constant gross moist stability. The impact on cloud hydrometers and microphysical properties is also examined and is consistent with the macro-physical picture.
Vaidya, Anand; Forman, John P.; Underwood, Patricia C.; Hopkins, Paul N.; Williams, Gordon H.; Pojoga, Luminita H.; Williams, Jonathan S.
2011-01-01
Objective Prior studies have suggested that circulating adiponectin concentrations are associated positively with vitamin D and negatively with body-mass index (BMI), but have not accounted for the influence of the renin-angiotensin-aldosterone system (RAAS) in this relationship. This is particularly relevant because increased RAAS activity is associated with obesity and is known to lower adiponectin levels. We evaluated the association between adiponectin and 25-hydroxyvitamin D (25[OH]D) after controlling RAAS activity with dietary sodium equilibration, and also evaluated whether this relationship was influenced by BMI. Design Cross-sectional study of 115 hypertensive Caucasian men from the HyperPATH Consortium. Methods To manipulate RAAS activity, all subjects underwent one week of high sodium (HS) diet to suppress RAAS, and one week of low sodium (LS) diet to stimulate RAAS. Linear regression was used to evaluate the association between adiponectin and 25(OH)D, and the effect of BMI on this relationship, in each dietary condition. Results Adiponectin was higher on HS, where circulating RAAS activity was low, when compared to LS (HS=2.9 versus LS=2.4 µg/mL, p<0.0001). 25(OH)D levels were positively associated with adiponectin, and BMI was a statistically significant effect modifier of the relationship between 25(OH)D and adiponectin on both diets (p-interaction < 0.01 between BMI and 25[OH]D). Conclusions Higher 25(OH)D concentrations were independently associated with higher adiponectin levels, particularly when BMI was high. Dietary sodium balance and circulating RAAS activity did not appear to affect this relationship. Future studies should explore whether vitamin D supplementation increases adiponectin levels in obesity. PMID:21402748
Chearskul, Supornpim; Delbridge, Elizabeth; Shulkes, Arthur; Proietto, Joseph; Kriketos, Adamandia
2008-05-01
Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior. The objective of this study was to investigate physiologic adaptations to weight loss that may encourage weight regain. The study had a within-subject repeated-measure design [12 healthy, obese men, 33-64 y, body mass index (in kg/m(2)) 30-46] and was a clinical intervention investigation of circulating metabolites and hunger-satiety responses before and after weight loss. Measures included anthropometry (bioelectrical impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and satiety at baseline, 8 wk after weight loss with a very-low-energy diet, and 1 wk after weight maintenance. Weight loss led to a reduction in postprandial CCK secretion (P = 0.016). However, when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss. After weight loss, there were reduced postprandial FFA concentrations (P = 0.0005). The presence of ketosis sustained FFA to concentrations before weight loss (P = 0.60). Rapid weight loss of approximately 10% of initial body weight results in a reduction in postprandial CCK and FFA concentrations.
Lectin-like oxidized low-density lipoprotein receptor (LOX-1) in sickle cell disease vasculopathy
Chen, Mingyi; Qiu, Hong; Lin, Xin; Nam, David; Ogbu-Nwobodo, Lucy; Archibald, Hannah; Joslin, Amelia; Wun, Ted; Sawamura, Tatsuya; Green, Ralph
2017-01-01
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL. Increased expression of LOX-1 has been demonstrated in atherosclerotic lesions and diabetic vasculopathy. In this study, we investigate the expression of LOX-1 receptor in sickle cell disease (SCD) vasculopathy. Expression of LOX-1 in brain vascular endothelium is markedly increased and LOX-1 gene expression is upregulated in cultured human brain microvascular endothelial cells by incubation with SCD erythrocytes. Also, the level of circulating soluble LOX-1 concentration is elevated in the plasma of SCD patients. Increased LOX-1 expression in endothelial cells is potentially involved in the pathogenesis of SCD vasculopathy. Soluble LOX-1 concentration in SCD may provide a novel biomarker for risk stratification of sickle cell vascular complications. PMID:27519944
Mariner, R.H.; Evans, William C.; Young, H.W.
2006-01-01
Circulation times of waters in geothermal systems are poorly known. In this study, we examine the thermal waters of the Idaho batholith to verify whether maximum system temperatures, helium concentrations, and 14C values are related to water age in these low-to-moderate temperature geothermal systems. He/N2 values of gas collected from thermal waters that circulate solely through distinct units of the Idaho batholith correlate linearly with Na-K-(4/3)Ca geothermometer temperatures, showing that both variables are excellent indicators of relative water age. Thermal waters that circulate in early Tertiary (45-50 Ma) granite of the Sawtooth batholith have 3.5 times more helium than thermal waters of the same aquifer temperature that circulate through the main Cretaceous granite (average 91 Ma). Hot spring waters circulating in hydrothermally altered parts of the batholith have very little dissolved helium and no correlation between He/N2 values and geothermometer temperatures. Thermal waters discharging from the Idaho batholith are more depleted in deuterium than modern precipitation in the area. Recharge to these geothermal systems occurred from at least 10,000 BP for the cooler systems up to about 33,000 BP for the hotter systems.
NASA Technical Reports Server (NTRS)
Lecroy, S. R. (Principal Investigator)
1981-01-01
The LANDSAT imagery was historically analyzed to determine the circulation and turbidity patterns of Kerr Lake, located on the Virginia-North Carolina border. By examining the seasonal and regional turbidity and circulation patterns, a record of sediment transport and possible disposition can be obtained. Sketches were generated, displaying different intensities of brightness observed in bands 5 and 7 of LANDSAT's multispectral scanner data. Differences in and between bands 5 and 7 indicate variances in the levels of surface sediment concentrations. High sediment loads are revealed when distinct patterns appear in the band 7 imagery. The upwelled signal is exponential in nature and saturates in band 5 at low wavelengths for large concentrations of suspended solids.
Clinical CVVH model removes endothelium-derived microparticles from circulation
Abdelhafeez, Abdelhafeez H.; Jeziorczak, Paul M.; Schaid, Terry R.; Hoefs, Susan L.; Kaul, Sushma; Nanchal, Rahul; Jacobs, Elizabeth R.; Densmore, John C.
2014-01-01
Background Endothelium-derived microparticles (EMPs) are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI) in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH) reduces serum EMP levels and may be adapted as a potential therapeutic intervention. Materials and methods EMPs were generated from plasminogen activation inhibitor-1 (PAI-1)-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL) was circulated through a standard CVVH filter (pore size 200 μm, flow rate 250 mL/hr) for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs. Results A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate) from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration. Conclusion These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI. PMID:24596654
García-Bailo, Bibiana; Roke, Kaitlin; Mutch, David M; El-Sohemy, Ahmed; Badawi, Alaa
2012-11-16
Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with altered concentrations of any inflammatory biomarkers. These findings suggest that α-tocopherol, but not ascorbic acid or 25(OH)D, is inversely associated with inflammation in healthy young adults.
de la Torre-Carbot, Karina; Chávez-Servín, Jorge L; Jaúregui, Olga; Castellote, Ana I; Lamuela-Raventós, Rosa M; Nurmi, Tarja; Poulsen, Henrik E; Gaddi, Antonio V; Kaikkonen, Jari; Zunft, Hans-Franz; Kiesewetter, Holger; Fitó, Montserrat; Covas, María-Isabel; López-Sabater, M Carmen
2010-03-01
In human LDL, the bioactivity of olive oil phenols is determined by the in vivo disposition of the biological metabolites of these compounds. Here, we examined how the ingestion of 2 similar olive oils affected the content of the metabolic forms of olive oil phenols in LDL in men. The oils differed in phenol concentrations as follows: high (629 mg/L) for virgin olive oil (VOO) and null (0 mg/L) for refined olive oil (ROO). The study population consisted of a subsample from the EUROLIVE study and a randomized controlled, crossover design was used. Intervention periods lasted 3 wk and were preceded by a 2-wk washout period. The levels of LDL hydroxytyrosol monosulfate and homovanillic acid sulfate, but not of tyrosol sulfate, increased after VOO ingestion (P < 0.05), whereas the concentrations of circulating oxidation markers, including oxidized LDL (oxLDL), conjugated dienes, and hydroxy fatty acids, decreased (P < 0.05). The levels of LDL phenols and oxidation markers were not affected by ROO consumption. The relative increase in the 3 LDL phenols was greater when men consumed VOO than when they consumed ROO (P < 0.05), as was the relative decrease in plasma oxLDL (P = 0.001) and hydroxy fatty acids (P < 0.001). Plasma oxLDL concentrations were negatively correlated with the LDL phenol levels (r = -0.296; P = 0.013). Phenols in LDL were not associated with other oxidation markers. In summary, the phenol concentration of olive oil modulates the phenolic metabolite content in LDL after sustained, daily consumption. The inverse relationship of these metabolites with the degree of LDL oxidation supports the in vivo antioxidant role of olive oil phenolics compounds.
Dabrowski, Wojciech
2007-09-01
There are many biochemical markers demonstrating the central nervous system (CNS) damage following coronary artery bypass grafting (CABG). The protein S100beta is one of them and its concentrations depend on the severity of CNS damage. On the other hand, it is well known that the brain injury results in a decrease in brain magnesium (Mg) concentration, which is strictly correlated with the serum Mg concentration. Therefore, analysis of the correlation between serum total Mg and S100beta concentrations may be important and interesting, particularly in patients undergoing surgical myocardial revascularization. Patients undergoing CABG with extracorporeal circulation under general anaesthesia were included in the study. Serum Mg and S100beta concentrations were measured at 5 measurement points: 1) just after the radial artery cannulation, 2) 10 min after completion of ECC, 3) just after surgery, 4) in the morning of the 1st postoperative day, 5) in the morning of the 2nd postoperative day. The Kruskall-Wallis ANOVA and Spearman correlation tests were used; p < 0.05 was considered as significant. Twenty male patients, aged 54-70 years (63.3 +/- 49.5) were examined. The mean blood concentration of S100beta was 0.13 microg/L +/- 0.08 and of Mg-0.99mmol/L +/- 0.13 at measurement point 1. S100beta increased from point 2 to 4. Mg decreased at points 2 and 3. Moreover, there were significant negative correlations between S100beta and Mg at point 3 and 4 (p < 0.001; R = -0.76; p < 0.05; R = -0.5, respectively) and between Mg at point 1 and S100beta at point 3 and 5 (p < 0.05, R = -0.498; p < 0.05, R = -0.488, respectively), Mg at point 2 and S100beta at point 4 (p < 0.05, R = -0.523) as well as Mg at point 4 and S100beta at point 5 (p < 0.01, R = -0.584). 1) S100beta increased while total Mg decreased during CABG, 2) The highest serum S100beta concentrations were noted just after surgery, 3) The changes in serum S100beta concentrations correlated with those in serum total Mg concentrations, 4) The decrease in serum magnesium concentrations resulted in an elevation in serum S100beta concentrations.
Fuglei, E; Mustonen, A-M; Nieminen, P
2004-03-01
The arctic fox (Alopex lagopus) is a medium-sized predator of the high Arctic experiencing extreme seasonal fluctuations in food availability, photoperiod and temperature. In this study, the plasma leptin, ghrelin and growth hormone (GH) concentrations of male arctic foxes were determined during a food deprivation period of 13 days and the subsequent recovery in November and May. Leptin, ghrelin and GH were present in arctic fox plasma in amounts comparable to other carnivores. The plasma leptin concentrations did not react to food deprivation unlike in humans and rodents. However, the leptin levels increased during re-feeding as an indicator of increasing energy reserves. The relatively high ghrelin-leptin ratio, decrease in the plasma ghrelin concentration, an increase in the circulating GH concentrations and the observed negative correlation between plasma ghrelin and free fatty acid levels during fasting suggest that these hormones take part in the weight-regulation and energy metabolism of this species by increasing fat utilisation during food deprivation. The results strengthen the hypothesis that the actions of these weight-regulatory hormones are species-specific and depend on seasonality and the life history of the animals.
Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J
2017-06-01
Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation. The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life. The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas. Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T 3 ), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation in vitro was reduced by T 3 in a dose-dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T 3 , insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
Andersson, Charlotte; Enserro, Danielle; Sullivan, Lisa; Wang, Thomas J; Januzzi, James L; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M; Larson, Martin G; Mitchell, Gary F; Vasan, Ramachandran S
2016-05-01
Growth differentiation factor-15 (GDF-15), soluble (s)ST2, and high-sensitivity troponin-I (hs-TnI) are associated with incident cardiovascular disease (CVD) including heart failure, yet the underlying mechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which may explain the relations of these biomarkers with CVD. We evaluated 1823 Framingham Study participants (mean age 61 ± 10 years, 54% women) who underwent routine assessment of vascular function. We related circulating GDF-15, sST2, and hs-TnI concentrations to measures of arterial stiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; and forward pressure wave amplitude, FW), endothelial-dependent vasodilation (flow-mediated dilation, FMD), and baseline and hyperemic brachial flow velocities using linear regression adjusting for standard risk factors. After multivariable adjustment, GDF-15 levels were positively associated with CFPWV (0.044 [95% confidence interval 0.007-0.081] standard deviation [SD] change per SD increase in loge[GDF-15], p = 0.02) and FW (0.076 [0.026-0.126] SD change per SD increase in loge[GDF-15], p = 0.003) and inversely related to FMD (-0.051 [-0.101-0.0003] SD change per SD increase in loge[GDF-15], p = 0.048). sST2 was positively associated with CFPWV (0.032 [0.0005-0.063] SD change per SD increase in loge[sST2], p = 0.046), and hs-TnI inversely associated with hyperemic flow velocity (-0.041 [-0.082-0.0004] SD change per SD increase in loge[hs-TnI], p = 0.048). In our community-based investigation, individual cardiac stress biomarkers were differentially related to select aspects of vascular function. These findings may contribute to the associations of circulating GDF-15, sST2, and hs-TnI with incident CVD and heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Petrick, Benjamin F.; McClymont, Erin L.; Marret, Fabienne; van der Meer, Marcel T. J.
2015-09-01
The Southeast Atlantic Ocean is an important component of global ocean circulation, as it includes heat and salt transfer into the Atlantic through the Agulhas leakage as well as the highly productive Benguela upwelling system. Here we reconstruct sea surface temperatures (SSTs) from Ocean Drilling Program (ODP) Site 1087 in the Southeast Atlantic to investigate surface ocean circulation patterns during the late Pleistocene (0-500 ka). The UK'37 index and dinoflagellate cyst assemblages are used to reconstruct SSTs, δDalkenone is used to reconstruct changes in sea surface salinity, and mass accumulation rates of alkenones and chlorine pigments are quantified to detect changing marine export productivity. The greatest amplitude of SST warming precedes decreases in benthic δ18O and therefore occurs early in the transition from glacials to interglacials. The δDalkenone, as a salinity indicator, increases before SSTs, suggesting that the pattern of Agulhas leakage is more complex than suggested by SST proxies. Marine isotope stage (MIS) 10 shows an anomalous pattern: it is marked by a pronounced increase in chlorine concentration, which may be related to enhanced/expanded Benguela upwelling reaching the core site. We find no evidence of an absence of Agulhas leakage throughout the record, suggesting that there is no Agulhas cutoff even during MIS 10. Finally, the ODP Site 1087 record shows an increasing strength of Agulhas leakage towards the present day, which may have impacted the intensity of the Atlantic meridional overturning circulation. As a result, the new analyses from ODP Site 1087 demonstrate a complex interaction between influences of the Benguela upwelling and the Agulhas leakage through the late Pleistocene, which are inferred here to reflect changing circulation patterns in the Southern Ocean and in the atmosphere.
Gao, F; Jiang, Y; Zhou, G H; Han, Z K
2007-08-01
1. The xylanase product used in this study was derived from a genetically modified isolate of Aspergillus niger. Two trials were conducted to investigate the effects of xylanase supplementation on growth, digestion, circulating hormone and metabolite levels, immune parameters and composition of the gut microflora in cockerels fed on wheat-based diets. 2. The experimental diets consisted of a wheat-based control diet supplemented with 0 or 0.1% enzyme preparation. The diets were fed between 7 and 21 d of age. 3. Enzyme supplementation improved growth and feed conversion efficiency. The addition of enzyme to wheat-based diet increased the apparent total digestibility of dry matter (DM), crude protein and fat. 4. Enzyme supplementation reduced the relative weight of digestive organs to a certain extent, but there was no significant difference. Enzyme supplementation reduced digesta viscosity in the jejunum. There was no significant difference between the two experimental groups in counts of lactobacillus and coliform bacteria in the caeca. 5. Enzyme supplementation increased the concentration of blood thyroxine (T(4)), insulin-like growth factor I (IGF-I) and insulin, reduced the concentrations of blood uric acid, but had no significant effect on the concentrations of blood glucose and triiodothyronine (T(3)). 6. Enzyme supplementation increased the relative weight of spleen of cockerels, serum antibody titres to Newcastle disease virus (NDV), lymphocyte proliferation in response to phytohaemagglutinin (PHA) and the natural killer (NK) cell activity. 7. It is concluded that supplementation with an enzyme preparation (xylanase), which hydrolyses non-starch polysaccharides can improve growth in cockerels fed on wheat-based diets. This improvement is achieved through enzyme effects on digestion, absorption, metabolism and immunity of cockerels.
Llanos, Adana A M; Krok, Jessica L; Peng, Juan; Pennell, Michael L; Vitolins, Mara Z; Degraffinreid, Cecilia R; Paskett, Electra D
2014-04-01
Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin, and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m(2) or >30 kg/m(2)) and randomized to a 12-week, two-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were IVR + coach and IVR + no-coach condition. Pre-post changes in serum adiponectin, leptin, and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95 % confidence intervals [CI]) corresponding to postintervention adipokine concentrations relative to preintervention concentrations. While postintervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (ratio = 0.86, 95 % CI 0.74-1.01, and ratio = 0.94, 95 % CI 0.87-1.01, respectively) and increase in A/L ratio = 1.09, 95 % CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention.
Llanos, Adana A.M.; Krok, Jessica L.; Peng, Juan; Pennell, Michael L.; Vitolins, Mara Z.; Degraffinreid, Cecilia R.; Paskett, Electra D.
2014-01-01
Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m2 or >30 kg/m2) and randomized to a 12-week, 2-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were: IVR + coach and IVR + no coach condition. Pre-post changes in serum adiponectin, leptin and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95% confidence intervals [CI]) corresponding to post-intervention adipokine concentrations relative to pre-intervention concentrations. While post-intervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (Ratio=0.86, 95% CI 0.74-1.01 and Ratio=0.94, 95% CI 0.87-1.01, respectively) and increase in A/L (Ratio=1.09, 95% CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention. PMID:24435584
Ferrandi, Peter J; Fico, Brandon G; Whitehurst, Michael; Zourdos, Michael C; Bao, Fanchen; Dodge, Katelyn M; Rodriguez, Alexandra L; Pena, Gabriel; Huang, Chun-Jung
2018-06-01
Obesity is associated with lipid aggregation in adipocytes and macrophage infiltration, leading to increased oxidative stress and inflammation. Increased cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of systemic inflammation. While the beneficial effects of regular physical activity on the release of circulating cfDNA still remain unknown, acute intense exercise has been shown to increase inflammatory cytokines and cfDNA concentrations in normal-weight individuals. Therefore, the primary purpose of this study was to examine the effect of acute high-intensity interval Exercise (HIIE) on plasma cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects. Fourteen male subjects (7 obese and 7 normal-weight) participated in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO 2max ) on a treadmill. Between HIIE intervals, subjects performed 3 min of active recovery at 50-60% VO 2max . Blood samples were collected prior to, immediately following exercise, and one hour into recovery for measurements of plasma cfDNA and IL-6. Our results demonstrated a significant elevation in plasma cfDNA immediately following acute HIIE in both obese and normal-weight subjects. A comparable elevation in the concentration of plasma IL-6 was also found between two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was not correlated with IL-6 either at baseline or in response to acute HIIE. These findings may support the utilization of HIIE as a time-efficient exercise protocol to understand the obesity-associated cfDNA and inflammatory responses. Published by Elsevier Inc.
Vitamin C prophylaxis promotes oxidative lipid damage during surgical ischemia-reperfusion.
Bailey, Damian M; Raman, Sudarsanam; McEneny, Jane; Young, Ian S; Parham, Kelly L; Hullin, David A; Davies, Bruce; McKeeman, Gareth; McCord, Joe M; Lewis, Michael H
2006-02-15
Reactive oxygen species (ROS) have been implicated in the cellular membrane damage and postoperative morbidity associated with obligatory ischemia-reperfusion (I-R) during vascular surgery. Thus, a clinical study was undertaken to evaluate the effects of ascorbate prophylaxis on ROS exchange kinetics in 22 patients scheduled for elective abdominal aortic aneurysm (AAA) or infra-inguinal bypass (IIB) repair. Patients were assigned double-blind to receive intravenous sodium ascorbate (2 g vitamin C, n=10) or placebo (0.9% saline, n=12) administered 2 h prior to surgery. Blood samples were obtained from the arterial and venous circulation proximal to the respective sites of surgical repair (local) and from an antecubital vein (peripheral) during cross-clamping (ischemia) and within 60 s of clamp release (reperfusion). Ascorbate supplementation increased the venoarterial concentration difference (v-adiff) of lipid hydroperoxides (LH), interleukin (IL)-6 and vascular endothelial growth factor (VEGF) protein during ischemia. This increased the peripheral concentration of LH, total creatine phosphokinase (CPK), and VEGF protein during reperfusion (P<0.05 vs placebo). Electron paramagnetic resonance (EPR) spectroscopy confirmed that free iron was available for oxidative catalysis in the local ischemic venous blood of supplemented patients. An increased concentration of the ascorbate radical (A.-) and alpha-phenyl-tert-butylnitrone (PBN) adducts assigned as lipid-derived alkoxyl (LO.) and alkyl (LC.) species were also detected in the peripheral blood of supplemented patients during reperfusion (P<0.05 vs ischemia). In conclusion, these findings suggest that ascorbate prophylaxis may have promoted iron-induced oxidative lipid damage via a Fenton-type reaction initiated during the ischemic phase of surgery. The subsequent release of LH into the systemic circulation may have catalyzed formation of second-generation radicals implicated in the regulation of vascular permeability and angiogenesis.
Brain regions involved in the development of acute phase responses accompanying fever in rabbits.
Morimoto, A; Murakami, N; Nakamori, T; Sakata, Y; Watanabe, T
1989-01-01
1. The effects of microinjection of rabbit endogenous pyrogen and human recombinant interleukin-1 alpha on rectal temperature and acute phase responses were extensively examined in forty different brain regions of rabbits. The acute phase responses that were investigated were the changes in plasma levels of iron, zinc and copper concentration and the changes in circulating leucocyte count. 2. The rostral hypothalamic regions, such as nucleus broca ventralis, preoptic area and anterior hypothalamic region, responded to the microinjection of endogenous pyrogen or interleukin-1 by producing both fever and acute phase responses. 3. The microinjection of endogenous pyrogen or interleukin-1 into the rostral hypothalamic regions significantly decreased the plasma levels of iron and zinc concentration 8 and 24 h after injection. The circulating leucocyte count increased 8 h after injection. However, neither the injections of endogenous pyrogen nor interleukin-1 affected the number of red blood cells. 4. The present results show that the rostral hypothalamic regions respond directly to endogenous pyrogen or interleukin-1 with the consequent development of fever and acute phase responses. PMID:2514261
Jung, Chiau-Jing; Zheng, Quan-Hau; Shieh, Ya-Hsiung; Lin, Chi-Shuan; Chia, Jean-San
2009-11-01
Streptococcus mutans, a commensal of the human oral cavity, can survive in the bloodstream and cause infective endocarditis (IE). However, the virulence factors associated with this manifestation of disease are not known. Here, we demonstrate that AtlA, an autolysin of S. mutans is a newly identified fibronectin (Fn) binding protein and contributes to bacterial resistance to phagocytosis and survival in the bloodstream. Interestingly, prior exposure to plasma at low concentrations was sufficient to enhance bacterial survival in the circulation. Calcium ions at physiological plasma concentrations induced maturation of AtlA from the 104-90 kDa isoform resulting in increased Fn binding and resistance to phagocytosis. An isogenic mutant strain defective in AtlA expression exhibited reduced survival and virulence when tested in a rat model of IE compared with the wild-type and complemented strains. The data presented suggest that plasma components utilized by S. mutans enhanced survival in the circulation and AtlA is a virulence factor associated with infective endocarditis.
Trottier, Jocelyn; Perreault, Martin; Rudkowska, Iwona; Levy, Cynthia; Dallaire-Theroux, Amélie; Verreault, Mélanie; Caron, Patrick; Staels, Bart; Vohl, Marie-Claude; Straka, Robert J.; Barbier, Olivier
2014-01-01
Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes detoxifies cholestatic bile acids (BAs). We aimed at i) characterizing the circulating BA-glucuronide (-G) pool composition in humans, ii) evaluating how sex and UGT polymorphisms influence this composition, and iii) analyzing the effects of lipid-lowering drug fenofibrate on the circulating BA-G profile in 300 volunteers and 5 cholestatic patients. Eleven BA-Gs were determined in pre- and post-fenofibrate samples. Men exhibited higher BA-G concentrations, and various genotype/BA-G associations were discovered in relevant UGT genes. The chenodeoxycholic acid-3G concentration was associated with the UGT2B7 802C>T polymorphism. Glucuronidation assays confirmed the predominant role of UGT2B7 and UGT1A4 in CDCA-3G formation. Fenofibrate exposure increased the serum levels of 5 BA-G species, including CDCA-3G, and up-regulated expression of UGT1A4, but not UGT2B7, in hepatic cells. This study demonstrates that fenofibrate stimulates BA glucuronidation in humans, and thus reduces bile acid toxicity in the liver. PMID:23756370
Mesoscale circulation systems and ozone concentrations during ESCOMPTE: a case study from IOP 2b
NASA Astrophysics Data System (ADS)
Kalthoff, N.; Kottmeier, C.; Thürauf, J.; Corsmeier, U.; Saїd, F.; Fréjafon, E.; Perros, P. E.
2005-03-01
The main objective of 'Expérience sur Site pour COntraindre les Modèles de Pollution atmosphérique et de Transport d'Emissions' (ESCOMPTE) is to generate a relevant data set for testing and evaluating mesoscale chemistry-transport models (CTMs). During ESCOMPTE, measurements have been performed at numerous surface stations, by radars and lidars, and several aircraft in the planetary boundary layer. The data from these different sources have been merged to obtain a consistent description of the spatial distribution of wind, temperature, humidity, and ozone for the photosmog episode on June 25, 2001 (IOP 2b). On this day, moderate synoptic winds favour the evolution of different mesoscale circulation systems. During daytime, the sea breeze penetrates towards the north in the Rhône valley. As the winds above the sea breeze layer come from the east, polluted air from the metropolitan area of Marseille leads to an increase of ozone at elevated layers above the convective boundary layer (CBL). At the mountainous station of Luberon about 55 km north of Marseille around noon, when the CBL top surpasses the height of the mountain summit, polluted air with ozone concentrations of about 120 ppbv arrived from southerly directions, thus indicating the passage of the city plume of Marseille. At Cadarache and Vinon in the Durance valley, about 60 km inland, the ozone maximum at the surface and at flight level 920 m MSL appears between 14 and 15 UTC. At this time, southwesterly valley winds prevail in the valley, while southerly winds occur above. This finding highlights the height-dependent advection of ozone due to interacting mesoscale circulation systems. These dynamical processes need to be represented adequately in CTMs to deliver a realistic description of the ozone concentration fields.
Meridional overturning circulation conveys fast acidification to the deep Atlantic Ocean.
Perez, Fiz F; Fontela, Marcos; García-Ibáñez, Maribel I; Mercier, Herlé; Velo, Anton; Lherminier, Pascale; Zunino, Patricia; de la Paz, Mercedes; Alonso-Pérez, Fernando; Guallart, Elisa F; Padin, Xose A
2018-02-22
Since the Industrial Revolution, the North Atlantic Ocean has been accumulating anthropogenic carbon dioxide (CO 2 ) and experiencing ocean acidification, that is, an increase in the concentration of hydrogen ions (a reduction in pH) and a reduction in the concentration of carbonate ions. The latter causes the 'aragonite saturation horizon'-below which waters are undersaturated with respect to a particular calcium carbonate, aragonite-to move to shallower depths (to shoal), exposing corals to corrosive waters. Here we use a database analysis to show that the present rate of supply of acidified waters to the deep Atlantic could cause the aragonite saturation horizon to shoal by 1,000-1,700 metres in the subpolar North Atlantic within the next three decades. We find that, during 1991-2016, a decrease in the concentration of carbonate ions in the Irminger Sea caused the aragonite saturation horizon to shoal by about 10-15 metres per year, and the volume of aragonite-saturated waters to reduce concomitantly. Our determination of the transport of the excess of carbonate over aragonite saturation ( xc [CO 3 2- ])-an indicator of the availability of aragonite to organisms-by the Atlantic meridional overturning circulation shows that the present-day transport of carbonate ions towards the deep ocean is about 44 per cent lower than it was in preindustrial times. We infer that a doubling of atmospheric anthropogenic CO 2 levels-which could occur within three decades according to a 'business-as-usual scenario' for climate change-could reduce the transport of xc [CO 3 2- ] by 64-79 per cent of that in preindustrial times, which could severely endanger cold-water coral habitats. The Atlantic meridional overturning circulation would also export this acidified deep water southwards, spreading corrosive waters to the world ocean.
Results on Jupiter's Atmosphere from the Juno Microwave Radiometer
NASA Astrophysics Data System (ADS)
Janssen, M. A.; Bolton, S. J.; Levin, S.; Adumitroaie, V.; Allison, M. D.; Arballo, J. K.; Atreya, S. K.; Bellotti, A.; Brown, S. T.; Gulkis, S.; Ingersoll, A. P.; Li, C.; Li, L.; Lunine, J. I.; Misra, S.; Orton, G. S.; Oyafuso, F. A.; Santos-Costa, D.; Sarkissian, E.; Steffes, P. G.; Zhang, Z.
2017-12-01
The Juno Microwave Radiometer (MWR) was designed to investigate Jupiter's atmosphere and radiation belts as one of a suite of instruments on the Juno mission. The MWR's main objective is to investigate the composition and dynamics of Jupiter's neutral atmosphere. Juno has now completed eight perijove passes that sample the atmosphere approximately every 45° in longitude, and the MWR has completed its main collection of data pertaining to the composition and structure of Jupiter's atmosphere. The primary results for atmospheric structure elaborate on the original discovery that the concentration of ammonia is far from uniformly mixed beneath its saturation level in the atmosphere and that deep atmospheric circulations control its distribution. Conversely, features of the deep circulation may be inferred from this distribution. Distinct circulation patterns are seen for three latitudinal regions: 1) Equatorial, where a column of increased ammonia concentration associated with the equatorial zone is sandwiched by off-equatorial regions of depleted ammonia in the north and south equatorial belts, with structure apparent to approximately the 100-bar pressure level, 2) Midlatitudes, where a stratified ammonia concentration appears stable, and 3) Polar, dominated by deep vertical structures associated with the observed surface vortices. Longitudinal structure is seen in the equatorial region primarily above the level of the water cloud around the 8-bar level, while significant structure appears small or absent outside and below this region. The ability of the MWR to detect lightning at its longest wavelengths was unexpected but sheds light on the presence of water and the distribution of strong convective regions in the atmosphere. The implications of these results for atmospheric dynamics and composition will be discussed.
Meridional overturning circulation conveys fast acidification to the deep Atlantic Ocean
NASA Astrophysics Data System (ADS)
Perez, Fiz F.; Fontela, Marcos; García-Ibáñez, Maribel I.; Mercier, Herlé; Velo, Anton; Lherminier, Pascale; Zunino, Patricia; de La Paz, Mercedes; Alonso-Pérez, Fernando; Guallart, Elisa F.; Padin, Xose A.
2018-02-01
Since the Industrial Revolution, the North Atlantic Ocean has been accumulating anthropogenic carbon dioxide (CO2) and experiencing ocean acidification, that is, an increase in the concentration of hydrogen ions (a reduction in pH) and a reduction in the concentration of carbonate ions. The latter causes the ‘aragonite saturation horizon’—below which waters are undersaturated with respect to a particular calcium carbonate, aragonite—to move to shallower depths (to shoal), exposing corals to corrosive waters. Here we use a database analysis to show that the present rate of supply of acidified waters to the deep Atlantic could cause the aragonite saturation horizon to shoal by 1,000-1,700 metres in the subpolar North Atlantic within the next three decades. We find that, during 1991-2016, a decrease in the concentration of carbonate ions in the Irminger Sea caused the aragonite saturation horizon to shoal by about 10-15 metres per year, and the volume of aragonite-saturated waters to reduce concomitantly. Our determination of the transport of the excess of carbonate over aragonite saturation (xc[CO32-])—an indicator of the availability of aragonite to organisms—by the Atlantic meridional overturning circulation shows that the present-day transport of carbonate ions towards the deep ocean is about 44 per cent lower than it was in preindustrial times. We infer that a doubling of atmospheric anthropogenic CO2 levels—which could occur within three decades according to a ‘business-as-usual scenario’ for climate change—could reduce the transport of xc[CO32-] by 64-79 per cent of that in preindustrial times, which could severely endanger cold-water coral habitats. The Atlantic meridional overturning circulation would also export this acidified deep water southwards, spreading corrosive waters to the world ocean.
Potential Therapeutic Use of Relaxin in Healing Cranial Bone Defects
2017-09-01
to measure circulating concentrations of relaxin during the infusion by ELISA ; 3. sacrifice the mice at 10-12 days after cranial defect; 4. fix the...osmotic pump for 10-12 days, and to measure circulating concentrations of relaxin during the infusion by ELISA . Values of 0.35, 0.69, 1.61, 0.66, 1.99...vehicle-infused mice, because in our previous work, none was detected. This makes sense, because the ELISA we use does not detect mouse relaxin
Wehbe, Mohamed; Anantha, Malathi; Shi, Minghan; Leung, Ada Wai-Yin; Dragowska, Wieslawa H; Sanche, Léon; Bally, Marcel B
2017-01-01
Copper diethyldithiocarbamate (Cu(DDC) 2 ) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC) 2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC) 2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC) 2 formulation prepared through a method that involves synthesis of Cu(DDC) 2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC) 2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4-11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC) 2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC) 2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC) 2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC (0-∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC) 2 formulation was subsequently evaluated in the MV-4-11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC) 2 formulation in vivo.
Wehbe, Mohamed; Anantha, Malathi; Shi, Minghan; Leung, Ada Wai-yin; Dragowska, Wieslawa H; Sanche, Léon; Bally, Marcel B
2017-01-01
Copper diethyldithiocarbamate (Cu(DDC)2) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC)2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC)2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC)2 formulation prepared through a method that involves synthesis of Cu(DDC)2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC)2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4–11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC)2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC)2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC)2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC(0−∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC)2 formulation was subsequently evaluated in the MV-4–11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC)2 formulation in vivo. PMID:28615941
Microgravity Diode Laser Spectroscopy Measurements in a Reacting Vortex Ring
NASA Technical Reports Server (NTRS)
Chen, Shin-Juh; Dahm, Werner J. A.; Silver, Joel A.; Piltch, Nancy D.
2001-01-01
The technique of Diode Laser Spectroscopy (DLS) with wavelength modulation is utilized to measure the concentration of methane in reacting vortex rings under microgravity conditions. From the measured concentration of methane, other major species such as water, carbon dioxide, nitrogen, and oxygen can be easily computed under the assumption of equilibrium chemistry with the method of Interactive Temperature with Assumed Chemistry (ITAC). The conserved scalar approach in modelling the coupling between fluid dynamics and combustion is utilized to represent the unknown variables in terms of the mixture fraction and scalar dissipation rate in conjunction with ITAC. Post-processing of the DLS measurements and the method of ITAC used in computing the species concentration are discussed. From the flame luminosity results, the increase in ring circulation appears to increase the fuel consumption rate inside the reacting vortex ring and the flame height for cases with similar fuel volumes. Preliminary results and application of ITAC show some potential capabilities of ITAC in DLS. The measured concentration of methane, and computed concentrations of water and carbon dioxide agree well with available results from numerical simulations.
Phosphate homeostasis in Bartter syndrome: a case-control study.
Bettinelli, Alberto; Viganò, Cristina; Provero, Maria Cristina; Barretta, Francesco; Albisetti, Alessandra; Tedeschi, Silvana; Scicchitano, Barbara; Bianchetti, Mario G
2014-11-01
Bartter patients may be hypercalciuric. Additional abnormalities in the metabolism of calcium, phosphate, and calciotropic hormones have occasionally been reported. The metabolism of calcium, phosphate, and calciotropic hormones was investigated in 15 patients with Bartter syndrome and 15 healthy subjects. Compared to the controls, Bartter patients had significantly reduced plasma phosphate {mean [interquartile range]:1.29 [1.16-1.46] vs. 1.61 [1.54-1.67] mmol/L} and maximal tubular phosphate reabsorption (1.16 [1.00-1.35] vs. 1.41 [1.37-1.47] mmol/L) and significantly increased parathyroid hormone (PTH) level (6.1 [4.5-7.7] vs. 2.8 [2.2-4.4] pmol/L). However, patients and controls did not differ in blood calcium, 25-hydroxyvitamin D, alkaline phosphatase, and osteocalcin levels. In patients, an inverse correlation (P < 0.05) was noted between total plasma calcium or glomerular filtration rate and PTH concentration. A positive correlation was also noted between PTH and osteocalcin concentrations (P < 0.005), as well as between chloriduria or natriuria and phosphaturia (P < 0.001). No correlation was noted between calciuria and PTH concentration or between urinary or circulating phosphate and PTH. The results of this study demonstrate a tendency towards renal phosphate wasting and elevated circulating PTH levels in Bartter patients.
Antfolk, Maria; Kim, Soo Hyeon; Koizumi, Saori; Fujii, Teruo; Laurell, Thomas
2017-01-01
The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis. This induces a high risk of sample loss of the collected rare cells. Here, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood concentration of the peripheral blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at a recovery of 76.2 ± 5.9% of the cancer cells and a minute contamination of 0.12 ± 0.04% PBMCs while simultaneously enabling a 20x volumetric concentration. This constitutes a first step towards a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice. PMID:28425472
Antfolk, Maria; Kim, Soo Hyeon; Koizumi, Saori; Fujii, Teruo; Laurell, Thomas
2017-04-20
The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis. This induces a high risk of sample loss of the collected rare cells. Here, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood concentration of the peripheral blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at a recovery of 76.2 ± 5.9% of the cancer cells and a minute contamination of 0.12 ± 0.04% PBMCs while simultaneously enabling a 20x volumetric concentration. This constitutes a first step towards a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Crump, Doug, E-mail: doug.crump@ec.gc.ca; Porter, Emily; Egloff, Caroline
1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900 ng/g and from 0 to 261,400 ng/g, respectively, to determine effects on pipping success,more » development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • DBE-DBCH and TMPP are not embryolethal to chicken embryos. • TMPP caused deformities, morphometric alterations, and increased plasma bile acids. • DBE-DBCH and TMPP altered mRNA levels of xenobiotic and lipid metabolism genes. • Elevated plasma bile acids suggest that TMPP causes liver dysfunction. • TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH.« less
Fat soluble vitamins in blood and tissues of free-ranging and captive rhinoceros.
Clauss, Marcus; Jessup, David A; Norkus, Edward B; Chen, Tai C; Holick, Michael F; Streich, W Juergen; Dierenfeld, Ellen S
2002-04-01
Several disease syndromes in captive rhinoceroses have been linked to low vitamin status. Blood samples from captive and free-ranging black (Diceros bicornis) and white rhinoceros (Ceratotherium simum) and tissue samples of captive individuals from four rhinoceros species were analysed for vitamins A and E. Circulating vitamin A levels measured as retinol for free-ranging versus captive black and white rhinoceros were 0.04 (+/- 0.03 SD) vs. 0.08 (+/- 0.08) and 0.07 (+/- 0.04) vs. 0.06 (+/- 0.02) microgram/ml, respectively. Circulating vitamin E levels measured as alpha-tocopherol were 0.58 (+/- 0.30) vs. 0.84 (+/- 0.96) and 0.62 (+/- 0.48) vs. 0.77 (+/- 0.32) microgram/ml, respectively. In contrast to earlier findings, there was no significant difference in vitamin E concentration between captive and free-ranging black rhinoceros. When the samples of captive black rhinoceros were grouped into those taken before 1990 and after 1990, however, those collected before 1990 had significantly lower (P < 0.001) vitamin E levels (0.46 +/- 0.83 microgram/ml) and those collected in 1990 or later significantly higher (P < 0.001) vitamin E levels (1.03 +/- 1.04 micrograms/ml) than the captive population as a whole. This is probably due to increased dietary supplementation. There were significant differences in circulating vitamin concentrations in black rhinoceroses from different regions in the wild. Serum 25-hydroxy (OH) vitamin D3 averaged 55.7 ng/ml in free-ranging rhinoceroses; no carotenoids were detected in any blood samples. Captive black and white rhinoceroses appear to be adequately supplemented in vitamin A and E. Captive Indian rhinoceroses (Rhinoceros unicornis) had significantly lower vitamin A concentrations in blood (P < 0.001) and higher vitamin A concentrations in liver tissue samples (P < 0.001) than other rhinoceros species. Equine requirements are not recommended as a model for rhinoceros vitamin requirements.
Effects of cardiac glycosides on sodium pump expression and function in LLC-PK1 and MDCK cells.
Liu, Jiang; Periyasamy, Sankaridrug M; Gunning, William; Fedorova, Olga V; Bagrov, Alexei Y; Malhotra, Deepak; Xie, Zijian; Shapiro, Joseph I
2002-12-01
The decreases in proximal tubule sodium reabsorption seen with chronic renal failure and volume expansion have been ascribed to circulating digitalis-like substances (DLS). However, the circulating concentrations of DLS do not acutely inhibit the sodium pump to a degree consistent with the observed changes in proximal tubule sodium reabsorption. We examined how cell lines that simulated proximal (LLC-PK1) and distal tubule (MDCK) cells responded to acute (30 min) and long-term (up to 12 hours) Na+,K+-ATPase inhibition with DLS. In LLC-PK1, but not MDCK cells, low concentrations of ouabain decreased 86Rb uptake profoundly in a time and dose dependent manner. In LLC-PK1 cells grown to confluence, transcellular 22Na flux was markedly reduced in concert with the decreases in 86Rb uptake. Similar findings were observed with marinobufagenin (MBG) and deproteinated extract of serum derived from patients with chronic renal failure. However, inhibition of the Na+,K+-ATPase with low extracellular potassium concentrations did not produce any of these effects. Western and Northern blots detected no change in alpha1 Na+,K+-ATPase protein and message RNA, respectively, in LLC-PK1 cells treated with ouabain for 12 hours. However, the decrease in enzymatic activity of Na+,K+-ATPase of these cells was comparable to observed decreases in 86Rb uptake. Differential centrifugation as well as biotinylation experiments demonstrated a shift of the Na+,K+-ATPase from the plasmalemma with prolonged ouabain treatment. The results show that binding of cardiac glycosides by proximal (but not distal) tubular cells results in internalization of Na+,K+-ATPase with the net effect to amplify inhibition of the Na+,K+-ATPase. As the circulating concentrations of DLS increase with chronic renal failure and volume expansion, we suggest that this phenomenon explains some of the decreased sodium reabsorption by the proximal tubule seen in these conditions.
Gao, Jinming; Xu, Xiaohua; Ying, Zhekang; Jiang, Lei; Zhong, Mianhua; Wang, Aixia; Chen, Lung-Chi; Lu, Bo; Sun, Qinghua
2017-08-01
This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2 months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.
Autumn Cooling of Western East Antarctica Linked to the Tropical Pacific
NASA Astrophysics Data System (ADS)
Clem, Kyle R.; Renwick, James A.; McGregor, James
2018-01-01
Over the past 60 years, the climate of East Antarctica cooled while portions of West Antarctica were among the most rapidly warming regions on the planet. The East Antarctic cooling is attributed to a positive trend in the Southern Annular Mode (SAM) and a strengthening of the westerlies, while West Antarctic warming is tied to zonally asymmetric circulation changes forced by the tropics. This study finds recent (post-1979) surface cooling of East Antarctica during austral autumn to also be tied to tropical forcing, namely, an increase in La Niña events. The recent increase in La Niña conditions forces a Rossby wave into the Southern Hemisphere that increases anticyclonic circulation over the South Atlantic. The South Atlantic anticyclone is associated with cold air advection, weakened northerlies, and increased sea ice concentrations across the western East Antarctic coast, which has increased the rate of cooling at Novolazarevskaya and Syowa stations after 1979. This enhanced cooling over western East Antarctica is tied more broadly to a zonally asymmetric temperature trend pattern across East Antarctica during autumn that is consistent with a tropically forced Rossby wave rather than a SAM pattern; the positive SAM pattern is associated with ubiquitous cooling across East Antarctica, which is not seen in temperature observations after 1979. We conclude that El Niño-Southern Oscillation-related circulation anomalies, particularly zonal asymmetries that locally enhance meridional wind, are an important component of East Antarctic climate variability during autumn, and future changes in tropical Pacific climate will likely have implications for East Antarctica.
Massage Improves Growth Quality by Decreasing Body Fat Deposition in Male Preterm Infants
Moyer-Mileur, Laurie J.; Haley, Shannon; Slater, Hillarie; Beachy, Joanna; Smith, Sandra L.
2012-01-01
Objectives To assess the effect of massage on weight gain and body fat deposition in preterm infants. Study design Preterm infants (29–32 wk) were randomized to Massage (n=22, 12F/10M) or Control (n=22, 12F/10M). Treatment was masked with Massage or Control administered twice-daily by licensed massage therapists (6 d/wk for 4 wk). Body weight (g), length (cm), ponderal index (PI g/cm3), body circumferences (cm), skinfold thickness (triceps TSF, mid-thigh MTSF, and subscapular SSF; mm) were measured. Circulating IGF-1, leptin, and adiponectin were determined by ELISA. Daily dietary intake was collected. Results Energy and protein intake as well as increase in weight (g/kg/d), length, and body circumferences were similar. Massage male infants had smaller PI, TSF, MTSF, and SSF, and increases over time than Control male infants (p<0.05). Massage female infants had larger SSF increase than Control females (p<0.05). Circulating adiponectin increased over time in Control male infants (group X time X sex interaction, p<0.01) and was correlated to PI (r=0.39, p<0.01). Conclusions Twice daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition, and in turn growth quality, of preterm infants in a sex-specific manner. PMID:23062248
Dinas, Petros C.; Lahart, Ian M.; Timmons, James A.; Svensson, Per-Arne; Koutedakis, Yiannis; Flouris, Andreas D.; Metsios, George S.
2017-01-01
Background: Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Methods: Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. Results: We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. Conclusions: The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews. PMID:28620456
Moreno-Navarrete, José Maria; Ricart, Wifredo; Ros, Emilio; Estruch, Ramon; Salas-Salvadó, Jordi
2012-01-01
Background: The intake of olive oil has been related to the prevention of osteoporosis in experimental and in in vitro models. Very few prospective studies have evaluated the effects of olive oil intake on circulating osteocalcin (OC) in humans. Objective: The objective of the study was to examine the longitudinal effects of a low-fat control diet (n = 34), a Mediterranean diet enriched with nuts (MedDiet+nuts, n = 51), or a Mediterranean diet enriched with virgin olive oil (MedDiet+VOO, n = 42) on circulating forms of OC and bone formation markers in elderly men at high cardiovascular risk. Design: Longitudinal associations between baseline and follow-up (2 yr) measurements of total OC, undercarboxylated osteocalcin, C-telopeptide of type I collagen, and procollagen I N-terminal propeptide (P1NP) concentrations were examined in 127 elderly men randomized to three healthy dietary interventions. Results: Baseline characteristics (age, body mass index, waist circumference, lipid profile, fasting insulin levels, and bone formation and resorption markers) were similar in all intervention groups. The total osteocalcin concentration increased robustly in the MedDiet+VOO group (P = 0.007) in parallel to increased P1NP levels (P = 0.01) and homeostasis model assessment-β-cell function (P = 0.01) but not in subjects on the MedDiet+nuts (P = 0.32) or after the control diet (P = 0.74). Interestingly, the consumption of olives was associated positively with both baseline total osteocalcin (r = 0.23, P = 0.02) and the 2-yr osteocalcin concentrations (r = 0.21, P = 0.04) in the total cohort. Conclusions: Consumption of a Mediterranean diet enriched with virgin olive oil for 2 years is associated with increased serum osteocalcin and P1NP concentrations, suggesting protective effects on bone. PMID:22855341
Eikenaar, Cas; Husak, Jerry; Escallón, Camilo; Moore, Ignacio T
2012-11-01
Latitudinal variation in life-history traits has been the focus of numerous investigations, but underlying hormonal mechanisms have received much less attention. Steroid hormones play a central role in vertebrate reproduction and may be associated with life-history trade-offs. Consequently, circulating concentrations of these hormones vary tremendously across vertebrates, yet interspecific geographic variation in male hormone concentrations has been studied in detail only in birds. We here report on such variation in amphibians and reptiles, confirming patterns observed in birds. Using phylogenetic comparative analyses, we found that in amphibians, but not in reptiles, testosterone and baseline corticosterone were positively related to latitude. Baseline corticosterone was negatively related to elevation in amphibians but not in reptiles. For both groups, testosterone concentrations were negatively related to breeding-season length. In addition, testosterone concentrations were positively correlated with baseline corticosterone in both groups. Our findings may best be explained by the hypothesis that shorter breeding seasons increase male-male competition, which may favor increased testosterone concentrations that modulate secondary sexual traits. Elevated energetic demands resulting from greater reproductive intensity may require higher baseline corticosterone. Thus, the positive relationship between testosterone and corticosterone in both groups suggests an energetic demand for testosterone-regulated behavior that is met with increased baseline glucocorticoid concentrations.
The chemical and radiative effects of the Mount Pinatubo eruption
NASA Technical Reports Server (NTRS)
Kinneson, Douglas E.; Grant, Keith E.; Connell, Peter S.; Rotman, Douglas A.; Wuebbles, Donald J.
1994-01-01
To clarify the mechanisms leading to effects on stratospheric ozone, time-dependent stratospheric aerosol and gas experiment II (SAGE II) and cryogenic limb array elaton spectrometer (CLAES) aerosol optical extinction data and SAGE II surface area density are used as parameters in a two-dimensional (2-D) zonally averaged chemical radiative transport model. The model was integrated with time from before the eruption through December 1993. The modeled impact on global ozone results from increased rates of heterogeneous reactions on sulfate aerosols and from the increased radiative heating and scattering caused by these aerosols. When the aerosol heating is allowed to modify the temperature distribution, the maximum change calculated in equatorial column ozone is -1.6%. The calculated equatorial temperature change and peak local ozone change in October 1991 are +6K and -4%, respectively. When aerosol heating perturbs the circulation in the model, the maximum change in equatorial column ozone is -6%. Increased heterogeneous processing on sulfate aerosols is calculated to have changed equatorial column ozone in late 1991 by -1.5%. Global column ozone in the model in 1992 and 1993 changed by -2.8% and -2.4%, respectively. The relationship of ozone-controlling processes in the lower stratosphere is altered as well; HO(x) becomes the most important catalytic cycle, followed by ClO(x) and NO(x). This is driven by significant changes in trace gas concentrations. In October 1991, lower stratospheric, equatorial NO(x) decreased by 40%, ClO(x) increased by 60%, and HO(x) increased by 25%. When the effect of heterogeneous chemical processing on sulfate aerosols is combined with aerosol heating, modifying either circulation or temperature, dramatically different ozone fingerprints with time and latitude are predicted. Model-derived changes in the equatorial region in column ozone best represented the observed data when perturbed circulation was combined with heterogeneous chemical effects. However, at high latitudes, the increased ozone production from the strengthening of the mean circulation tends to cancel the heterogeneous reduction of ozone. This is not in good agreement with observed data, especially in 1992 and 1993. When the circulation is held fixed and the temperature allowed to change, and heterogeneous chemical effects are included, the equatorial ozone decrease predicted was too small for 1991. However, the mid- to high-latitude decrease in 1992 and 1993 is in better agreement with observed data.
NASA Astrophysics Data System (ADS)
Demuzere, Matthias; Kassomenos, P.; Philipp, A.
2011-08-01
In the framework of the COST733 Action "Harmonisation and Applications of Weather Types Classifications for European Regions" a new circulation type classification software (hereafter, referred to as cost733class software) is developed. The cost733class software contains a variety of (European) classification methods and is flexible towards choice of domain of interest, input variables, time step, number of circulation types, sequencing and (weighted) target variables. This work introduces the capabilities of the cost733class software in which the resulting circulation types (CTs) from various circulation type classifications (CTCs) are applied on observed summer surface ozone concentrations in Central Europe. Firstly, the main characteristics of the CTCs in terms of circulation pattern frequencies are addressed using the baseline COST733 catalogue (cat 2.0), at present the latest product of the new cost733class software. In a second step, the probabilistic Brier skill score is used to quantify the explanatory power of all classifications in terms of the maximum 8 hourly mean ozone concentrations exceeding the 120-μg/m3 threshold; this was based on ozone concentrations from 130 Central European measurement stations. Averaged evaluation results over all stations indicate generally higher performance of CTCs with a higher number of types. Within the subset of methodologies with a similar number of types, the results suggest that the use of CTCs based on optimisation algorithms are performing slightly better than those which are based on other algorithms (predefined thresholds, principal component analysis and leader algorithms). The results are further elaborated by exploring additional capabilities of the cost733class software. Sensitivity experiments are performed using different domain sizes, input variables, seasonally based classifications and multiple-day sequencing. As an illustration, CTCs which are also conditioned towards temperature with various weights are derived and tested similarly. All results exploit a physical interpretation by adapting the environment-to-circulation approach, providing more detailed information on specific synoptic conditions prevailing on days with high surface ozone concentrations. This research does not intend to bring forward a favourite classification methodology or construct a statistical ozone forecasting tool but should be seen as an introduction to the possibilities of the cost733class software. It this respect, the results presented here can provide a basic user support for the cost733class software and the development of a more user- or application-specific CTC approach.
Effect of solubilizing agents on mupirocin loading into and release from PEGylated nanoliposomes.
Cern, Ahuva; Nativ-Roth, Einat; Goldblum, Amiram; Barenholz, Yechezkel
2014-07-01
Mupirocin was identified by quantitative structure property relationship models as a good candidate for remote liposomal loading. Mupirocin is an antibiotic that is currently restricted to topical administration because of rapid hydrolysis in vivo to its inactive metabolite. Formulating mupirocin in PEGylated nanoliposomes may potentially expand its use to parenteral administration by protecting it from degradation in the circulation and target it (by the enhanced permeability effect) to the infected tissue. Mupirocin is slightly soluble in aqueous medium and its solubility can be increased using solubilizing agents. The effect of the solubilizing agents on mupirocin remote loading was studied when the solubilizing agents were added to the drug loading solution. Propylene glycol was found to increase mupirocin loading, whereas polyethylene glycol 400 showed no effect. Hydroxypropyl-β-cyclodextrin (HPCD) showed a concentration-dependent effect on mupirocin loading; using the optimal HPCD concentration increased loading, but higher concentrations inhibited it. The inclusion of HPCD in the liposome aqueous phase while forming the liposomes resulted in increased drug loading and substantially inhibited drug release in serum. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
NASA Astrophysics Data System (ADS)
Costa, Marcos Heil; Foley, Jonathan A.
2000-01-01
It is generally expected that the Amazon basin will experience at least two major environmental changes during the next few decades and centuries: 1) increasing areas of forest will be converted to pasture and cropland, and 2) concentrations of atmospheric CO2 will continue to rise. In this study, the authors use the National Center for Atmospheric Research GENESIS atmospheric general circulation model, coupled to the Integrated Biosphere Simulator, to determine the combined effects of large-scale deforestation and increased CO2 concentrations (including both physiological and radiative effects) on Amazonian climate.In these simulations, deforestation decreases basin-average precipitation by 0.73 mm day1 over the basin, as a consequence of the general reduction in vertical motion above the deforested area (although there are some small regions with increased vertical motion). The overall effect of doubled CO2 concentrations in Amazonia is an increase in basin-average precipitation of 0.28 mm day1. The combined effect of deforestation and doubled CO2, including the interactions among the processes, is a decrease in the basin-average precipitation of 0.42 mm day1. While the effects of deforestation and increasing CO2 concentrations on precipitation tend to counteract one another, both processes work to warm the Amazon basin. The effect of deforestation and increasing CO2 concentrations both tend to increase surface temperature, mainly because of decreases in evapotranspiration and the radiative effect of CO2. The combined effect of deforestation and doubled CO2, including the interactions among the processes, increases the basin-average temperature by roughly 3.5°C.
The impact of bacteria of circulating water on apatite-nepheline ore flotation.
Evdokimova, G A; Gershenkop, A Sh; Fokina, N V
2012-01-01
A new phenomenon has been identified and studied-the impact of bacteria on the benefication process of non-sulphide ores using circulating water supply-a case study of apatite-nepheline ore. It is shown that bacteria deteriorate the floatability of apatite due to their interaction with active centres of calcium-containing minerals and intense flocculation, resulting in a decrease of the flotation process selectivity thus deteriorating the quality of concentrate. Based on the comparative analysis of primary sequences of 16S rRNA genes, there have been identified dominating bacteria species, recovered from the circulating water used at apatite-nepheline concentrating mills, and their phylogenetic position has been determined. All the bacteria were related to γ-Proteobacteria, including the Acinetobacter species, Pseudomonas alcaliphila, Ps. plecoglossicida, Stenotrophomonas rhizophila. A method of non-sulphide ores flotation has been developed with consideration of the bacterial factor. It consists in use of small concentrations of sodium hypochlorite, which inhibits the development of bacteria in the flotation of apatite-nepheline ores.
NASA Astrophysics Data System (ADS)
Oudar, Thomas; Sanchez-Gomez, Emilia; Chauvin, Fabrice; Cattiaux, Julien; Terray, Laurent; Cassou, Christophe
2017-12-01
The large-scale and synoptic-scale Northern Hemisphere atmospheric circulation responses to projected late twenty-first century Arctic sea ice decline induced by increasing Greenhouse Gases (GHGs) concentrations are investigated using the CNRM-CM5 coupled model. An original protocol, based on a flux correction technique, allows isolating the respective roles of GHG direct radiative effect and induced Arctic sea ice loss under RCP8.5 scenario. In winter, the surface atmospheric response clearly exhibits opposing effects between GHGs increase and Arctic sea ice loss, leading to no significant pattern in the total response (particularly in the North Atlantic region). An analysis based on Eady growth rate shows that Arctic sea ice loss drives the weakening in the low-level meridional temperature gradient, causing a general decrease of the baroclinicity in the mid and high latitudes, whereas the direct impact of GHGs increase is more located in the mid-to-high troposphere. Changes in the flow waviness, evaluated from sinuosity and blocking frequency metrics, are found to be small relative to inter-annual variability.
Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study
Dimitrakopoulou, Vasiliki I; Haycock, Philip C; Dimou, Niki L; Al-Dabhani, Kawthar; Martin, Richard M; Lewis, Sarah J; Gunter, Marc J; Mondul, Alison; Shui, Irene M; Theodoratou, Evropi; Nimptsch, Katharina; Lindström, Sara; Albanes, Demetrius; Kühn, Tilman; Key, Timothy J; Travis, Ruth C; Vimaleswaran, Karani Santhanakrishnan; Kraft, Peter; Pierce, Brandon L; Schildkraut, Joellen M
2017-01-01
Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer. Design Mendelian randomisation study. Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform). Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls. Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations. Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined. Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated. Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention. PMID:29089348
Targeting of drugs and nanoparticles to tumors
Bhatia, Sangeeta N.; Sailor, Michael J.
2010-01-01
The various types of cells that comprise the tumor mass all carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These differentially expressed molecules can be used as docking sites to concentrate drug conjugates and nanoparticles at tumors. Specific markers in tumor vessels are particularly well suited for targeting because molecules at the surface of blood vessels are readily accessible to circulating compounds. The increased concentration of a drug in the site of disease made possible by targeted delivery can be used to increase efficacy, reduce side effects, or achieve some of both. We review the recent advances in this delivery approach with a focus on the use of molecular markers of tumor vasculature as the primary target and nanoparticles as the delivery vehicle. PMID:20231381
Circulating cell-free DNA: an up-coming molecular marker in exercise physiology.
Breitbach, Sarah; Tug, Suzan; Simon, Perikles
2012-07-01
The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.
ERIC Educational Resources Information Center
Mangset, Marte
2017-01-01
According to classical elite theory, increased circulation is related to increased integration which is thought to increase elites' power. Based on a comparative analysis of some European countries' elite education systems, recruitment to elite positions and degrees of circulation--with a specific focus on administrative elites--this article…
Liu, Wei; Xie, Shang-Ping; Liu, Zhengyu; Zhu, Jiang
2017-01-01
Changes in the Atlantic Meridional Overturning Circulation (AMOC) are moderate in most climate model projections under increasing greenhouse gas forcing. This intermodel consensus may be an artifact of common model biases that favor a stable AMOC. Observationally based freshwater budget analyses suggest that the AMOC is in an unstable regime susceptible for large changes in response to perturbations. By correcting the model biases, we show that the AMOC collapses 300 years after the atmospheric CO 2 concentration is abruptly doubled from the 1990 level. Compared to an uncorrected model, the AMOC collapse brings about large, markedly different climate responses: a prominent cooling over the northern North Atlantic and neighboring areas, sea ice increases over the Greenland-Iceland-Norwegian seas and to the south of Greenland, and a significant southward rain-belt migration over the tropical Atlantic. Our results highlight the need to develop dynamical metrics to constrain models and the importance of reducing model biases in long-term climate projection.
Overlooked possibility of a collapsed Atlantic Meridional Overturning Circulation in warming climate
Liu, Wei; Xie, Shang-Ping; Liu, Zhengyu; Zhu, Jiang
2017-01-01
Changes in the Atlantic Meridional Overturning Circulation (AMOC) are moderate in most climate model projections under increasing greenhouse gas forcing. This intermodel consensus may be an artifact of common model biases that favor a stable AMOC. Observationally based freshwater budget analyses suggest that the AMOC is in an unstable regime susceptible for large changes in response to perturbations. By correcting the model biases, we show that the AMOC collapses 300 years after the atmospheric CO2 concentration is abruptly doubled from the 1990 level. Compared to an uncorrected model, the AMOC collapse brings about large, markedly different climate responses: a prominent cooling over the northern North Atlantic and neighboring areas, sea ice increases over the Greenland-Iceland-Norwegian seas and to the south of Greenland, and a significant southward rain-belt migration over the tropical Atlantic. Our results highlight the need to develop dynamical metrics to constrain models and the importance of reducing model biases in long-term climate projection. PMID:28070560
Neutrophil Kinetics in Acute Infection*
Marsh, J. C.; Boggs, D. R.; Cartwright, G. E.; Wintrobe, M. M.
1967-01-01
Neutrophil kinetics of acute experimental infection were studied with diisopropylfluorophosphate-32P labeling in 31 dogs inoculated intrabronchially with pneumococci. In vitro neutrophil labeling indicated a rapid transit time through the blood in early infections, with an elevated marginal granulocyte pool sometimes preceding an elevation of the circulating granulocyte pool. 13 hr after infection, the circulating and total blood granulocyte pools were increased but the rate of neutrophil transit through the blood was normal. During the recovery from infection there was a marked prolongation of neutrophil blood transit time, suggesting virtually complete cessation of bone marrow release of neutrophils into the blood. Labeling of neutrophils in vivo indicated an increased rate of emptying of the bone marrow storage pool proportional to the severity of infection as measured by the fever index. The change in the blood ratio of nonsegmented to segmented neutrophils was a much more accurate index of the severity of infection than the blood granulocyte concentration, correlating significantly with the fever index. PMID:6073999
Heibel, André B.; Perim, Pedro H. L.; Oliveira, Luana F.; McNaughton, Lars R.; Saunders, Bryan
2018-01-01
Blood alkalosis, as indicated by an increased blood bicarbonate concentration and pH, has been shown to be beneficial for exercise performance. Sodium bicarbonate, sodium citrate, and sodium or calcium lactate, can all result in increased circulating bicarbonate and have all independently been shown to improve exercise capacity and performance under various circumstances. Although there is considerable evidence demonstrating the efficacy of these supplements in several sports-specific situations, it is commonly acknowledged that their efficacy is equivocal, due to contrasting evidence. Herein, we discuss the physiological and environmental factors that may modify the effectiveness of these supplements including, (i) absolute changes in circulating bicarbonate; (ii) supplement timing, (iii) the exercise task performed, (iv) monocarboxylate transporter (MCT) activity; (v) training status, and (vi) associated side-effects. The aim of this narrative review is to highlight the factors which may modify the response to these supplements, so that individuals can use this information to attempt to optimize supplementation and allow the greatest possibility of an ergogenic effect.
4G/5G polymorphism modulates PAI-1 circulating levels in obese women.
Fernandes, Karla S; Sandrim, Valéria C
2012-05-01
The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.
Stengel, Andreas; Keire, David; Goebel, Miriam; Evilevitch, Lena; Wiggins, Brian; Taché, Yvette; Reeve, Joseph R
2009-11-01
The correct identification of circulating molecular forms and measurement of peptide levels in blood entails that the endocrine peptide being studied is stable and recovered in good yields during blood processing. However, it is not clear whether this is achieved in studies using standard blood processing. Therefore, we compared peptide concentration and form of 12 (125)I-labeled peptides using the standard procedure (EDTA-blood on ice) and a new method employing Reduced temperatures, Acidification, Protease inhibition, Isotopic exogenous controls, and Dilution (RAPID). During standard processing there was at least 80% loss for calcitonin-gene-related peptide and cholecystokinin-58 (CCK-58) and more than 35% loss for amylin, insulin, peptide YY forms (PYY((1-36)) and PYY((3-36))), and somatostatin-28. In contrast, the RAPID method significantly improved the recovery for 11 of 12 peptides (P < 0.05) and eliminated the breakdown of endocrine peptides occurring after standard processing as reflected in radically changed molecular forms for CCK-58, gastrin-releasing peptide, somatostatin-28, and ghrelin. For endogenous ghrelin, this led to an acyl/total ghrelin ratio of 1:5 instead of 1:19 by the standard method. These results show that the RAPID method enables accurate assessment of circulating gut peptide concentrations and forms such as CCK-58, acylated ghrelin, and somatostatin-28. Therefore, the RAPID method represents an efficacious means to detect circulating variations in peptide concentrations and form relevant to the understanding of physiological function of endocrine peptides.
Organic compounds in re-circulated leachates of aerobic biological treated municipal solid waste.
Franke, Matthias; Jandl, Gerald; Leinweber, Peter
2006-10-01
Biodegradation of organic matter is required to reduce the potential of municipal solid waste for producing gaseous emissions and leaching contaminants. Therefore, we studied leachates of an aerobic-treated waste from municipal solids and a sewage sludge mixture that were re-circulated to decrease the concentration of biodegradable organic matter in laboratory-scale reactors. After 12 months, the total organic C and biological and chemical oxygen demands were reduced, indicating the biodegradation of organic compounds in the leachates. Curie-point pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and pyrolysis-field ionization mass spectrometry (Py-FIMS) revealed that phenols, alkylaromatic compounds, N-containing compounds and carbohydrates were the predominate compounds in the leachates and solid waste. Leachate re-circulation led to a higher thermal stability of the residual organic matter as indicated by temperature-resolved Py-FIMS. Admixture of sewage sludge to solid waste was less effective in removing organic compounds from the leachates. It resulted in drastic higher and more bio-resistant loads of organic matter in the leachates and revealed increased proportions of alkylaromatic compounds. The biodegradation of organic matter in leachates, re-circulated through municipal solid waste, offers the potential for improved aerobic waste treatments and should be investigated on a larger scale.
McCormack, Shana E.; Shaham, Oded; McCarthy, Meaghan A.; Deik, Amy A.; Wang, Thomas J.; Gerszten, Robert E.; Clish, Clary B.; Mootha, Vamsi K.; Grinspoon, Steven K.; Fleischman, Amy
2012-01-01
Background Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. Objective To determine whether pediatric obesity is associated with elevations in fasting circulating concentrations of branched-chain amino acids (isoleucine, leucine, and valine), and whether these elevations predict future insulin resistance. Research Design and Methods Sixty-nine healthy subjects, ages 8 to18 years, were enrolled as a cross-sectional cohort. A subset who were pre- or early-pubertal, ages 8 to 13 years, were enrolled in a prospective longitudinal cohort for 18 months (n=17 with complete data). Results Elevations in the concentrations of BCAA’s were significantly associated with BMI Z-score (Spearman’s Rho 0.27, p=0.03) in the cross-sectional cohort. In the subset of subjects followed longitudinally, baseline BCAA concentrations were positively associated with HOMA-IR measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex, and pubertal stage (p=0.046). Conclusions Elevations in the concentrations of circulating branched-chain amino acids are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. PMID:22961720
Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations
USDA-ARS?s Scientific Manuscript database
Background: Poor vitamin K status is linked to greater risk of several chronic diseases. Age, sex, and diet are determinants of circulating vitamin K; however, there is still large unexplained interindividual variability in vitamin K status. Although a strong genetic component has been hypothesized,...
Body-induced vortical flows: a common mechanism for self-corrective trimming control in boxfishes.
Bartol, Ian K; Gharib, Morteza; Webb, Paul W; Weihs, Daniel; Gordon, Malcolm S
2005-01-01
Boxfishes (Teleostei: Ostraciidae) are marine fishes having rigid carapaces that vary significantly among taxa in their shapes and structural ornamentation. We showed previously that the keels of the carapace of one species of tropical boxfish, the smooth trunkfish, produce leading edge vortices (LEVs) capable of generating self-correcting trimming forces during swimming. In this paper we show that other tropical boxfishes with different carapace shapes have similar capabilities. We conducted a quantitative study of flows around the carapaces of three morphologically distinct boxfishes (spotted boxfish, scrawled cowfish and buffalo trunkfish) using stereolithographic models and three separate but interrelated analytical approaches: digital particle image velocimetry (DPIV), pressure distribution measurements, and force balance measurements. The ventral keels of all three forms produced LEVs that grew in circulation along the bodies, resembling the LEVs produced around delta-winged aircraft. These spiral vortices formed above the keels and increased in circulation as pitch angle became more positive, and formed below the keels and increased in circulation as pitch angle became more negative. Vortices also formed along the eye ridges of all boxfishes. In the spotted boxfish, which is largely trapezoidal in cross section, consistent dorsal vortex growth posterior to the eye ridge was also present. When all three boxfishes were positioned at various yaw angles, regions of strongest concentrated vorticity formed in far-field locations of the carapace compared with near-field areas, and vortex circulation was greatest posterior to the center of mass. In general, regions of localized low pressure correlated well with regions of attached, concentrated vorticity, especially around the ventral keels. Although other features of the carapace also affect flow patterns and pressure distributions in different ways, the integrated effects of the flows were consistent for all forms: they produce trimming self-correcting forces, which we measured directly using the force balance. These data together with previous work on smooth trunkfish indicate that body-induced vortical flows are a common mechanism that is probably significant for trim control in all species of tropical boxfishes.
The effect of aerosols on northern hemisphere wintertime stationary waves
NASA Astrophysics Data System (ADS)
Lewinschal, Anna; Ekman, Annica M. L.
2010-05-01
Aerosol particles have a considerable impact on the energy budget of the atmosphere because of their ability to scatter and absorb incoming solar radiation. Since the beginning of the industrialisation a large increase has been seen mainly in the concentrations of sulphate and black carbon as a result of combustion of fossil fuel and biomass burning. Aerosol particles have a relatively short residence time in the atmosphere why the aerosol concentration shows a large variation spatially as well as in time where high concentrations are found close to emission sources. This leads to a highly varying radiative forcing pattern which modifies temperature gradients which in turn can alter the pressure distribution and lead to changes in the circulation in the atmosphere. In this study, the effect on the wintertime planetary scale waves on the northern hemisphere is specifically considered together with the regional climate impact due to changes in the stationary waves. To investigate the effect of aerosols on the circulation a global general circulation model based on the ECMWF operational forecast model is used (EC-Earth). The aerosol description in EC-Earth consists of prescribed monthly mean mass concentration fields of five different types of aerosols: sulphate, black carbon, organic carbon, dust and sea salt. Only the direct radiative effect is considered and the different aerosol types are treated as external mixtures. Changes in the stationary wave pattern are determined by comparing model simulations using present-day and pre-industrial concentrations of aerosol particles. Since the planetary scale waves largely influence the storm tracks and are an important part of the meridional heat transport, changes in the wave pattern may have substantial impact on the climate globally and locally. By looking at changes in the model simulations globally it can be found that the aerosol radiative forcing has the potential to change the stationary wave pattern. Furthermore, it shows that regional changes in the climate occur also where the radiative forcing from aerosol particles is not particularly strong, which would indicate that the large scale dynamical response to aerosol forcing can induce changes in temperature, precipitation and wind patterns outside the region where the forcing is initially located.
Fanidi, Anouar; Muller, David C; Yuan, Jian-Min; Stevens, Victoria L; Weinstein, Stephanie J; Albanes, Demetrius; Prentice, Ross; Thomsen, Cynthia A; Pettinger, Mary; Cai, Qiuyin; Blot, William J; Wu, Jie; Arslan, Alan A; Zeleniuch-Jacquotte, Anne; McCullough, Marjorie L; Le Marchand, Loic; Wilkens, Lynne R; Haiman, Christopher A; Zhang, Xuehong; Han, Jiali; Stampfer, Meir J; Smith-Warner, Stephanie A; Giovannucci, Edward; Giles, Graham G; Hodge, Allison M; Severi, Gianluca; Johansson, Mikael; Grankvist, Kjell; Langhammer, Arnulf; Krokstad, Steinar; Næss, Marit; Wang, Renwei; Gao, Yu-Tang; Butler, Lesley M; Koh, Woon-Puay; Shu, Xiao-Ou; Xiang, Yong-Bing; Li, Honglan; Zheng, Wei; Lan, Qing; Visvanathan, Kala; Bolton, Judith Hoffman; Ueland, Per Magne; Midttun, Øivind; Ulvik, Arve; Caporaso, Neil E; Purdue, Mark; Ziegler, Regina G; Freedman, Neal D; Buring, Julie E; Lee, I-Min; Sesso, Howard D; Gaziano, J Michael; Manjer, Jonas; Ericson, Ulrika; Relton, Caroline; Brennan, Paul; Johansson, Mattias
2018-01-01
Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Lycopene and Risk of Prostate Cancer
Chen, Ping; Zhang, Wenhao; Wang, Xiao; Zhao, Keke; Negi, Devendra Singh; Zhuo, Li; Qi, Mao; Wang, Xinghuan; Zhang, Xinhua
2015-01-01
Abstract Prostate cancer (PCa) is a common illness for aging males. Lycopene has been identified as an antioxidant agent with potential anticancer properties. Studies investigating the relation between lycopene and PCa risk have produced inconsistent results. This study aims to determine dietary lycopene consumption/circulating concentration and any potential dose–response associations with the risk of PCa. Eligible studies published in English up to April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online, Wiley online library databases and hand searching. The STATA (version 12.0) was applied to process the dose–response meta-analysis. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) and to incorporate variation between studies. The linear and nonlinear dose–response relations were evaluated with data from categories of lycopene consumption/circulating concentrations. Twenty-six studies were included with 17,517 cases of PCa reported from 563,299 participants. Although inverse association between lycopene consumption and PCa risk was not found in all studies, there was a trend that with higher lycopene intake, there was reduced incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity analysis, or recalculation using data from only high-quality studies for subgroup analysis, indicated that higher lycopene consumption significantly lowered PCa risk. Furthermore, our dose–response meta-analysis demonstrated that higher lycopene consumption was linearly associated with a reduced risk of PCa with a threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene levels significantly reduced the risk of PCa. Interestingly, the concentration of circulating lycopene between 2.17 and 85 μg/dL was linearly inversed with PCa risk whereas there was no linear association >85 μg/dL. In addition, greater efficacy for the circulating lycopene concentration on preventing PCa was found for studies with high quality, follow-up >10 years and where results were adjusted by the age or the body mass index. In conclusion, our novel data demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa. However, further studies are required to determine the mechanism by which lycopene reduces the risk of PCa and if there are other factors in tomato products that might potentially decrease PCa risk and progression. PMID:26287411
Diepenbroek, C; Rijnsburger, M; Eggels, L; van Megen, K M; Ackermans, M T; Fliers, E; Kalsbeek, A; Serlie, M J; la Fleur, S E
2017-01-10
The brain is well known to regulate blood glucose, and the hypothalamus and hindbrain, in particular, have been studied extensively to understand the underlying mechanisms. Nuclei in these regions respond to alterations in blood glucose concentrations and can alter glucose liver output or glucose tissue uptake to maintain blood glucose concentrations within strict boundaries. Interestingly, several cortico-limbic regions also respond to alterations in glucose concentrations and have been shown to project to hypothalamic nuclei and glucoregulatory organs. For instance, electrical stimulation of the shell of the nucleus accumbens (sNAc) results in increased circulating concentrations of glucose and glucagon and activation of the lateral hypothalamus (LH). Whether this is caused by the simultaneous increase in serotonin release in the sNAc remains to be determined. To study the effect of sNAc serotonin on systemic glucose metabolism, we implanted bilateral microdialysis probes in the sNAc of male Wistar rats and infused fluoxetine, a serotonin reuptake inhibitor, or vehicle after which blood glucose, endogenous glucose production (EGP) and glucoregulatory hormones were measured. Fluoxetine in the sNAc for 1h significantly increased blood glucose concentrations without an effect on glucoregulatory hormones. This increase was accompanied by a higher EGP in the fluoxetine infused rats compared to the controls. These data provide further evidence for a role of sNAc-serotonin in the regulation of glucose metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Pozzoli, Luca; Dobricic, Srdan; Russo, Simone; Vignati, Elisabetta
2017-10-01
Winter warming and sea-ice retreat observed in the Arctic in the last decades may be related to changes of large-scale atmospheric circulation pattern, which may impact the transport of black carbon (BC) to the Arctic and its deposition on the sea ice, with possible feedbacks on the regional and global climate forcing. In this study we developed and applied a statistical algorithm, based on the maximum likelihood estimate approach, to determine how the changes of three large-scale weather patterns associated with increasing temperatures in winter and sea-ice retreat in the Arctic impact the transport of BC to the Arctic and its deposition. We found that two atmospheric patterns together determine a decreasing winter deposition trend of BC between 1980 and 2015 in the eastern Arctic while they increase BC deposition in the western Arctic. The increasing BC trend is mainly due to a pattern characterized by a high-pressure anomaly near Scandinavia favouring the transport in the lower troposphere of BC from Europe and North Atlantic directly into to the Arctic. Another pattern with a high-pressure anomaly over the Arctic and low-pressure anomaly over the North Atlantic Ocean has a smaller impact on BC deposition but determines an increasing BC atmospheric load over the entire Arctic Ocean with increasing BC concentrations in the upper troposphere. The results show that changes in atmospheric circulation due to polar atmospheric warming and reduced winter sea ice significantly impacted BC transport and deposition. The anthropogenic emission reductions applied in the last decades were, therefore, crucial to counterbalance the most likely trend of increasing BC pollution in the Arctic.
Marcaccini, Andrea M; Meschiari, César A; Sorgi, Carlos A; Saraiva, Maria C P; de Souza, Ana M; Faccioli, Lúcia H; Tanus-Santos, José E; Novaes, Arthur B; Gerlach, Raquel F
2009-04-01
Periodontal disease has been associated with many chronic inflammatory systemic diseases, and a common chronic inflammation pathway has been suggested for these conditions. However, few studies have evaluated whether periodontal disease, in the absence of other known inflammatory conditions and smoking, affects circulating markers of chronic inflammation. This study compared chronic inflammation markers in control individuals and patients with periodontal disease and observed whether non-surgical periodontal therapy affected inflammatory disease markers after 3 months. Plasma and serum of 20 controls and 25 patients with periodontal disease were obtained prior to and 3 months after non-surgical periodontal therapy. All patients were non-smokers, they did not use any medication, and they had no history or detectable signs and symptoms of systemic diseases. Periodontal and systemic parameters included probing depth, bleeding on probing, clinical attachment level, hematologic parameters, as well as the following inflammatory markers: interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), CD40 ligand, monocyte chemoattractant protein (MCP)-1, soluble P-selectin (sP-selectin), soluble vascular adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. There were no differences in the hematologic parameters of the patients in the control and periodontal disease groups. Among the tested inflammatory markers, IL-6 concentrations were higher in the periodontal disease group at baseline compared to the controls (P = 0.006). Therapy was highly effective (P <0.001 for all the analyzed clinical parameters), and a decrease in circulating IL-6 and hs-CRP concentrations was observed 3 months after therapy (P = 0.001 and P = 0.006, respectively). Our results also suggest that the CD40 ligand marker may have been different in the control and periodontal disease groups prior to the therapy (P = 0.009). In apparently otherwise healthy patients, periodontal disease is associated with increased circulating concentrations of IL-6 and hs-CRP, which decreased 3 months after non-surgical periodontal therapy. With regard to the CD40 ligand, MCP-1, sP-selectin, sVCAM-1, and sICAM-1, no changes were seen in the periodontal disease group between baseline and 3 months after therapy.
van Duijnhoven, Fränzel J B; Jenab, Mazda; Hveem, Kristian; Siersema, Peter D; Fedirko, Veronika; Duell, Eric J; Kampman, Ellen; Halfweeg, Anouk; van Kranen, Henk J; van den Ouweland, Jody M W; Weiderpass, Elisabete; Murphy, Neil; Langhammer, Arnulf; Ness-Jensen, Eivind; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Cadeau, Claire; Kvaskoff, Marina; Boutron-Ruault, Marie-Christine; Katzke, Verena A; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Kotanidou, Anastasia; Kritikou, Maria; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Panico, Salvatore; Matullo, Giuseppe; Peeters, Petra; Brustad, Magritt; Olsen, Karina Standahl; Lasheras, Cristina; Obón-Santacana, Mireia; Sánchez, María-José; Dorronsoro, Miren; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Manjer, Jonas; Almquist, Martin; Renström, Frida; Ye, Weimin; Wareham, Nick; Khaw, Kay-Tee; Bradbury, Kathryn E; Freisling, Heinz; Aune, Dagfinn; Norat, Teresa; Riboli, Elio; Bueno-de-Mesquita, H B As
2018-03-15
Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D 2 and 25(OH)D 3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Does Formaldehyde Increase Cell Free DNA in Maternal Plasma Specimens?
Jacob, Rintu R; Saxena, Renu; Verma, Ishwar C
2016-11-01
There have been conflicting observations reported in the literature regarding the effects of formaldehyde in the recovery of cell free fetal DNA (CFF DNA) from maternal plasma. The aim of the present study was to assess the effect of formaldehyde treatment on circulating cell free DNA. We conducted this study using blood specimens collected from 11 pregnant women, each of whom was carrying a male fetus. DYS14 and HBB real time assays were performed to quantify fetal and total circulating cell free DNA from formaldehyde treated and untreated maternal plasma specimens, respectively. The concentration of total circulating cell free DNA in formaldehyde-treated maternal plasma was reduced, compared with untreated maternal plasma (n = 11; P = .02). The percentage of CFF DNA between formaldehyde-treated and untreated maternal plasma specimens did not differ significantly (n = 11; P = .15). Addition of formaldehyde does not significantly enhance the proportion of cell free fetal DNA when blood specimens are processed without delay. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Ovarian Cancer, Stem Cells, and Bioreactors
2009-10-01
also indirectly assessed by measuring CEA and CA125 levels in the circulating medium. CEA and CA125, belonging to the CEA antigen family, are...with OVC#6 could not be detected. The low level of CA125 may be due to a dilution of the protein in the circulating medium as protein concentrations...lower than 8.7U/ml are below the assay sensitivity. Unfortunately, we have been unable to obtain the CA125 circulating level for either patient so
Urbanová, M; Dostálová, I; Trachta, P; Drápalová, J; Kaválková, P; Haluzíková, D; Matoulek, M; Lacinová, Z; Mráz, M; Kasalický, M; Haluzík, M
2014-01-01
Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.
Korabecna, Marie; Ulcova-Gallova, Zdenka; Horinek, Ales; Pazourková, Eva; Calda, Pavel
2014-11-01
Apoptosis of tissues of fetal origin is thought to be one of the main sources of cell-free fetal DNA (cffDNA) in maternal circulation, impaired apoptosis is also involved in the mechanisms contributing to recurrent spontaneous miscarriages (RSM) associated with antiphospholipid syndrome (APS). The APS increases the risk for preeclampsia nine times. In preeclampsia, the elevated levels of cffDNA were described by different authors. To our knowledge, cffDNA in pregnant patients with APS was never studied. In our pilot study, we focused on the levels of cffDNA in four pregnant patients with treated primary APS and compared them with values obtained in twenty-one healthy subjects of comparable gestation age (the third trimester of pregnancy). We supposed that the increase of cffDNA concentration in our treated patients would signalize the elevated apoptosis of fetal tissues as in other pathological changes of placentation. The aim of our pilot study was to determine cffDNA concentrations in patients with treated APS and to compare them with values detected in healthy pregnant women of comparable gestation age in order to discover potential non-physiological elevations in patients. The elevated values of cffDNA were not observed in our patients (p value = 0.4363, Mann-Whitney test). All patients delivered healthy children. The measurement of concentrations of cffDNA seems to be a promising tool for monitoring of therapy effectiveness in pregnant women with APS but evaluation of randomized controlled trials would be necessary to determine the specificity and the sensitivity of this test.
NASA Astrophysics Data System (ADS)
Umling, Natalie E.; Thunell, Robert C.
2018-06-01
A growing body of evidence suggests that respired carbon was stored in mid-depth waters (∼1-3 km) during the last glacial maximum (LGM) and released to the atmosphere from upwelling regions during deglaciation. Decreased ventilation, enhanced productivity, and enhanced carbonate dissolution are among the mechanisms that have been cited as possible drivers of glacial CO2 drawdown. However, the relative importance of each of these mechanisms is poorly understood. New approaches to quantitatively constrain bottom water carbonate chemistry and oxygenation provide methods for estimating historic changes in respired carbon storage. While increased CO2 drawdown during the LGM should have resulted in decreased oxygenation and a shift in dissolved inorganic carbon (DIC) speciation towards lower carbonate ion concentrations, this is complicated by the interplay of carbonate compensation, export productivity, and circulation. To disentangle these processes, we use a multiproxy approach that includes boron to calcium (B/Ca) ratios of the benthic foraminifera Cibicidoides wuellerstorfi to reconstruct deep-water carbonate ion concentrations ([CO32-]) and the uranium to calcium (U/Ca) ratio of foraminiferal coatings in combination with benthic foraminiferal carbon isotopes to reconstruct changes in bottom water oxygen concentrations ([O2]) and organic carbon export. Our records indicate that LGM [CO32-] and [O2] was reduced at mid water depths of the eastern equatorial Pacific (EEP), consistent with increased respired carbon storage. Furthermore, our results suggest enhanced mixing of lower Circumpolar Deep Water (LCDW) to EEP mid water depths and provide evidence for the importance of circulation for oceanic-atmospheric CO2 exchange.
Deglacial upwelling, productivity and CO2 outgassing in the North Pacific Ocean
NASA Astrophysics Data System (ADS)
Gray, William R.; Rae, James W. B.; Wills, Robert C. J.; Shevenell, Amelia E.; Taylor, Ben; Burke, Andrea; Foster, Gavin L.; Lear, Caroline H.
2018-05-01
The interplay between ocean circulation and biological productivity affects atmospheric CO2 levels and marine oxygen concentrations. During the warming of the last deglaciation, the North Pacific experienced a peak in productivity and widespread hypoxia, with changes in circulation, iron supply and light limitation all proposed as potential drivers. Here we use the boron-isotope composition of planktic foraminifera from a sediment core in the western North Pacific to reconstruct pH and dissolved CO2 concentrations from 24,000 to 8,000 years ago. We find that the productivity peak during the Bølling-Allerød warm interval, 14,700 to 12,900 years ago, was associated with a decrease in near-surface pH and an increase in pCO2, and must therefore have been driven by increased supply of nutrient- and CO2-rich waters. In a climate model ensemble (PMIP3), the presence of large ice sheets over North America results in high rates of wind-driven upwelling within the subpolar North Pacific. We suggest that this process, combined with collapse of North Pacific Intermediate Water formation at the onset of the Bølling-Allerød, led to high rates of upwelling of water rich in nutrients and CO2, and supported the peak in productivity. The respiration of this organic matter, along with poor ventilation, probably caused the regional hypoxia. We suggest that CO2 outgassing from the North Pacific helped to maintain high atmospheric CO2 concentrations during the Bølling-Allerød and contributed to the deglacial CO2 rise.
Impact of being overweight on factor VIII dosing in children with haemophilia A.
Henrard, S; Hermans, C
2016-05-01
Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%. The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)-for-age, height), age and type of FVIII concentrate on FVIII recovery in children with HA. A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery. The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI-for-age percentile
Zapata, Rizaldy C; Salehi, Reza; Ambrose, Divakar J; Chelikani, Prasanth K
2015-10-01
Dietary fat supplementation during the periparturient period is one strategy to increase energy intake and attenuate the degree of negative energy balance during early lactation; however, little is known of the underlying hormonal and metabolic adaptations. We evaluated the effects of prepartum fat supplementation on energy-balance parameters and plasma concentrations of glucagon-like peptide-1, peptide tyrosine-tyrosine (PYY), adropin, insulin, leptin, glucose, nonesterified fatty acid, and β-hydroxybutyric acid in dairy cows. Twenty-four pregnant dairy cows were randomized to diets containing either rolled canola or sunflower seed at 8% of dry matter, or no oilseed supplementation, during the last 5 wk of gestation and then assigned to a common lactation diet postpartum. Blood samples were collected at -2, +2, and +14 h relative to feeding, at 2 wk after the initiation of the diets, and at 2 wk postpartum. Dietary canola and sunflower supplementation alone did not affect energy balance, body weight, and plasma concentrations of glucagon-like peptide-1, PYY, adropin, insulin, leptin, nonesterified fatty acid, and β-hydroxybutyric acid; however, canola decreased and sunflower tended to decrease dry matter intake. We also observed that the physiological stage had a significant, but divergent, effect on circulating hormones and metabolite concentrations. Plasma glucagon-like peptide-1, PYY, adropin, nonesterified fatty acid, and β-hydroxybutyric acid concentrations were greater postpartum than prepartum, whereas glucose, insulin, leptin, body weight, and energy balance were greater prepartum than postpartum. Furthermore, the interaction of treatment and stage was significant for leptin and adropin, and tended toward significance for PYY and insulin; only insulin exhibited an apparent postprandial increase. Postpartum PYY concentrations exhibited a strong negative correlation with body weight, suggesting that PYY may be associated with body weight regulation during the transition period. These novel findings demonstrate that the transition from pregnancy to lactation is a stronger determinant of circulating gut hormone concentrations than dietary lipid in transition dairy cows. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Time-varying changes in the simulated structure of the Brewer-Dobson Circulation
NASA Astrophysics Data System (ADS)
Garfinkel, Chaim I.; Aquila, Valentina; Waugh, Darryn W.; Oman, Luke D.
2017-01-01
A series of simulations using the NASA Goddard Earth Observing System Chemistry Climate Model are analyzed in order to assess changes in the Brewer-Dobson Circulation (BDC) over the past 55 years. When trends are computed over the past 55 years, the BDC accelerates throughout the stratosphere, consistent with previous modeling results. However, over the second half of the simulations (i.e., since the late 1980s), the model simulates structural changes in the BDC as the temporal evolution of the BDC varies between regions in the stratosphere. In the mid-stratosphere in the midlatitude Northern Hemisphere, the BDC does not accelerate in the ensemble mean of our simulations despite increases in greenhouse gas concentrations and warming sea surface temperatures, and it even decelerates in one ensemble member. This deceleration is reminiscent of changes inferred from satellite instruments and in situ measurements. In contrast, the BDC in the lower stratosphere continues to accelerate. The main forcing agents for the recent slowdown in the mid-stratosphere appear to be declining ozone-depleting substance (ODS) concentrations and the timing of volcanic eruptions. Changes in both mean age of air and the tropical upwelling of the residual circulation indicate a lack of recent acceleration. We therefore clarify that the statement that is often made that climate models simulate a decreasing age throughout the stratosphere only applies over long time periods and is not necessarily the case for the past 25 years, when most tracer measurements were taken.
Time-Varying Changes in the Simulated Structure of the Brewer-Dobson Circulation
NASA Technical Reports Server (NTRS)
Garfinkel, Chaim I.; Aquila, Valentina; Waugh, Darryn W.; Oman, Luke D.
2017-01-01
A series of simulations using the NASA Goddard Earth Observing System Chemistry Climate Model are analyzed in order to assess changes in the Brewer-Dobson Circulation (BDC) over the past 55 years. When trends are computed over the past 55 years, the BDC accelerates throughout the stratosphere, consistent with previous modeling results. However, over the second half of the simulations (i.e., since the late 1980s), the model simulates structural changes in the BDC as the temporal evolution of the BDC varies between regions in the stratosphere. In the mid-stratosphere in the midlatitude Northern Hemisphere, the BDC does not accelerate in the ensemble mean of our simulations despite increases in greenhouse gas concentrations and warming sea surface temperatures, and it even decelerates in one ensemble member. This deceleration is reminiscent of changes inferred from satellite instruments and in situ measurements. In contrast, the BDC in the lower stratosphere continues to accelerate. The main forcing agents for the recent slowdown in the mid-stratosphere appear to be declining ozone-depleting substance (ODS) concentrations and the timing of volcanic eruptions. Changes in both mean age of air and the tropical upwelling of the residual circulation indicate a lack of recent acceleration. We therefore clarify that the statement that is often made that climate models simulate a decreasing age throughout the stratosphere only applies over long time periods and is not necessarily the case for the past 25 years, when most tracer measurements were taken.
Zoia, Andrea; Augusto, Monica; Drigo, Michele; Caldin, Marco
2012-11-15
To determine whether dogs with ascites secondary to right-sided congestive heart failure (CHF) have bleeding disorders associated with hypofibrinogenemia and discordant plasma fibrin-fibrinogen degradation products (FDPs) and D-dimer assay results (ie, a circulating concentration of FDPs higher than the reference range and a circulating concentration of D-dimer within the reference range). Retrospective case-control study. 80 client-owned dogs. Dogs with ascites secondary to right-sided CHF (group 1; n = 20), unhealthy dogs without cardiac disease (group 2; 40), and dogs with left-sided CHF (group 3; 20) were included in the study. Urine bile acids-to-creatinine concentration ratios were calculated as a marker of liver function. Differences among groups regarding coagulation profile analysis results and prevalence of discordant FDPs and D-dimer assay results were determined. No significant differences were detected among the 3 groups regarding urine bile acids-to-creatinine concentration ratios. Plasma fibrinogen concentration was significantly lower for group 1 versus groups 2 or 3. Prevalence of discordant FDPs and D-dimer assay results was significantly higher for group 1 versus groups 2 or 3. Eighteen group 1 dogs had discordant FDPs and D-dimer assay results. Ten of these dogs had concurrent hypofibrinogenemia, 2 of which had clinical signs of bleeding. Only 10 dogs in groups 2 or 3 had discordant FDPs and D-dimer assay results; none of these dogs had hypofibrinogenemia or clinical signs of bleeding. Dogs with right-sided CHF and ascites may be at increased risk for primary hyperfibrinogenolysis (ie, hypofibrinogenemia and discordant FDPs and D-dimer assay results).
NASA Astrophysics Data System (ADS)
Ravinder, T.; Ali, U. F. M.; Ridwan, F. M.; Ibrahim, N.; Azmi, N. H.
2017-06-01
The utilization of electrochemical process recovery involving low reactant concentrations of metal requires electrodes with high mass transport rates and specific surface areas. This is essential to increase cross-sectional current densities whilst optimizing the capital and operating costs. Experimental results demonstrated that Circulating Particulate Bed Reactor (CPBE) is suitable for the recovery of low concentrations of gold from aqueous chloride solution containing {{AuCl}}4- and {{AuCl}}2- of less than 0.5 mol m-3(< 102 g m-3). Elemental gold was successfully obtained on 0.5-1 mm gr particles in an electrochemical reactor incorporating a cation- permeable membrane and operated in bath recycle mode. Depletion to concentration < 5 × 10-3 mol m-3 (< 1 g m-3) appeared to be mass transport controlled at an applied potential of +0.20 V (SCE), specific electrical energy consumption (SEEC) of ca. 800-1300 kWh h (tonne Au)-1 for cell voltages (U) of 2.0-3.0 V, and fractional current efficiencies of ca. 0.95. However, atomic absorption and UV spectrophotometry established that as the ([{{AuCl}}4-+[{{AuCl}}2-]) concentration decayed, the [{{AuCl}}4-]:[{{AuCl}}2-] molar ratio changed. A multi-step mechanism for reduction of {{AuCl}}4- ions explained this behavior in terms of changing overpotentials for {{AuCl}}4- and {{AuCl}}2- reduction as total dissolved gold concentration decreased. In addition, SEM images confirmed that adherent and coherent Au deposits were achieved with CPBE for Au deposition under mass transport control at 0.20 V (SCE).
[The Relevance of Hemolysis in Anesthesia and Intensive Care Medicine].
Graw, Jan A; Baron, David M; Francis, Roland C E
2018-04-01
Hemolysis leads to an increase of circulating intravascular cell-free hemoglobin. Increased plasma concentrations of cell-free hemoglobin are relevant in critically ill patients because cell-free hemoglobin causes vasoconstriction by depletion of endothelial nitric oxide, oxidative stress, and inflammation. Furthermore, cell-free hemoglobin contributes to tissue injuries such as renal failure and intestinal mucosa damage after cardiac surgery. High concentrations of cell-free hemoglobin are associated with an increased mortality in patients with sepsis. Currently, it is unclear if hemolysis associated with transfusion of packed red blood cells that have been stored for prolonged periods of time is relevant for the clinical outcome. However, humans possess plasma proteins haptoglobin and hemopexin which bind to plasma hemoglobin and cell-free heme, respectively. The haptoglobin-hemoglobin and hemopexin-heme complexes are then eliminated from the plasma by hepatic or splenic uptake. Georg Thieme Verlag KG Stuttgart · New York.
Mann, S; Urh, C; Sauerwein, H; Wakshlag, J J; Yepes, F A Leal; Overton, T R; Nydam, D V
2018-01-01
Adipokines-hormones produced by adipose tissue-have important regulatory functions, and their concentrations can change around the time of calving when energy balance rapidly decreases. Hence, energy balance may be an important factor in determining the circulating concentrations of adipokines, particularly adiponectin and leptin. The objective of our study was to investigate the association between the level of energy fed to prepartum Holstein cows and circulating concentrations of adiponectin and leptin before and after calving. Holstein dairy cows entering second or greater lactation were fed either a controlled-energy diet formulated to supply approximately 100% of energy requirements (n = 28) or a high-energy diet formulated to supply approximately 150% of energy requirements throughout the entire dry period (n = 28). Serum samples were analyzed for adiponectin and leptin concentrations at 56, 28, 10, and 1 d prepartum as well as on d 1, 10, 21, and 42 postpartum using ELISA. Parity was dichotomized into cows entering second versus higher parity. Average peripartum body condition score (BCS) was computed from weekly measurements and dichotomized into animals with an average BCS of ≤3.25 and >3.25. In addition, cows were classified according to the occurrence of hyperketonemia (β-hydroxybutyrate concentrations ≥1.2 mmol/L at any time between 3 and 21 d in milk). Data were analyzed using repeated-measures ANOVA. Serum leptin but not adiponectin concentrations were associated with prepartum feeding level such that leptin concentrations increased transiently during the dry period in cows overfed energy, but concentrations were not different postpartum. Cows entering second parity had higher adiponectin and lower leptin concentrations compared with cows in higher parities. Cows that developed hyperketonemia postpartum had consistently lower adiponectin concentrations during the study period. Cows with average BCS >3.25 had higher leptin concentrations during the dry period only, but adiponectin concentrations were not associated with BCS. In conclusion, prepartum energy level had only transient effects on leptin concentrations and did not lead to changes in adiponectin concentrations. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Appleby, Paul N.; Albanes, Demetrius; Black, Amanda; Chan, June M.; Chen, Chu; Cirillo, Piera M.; Cohn, Barbara A.; Cook, Michael B.; Donovan, Jenny L.; Ferrucci, Luigi; Garland, Cedric F.; Giles, Graham G.; Goodman, Phyllis J.; Habel, Laurel A.; Haiman, Christopher A.; Holly, Jeff M. P.; Hoover, Robert N.; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N.; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J.; Mäenpää, Hanna O.; Männistö, Satu; Metter, E. Jeffrey; Milne, Roger L.; Nomura, Abraham M. Y.; Oliver, Steven E.; Parsons, J. Kellogg; Peeters, Petra H.; Platz, Elizabeth A.; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A.; Schenk, Jeannette M.; Stanczyk, Frank Z.; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M.; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S.; Ziegler, Regina G.
2017-01-01
Introduction Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Methods Statistical analyses of individual participant data from 12,330 male controls aged 25–85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Results Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Conclusion Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption. PMID:29281666
Watts, Eleanor L; Appleby, Paul N; Albanes, Demetrius; Black, Amanda; Chan, June M; Chen, Chu; Cirillo, Piera M; Cohn, Barbara A; Cook, Michael B; Donovan, Jenny L; Ferrucci, Luigi; Garland, Cedric F; Giles, Graham G; Goodman, Phyllis J; Habel, Laurel A; Haiman, Christopher A; Holly, Jeff M P; Hoover, Robert N; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Milne, Roger L; Nomura, Abraham M Y; Oliver, Steven E; Parsons, J Kellogg; Peeters, Petra H; Platz, Elizabeth A; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A; Schenk, Jeannette M; Stanczyk, Frank Z; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S; Ziegler, Regina G; Allen, Naomi E; Key, Timothy J; Travis, Ruth C
2017-01-01
Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.
Land-atmosphere-aerosol coupling in North China during 2000-2013
NASA Astrophysics Data System (ADS)
Wei, J.; Jin, Q.; Yang, Z. L.; Zhou, L.
2017-12-01
North China is one of the most densely populated regions in the world. To its west, north, and northwest, the world's largest afforestation project has been going on for decades. At the same time, North China has been suffering from air pollution because of its large fossil fuel consumption. Here we show that the changes in land cover and aerosol concentration are coupled with the variations of land surface temperature, cloud cover, and surface solar radiation during the summer 2000-2013. Model experiments show that the interannual variation of aerosol concentration in North China is mainly a result of the varying atmospheric circulation. The increasing vegetation cover due to afforestation has enhanced surface evapotranspiration (ET) and cooled the local surface, and precipitation is observed to be increasing with ET. The model with prescribed increasing vegetation cover can simulate the increasing ET but cannot reproduce the increasing precipitation. Although this may be caused by model biases, the lack of aerosol processes in the model could also be a potential cause.
A Conceptual Model for Tropical Cyclone Formation
NASA Astrophysics Data System (ADS)
Wang, Z.
2014-12-01
The role of cumulus congestus (shallow and congestus convection) in tropical cyclone (TC) formation is examined in a high-resolution simulation of Tropical Cyclone Fay (2008). It is found that cumulus congestus plays a dominant role in moistening the lower to middle troposphere and spinning up the near-surface circulation before genesis, while deep convection plays a key role in moistening the upper troposphere and intensifying the cyclonic circulation over a deep layer. The transition from the tropical wave stage to the TC stage is marked by a substantial increase in net condensation and potential vorticity generation by deep convection in the inner wave pouch region. This study suggests that TC formation can be regarded as a two-stage process. The first stage is a gradual process of moisture preconditioning and the low-level spinup, in which cumulus congestus plays a dominant role. The second stage commences with the rapid development of deep convection in the inner pouch region after the air column is moistened sufficiently, whereupon the concentrated convective heating near the pouch center strengthens the transverse circulation and leads to the amplification of the cyclonic circulation over a deep layer. The rapid development of deep convection can be explained by the power-law increase of precipitation rate with column water vapor (CWV) above a critical value. The high CWV near the pouch center thus plays an important role in convective organization. It is also shown that cumulus congestus can effectively drive the low-level convergence and provides a direct and simple pathway for the development of the TC proto-vortex near the surface.
Bui, T D; Dabdub, D; George, S C
1998-06-01
The steady-state exchange of inert gases across an in situ canine trachea has recently been shown to be limited equally by diffusion and perfusion over a wide range (0.01-350) of blood solubilities (betablood; ml . ml-1 . atm-1). Hence, we hypothesize that the exchange of ethanol (betablood = 1,756 at 37 degrees C) in the airways depends on the blood flow rate from the bronchial circulation. To test this hypothesis, the dynamics of the bronchial circulation were incorporated into an existing model that describes the simultaneous exchange of heat, water, and a soluble gas in the airways. A detailed sensitivity analysis of key model parameters was performed by using the method of Latin hypercube sampling. The model accurately predicted a previously reported experimental exhalation profile of ethanol (R2 = 0.991) as well as the end-exhalation airstream temperature (34.6 degrees C). The model predicts that 27, 29, and 44% of exhaled ethanol in a single exhalation are derived from the tissues of the mucosa and submucosa, the bronchial circulation, and the tissue exterior to the submucosa (which would include the pulmonary circulation), respectively. Although the concentration of ethanol in the bronchial capillary decreased during inspiration, the three key model outputs (end-exhaled ethanol concentration, the slope of phase III, and end-exhaled temperature) were all statistically insensitive (P > 0.05) to the parameters describing the bronchial circulation. In contrast, the model outputs were all sensitive (P < 0.05) to the thickness of tissue separating the core body conditions from the bronchial smooth muscle. We conclude that both the bronchial circulation and the pulmonary circulation impact soluble gas exchange when the entire conducting airway tree is considered.
Concentration Response Curve for Ozone related Mortality at High Concentrations Ana G. Rappold, James Crooks, Lucas M. Neas Background Rising temperatures and decreased global circulation in the upcoming decades are expected to have a detrimental impact on air quality, particular...
RTD-03-031
Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations in Circulating Estradiol: Effects in Both Cycling and Ovariectomized/Steroid-primed Female Rats. Reproductive Toxicology (in press).
Abstract
Oral exposures to high concentrations of th...
Glucogenic treatment creates an optimal metabolic milieu for the conception period in ewes.
Porcu, C; Pasciu, V; Succu, S; Baralla, E; Manca, M E; Serra, E; Leoni, G G; Dattena, M; Bomboi, G C; Molle, G; Naitana, S; Berlinguer, F
2017-04-01
This study determined the influence of a short-term glucogenic nutritional treatment on circulating concentrations of glucose, insulin, insulin-like growth factor 1 (IGF-1), nonesterified fatty acids (NEFA), and urea, and on their correspondent levels in follicular fluid (FF) collected 12 h after the end of the treatment. After estrous synchronization with intravaginal progestagen-impregnated sponges, 20 Sarda ewes were randomly allocated into two experimental groups (GLU and WAT) and, from day 7 to day 10 (day 0 = day of sponge removal), the GLU group was gavaged with a glycogenic mixture, whereas the WAT group was gavaged with water (control group). Follicular development was stimulated by FSH administration from day 8 to 10. At day 11, ovaries were collected and follicular fluid processed. Plasma changes were assessed from day 6 to 11. In GLU group, circulating concentration of glucose (P < 0.0001), insulin (P < 0.0001), and IGF-1 (P < 0.01) rose significantly, whereas NEFA and urea concentrations decreased (P < 0.0001), as compared with controls. In particular, in FF the higher glucose concentrations found in GLU ewes compared with controls (P < 0.0001) were not accompanied by any increase in insulin and IGF-1 concentrations. NEFA (P < 0.0001) and urea (P < 0.0001) were lower in FF of GLU than WAT group, although NEFA clearance in the ovary proved to be less efficient than at the systemic level. No significant difference between groups was found in FF concentrations of pregnancy-associated plasma protein A (a protease regulating the levels of free IGF-1 in follicles), glutathione, and in its total antioxidant capacity. These results suggest that glycogenic mixture administration creates a suitable follicular microenvironment for the conception period in dairy ewes. Copyright © 2016 Elsevier Inc. All rights reserved.
Škereňová, Markéta; Mikulová, Veronika; Čapoun, Otakar; Zima, Tomáš
2016-01-01
Nowadays, on-a-chip capillary electrophoresis is a routine method for the detection of PCR fragments. The Agilent 2100 Bioanalyzer was one of the first commercial devices in this field. Our project was designed to study the characteristics of Agilent DNA 1000 kit in PCR fragment analysis as a part of circulating tumour cell (CTC) detection technique. Despite the common use of this kit a complex analysis of the results from a long-term project is still missing. A commercially available Agilent DNA 1000 kit was used as a final step in the CTC detection (AdnaTest) for the determination of the presence of PCR fragments generated by Multiplex PCR. Data from 30 prostate cancer patients obtained during two years of research were analyzed to determine the trueness and precision of the PCR fragment size determination. Additional experiments were performed to demonstrate the precision (repeatability, reproducibility) and robustness of PCR fragment concentration determination. The trueness and precision of the size determination was below 3% and 2% respectively. The repeatability of the concentration determination was below 15%. The difference in concentration determination increases when Multiplex-PCR/storage step is added between the two measurements of one sample. The characteristics established in our study are in concordance with the manufacturer's specifications established for a ladder as a sample. However, the concentration determination may vary depending on chip preparation, sample storage and concentration. The 15% variation of concentration determination repeatability was shown to be partly proportional and can be suppressed by proper normalization.
Developing confidence in adverse outcome pathway-based ...
An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17β-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 concentrations, and significant increases in
Medeiros, N; Dai, L; Ferguson, A V
2012-01-10
Glucose-sensitive neurons have been identified in a number of CNS regions including metabolic control centers of the hypothalamus. The location of these regions behind the blood-brain barrier restricts them to sensing central, but not circulating glucose concentrations. In this study, we have used patch-clamp electrophysiology to examine whether neurons in a specialized region lacking the blood-brain barrier, the subfornical organ (SFO), are also glucose sensitive. In dissociated SFO neurons, altering the bath concentration of glucose (1 mM, 5 mM, 10 mM) influenced the excitability of 49% of neurons tested (n=67). Glucose-inhibited (GI) neurons depolarized in response to decreased glucose (n=10; mean, 4.6±1.0 mV) or hyperpolarized in response to increased glucose (n=8; mean,-4.4±0.8 mV). In contrast, glucose-excited (GE) neurons depolarized in response to increased glucose (n=9; mean, 6.4±0.4 mV) or hyperpolarized in response to decreased glucose (n=6; mean,-4.8±0.6 mV). Using voltage-clamp recordings, we also identified GI (outward current to increased glucose) and GE (inward current to increased glucose) SFO neurons. The mean glucose-induced inward current had a reversal potential of -24±12 mV (n=5), while GE responses were maintained during sodium-dependent glucose transporter inhibition, supporting the conclusion that GE properties result from the activation of a nonselective cation conductance (NSCC). The glucose-induced outward current had a mean reversal potential of -78±1.2 mV (n=5), while GI responses were not observed in the presence of glibenclamide, suggesting that these properties result from the modulation of K(ATP) channels. These data demonstrate that SFO neurons are glucose responsive, further emphasizing the potential roles of this circumventricular organ as an important sensor and integrator of circulating signals of energy status. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
Mallard, Simonette R; Howe, Anna S; Houghton, Lisa A
2016-10-01
Obesity is associated with lower concentrations of serum 25-hydroxyvitamin D; however, uncertainty exists as to the direction of causation. To date, meta-analyses of randomized controlled vitamin D-supplementation trials have shown no effect of raising circulating vitamin D on body weight, although several weight-loss-intervention trials have reported an increase in circulating vitamin D after weight reduction. We undertook a systematic review and meta-analysis of randomized and nonrandomized controlled trials to determine whether weight loss compared with weight maintenance leads to an increase in serum 25-hydroxyvitamin D. A systematic search for controlled weight-loss-intervention studies published up to 31 March 2016 was performed. Studies that included participants of any age with changes in adiposity and serum 25-hydroxyvitamin D as primary or secondary outcomes were considered eligible. We identified 4 randomized controlled trials (n = 2554) and 11 nonrandomized controlled trials (n = 917) for inclusion in the meta-analysis. Random assignment to weight loss compared with weight maintenance resulted in a greater increase in serum 25-hydroxyvitamin D with a mean difference of 3.11 nmol/L (95% CI: 1.38, 4.84 nmol/L) between groups, whereas a mean difference of 4.85 nmol/L (95% CI: 2.59, 7.12 nmol/L) was observed in nonrandomized trials. No evidence for a dose-response effect of weight loss on the change in serum 25-hydroxyvitamin D was shown overall. Our results indicate that vitamin D status may be marginally improved with weight loss in comparison with weight maintenance under similar conditions of supplemental vitamin D intake. Although additional studies in unsupplemented individuals are needed to confirm these findings, our results support the view that the association between obesity and lower serum 25-hydroxyvitamin D may be due to reversed causation with increased adiposity leading to suboptimal concentrations of circulating vitamin D. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015023836. © 2016 American Society for Nutrition.
Hu, Yun; Hoerle, Reece; Ehrich, Marion; Zhang, Chenming
2015-12-01
Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid-PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long-term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement. This paper reports the engineering of the lipid layer that encloses a polymeric nanoparticle, which can be used as a carrier for drug and vaccine molecules for targeted delivery. We demonstrated that the concentration of cholesterol is critical for the stability and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for the delivery of immune effector molecules. However, we found that hybrid nanoparticles with high cholesterol concentration tend to fuse during storage resulting in larger particles with decreased cellular uptake. This problem is subsequently solved by PEGylating the hybrid nanoparticles. With increased research and clinical applications of lipid-polymer hybrid nanoparticles in drug and vaccine delivery, this work will significantly impact the design of the hybrid nanoparticles for minimized molecule release during circulation and increased bioavailability of the target molecules. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Weather conditions conducive to Beijing severe haze more frequent under climate change
NASA Astrophysics Data System (ADS)
Cai, Wenju; Li, Ke; Liao, Hong; Wang, Huijun; Wu, Lixin
2017-03-01
The frequency of Beijing winter severe haze episodes has increased substantially over the past decades, and is commonly attributed to increased pollutant emissions from China’s rapid economic development. During such episodes, levels of fine particulate matter are harmful to human health and the environment, and cause massive disruption to economic activities, as occurred in January 2013. Conducive weather conditions are an important ingredient of severe haze episodes, and include reduced surface winter northerlies, weakened northwesterlies in the midtroposphere, and enhanced thermal stability of the lower atmosphere. How such weather conditions may respond to climate change is not clear. Here we project a 50% increase in the frequency and an 80% increase in the persistence of conducive weather conditions similar to those in January 2013, in response to climate change. The frequency and persistence between the historical (1950-1999) and future (2050-2099) climate were compared in 15 models under Representative Concentration Pathway 8.5 (RCP8.5). The increased frequency is consistent with large-scale circulation changes, including an Arctic Oscillation upward trend, weakening East Asian winter monsoon, and faster warming in the lower troposphere. Thus, circulation changes induced by global greenhouse gas emissions can contribute to the increased Beijing severe haze frequency.
Sahebkar, Amirhossein; Cicero, Arrigo F G; Simental-Mendía, Luis E; Aggarwal, Bharat B; Gupta, Subash C
2016-05-01
Tumor necrosis factor-α (TNF-α) is a key inflammatory mediator and its reduction is a therapeutic target in several inflammatory diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in several preclinical studies to block TNF-α effectively. However, clinical evidence has not been fully conclusive. The aim of the present meta-analysis was to evaluate the efficacy of curcumin supplementation on circulating levels of TNF-α in randomized controlled trials (RCTs). The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to September 21, 2015, to identify RCTs investigating the impact of curcumin on circulating TNF-α concentration. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analyses were performed to assess the modifiers of treatment response. Eight RCTs comprising nine treatment arms were finally selected for the meta-analysis. There was a significant reduction of circulating TNF-α concentrations following curcumin supplementation (WMD: -4.69pg/mL, 95% CI: -7.10, -2.28, p<0.001). This effect size was robust in sensitivity analysis. Meta-regression did not suggest any significant association between the circulating TNF-α-lowering effects of curcumin with either dose or duration (slope: 0.197; 95% CI: -1.73, 2.12; p=0.841) of treatment. This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating TNF-α concentration. Copyright © 2016 Elsevier Ltd. All rights reserved.
Effect of metformin therapy on circulating amino acids in a randomized trial: the CAMERA study.
Preiss, D; Rankin, N; Welsh, P; Holman, R R; Kangas, A J; Soininen, P; Würtz, P; Ala-Korpela, M; Sattar, N
2016-11-01
To investigate whether metformin therapy alters circulating aromatic and branched-chain amino acid concentrations, increased levels amino acid concentrations, increased levels of which have been found to predict Type 2 diabetes. In the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) study (NCT00723307), 173 individuals without Type 2 diabetes, but with coronary disease, were randomized to metformin (n=86) or placebo (n=87) for 18 months. Plasma samples, taken every 6 months, were analysed using quantitative nuclear magnetic resonance spectroscopy. Ten metabolites consisting of eight amino acids [three branched-chain (isoleucine, leucine, valine), three aromatic (tyrosine, phenylalanine, histidine) and two other amino acids (alanine, glutamine)], lactate and pyruvate were quantified and analysed using repeated-measures models. On-treatment analyses were conducted to investigate whether amino acid changes were dependent on changes in weight, fat mass or insulin resistance estimated using homeostasis model assessment (HOMA-IR). Tyrosine decreased [-6.1 μmol/l (95% CI -8.5, -3.7); P<0.0001], while alanine [42 umol/l (95% CI 25, 59); P<0.0001] increased in the metformin-treated group compared with the placebo-treated group. Decreases in phenylalanine [-2.0 μmol/l (95% CI -3.6, -0.3); P=0.018] and increases in histidine [2.3 μmol/l (95% CI 0.1, 4.6); P=0.045] were also observed in the metformin group, although these changes were less statistically robust. Changes in these four amino acids were not accounted for by changes in weight, fat mass or HOMA-IR values. Levels of branched-chain amino acids, glutamine, pyruvate and lactate were not altered by metformin therapy. Metformin therapy results in a sustained and specific pattern of changes in aromatic amino acid and alanine concentrations. These changes are independent of any effects on weight and insulin sensitivity. Any causal link to metformin's unexplained cardiometabolic benefit requires further study. © 2016 Diabetes UK.
New approaches to evaluate sympathoadrenal system activity in experiments on Earth and in space
NASA Astrophysics Data System (ADS)
Kvetnansky, R.; Noskov, V. B.; Blazicek, P.; Macho, L.; Grigoriev, A. I.; Goldstein, D. S.; Kopin, I. J.
In previous studies the activity of the sympathoadrenal system (SAS) in cosmonauts during space flights was evaluated by measuring plasma catecholamines (CA) levels and urinary CA and their metabolites concentrations. Plasma CA levels are accepted indicators of SAS activity, however, they are determined by the plasma clearances as well as the rates of CA release (spillover-SO) into the bloodstream. Nowadays methods are available which evaluate not only plasma levels of CA but also their release, spillover, uptake, reuptake, degradation and also CA synthesis in vivo measured by plasma levels of dihydroxyphenylalanine (DOPA). Plasma concentrations of DOPA, the CA noradrenaline (NE), adrenaline (ADR), and dopamine (DA), the deaminated catechol metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), and the O-methylated metabolites methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured during immobilization stress (IMO) in conscious rats. Radiotracer methods were used to measure NE SO. IMO markedly increased arterial NE levels but NE SO was less elevated bacause the NE clearance was slightly reduced in IMO rats. Simultaneous measurements of plasma CA and their metabolites provide another means to obtain information about SAS function. For instance, dissociation between changes of plasma DHPG and NE levels can indicate changes in neuronal reuptake of NE. We found marked parallel increases in plasma NE and DHPG levels during acute IMO; however after repeated IMO, plasma NE levels were increased but DHPG responses were less pronounced suggesting a reduced NE reuptake. DOPA, the CA precursor, circulates in plasma at a concentration higher than NE. During stress, increased sympathoneural outflow stimulates DOPA synthesis and release into the circulation supporting the view that changes in plasma DOPA levels during stress reflect in vivo changes in the rate of CA synthesis. We propose to measure the new plasma indicators of SAS activity in cosmonauts and/or in animals before, during and after space flights.
Zhong, Huiyun; Liu, Fang; Lu, Jinjin; Yang, Wei; Zhao, Chaocheng
2015-01-01
Petroleum products leakage results in adverse effect on the normal operation of a circulating cooling water system. However, relatively little research has been done to explore the effect of petroleum products leakage on circulating cooling water quality and biofilm preponderant bacteria diversity. Also, normal biocides application modes cannot fulfil the need for biofilm control. In this study, diesel oil was used as the experimental subject representing leaking petroleum products; the effect of diesel addition on biofilm preponderant bacteria diversity and the bactericidal effect of chlorine dioxide and tetradecyl dimethyl benzyl ammonium chloride (1427) was investigated. Bacterial community structures were examined by PCR-denaturing gradient gel electrophoresis and PCR cloning of 16S rDNA genes. Except for 100 mg/L diesel, increasing diesel concentration enhanced the biofilm detachment ratio compared with the control test. The microstructure of biofilm samples with 0, 300 and 900 mg/L diesel addition was observed. The species of preponderant bacteria in the biofilm sample with 300 mg/L diesel addition were more and the bacterial distribution was more uniform than those in the biofilm sample with 900 mg/L diesel addition. With ClO2 and 1427 addition, chemical oxygen demand increased, lipid phosphorus and bacterial count first decreased and then remained stable, and the bactericidal ratio first increased and then remained stable. Diesel addition variation has more obvious effect on ClO2 than 1427.
Dengue in Rio Grande do Sul, Brazil: 2014 to 2016.
Gregianini, Tatiana Schaffer; Tumioto-Giannini, Gabriela Luchiari; Favreto, Cátia; Plentz, Luciana Ciarelli; Ikuta, Nilo; da Veiga, Ana B Gorini
2018-01-01
The first autochthonous dengue case in Rio Grande do Sul (RS), Southern Brazil, occurred in 2007. In 2008 and 2009, only imported cases were reported in RS, but from 2010 to 2013, reports of autochthonous infections increased significantly. This study analyzes and discusses laboratory, demographic, and clinical data regarding dengue cases in RS, from 2014 to 2016. This study analyzed 13,420 serum samples from notified patients with suspicion of dengue fever in RS from 2014 to 2016. Seasonality of positive cases, viral serotypes, and clinical and epidemiological aspects were analyzed. There was no difference in gender (P = .4); dengue fever occurred mainly in adults, with similar distribution among age groups. The number of dengue virus (DENV) cases increased from 89 cases in 2014 to 2518 in 2016. Dengue virus 1 was the most prevalent circulating serotype during this period (97.5% of cases). Dengue virus infections show peaks in March and April (late summer and early autumn), after periods of high temperatures and rainfall. In 2014, dengue cases were concentrated in the northwestern and eastern regions of RS, and in 2015 and 2016, the northern region also confirmed a high number of cases. With increase in DENV circulation in RS, a rise in the number of autochthonous infections was also observed, mainly in highly urbanized areas. This study revealed that circulation of DENV in RS increased significantly in 2015 and 2016, with a rise in the number of autochthonous infections and cocirculation with Chikungunya and Zika viruses, recently introduced into RS. Copyright © 2017 John Wiley & Sons, Ltd.
Ichikawa, Shoji; Sorenson, Andrea H; Austin, Anthony M; Mackenzie, Donald S; Fritz, Timothy A; Moh, Akira; Hui, Siu L; Econs, Michael J
2009-06-01
Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generated mice lacking the Galnt3 gene, which developed hyperphosphatemia without apparent calcifications. In response to hyperphosphatemia, Galnt3-deficient mice had markedly increased Fgf23 expression in bone. However, compared with wild-type and heterozygous littermates, homozygous mice had only about half of circulating intact Fgf23 levels and higher levels of C-terminal Fgf23 fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Furthermore, renal expression of sodium-phosphate cotransporters and Kl were elevated in Galnt3-deficient mice. Interestingly, there were sex-specific phenotypes; only Galnt3-deficient males showed growth retardation, infertility, and significantly increased bone mineral density. In summary, ablation of Galnt3 impaired secretion of intact Fgf23, leading to decreased circulating Fgf23 and hyperphosphatemia, despite increased Fgf23 expression. Our findings indicate that Galnt3-deficient mice have a biochemical phenotype of tumoral calcinosis and provide in vivo evidence that Galnt3 plays an essential role in proper secretion of Fgf23 in mice.
Benzene exposure is associated with cardiovascular disease risk.
Abplanalp, Wesley; DeJarnett, Natasha; Riggs, Daniel W; Conklin, Daniel J; McCracken, James P; Srivastava, Sanjay; Xie, Zhengzhi; Rai, Shesh; Bhatnagar, Aruni; O'Toole, Timothy E
2017-01-01
Benzene is a ubiquitous, volatile pollutant present at high concentrations in toxins (e.g. tobacco smoke) known to increase cardiovascular disease (CVD) risk. Despite its prevalence, the cardiovascular effects of benzene have rarely been studied. Hence, we examined whether exposure to benzene is associated with increased CVD risk. The effects of benzene exposure in mice were assessed by direct inhalation, while the effects of benzene exposure in humans was assessed in 210 individuals with mild to high CVD risk by measuring urinary levels of the benzene metabolite trans,trans-muconic acid (t,t-MA). Generalized linear models were used to assess the association between benzene exposure and CVD risk. Mice inhaling volatile benzene had significantly reduced levels of circulating angiogenic cells (Flk-1+/Sca-1+) as well as an increased levels of plasma low-density lipoprotein (LDL) compared with control mice breathing filtered air. In the human cohort, urinary levels of t,t-MA were inversely associated several populations of circulating angiogenic cells (CD31+/34+/45+, CD31+/34+/45+/AC133-, CD34+/45+/AC133+). Although t,t-MA was not associated with plasma markers of inflammation or thrombosis, t,t-MA levels were higher in smokers and in individuals with dyslipidemia. In smokers, t,t-MA levels were positively associated with urinary metabolites of nicotine (cotinine) and acrolein (3-hydroxymercapturic acid). Levels of t,t-MA were also associated with CVD risk as assessed using the Framingham Risk Score and this association was independent of smoking. Thus, benzene exposure is associated with increased CVD risk and deficits in circulating angiogenic cells in both smokers and non-smokers.
Effects of Experimental Sleep Restriction on Caloric Intake and Activity Energy Expenditure
Calvin, Andrew D.; Carter, Rickey E.; Adachi, Taro; G. Macedo, Paula; Albuquerque, Felipe N.; van der Walt, Christelle; Bukartyk, Jan; Davison, Diane E.; Levine, James A.
2013-01-01
Background: Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Methods: We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Results: Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P = .006) and decreased in the control group by −118 kcal/d (SD, 386 kcal/d, P = .51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P = .014). Sleep restriction was not associated with changes in activity energy expenditure (P = .62). No change was seen in levels of leptin (P = .27) or ghrelin (P = .21). Conclusions: Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. Trial Registration: ClinicalTrials.gov; No.: NCT01334788; URL: www.clinicaltrials.gov PMID:23392199
Nieva, Jorge; Wendel, Marco; Luttgen, Madelyn S; Marrinucci, Dena; Bazhenova, Lyudmila; Kolatkar, Anand; Santala, Roger; Whittenberger, Brock; Burke, James; Torrey, Melissa; Bethel, Kelly; Kuhn, Peter
2012-02-01
Sampling circulating tumor cells (CTCs) from peripheral blood is ideally accomplished using assays that detect high numbers of cells and preserve them for downstream characterization. We sought to evaluate a method using enrichment free fluorescent labeling of CTCs followed by automated digital microscopy in patients with non-small cell lung cancer. Twenty-eight patients with non-small cell lung cancer and hematogenously seeded metastasis were analyzed with multiple blood draws. We detected CTCs in 68% of analyzed samples and found a propensity for increased CTC detection as the disease progressed in individual patients. CTCs were present at a median concentration of 1.6 CTCs ml⁻¹ of analyzed blood in the patient population. Higher numbers of detected CTCs were associated with an unfavorable prognosis.
Barker, Gillian; Lim, Ratana; Rice, Gregory E; Lappas, Martha
2012-11-01
The aim of this study was to determine the effect of maternal obesity and gestational diabetes mellitus (GDM) on (i) the circulating concentrations of chemerin in cord and maternal plasma, and (ii) gene expression and release of chemerin from human placenta and adipose tissue. Chemerin concentrations were measured in maternal and cord plasma from 62 normal glucose tolerant women (NGT) and 69 women with GDM at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of chemerin was measured from 22 NGT and 22 GDM women. There was no effect of maternal obesity or GDM on maternal chemerin concentrations. Chemerin concentrations were significantly higher in cord plasma from women with maternal obesity. Cord chemerin concentrations in NGT women negatively correlated with the concentrations of maternal insulin sensitivity. There was no effect of GDM on maternal and cord chemerin concentrations, and on the release of chemerin from placenta and adipose tissue. At the time of term Caesarean section, preexisting maternal obesity, and its associated insulin resistance, is associated with higher cord plasma chemerin concentrations.
Guadalupe-Grau, Amelia; Ara, Ignacio; Dorado, Cecilia; Vicente-Rodríguez, German; Perez-Gomez, Jorge; Cabrero, Javier Chavarren; Serrano-Sanchez, José A; Santana, Alfredo; Calbet, Jose A L
2010-10-01
Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.
Beyond Reasonable Doubt: Who Is the Culprit in Lipotoxicity in NAFLD/NASH?
Arteel, Gavin E.
2016-01-01
BACKGROUND & AIMS Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. METHODS Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. RESULTS Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. CONCLUSIONS In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. PMID:22422583
Van Rooyen, Derrick M; Larter, Claire Z; Haigh, W Geoffrey; Yeh, Matthew M; Ioannou, George; Kuver, Rahul; Lee, Sum P; Teoh, Narci C; Farrell, Geoffrey C
2011-10-01
Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Van Rooyen, Derrick M; Larter, Claire Z; Haigh, W Geoffrey; Yeh, Matthew M; Ioannou, George; Kuver, Rahul; Lee, Sum P; Teoh, Narci C; Farrell, Geoffrey C
2011-01-01
Background & Aims Type-2 diabetes and non-alcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to pathogenesis of NASH. Methods Alms1 mutant (foz/foz) and wild-type (WT) NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. Results Hepatic cholesterol accumulation was attributed to up-regulation of low density lipoprotein receptor (LDLR) via activation of sterol regulatory element binding protein-2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and LDLR and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. Conclusions In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. PMID:21703998
Brook, Robert D.; Bard, Robert L.; Kaplan, Mariana J.; Yalavarthi, Srilakshmi; Morishita, Masako; Dvonch, J. Timothy; Wang, Lu; Yang, Hui-yu; Spino, Catherine; Mukherjee, Bhramar; Oral, Elif A.; Sun, Qinghua; Brook, Jeffrey R.; Harkema, Jack; Rajagopalan, Sanjay
2015-01-01
Context Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown. Objective We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels. Methods Thirty-two adults (25.9±6.6 years) were exposed to coarse CAP (76.2±51.5 μgm−3) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n=21), white blood cell (n=24) and vascular endothelial growth factor (VEGF) (n=16–19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests. Results Circulating EPC levels were elevated 2 [108.29 (6.24–249.71) EPC mL−1; median (25th–75th percentiles), p=0.052] and 20 h [106.86 (52.91–278.35) EPC mL−1, p=0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00–84.83) and 50.16 (0.00–104.79) EPC mL−1]. VEGF and white blood cell (WBC) levels did not differ between exposures. Conclusions Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute “endothelial injury” and/or a circulating EPC response to sympathetic nervous system activation. PMID:23919441
Hoyo, Cathrine; Murphy, Susan K.; Schildkraut, Joellen M.; Vidal, Adriana C.; Skaar, David; Millikan, Robert C.; Galanko, Joseph; Sandler, Robert S.; Jirtle, Randy; Keku, Temitope
2012-01-01
The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2. PMID:22377707
Hoyo, Cathrine; Murphy, Susan K; Schildkraut, Joellen M; Vidal, Adriana C; Skaar, David; Millikan, Robert C; Galanko, Joseph; Sandler, Robert S; Jirtle, Randy; Keku, Temitope
2012-01-01
The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9-5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.
Change in circulating microRNA profile of obese children indicates future risk of adult diabetes.
Cui, Xianwei; You, Lianghui; Zhu, Lijun; Wang, Xing; Zhou, Yahui; Li, Yun; Wen, Juan; Xia, Yankai; Wang, Xinru; Ji, Chenbo; Guo, Xirong
2018-01-01
Childhood obesity increases susceptibility to type 2 diabetes (T2D) in adults. Circulating microRNAs (miRNAs) in serum have been proposed as potential diagnostic biomarkers, and they may contribute to the progression toward T2D. Here, we investigated the possibility of predicting the future risk of adult T2D in obese children by using circulating miRNAs. We performed miRNA high-throughput sequencing to screen relevant circulating miRNAs in obese children. The expression patterns of targeted miRNAs were further explored in obese children and adults with T2D. To investigate the underlying contributions of these miRNAs to the development of T2D, we detected the impacts of the candidate miRNAs on preadipocyte proliferation, insulin secretion by pancreatic β-cell, and glucose uptake by skeletal muscle cells. Three miRNAs (miR-486, miR-146b and miR-15b), whose expression in the circulation was most dramatically augmented in obese children and adult T2D patients, were selected for further investigation. Of these 3 miRNAs, miR-486 was implicated in accelerating preadipocyte proliferation and myotube glucose intolerance, miR-146b and miR-15b were engaged in the suppression of high concentration glucose-induced pancreatic insulin secretion, and they all contributed to the pathological processes of obesity and T2D. Our results provide a better understanding of the role of circulating miRNAs, particularly miR-486, miR-146b and miR-15b, in predicting the future risk of T2D in obese children. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Harauchi, Satoe; Osawa, Takashi; Kubono, Naoko; Itoh, Hiroaki; Naito, Takafumi; Kawakami, Junichi
2017-07-01
Few clinical studies have determined the quantitative transfer of vaginal chloramphenicol to circulating blood in pregnant women. This study aimed to evaluate the plasma concentration of chloramphenicol in pregnant women treated with trans-vaginal tablets and its relationship with maternal background and neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal chloramphenicol once daily for bacterial vaginosis and its suspected case were enrolled. The plasma concentration of chloramphenicol was determined using liquid chromatography coupled to tandem mass spectrometry at day 2 or later after starting the medication. The correlations between the maternal plasma concentration of chloramphenicol and the background and neonatal health at birth were investigated. Chloramphenicol was detected from all maternal plasma specimens and its concentration ranged from 0.043 to 73.1 ng/mL. The plasma concentration of chloramphenicol declined significantly with the administration period. The plasma concentration of chloramphenicol was lower at the second than the first blood sampling. No correlations were observed between the maternal plasma concentration of chloramphenicol and background such as number of previous births, gestational age at dosing, and clinical laboratory data. Neonatal infant health parameters such as birth-weight, Apgar score at birth, and gestational age at the time of childbearing were not related to the maternal plasma concentration of chloramphenicol. Vaginal chloramphenicol transfers to circulating blood in pregnant women. The maternal plasma concentration of chloramphenicol varied markedly and was associated with the administration day, but not with maternal background or her neonatal health. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
De Luis, D A; Gonzalez Sagrado, M; Conde, R; Aller, R; Izaola, O; Castro, M J; Romero, E
2010-12-01
The insulin-mimetic adipocytokine visfatin has been related to obesity. The aim of this study was to examine whether weight loss could change visfatin concentrations in morbidly obese patients and its relationship with insulin resistance. This was an interventional study analyzing a population of 41 morbidly obese patients. A biochemical analysis was realized before and after 2 months on a hypocaloric diet. After weight loss (average 4.41%), BMI, weight, fat mass, fat free mass, waist circumference, systolic blood pressure, serum glucose, total cholesterol, insulin and HOMA decreased. The serum concentrations of visfatin did not decrease (43.5 + 30.8 vs. 47.1 + 38.1 ng/ml). In the multivariate analysis visfatin concentrations as a dependent variable, only C reactive protein remained as an independent predictor in the model before diet, with an increase of 1.82 ng/ml (CI 95%: 0.02 - 3.61) basal visfatin concentrations with each increase of 1 mg/dl of CRP. Only HOMA remained as an independent predictor in the model after diet, with an increase of 11.4 ng/ml (CI 95%: 1.76 - 21.11) posttreatment visfatin concentrations with each increase of 1 unit HOMA. Weight reduction after a 2 months on a hypocaloric diet is not associated with a significant change in circulating visfatin in morbidly obese patients.
Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease.
Kim, H-S; Kang, J-H; Jeung, E-B; Yang, M-P
2016-09-01
The concentrations of circulating adipokines in dogs with myxomatous mitral valve disease (MMVD) have not been investigated in detail. To determine whether serum concentrations of adipokines differ between healthy dogs and dogs with MMVD and whether circulating concentrations depend on the severity of heart failure resulting from MMVD. In the preliminary study, 30 healthy dogs and 17 client-owned dogs with MMVD, and in the subsequent study, 30 healthy dogs and 46 client-owned dogs with MMVD. Prospective case-controlled observational study. In the preliminary study, serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)-1β, IL-6, IL-10, IL-18, and tumor necrosis factor-α were measured. In the subsequent study, MMVD dogs were divided into three groups according to the International Small Animal Cardiac Health Council (ISACHC) classification, and serum concentrations of leptin and adiponectin were measured. In the preliminary study, serum leptin and adiponectin concentrations differed significantly between dogs with MMVD and healthy dogs. Serum leptin (P = .0013) concentrations were significantly higher in dogs with MMVD than in healthy dogs, whereas adiponectin (P = .0009) concentrations were significantly lower in dogs with MMVD. However, we observed no significant differences in the other variables. In the subsequent study, dogs classified as ISACHC class 3 had higher serum concentrations of leptin (P = .0022) than healthy dogs but ISACHC class 1 or 2 dogs did not. Serum adiponectin concentrations were significantly lower in ISACHC class 1 (P < .0001) dogs than in healthy dogs, whereas adiponectin concentrations in ISACHC class 3 dogs were significantly higher than in ISACHC class 1 dogs (P = .0081). Circulating concentrations of leptin and adiponectin might be altered in dogs with MMVD. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Effect of feed restriction on reproductive and metabolic hormones in dairy cows.
Ferraretto, L F; Gencoglu, H; Hackbart, K S; Nascimento, A B; Dalla Costa, F; Bender, R W; Guenther, J N; Shaver, R D; Wiltbank, M C
2014-02-01
The objective of this trial was to evaluate the effects of feed restriction (FR) on serum glucose, nonesterified fatty acids, progesterone (P4), insulin, and milk production in dairy cows. Eight multiparous Holstein cows, 114 ± 14 d pregnant and 685 ± 39 kg of body weight, were randomly assigned to a replicated 4 × 4 Latin square design with 14-d periods. During the first 8 d of each period, cows in all treatments were fed for ad libitum feed intake. Beginning on d 9 of each period, cows received 1 of 4 treatments: ad libitum (AL), 25% feed restriction (25 FR), 50% feed restriction (50 FR), and 50% of TMR replaced with wheat straw (50 ST). Daily feed allowance was divided into 3 equal portions allocated every 8h with jugular blood samples collected immediately before each feeding through d 14. In addition, on d 12 of each period, blood samples were collected before and at 60, 120, 180, 240, 300, 360, 420, and 480 min after morning feeding. The conventional total mixed ration and total mixed ration with straw averaged 15.1 and 10.8%, 32.1 and 50.5%, and 26.8 and 17.0% for concentrations of crude protein, neutral detergent fiber, and starch, respectively. Cows that were feed and energy restricted had reduced dry matter intake, net energy for lactation intake, circulating glucose concentrations, and milk production, but greater body weight and body condition score losses than AL cows. Circulating concentrations of insulin were lower for cows fed 50 FR (8.27 μIU/mL) and 50 ST (6.24 μIU/mL) compared with cows fed AL (16.65 μIU/mL) and 25 FR (11.16 μIU/mL). Furthermore, the greatest plasma nonesterified fatty acids concentration was observed for 50 ST (647.7 μ Eq/L), followed by 50 FR (357.5 μEq/L), 25 FR (225.3 μEq/L), and AL (156.3 μEq/L). In addition, serum P4 concentration was lower for cows fed AL than cows fed 50 ST and 25 FR. Thus, FR reduced circulating glucose and insulin but increased P4 concentration, changes that may be positive in reproductive management programs. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Effect of feed restriction on reproductive and metabolic hormones in dairy cows
Ferraretto, L. F.; Gencoglu, H.; Hackbart, K. S.; Nascimento, A. B.; Costa, F. Dalla; Bender, R. W.; Guenther, J. N.; Shaver, R. D.; Wiltbank, M. C.
2018-01-01
The objective of this trial was to evaluate the effects of feed restriction (FR) on serum glucose, nonesterified fatty acids, progesterone (P4), insulin, and milk production in dairy cows. Eight multiparous Holstein cows, 114 ± 14 d pregnant and 685 ± 39 kg of body weight, were randomly assigned to a replicated 4 × 4 Latin square design with 14-d periods. During the first 8 d of each period, cows in all treatments were fed for ad libitum feed intake. Beginning on d 9 of each period, cows received 1 of 4 treatments: ad libitum (AL), 25% feed restriction (25FR), 50% feed restriction (50FR), and 50% of TMR replaced with wheat straw (50ST). Daily feed allowance was divided into 3 equal portions allocated every 8 h with jugular blood samples collected immediately before each feeding through d 14. In addition, on d 12 of each period, blood samples were collected before and at 60, 120, 180, 240, 300, 360, 420, and 480 min after morning feeding. The conventional total mixed ration and total mixed ration with straw averaged 15.1 and 10.8%, 32.1 and 50.5%, and 26.8 and 17.0% for concentrations of crude protein, neutral detergent fiber, and starch, respectively. Cows that were feed and energy restricted had reduced dry matter intake, net energy for lactation intake, circulating glucose concentrations, and milk production, but greater body weight and body condition score losses than AL cows. Circulating concentrations of insulin were lower for cows fed 50FR (8.27 μIU/mL) and 50ST (6.24 μIU/mL) compared with cows fed AL (16.65 μIU/mL) and 25FR (11.16 μIU/mL). Furthermore, the greatest plasma nonesterified fatty acids concentration was observed for 50ST (647.7 μEq/L), followed by 50FR (357.5 μEq/L), 25FR (225.3 μEq/L), and AL (156.3 μEq/L). In addition, serum P4 concentration was lower for cows fed AL than cows fed 50ST and 25FR. Thus, FR reduced circulating glucose and insulin but increased P4 concentration, changes that may be positive in reproductive management programs. PMID:24359832
DOE Office of Scientific and Technical Information (OSTI.GOV)
Costa, M.H.; Foley, J.A.
2000-01-01
It is generally expected that the Amazon basin will experience at least two major environmental changes during the next few decades and centuries: (1) increasing areas of forest will be converted to pasture and cropland, and (2) concentrations of atmospheric CO{sub 2} will continue to rise. In this study, the authors use the National Center for Atmospheric Research GENESIS atmospheric general circulation model, coupled to the Integrated Biosphere Simulator, to determine the combined effects of large-scale deforestation and increased CO{sub 2} concentrations (including both physiological and radiative effects) on Amazonian climate. In these simulations, deforestation decreases basin-average precipitation by 0.73more » mm day{sup {minus}1} over the basin, as a consequence of the general reduction in vertical motion above the deforested area (although there are some small regions with increased vertical motion). The overall effect of doubled CO{sub 2} concentrations in Amazonia is an increase in basin-average precipitation of 0.28 mm day{sup {minus}1}. The combined effect of deforestation and doubled CO{sub 2}, including the interactions among the processes, is a decrease in the basin-average precipitation of 0.42 mm day{sup {minus}1}. While the effects of deforestation and increasing CO{sub 2} concentrations on precipitation tend to counteract one another, both processes work to warm the Amazon basin. The effect of deforestation and increasing CO{sub 2} concentrations both tent to increase surface temperature, mainly because of decreases in evapotranspiration and the radiative effect of CO{sub 2}. The combined effect of deforestation and doubled CO{sub 2}, including the interactions among the processes, increases the basin-average temperature by roughly 3.5 C.« less
NASA Astrophysics Data System (ADS)
Spracklen, D. V.; Logan, J. A.; Mickley, L. J.; Park, R. J.; Flannigan, M. D.; Westerling, A. L.
2006-12-01
Increased forest fire activity in the Western United States appears to be driven by increasing spring and summer temperatures. Here we make a first estimate of how climate-driven changes in fire activity will influence summertime organic carbon (OC) concentrations in the Western US. We use output from a general circulation model (GCM) combined with area burned regressions to predict how area burned will change between present day and 2050. Calculated area burned is used to create future emission estimates for the Western U.S. and we use a global chemical transport model (CTM) to predict future changes in OC concentrations. Stepwise linear regression is used to determine the best relationships between observed area burned for 1980- 2004 and variables chosen from temperature, relative humidity, wind speed, rainfall and drought indices from the Candaian Fire Weather Index Model. Best predictors are ecosytem dependent but typically include mean summer temperature and mean drought code. In forest ecosystems of the Western U.S. our regressions explain 50-60% of the variance in annual area burned. Between 2000 and 2050 increases in temperature and reductions in precipitation, as predicted by the GISS GCM, cause mean area burned in the western U.S. to increase by 30-55%. We use the GEOS-Chem CTM to show that these increased emissions result in an increase in summertime western U.S. OC concentrations by 55% over current concentrations. Our results show that the predicted increase in future wild fires will have important consequences for western US air quality and visibility.
The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders
Lee, David B. N.; Zawada, Edward T.; Kleeman, Charles R.
1978-01-01
For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism. PMID:362722
Understanding recent climate change.
Serreze, Mark C
2010-02-01
The Earth's atmosphere has a natural greenhouse effect, without which the global mean surface temperature would be about 33 degrees C lower and life would not be possible. Human activities have increased atmospheric concentrations of carbon dioxide, methane, and other gases in trace amounts. This has enhanced the greenhouse effect, resulting in surface warming. Were it not for the partly offsetting effects of increased aerosol concentrations, the increase in global mean surface temperature over the past 100 years would be larger than observed. Continued surface warming through the 21st century is inevitable and will likely have widespread ecological impacts. The magnitude and rate of warming for the global average will be largely dictated by the strength and direction of climate feedbacks, thermal inertia of the oceans, the rate of greenhouse gas emissions, and aerosol concentrations. Because of regional expressions of climate feedbacks, changes in atmospheric circulation, and a suite of other factors, the magnitude and rate of warming and changes in other key climate elements, such as precipitation, will not be uniform across the planet. For example, due to loss of its floating sea-ice cover, the Arctic will warm the most.
Morales, Eva; Romieu, Isabelle; Guerra, Stefano; Ballester, Ferrán; Rebagliato, Marisa; Vioque, Jesús; Tardón, Adonina; Rodriguez Delhi, Cristina; Arranz, Leonor; Torrent, Maties; Espada, Mercedes; Basterrechea, Mikel; Sunyer, Jordi
2012-01-01
Adequate vitamin D status in mothers during pregnancy may influence the health status of the child later in life. We assessed whether maternal circulating 25-hydroxyvitamin D (25[OH]D) concentrations in pregnancy are associated with risk of lower respiratory tract infections, wheezing, and asthma in the offspring. Data were obtained from 1724 children of the INfancia y Medio Ambiente (INMA) Project, a population-based birth cohort study. Maternal circulating 25(OH)D concentrations were measured in pregnancy (mean gestational age = 12.6 [SD = 2.5] weeks). When the child was age 1 year, parents were asked if their child had a physician-confirmed history of lower respiratory tract infections or a history of wheezing. The questions about wheezing were repeated annually thereafter. Asthma was defined as parental report of doctor diagnosis of asthma or receiving treatment at the age of 4-6 years or wheezing since the age of 4 years. The median maternal circulating 25(OH)D concentration in pregnancy was 29.5 ng/mL (interquartile range, 22.5-37.1 ng/mL). After multivariable adjustment, there was a trend for an independent association between higher levels of maternal circulating 25(OH)D levels in pregnancy and decreased odds of lower respiratory tract infections in offspring (for cohort- and season-specific quartile Q4 vs. Q1, odds ratio = 0.67 [95% confidence interval = 0.50-0.90]; test for trend, P = 0.016). We found no association between 25(OH)D levels in pregnancy and risk of wheezing at age 1 year or 4 years, or asthma at age 4-6 years. Higher maternal circulating 25(OH)D concentrations in pregnancy were independently associated with lower risk of lower respiratory tract infections in offspring in the first year of life but not with wheezing or asthma in childhood.
NASA Technical Reports Server (NTRS)
Halpern, David; Feldman, Gene C.
1994-01-01
The following variables along the Pacific equator from 145 deg E to 95 deg W were employed: surface layer phytoplankton pigment concentrations derived from Nimbus 7 coastal zone color scanner (CZCS) measurements of ocean color radiances; vertical velocities simulated at the 90-m bottom of the euphotic layer from a wind-driven ocean general circulation model; and nitrate concentrations estimated from model-simulated temperature. The upward flux of nitrate into the euphotic layer was calculated from the simulated vertical motion and nitrate concentration. The CZCS-derived phytoplankton pigment concentration was uniform from 175 deg to 95 deg W. Longitudinal profiles of upwelling, phytoplankton biomass, and 90-m nitrate flux were of different shapes. The small annual cycles of the phytoplankton pigment and nitrate flux were in phase: increased phytoplankton biomass was associated with increased upward nitrate flux, but the phase was not consistent with the annual cycles of the easterly wind or of the upwelling intensity. Variation of phytoplankton pigment concentration was greater during El Nino than during the annual cycle. The substantially reduced phytoplankton pigment concentration observed during El Nino was associated with smaller upward nitrate flux. Phytoplankton biomass during non-El Nino conditions was not related to nitrate flux into the euphotic layer.
Pereira, M H C; Wiltbank, M C; Guida, T G; Lopes, F R; Vasconcelos, J L M
2017-10-01
Two treatments designed to increase circulating progesterone concentration (P4) during preovulatory follicle development were compared. One treatment used 2 intravaginal P4 implants (controlled internal drug-releasing inserts; CIDR) and the other used a GnRH treatment at beginning of the protocol. Lactating Holstein cows that had been diagnosed as nonpregnant were randomly assigned to receive timed artificial insemination (TAI) following 1 of 2 treatments (n = 1,638 breedings): (1) GnRH: CIDR+ 2 mg of estradiol (E2) benzoate + 100 µg of GnRH on d -11, PGF 2α on d -4, CIDR withdrawal + 1.0 mg of E2-cypionate + PGF 2α ) on d -2, and TAI on d 0; or (2) 2CIDR: 2 CIDR + 2 mg of E2-benzoate on d -11, 1 CIDR withdrawn + PGF 2α on d -4, second CIDR withdrawn + 1.0 mg of E2-cypionate + PGF 2α on d -2, and TAI on d 0. Milk yield was measured daily between d 0 and d 7. Rectal temperature was measured using a digital thermometer at d 0 and 7, and elevated body temperature was defined as an average rectal temperature ≥39.1°C. Pregnancy diagnoses were performed on d 32 and 60 after TAI. We detected no effect of treatments on pregnancy per AI or pregnancy loss regardless of elevated body temperature, body condition score, parity, milk yield, or presence or absence of a corpus luteum (CL) on d -11 or d -4. Pregnancy per AI at 60 d was reduced [elevated body temperature = 22.8% (162/709), no elevated body temperature 34.1% (279/817)] and pregnancy loss tended to increase [elevated body temperature = 20.2% (41/203), no elevated body temperature 14.4% (47/326)] in cows with elevated body temperature. Various physiological measurements associated with greater fertility were also reduced in cows with elevated body temperature, such as percentage of cows with a CL at PGF 2α (decreased 7.9%), ovulatory follicle diameter (decreased 0.51 mm), expression of estrus (decreased 5.1%), and ovulation near TAI (decreased 2.8%) compared with cows without elevated body temperature. A greater proportion of cows (30.2%) had a CL at PGF 2α in the GnRH treatment [74.1% (570/763)] than in the 2CIDR treatment [56.9% (434/763)]; however, circulating P4 concentration was greater at the time of PGF 2α treatment (d -4) for cows 2CIDR (4.26 ± 0.13 ng/mL) than in cows in GnRH (3.99 ± 0.14 ng/mL). Thus, these 2 protocols yield similar fertility results that might be due to somewhat different physiological alterations. Treatment with GnRH increased the proportion of cows with a CL at PGF 2α ; however, the 2CIDR protocol increased circulating P4 under all circumstances. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Simulation of Venus polar vortices with the non-hydrostatic general circulation model
NASA Astrophysics Data System (ADS)
Rodin, Alexander V.; Mingalev, Oleg; Orlov, Konstantin
2012-07-01
The dynamics of Venus atmosphere in the polar regions presents a challenge for general circulation models. Numerous images and hyperspectral data from Venus Express mission shows that above 60 degrees latitude atmospheric motion is substantially different from that of the tropical and extratropical atmosphere. In particular, extended polar hoods composed presumably of fine haze particles, as well as polar vortices revealing mesoscale wave perturbations with variable zonal wavenumbers, imply the significance of vertical motion in these circulation elements. On these scales, however, hydrostatic balance commonly used in the general circulation models is no longer valid, and vertical forces have to be taken into account to obtain correct wind field. We present the first non-hydrostatic general circulation model of the Venus atmosphere based on the full set of gas dynamics equations. The model uses uniform grid with the resolution of 1.2 degrees in horizontal and 200 m in the vertical direction. Thermal forcing is simulated by means of relaxation approximation with specified thermal profile and time scale. The model takes advantage of hybrid calculations on graphical processors using CUDA technology in order to increase performance. Simulations show that vorticity is concentrated at high latitudes within planetary scale, off-axis vortices, precessing with a period of 30 to 40 days. The scale and position of these vortices coincides with polar hoods observed in the UV images. The regions characterized with high vorticity are surrounded by series of small vortices which may be caused by shear instability of the zonal flow. Vertical velocity component implies that in the central part of high vorticity areas atmospheric flow is downwelling and perturbed by mesoscale waves with zonal wavenumbers 1-4, resembling observed wave structures in the polar vortices. Simulations also show the existence of areas with strong vertical flow, concentrated in spiral branches extending from low latitude to the circumpolar vortex. Qualitatively this pattern suggest that the dynamics of the polar Venus atmosphere resembles that of terrestrial hurricanes, but is characterized with preferentially poleward and downwelling motions.
Ramos, Joyce S; Dalleck, Lance C; Borrani, Fabio; Mallard, Alistair R; Clark, Bronwyn; Keating, Shelley E; Fassett, Robert G; Coombes, Jeff S
2016-11-01
The continuous demand for insulin in the face of insulin resistance, coupled with the glucolipotoxic environment associated with the metabolic syndrome (MetS), adversely affects the quality of insulin produced and secreted by the pancreatic beta cells. This is depicted by increased circulating intact proinsulin concentration, which is associated with increased MetS severity and risk of cardiovascular (CV) mortality. High-intensity interval training (HIIT) has been shown to reduce insulin resistance and other CV disease risk factors to a greater degree than moderate-intensity continuous training (MICT). We therefore aimed to investigate the impact of MICT and different volumes of HIIT on circulating intact proinsulin concentration. This was a substudy of the 'Exercise in prevention of Metabolic Syndrome' (EX-MET) multicentre trial. Sixty-six individuals with MetS were randomised to 16 weeks of: (1) MICT (n = 21, 30 min at 60-70% peak heart rate [HRpeak], five times/week); (2) 4HIIT (n = 22, 4 × 4 min bouts at 85-95% HRpeak, interspersed with 3 min of active recovery at 50-70% HRpeak, three times/week); or (3) 1HIIT (n = 23, 1 × 4 min bout at 85-95% HRpeak, three times/week). A subanalysis investigated the differential impact of these training programmes on intact proinsulin concentration in MetS individuals with type 2 diabetes (MICT, n = 6; 4HIIT, n = 9; 1HIIT, n = 12) and without type 2 diabetes (MICT, n = 15; 4HIIT, n = 13; 1HIIT, n = 11). Intact proinsulin, insulin and C-peptide concentrations were measured in duplicate via ELISA, following a 12 h fast, before and after the exercise programme. Fasting intact proinsulin concentration was also expressed relative to insulin and C-peptide concentrations. Following the exercise training, there were no significant (p > 0.05) changes in fasting intact proinsulin concentration indices in all participants (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: MICT 19% decrease, 6% increase, 4% increase; 4HIIT 19% decrease, 8% decrease, 11% decrease; 1HIIT 34% increase, 49% increase, 36% increase). In participants who did not have type 2 diabetes, only 4HIIT significantly (p < 0.05) reduced fasting intact proinsulin concentration indices from pre to post intervention (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: 4HIIT 32% decrease, 26% decrease, 32% decrease, p < 0.05; 1HIIT, 14% increase, 32% increase, 16% increase, p > 0.05; MICT 27% decrease, 17% decrease, 11% decrease), with a group × time interaction effect, indicating a greater reduction in intact proinsulin indices following 4HIIT compared with MICT and 1HIIT. There were no significant (p > 0.05) changes in intact proinsulin concentration indices in participants with type 2 diabetes. Higher-volume HIIT (4HIIT) improved insulin quality in MetS participants without type 2 diabetes. ClinicalTrials.gov NCT01676870 FUNDING: The study was funded by the Norwegian University of Science and Technology and from an unrestricted research grant from the Coca-Cola company. Funding for the collection of physical activity data was derived from a 'UQ New Staff Start Up' grant awarded to B. Clark.
Ying, Hou-Qun; Sun, Hui-Ling; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Deng, Qi-Wen; Chen, Jie; Liu, Xian; Wang, Shu-Kui
2015-01-01
Epidemiological investigation have suggested that there is a significantly inverse association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk for developing colorectal cancer (CRC) in humans. However, little is known about the role of vitamin D binding protein (VDBP) in colorectal carcinogenesis. Blood samples were collected from 212 CRC patients and 212 controls matched with age, gender and blood collection time. We used logistic regression to calculate the odds ratios and 95% confidence intervals for further estimation of the association of the quartiles of VDBP, total, free and bioavailable 25(OH)D with CRC risk. The results revealed that there was no significant association between circulating VDBP concentrations and CRC in the present study, and that a negative association existed between total 25(OH)D and the risk of CRC, which was unchanged after adjustment for VDBP. Higher levels of free and bioavailable 25(OH)D were significantly associated with decreased risk of CRC. After stratifying by VDBP, high levels of total, free and bioavailable 25(OH)D were associated significantly with decreased CRC risk among participants with circulating VDBP below the median. These findings indicate that VDBP is not directly associated with the risk of CRC, but it modulates circulating free and bioavailable 25(OH)D concentration. PMID:25609140
Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel
2012-10-01
We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.
NASA Technical Reports Server (NTRS)
Isaksen, I. S. A.; Stordal, F.
1986-01-01
Observations made over the last few years suggest that the tropospheric concentrations of N2O, CH4, and O3 are increasing. Increases in the concentration of chlorofluorocarbons (CFCs) have been observed for some time. The present study is concerned with combined scenarios of future releases of N2O, CH4, and CFCs, which can affect the height profiles of ozone, while changes in latitudinal gradients of ozone may also be expected. Ozone perturbation calculations performed in the two-dimensional transport-chemistry model described by Stordal et al. (1985) are also presented, and the effects of increased levels of CFCs, N2O, and CH4 are examined. It is found that CH4 may be the most important ozone-perturbing trace species in connection with future tropospheric climatic impacts. A substantial increase in the tropospheric abundancy of CH4 could lead to large future ozone enhancements throughout the troposphere and lower stratosphere at middle and low latitudes.
Local biomass burning is a dominant cause of the observed precipitation reduction in southern Africa
Hodnebrog, Øivind; Myhre, Gunnar; Forster, Piers M.; Sillmann, Jana; Samset, Bjørn H.
2016-01-01
Observations indicate a precipitation decline over large parts of southern Africa since the 1950s. Concurrently, atmospheric concentrations of greenhouse gases and aerosols have increased due to anthropogenic activities. Here we show that local black carbon and organic carbon aerosol emissions from biomass burning activities are a main cause of the observed decline in southern African dry season precipitation over the last century. Near the main biomass burning regions, global and regional modelling indicates precipitation decreases of 20–30%, with large spatial variability. Increasing global CO2 concentrations further contribute to precipitation reductions, somewhat less in magnitude but covering a larger area. Whereas precipitation changes from increased CO2 are driven by large-scale circulation changes, the increase in biomass burning aerosols causes local drying of the atmosphere. This study illustrates that reducing local biomass burning aerosol emissions may be a useful way to mitigate reduced rainfall in the region. PMID:27068129
Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D
2011-01-01
Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329
Farmer, C; Lapointe, J; Palin, M-F
2014-07-01
The impacts of supplementing the diet of gestating gilts twice daily with 4 g of the plant extract silymarin on circulating hormonal concentrations, oxidative status, mammary development, and mammary gene expression at the end of gestation were determined. Gilts were fed conventional diets during gestation and on d 90 they were assigned as controls (CTL; n = 16) or treated (TRT; n = 17) animals. Treatment consisted of providing 4 g of silymarin twice daily until d 110, at which time all gilts were slaughtered to collect mammary tissue for compositional analyses and measures of gene expression and oxidative status, and liver and corpora lutea for measures of oxidative stress variables. Blood samples for hormonal assays and evaluation of oxidative stress biomarkers were obtained on d 89, 94, and 109 of gestation. Silymarin increased (P = 0.05) circulating concentrations of prolactin over all samples in the repeated in time analysis. In separate analyses for each sampling time, prolactin concentrations in TRT gilts tended (P < 0.10) to be greater than in CTL gilts on d 94 of gestation. Repeated in time analysis also revealed that silymarin reduced (P ≤ 0.05) plasmatic accumulation of biomarkers of oxidative damage to protein (protein carbonyls) between d 89 and 109. There was no effect (P > 0.10) of treatment on progesterone, estradiol, leptin, or 8-hydroxy-2'-deoxyguanosine concentrations. Percent fat in mammary parenchyma was greater (P ≤ 0.05), percent protein was lesser (P ≤ 0.05), and concentrations of both RNA (P ≤ 0.01) and DNA (P < 0.05) were lesser in TRT than CTL gilts. Mammary parenchyma from TRT gilts had lower (P ≤ 0.05) mRNA abundance for STAT5A and leptin and tended to have lower (P ≤ 0.10) abundance for STAT5B than CTL gilts. Silymarin reduced (P ≤ 0.001) protein carbonyls concentrations in liver of TRT gilts. No effect of treatment was observed on antioxidant gene expression and enzymatic activities in liver samples while total superoxide dismutase activity tended to be higher (P ≤ 0.10) in the corpora lutea of TRT animals when compared with CTL. This is the first demonstration that, in female pigs, silymarin can increase prolactin concentrations and protect against oxidative stress, yet the increase in prolactin was not enough to have beneficial effects on mammary gland development in late gestation.
Predicting the physical effects of relocating Boston's sewage outfall
Signell, R.P.; Jenter, H.L.; Blumberg, A.F.
2000-01-01
Boston is scheduled to cease discharge of sewage effluent in Boston Harbor in Spring 2000 and begin discharge at a site 14 km offshore in Massachusetts Bay in a water depth of about 30 m. The effects of this outfall relocation on effluent dilution, salinity and circulation are predicted with a three-dimensional hydrodynamic model. The simulations predict that the new bay outfall will greatly decrease effluent concentrations in Boston Harbor (relative to the harbour outfall) and will not significantly change mean effluent concentrations over most of Massachusetts Bay. With the harbour outfall, previous observations and these simulations show that effluent concentrations exceed 0??5% throughout the harbour, with a harbour wide average of 1-2%. With the bay outfall, effluent concentrations exceed 0??5% only within a few km of the new outfall, and harbour concentrations drop to 0??1-0??2%, a 10-fold reduction. During unstratified winter conditions, the local increase in effluent concentration at the bay outfall site is predicted to exist throughout the water column. During stratified summer conditions, however, effluent released at the sea bed rises and is trapped beneath the pycnocline. The local increase in effluent concentration is limited to the lower layer, and as a result, surface layer effluent concentrations in the vicinity of the new outfall site are predicted to decrease (relative to the harbour outfall) during the summer. Slight changes are predicted for the salinity and circulation fields. Removing the fresh water associated with the effluent discharge in Boston Harbor is predicted to increase the mean salinity of the harbour by 0??5 and decrease the mean salinity by 0??10-0??15 within 2-3 km of the outfall. Relative to the existing mean flow, the buoyant discharge at the new outfall is predicted to generate density-driven mean currents of 2-4 cm s-1 that spiral out in a clockwise motion at the surface during winter and at the pycnocline (15-20 m depth) during summer. Compensating counterclockwise currents are predicted to spiral in toward the source at the bottom. Because the scale of the residual current structure induced by the new discharge is comparable to or smaller than typical subtidal water parcel excursions, Lagrangian trajectories will not follow the Eulerian residual flow. Thus, mean currents measured from moorings within 5 km of the bay outfall site will be more useful for model comparison than to indicate net transport pathways.
Influence of Oil on Refrigerant Evaporator Performance
NASA Astrophysics Data System (ADS)
Kim, Jong-Soo; Nagata, Karsuya; Katsuta, Masafumi; Tomosugi, Hiroyuki; Kikuchi, Kouichiro; Horichi, Toshiaki
In vapor compression refrigeration system using oil-lubricated compressors, some amount of oil is always circulated through the system. Oil circulation can have a significant influence on the evaporator performance of automotive air conditioner which is especially required to cool quickly the car interior after a period standing in the sun. An experimental investigation was carried out an electrically heated horizontal tube to measure local heat transfer coefficients for various flow rates and heat fluxes during forced convection boiling of pure refrigerant R12 and refrigerant-oil mixtures (0-11% oil concentration by weight) and the results were compared with oil free performance. Local heat transfer coefficients increased at the region of low vapor quality by the addition of oil. On the other hand, because the oil-rich liquid film was formed on the heat transfer surface, heat transfer coefficients gradually decreased as the vapor quality became higher. Average heat transfer coefficient reached a maximum at about 4% oil concentration and this trend agreed well with the results of Green and Furse. Previous correlations, using the properties of the refrigerant-oil mixture, could not predict satisfactorily the local heat transfer coefficients data. New correlation modified by oil concentration factor was developed for predicting the corresponding heat transfer coefficient for refrigerant-oil mixture convection boiling. The maximum percent deviation between predicted and measured heat transfer coefficient was within ±30%.
Sodi, R; Hazell, M J; Durham, B H; Rees, C; Ranganath, L R; Fraser, W D
2009-09-01
There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. We observed a positive correlation between BMI and BMD (r=0.44, p<0.001). When normalised for BMI, total-, HMW-adiponectin concentrations and HMW/total-adiponectin ratio were significantly lower in obese compared to lean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, p<0.001). Our data suggests that there is no significant difference in the circulating concentration of fasting early morning total- or HMW-adiponectin in post-menopausal women with or without osteoporosis. The correlation between HMW/total-adiponectin ratio and OPG may indicate that adiponectin could influence bone metabolism by altering osteoblast production of OPG thereby affecting osteoclasts mediated bone resorption.
Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation.
Webber, C E; Chettle, D R; Bowins, R J; Beaumont, L F; Gordon, C L; Song, X; Blake, J M; McNutt, R H
1995-01-01
Hormone replacement therapy (HRT) in postmenopausal women suppresses the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty six women who at recruitment were on average 35 years postmenopausal were placed on calcium supplementation. Six months later 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p = 0.007). Tibia lead content (mean +/- SD) for women on calcium only was 11.13 +/- 6.22 microgram/g bone mineral. For women on HRT, tibia bone lead was 19.37 +/- 8.62 micrograms/g bone mineral on low-dose HRT and 16.87 +/- 11.68 micrograms/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone. Images Figure 1. PMID:8747022
Gastrointestinal and pancreatic hormones in the human fetus and mother at 18-21 weeks of gestation.
Adrian, T E; Soltesz, G; MacKenzie, I Z; Bloom, S R; Aynsley-Green, A
1995-01-01
Several gastrointestinal hormones appear to play an important developmental role in the newborn, particularly in preterm neonates. Although the cells producing these peptides develop towards the end of the first trimester, fetal secretion of these regulatory peptides has not hitherto been demonstrated. Using samples collected by fetoscopy at 19-21 weeks of gestation we have measured concentrations of several gastrointestinal and pancreatic hormones. Maternal venous and amniotic fluid hormone concentrations were measured simultaneously. Concentrations of the pancreatic hormones, insulin, glucagon and pancreatic polypeptide (PP) were similar in fetal and maternal blood. Gastrin and motilin were present in the fetal circulation but at about 30% (p < 0.05) and 60% (p < 0.01) of the maternal levels, respectively. In contrast, enteroglucagon concentrations were more than twofold higher in the fetal circulation compared with maternal levels (p < 0.05). Concentrations of gastric inhibitory polypeptide (GIP) in fetal blood were higher than levels in maternal blood but not significantly. Concentrations of GIP (p < 0.001) were higher in the amniotic fluid than the fetal circulation. Gastrin and glucagon levels were similar in amniotic fluid and fetal blood. In contrast, PP and motilin were present in amniotic fluid, but at lower concentrations than in fetal blood. Enteroglucagon was not detectable in amniotic fluid. In conclusion, several alimentary hormones are secreted in the fetus at midterm. Since these peptides have trophic, secretory and motor effects on the gut, it is likely that these regulatory peptides are involved in the functional development of the fetal intestine.
Transient neutropenia: Neutrophil distribution and replacement
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thakur, M.L.; Li, Jinghua; Binoy, Li
Radiolabeled polymorphonuclear (PMN) receptor-specific proteins or peptides lead the list of agents being evaluated for imaging inflammatory foci. Some of these agents induce transient neutropenia. This study was designed to quantify the degree of dose dependency of neutropenia, determine the duration of neutropenia, identify the organs in which these PMNs sequester and ascertain if these PMNs return to the circulation. Rodent anti-PMN (Gr-1) MAb RB6-8C5 (lgG-2A) and Balb/c mice served as the model, and PMN nonspecific ME 31.3 (lgG-2A) as a control. Circulating PMN number was determined several times, 30 min prior to and between 1 min and 120 hrmore » after MAb administration. Iodine-125-MAbs provided quantification of circulating activity and tissue distribution as a function of time. Data showed the severity of neutropenia increased with the amount of MAb administered (>95% PMNs lost after 150 {mu}g versus <85% after 10 {mu}g). Moreover, the recovery time for PMN counts to reach the pretreatment level also increased in a dose-dependent manner (96 hr at 150 {mu}g versus 4 hr at 10 {mu}g and 2 hr at 2 {mu}g). The blood activity, however, which declined quickly with the neutropenia, never rose again with PMN recovery. As a function of time, radioactivity in the study group decreased from all organs except from the liver and spleen, whereas in the control group; and spleen, 15.5% decrease versus 63.6% decrease in control group. The degree and duration of neutropenia is dose-dependent. PMNs, lost from the circulation, sequester in the reticuloendothelial system, and do not return to circulation. Therefore, they are not available to image inflammatory foci. The PMN concentration is restored to a pretreatment level in a dose-dependent fashion, presumably by freshly released PMNs from bone marrow. 32 refs., 5 figs.« less
Caba, Mario; Meza, Enrique; Waliszewski, Stefan M; Martínez-Valenzuela, Carmen
2015-07-01
Organochlorine pesticides, due to their hydrophobic nature and persistence, accumulate in tissues rich in lipids, which had been used as a biomarker for environmental pollution. In humans, organochlorine pesticides are continuously circulating and equilibrating among body compartments. The objective of the study was to evaluate the concentrations of organochlorine pesticides in blood serum and compare their levels to the total lipid contents in Veracruz, México inhabitants. Our hypothesis is that concentrations of organochlorine pesticides will increase just as lipid concentrations. Levels of organochlorine pesticides were divided in ascending tertils according to their total lipid content. The linear trend model applied surprisingly reveals that the average level of all organochlorine pesticides decreases as the lipid concentration increases. From one tertil to the next β-HCH, it shows a decrease of -3.19 mg kg(-1) on lipid basis, pp.'DDE levels decrease by -3.70 mg kg(-1) on lipid basis and pp.'DDT levels decrease -1.13 mg kg(-1) on lipid basis. We conclude that the levels and the orderly sequence of organochlorine pesticide distributions in the blood serum maintain an inverse relationship to total lipid blood serum concentrations.
Tang, Xiaoyun; Wang, Xianyan; Zhao, Yuan Y; Curtis, Jonathan M; Brindley, David N
2017-02-08
We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces. In this work, we used a syngeneic orthotopic mouse model of breast cancer to determine the impact of doxycycline on circulating lysophosphatidate concentrations and tumor growth. Cytokine/chemokine concentrations in tumor tissue and plasma were measured by multiplexing laser bead technology. Leukocyte infiltration in tumors was analyzed by immunohistochemistry. The expression of IL-6 in breast cancer cell lines was determined by RT-PCR. Cell growth was measured in Matrigel™ 3D culture. The effects of doxycycline on NF-κB-dependent signaling were analyzed by Western blotting. Doxycycline decreased plasma lysophosphatidate concentrations, delayed tumor growth and decreased the concentrations of several cytokines/chemokines (IL-1β, IL-6, IL-9, CCL2, CCL11, CXCL1, CXCL2, CXCL9, G-CSF, LIF, VEGF) in the tumor. These results were compatible with the effects of doxycycline in decreasing the numbers of F4/80 + macrophages and CD31 + blood vessel endothelial cells in the tumor. Doxycycline also decreased the lysophosphatidate-induced growth of breast cancer cells in three-dimensional culture. Lysophosphatidate-induced Ki-67 expression was inhibited by doxycycline. NF-κB activity in HEK293 cells transiently expressing a NF-κB-luciferase reporter vectors was also inhibited by doxycycline. Treatment of breast cancer cells with doxycycline also decreased the translocation of NF-κB to the nucleus and the mRNA levels for IL-6 in the presence or absence of lysophosphatidate. These results contribute a new dimension for understanding the anti-inflammatory effects of tetracyclines, which make them potential candidates for adjuvant therapy of cancers and other inflammatory diseases.
Effects of thyroid state on respiration of perfused rat and guinea pig hearts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Read, L.C.; Wallace, P.G.; Berry, M.N.
1987-09-01
The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na{sup 131}I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. Inmore » the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.« less
NASA Astrophysics Data System (ADS)
Sutton, Patrick T.; Ginn, Timothy R.
2014-12-01
A sustainable in-well vapor stripping system is designed as a cost-effective alternative for remediation of shallow chlorinated solvent groundwater plumes. A solar-powered air compressor is used to inject air bubbles into a monitoring well to strip volatile organic compounds from a liquid to vapor phase while simultaneously inducing groundwater circulation around the well screen. An analytical model of the remediation process is developed to estimate contaminant mass flow and removal rates. The model was calibrated based on a one-day pilot study conducted in an existing monitoring well at a former dry cleaning site. According to the model, induced groundwater circulation at the study site increased the contaminant mass flow rate into the well by approximately two orders of magnitude relative to ambient conditions. Modeled estimates for 5 h of pulsed air injection per day at the pilot study site indicated that the average effluent concentrations of dissolved tetrachloroethylene and trichloroethylene can be reduced by over 90% relative to the ambient concentrations. The results indicate that the system could be used cost-effectively as either a single- or multi-well point technology to substantially reduce the mass of dissolved chlorinated solvents in groundwater.
Chen, Chunyan; Long, Sihua; Li, Airong; Xiao, Guoqing; Wang, Linyuan; Xiao, Zeyi
2017-03-16
Since both ethanol and butanol fermentations are urgently developed processes with the biofuel-demand increasing, performance comparison of aerobic ethanol fermentation and anerobic butanol fermentation in a continuous and closed-circulating fermentation (CCCF) system was necessary to achieve their fermentation characteristics and further optimize the fermentation process. Fermentation and pervaporation parameters including the average cell concentration, glucose consumption rate, cumulated production concentration, product flux, and separation factor of ethanol fermentation were 11.45 g/L, 3.70 g/L/h, 655.83 g/L, 378.5 g/m 2 /h, and 4.83, respectively, the corresponding parameters of butanol fermentation were 2.19 g/L, 0.61 g/L/h, 28.03 g/L, 58.56 g/m 2 /h, and 10.62, respectively. Profiles of fermentation and pervaporation parameters indicated that the intensity and efficiency of ethanol fermentation was higher than butanol fermentation, but the stability of butanol fermentation was superior to ethanol fermentation. Although the two fermentation processes had different features, the performance indicated the application prospect of both ethanol and butanol production by the CCCF system.
Teas, Jane; Irhimeh, Mohammad R.; Druker, Susan; Hurley, Thomas G.; Hébert, James R.; Savarese, Todd M.; Kurzer, Mindy S.
2011-01-01
Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations. PMID:21711174
Teas, Jane; Irhimeh, Mohammad R; Druker, Susan; Hurley, Thomas G; Hébert, James R; Savarese, Todd M; Kurzer, Mindy S
2011-01-01
Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations.
Hyperthyroidism affects lipid metabolism in lactating and suckling rats.
Varas, S M; Jahn, G A; Giménez, M S
2001-08-01
Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.
Feng, Xuebing; Wang, Dandan; Chen, Jingjing; Lu, Lin; Hua, Bingzhu; Li, Xia; Tsao, Betty P; Sun, Lingyun
2012-01-01
To observe the proportion of peripheral T follicular helper (Tfh) cells in patients with systemic lupus erythematosus (SLE) and to assess the role of steroids on Tfh cells from SLE patients. Peripheral blood mononuclear cells (PBMCs) from 42 SLE patients and 22 matched healthy subjects were collected to assess proportions of circulating CXCR5(+)PD1(+)/CD4(+) T cells (Tfh), CD4(+)CCR6(+) T cells (Th17-like) and CD19(+)CD138(+) plasma cells by flow cytometry. 8 of the patients had their blood redrawn within one week after receiving methylprednisolone pulse treatment. Disease activity was evaluated by SLE disease activity index. To test the effect of IL-21 and corticosteroids on Tfh cells in vitro, PBMCs harvested from another 15 SLE patients were cultured with medium, IL-21, or IL-21+ dexamethasone for 24 hours and 72 hours. PBMCs from an independent 23 SLE patients were cultured with different concentrations of dexamethasone for 24 hours. Compared to normal controls, percentages of circulating Tfh cells, but not Th17 cells, were elevated in SLE patients and correlated with disease activity. Proportions of Tfh cells in SLE patients were positively correlated with those of plasma cells and serum levels of antinuclear antibodies. After methylprednisolone pulse treatment, both percentages and absolute numbers of circulating Tfh cells were significantly decreased. In vitro cultures showed an increase of Tfh cell proportion after IL-21 stimulation that was totally abolished by the addition of dexamethasone. Both 0.5 and 1 µM dexamethasone decreased Tfh cells dose dependently (overall p = 0.013). We demonstrated that elevated circulating Tfh cell proportions in SLE patients correlated with their disease activities, and circulating levels of plasma cells and ANA. Corticosteroids treatment down-regulated aberrant circulating Tfh cell proportions both in vivo and in vitro, making Tfh cells a new treatment target for SLE patients.
Cavalieri, J; Wang, M
2015-08-01
The aim of this study was to determine the effects in Bos indicus calves of intra-testicular injection of either saline (n=9) or one of two doses of zinc acetate ((ZA1, 57.75mg, n=10, or ZA2, 71.75mg, n=10) or surgical castration (n=9) on circulating concentrations of testostosterone and liveweight. Human chorionic gonadotrophin (hCG, 1500IU) was administered 202 and 525 days after treatment on Day 0 and animals were slaughtered on Day 860. In animals left intact treatment with ZA reduced mean serum concentrations of testosterone (Saline: 5.58±0.79ng/mL, ZA1: 1.28±0.27ng/mL, ZA2: 1.01±0.17ng/mL; P<0.001) and concentrations 48h following administration of hCG. The maximum concentration of testosterone recorded throughout the study in six out of 19 animals treated with ZA was ≤0.21ng/mL. Treatment with ZA did not significantly affect live weights or carcass weights or result in any detectable scrotal lesions. Animals with concentrations of testosterone ≥1.0ng/mL exhibited greater liveweights throughout most of the study and yielded heavier carcass weights (340.9±7.02 versus 309.3±6.17kg, P=0.002). It is concluded that a single, intra-testicular administration of either 57.75mg or 71.75mg of ZA was able to similarly reduce circulating concentrations of testosterone without significantly affecting liveweights or carcass weights. Treatment with ZA can result in variation in circulating concentrations of testosterone which could lead to differences in behaviour, liveweights and carcass characteristics. Copyright © 2015 Elsevier B.V. All rights reserved.
Genetic Variants Associated with Circulating Parathyroid Hormone
Lutsey, Pamela L.; Kleber, Marcus E.; Nielson, Carrie M.; Mitchell, Braxton D.; Bis, Joshua C.; Eny, Karen M.; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L.; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W.; Orwoll, Eric; Zmuda, Joseph M.; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J.; Ryan, Kathleen A.; Ohlsson, Claes; Paterson, Andrew D.; Psaty, Bruce M.; Siscovick, David S.; Rotter, Jerome I.; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S.; de Boer, Ian H.; Kestenbaum, Bryan
2017-01-01
Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10−53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10−17), rs219779 adjacent to CLDN14 (P=3.5 × 10−16), rs4443100 near RTDR1 (P=8.7 × 10−9), and rs73186030 near CASR (P=4.8 × 10−8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. PMID:27927781