Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics: a case-control study.

PubMed

Jorgensen, Anders; Knorr, Ulla; Soendergaard, Mia Greisen; Lykkesfeldt, Jens; Fink-Jensen, Anders; Poulsen, Henrik Enghusen; Jorgensen, Martin Balslev; Olsen, Niels Vidiendal; Staalsø, Jonatan Myrup

2015-04-03

Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA ratio are positively correlated to measures of oxidative stress. We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography. Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology. Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores. Schizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma levels of ADMA were not associated with levels of systemic oxidative stress in vivo.

The endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) predicts LV mass independent of afterload.

PubMed

Sverdlov, A L; Ngo, D T M; Nightingale, A K; Rajendran, S; Mishra, K; Heresztyn, T; Ritchie, R H; Marwick, T H; Frenneaux, M P; Horowitz, J D

2011-06-30

Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass. Copyright © 2011. Published by Elsevier Inc.

Evaluation of asymmetric dimethylarginine (ADMA) levels in children with growth hormone deficiency.

PubMed

Önder, Aşan; Aycan, Zehra; Koca, Cemile; Ergin, Merve; Çetinkaya, Semra; Ağladıoğlu, Sebahat Yılmaz; Peltek Kendirci, Havva Nur; Baş, Veysel Nijat

2014-01-01

To investigate serum asymmetric dimethylarginine (ADMA) levels in children with isolated growth hormone deficiency (GHD) and to determine the effect of GH replacement therapy on these levels. 31 patients diagnosed with isolated GHD and 29 age-and sex-matched healthy children were enrolled in the study. Height, weight and waist circumference were measured in all subjects. Fasting serum insulin-like growth factor-1 (IGF-1), IGF binding protein-3, glucose, insulin and lipid levels were evaluated. Serum ADMA levels were assessed using the enzyme-linked immunosorbent assay technique. The same evaluations were repeated on the 3rd and 6th months of treatment in 28 of the GHD cases. There were no significant differences in ADMA levels between the patient and control groups [0.513±0.130 (0.291-0.820) µmol/L vs. 0.573±0.199 (0.241-1.049) µmol/L]. There was a positive correlation between serum ADMA and HbA1c levels in the control group. In the GHD cases, ADMA levels negatively correlated with high-density lipoprotein levels and positively correlated with low-density lipoprotein levels. There was also a significant increase in ADMA levels in patients receiving GH therapy compared to pre-treatment levels [serum ADMA level, 1.075±0.133 (0.796-1.303) µmol/L at the 3rd month and 0.923±0.121 (0.695-1.159) µmol/L at the 6th month of treatment]. There was a negative correlation between ADMA levels and homeostasis model assessment of insulin resistance values at the 6th month evaluation. There were no relationships between ADMA levels and age, sex, or pubertal state either before or during the treatment. Serum ADMA levels were found to be similar in patients with GHD and in healthy children. However, serum ADMA levels showed a significant increase in GHD patients following GH replacement therapy.

HPLC determination of plasma dimethylarginines: method validation and preliminary clinical application.

PubMed

Ivanova, Mariela; Artusi, Carlo; Boffa, Giovanni Maria; Zaninotto, Martina; Plebani, Mario

2010-11-11

Asymmetric dimethylarginine (ADMA) has been suggested as a possible marker of endothelial dysfunction, and interest in its use in clinical practice is increasing. However, the potential role of symmetric dimethylarginine (SDMA) as an endogenous marker of renal function, has been less widely investigated. The aims of the present study were therefore to determine reference values for dimethylarginines in plasma after method validation, and to ascertain ADMA plasma concentrations in patients with disorders characterized by endothelial dysfunction; a further end-point was to investigate the relationship between SDMA plasma concentrations and estimated GFR (eGFR) as well as plasmatic creatinine in patients with chronic kidney disease (CKD). HPLC with fluorescence detection was used for the determination of plasma dimethylarginines. To verify the clinical usefulness of ADMA and SDMA, values from 4 groups of patients at a high risk of cardiovascular complications as well renal dysfunction (chronic heart failure n=126; type II diabetes n=43; pulmonary arterial hypertension n=17; chronic kidney disease n=42) were evaluated, and compared with the reference values, obtained from 225 blood donors. The intra- and inter-assay CVs (<5.2%), the absolute and relative recoveries (96-106%) were highly satisfactory. ADMA levels were significantly elevated in all groups of patients compared with controls (p<0.001) with the exception of samples from patients with type II diabetes. SDMA levels were significantly elevated both in the patients with chronic kidney disease and in the patients with type II diabetes complicated by renal insufficiency, the values being closely correlated with both eGFR (R=0.740) and plasmatic creatinine (R=0.700). The findings made in the present study shows that ADMA levels are significantly increased in patients with diseases associated with endothelial dysfunction This molecule might, therefore, be used as a biochemical marker for the evaluation of endothelial function. Furthermore, the preliminary results reported suggest that SDMA might be a reliable marker of renal function, especially in peadiatric populations, for which the use of eGFR is not recommended. 2010 Elsevier B.V. All rights reserved.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism.

PubMed

Haymana, Cem; Sonmez, Alper; Aydogdu, Aydogan; Tapan, Serkan; Basaran, Yalcin; Meric, Coskun; Baskoy, Kamil; Dinc, Mustafa; Yazici, Mahmut; Taslipinar, Abdullah; Barcin, Cem; Yilmaz, Mahmut Ilker; Bolu, Erol; Azal, Omer

2017-01-01

Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = -0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = -0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

[Asymmetric dimethylarginine (ADMA) in children with diabetes type 1].

PubMed

Głowińska-Olszewska, Barbara; Luczyński, Włodzimierz; Jabłońska, Jolanta; Otocka, Agnieszka; Florys, Bożena; Bossowski, Artur

2010-01-01

Asymmetric dimethylarginine (ADMA), a naturally occurring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase. ADMA is now recognized as an independent marker of endothelial dysfunction and atherosclerosis. Data concerning ADMA level in type 1 diabetes (DM1) are controversial. The aim of the study was to evaluate ADMA level in children with DM1, without clinical evidence of vascular complications, with particular attention to additional cardiovascular risk factors (hypertension, obesity, hyperlipidemia). The study group included 72 children with DM1, aged mean 15±3 yrs (8-20 yrs), 33 boys and 39 girls, with diabetes duration time mean 6.6±3.5 yrs (1-14 yrs), HBA1c mean level 8.2±2.3% (5.6-15%). The control group consisted of 41 (19 boys and 22 girls) healthy children, aged mean--14.8±2.6 yrs, from 8 to 18 yrs, gender matched, with no family history of cardiovascular disease. ADMA level was determined in plasma using ELISA kit (DLD Diagnostica, Hamburg, Germany) ADMA level was similar in children with diabetes and in the control group: 0.69±0.33 vs. 0.7±0.27 μmol/L, ns. We did not find differences in ADMA level in diabetic children with the presence of additional diseases being cardiovascular risk factors. In the group of 13 children with hypertension ADMA level was the highest: 0.79±0.25 μmol/L, but the difference was statistically insignificant in comparison to children with diabetes without hypertension and in comparison to healthy controls. Children with DM1, without clinically evident vascular complications, have ADMA levels similar to healthy children. A possible relationship between ADMA and hypertension in these patients requires further investigation.

Serum asymmetric dimethylarginine and nitric oxide levels in obese postmenopausal women.

PubMed

Kocak, Hikmet; Oner-Iyidogan, Yıldız; Gurdol, Figen; Oner, Pernur; Esin, Deniz

2011-01-01

It has been reported that estrogen deficiency after menopause might cause a decrement in nitric oxide (NO) bioavailability by increasing the level of asymmetric dimethylarginine (ADMA), a major endogenous nitric oxide synthase inhibitor, thus leading to abnormalities in endothelial function. Because NO plays an important role on feeding behavior, ADMA may be involved in the pathogenesis of obesity, too. This cross-sectional study aimed to evaluate the relations of ADMA and NO with the obesity-linked peptides, such as ghrelin, leptin, and adiponectin in postmenopausal women free of hormone replacement therapy. Adiponectin, ghrelin, leptin, ADMA, and NO(x) (total nitrite/nitrate) were measured in 22 obese (BMI: 30-47 kg/m(2)) and 19 normal weight (BMI: 21.5-26 kg/m(2)) postmenopausal women.Anthropometric measurements (height, weight, BMI, waist, and hip circumferences) were recorded. Statistics were made by the Mann-Whitney U-test. Ghrelin and adiponectin levels were significantly lower (P<0.001), whereas ADMA and leptin levels were higher in obese women than in normal weight controls (P<0.01 and 0.001, respectively). BMI was correlated negatively with adiponectin and ghrelin and positively with ADMA and leptin levels. No correlation existed between ADMA and NO. Estrogen deficiency alone may not cause an increase in ADMA levels unless the women are prone to disturbances in energy homeostasis. In spite of the high ADMA levels, the unaltered NO levels in plasma may be owing to ongoing inflammatory conditions. © 2011 Wiley-Liss, Inc.

The relationship between serum asymmetric dimethylarginine levels and subjective sleep quality in normotensive patients with type 2 diabetes mellitus.

PubMed

Aribas, Alpay; Kayrak, Mehmet; Tekinalp, Mehmet; Akilli, Hakan; Alibasic, Hayrudin; Yildirim, Serkan; Gunduz, Mehmet; Taner, Alpaslan; Unlu, Ali

2015-05-01

Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus. The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography. The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood pressure. Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.

Evaluation of serum Asymmetric Dimethyl Arginine concentrations in coronary artery disease patients without traditional cardiovascular risk factors.

PubMed

Ghayour-Mobarhan, Majid; Ayati, Nayyereh; Sahebkar, Amirhossein; Moohebati, Mohsen; Ayati, Narjes; Elyasi, Sepideh; Mohammadpour, Amir Houshang

2018-06-07

Previous studies have shown that Asymmetric Dimethyl Arginine (ADMA) is increased significantly during coronary artery diseases (CAD). However it is not clear either this increase is due to cardiovascular disease (CVD) risk factors or ADMA is increased independently in CAD. The aim of this study is to evaluate ADMA's plasma level as an independent biomarker in CADs. In current study a total of 165 subjects with no traditional CVD's RFs, who fulfilled the inclusion and exclusion criteria, were recruited; 55 CAD+ patients which had more than 50% stenosis (CAD+); 55 CAD- patients which had less than 50% stenosis in their coronary arteries (CAD-), based on their angiography record and 55 healthy individuals as controls. CAD+ patients were divided into three groups: single (SVD), double (2VD), and triple vessel (3VD) disease. Plasma level of soluble ADMA was measured with an enzyme-linked immono sorbent assay (ELISA) kit. No significant difference between ADMA's plasma levels was found between CAD+, CAD- and healthy groups. In addition ADMA's plasma levels was not significantly different between CAD+'s subgroups. The result of this study indicates no significant relation between ADMA's plasma levels and either presence or severity of coronary artery stenosis. Therefore, it is presumed that ADMA may not be an independent biomarker for CADs.

The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion injury

PubMed Central

Berardo, Clarissa; Siciliano, Veronica; Rizzo, Vittoria; Adorini, Luciano; Richelmi, Plinio

2018-01-01

Background We previously showed that increased asymmetric dimethylarginine (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R), prompting us to study the effects of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R. Material and methods Male Wistar rats were orally administered 10mg/kg/day of OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia or sham-operated. After a 60 min reperfusion, serum, tissue and bile ADMA levels, liver mRNA and protein expression of ADMA transporters (CAT-1, CAT-2A, CAT-2B, OCT-1, MATE-1), and enzymes involved in ADMA synthesis (protein-arginine-N-methyltransferase-1, PRMT-1) and metabolism (dimethylarginine-dimethylaminohydrolase-1, DDAH-1) were measured. Results OCA administration induced a further increase in biliary ADMA levels both in sham and I/R groups, with no significant changes in hepatic ADMA content. A reduction in CAT-1, CAT-2A or CAT-2B transcripts was found in OCA-treated sham-operated rats compared with vehicle. Conversely, OCA administration did not change CAT-1, CAT-2A or CAT-2B expression, already reduced by I/R. However, a marked decrease in OCT-1 and increase in MATE-1 expression was observed. A similar trend occurred with protein expression. Conclusion The reduced mRNA expression of hepatic CAT transporters suggests that the increase in serum ADMA levels is probably due to decreased liver uptake of ADMA from the systemic circulation. Conversely, the mechanism involved in further increasing biliary ADMA levels in sham and I/R groups treated with OCA appears to be MATE-1-dependent. PMID:29346429

Nitric oxide synthase inhibitors and hypertension in children and adolescents.

PubMed

Goonasekera, C D; Rees, D D; Woolard, P; Frend, A; Shah, V; Dillon, M J

1997-08-01

To establish the role played by the circulating nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine (L-NMMA), asymmetrical dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) and its association with hypertension of children and adolescents. We measured plasma concentrations of L-NMMA, ADMA and SDMA in 38 hypertensives (median age 7.7 years) and in nine healthy normotensive controls (median age 8.2 years) using high-performance liquid chromatography. In addition, their plasma renin activity was determined. The subjects' glomerular filtration rates were calculated from plasma creatinine and height measurements. To determine the vasoactive potency of the arginine analogues, concentration-response curves were plotted for the responses in isolated endothelium-intact and endothelium-denuded mouse aortic rings that had been pre-contracted by administration of a threshold concentration of phenylephrine. Plasma ADMA and SDMA concentrations in members of the hypertensive group [0.23 +/- 0.03 and 1.37 +/- 0.06 micromol/l, respectively (means +/- SEM)] were significantly higher than those in members of the control group (ADMA 0.10 +/- 0.01 micromol/l and SDMA 1.18 +/- 0.06 micromol/l). Plasma concentrations of L-NMMA were similar in members of the hypertensive (0.21 +/- 0.01 micromol/l) and control (0.18 +/- 0.02 micromol/l) groups. The glomerular filtration rate of the hypertensive group was below normal [70.4 +/- 5.4 ml/min per 1.73 m2 (mean +/- SEM)] and was significantly associated with elevated plasma concentrations of ADMA (r = -0.77, P < 0.001), SDMA (r = -0.38, P = 0.02) and L-NMMA (r = 0.35, P = 0.03). Higher plasma ADMA concentrations were associated with a lower plasma renin activity (r = -0.36, P = 0.04). The vasoactive potencies of ADMA (concentration for half-maximal effect with the endothelium intact 25.4 +/- 7.1 micromol/l) and L-NMMA (concentration for half-maximal effect with the endothelium intact 8.2 +/- 2.9 micromol/l) was significantly (P < 0.05) greater than that of SDMA. Both ADMA and L-NMMA (at 3 micromol/l concentrations) initiated a significant vasocontractile response from baseline (P = 0.03 and P < 0.001, respectively). These effects were absent after the endothelium had been removed. SDMA had no effect. Plasma ADMA and SDMA levels are increased in hypertensive children. By inference from in-vitro data, ADMA appears to attain sufficient concentrations to produce a significant change in vascular tone and hence might play a role in the pathophysiology of childhood hypertension.

Effects of ADMA upon Gene Expression: An Insight into the Pathophysiological Significance of Raised Plasma ADMA

PubMed Central

Smith, Caroline L; Anthony, Shelagh; Hubank, Mike; Leiper, James M; Vallance, Patrick

2005-01-01

Background Asymmetric dimethylarginine (ADMA) is a naturally occurring inhibitor of nitric oxide synthesis that accumulates in a wide range of diseases associated with endothelial dysfunction and enhanced atherosclerosis. Clinical studies implicate plasma ADMA as a major novel cardiovascular risk factor, but the mechanisms by which low concentrations of ADMA produce adverse effects on the cardiovascular system are unclear. Methods and Findings We treated human coronary artery endothelial cells with pathophysiological concentrations of ADMA and assessed the effects on gene expression using U133A GeneChips (Affymetrix). Changes in several genes, including bone morphogenetic protein 2 inducible kinase (BMP2K), SMA-related protein 5 (Smad5), bone morphogenetic protein receptor 1A, and protein arginine methyltransferase 3 (PRMT3; also known as HRMT1L3), were confirmed by Northern blotting, quantitative PCR, and in some instances Western blotting analysis to detect changes in protein expression. To determine whether these changes also occurred in vivo, tissue from gene deletion mice with raised ADMA levels was examined. More than 50 genes were significantly altered in endothelial cells after treatment with pathophysiological concentrations of ADMA (2 μM). We detected specific patterns of changes that identify pathways involved in processes relevant to cardiovascular risk and pulmonary hypertension. Changes in BMP2K and PRMT3 were confirmed at mRNA and protein levels, in vitro and in vivo. Conclusion Pathophysiological concentrations of ADMA are sufficient to elicit significant changes in coronary artery endothelial cell gene expression. Changes in bone morphogenetic protein signalling, and in enzymes involved in arginine methylation, may be particularly relevant to understanding the pathophysiological significance of raised ADMA levels. This study identifies the mechanisms by which increased ADMA may contribute to common cardiovascular diseases and thereby indicates possible targets for therapies. PMID:16190779

Increased plasma asymmetric dimethylarginine level is associated with ascending aorta dilatation: a case-control study.

PubMed

Satılmışoğlu, Muhammet Hulusi; Örnek Diker, Vesile; Taşbulak, Ömer; Diker, Mustafa; Birand, Ali; Kaya, Mehmet; İyigün, Taner; Eksik, Abdurrahman

2017-01-01

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. We aimed to determine plasma ADMA levels in patients with ascending aorta dilatation in comparison to those without aorta dilatation, and to evaluate the diagnostic, predictive, and prognostic value of serum ADMA level for aorta dilatation. This was a cross-sectional case-control study. A total of 104 consecutive patients (female/male, 35/69; mean age, 62.75 ± 13.11 years) diagnosed with ascending aorta dilatation (≥ 4.5 cm) on echocardiography (case group), and 52 age-and gender-matched patients (female/male, 17/35; mean age, 63.44 ± 7.56 years) with normal aorta dimensions (≤ 3.8 cm) (control group) were included. Routine biochemical and haematological analysis in addition to measurement of serum ADMA level were performed. The mean diameter of ascending aorta measured on echocardiography was 4.95 ± 0.57 cm and 3.34 ± 0.36 cm in patients with aorta dilatation and those without aorta dilatation, respectively (p < 0.001). Serum ADMA level was significantly higher in patients with aorta dilatation than in the control group (1.70 ± 1.12 μmol/L vs. 0.79 ± 0.76 μmol/L, respectively, p < 0.001). There was significant positive correlation between ADMA level and aortic diameter in Spearman correlation analysis (r = 0.317, p < 0.001). In linear regression analysis, ADMA was found to be a significant independent predictor of aorta diameter (Beta = 0.26, p < 0.001). Receiver-operator characteristic curve analysis also revealed that serum ADMA cut-off level over 0.29 μmol/L predicts aorta dilatation (≥ 4.5 cm) with 94% sensitivity and 92% specificity and with high ac-curacy (area under curve: 0.786; 95% confidence interval: 0.709-0.863, p < 0.001). Serum ADMA level is diagnostic for ascending aorta dilatation with high sensitivity and specificity, and should be considered for use in clinical diagnosis of aorta dilatation.

Increased ADMA levels are associated with poor pulmonary outcome in preterm neonates.

PubMed

Kavurt, Sumru; Demirel, Nihal; Bas, Ahmet Yagmur; Ulubas Isık, Dilek; Ozcan, Beyza; Aydemir, Ozge

2017-04-01

Nitric oxide (NO), synthesized from the amino acid L-arginine by the action of NO synthases (NOS), is a pulmonary vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. Preterm infants have higher plasma ADMA concentrations than term infants which could cause inhibition of NO synthesis and deterioration in pulmonary functions. We aimed to investigate the relationship between serum ADMA and L-arginine levels of preterm infants and respiratory distress syndrome (RDS), requirement of surfactant treatment, duration of mechanical ventilation, oxygen treatment, and development of bronchopulmonary dysplasia (BPD). A prospective cohort study was conducted including 80 preterm infants born with gestational age (GA) ≤ 32 weeks and birth weight (BW) ≤ 1500 g. Blood samples were obtained from all infants immediately after birth, and at postnatal 28th day of age. The relationship of first-day serum ADMA and L-arginine levels and surfactant requirement, duration of mechanical ventilation, oxygen treatment was investigated. Serum ADMA and L-arginine levels at 1st and 28th days were compared at patients with and without BPD. The role of serum ADMA levels at postnatal 28th day of age to predict the requirement of oxygen at postmenstrual 36 weeks of age was also investigated. Eighty preterm infants (42 male, 38 female) were enrolled in the study. Mean BW and GA for the total cohort was 1144.81 ± 220.44 g and 28.3 ± 1.8 weeks, respectively. Sixty-one infants were diagnosed as RDS and 44 infants treated with surfactant. The first-day ADMA levels were significantly higher in infants with surfactant requirement (1.14 ± 0.23 versus 0.86 ± 0.37, p < 0.01). First-day L-arginine levels were lower in infants with surfactant requirement compared to infants without surfactant requirement (22.32 ± 2.33 versus 23.75 ± 2.42, p > 0.05) but not significantly. Serum ADMA and L-arginine concentrations at first day were not different among infants with and without BPD (p > 0.05). ADMA concentrations at 28th day was significantly higher in infants with BPD (1.00 ± 0.25 versus 0.81 ± 0.25, p < 0.05). The cutoff level of 0.875 μmol/L for ADMA at 28th day offered the best predictive value for oxygen requirement at postnatal 36 weeks of age with a sensitivity of 88% and a specificity of 54%. Conclusıon: Serum ADMA and L-arginine levels are related to pulmonary morbidities in newborn. The results of this study show that increased ADMA levels are associated with poor pulmonary outcomes in preterm infants.

High-tone external muscle stimulation in patients with acute kidney injury (AKI): beneficial effects on NO metabolism, asymmetric dimethylarginine, and endothelin-1.

PubMed

Di Iorio, Biagio; Marzocco, Stefania; Di Micco, Lucia; Adesso, Simona; De Blasio, Antonella; Autore, Giuseppina; Sirico, Maria Luisa; Fazeli, Gholamreza; Heidland, August

2014-11-01

The aim of this study was to assess potential effects of high-tone external muscle stimulation (HTEMS) on parameters of endothelial dysfunction (ED) in patients with acute kidney injury (AKI). The bad outcome of AKI patients is markedly influenced by ED, microinflammation, oxidative stress and protein hypercatabolism. Recently, we have shown that intradialytic application of HTMS was associated with a faster resolution of AKI. Here, we investigated in the same cohort of patients whether parameters of ED such as nitric oxide (NO), asymmetric-dimethylarginine (ADMA), and endothelin 1 (ET-1) are modulated by HTEMS as compared to non-HTEMS-treated AKI patients. In a post-hoc study we analyzed plasma samples of the 34 AKI patients stage 5, of whom 17 underwent intradialytic HTEMS treatment while the other 17 served as AKI dialysis controls. Measurements included plasma nitrate and nitrite (NOx), ADMA, ET-1 and were performed before and on days 3, 7, 14, 21, and 28 after start of daily dialysis. Additional 16 healthy volunteers served as controls. Initially, in both AKI groups NOx levels were markedly lower and ADMA and ET-1 levels were higher compared to the healthy controls. After initiation of daily hemodialysis the HTEMS group showed a faster improvement of NOx and ET-1 (after 1 week) and ADMA levels (after 2 weeks) compared to the No- HTEMS group. After 2 weeks, all parameters of the HTEMS group were not different from healthy controls, while the No-HTEMSAKI group needed 3 - 4 weeks. Our findings suggest for the first time that in AKI patients, application of HTEMS is associated with a faster normalization of lowered NOx and elevated ADMA and ET-1 plasma levels. We hypothesize that the more rapid amelioration of these parameters in the HTEMS group contributed to the accelerated recovery of AKI. With regard to the small study groups with different causes of AKI, investigations in a greater number of AKI patients is required.

Plasma asymmetric dimethylarginine (ADMA) levels in Mexican women exposed to polycyclic aromatic hydrocarbons (PAHs): A preliminary study.

PubMed

Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Vázquez, Francisco J; González Palomo, Ana K; Ilizaliturri-Hernández, Cesar A; Pérez-Maldonado, Iván N

2016-12-01

Recent studies indicate that exposure to environmental pollutants (as polycyclic aromatic hydrocarbons) is a very important risk factor for development of cardiovascular diseases (CVDs). Correspondingly, in recent times asymmetric dimethylarginine (ADMA) has been proposed as a new and meaningful biomarker predictor for the risk of CVDs. Therefore, the objective of this study was to evaluate plasma ADMA concentrations in Mexican women (n=155) exposed to polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene [(1-OHP), exposure biomarker for PAHs] levels were quantified using a high performance liquid chromatography (HPLC) technique and plasma ADMA concentrations were analyzed using a commercially available ELISA kit. Urinary 1-OHP levels in all women assessed ranged from

Urinary NGAL and hematic ADMA levels: an early sign of cardio-renal syndrome in young adults born preterm?

PubMed

Bassareo, Pier Paolo; Fanos, Vassilios; Mussap, Michele; Flore, Giovanna; Noto, Antonio; Puddu, Melania; Saba, Luca; Mercuro, Giuseppe

2013-10-01

Prematurity at birth is a known risk factor for the development of an early chronic renal disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well established biomarker of kidney injury, while high blood levels of asymmetric dimethylarginine (ADMA) are associated with the future development of adverse cardiovascular events and cardiac death. (1) to verify the presence of statistically significant differences between urinary NGAL and hematic ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) (2) to seek correlations between NGAL and ADMA levels, which would indicate the presence of an early cardio-renal involvement in ex-ELBW. Twelve ex-ELBW subjects (six males and six female, mean age: 23.9 ± 3.2 years) were compared with 12 C (six males and six female). Urinary NGAL and hematic ADMA levels were assessed. Urinary NGAL levels were higher in ex- ELBW subjects compared to C (p < 0.05), as well as hematic ADMA concentrations (p < 0.05). A statistically significant correlation was found between urinary NGAL and ADMA (r = -0.60, p < 0.04). Our preliminary findings support the hypothesis that in ex-ELBW subjects the development of an early chronic kidney disease contributes towards inducing an increase in the atherosclerotic process and in the risk of future adverse cardiovascular events.

Repetitive ischemia increases myocardial dimethylarginine dimethylaminohydrolase 1 expression.

PubMed

Zhang, Ping; Fassett, John T; Zhu, Guangshuo; Li, Jingxin; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J

2017-06-01

Pharmacologic inhibition of nitric oxide production inhibits growth of coronary collateral vessels. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme that degrades asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. Here we examined regulation of the ADMA-DDAH1 pathway in a canine model of recurrent myocardial ischemia during the time when coronary collateral growth is known to occur. Under basal conditions, DDAH1 expression was non-uniform across the left ventricular (LV) wall, with expression strongest in the subepicardium. In response to ischemia, DDAH1 expression was up-regulated in the midmyocardium of the ischemic zone, and this was associated with a significant reduction in myocardial interstitial fluid (MIF) ADMA. The decrease in MIF ADMA during ischemia was likely due to increased DDAH1 because myocardial protein arginine N-methyl transferase 1 (PRMT1) and the methylated arginine protein content (the source of ADMA) were unchanged or increased, respectively, at this time. The inflammatory mediators interleukin (IL-1β) and tumor necrosis factor (TNF-α) were also elevated in the midmyocardium where DDAH1 expression was increased. Both of these factors significantly up-regulated DDAH1 expression in cultured human coronary artery endothelial cells. Taken together, these results suggest that inflammatory factors expressed in response to myocardial ischemia contributed to up-regulation of DDAH1, which was responsible for the decrease in MIF ADMA.

Endocan, TGF-beta, and ADMA as Risk Factors for Endothelial Dysfunction and Possible Vascular Disease in Patients with Subclinical Hypothyroidism.

PubMed

Arpaci, Dilek; Karakece, Engin; Tocoglu, Aysel Gurkan; Ergenc, Hasan; Gurol, Gonul; Ciftci, Ihsan Hakki; Tamer, Ali

2016-12-01

Although the relationship between atherosclerosis and overt hypothyroidism has been confirmed, it remains controversial in cases of subclinical hypothyroidism. Higher TSH and similar T4 suggest differences in set-points or differences due to diagnostic limitations regarding subclinical hypothyroidism. Endothelial dysfunction (ED) is a marker rather than a precursor of cardiovascular disease. Asymmetric dimethylarginine (ADMA) and endocan are known as novel markers of ED in various diseases. Transforming growth factor-beta (TGF-β) has a protective role against autoimmune diseases such as thyroiditis. This study aimed to determine the relationships between serum ADMA, endocan, TGF-β, and the high-sensitivity C-reactive protein (hs-CRP) levels, a proven indicator of ED, in patients with SH. Thirty-five patients with SH and 21 age- and sex-matched euthyroid subjects were included in the study. The levels of TSH, FT4, lipid parameters, endocan, ADMA, TGF-β, and hs-CRP were measured. No significant differences in age or sex were found between the patient and control groups (p=0.294 and 0.881, respectively). Mean TSH level was higher in the patient group (p=0.005), whereas mean fT4 level was similar in two groups (p=0.455). The average hs-CRP, endocan, TGF-β l level in the patient group was higher than control group (p=0.001; P=0.012; P=0.025; P<0.01 respectively). A positive correlation was found between the endocan and ADMA levels (r=0.760, p=0.000). ADMA levels also were positively correlated with hs-CRP. Both the TSH and low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with the hs-CRP level. Subclinical hypothyroidism is associated with increased levels of serum endocan, ADMA, and TGF-β, which are new markers for ED. In particular, ADMA was correlated with both endocan and hs-CRP levels. These findings are suggestive for increased risk of ED and subsequent development of atherosclerosis in patients with SH. © 2016 by the Association of Clinical Scientists, Inc.

Effect of 18β-glycyrrhetinic acid on cerebral vasospasm caused by asymmetric dimethylarginine after experimental subarachnoid hemorrhage in rats.

PubMed

Zhao, Dong; Liu, Qi; Ji, Yunxiang; Wang, Ganggang; He, Xuejun; Tian, Weidong; Xu, Hui; Lei, Ting; Wang, Yezhong

2015-06-01

Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is characterized by the severe constriction of an artery, which often leads to unfavorable outcomes. CVS after SAH is closely associated with asymmetric dimethylarginine (ADMA) and connexin. The effect of 18β-glycyrrhetinic acid (18β-GA), an inhibitor of gap junction, on ADMA, connexin, and CVS after SAH were investigated. Sprague-Dawley rats (n  =  120), weighing 300-350 g, were divided into the control group, sham, SAH, and SAH + 18β-GA groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats, and 18β-GA (10 mg/kg) was intraperitoneally injected. The neurological score, basilar artery diameter, ADMA, and connexin protein contents (Cx40, Cx43, and Cx45) were measured using Kaoutzanis scoring system, pressure myograph, enzyme linked immunosorbent assay kit, and Western blot, respectively, 1, 3, 5, 7, and 14 days after SAH. The neurological score significantly decreased 3, 5, 7, and 14 days after SAH. The basilar artery diameter significantly decreased, and the ADMA level in the cerebrospinal fluid (CSF) significantly increased at all time points. The level of Cx40 significantly decreased on days 3, 5, 7, and 14, and the level of Cx43 and Cx45 significantly increased at all time points. ADMA and Cx43 are positively correlated. However, the upregulated level of ADMA, Cx43, and Cx45 were attenuated. The neurology result significantly improved in the SAH + 18β-GA group. Treatment with 18β-GA in SAH rats decreases Cx43 and Cx45 in basilar artery and ADMA in CSF. ADMA is probably involved in the pathophysiological events of CVS after SAH by altering connexin proteins. The mechanism of connexin protein changes caused by ADMA needs to be further studied.

MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.

PubMed

Di Pasqua, Laura G; Berardo, Clarissa; Rizzo, Vittoria; Richelmi, Plinio; Croce, Anna Cleta; Vairetti, Mariapia; Ferrigno, Andrea

2016-08-01

Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH.

Protective effects of low-dose rosuvastatin on isoproterenol-induced chronic heart failure in rats by regulation of DDAH-ADMA-NO pathway.

PubMed

Zhou, Ru; Ma, Ping; Xiong, Aiqin; Xu, Yehua; Wang, Yang; Xu, Qingbin

2017-04-01

Cardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms. Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection. Simultaneously, low-dose rosuvastatin (5 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by hemodynamic parameter, histopathological variables, serum asymmetric dimethylarginine (ADMA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and myocardial nitric oxide (NO), and the levels of dimethylarginine dimethylaminohydrolase 2 (DDAH2), arginine methyltransferases 1 (PRMT1) and endothelial nitric oxide synthase (eNOS) expression were analyzed. Therapeutic rosuvastatin (5 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of ventricle, reduced the increased serum content of ADMA, cTnI, and BNP, and elevated myocardial NO in rats (P<.05). Besides, rosuvastatin also significantly inhibited fibrosis of myocardium, normalized the increased PRMT1 and decreased DDAH2 expression. Low-dose rosuvastatin exerted cardioprotective effects on isoproterenol-induced heart failure in rats by modulating DDAH-ADMA-NO pathway, and it may present the new therapeutic value in ameliorating chronic heart failure. © 2016 John Wiley & Sons Ltd.

Effect of vildagliptin add-on treatment to metformin on plasma asymmetric dimethylarginine in type 2 diabetes mellitus patients.

PubMed

Cakirca, Mustafa; Karatoprak, Cumali; Zorlu, Mehmet; Kiskac, Muharrem; Kanat, Mustafa; Cikrikcioglu, Mehmet Ali; Soysal, Pinar; Hursitoglu, Mehmet; Camli, Ahmet Adil; Erkoc, Reha; Abdul-Ghani, Muhammad

2014-01-01

A close association has been demonstrated between increased cardiovascular risk and high asymmetric dimethylarginine (ADMA) levels in type 2 diabetes mellitus (DM) patients. We planned to measure serum ADMA levels in type 2 DM patients using vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. A total of 68 type 2 DM patients who were on metformin were enrolled in the study. Based on the glycemic levels of patients, vildagliptin was added on to treatment in 33 patients. Patients were followed for 6 months. Serum ADMA, C-reactive protein, and fibrinogen levels were compared in groups of patients using metformin or metformin + vildagliptin, after 6 months. Serum ADMA levels were found to be significantly lower in the group using vildagliptin compared to the group using metformin + vildagliptin (P<0.001). However, serum C-reactive protein and fibrinogen levels were statistically similar in the two study groups (P=0.34 and P=0.23, respectively). Metformin + vildagliptin treatment was observed to lower serum ADMA levels in type 2 DM patients. Our findings notwithstanding, large-scale prospective randomized controlled studies are warranted to conclude that vildagliptin provides cardiovascular protection along with diabetes regulation.

Effect of alpha-lipoic acid on asymmetric dimethylarginine and disability in multiple sclerosis patients: A randomized clinical trial.

PubMed

Khalili, Mohammad; Soltani, Madjid; Moghadam, Shirin Amiri; Dehghan, Parvin; Azimi, Amirreza; Abbaszadeh, Omid

2017-07-01

Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system. Oxidative stress plays a major role in the onset and progression of MS. Asymmetric dimethylarginine (ADMA) formation is dependent on oxidative stress status. We examined whether alpha-lipoic acid (ALA) as a potent antioxidant could improve the Expanded Disability Status Scale (EDSS) and decrease plasma level of ADMA in multiple sclerosis patients. In a randomized, double-blinded clinical trial conducted at Sina Hospital in Tehran, Iran, from September 2009 to July 2011, 24 patients with relapsing-remitting MS were divided into a treatment group receiving ALA (1200mg/day) for 12 weeks and a control group receiving placebo. Then patients' EDSS and Plasma levels of ADMA were measured at baseline and 12 weeks later. Statistical analysis was done by SPSS software version 16 using the K-S test, Chi square, Mann-Whitney U-test and Wilcoxon test. The plasma levels of ADMA in the intervention group were decreased significantly (p=0.04). Also, no patient had increased EDSS score in the supplement group, where 2 out of 12 patients in the placebo group experienced so. Comparing the serum level of ADMA between the two groups failed to show any significant change in the supplement group compared with the control group. Considering that ADMA is produced by oxidative stress in MS patients and leads to increase of inflammation, ALA may have the potential of beneficial effects in them, in part, by decreasing the plasma level of ADMA and stopping progression. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: No. IRCT138812222602N2. The authors received no financial support for the research, authorship, and/or publication of this article.

Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

PubMed Central

Schlesinger, Sabrina; Sonntag, Svenja R.

2016-01-01

Background A growing number of studies linked elevated concentrations of circulating asymmetric (ADMA) and symmetric (SDMA) dimethylarginine to mortality and cardiovascular disease (CVD) events. To summarize the evidence, we conducted a systematic review and quantified associations of ADMA and SDMA with the risks of all-cause mortality and incident CVD in meta-analyses accounting for different populations and methodological approaches of the studies. Methods Relevant studies were identified in PubMed until February 2015. We used random effect models to obtain summary relative risks (RR) and 95% confidence intervals (95%CIs), comparing top versus bottom tertiles. Dose-response relations were assessed by restricted cubic spline regression models and potential non-linearity was evaluated using a likelihood ratio test. Heterogeneity between subgroups was assessed by meta-regression analysis. Results For ADMA, 34 studies (total n = 32,428) investigating associations with all-cause mortality (events = 5,035) and 30 studies (total n = 30,624) investigating the association with incident CVD (events = 3,396) were included. The summary RRs (95%CI) for all-cause mortality were 1.52 (1.37–1.68) and for CVD 1.33 (1.22–1.45), comparing high versus low ADMA concentrations. Slight differences were observed across study populations and methodological approaches, with the strongest association of ADMA being reported with all-cause mortality in critically ill patients. For SDMA, 17 studies (total n = 18,163) were included for all-cause mortality (events = 2,903), and 13 studies (total n = 16,807) for CVD (events = 1,534). High vs. low levels of SDMA, were associated with increased risk of all-cause mortality [summary RR (95%CI): 1.31 (1.18–1.46)] and CVD [summary RR (95%CI): 1.36 (1.10–1.68) Strongest associations were observed in general population samples. Conclusions The dimethylarginines ADMA and SDMA are independent risk markers for all-cause mortality and CVD across different populations and methodological approaches. PMID:27812151

Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with type I diabetes mellitus.

PubMed

Chrysis, Dionisios; Efthymiadou, Alexandra; Mermigka, Alexandra; Kritikou, Dimitra; Spiliotis, Bessie E

2017-06-01

Patients with type I diabetes mellitus (T1DM) have increased incidence of atherosclerosis and cardiovascular disease. Although these complications are unusual in children with T1DM, prevention, and early intervention could decrease morbidity and mortality. Osteoprotegerin (OPG), asymmetric dimethylarginine (ADMA), and Fetuin-A have been associated with increased cardiovascular risk (CVR). Increased OPG and ADMA, and decreased or increased Fetuin-A serum levels have been associated with increased CVR. Because patients with T1DM have higher CVR we investigated OPG, ADMA, and Fetuin-A, in children with T1DM. We determined the serum levels of OPG, receptor activator of nuclear factor-κB ligand (RANKL), ADMA, and Fetuin-A by enzyme-linked immunosorbent assay (ELISA) in 56 children with T1DM aged 12.1 ± 3.4 yr and in 46 normal control children, (C) aged 11.3 ± 3.0 yr. Serum OPG levels were significantly increased in patients with T1DM (3.352 ± 0.73 pmol/L) compared with C (2.75 ± 0.67 pmol/L, p < 0.0001) but RANKL did not change. ADMA was significantly decreased in T1DM compared with C (0.68 ± 0.13 µmol/L versus 0.82 ± 0.18 µmol/L, p < 0.0001). Fetuin-A was similar in T1DM (0.551 ± 0.13 g/L) and C (0.540 ± 0.11 g/L) subjects. OPG was positively associated with glycosylated hemoglobin A1c (p < 0.001) and negatively associated with BMI (p < 0.01). ADMA and Fetuin-A were not associated with A1c and ADMA was only negatively associated with age (p < 0.05). OPG is increased, ADMA is decreased, but RANKL and Fetuin-A are unchanged in T1DM children. Whereas increased OPG has been firmly related to increased CVR, more studies, especially longitudinal studies, are needed to delineate the role and clinical significance of decreased ADMA and if Fetuin-A has any role in T1DM. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment.

PubMed

Kilic, Sevtap; Yilmaz, Nafiye; Zulfikaroglu, Ebru; Erdogan, Gokcen; Aydin, Murat; Batioglu, Sertac

2011-09-01

Our aim was to evaluate the optimal treatment strategy addressing cardiovascular risk in obese and nonobese patients with polycystic ovary syndrome (PCOS). We planned a prospectıve randomized clinical study. Normoandrogenemic and oligoamenorrheic women with PCOS and impaired glucose tolerance (n = 96) were enrolled in the study. Six months of treatment with metformin HCL or oral contraceptive pills (OCPs) were given to the patients. Group 1 were obese and receiving metformin. Group 2 were obese and receiving OCPs. Group 3 were nonobese and receiving metformin, and Group 4 were nonobese receiving OCPs. ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated. ADMA, homocysteine, hs-CRP and HOMA-IR were similar in obese and nonobese groups before the treatment. After 6 months of treatment, a significant decrease was observed in ADMA, homocysteine and HOMA-IR levels in Groups 1 and 3. An increase in ADMA and hs-CRP levels was observed in Groups 2 and 4. In this study, metformin treatment leads to improvement in hormonal and metabolic parameters and decreases ADMA and homocysteine levels possibly independent of BMI. However, the use of oral contraceptives in obese and nonobese patients with PCOS with impaired glucose tolerance increases ADMA and hs-CRP levels and creates an increase in the metabolic risk.

Effect of vildagliptin add-on treatment to metformin on plasma asymmetric dimethylarginine in type 2 diabetes mellitus patients

PubMed Central

Cakirca, Mustafa; Karatoprak, Cumali; Zorlu, Mehmet; Kiskac, Muharrem; Kanat, Mustafa; Cikrikcioglu, Mehmet Ali; Soysal, Pinar; Hursitoglu, Mehmet; Camli, Ahmet Adil; Erkoc, Reha; Abdul-Ghani, Muhammad

2014-01-01

Aims A close association has been demonstrated between increased cardiovascular risk and high asymmetric dimethylarginine (ADMA) levels in type 2 diabetes mellitus (DM) patients. We planned to measure serum ADMA levels in type 2 DM patients using vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. Materials and methods A total of 68 type 2 DM patients who were on metformin were enrolled in the study. Based on the glycemic levels of patients, vildagliptin was added on to treatment in 33 patients. Patients were followed for 6 months. Serum ADMA, C-reactive protein, and fibrinogen levels were compared in groups of patients using metformin or metformin + vildagliptin, after 6 months. Results Serum ADMA levels were found to be significantly lower in the group using vildagliptin compared to the group using metformin + vildagliptin (P<0.001). However, serum C-reactive protein and fibrinogen levels were statistically similar in the two study groups (P=0.34 and P=0.23, respectively). Conclusion Metformin + vildagliptin treatment was observed to lower serum ADMA levels in type 2 DM patients. Our findings notwithstanding, large-scale prospective randomized controlled studies are warranted to conclude that vildagliptin provides cardiovascular protection along with diabetes regulation. PMID:24627624

The usefulness of plasma asymmetric dimethylarginine (ADMA) levels and tissue doppler echocardiography for heart function in term infants born to mothers with gestational diabetes mellitus.

PubMed

Arslan, Derya; Oran, Bulent; Vatansev, Husamettin; Cimen, Derya; Guvenc, Osman

2013-11-01

The aim of this study was to examine whether asymmetric dimethylarginine (ADMA) concentrations are associated with ventricular function in the infants of mothers with gestational diabetes. Twenty-five term newborns of mothers with gestational diabetes and term newborns as the control group (n = 25) with normal general health status were evaluated at two time points, on the 3rd postnatal day, at the 3th months. Echocardiographic evaluations of all participants were performed and ADMA level was measured. In the first analysis, 10 patients (40%) had a septal thickness of 6 mm or more, indicating septal hypertrophy. In the first and second analysis, interventricular septum end-diastolic thickness (IVSTd) and the left ventricular posterior wall end-diastolic thickness (LVPWTd) in the patient group were higher than the control group. ADMA level measurement was not significantly different between the groups the first and second analysis. There was no difference in ADMA levels of the group with septal thickness ≥6 mm and the group with <6 mm. Newborn cardiac wall thickness was increased in pregnancies complicated by Gestational diabetes mellitus (GDM), and the increase was independent of glycemic control. Diastolic newborn cardiac function was impaired in GDM, and this effect was independent of septal thickness. We found no association between ADMA levels and cardiac systolic, diastolic functions or septum thickness in the GDM newborn.

Body size, but neither age nor asymptomatic mitral regurgitation, influences plasma concentrations of dimethylarginines in dogs.

PubMed

Pedersen, L G; Tarnow, I; Olsen, L H; Teerlink, T; Pedersen, H D

2006-06-01

Asymmetric dimethylarginine (ADMA) is a marker of various cardiovascular diseases in man. The aim of the present study was to test if Cavalier King Charles Spaniels (CKCS) with varying degrees of mitral regurgitation (MR) had increased plasma concentration of ADMA and furthermore, characterize the plasma level of ADMA and symmetric dimethylarginine (SDMA) in normal dogs. Seventy-six dogs were included (44 CKCS and 32 dogs of other breeds). The CKCS had various degrees of MR, whereas the remaining dogs had either no or minimal MR. Apart from cardiac murmurs, no dogs showed signs of cardiac or systematic disease. The degree of MR had no significant influence on ADMA (P = 0.33). Body weight was directly associated with ADMA (P = 0.0004) and creatinine was directly associated with SDMA (P<0.0001). Furthermore, the plasma concentration of ADMA was three to four times higher than found in healthy humans.

l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy.

PubMed

Szabo, P; Lantos, J; Nagy, L; Keki, S; Volgyi, E; Menyhei, G; Illes, Z; Molnar, T

2016-12-01

Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis and is a marker of atherosclerosis. This study examined the correlation between pre-operative l-arginine and ADMA concentration during carotid endarterectomy (CEA), and jugular lactate indicating anaerobic cerebral metabolism, jugular S100B reflecting blood-brain barrier integrity, and with factors of surgical intervention. The concentration of l-arginine, ADMA, and symmetric dimethylarginine was measured in blood taken under regional anaesthesia from the radial artery of 55 patients prior to CEA. Blood gas parameters, concentration of lactate, and S100B were also serially measured in blood taken from both the radial artery and the jugular bulb before and after carotid clamping, and after release of the clamp. To estimate anaerobic metabolism, the jugulo-arterial ratio of CO 2 gap/oxygen extraction was calculated. Positive correlation was found between pre-operative ADMA levels and the ratio of jugulo-arterial CO 2 gap/oxygen extraction during clamp and reperfusion (p = .005 and p = .01, respectively). An inverse correlation was found between the pre-operative l-arginine concentration and jugular lactate at each time point (both p = .002). The critical pre-operative level of l-arginine was determined by receiver operator curve analysis. If l-arginine was below the cutoff value of 35 μmol/L, jugular S100B concentration was higher 24 h post-operatively (p = .03), and jugular lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range 42.3-74.5 μmol/L]; p = .002). High pre-operative ADMA concentration predicts poor cerebral perfusion indicated by elevated jugulo-arterial CO 2 gap/oxygen extraction. Low pre-operative l-arginine concentration predicts the need for a shunt. The inverse correlation between pre-operative l-arginine concentration and both jugular lactate and S100B during carotid clamping suggests a protective role of the NO donor l-arginine. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

High asymmetric dimethylarginine, symmetric dimethylarginine and L-arginine levels in migraine patients.

PubMed

Reyhani, Aylin; Celik, Yahya; Karadag, Hakan; Gunduz, Ozgur; Asil, Talip; Sut, Necdet

2017-07-01

Experimental and clinical data strongly suggests that nitric oxide (NO) plays a pivotal role in migraine. This is also supported by studies of migraine induced by substances that release NO. NO is synthesized from L-arginine by endothelial NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is the major endogenous competitive inhibitor of NOS. Symmetric dimethylarginine (SDMA) is an inactive stereoisomer of ADMA. It may reduce NO production by competing with arginine for cellular uptake. The aim of this study was to measure the levels of ADMA, SDMA and L-arginine in migraine patients during the interictal period. One hundred migraine patients and 100 healthy volunteers were recruited. The patients were in the interictal period and classified into two groups as having migraine with aura and migraine without aura. Their serum ADMA, SDMA and L-arginine levels were measured by high-performance liquid chromotography (HPLC) method. ADMA, SDMA and L-arginine levels were significantly higher in migraine patients compared to the control group. But there was no difference between the patients with and without aura. These results suggest that NOS inhibitors and L-arginine/NO pathway plays an important role in migraine pathopysiology.

Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia.

PubMed

Doshi, Sagar; McDowell, Ian; Goodfellow, Jonathan; Stabler, Sally; Boger, Rainer; Allen, Robert; Newcombe, Robert; Lewis, Malcolm; Moat, Stuart

2005-03-01

Experimental hyperhomocysteinemia after an oral methionine or homocysteine load is associated with impaired nitric oxide-dependent vasodilatation in healthy human beings. However, it remains unproven that this effect is mediated by elevations in plasma homocysteine. There is evidence that an increase in plasma homocysteine may increase the formation of asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase. The methyl groups within ADMA are derived from the conversion of S -adenosylmethionine to S -adenosylhomocysteine intermediates in the methionine/homocysteine pathway. No previous study has assessed the role of methylation status, its impact on ADMA formation, and their association with endothelial function in healthy human beings. In a randomized, placebo-controlled, crossover study, 10 healthy subjects (mean age, 29.1 +/- 3.9 years) were administered an oral dose of methionine (0.1 g/kg), l -homocysteine (0.01 g/kg), N-acetylcysteine (NAC) (0.1 g/kg), or placebo. Endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery was impaired after both the methionine and homocysteine load compared with placebo at 4 hours (36 +/- 15, 67 +/- 23 vs 219 +/- 26 microm, respectively, P < .001). N-Acetylcysteine had no effect on flow-mediated dilatation. Plasma total homocysteine was significantly elevated at 4 hours after methionine (23.1 +/- 6.2) and homocysteine (41.5 +/- 8.9) loading, but significantly reduced after NAC 2.4 +/- 0.6 vs 7.1 +/- 2.1 micromol/L in the placebo (P < .001). Plasma S-adenosylmethionine/S-adenosylhomocysteine ratio was significantly (P < .001) increased at 4 hours after methionine (10.9 +/- 0.7) compared with homocysteine (5.4 +/- 0.4), NAC (5.0 +/- 0.3), and placebo (6.0 +/- 0.5). Plasma ADMA concentrations were not altered by any intervention. Our results suggest that endothelial dysfunction due to methionine or homocysteine loading is not associated with an increase in plasma ADMA or a disruption in methylation status.

Determination of Asymmetric and Symmetric Dimethylarginine in Serum from Patients with Chronic Kidney Disease: UPLC-MS/MS versus ELISA.

PubMed

Boelaert, Jente; Schepers, Eva; Glorieux, Griet; Eloot, Sunny; Vanholder, Raymond; Lynen, Frédéric

2016-05-13

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, and its structural isomer symmetric dimethylarginine (SDMA) are uremic toxins accumulating in chronic kidney disease (CKD) patients. The objective of this study was to develop and validate a robust UPLC-MS/MS method for the simultaneous determination of ADMA and SDMA in human serum. Chromatographic separation after butyl ester derivatization was achieved on an Acquity UPLC BEH C18 column, followed by tandem mass spectrometric detection. After validation, the applicability of the method was evaluated by the analysis of serum samples from 10 healthy controls and 77 CKD patients on hemodialysis (CKD5HD). Both ADMA (0.84 ± 0.19 µM vs. 0.52 ± 0.07 µM) and SDMA concentrations (2.06 ± 0.82 µM vs. 0.59 ± 0.13 µM) were significantly (p < 0.001) elevated in CKD5HD patients compared to healthy controls. In general, low degrees of protein binding were found for both ADMA and SDMA. In addition, an established commercially available ELISA kit was utilized on the same samples (n = 87) to compare values obtained both with ELISA and UPLC-MS/MS. Regression analysis between these two methods was significant (p < 0.0001) but moderate for both ADMA (R = 0.78) and SDMA (R = 0.72).

Skin autofluorescence as a novel marker of vascular damage in children and adolescents with chronic kidney disease.

PubMed

Makulska, Irena; Szczepańska, Maria; Drożdż, Dorota; Polak-Jonkisz, Dorota; Zwolińska, Danuta

2015-05-01

Skin autofluorescence (sAF) was examined as a marker of the accumulation of advanced glycation end products (AGEs) in tissues of children with chronic kidney disease (CKD) in relation to renal function, dialysis modality and markers of endothelial inflammation and dysfunction. A total of 76 children with CKD were enrolled in the study, of whom 20 children were on hemodialysis (HD), 20 were on peritoneal dialysis (PD) and 36 were treated conservatively. A control group of 26 healthy subjects was also included in the study. In all children, sAF intensity, carotid intima-media (cIMT) thickness and plasma concentrations of sE-selectin, matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and plasminogen activator inhibitor type 1 (PAI-1) were measured. Compared to the controls, children with CKD had significantly elevated sAF levels. sAF in the children with CKD was positively correlated with sE-selectin, MMP-9, TIMP-1, ADMA, SDMA and PAI-1 levels. In the predialysis group (conservative treatment) sAF levels were positively correlated with sE-selectin and ADMA levels and negatively correlated with glomerular filtration rate. Multiple regression analysis showed a significant association of sAF with sE-selectin and MMP-9 in CKD children. The results reveal that AGEs were accumulated in the children with CKD. This accumulation was related to early vascular changes and a number of biochemical vascular risk markers. sAF measurement, as a noninvasive method, may be useful for identification of clinical risk factors of vascular disease in CKD children.

Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D.

PubMed

Ngo, D T M; Chan, W P; Rajendran, S; Heresztyn, T; Amarasekera, A; Sverdlov, A L; O'Loughlin, P D; Morris, H A; Chirkov, Y Y; Norman, R J; Horowitz, J D

2011-10-30

Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects; this may contribute to the increased cardiovascular risk associated with this syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

PubMed

Osorio-Yáñez, Citlalli; Chin-Chan, Miguel; Sánchez-Peña, Luz C; Atzatzi-Aguilar, Octavio G; Olivares-Reyes, Jesus A; Segovia, José; Del Razo, Luz M

2017-08-01

Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5μM of arsenite for 24h. We proved that arsenite at 5μM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5μM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5μM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Asymmetric dimethylarginine in young people with Type 1 diabetes: a paradoxical association with HbA(1c).

PubMed

Marcovecchio, M L; Widmer, B; Turner, C; Dunger, D B; Dalton, R N

2011-06-01

Asymmetric dimethylarginine (ADMA) is an independent risk factor for cardiovascular disease and its concentrations are increased in several diseases, including diabetes. However, there is limited information on this plasma marker in young people, particularly in those with Type 1 diabetes. The aim of the present study was therefore to perform a longitudinal evaluation of plasma ADMA and of its determinants in young people with childhood-onset Type 1 diabetes. For measurement of ADMA using mass spectrometry, 1018 longitudinal stored blood samples were available from 330 young people with Type 1 diabetes followed in the Oxford Regional Prospective Study. Additional data concerning annual assessments of HbA(1c) , height, weight, insulin dose and three early morning urine samples for measurement of the albumin/creatinine ratio were available. ADMA levels were significantly higher in males than in females (mean ± SD: 0.477 ± 0.090 vs. 0.460 ± 0.089 μmol/l, P=0.002) and declined with chronological age (estimate ± SE: -0.0106 ± 0.0008, P<0.001). A significant inverse association was detected between ADMA and HbA(1c) (estimate ± SE:-0.0113 ± 0.001, P<0.001). ADMA levels were lower in subjects developing microalbuminuria (mean ± SD: 0.455 ± 0.093 vs. 0.476 ± 0.087 μmol/l, P=0.001) than in subjects with normoalbuminuria, but this difference disappeared after adjusting for HbA(1c) . In this longitudinal study, ADMA concentrations decreased with age and were significantly higher in males and lower in subjects developing microalbuminuria. These associations were largely explained by a paradoxical negative association between HbA(1c) and ADMA. We suggest that chronic hyperglycaemia might down-regulate mechanisms implicated in ADMA production or stimulate its metabolism confounding short-term associations with complications risk. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Association between vitamin D status and asymmetric dimethylarginine (ADMA) concentration in the Korean elderly population.

PubMed

Choi, Hye Rin; Lee, Seung Won; Yeom, Hyungseon; Jeon, Da-Hye; Kim, Hyeon Chang; Youm, Yoosik

2017-08-01

Vitamin D deficiency has been reported to be associated with the risk of cardiovascular disease. We investigated the relationship between vitamin D status and asymmetric dimethylarginine (ADMA) concentration, a marker of endothelial dysfunction, in the Korean elderly population. A cross-sectional study was conducted on 269 men and 382 women (mean age, 71.6 years) enrolled in the Korean Social Life, Health, and Aging Project (KSHAP), a population-based longitudinal study of health determinants in elderly Koreans. We stratified patients by vitamin D status into three groups according to serum 25-hydroxyvitamin D [25(OH)D] level: sufficient (≥30ng/mL, n=25), insufficient (10-<30ng/mL, n=516), and deficient (<10ng/mL, n=110). To measure endothelial dysfunction, ADMA concentration was assayed by high-performance liquid chromatography. The association between 25(OH)D status and ADMA concentration was analyzed by multiple linear regression models. The mean ADMA concentration was significantly higher in the insufficient 25(OH)D group (0.665μmol/L, p=0.001) and the deficient 25(OH)D group (0.734μmol/L, p<0.001) compared with the sufficient 25(OH)D group (0.589μmol/L). Even after adjusting for sex, age, body mass index, blood pressure, diabetes mellitus, total and HDL cholesterol, estimated glomerular filtration rate (eGFR), smoking status, and drinking status, ADMA concentrations were higher in the insufficient group (β=0.0742μmol/L, p=0.001) and the deficient group (β=0.1417μmol/L, p<0.001) compared than in the sufficient group. In a sex-stratified analysis, 25(OH)D deficiency was associated with higher ADMA levels in both women (p<0.001) and men (p=0.007), while 25(OH)D deficiency was associated with higher ADMA levels in women (p<0.001) but not in men (p=0.631). Our findings suggest that low serum 25(OH)D level may be associated with endothelial dysfunction in elderly Korean people. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

PubMed

Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

2016-01-01

To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

Angiotensin-converting Enzyme Inhibition Improves the Effectiveness of Transcutaneous Carbon Dioxide Treatment

PubMed Central

NEMETH, BALAZS; KISS, ISTVAN; JENCSIK, TIMEA; PETER, IVAN; KRESKA, ZITA; KOSZEGI, TAMAS; MISETA, ATTILA; KUSTAN, PETER; BONCZ, IMRE; LACZO, ANDREA; AJTAY, ZENO

2017-01-01

Aim: To study the effect of carbon dioxide (CO2) therapy on the nitric oxide (NO) pathway by monitoring plasma asymmetric dimethylarginine (ADMA) concentrations. Patients and Methods: Forty-seven hypertensive patients who underwent transcutaneous CO2 therapy were enrolled. Thirty healthy individuals were recruited for the control group. Blood samples were taken one hour before, as well as one hour, 24 hours and 3 weeks after the first CO2 treatment. Controls did not undergo CO2 treatment. Plasma ADMA levels were measured by ELISA. Results: ADMA levels decreased significantly one hour after the first CO2 treatment compared to the baseline concentrations (p=0.003). Significantly greater reduction was found among patients in whom angiotensin converting enzyme inhibitors (ACEIs) were administered (p=0.019). Conclusion: The short- and long-term decrease of ADMA levels suggests that CO2 is not only a vasodilator, but also has a beneficial effect on the NO pathway. ACE inhibition seems to enhance the effect of CO2 treatment. PMID:28438873

Oxidative stress in patients with essential hypertension: a comparison of dippers and non-dippers.

PubMed

Gönenç, Aymelek; Hacışevki, Aysun; Tavil, Yusuf; Çengel, Atiye; Torun, Meral

2013-03-01

Oxidative stress seems to play an important role in the pathophysiology of essential hypertension. We aimed to examine serum MDA, NO, 8-OHdG, ADMA, NT, CoQ10 and TAC as biomarkers of oxidative stress in dipper and non-dipper hypertensive patients. Eighteen dipper hypertensives, 20 non-dipper hypertensives and 22 healthy control subjects were included in the study. Clinical assessment and ambulatory blood pressure monitoring were performed in patients. Serum MDA, TAC and NO levels were measured by using spectrophotometric methods. CoQ10 levels were measured by HPLC method. 8-OHdG, ADMA and NT were quantitated by ELISA methods. MDA levels were significantly higher in dipper and non-dipper groups compared to controls (p<0.05 and p<0.01, respectively). TAC levels were found at low level in patients dipper and non-dipper patients compared to control group (p<0.01). Higher ADMA and NT levels but lower CoQ10 levels were found in non-dipper group compared to healthy controls (p<0.01, p<0.05, and p<0.05, respectively). ADMA levels were found higher in non-dipper group than those of dipper group (p<0.01). Increased ADMA, NT levels and decreased CoQ10 levels in non-dipper hypertensive patients might indicate more severe oxidative stres compared with dipper hypertensive patients, which plays an important role in the development of cardiovascular diseases. Increased MDA and reduced TAC levels might be considered as prospective prognostic markers of the development of cardiovascular diseases in dipper and non-dipper hypertensive patients. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Influence on serum asymmetric dimethylarginine (ADMA) concentrations of human paraoxonase 1 polymorphism (Q192R) and exposure to polycyclic aromatic hydrocarbons (PAHs) in Mexican women, a gene-environment interaction.

PubMed

Ochoa-Martínez, Ángeles C; Ruíz-Vera, Tania; Almendarez-Reyna, Claudia I; Orta-García, Sandra T; Pérez-Maldonado, Iván N

2017-11-01

It has been demonstrated that Cardiovascular Diseases (CVD) are a consequence of the combination of genetic and environmental factors and/or the interaction between them. Therefore, the aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbon (PAHs) exposure and PON1 Q192R polymorphism (genetic susceptibility) on serum asymmetric dimethylarginine (ADMA) levels in Mexican women (n = 206). Urinary 1-hydroxypyrene concentrations (1-OHP; exposure biomarker for PAHs) were quantified using a high-performance liquid chromatography technique, PON1 Q192R polymorphism was genotyped using TaqMan probes and serum ADMA concentrations were evaluated using a commercially available ELISA kit. Urinary 1-OHP levels detected in this study ranged from 0.07 to 9.37 μmol/mol of creatinine (0.13-18.0 μg/g of creatinine). Regarding allele frequency (PON1 Q192R polymorphism), the 192Q-allele frequency was 0.43 and for the 192R-allele it was 0.57. In relation to serum ADMA levels, the levels ranged from 0.06 to 1.46 μmol/L. Moreover, multiple linear regression analysis was performed and associations between urinary 1-OHP levels (β = 0.05, p = 0.002), PON1 Q192R polymorphism (β = 0.04, p = 0.003) and serum ADMA concentrations were found. Besides, an interaction (gene-environment interaction) of both independent variables (1-OHP and PON1 polymorphism) on serum ADMA levels was found (β = 0.04, p = 0.02) in the constructed multiple linear model. Therefore, according to the significance of this research, it is necessary to execute health programs to reduce cardiovascular risk in the assessed population. Copyright © 2017 Elsevier Ltd. All rights reserved.

The relationship of nitric oxide synthesis capacity, oxidative stress, and albumin-to-creatinine ratio in black and white men: the SABPA study.

PubMed

Mels, Catharina M C; Huisman, Hugo W; Smith, Wayne; Schutte, Rudolph; Schwedhelm, Edzard; Atzler, Dorothee; Böger, Rainer H; Ware, Lisa J; Schutte, Aletta E

2016-02-01

Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R (2) = 0.15; β = -0.20; p = 0.050) and GPx/SOD ratio (R (2) = 0.24; β = -0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R (2) = 0.18; β = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R (2) = 0.26; β = -0.29; p = 0.002) and GR/GPx ratio (R (2) = 0.25; β = -0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

NASA Astrophysics Data System (ADS)

Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2017-12-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio.

PubMed

Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2018-05-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O 2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

NASA Astrophysics Data System (ADS)

Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2018-05-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation.

PubMed

Lundgren, Jakob; Sandqvist, Anna; Hedeland, Mikael; Bondesson, Ulf; Wikström, Gerhard; Rådegran, Göran

2018-04-12

Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

Angiotensin-converting Enzyme Inhibition Improves the Effectiveness of Transcutaneous Carbon Dioxide Treatment.

PubMed

Nemeth, Balazs; Kiss, Istvan; Jencsik, Timea; Peter, Ivan; Kreska, Zita; Koszegi, Tamas; Miseta, Attila; Kustan, Peter; Boncz, Imre; Laczo, Andrea; Ajtay, Zeno

2017-01-01

To study the effect of carbon dioxide (CO 2 ) therapy on the nitric oxide (NO) pathway by monitoring plasma asymmetric dimethylarginine (ADMA) concentrations. Forty-seven hypertensive patients who underwent transcutaneous CO 2 therapy were enrolled. Thirty healthy individuals were recruited for the control group. Blood samples were taken one hour before, as well as one hour, 24 hours and 3 weeks after the first CO 2 treatment. Controls did not undergo CO 2 treatment. Plasma ADMA levels were measured by ELISA. ADMA levels decreased significantly one hour after the first CO2 treatment compared to the baseline concentrations (p=0.003). Significantly greater reduction was found among patients in whom angiotensin converting enzyme inhibitors (ACEIs) were administered (p=0.019). The short- and long-term decrease of ADMA levels suggests that CO 2 is not only a vasodilator, but also has a beneficial effect on the NO pathway. ACE inhibition seems to enhance the effect of CO 2 treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

PubMed

Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

2018-03-01

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

De novo synthesis of trideuteromethyl esters of amino acids for use in GC-MS and GC-tandem MS exemplified for ADMA in human plasma and urine: standardization, validation, comparison and proof of evidence for their aptitude as internal standards.

PubMed

Tsikas, Dimitrios

2009-08-01

Asymmetric dimethylarginine (ADMA, N(G),N(G)-dimethyl-L-arginine) is an endogenous inhibitor of nitric oxide (NO) synthesis, a potential risk factor for cardiovascular diseases and a powerful biochemical parameter in clinical studies. In our previous work we have reported on a GC-tandem MS method for the accurate and precise quantification of ADMA in biological fluids using de novo synthesized [(2)H(3)]-methyl ester ADMA (d(3)Me-ADMA) as internal standard (IS). This method provides basal ADMA concentrations in biological fluids that agree with those obtained by other groups using other validated methods for ADMA. Unanimously, de novo synthesized stable-isotope labeled analogues are considered not ideal IS, because they must be prepared in a matrix different from the biological sample. Recently, [2,3,3,4,4,5,5-(2)H(7)]-ADMA (d(7)-ADMA) has become commercially available and we took this opportunity to test the reliability of the de novo synthesized d(3)Me-ADMA as an IS for ADMA in GC-tandem MS. In this article, we report on the re-validation of the previously reported GC-tandem MS method for ADMA in human plasma and urine using d(7)-ADMA as IS, and on comparative quantitative analyses of ADMA by GC-tandem MS using d(7)-ADMA and d(3)Me-ADMA. After thorough standardization of d(7)-ADMA and methods validation, we obtained by GC-tandem MS very similar ADMA concentrations in plasma and urine using d(7)-ADMA and d(3)Me-ADMA. The present study gives a proof of evidence for the aptitude of (2)H(3)-ADMA as IS in GC-tandem MS and suggests that de novo synthesis of stable-isotope labeled alkyl esters of amino acids and amino acid derivates may be a generally applicable method in mass spectrometry-based methods for amino acids. This approach is especially useful for amino acids for which no stable-isotope labeled analogues are commercially available.

Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

PubMed Central

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

Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

PubMed Central

Sydow, Karsten; Mondon, Carl E.; Schrader, Joerg; Konishi, Hakuoh; Cooke, John P.

2011-01-01

Objective Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity. Methods and Results To test this hypothesis we employed a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22–70 weeks) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2μM) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle. Conclusions These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity. PMID:18239148

Serum Concentrations of New Predictive Cardiovascular Disease Biomarkers in Mexican Women Exposed to Lead.

PubMed

Ochoa-Martínez, Ángeles C; Cardona-Lozano, Elvia D; Carrizales-Yáñez, Leticia; Pérez-Maldonado, Iván N

2018-02-01

The purpose of this study was to evaluate lead exposure and its relationship with serum levels of predictive CVD biomarkers [asymmetric dimethylarginine (ADMA), adipocyte fatty acid-binding protein (FABP4), adiponectin, and chemerin] in women living in San Luis Potosi, Mexico. A mean blood lead level (BLL) of 11.5 ± 9.00 μg/dL (mean ± standard deviation) was found after all blood samples were analyzed. Regarding serum predictive CVD biomarkers, mean serum level of 0.68 ± 0.38 μmol/L, 20.5 ± 16.5 ng/mL, 12.5 ± 3.30 μg/mL, and 255 ± 130 ng/mL were found for ADMA, FABP4, adiponectin, and chemerin, respectively. Simple significant associations (Pearson´s correlations) between BLL and ADMA (r = 0.17; p = 0.04) and FABP4 (r = 0.23; p = 0.03) were found. Furthermore, a multivariate linear regression model showed that BLL was a significant predictor of serum ADMA (β = 0.06; p = 0.001) and FABP4 (β = 1.75; p = 0.0004) concentrations after adjusting by confounders. For serum chemerin and adiponectin levels, no associations were found with BLL. In conclusion, high serum ADMA and FABP4 (predictive CVD biomarkers) levels were found in women exposed to lead. Consequently, this research can be used as a point of departure for the prevention of CVD events in populations living in sites environmentally impacted with lead.

Reduction of plasma asymmetric dimethylarginine in obese patients with chronic kidney disease after three years of a low-protein diet supplemented with keto-amino acids: a randomized controlled trial.

PubMed

Teplan, Vladimir; Schück, Otto; Racek, Jaroslav; Mareckova, Olga; Stollova, Milena; Hanzal, Vladimir; Malý, Jan

2008-01-01

Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are elevated in chronic kidney disease (CKD) and may contribute to vascular complications. In this study we tested the hypothesis that elevated ADMA can be reduced in obese CKD patients by long-term administration of a low-protein diet supplemented with keto-amino acids. In a long-term prospective double-blind placebo-controlled randomized trial, we evaluated for a period of 36 months a total of 111 CKD patients (54 men, 57 women) aged 22-76 years with obesity (BMI >or= 30 kg/m(2)) and an inulin clearance rate (C(in)) of 22-40 ml/min/1.73 m(2). All patients were on a low-protein diet containing 0.6 g protein/kg BW per day and 120-125 kJ/kg BW per day. The diet was randomly supplemented with keto-amino acids at a dosage of 100 mg/kg BW per day (66 patients, Group I); 65 patients received placebo (Group II). During the study period, the glomerular filtration rate decreased slightly in Group I (C(in) from 32.4 +/- 12.6 to 29.8 +/- 8.6 ml/min/1.73 m(2)) and more markedly in Group II (from 33.2 +/- 12.6 to 23.2 +/- 98.4 ml/min/1.73 m(2), P < 0.01). BMI decreased significantly in Group I (from 32.0 +/- 3.3 to 26.1 +/- 4.0 kg/m(2), P < 0.01) and was linked to reduced volume of visceral fat measured by MRI (P < 0.01). Reduction of BMI in Group II was not significant. In Group I, there was a significant decrease in the plasma level of ADMA (from 2.5 +/- 0.5 to 1.3 +/- 0.4 micromol/l, P < 0.01), but ADMA remained unchanged in Group II. A further remarkable finding in Group I was reduction in the plasma concentration of pentosidine (from 480 +/- 170 to 320 +/- 120 microg/l, P < 0.01) and decrease of proteinuria (from 3.8 +/- 2.24 to 1.6 +/- 1.0 g/24 h, P < 0.02). Plasma adiponectin rose in Group I (P < 0.01). Analysis of the lipid spectrum revealed a mild but significant decrease in total cholesterol and LPD-cholesterol (P < 0.02), more pronounced in Group I. There was also a decrease in plasma triglycerides in Group I (from 3.9 +/- 1.6 down to 2.2 +/- 0.6 mmol/l, P < 0.01) and a decrease in glycated hemoglobin (from 7.2 +/- 1.4% to 4.2 +/- 0.8%, P < 0.02). Compared with the placebo group, long term co-administration of a low-protein diet and keto-amino acids in CKD patients with obesity led to decreases of ADMA, visceral body fat and proteinuria. Concomitant decreases of glycated hemoglobin, LDL-cholesterol and pentosidine may also contribute to the delay in progression of renal failure.

Plasma dimethylarginine levels in chronic hemodialysis patients are independent of the type of dialyzer applied.

PubMed

Grooteman, Muriel P C; Wauters, Inge M P M J; Teerlink, Tom; Twisk, Jos W R; Nubé, Menso J

2007-01-01

Asymmetric dimethylarginine (ADMA) levels are increased in hemodialysis (HD) patients. Reports on the effect of various dialysis strategies on ADMA, symmetric dimethylarginine (SDMA) and L-arginine levels are inconclusive. In this randomized crossover study, 15 patients were dialyzed for 4 weeks with 4 dialyzers, differing in biocompatibility and flux. Dimethylarginine and L-arginine levels were assessed at baseline, and after 4 weeks both before and after HD. During HD, ADMA and SDMA levels decreased significantly with all dialyzers. Dimethylarginine and L-arginine levels remained stable after 4 weeks of HD with each membrane. After pooling all data, values were mainly explained by variation between time points and patients, not by the type of dialyzer. Despite an intradialytic decrease in dimethylarginines, no changes occurred after 4 weeks of HD with either membrane. Furthermore, the variability of AMDA, SDMA and L-arginine levels was far more dependent on patient-related factors than on the type of dialyzer applied. Copyright 2007 S. Karger AG, Basel.

Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS.

PubMed

Bayrak, Tulin; Dursun, Polat; Bayrak, Ahmet; Gültekin, Murat; Kolusarı, Ali; Cakır, Erdinç; Ozyurt, Merve; Zeyneloğlu, Hulusi B

2012-11-01

Paraoxonase1 (PON1), exhibits both esterase activity (PON1-AREase) and homocysteine thiolactonase activity (PON1-HTLase) which respectively prevent LDL oxidation and detoxify homocysteine thiolactone (HTL). Platelet-activating factor-acetylhydrolase (PAF-AH) is an antioxidant enzyme preventing LDL oxidation by hydrolysis of oxidized phospholipids. Both of these enzymes exhibit a proatherogenic role. ADMA is an endogenous inhibitor of nitric oxide (NO) synthesis causing endothelial dysfunction. The aim was to compare non-obese PCOS patients with a BMI matched control group using the following characteristics: serum PON1-HTLase, ADMA, PAF-AH, and lipid and hormonal parameters. 77 women with PCOS and 25 healthy subject were recruited for this study, The controls were non-obese BMI and age matched with the patients. There were no significant differences with respect to age, BMI, FSH, free testosterone, DHEA, androstenadion, total cholesterol, triglycerides, HDL, LDL, VLDL, fasting glucose/insulin ratio and HOMA-IR among the groups (p > 0.05). However, total testosterone and fasting glucose levels were significantly higher in the PCOS group (p < 0.05). On the other hand, PON1-HTLase levels (39.6 ± 5.77 vs. 33.8 ± 8.2, p = 0.02) were significantly lower in the PCOS group while ADMA levels (1.14 ± 0.6 vs. 3.37 ± 6.4, p = 0.004) were significantly higher in the PCOS group. However, there was no significant difference in PAF-AH activity among the groups. Decreased PON1-HTLase and increased ADMA levels might be a relevant marker for the development of future atherosclerotic heart disease (AHD) in non-obese PCOS patients. Further studies are needed to confirm our results.

Dimethylarginine Dimethylaminohydrolase 1 Protects Against High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice.

PubMed

Li, Tianhe; Feng, Run; Zhao, Chenyang; Wang, Yue; Wang, Jian; Liu, Shasha; Cao, Jianwei; Wang, Hongyun; Wang, Ting; Guo, Yuting; Lu, Zhongbing

2017-04-10

High plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are associated with hepatic dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). However, it is unknown whether ADMA is involved in the pathogenesis of NAFLD. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that degrades ADMA. In this study, we used Ddah1 -/- mice to investigate the effects of the ADMA/DDAH1 pathway on high-fat diet (HFD)-induced hepatic steatosis. After HFD feeding for 20 weeks, Ddah1 -/- mice were more obese and had developed more severe hepatic steatosis and worse insulin resistance compared with wild-type (WT) mice. In the livers of HFD-fed mice, loss of DDAH1 resulted in higher levels of lipogenic genes, lower expression of β-oxidation genes, and greater induction of oxidative stress, endoplasmic reticulum stress, and inflammation than in the WT livers. Furthermore, ADMA treatment in HepG2 cells led to oxidative stress and steatosis, whereas overexpression of DDAH1 attenuated palmitic acid-induced steatosis, oxidative stress, and inflammation. Innovation and Conclusion: Our results provide the first direct evidence that the ADMA/DDAH1 pathway has a marked effect on hepatic lipogenesis and steatosis induced by HFD feeding. Our findings suggest that strategies to increase DDAH1 activity in hepatocytes may provide a novel approach to attenuate NAFLD development. Antioxid. Redox Signal. 26, 598-609.

Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study.

PubMed

Kruszelnicka, Olga; Świerszcz, Jolanta; Bednarek, Jacek; Chyrchel, Bernadeta; Surdacki, Andrzej; Nessler, Jadwiga

2016-04-15

A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients' age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies.

The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

PubMed

Angel, Kristin; Provan, Sella Aarrestad; Mowinckel, Petter; Seljeflot, Ingebjørg; Kvien, Tore Kristian; Atar, Dan

2012-11-01

Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

PubMed Central

Osorio-Yáñez, Citlalli; Ayllon-Vergara, Julio C.; Aguilar-Madrid, Guadalupe; Arreola-Mendoza, Laura; Hernández-Castellanos, Erika; Barrera-Hernández, Angel; De Vizcaya-Ruiz, Andrea

2013-01-01

Background: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk. Objectives: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs). Methods: We conducted a cross-sectional study in 199 children 3–14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry. Results: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-μmol/L increase in ADMA per 1-mm increase in cIMT). Conclusions: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water. Citation: Osorio-Yáñez C, Ayllon-Vergara JC, Aguilar-Madrid G, Arreola-Mendoza L, Hernández-Castellanos E, Barrera-Hernández A, De Vizcaya-Ruíz A, Del Razo LM. 2013. Carotid intima-media thickness and plasma asymmetric dimethylarginine in Mexican children exposed to inorganic arsenic. Environ Health Perspect 121:1090–1096; http://dx.doi.org/10.1289/ehp.1205994 PMID:23757599

In vivo microvascular and macrovascular endothelial function is not associated with circulating dimethylarginines in patients with rheumatoid arthritis: a prospective analysis of the DRACCO cohort.

PubMed

Dimitroulas, Theodoros; Sandoo, Aamer; Hodson, James; Smith, Jacqueline P; Kitas, George D

2016-07-01

To examine associations between asymmetric (ADMA), symmetric dimethylarginine (SDMA) and ADMA:SDMA ratio with assessments of endothelial function and coronary artery perfusion in RA patients. ADMA and SDMA levels were measured in 197 RA individuals [144 (77.4%) females, median age: 66 years (quartiles: 59-73)]. Patients underwent assessments of microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-dependent and endothelium-independent function and vascular morphology (pulse wave analysis, carotid intima-media thickness (cIMT), and carotid plaque). Coronary perfusion was assessed by subendocardial viability ratio (SEVR). SEVR correlated with SDMA (r = 0.172, p = 0.026) and ADMA:SDMA (r = -0.160, p = 0.041) in univariable analysis, but not in multivariable analysis accounting for confounding factors. Neither ADMA:SDMA ratio nor SDMA were significantly correlated with microvascular or macrovascular endothelial function, or with arterial stiffness and cIMT. Within subgroup of patients (n = 26) with high inflammatory markers, a post-hoc analysis showed that SDMA and the ADMA:SDMA ratio were significantly associated with endothelium-dependent microvascular function in univariable analysis, with Pearson's r correlation coefficients of -0.440 (p = 0.031) and 0.511 (p = 0.011), respectively. Similar finding were established between ADMA:SDMA ratio and arterial stiffness in univariable analysis, with Pearson's r of 0.493, (p = 0.024). Dimethylarginines were not found to be significantly associated with several assessments of vascular function and morphology in patients with RA, however, post-hoc analysis indicates that there may be associations in patients with raised inflammatory markers. Our results suggest that dysregulated NO metabolism may not be the sole mechanism for the development of preclinical atherosclerosis in RA.

Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains.

PubMed

Vanaveski, Taavi; Narvik, Jane; Innos, Jürgen; Philips, Mari-Anne; Ottas, Aigar; Plaas, Mario; Haring, Liina; Zilmer, Mihkel; Vasar, Eero

2018-01-01

The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days) of d-amphetamine (AMPH, 3 mg/kg i. p.), indirect agonist of dopamine (DA), in widely used 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6) mouse strains. Acute administration of AMPH (acute AMPH) induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH) caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA), whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA), alpha-aminoadipic acid (alpha-AAA), kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4), phosphatidylcholine (PC) diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4) and alkyl-acyls (PC ae C38:4, PC ae C40:4). However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1), PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6), PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3) and sphingolipids [SM(OH)C22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization. Simultaneously a significant decline of hexoses, citrulline, ADMA, and kynurenine occurred. The reduced levels of kynurenine, ADMA, and citrulline likely reflect altered function of N-methyl-D-aspartate (NMDA) and NO systems caused by repeated AMPH. Altogether, 129Sv strain displays stronger sensitization toward AMPH and larger variance in metabolite levels than Bl6.

The role of profilin-1 in endothelial cell injury induced by advanced glycation end products (AGEs).

PubMed

Li, Zhenyu; Zhong, Qiaoqing; Yang, Tianlun; Xie, Xiumei; Chen, Meifang

2013-10-04

Accumulation of advanced glycation end products (AGEs) in the vasculature triggers a series of morphological and functional changes contributing to endothelial hyperpermeability. The reorganisation and redistribution of the cytoskeleton regulated by profilin-1 mediates endothelial cell contraction, which results in vascular hyperpermeability. This study aimed to investigate the pivotal role of profilin-1 in the process of endothelial cell damage induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were incubated with AGEs. The mRNA and protein expression of profilin-1 was determined using real-time PCR and western blotting analyses. The levels of intercellular adhesion molecule-1 (ICAM-1), nitric oxide (NO) and reactive oxygen species (ROS), as well as the activities of nuclear factor-κB (NF-κB) and protein kinase C (PKC), were detected using the appropriate kits. The levels of asymmetric dimethylarginine (ADMA) were determined using HPLC. The distribution of the cytoskeleton was visualised using immunofluorescent staining. Compared with the control, incubation of endothelial cells with AGEs (200 μg/ml) for 4 or 24 h significantly up-regulated the mRNA and protein expression of profilin-1, markedly increased the levels of ICAM-1 and ADMA and decreased the production of NO (P<0.05, P<0.01), which was significantly attenuated by pretreatment with DPI (an antioxidant), GF 109203X (PKC inhibitor) or BAY-117082 (NF-κB inhibitor). DPI (10 μmol/L) markedly decreased the elevated levels of ROS induced by AGEs (200 μg/ml, 24 h); however, GF 109203X (10 μmol/L) and BAY-117082 (5 μmol/L) exhibited no significant effect on the formation of ROS by AGEs. Immunofluorescent staining indicated that AGEs markedly increased the expression of profilin-1 in the cytoplasm and the formation of actin stress fibres, resulting in the rearrangement and redistribution of the cytoskeleton. This effect was significantly ameliorated by DPI, GF 109203X, BAY-117082 or siRNA treatment of profilin-1. Incubation with DPI and GF 109203X markedly inhibited the activation of PKC triggered by AGEs, and DPI and BAY-117082 significantly decreased the activity of NF-κB mediated by AGEs. Disruption of profilin-1 gene expression attenuated the extent of endothelial abnormalities by reducing ICAM-1 and ADMA levels and elevating NO levels (P<0.05, P<0.01), but this disruption had no effect on the activities of NF-κB and PKC (P>0.05). These findings suggested that profilin-1 might act as an ultimate and common cellular effector in the process of metabolic memory (endothelial abnormalities) mediated by AGEs via the ROS/PKC or ROS/NF-қB signalling pathways.

Effect of metabolic abnormalities on endothelial dysfunction in normotensive offspring of subject with hypertension.

PubMed

Žižek, B; Žižek, D; Bedenčič, K; Jerin, A; Poredoš, P

2013-08-01

Essential hypertension (EH) is often accompanied by hyperinsulinemia/insulin resistance (IR) and deranged adiponectin secretion. IR may in turn be associated with endothelial dysfunction and increased levels of asymmetric dimethylarginine (ADMA). Therefore, we aimed to determine metabolic abnormalities in normotensive offspring of subjects with essential hypertension (familial trait-FT) and to examine their relations to endothelium-dependent vasodilation of the brachial artery (BA). We included 77 subjects, 38 were normotensive individuals with FT aged 28-39 (mean 33) years and 39 age-matched Controls without FT. Insulin, adiponectin and ADMA plasma levels were determined by radioimmunoassay. Using high-resolution ultrasound, BA diameters at rest and during reactive hyperemia (flow-mediated dilation-FMD) were measured. Subjects with FT had higher insulin and lower adiponectin levels than controls (13.65±6.70 vs. 7.09±2.20 mE/L; P<0.001 and 13.60±5.98 vs. 17.27±7.17 mg/L respectively; P<0.05). Insulin and adiponectin levels were negatively interrelated (r=-0.33, P=0.003). ADMA levels were comparable in both groups. The study group had worse FMD than Controls (6.11±3.28 vs. 10.20±2.07%; P<0.001). IR was independently associated with FMD (partial R2=0.23, P<0.001). Increased insulin and decreased adiponectin levels along with endothelial dysfunction are present in normotensive subjects with FT. IR and hypoadiponectinemia are interrelated, but only hyperinsulinemia has an independent adverse influence on endothelial function. Results of our study did not confirm the role of ADMA in pathogenesis of evolving hypertension.

Effect of in vitro gingival fibroblast seeding on the in vivo incorporation of acellular dermal matrix allografts in dogs.

PubMed

Novaes, Arthur B; Marchesan, Julie Teresa; Macedo, Guilherme O; Palioto, Daniela B

2007-02-01

Acellular dermal matrix allograft (ADMA) has been used in various periodontal procedures with successful results. Because ADMA has no blood vessels or cells, slower healing and incorporation are observed compared to a subepithelial connective tissue graft. Fibroblasts accelerate the healing process by regulation of matrix deposition and synthesis of a variety of growth factors. Thus, the objective of this study was to evaluate histologically if gingival fibroblasts affect healing and incorporation of ADMA in dogs when used as a subepithelial allograft. Gingival fibroblasts were established from explant culture from the connective tissue of keratinized gingiva collected from the maxilla of seven mongrel dogs. ADMA was seeded with gingival fibroblasts and transferred to dogs. Surgery was performed bilaterally, and the regions were divided into two groups: ADMA+F (ADMA containing fibroblasts) and ADMA (ADMA only). Biopsies were performed after 2, 4, and 8 weeks of healing. The quantity of blood vessels was significantly higher in the ADMA+F group at 2 weeks of healing (Kruskal-Wallis; P <0.05). There was no statistical difference (P >0.05) in the number of cell layers, epithelial area, or inflammatory infiltrate between the two groups at any stage of healing. The enhanced vascularization in vivo in early stages supports the important role of fibroblasts in improving graft performance and wound healing of cultured graft substitutes.

Effects of acute and chronic stress on the L-arginine nitric oxide pathway in black and white South Africans: the sympathetic activity and ambulatory blood pressure in Africans study.

PubMed

Reimann, Manja; Hamer, Mark; Malan, Nicolaas T; Schlaich, Markus P; Lambert, Gavin W; Ziemssen, Tjalf; Boeger, Rainer H; Malan, Leoné

2013-10-01

This study investigated the impact of stress on effectors of the L-arginine/nitric oxide (NO) system including the endogenous inhibitor asymmetric dimethylarginine (ADMA). Black (n = 168) and white (n = 206) South African teachers were exposed to a mental and a physical stressor for 1 minute, respectively. Serum samples for determination of l-arginine, NO metabolites, ADMA, and symmetric dimethylarginine (SDMA) were obtained at rest and during stress exposure. Perception of task stressfulness was assessed on a 7-point Likert scale, and psychological distress was estimated by the General Health Questionnaire. Black South Africans exhibited higher resting levels of NO metabolites (adjusted mean [standard error of the mean] = 11.3 [1.3] versus 3.9 [1.1] μmol/l, p < .001) but lower circulating ADMA (0.62 [0.02] versus 0.70 [0.02] μmol/l, p = .004) and SDMA (0.41 [0.01] versus 0.53 [0.01] μmol/l, p < .001) than did white South Africans. Ethnicity-by-psychological distress interaction was observed for resting levels of ADMA (p = .002), SDMA (p = .038), and L-arginine (p = .048). Ethnic differences in responses to experimental stress were evident for NO metabolites (blacks versus whites: 5.94 [1.55] versus -0.74 [1.25] μmol/l, p = .004) and SDMA (blacks versus whites: -0.02 [0.01] versus 0.02 [0.01] μmol/l, p = .004). Ethnicity-by-psychological distress interaction for stress responses was found for l-arginine/ADMA ratio (p = .027). The l-arginine/NO system is affected by psychosocial distress with higher susceptibility in black South Africans. This interaction may contribute to the higher cardiovascular disease risk in black South Africans.

Exercise capacity in polycystic kidney disease.

PubMed

Reinecke, Natália Lopes; Cunha, Thulio Marquez; Heilberg, Ita Pfeferman; Higa, Elisa Mieko Suemitsu; Nishiura, José Luiz; Neder, José Alberto; Almeida, Waldemar Silva; Schor, Nestor

2014-08-01

Reports about exercise performance in autosomal dominant polycystic kidney disease (ADPKD) are scarce. We aimed to evaluate exercise capacity and levels of nitric oxide and asymmetric dimethylarginine (ADMA) in normotensive patients with ADPKD. Prospective controlled cohort study. 26 patients with ADPKD and 30 non-ADPKD control participants (estimated glomerular filtration rate>60 mL/min/1.73 m2, aged 19-39 years, and blood pressure [BP]<140/85 mmHg). We excluded smokers, obese people, and individuals with associated diseases. ADPKD versus control. Exercise capacity and nitric oxide and ADMA levels in response to exercise. Cardiopulmonary exercise testing and serum and urinary nitric oxide, plasma ADMA, and BP levels before and after exercise. Mean basal systolic and diastolic BP, estimated glomerular filtration rate, and age did not differ between the ADPKD and control groups (116±12 vs. 110±11 mmHg, 76±11 vs 71±9 mmHg, 113±17 vs. 112±9.6 mL/min/1.73 m2, and 30±8 vs. 28.9±7.3 years, respectively). Peak oxygen uptake and anaerobic threshold were significantly lower in the ADPKD group than in controls (22.2±3.3 vs. 31±4.8 mL/kg/min [P<0.001] and 743.6±221 vs. 957.4±301 L/min [P=0.01], respectively). Postexercise serum and urinary nitric oxide levels in patients with ADPKD were not significantly different from baseline (45±5.1 vs. 48.3±4.6 μmol/L and 34.7±6.5 vs. 39.8±6.8 μmol/mg of creatinine, respectively), contrasting with increased postexercise values in controls (63.1±1.9 vs. 53.9±3.1 μmol/L [P=0.01] and 61.4±10.6 vs. 38.7±5.6 μmol/mg of creatinine [P=0.01], respectively). Similarly, whereas postexercise ADMA level did not change in the ADPKD group compared to those at rest (0.47±0.04 vs. 0.45±0.02 μmol/L [P=0.6]), it decreased in controls (0.39±0.02 vs. 0.47±0.02 μmol/L [P=0.006]), as expected. A negative correlation between nitric oxide and ADMA levels after exercise was found in only the control group (r = -0.60; P<0.01). Absence of measurements of flow-mediated dilatation and oxidative status. We found lower aerobic capacity in young normotensive patients with ADPKD with preserved kidney function and inadequate responses of nitric oxide and ADMA levels to acute exercise, suggesting the presence of early endothelial dysfunction in this disease. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Predictive value of vascular disease biomarkers for digital ulcers in systemic sclerosis patients.

PubMed

Silva, Ivone; Teixeira, Andreia; Oliveira, José; Almeida, Isabel; Almeida, Rui; Vasconcelos, Carlos

2015-01-01

To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients. Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9 pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of endoglin>4.215 ng/ml (p=0.053) was associated to a new DU episode. No predictive serum value was found for ADMA (p=0.075) and endostatin (p=0.130). Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis. Increased serum levels of ET-1, ADMA and VEGF are strong predictors of severe microangiopathy complications, namely ischaemic digital ulcers.

Calycosin and formononetin from astragalus root enhance dimethylarginine dimethylaminohydrolase 2 and nitric oxide synthase expressions in Madin Darby Canine Kidney II cells.

PubMed

Bai, Fan; Makino, Toshiaki; Kono, Keiko; Nagatsu, Akito; Ono, Takahiko; Mizukami, Hajime

2013-10-01

Nitric oxide (NO) is a crucial vasodilator produced by nitric oxide synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor and mainly catabolized by dimethylarginine dimethylaminohydrolase (DDAH). As we reported, the antihypertensive effect of shichimotsukokato (SKT), a formula of Japanese traditional kampo medicine consisting of 7 crude drugs, in 5/6 nephrectomized rats, is mediated by the DDAH-ADMA-NO pathway. Our present study aimed to explore the effective compounds of SKT using Madin Darby Canine Kidney (MDCK) II cells. We isolated two isoflavones, calycosin and formononetin from astragalus root, one of the components of SKT, which can promote DDAH2 protein and mRNA expressions in MDCK II cells. The neuronal NOS levels were also upregulated by the treatment of calycosin and formononetin. These results suggest that calycosin and formononetin could be the active ingredients of astragalus root and SKT that cause antihypertensive effects. The increased levels of DDAH2 and NOS may enhance NO production, decrease ADMA level and improve endothelial and cardiovascular dysfunction.

Post-challenge hyperglycaemia, nitric oxide production and endothelial dysfunction: the putative role of asymmetric dimethylarginine (ADMA).

PubMed

Siervo, M; Corander, M; Stranges, S; Bluck, L

2011-01-01

The endothelium is a thin layer of cells at the internal surface of blood vessels in continuous contact with the circulating fluids. The endothelial cells represent the primary barrier for the transport of glucose from the vascular conduits into the interstitial space. Insulin and nitric oxide have an important role in the regulation of glucose transport and metabolism. Hyperglycaemia is the main criteria for the diagnosis of diabetes and is responsible for the micro- and macro-vascular pathology seen in diabetic patients. Recent evidence suggests that post-challenge hyperglycaemia is a better predictor of cardiovascular risk than fasting glucose. Acute glucose elevations have been associated with a reduced endothelial-dependent flow mediated dilation indicating a decrease in nitric oxide production. Post-prandial hyperglycaemic peaks have been directly associated with increased intima media thickness in type 2 diabetic patients indicative of an increased atherosclerotic risk. The increase in intra-cellular glucose concentrations in the endothelial cells induces a hyper-generation of reactive oxygen species via the activation of different pathways (polyol-sorbitol, hexosamine, advanced glycated end products, activation of PKC, asymmetric dimethylarginine (ADMA)). These mechanisms influence the expression of genes and release of signalling and structural molecules involved in several functions (inflammation, angiogenesis, coagulation, vascular tone and permeability, cellular migration, nutrient metabolism). ADMA is considered as a biomarker of endothelial dysfunction and it has been associated with an increased risk of atherosclerosis and cardiovascular diseases. The increased generation of ADMA and reactive oxygen species in subjects with persistent hyperglycaemia could lead to an impairment of nitric oxide synthesis. Copyright © 2010 Elsevier B.V. All rights reserved.

Arginine-Nitric Oxide Metabolites and Cardiac Dysfunction in Patients With Breast Cancer.

PubMed

Finkelman, Brian S; Putt, Mary; Wang, Teresa; Wang, Le; Narayan, Hari; Domchek, Susan; DeMichele, Angela; Fox, Kevin; Matro, Jennifer; Shah, Payal; Clark, Amy; Bradbury, Angela; Narayan, Vivek; Carver, Joseph R; Tang, W H Wilson; Ky, Bonnie

2017-07-11

Oxidative/nitrosative stress and endothelial dysfunction are hypothesized to be central to cancer therapeutics-related cardiac dysfunction (CTRCD). However, the relationship between circulating arginine-nitric oxide (NO) metabolites and CTRCD remains unstudied. This study sought to examine the relationship between arginine-NO metabolites and CTRCD in a prospective cohort of 170 breast cancer patients treated with doxorubicin with or without trastuzumab. Plasma levels of arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and N-monomethylarginine (MMA) were quantified at baseline, 1 month, and 2 months after doxorubicin initiation. Determinants of baseline biomarker levels were identified using multivariable linear regression, and Cox regression defined the association between baseline levels and 1- or 2-month biomarker changes and CTRCD rate in 139 participants with quantitated echocardiograms at all time points. Age, hypertension, body mass index, and African-American race were independently associated with ≥1 of baseline citrulline, ADMA, SDMA, and MMA levels. Decreases in arginine and citrulline and increases in ADMA were observed at 1 and 2 months (all p < 0.05). Overall, 32 participants experienced CTRCD over a maximum follow-up of 5.4 years. Hazard ratios for ADMA and MMA at 2 months were 3.33 (95% confidence interval [CI]: 1.12 to 9.96) and 2.70 (95% CI: 1.35 to 5.41), respectively, and 0.78 (95% CI: 0.64 to 0.97) for arginine at 1 month. In breast cancer patients undergoing doxorubicin therapy, early alterations in arginine-NO metabolite levels occurred, and early biomarker changes were associated with a greater CTRCD rate. Our findings highlight the potential mechanistic and translational relevance of this pathway to CTRCD. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Regulation of post-translational protein arginine methylation during HeLa cell cycle.

PubMed

Kim, Chongtae; Lim, Yongchul; Yoo, Byong Chul; Won, Nam Hee; Kim, Sangduk; Kim, Gieun

2010-09-01

Post-translational arginine methylation which modifies protein-arginyl residues by protein arginine methyltransferase (PRMT) was investigated during synchronized HeLa cell cycle. The lysates of cells synchronized at each stage were subjected to one and/or two dimensional electrophoresis followed by Western immunoblot using against anti-asymmetric-dimethyl-arginine (ASYM24), anti-symmetric-dimethyl-arginine (SYM10), and subclasses of PRMTs, including PRMT1, PRMT3, PRMT4 (CARM1), PRMT5, PRMT6, and PRMT7 antibodies. Proteins with approximate molecular masses of 80 kDa, 68 kDa, and 64 kDa, containing asymmetric-dimethyl-arginine (aDMA) were increased at G0/G1 to G1, which lasted until S phase. In addition, 25 kDa protein of symmetric-dimethyl-arginine (sDMA) was also markedly up-regulated from G0/G1 to G1. The levels of PRMT3, PRMT6 and PRMT7 were concurrently increased during the cell cycle. Two-dimensional gel electrophoresis followed by MALDI-TOF-MS was identified as aDMA-80 kDa and aDMA-68 kDa proteins as heterogeneous nuclear ribonucleoprotein R (hnRNPR), aDMA-64 kDa proteins as cleavage stimulation factor 64 kDa subunit (CstF-64), and sDMA-25 kDa protein as triosephosphate isomerase (TPI). The levels of increased aDMA of hnRNPR were reduced, when HeLa cells were transfected with siRNA for PRMT1, and the aDMA of CstF-64 with siRNA for PRMT3, while depletion of PRMT5 down-regulated sDMA of TPI. Protein arginine dimethylations of hnRNPR, CstF-64, and TPI were regulated during HeLa cell cycle by respective PRMTs. These results suggest that regulation of arginine dimethylation of hnRNPR, CstF-64, and TPI at G0/G1 to G1 are most likely to modulate the cellular growth and proliferation in HeLa cell cycle. Copyright © 2010 Elsevier B.V. All rights reserved.

ASYMMETRIC DIMETHYLARGININE LEVELS AND ATHEROSCLEROSIS MARKERS IN CUSHING SYNDROME.

PubMed

Ozsurekci, Cemile Gulbas; Akturk, Mujde; Ozkan, Cigdem; Gulbahar, Ozlem; Altinova, Alev Eroglu; Yalcin, Muhittin; Arslan, Emre; Toruner, Fusun

2016-09-01

As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS. Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease-matched control subjects. Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P<.05). We did not find any statistically significant differences in levels of hsCRP, Lp-PLA2, or homocysteine or CIMT and ABI measurements between the CS group and comorbidity-matched control group (P>.05). We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS. ABI = ankle-brachial index Apo = apolipoprotein ADMA = asymmetric dimethylarginine BMI = body mass index CVD = cardiovascular disease CIMT = carotid intima-media thickness CS = Cushing syndrome DM = diabetes mellitus DDAH = dimethylarginine dimethylaminohydrolase ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein hsCRP = high-sensitive C-reactive protein HOMA-IR = homeostatic model assessment of insulin resistance HT = hypertension LDL = low-density lipoprotein Lp-PLA2 = lipoprotein-associated phospholipase A2 Lp-a = lipoprotein a NO = nitric oxide.

Evaluation of ADMA, carbonyl groups, CAT and NKA in depressed patients with and without posttraumatic stress disorder.

PubMed

Ogłodek, Ewa A

2017-08-01

It has been shown that asymmetric dimethylarginine (ADMA), carbonyl groups, catalase (CAT) and neurokinin A (NKA) are actively involved in neuronal processes such as depression and posttraumatic stress disorder (PTSD). One of their roles is to protect the body from oxidative damage. This is done by affecting neuronal growth, development and plasticity. The study aimed at assessing the concentrations of ADMA, carbonyl groups, CAT and NKA in patients with varying levels of depression severity, PTSD, and depression concurrent with PTSD. The study covered 460 people. Out of them, 120 suffered from different types of depression. The study groups comprised: 60 subjects with mild depression (MD), 60 subjects with moderate depression (MOD), 60 subjects with severe depression (SeD), 60 subjects with MD and PTSD (MD+PTSD), 60 subjects with MOD and PTSD (MOD+PTSD), 60 subjects with SeD and PTSD (SeD+PTSD), and 60 subjects with PTSD alone. Each group of 60 participants included 30 males and 30 females. The concentrations of all blood parameters were determined at 7 a.m. using the ELISA method. Depressive episodes became more severe as the concentration levels of studied markers increased. ADMA, carbonyl groups, CAT and NKA can be useful markers of chronic stress in both males and females with depression, PTSD, and depression concurrent with PTSD. They can be utilized when making an initial diagnosis and evaluating the severity of disease. Changes in their concentration levels may show a biological response to oxidative stress characteristic of depression. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease.

PubMed

Sonmez, Alper; Yilmaz, Mahmut Ilker; Saglam, Mutlu; Unal, Hilmi Umut; Gok, Mahmut; Cetinkaya, Hakki; Karaman, Murat; Haymana, Cem; Eyileten, Tayfun; Oguz, Yusuf; Vural, Abdulgaffar; Rizzo, Manfredi; Toth, Peter P

2015-04-16

Cardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD. A total of 197 patients (age 53±12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography. A total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p=0.04, p=0.02, p=0.01 respectively) and lower eGFR and FMD values (p=0.03, p<0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (β=-0.25 p=0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p=0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p<0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p<0.001)]. This study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD. Clinical trial registration number and date: NCT02113462 / 10-04-2014.

Ammonia Reduces Intracellular Asymmetric Dimethylarginine in Cultured Astrocytes Stimulating Its y⁺LAT2 Carrier-Mediated Loss.

PubMed

Milewski, Krzysztof; Bogacińska-Karaś, Małgorzata; Fręśko, Inez; Hilgier, Wojciech; Jaźwiec, Radosław; Albrecht, Jan; Zielińska, Magdalena

2017-11-02

Previously we had shown that ammonia stimulates nitric oxide (NO) synthesis in astrocytes by increasing the uptake of the precursor amino acid, arginine via the heteromeric arginine/glutamine transporter y⁺LAT2. Ammonia also increases the concentration in the brain of the endogenous inhibitor of nitric oxide synthases (NOS), asymmetric dimethylarginine (ADMA), but distribution of ADMA surplus between the intraastrocytic and extracellular compartments of the brain has not been studied. Here we tested the hypothesis that ammonia modulates the distribution of ADMA and its analog symmetric dimethylarginine (SDMA) between the two compartments of the brain by competition with arginine for the y⁺LAT2 transporter. In extension of the hypothesis we analyzed the ADMA/Arg interaction in endothelial cells forming the blood-brain barrier. We measured by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) technique the concentration of arginine, ADMA and SDMA in cultured cortical astrocytes and in a rat brain endothelial cell line (RBE-4) treated with ammonia and the effect of silencing the expression of a gene coding y⁺LAT2. We also tested the expression of ADMA metabolism enzymes: protein arginine methyltransferase (PRMT) and dimethylarginine dimethyl aminohydrolase (DDAH) and arginine uptake to astrocytes. Treatment for 48 h with 5 mM ammonia led to an almost 50% reduction of ADMA and SDMA concentration in both cell types, and the effect in astrocytes was substantially attenuated by silencing of the Slc7a6 gene. Moreover, the y⁺LAT2-dependent component of ammonia-evoked arginine uptake in astrocytes was reduced in the presence of ADMA in the medium. Our results suggest that increased ADMA efflux mediated by upregulated y⁺LAT2 may be a mechanism by which ammonia interferes with intra-astrocytic (and possibly intra-endothelial cell) ADMA content and subsequently, NO synthesis in both cell types.

Asymmetric dimethylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease.

PubMed

Liu, Xiaohong; Xu, Xin; Shang, Ruru; Chen, Yingjie

2018-06-19

Patients with chronic kidney disease have an increased cardiovascular morbidity and mortality. It has been recognized that the traditional cardiovascular risk factors could only partially explain the increased cardiovascular morbidity and mortality in patients with chronic kidney disease. Asymmetric dimethylarginine (ADMA) and N-monomethy l-arginine (L-NMMA) are endogenous inhibitors of nitric oxide synthases that attenuate nitric oxide production and enhance reactive oxidative specie generation. Increased plasma ADMA and/or L-NMMA are strong and independent risk factor for chronic kidney disease, and various cardiovascular diseases such as hypertension, coronary artery disease, atherosclerosis, diabetes, and heart failure. Both ADMA and L-NMMA are also eliminated from the body through either degradation by dimethylarginine dimethylaminohydrolase-1 (DDAH1) or urine excretion. This short review will exam the literature of ADMA and L-NMMA degradation and urine excretion, and the role of chronic kidney diseases in ADMA and L-NMMA accumulation and the increased cardiovascular disease risk. Based on all available data, it appears that the increased cardiovascular morbidity in chronic kidney disease may relate to the dramatic increase of systemic ADMA and L-NMMA after kidney failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2013-01-01

The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction. The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays. A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia. These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation.

PubMed

Schnabel, Renate B; Maas, Renke; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Levy, Daniel; Ellinor, Patrick T; Lubitz, Steven A; McManus, David D; Magnani, Jared W; Atzler, Dorothee; Böger, Rainer H; Schwedhelm, Edzard; Vasan, Ramachandran S; Benjamin, Emelia J

2016-06-01

Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain. In 3,310 individuals (mean age 58 ± 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, l-arginine, symmetric dimethylarginine (SDMA), and the ratio of l-arginine/ADMA to incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age- and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI 1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither l-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755-0.809). Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement. Copyright © 2016 Elsevier Inc. All rights reserved.

Premature aging of cardiovascular/platelet function in polycystic ovarian syndrome.

PubMed

Chan, Wai Ping A; Ngo, Doan T; Sverdlov, Aaron L; Rajendran, Sharmalar; Stafford, Irene; Heresztyn, Tamila; Chirkov, Yuliy Y; Horowitz, John D

2013-07-01

The objective of this study was to compare the impact of aging on nitric oxide (NO) modulation of platelet and vascular function in healthy women and women with polycystic ovary syndrome. A case-control study of women ages 18 to 60 years, comparing women with polycystic ovarian syndrome against age-matched healthy controls, was performed. A total of 242 women, of whom 109 had polycystic ovarian syndrome (based on Rotterdam criteria), participated in the study. Women who were pregnant or on clopidogrel were excluded from the study. Inhibition of platelet aggregation by nitric oxide (primary outcome measure), vascular endothelial function, plasma concentrations of N(G), N(G)-dimethyl-L-arginine (ADMA), endothelial progenitor cell count, and high-sensitivity C-reactive protein (markers of endothelial dysfunction and inflammation) were assessed. With increasing age in control women, there was progressive attenuation of platelet responses to NO, impairment of endothelial function, and elevation of ADMA levels (P ≤.001). Irrespective of age, women with polycystic ovarian syndrome exhibited greater impairment of all these parameters (all P <.05, 2-way analysis of variance) and demonstrated these anomalies earlier in life. Normal aging in women is associated with attenuation of NO-based signaling in platelets and blood vessels. In women with polycystic ovarian syndrome, these changes are present from early adult life and may contribute to premature atherogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease.

PubMed

Kielstein, Jan T; Suntharalingam, Mayuren; Perthel, Ronny; Rong, Song; Martens-Lobenhoffer, Jens; Jäger, Kristin; Bode-Böger, Stefanie M; Nave, Heike

2012-03-01

Thermal sensitivity in uraemia is decreased. Non-selective synthetic nitric oxide synthase (NOS) inhibitors significantly attenuate thermal hyperalgesia in preclinical models. The aim of our study was to evaluate the effect of experimental uraemia, which is associated with an increase of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), on thermal sensitivity in rats. Furthermore, we intended to study the effect of chronic ADMA infusion alone on thermal sensitivity. Male Sprague-Dawley rats (n = 54), 10 weeks old, weight 370-430 g, were randomly assigned to three groups receiving either (i) isotonic saline or (ii) ADMA via osmotic mini pumps or (iii) underwent 5/6 nephrectomy (Nx). After 14 days, 50% of all animals from all groups underwent thermal sensitivity testing and terminal blood draw. After 28 days, the remaining animals underwent the same procedures. Thermal sensitivity examination was performed by the hot-plate test, measuring time from heat exposition to first paw licking or jumping of the animal. While the median [interquartile range] latency time between heat exposition to first paw licking or jumping of the animal in the NaCl infusion group remained unchanged between Day 14 (8.4 [6.75-11.50] s) and Day 28 (7.35 [6.10-7.90] s) both, ADMA infusion and 5/6 nephrectomy tended to increase the thermal pain threshold at Day 14 (9.25 [6.55-12.18] s) and (9.50 [5.8 ± 11.0] s), respectively, compared to NaCl on Day 14 (8.4 [6.75-11.50] s). This difference became statistical significant at Day 28 where the median latency time in the ADMA group (13.10 [11.85-15.95] s) and in the 5/6 Nx group (13.50 [10.85-17.55] s) were significantly higher than in the NaCl group (7.35 [6.10-7.90] s). Induction of progressive renal failure in rats by 5/6 nephrectomy, which is accompanied by a marked increase of the serum levels of the endogenous NOS inhibitor ADMA, leads to a significantly increased heat pain threshold at 28 days. The sole infusion of ADMA into healthy rats leads to the same increase in heat pain threshold.

Comparative clinical evaluation of acellular dermal matrix allograft and connective tissue graft for the treatment of gingival recession.

PubMed

Rahmani, M E; Lades, Mohammad A Rigi

2006-05-01

"Gingival recession is a condition reported to occur due to abnormal periodontal anatomy, poor hygiene, excessive occlusal forces, toothbrush abrasion, and even iatrogenic or factitious causes. Though various surgical techniques are available to treat this problem, the most common is the palatal soft tissue autograft. Recently, an acellular dermal matrix allograft (ADMA) has been available as a substitute for the palatal tissue harvest. The aim of this study is to compare the ADMA with the conventional subepithelial connective tissue graft (SCTG) in the treatment of gingival recession." Fourteen patients with 20 gingival recessions of Miller's grade I and II were selected and randomized in two groups of control (SCTG ) and test (ADMA). In each group ten recession defects were treated. The following parameters were measured at baseline and then at six months post surgery: recession height (RH), recession width (RW), probing depth (PD), attached gingiva (AG), keratinized gingiva (KG), and clinical attachment level (CAL). All parameters were analyzed using the two-sample t-test. Data analysis was performed using SPSS (version 11) software. The following mean changes (mm) occurred in SCTG and ADMA, respectively: 2.60+/-0.97 and 2.90+/-0.81 decrease in RH; 1.70+/-1.01 and 1.65+/-0.67 decrease in RW; 2.50+/-0.97 and 2.95+/-0.69 increase in KG; 2.25+/-0.92 and 2.65+/-0.85 increase in AG; 2.60+/-1.08 and 2.75+/-0.92 decrease in CAL; and finally 0.05+/-0.50 and 0.10+/-0.46 decrease in PD for the SCTG and ADMA groups, respectively. The percentage of root coverage for the two groups was 70.12%+/-22.81% and 72.08%+/-14.12%, respectively. The changes from baseline to the six-month visit were significant for both groups in terms of all parameters but PD. However, the differences in mean changes were not significant between the two groups in any of the parameters. These findings imply the ADMA and SCTG techniques could produce the same results when used for the successful treatment of gingival recessions. In addition the ADMA could be used as an adequate alternative treatment modality for conventional techniques.

Imbalance of arginine and asymmetric dimethylarginine is associated with markers of circulatory failure, organ failure and mortality in shock patients.

PubMed

Visser, Marlieke; Vermeulen, Mechteld A R; Richir, Milan C; Teerlink, Tom; Houdijk, Alexander P J; Kostense, Piet J; Wisselink, Willem; de Mol, Bas A J M; van Leeuwen, Paul A M; Oudemans-van Straaten, Heleen M

2012-05-01

In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (SD 17·9) μmol/l) while ADMA concentration was within the normal range (0·46 (SD 0·18) μmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.

Inverse correlation between maternal plasma asymmetric dimethylarginine (ADMA) and birthweight percentile in women with impaired placental perfusion: circulating ADMA as an NO-independent indicator of fetal growth restriction?

PubMed

Tsikas, Dimitrios; Bollenbach, Alexander; Savvidou, Makrina D

2018-02-01

L-Arginine (Arg) is the enzymatic precursor of nitric oxide (NO) which has multiple biological functions. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of NO. We hypothesized that the ADMA and SDMA have additional biological functions in pregnancy, beyond NO synthesis, and may play a role in the regulation of birthweight (BW). To investigate this issue, we measured the plasma concentration of ADMA, SDMA, Arg and the NO metabolites nitrite and nitrate, at 23-25 weeks of gestation in women with normal placental function (Group 1) and in women with impaired placental perfusion; 19 of these women had normal outcome (Group 2), 14 had a fetus that was growth restricted (Group 3), and 10 women eventually developed preeclampsia (Group 4). BW percentile was found to inversely correlate with maternal plasma ADMA concentration in Group 3 (r = - 0.872, P < 0.001) and in Group 4 (r = - 0.800, P < 0.05). But, BW percentile did not correlate with the maternal plasma concentration of Arg, SDMA, nitrate or nitrite. Our results suggest that maternal plasma ADMA concentration is an important indicator of fetal growth restriction in women with impaired placental perfusion independent of NO.

Asymmetric dimethylarginine association with antioxidants intake in healthy young adults: a role as an indicator of metabolic syndrome features.

PubMed

Puchau, Blanca; Zulet, María A; Urtiaga, Goizane; Navarro-Blasco, Iñigo; Martínez, J Alfredo

2009-10-01

The purpose of this study was to evaluate the potential associations between serum asymmetric dimethylarginine (ADMA) and several anthropometric, biochemical, and lifestyle features in healthy young adults, emphasizing on the putative effects of the antioxidant intake on ADMA concentrations. Anthropometric and blood pressure measurements as well as lifestyle features and antioxidant intake were analyzed in 93 healthy young adults aged 18 to 34 years. Fasting blood samples were collected for the measurement of glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerols, and ADMA concentrations, as well as erythrocyte glutathione peroxidase activity. Nail samples were collected for the analysis of selenium and zinc concentrations. Values of body mass index (P = .004), waist circumference (P = .008), waist-to-height ratio (P = .046), systolic blood pressure (P < .001), serum glucose (P < .001), and nail selenium (P = .004) and zinc (P = .018) were significantly different between subjects with serum ADMA higher and lower than the median (cutoff, 458 nmol/L). Furthermore, ADMA showed a positive association with several adiposity markers such as body weight (P < .001), body mass index (P < .001), waist circumference (P = .006), waist-to-height ratio (P = .020), body fat mass (P = .001), systolic blood pressure (P = .001), and serum glucose (P < .001), whereas erythrocyte glutathione peroxidase activity (P = .021) and nail selenium (P = .040) and zinc values (P = .013) were statistically significant negative predictors of ADMA concentrations. In conclusion, ADMA seems to be related with selenium and zinc status and several anthropometric and biochemical measurements linked to metabolic syndrome in apparently healthy young adults. These findings support a role for antioxidant/trace element intake in the modulation of ADMA, whose assessment may be a marker of metabolic syndrome manifestations.

Serum concentrations of asymmetric and symmetric dimethylarginine are associated with mortality in acute heart failure patients.

PubMed

Potočnjak, Ines; Radulović, Bojana; Degoricija, Vesna; Trbušić, Matias; Pregartner, Gudrun; Berghold, Andrea; Meinitzer, Andreas; Frank, Saša

2018-06-15

Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine are established predictors of total and cardiovascular mortality. However, the predictive capacity of ADMA and SDMA for hospital and 3-months mortality of patients with acute heart failure (AHF) is unknown. Out of 152 included AHF patients, 79 (52%) were female, and the mean patient age was 75.2 ± 10.3 years. Hospital and three-month mortality rates were 14.5% and 27.4%, respectively. Serum ADMA and SDMA levels at admission, determined by reversed phase high performance liquid chromatography, were higher in patients having at least one of the three signs implying venous volume overload (enlarged liver, ascites, peripheral edema), a consequence of right-sided heart failure, compared to patients without those signs. Univariable logistic regression analyses revealed a significant positive association of ADMA and SDMA concentrations with hospital mortality [odds ratio (OR) and 95% confidence interval (CI) per standard deviation (SD) increase: 2.22 (1.37-3.79), p = 0.002, and 2.04 (1.34-3.18), p = 0.001, respectively], and 3-months mortality [2.06 (1.36-3.26), p = 0.001, and 2.52 (1.67-4.04), p < 0.001, respectively]. These associations remained significant after adjusting for age, sex, mean arterial pressure, low-density lipoprotein cholesterol, glomerular filtration rate, and N-terminal pro-brain natriuretic peptide. We conclude that ADMA and SDMA concentrations are associated with hospital and 3-month mortality and are increased by venous volume overload in AHF patients. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine

PubMed Central

Lüneburg, Nicole; Lieb, Wolfgang; Zeller, Tanja; Chen, Ming-Huei; Maas, Renke; Carter, Angela M.; Xanthakis, Vanessa; Glazer, Nicole L; Schwedhelm, Edzard; Seshadri, Sudha; Ikram, M. Arfan; Longstreth, W.T.; Fornage, Myriam; König, Inke R.; Loley, Christina; Ojeda, Francisco M.; Schillert, Arne; Wang, Thomas J.; Sticht, Heinrich; Kittel, Anja; König, Jörg; Benjamin, Emelia J.; Sullivan, Lisa M.; Bernges, Isabel; Anderssohn, Maike; Ziegler, Andreas; Gieger, Christian; Illig, Thomas; Meisinger, Christa; Wichmann, H.-Erich; Wild, Philipp S.; Schunkert, Heribert; Psaty, Bruce M.; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas; Lackner, Karl; Lunetta, Kathryn L.; Blankenberg, Stefan; Erdmann, Jeanette; Munzel, Thomas; Grant, Peter J.; Vasan, Ramachandran S.; Böger, Rainer H.

2016-01-01

Background Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers. Methods and Results This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium. Conclusion These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation. PMID:25245031

Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt.

PubMed

Nagasaka, Hironori; Okano, Yoshiyuki; Aizawa, Madoka; Miida, Takashi; Yorifuji, Tohru; Tajima, Go; Sakura, Nobuo; Takatani, Tomozumi; Sanayama, Yoshitami; Sugamoto, Kenji; Mayumi, Mitsufumi; Kobayashi, Kunihiko; Hirano, Kenichi; Takayanagi, Masaki; Tsukahara, Hirokazu

2010-01-01

Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS.

Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin.

PubMed

Wipff, J; Avouac, J; Borderie, D; Zerkak, D; Lemarechal, H; Kahan, A; Boileau, C; Allanore, Y

2008-07-01

SSc is a CTD characterized by early generalized microangiopathy with disturbed angiogenesis. Soluble endoglin (sENG), a serum anti-angiogenic protein, has recently been described as a major actor in pre-eclampsia, another severe vascular disease with abnormal angiogenesis. The aim of this study was to investigate, in a cross-sectional study, sENG levels together with other serum vascular markers. Serum levels of sENG were assessed by ELISA in consecutive SSc patients and controls matched for age and sex. We also measured by ELISA serum levels of VEGF and asymmetric dimethylarginine (ADMA), as respective markers of angiogenesis and endothelial dysfunction. We included 235 unrelated subjects: 187 SSc patients and 48 controls. Higher concentrations of sENG (P = 0.002) and sVEGF (P < 0.0001) were found in SSc patients compared with controls whereas there was no difference for ADMA. In multivariate analysis, sENG levels were significantly increased in SSc patients with cutaneous ulcerations (P = 0.0003), positive for ACAs (P = 0.009) and with abnormal diffusing capacity for carbon monoxide divided by alveolar volume (P = 0.03). Soluble ENG levels negatively correlated with ADMA, but no relationship was found between sENG and sVEGF. This study shows increased values of sENG in a large SSc cohort and a relevant association with a vascular phenotype. The predictive value of the biomarker sENG and its potential role on cellular endothelial disturbances remain to be determined.

Endodontic infection and endothelial dysfunction are associated with different mechanisms in men and women.

PubMed

Cotti, Elisabetta; Zedda, Angela; Deidda, Martino; Piras, Alessandra; Flore, Giovanna; Ideo, Francesca; Madeddu, Clelia; Pau, Valentina Maria; Mercuro, Giuseppe

2015-05-01

To investigate the potential link between apical periodontitis (AP) and cardiovascular (CV) function, inflammation markers, endothelial flow reserve (EFR), and levels of asymmetrical dimethylarginine (ADMA), the endogenous inhibitor of nitric oxide synthase (NOS), were measured in young adults with AP aged 20-40 years of both sexes. Forty men and 41 women (31 ± 5.71 years) free from periodontal disease, CV disease, and traditional CV risk factors were enrolled in the study. Twenty men and 21 women had AP; 40 healthy individuals matched for age, sex, and physical characteristics were also recruited as controls. All subjects underwent dental and complete physical examination, electrocardiography, conventional and tissue Doppler imaging echocardiography, and measurement of EFR. Interleukin (IL)-2, tumor necrosis factor alpha, reactive oxygen species (ROS), and ADMA were also assessed. Data were analyzed using the 2-tailed Student t test, the Pearson t test (or the Spearman t test for nonparametric variables), and multivariate linear regression analysis. Echocardiography excluded any morphologic and functional cardiac alteration in all the subjects studied. Patients with AP of both sexes showed a significant reduction in EFR (P < .05) and a significant increase in IL-2 (men: P < .01, women: P < .05), whereas ROS were increased significantly only in women (P < .05). ADMA levels were unchanged in women with AP, but they were significantly increased in men (P < .05). A significant direct correlation between ADMA and IL-2 (r = 0.67, P < .001) and an inverse correlation between ADMA and EFR (r = -0.42, P < .05) in men and a significant inverse correlation between ROS and EFR (r = -0.71, P < .01) in female patients were observed. The presence of chronic inflammation in young adults with AP may cause early endothelial dysfunction documented by the reduced EFR. AP in men may influence the metabolism of NOS, whereas in women it appears to implicate a more direct detrimental mechanism. This difference is sex dependent and may be attributable to the protective action of estrogen in women. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

PubMed Central

Segarra, Gloria; Cortina, Belén; Mauricio, María Dolores; Novella, Susana; Lluch, Paloma; Navarrete-Navarro, Javier; Noguera, Inmaculada; Medina, Pascual

2016-01-01

AIM To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats. METHODS Rat renal arteries from Sham (n = 15), pre-hepatic portal hypertension (PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis (BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10-9-3 × 10-6 mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD2 values to ADMA were similar in the Sham and PPVL groups (4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group (4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of pD2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA (3 × 10-4 mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher (P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The mRNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased (P < 0.05) in PPVL and further enhanced (P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney. PMID:28082806

Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis.

PubMed

Segarra, Gloria; Cortina, Belén; Mauricio, María Dolores; Novella, Susana; Lluch, Paloma; Navarrete-Navarro, Javier; Noguera, Inmaculada; Medina, Pascual

2016-12-28

To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats. Rat renal arteries from Sham ( n = 15), pre-hepatic portal hypertension (PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis (BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10 -6 -10 -3 mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10 -9 -3 × 10 -6 mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catabolizes ADMA. In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups (4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group (4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of pD 2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA (3 × 10 -4 mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher ( P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The mRNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased ( P < 0.05) in PPVL and further enhanced ( P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.

Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.

PubMed

Barber, Bridget E; William, Timothy; Grigg, Matthew J; Piera, Kim A; Chen, Youwei; Wang, Hao; Weinberg, J Brice; Yeo, Tsin W; Anstey, Nicholas M

2016-11-15

 Pathogenesis of severe Plasmodium vivax malaria is poorly understood. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability characterize severe falciparum malaria, but have not been assessed in severe vivax malaria.  In patients with severe vivax malaria (n = 9), patients with nonsevere vivax malaria (n = 58), and healthy controls (n = 79), we measured NO-dependent endothelial function by using reactive hyperemia-peripheral arterial tonometry (RH-PAT) and assessed associations with arginine, asymmetric dimethylarginine (ADMA), and hemolysis.  The L-arginine level and the L-arginine to ADMA ratio (a measure of L-arginine bioavailability) were reduced in patients with severe vivax malaria and those with nonsevere vivax malaria, compared with healthy controls (median L-arginine level, 65, 66, and 98 µmol/mL, respectively [P = .0001]; median L-arginine to ADMA ratio, 115, 125, and 187, respectively [P = .0001]). Endothelial function was impaired in proportion to disease severity (median RH-PAT index, 1.49, 1.73, and 1.97 in patients with severe vivax malaria, those with nonsevere vivax malaria, and healthy controls, respectively; P = .018) and was associated with the L-arginine to ADMA ratio. While the posttreatment fall in hemoglobin level was greater in severe vivax malaria as compared to nonsevere vivax malaria (2.5 vs 1 g/dL; P = .0001), markers of intravascular hemolysis were not higher in severe disease.  Endothelial function is impaired in nonsevere and severe vivax malaria, is associated with reduced L-arginine bioavailability, and may contribute to microvascular pathogenesis. Severe disease appears to be more associated with extravascular hemolysis than with intravascular hemolysis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Heat Shock Proteins, L-Arginine, and Asymmetric Dimethylarginine Levels in Patients With Obstructive Sleep Apnea Syndrome.

PubMed

İn, Erdal; Özdemir, Cengiz; Kaman, Dilara; Sökücü, Sinem Nedime

2015-11-01

Vascular endothelial inflammation and enhanced oxidative stress are important factors in the pathogenesis of obstructive sleep apnea syndrome (OSAS). The aim of this study was to determine the levels of heat shock protein (HSP) 27, HSP70, HSP90, L-arginine, and asymmetric dimethylarginine (ADMA) in patients with OSAS and determine their relationship with cardiovascular (CV) risk factors. Forty patients with OSAS, comprising 26 with and 14 without traditional CV risk factors (obesity, hypercholesterolemia, diabetes, hypertension, and smoking), and 20 control subjects without OSAS were included. All patients underwent a full polysomnographic evaluation, and blood samples were obtained in the morning after the night the diagnostic study was performed. No significant differences were found in serum HSP27 and HSP70 levels between the groups. HSP90 and ADMA levels increased significantly, whereas L-arginine levels decreased significantly in patients with OSAS, both with and without CV risk factors, compared with controls, but were not different among the subgroups. In all patients with OSAS, serum HSP70 levels were positively correlated with a percent time with saturation<90% (r=.349, P=.027). Serum L-arginine levels were negatively correlated with desaturation number (r=-.360, P=.022) and apnea-hypopnea index (r=-.354, P=.025) and positively correlated with mean oxygen saturation (r=.328, P=.039). Serum levels of HSP90 and ADMA increased, whereas those of L-arginine decreased in patients with OSAS regardless of CV risk factors. These findings indicate the presence of oxidative stress and endothelial dysfunction in patients with OSAS. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Effect of testosterone replacement therapy on vitamin D and FGF-23 levels in congenital hypogonadism.

PubMed

Haymana, Cem; Sonmez, Alper; Aydogdu, Aydogan; Tapan, Serkan; Basaran, Yalcin; Meric, Coskun; Baskoy, Kamil; Taslipinar, Abdullah; Yilmaz, Mahmut Ilker; Azal, Omer

2017-01-01

Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p<0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.

Nebivolol ameliorated kidney damage in Zucker diabetic fatty rats by regulation of oxidative stress/NO pathway: comparison with captopril.

PubMed

Wang, Yan; An, Wenjing; Zhang, Fei; Niu, Mengzhen; Liu, Yu; Shi, Ruizan

2018-06-23

The aim was to evaluate the effects and mechanisms of nebivolol on renal damage in Zucker diabetic fatty (ZDF) rats, in comparison with those of atenolol and captopril. Animals were divided into: control lean Zucker rats, ZDF rats, ZDF rats orally treated with nebivolol (10 mg/kg), atenolol (100 mg/kg) or captopril (40 mg/kg) for 6 months. Systolic blood pressure (SBP), blood glucose, kidney structure and function, plasma and kidney levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA), and oxidant status were evaluated. Kidney expressions of AMP-activated protein kinase (AMPK), NADPH oxidase (NOX) isoforms 2 and 4 and subunit p22 phox , nitric oxide synthase (NOS) isoforms, eNOS uncoupling, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 were tested. All drugs induced a similar control of SBP. Nebivolol did not affect the increased plasma glucose. Unlike atenolol, nebivolol prevented the decrease in plasma insulin, and, like captopril, it reduced plasma lipid contents. Nebivolol ameliorated, to a greater extent than captopril, damages to renal structure and function, which were associated with an improvement in interlobular artery dysfunction. Nebivolol elevated kidney phosphorylation of AMPK, attenuated NOX4 and p22 phox expression and oxidative stress marker levels. Nebivolol increased plasma and renal NO, enhanced expressions of eNOS, p-eNOS and nNOS, and suppressed eNOS uncoupling and iNOS expression. High ADMA in plasma and kidney were decreased by nebivolol through increasing DDAH2 and decreasing PRMT1. Long-term treatment of nebivolol ameliorated diabetic nephropathy, at least in part, via regulation of renal oxidative stress/NO pathway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Periodontal treatment in patients with chronic kidney disease: a pilot study.

PubMed

Almeida, S; Figueredo, C M; Lemos, C; Bregman, R; Fischer, R G

2017-04-01

This pilot cohort study evaluated the effect of periodontal treatment on renal function, metabolic markers and asymmetric dimethylarginine (ADMA) in patients with pre-dialysis chronic kidney disease (CKD) presenting chronic periodontitis. Twenty-six patients with CKD and severe chronic periodontitis were selected. Periodontal parameters included plaque index, bleeding on probing, probing pocket depth and clinical attachment level. Estimated glomerular filtration rate (eGFR), triglycerides, total cholesterol, albumin and ADMA levels were evaluated at baseline, 90 and 180 d after periodontal therapy. eGFR was evaluated by the Modification of Diet in Renal Disease equation. All periodontal clinical parameters significantly improved (p < 0.05) 180 d after periodontal therapy. There was a significant improvement on the median values (25%; 75% percentiles) of eGFR from 34.6 (27; 44.7) mL/min/1.73 m 2 on baseline to 37.6 (29.7; 57) mL/min/1.73 m 2 on day 90, and to 37.6 (28.6; 56) mL/min/1.73 m 2 (p < 0.05) on day 180. ADMA levels significantly reduced 180 d after periodontal treatment. No significant differences were observed at the median values of metabolic markers comparing baseline and 180 d after periodontal treatment. The results point to a link of kidney disease with endothelium dysfunction and periodontitis, suggesting that periodontal treatment may be beneficial to the course of CKD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cardiovascular disease markers in women with polycystic ovary syndrome with emphasis on asymmetric dimethylarginine and homocysteine

PubMed Central

Mohamadin, Ahmed M.; Habib, Fawzia A.; Al-Saggaf, Abdulrahman A.

2010-01-01

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Little is known about cardiovascular risk factors in patients with PCOS. We investigated plasma markers of cardiovascular disease in Saudi women with PCOS, with an emphasis on asymmetric dimethylarginine (ADMA) and total homocysteine (tHcy). PATIENTS AND METHODS: Fifty Saudi women with PCOS diagnosed by the Rotterdam criteria (mean age [SD] 30.2 [3.0] years) and 40 controls without PCOS (mean age 29.3 [2.5] years) had measyrements taken of clinical, metabolic, and hormonal parameters, including plasma ADMA, tHcy, lipoprotein (a) ([Lp(a)], and serum high sensitivity C-reactive protein (hs-CRP), nitric oxid, and fibrinogen. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). RESULTS: Women with PCOS had significantly higher fasting insulin, HOMA-IR, and luteinizing hormone (LH) levels than healthy controls (P<.001). Lipid profile, free androgen index (FAI), ADMA, tHcy, hsCRP, and Lp(a) were significantly higher in women with PCOS compared with healthy controls (P<.001). The women with PCOS had significantly lower nitric oxide and high-density lipoprotein cholesterol (HDL-C) levels compared with healthy controls (P<.001). CONCLUSION: Our study revealed that Saudi women with PCOS had a significantly different levels of plasma markers of cardiovascular disease compared with normal controls. Therefore, clinicians who manage women with PCOS should follow up on these markers to reduce the risk of cardiovascular disease. PMID:20622344

Associations between endogenous dimethylarginines and renal function in healthy children and adolescents.

PubMed

Jaźwińska-Kozuba, Aleksandra; Martens-Lobenhoffer, Jens; Surdacki, Andrzej; Kruszelnicka, Olga; Rycaj, Jarosław; Godula-Stuglik, Urszula; Bode-Böger, Stefanie M

2012-11-21

The structural isomer of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), is eliminated almost entirely by urinary excretion and considered a sensitive index of glomerular filtration rate (GFR). However, reports on this relationship in healthy subjects younger than 18 years of age are rare. Therefore, our aim was to investigate relations between endogenous dimethylarginines and renal function indices in healthy children and adolescents. We studied 40 subjects aged 3–18 years free of coexistent diseases or subclinical carotid atherosclerosis. A serum creatinine-derived estimated GFR (eGFR) was calculated by the revised bedside Schwartz equation. L-arginine, ADMA and SDMA were measured by liquid chromatography-tandem mass spectrometry. Mean eGFR was 122 ± 22 (SD) mL/min per 1.73 m2. Creatinine and eGFR exhibited closer correlations with the SDMA/ADMA ratio (r = 0.64, p < 0.0001; r = −0.63, p < 0.0001, respectively) than with SDMA (r = 0.31, p = 0.05; r = −0.35, p = 0.03). Neither creatinine nor eGFR correlated with ADMA or L-arginine. Adjustment for age or height only slightly attenuated the associations between the SDMA/ADMA ratio and eGFR or creatinine. Our findings suggest the superiority of the SDMA/ADMA ratio over SDMA as a renal function index in healthy children. Thus, further studies are warranted to verify our preliminary results in a larger group of subjects below 18 years of age.

Physical activity below the minimum international recommendations improves oxidative stress, ADMA levels, resting heart rate and small artery endothelial function.

PubMed

Merino, J; Ferré, R; Girona, J; Aguas, D; Cabré, A; Plana, N; Vinuesa, A; Ibarretxe, D; Basora, J; Buixadera, C; Masana, L

2015-01-01

A moderate level of physical activity (PA), such as a daily 30-min walk, reduces cardiovascular risk. There is a lack of evidence about the cardiovascular benefits of PA below this recommendation of minimum PA level. We aimed to study the impact of a lower level of PA on cardiovascular health. Sixty-four overweight/obese men and women were enrolled in a community programme consisting of 4 months of 1h, low-intensity PA two days per week. Before and after the intervention, PA level (METs/h/wk), endogenous antioxidant status (SOD and GPX concentration and activity and oxidised LDL), ADMA concentrations, endothelial function by small artery reactive hyperaemia index (saRHI), and resting heart rate (RHR) were assessed. After the intervention, significant increases in saRHI (P=0.031), SOD and GPX activities, and a decrease in ADMA plasma concentrations, and RHR (P<0.001 for all) were observed. Increases in PA were positively associated with increases in saRHI (r=0.341, P=0.022), GPx (r=0.303, P=0.047) and decreases in RHR (r=-0.302, P=0.047). Multivariate analyses showed that independent predictors of saRHI improvement were an increase in PA (2.65, 95%CI: 1.21-4.01), decrease in RHR (1.91, 95%CI: 1.01-4.98), and an increase in GPx (2.61, 95%CI: 1.16-5.01). In obese and overweight men and women, an increase in PA, even below the minimal international recommendations, improves antioxidant capacity, RHR and peripheral small artery reactivity. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Medium-term methionine supplementation increases plasma homocysteine but not ADMA and improves blood pressure control in rats fed a diet rich in protein and adequate in folate and choline.

PubMed

Mariotti, François; Hammiche, Alexia; Blouet, Clémence; Daré, Sophie; Tomé, Daniel; Huneau, Jean François

2006-10-01

Hyperhomocysteinemia (HHcy) is associated with cardiovascular risk, possibly because it increases asymmetric dimethyl-arginine (ADMA), but the general association remains unclear and may vary with nutritional and physiological conditions. We aimed to monitor the effect of methionine supplementation, and subsequent HHcy, on plasma ADMA and hemodynamics in the context of a diet rich in protein and adequate in folic acid and choline. For 6 weeks, rats were fed a 29% protein diet supplemented (M) or not (C) with 8 g/kg L: -methionine. Blood pressure and plasma amino acids, including homocysteine and ADMA, were measured throughout the experiment and additional parameters, including in vivo hemodynamic response to acetylcholine, were measured at week 5-6. As compared to the C diet, the M diet induced a marked HHcy during the first 3 weeks, which lessened at week 5. In contrast, plasma ADMA stayed similar in the C and M diet. Paradoxically, M rats had lower mean and diastolic blood pressure values over the experiment, together with a lower left ventricular mass at week 6, when compared with C rats. No difference was observed between groups regarding vascular reactivity and plasma NOx at week 6. In a context of a diet rich in protein and adequate in methyl donors, rats exhibit a complex adaptation to the medium-term methionine supplementation, with improvement in blood pressure control despite marked HHcy. The lack of increase in plasma ADMA may account for the absence of detrimental effects of HHcy on hemodynamics.

Root coverage of advanced gingival recession: a comparative study between acellular dermal matrix allograft and subepithelial connective tissue grafts.

PubMed

Tal, Haim; Moses, Ofer; Zohar, Ron; Meir, Haya; Nemcovsky, Carlos

2002-12-01

Acellular dermal matrix allograft (ADMA) has successfully been applied as a substitute for free connective tissue grafts (CTG) in various periodontal procedures, including root coverage. The purpose of this study was to clinically compare the efficiency of ADMA and CTG in the treatment of gingival recessions > or = 4 mm. Seven patients with bilateral recession lesions participated. Fourteen teeth presenting gingival recessions > or = 4 mm were randomly treated with ADMA or CTG covered by coronally advanced flaps. Recession, probing depth, and width of keratinized tissue were measured preoperatively and 12 months postoperatively. Changes in these clinical parameters were calculated within and compared between groups and analyzed statistically. Baseline recession, probing depth, and keratinized tissue width were similar for both groups. At 12 months, root coverage gain was 4.57 mm (89.1%) versus 4.29 mm (88.7%) (P = NS), and keratinized tissue gain was 0.86 mm (36%) versus 2.14 mm (107%) (P < 0.05) for ADMA and CTG, respectively. Probing depth remained unchanged (0.22 mm/0 mm), with no difference between the groups. Recession defects may be covered using ADMA or CTG, with no practical difference. However, CTG results in significantly greater gain of keratinized gingiva.

Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy.

PubMed

Gozal, David; Kheirandish-Gozal, Leila; Serpero, Laura D; Sans Capdevila, Oscar; Dayyat, Ehab

2007-11-13

Obstructive sleep apnea (OSA) in children is associated with cardiovascular morbidity such as systemic and pulmonary hypertension. However, it remains unclear whether endothelial dysfunction occurs in pediatric OSA and whether it is reversible on effective treatment of OSA. Consecutive nonobese children (aged 6 to 11 years) who were diagnosed with OSA after overnight polysomnography and control children matched on the basis of age, gender, ethnicity, and body mass index underwent blood draw the next morning for soluble CD40 ligand, asymmetric dimethylarginine (ADMA), and nitrotyrosine levels, as well as 2 iterations of 60-second cuff-occlusion tests for assessment of endothelial function. These tests were repeated 4 to 6 months after adenotonsillectomy. OSA children showed blunted reperfusion kinetics after release of occlusion, which completely normalized in 20 of 26 patients after adenotonsillectomy. All 6 children in whom no improvements occurred had a strong family history of cardiovascular disease (versus 2 of the remaining 20 patients; P<0.04). Plasma nitrotyrosine and ADMA levels were similar in OSA and control children; however, soluble CD40 ligand levels were higher in OSA children and were reduced after treatment, particularly in those with normalized hyperemic responses. Postocclusive hyperemia is consistently blunted in children with OSA, and such altered endothelial function is reversible 4 to 6 months after treatment, particularly if a family history of cardiovascular disease is not present. Although no evidence for either nitric oxide-dependent oxidative/nitrosative stress or for the increased presence of the circulating nitric oxide synthase inhibitor ADMA was found in children with OSA, soluble CD40 ligand levels were increased in OSA and reflected the changes in endothelial function after treatment.

Carotid Plaque Score and Risk of Cardiovascular Mortality in the Oldest Old: Results from the TOOTH Study.

PubMed

Hirata, Takumi; Arai, Yasumichi; Takayama, Michiyo; Abe, Yukiko; Ohkuma, Kiyoshi; Takebayashi, Toru

2018-01-01

Accumulating evidence suggests that predictability of traditional cardiovascular risk factors declines with advancing age. We investigated whether carotid plaque scores (CPSs) were associated with cardiovascular disease (CVD) death in the oldest old, and whether asymmetrical dimethylarginine (ADMA), a marker of endothelial dysfunction, moderated the association between the CPS and CVD death. We conducted a prospective cohort study of Japanese subjects aged ≥85 years without CVD at baseline. We followed this cohort for 6 years to investigate the association of CPS with CVD death via multivariable Cox proportional hazard analysis. We divided participants into three groups according to CPS (no, 0 points; low, 1.2-4.9 points; high, ≥5.0 points). The predictive value of CPS for estimating CVD death risk over CVD risk factors, including ADMA, was examined using C-statistics. We analyzed 347 participants (151 men, 196 women; mean age, 87.6 years), of which 135 (38.9%) had no carotid plaque at baseline, and 48 (13.8%) had high CPS. Of the total, 29 (8.4%) participants experienced CVD-related death during the study period. Multivariable analysis revealed a significant association of high CPS with CVD-related mortality relative to no CPS (hazard ratio, 3.90; 95% confidence interval: 1.47-10.39). ADMA was not associated with CVD death, but the significant association between CPS and CVD death was observed only in lower ADMA level. The addition of CPS to other risk factors improved the predictability of CVD death (p=0.032). High CPS correlated significantly with a higher CVD death risk in the oldest old with low cardiovascular risk. Ultrasound carotid plaque evaluation might facilitate risk evaluations of CVD death in the very old.

Dimethylarginine dimethylaminohydrolase 1 modulates endothelial cell growth through NO and Akt

PubMed Central

Zhang, Ping; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J.

2011-01-01

Objective Dimethylarginine dimethylaminohydrolase 1 (DDAH1) modulates NO production by degrading the endogenous NO synthase (NOS) inhibitors ADMA and L-NMMA. This study examined whether, in addition to degrading ADMA, DDAH1 exerts ADMA independent effects that influence endothelial function. Methods and Results Using selective gene silencing of DDAH1 with small interfering RNA and overexpression of DDAH1 in HUVEC, we found that DDAH1 acts to promote endothelial cell proliferation, migration and tube formation both by Akt phosphorylation as well as through the traditional role of degrading ADMA. Incubation of HUVEC with the NOS inhibitors L-NAME or ADMA, the soluble guanylyl cyclase inhibitor ODQ, or the cGMP analog 8-pCPT-cGMP had no effect on p-AktSer473, indicating that the increase of p-AktSer473 produced by DDAH1 was independent of the NO-cGMP signaling pathway. DDAH1 formed a protein complex with Ras, and DDAH1 overexpression increased Ras activity. The Ras inhibitor manumycin-A or dominant-negative Ras significantly attenuated the DDAH1-induced increase of p-AktSer473. Furthermore, DDAH1 knockout impaired endothelial sprouting from cultured aortic rings, and overexpression of constitutively active Akt or DDAH1 rescued endothelial sprouting in the aortic rings from these mice. Conclusions DDAH1 exerts a unique role in activating Akt that affects endothelial function independent of degrading endogenous NOS inhibitors. PMID:21212404

Involvement of DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP Pathways in Human Tissue Kallikrein 1 Protecting Erectile Function in Aged Rats

PubMed Central

Tang, Zhe; Rao, Ke; Wang, Tao; Chen, Zhong; Wang, Shaogang; Liu, Jihong; Wang, Daowen

2017-01-01

Our previous studies had reported that Human Tissue Kallikrein 1 (hKLK1) preserved erectile function in aged transgenic rats, while the detailed mechanism of hKLK1 protecting erectile function in aged rats through activation of cGMP and cAMP was not mentioned. To explore the latent mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 18 months old and divided into four groups: young WTR (yWTR) as the control, aged WTR (aWTR), aged TGR (aTGR) and aged TGRs with HOE140 (aTGRH). Erectile function of all rats was evaluated by cavernous nerve electrostimulation method and measured by the ratio of intracavernous pressure/ mean arterial pressure (ICP/MAP) in rats. Expression levels of cAMP and cGMP were assessed, and related signaling pathways were detected by western blot, immunohistochemistry and RT-PCR. Our experiment results showed erectile function of the aWTR group and aTGRH group was lower compared with those of other two groups. Also, expression levels of cAMP and cGMP were significantly lower than those of other two groups. Moreover, expressions of related signaling pathways including DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP were also downregulated in the corpus cavernosum of rats in aWTR group. Our finding revealed hKLK1 played a protective role in age-related ED. The DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP pathways that were linked to the mechanism hKLK1 could increase the levels of cGMP and cAMP, which might provide novel therapy targets for age-related ED. PMID:28103290

Asymmetric Dimethylarginine as a Surrogate Marker of Endothelial Dysfunction and Cardiovascular Risk in Patients with Systemic Rheumatic Diseases

PubMed Central

Dimitroulas, Theodoros; Sandoo, Aamer; Kitas, George D.

2012-01-01

The last few decades have witnessed an increased life expectancy of patients suffering with systemic rheumatic diseases, mainly due to improved management, advanced therapies and preventative measures. However, autoimmune disorders are associated with significantly enhanced cardiovascular morbidity and mortality not fully explained by traditional cardiovascular disease (CVD) risk factors. It has been suggested that interactions between high-grade systemic inflammation and the vasculature lead to endothelial dysfunction and atherosclerosis, which may account for the excess risk for CVD events in this population. Diminished nitric oxide synthesis—due to down regulation of endothelial nitric oxide synthase—appears to play a prominent role in the imbalance between vasoactive factors, the consequent impairment of the endothelial hemostasis and the early development of atherosclerosis. Asymmetric dimethylarginine (ADMA) is one of the most potent endogenous inhibitors of the three isoforms of nitric oxide synthase and it is a newly discovered risk factor in the setting of diseases associated with endothelial dysfunction and adverse cardiovascular events. In the context of systemic inflammatory disorders there is increasing evidence that ADMA contributes to the vascular changes and to endothelial cell abnormalities, as several studies have revealed derangement of nitric oxide/ADMA pathway in different disease subsets. In this article we discuss the role of endothelial dysfunction in patients with rheumatic diseases, with a specific focus on the nitric oxide/ADMA system and we provide an overview on the literature pertaining to ADMA as a surrogate marker of subclinical vascular disease. PMID:23202900

Structure and function of large arteries in hypertension in relation to oxidative stress markers.

PubMed

Klima, Łukasz; Kawecka-Jaszcz, Kalina; Stolarz-Skrzypek, Katarzyna; Menne, Jan; Fijorek, Kamil; Olszanecka, Agnieszka; Wojciechowska, Wiktoria; Bilo, Grzegorz; Czarnecka, Danuta

2013-01-01

The relationship between hypertension and oxidative stress remains unexplained. Nevertheless, it is well established that reactive oxygen species have an influence on the arterial wall, endothelial function and therefore determine blood pressure. The evaluation of selected oxidative stress markers in hypertensive patients and an assessment of the relationship between oxidative stress markers and the arterial structure and function. We also aimed to investigate whether the influence of oxidative stress on remodelling of arteries, their structural and functional changes is independent of hypertension or is related to hypertension. Altogether 217 subjects (114 female, 103 male) were enrolled from hypertensive families. The mean age was 45.5 ± 16 years, and the group included 155 hypertensives. In every subject, the pulse wave velocity and intima-media thickness (IMT) in carotid arteries were measured as well as selected oxidative stress markers such as asymmetric dimethylarginin (ADMA), symmetric dimethylarginin (SDMA), advanced oxidation protein products (AOPP) and oxidised low density lipoproteins (ox-LDL). The results of multivariate analysis show that in hypertensive patients: the ADMA level increased with increasing peripheral pulse pressure (b = 0.003; p < 0.001), and AOPP was related to higher carotid IMT (b = 0.91; p = 0.036). In normotensive subjects, the following associations were found: between ADMA and central pulse pressure (b = 0.006; p = 0.008), between SDMA and the peripheral augmentation index (b = -0.03; p = 0.014), between AOPP and the peripheral augmentation index (b = 0.011; p = 0.04), and between ox-LDL/LDL ratio and the peripheral augmentation index (b = -0.025; p = 0.004). The SDMA/ADMA ratio was associated with estimated glomerular filtration rate in both groups (b = -0.0061; p < 0.0001 and b = -0.005; p < 0.017, respectively). In hypertensives, we observed a relation with peripheral pulse pressure (b = -0.0067; p = 0.0143). Moreover, in normotensives there was an association between the SDMA/ADMA ratio and uric acid (b = 1.3629; p = 0.046). We found that the influence of oxidative stress on the structure and function of large arteries was independent of hypertension. Therefore oxidative stress may play a significant role in the development of arterial stiffness. Higher oxidative stress is associated with more advanced arterial remodelling in hypertension.

Effect of trelagliptin on vascular endothelial functions and serum adiponectin level in patients with type 2 diabetes: a preliminary single-arm prospective pilot study.

PubMed

Ida, Satoshi; Murata, Kazuya; Betou, Katunori; Kobayashi, Chiaki; Ishihara, Yuki; Imataka, Kanako; Uchida, Akihiro; Monguchi, Kou; Kaneko, Ryutaro; Fujiwara, Ryoko; Takahashi, Hiroka

2016-11-04

Trelagliptin, an oral DPP-4 inhibitor, which is administered once per week and characterized by a long half-life in blood. The effects of trelagliptin on vascular endothelial functions have not been clarified to date. The objective of the present study was to examine the effects of trelagliptin on vascular endothelial functions in patients with type 2 diabetes mellitus (DM) using flow-mediated dilatation (FMD), adiponectin, and asymmetric dimethylarginine (ADMA) as evaluation indicators. This study was a preliminary single-arm prospective pilot study. The subjects of this study were type 2 DM patients aged 20-74 years, who visited our outpatient department. The patients were treated with trelagliptin, and their FMD, adiponectin, and ADMA levels were measured at baseline and at 12 weeks after initial treatment to determine the changes during the study period. A total of 27 patients, excluding three dropouts, were included in the population for analysis. Trelagliptin treatment showed no significant changes in FMD (2.42 ± 2.7% at baseline vs. 2.66 ± 3.8% post-treatment, P = 0.785) and ADMA (0.41 ± 0.0 µg/mL at baseline vs. 0.40 ± 0.0 µg/mL post-treatment, P = 0.402). Trelagliptin treatment resulted in a significant increase of serum adiponectin level (7.72 ± 6.9 µg/mL at baseline vs. 8.82 ± 8.3 µg/mL post-treatment, P < 0.002). In this pilot study, trelagliptin treatment showed no significant changes in FMD. On the other hand, it was believed that trelagliptin treatment may increase serum adiponectin level. Trial Registration http://www.umin.ac.jp (Trial ID UMIN000018311).

A relative L-arginine deficiency contributes to endothelial dysfunction across the stages of the menopausal transition.

PubMed

Klawitter, Jelena; Hildreth, Kerry L; Christians, Uwe; Kohrt, Wendy M; Moreau, Kerrie L

2017-09-01

Vascular endothelial function declines across the menopause transition in women. We tested the hypothesis that reduced availability of the endothelial nitric oxide synthase [eNOS] substrate L-arginine is an underlying mechanism to vascular endothelial dysfunction across menopause stages. Endothelial function (brachial artery flow-mediated dilation [FMD]) and plasma markers of L-arginine metabolism (citrulline, N G -mono-methyl-ւ-arginine [L-NMMA] asymmetric dimethylarginine [ADMA] and N G -N 'G -dimethyl-l-arginine [SDMA]), were measured in 129 women: 36 premenopausal (33 ± 7 years), 16 early- (49 ± 3 years) or 21 late- (50 ± 4 years) perimenopausal, and 21 early- (55 ± 3 years) or 35 late- (61 ± 4 years) postmenopausal. FMD was progressively reduced across menopause stages ( P  < 0.001). Menopause stage was associated with L-arginine concentrations ( P  = 0.012), with higher levels in early postmenopausal compared to early and late perimenopausal women ( P  < 0.05). The methylarginine and eNOS inhibitor L-NMMA was higher in early and late postmenopausal women compared to premenopausal and early and late perimenopausal women (all P  < 0.001), and was inversely correlated with FMD ( r  = -0.30, P  = 0.001). The L-arginine/L-NMMA ratio, a potential biomarker of relative L-arginine levels, was lower in postmenopausal compared to either premenopausal or perimenopausal women (both P  < 0.001), and was positively correlated with FMD ( r  = 0.33, P  < 0.001). There were no differences in plasma citrulline, ADMA or SDMA across groups. These data suggest that a relative L-arginine deficiency may be a mechanism underlying the decline in endothelial function with the menopause transition in women. The relative L-arginine deficiency may be related to elevated levels of the methylarginine L-NMMA, which would compete with L-arginine for eNOS and for intracellular transport, reducing NO biosynthesis. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Dimethylarginine dimethylaminohydrolase 1 modulates endothelial cell growth through nitric oxide and Akt.

PubMed

Zhang, Ping; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J

2011-04-01

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) modulates NO production by degrading the endogenous nitric oxide (NO) synthase (NOS) inhibitors asymmetrical dimethylarginine (ADMA) and L-NG-monomethyl arginine (L-NMMA). This study examined whether, in addition to degrading ADMA, DDAH1 exerts ADMA-independent effects that influence endothelial function. Using selective gene silencing of DDAH1 with small interfering RNA and overexpression of DDAH1 in human umbilical vein endothelial cells, we found that DDAH1 acts to promote endothelial cell proliferation, migration, and tube formation by Akt phosphorylation, as well as through the traditional role of degrading ADMA. Incubation of human umbilical vein endothelial cells with the NOS inhibitors l-NG-nitro-arginine methyl ester (L-NAME) or ADMA, the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo-(4,3-2)quinoxalin-1-one, or the cGMP analog 8-(4-Chlorophenylthio)-cGMP had no effect on phosphorylated (p)-Akt(Ser473), indicating that the increase in p-Akt(Ser473) produced by DDAH1 was independent of the NO-cGMP signaling pathway. DDAH1 formed a protein complex with Ras, and DDAH1 overexpression increased Ras activity. The Ras inhibitor manumycin-A or dominant-negative Ras significantly attenuated the DDAH1-induced increase in p-Akt(Ser473). Furthermore, DDAH1 knockout impaired endothelial sprouting from cultured aortic rings, and overexpression of constitutively active Akt or DDAH1 rescued endothelial sprouting in the aortic rings from these mice. DDAH1 exerts a unique role in activating Akt that affects endothelial function independently of degrading endogenous NOS inhibitors.

Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study.

PubMed

Moslemi, Neda; Mousavi Jazi, Mahvash; Haghighati, Farideh; Morovati, Seyyedeh Pouya; Jamali, Raika

2011-12-01

The present randomized clinical trial compared the long-term results of subepithelial connective tissue graft (SCTG) versus acellular dermal matrix allograft (ADMA) in treatment of gingival recessions. In 16 patients with bilateral Miller Class I/II gingival recessions, one side was treated with SCTG and the other side with ADMA. Clinical parameters were measured at baseline, 6 months, and at 5 years post-surgery. Fifteen patients completed the study. At 6 months, all parameters showed significant improvement in ADMA and SCTG groups [complete root coverage (CRC): 73.3% versus 26.7%, p = 0.027; reduction of recession depth (RD): 2.6 ± 1.1 mm versus 2.2 ± 1.1 mm, p = 0.376; reduction of recession width (RW): 3.0 ± 1.4 mm versus 2.4 ± 1.4 mm, p = 0.207 respectively]. At 5 years, significant relapses were detected in CRC and reduction of RD and RW in both groups with no statistically significant difference (CRC: 20.0% versus 13.3%, p = 1.00; RD: 1.6 ± 1.2 mm versus 1.5 ± 1.4mm, p = 0.838; RW: 1.8 ± 1.4 mm versus 1.3 ± 1.5mm, p = 0.367). Patients practicing horizontal toothbrushing habit showed more relapse (OR = 11.2; p = 0.01). Compared with baseline, the gingival width (GW) did not increase in ADMA-treated sites (p = 0.903). Five-year results of SCTG and ADMA were similar in terms of CRC and reduction of RD and RW. Both techniques showed a significant relapse associated with returning to horizontal toothbrushing habit. Increase of GW was stable in SCTG-treated sites, but reached to pre-surgical values in ADMA-treated cases. © 2011 John Wiley & Sons A/S.

Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine metabolomics.

PubMed

Radhakutty, Anjana; Mangelsdorf, Brenda L; Drake, Sophie M; Rowland, Andrew; Smith, Malcolm D; Mangoni, Arduino A; Thompson, Campbell H; Burt, Morton G

2017-11-01

The effects of low dose prednisolone on circulating markers of endothelial function, the arginine metabolites asymmetric dimethyl arginine (ADMA), mono methyl arginine (MMA), and homoarginine, are uncertain. We assessed whether patients with rheumatoid arthritis have perturbations in arginine metabolite concentrations that are reversed by low dose prednisolone. Eighteen rheumatoid arthritis patients who had not taken prednisolone for >6 months (non-glucocorticoid (GC) users), 18 rheumatoid arthritis patients taking continuous oral prednisolone (6.5 ± 1.8 mg/day) for >6 months (GC users) and 20 healthy controls were studied. Fasting plasma concentrations of ADMA, MMA, and homoarginine were measured by ultra-performance liquid-chromatography. Baseline data from non-GC users were compared with healthy controls to assess the effect of rheumatoid arthritis. The change in arginine metabolites in non-GC users after 7 days of prednisolone (6 mg/day) was used to assess the acute effects of prednisolone. Baseline data from non-GC users were compared with GC users to assess the chronic effects of prednisolone. Non-GC users had higher ADMA (0.59 ± 0.03 vs. 0.47 ± 0.01 μM, p = 0.004) and MMA concentrations (0.10 ± 0.01 vs. 0.05 ± 0.00 μM, p < 0.001) than controls. The only change with acute prednisolone was a reduction in homoarginine (1.23 ± 0.06 vs. 1.08 ± 0.06 μM, p = 0.04) versus baseline. GC users had lower concentrations of ADMA (0.51 ± 0.02 vs. 0.59 ± 0.03 μM, p = 0.03) than non-GC users. Rheumatoid arthritis patients have higher concentrations of ADMA and MMA, inhibitors of endothelial function. Chronic, but not acute, prednisolone therapy is associated with a lower ADMA concentration, suggesting a salutary effect of long-term glucocorticoid treatment on endothelial function. Copyright © 2017 Elsevier B.V. All rights reserved.

Weight loss and vascular inflammatory markers in overweight women with and without polycystic ovary syndrome.

PubMed

Moran, Lisa J; Noakes, Manny; Wittert, Gary A; Clifton, Peter M; Norman, Robert J

2012-11-01

Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular disease risk. The effect of weight loss on the vascular inflammatory markers plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1) and intracellular adhesion molecule-1 (sICAM-1) is unknown. Overweight women with (n=14) and without (n=13) PCOS of comparable age and body mass index undertook an 8-week weight-loss programme. Women with PCOS had elevated PAI-1, sVCAM-1 and sICAM-1 before and after weight loss compared with the controls. For all women, sVCAM-1 (P=0.026) and sICAM-1 (P=0.04) decreased with weight loss. Women with PCOS have elevated inflammatory markers, which are partially reduced by weight loss. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The Effect of Nebivolol versus Metoprolol Succinate Extended Release on Asymmetric Dimethylarginine in Hypertension

PubMed Central

Kandavar, Ramprasad; Higashi, Yusuke; Chen, Wei; Blackstock, Christopher; Vaughn, Charlotte; Sukhanov, Sergiy; Sander, Gary E.; Roffidal, Louise E.; Delafontaine, Patrice; Giles, Thomas D.

2011-01-01

Objectives This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a β1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives. Background It was hypothesized that NEB, a β1-AR antagonist and β3-AR agonist with NO- releasing properties and MET, only a β1-AR antagonist, would have different effects on plasma ADMA concentration. Methods Forty-one hypertensive subjects randomly received either 50 mg of MET (n = 19) or 5 mg of NEB (n = 22) for 4 weeks followed by 100 mg MET and 10 mg NEB for 4 weeks. ADMA and IGF-1 were measured by ELISA kit; endothelial progenitor cells were estimated using fluorescein-labeled monoclonal antibody to KDR and CD133 receptors; arterial augmentation index was measured by radial tonometry. Results Baseline systolic/diastolic blood pressure was 155.1 ± 18.7/85.3 ± 12.5 mm Hg for MET subjects and 157.6 ± 20.7/87.1 ± 14.0 mm Hg for NEB subjects. Baseline ADMA was 0.32 ± 0.123 μmol/L in the MET group and 0.4035 ± 0.1378 in the NEB group. ADMA increased 44.78% and 72% in the MET group at weeks 4 and 8 (p < 0.05 for both), respectively, without increase in the NEB group. At week 8 augmentation index was increased in the MET group (p<0.05). IGF-1 and EPC were unchanged by treatment. Conclusions Plasma ADMA and augmentation index are increased in a dose-dependent fashion by MET but not with NEB. PMID:21251896

Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects.

PubMed

Nagasaka, Hironori; Tsukahara, Hirokazu; Yorifuji, Tohru; Miida, Takashi; Murayama, Kei; Tsuruoka, Tomoko; Takatani, Tomozumi; Kanazawa, Masaki; Kobayashi, Kunihiko; Okano, Yoshiyuki; Takayanagi, Masaki

2009-03-01

Nitric oxide (NO) is synthesized from arginine and O(2) by nitric oxide synthase (NOS). Citrulline, which is formed as a by-product of the NOS reaction, can be recycled to arginine by the 2 enzymes acting in the urea cycle: argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). Although the complete urea cycle is expressed only in the liver, ASS and ASL are expressed in other organs including the kidney and vascular endothelium. To examine possible alterations of the NO pathway in urea cycle defects, we measured plasma concentrations of arginine and citrulline and serum concentrations of nitrite/nitrate (NOx(-), stable NO metabolites) and asymmetric dimethylarginine (ADMA, an endogenous NOS inhibitor) in patients with congenital urea cycle disorders of 3 types: ornithine transcarbamylase (OTC) deficiency, ASS deficiency, and ASL deficiency. All were receiving oral arginine replacement at the time of this study. The same parameters were also measured in healthy subjects, who participated as controls. The OTC-deficient patients had significantly high NOx(-) and nonsignificantly high ADMA concentrations. Their NOx(-) was significantly positively correlated with arginine. The ASS-deficient patients had significantly low NOx(-) and significantly high ADMA concentrations. The ASL-deficient patients had normal NOx(-) and nonsignificantly high ADMA concentrations. In ASS-deficient and ASL-deficient patients, the NOx(-) was significantly inversely correlated with citrulline. These results suggest that NO synthesis is enhanced in OTC-deficient patients while receiving arginine but that NO synthesis remains low in ASS-deficient patients despite receiving arginine. They also suggest that endogenous NO synthesis is negatively affected by citrulline and ADMA in ASS-deficient and ASL-deficient patients. Although the molecular mechanisms remain poorly understood, we infer that the NO pathway might play a role in the pathophysiology related to congenital urea cycle disorders.

Retraction Statement: "High-Volumetric Performance Aligned Nano-Porous Microwave Exfoliated Graphite Oxide-based Electrochemical Capacitors" and "Aligned Nano-Porous Microwave Exfoliated Graphite Oxide Ionic Actuators with High Strain and Elastic Energy Density".

PubMed

2016-11-01

These articles first published on 15 August 2013 and 21 August 2013 on the Wiley Online Library have been retracted at the request of the Research Integrity Officer (RIO) of The Pennsylvania State University, in agreement with the corresponding authors, the journal's Editor-in-Chief, and Wiley-VCH Verlag GmbH & Co. KGaA, because portions of the reported results cannot be considered reliable or reproducible. Following an investigation by the RIO of The Pennsylvania State University, it was found that the data in Figure 2a,b and Figure S1a,b (Supporting Information) of the article with DOI: 10.1002/adma.201301243, and Figure S3 (Supporting Information) of the article with DOI: 10.1002/adma.201301370 were falsified. Data regarding the carbon electrode material, A-aMEGO, reported to have a density of 1.15 g cm -3 , in the article with DOI: 10.1002/adma.201301243, were falsified. The RIO of The Pennsylvania State University confirms that the investigation found that the mentioned data were falsified by the first author. No findings of research misconduct were made against the co-authors of these publications. [1] M. Ghaffari, Y. Zhou, H. Xu, M. Lin, T. Y. Kim, R. S. Ruoff, Q. M. Zhang, Adv. Mater. 25: 2013, 4879. doi:10.1002/adma.201301243 [2] M. Ghaffari, W. Kinsman, Y. Zhou, S. Murali, Q. Burlingame, M. Lin, R. S. Ruoff, Q. M. Zhang, Adv. Mater. 25: 2013, 6277. doi:10.1002/adma.201301370. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors

PubMed Central

Brito, Julio; Siques, Patricia; López, Rosario; Romero, Raul; León-Velarde, Fabiola; Flores, Karen; Lüneburg, Nicole; Hannemann, Juliane; Böger, Rainer H.

2018-01-01

Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition. Methods: A cross-sectional study of 120 healthy miners working at an altitude of 4,400–4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level. Results: The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5–29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3–5 points, including cephalea; moderate was LLS of 6–10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18–66.39); p < 0.05) and insulin (OR: 1.11 (1.02–1.20); p < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP. Conclusions: Working intermittently at high altitude involves a distinctive pattern. The most relevant and novel characteristics are a greater prevalence of elevated mPAP and HAPH than previously reported at chronic intermittent hypobaric hypoxia (CIHH), which is accompanied by subsequent morphological characteristics. These findings are associated with cardiometabolic factors (insulin and ADMA). However, the functional repercussions seem to be minor or negligible. This research contributes to our understanding and surveillance of this unique model of chronic intermittent high-altitude exposure. PMID:29623044

Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors.

PubMed

Brito, Julio; Siques, Patricia; López, Rosario; Romero, Raul; León-Velarde, Fabiola; Flores, Karen; Lüneburg, Nicole; Hannemann, Juliane; Böger, Rainer H

2018-01-01

Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition. Methods: A cross-sectional study of 120 healthy miners working at an altitude of 4,400-4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level. Results: The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5-29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3-5 points, including cephalea; moderate was LLS of 6-10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18-66.39); p < 0.05) and insulin (OR: 1.11 (1.02-1.20); p < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP. Conclusions: Working intermittently at high altitude involves a distinctive pattern. The most relevant and novel characteristics are a greater prevalence of elevated mPAP and HAPH than previously reported at chronic intermittent hypobaric hypoxia (CIHH), which is accompanied by subsequent morphological characteristics. These findings are associated with cardiometabolic factors (insulin and ADMA). However, the functional repercussions seem to be minor or negligible. This research contributes to our understanding and surveillance of this unique model of chronic intermittent high-altitude exposure.

Proton pump inhibitors and vascular function: A prospective cross-over pilot study.

PubMed

Ghebremariam, Yohannes T; Cooke, John P; Khan, Fouzia; Thakker, Rahul N; Chang, Peter; Shah, Nigam H; Nead, Kevin T; Leeper, Nicholas J

2015-08-01

Proton pump inhibitors (PPIs) are commonly used drugs for the treatment of gastric reflux. Recent retrospective cohorts and large database studies have raised concern that the use of PPIs is associated with increased cardiovascular (CV) risk. However, there is no prospective clinical study evaluating whether the use of PPIs directly causes CV harm. We conducted a controlled, open-label, cross-over pilot study among 21 adults aged 18 and older who are healthy (n=11) or have established clinical cardiovascular disease (n=10). Study subjects were assigned to receive a PPI (Prevacid; 30 mg) or a placebo pill once daily for 4 weeks. After a 2-week washout period, participants were crossed over to receive the alternate treatment for the ensuing 4 weeks. Subjects underwent evaluation of vascular function (by the EndoPAT technique) and had plasma levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of endothelial function previously implicated in PPI-mediated risk) measured prior to and after each treatment interval. We observed a marginal inverse correlation between the EndoPAT score and plasma levels of ADMA (r = -0.364). Subjects experienced a greater worsening in plasma ADMA levels while on PPI than on placebo, and this trend was more pronounced amongst those subjects with a history of vascular disease. However, these trends did not reach statistical significance, and PPI use was also not associated with an impairment in flow-mediated vasodilation during the course of this study. In conclusion, in this open-label, cross-over pilot study conducted among healthy subjects and coronary disease patients, PPI use did not significantly influence vascular endothelial function. Larger, long-term and blinded trials are needed to mechanistically explain the correlation between PPI use and adverse clinical outcomes, which has recently been reported in retrospective cohort studies. © The Author(s) 2015.

Pathogenesis of chronic cluster headache and bouts: role of tryptamine, arginine metabolism and α1-agonists.

PubMed

D'Andrea, G; Bussone, G; Di Fiore, P; Perini, F; Gucciardi, A; Bolner, A; Aguggia, M; Saracco, G; Galloni, E; Giordano, G; Leon, A

2017-05-01

The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

Cardiovascular disease markers in women with polycystic ovary syndrome with emphasis on asymmetric dimethylarginine and homocysteine.

PubMed

Mohamadin, Ahmed M; Habib, Fawzia A; Al-Saggaf, Abdulrahman A

2010-01-01

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Little is known about cardiovascular risk factors in patients with PCOS. We investigated plasma markers of cardiovascular disease in Saudi women with PCOS, with an emphasis on asymmetric dimethylarginine (ADMA) and total homocysteine (tHcy). Fifty Saudi women with PCOS diagnosed by the Rotterdam criteria (mean age [SD] 30.2 [3.0] years) and 40 controls without PCOS (mean age 29.3 [2.5] years) had measyrements taken of clinical, metabolic, and hormonal parameters, including plasma ADMA, tHcy, lipoprotein (a) ([Lp(a)], and serum high sensitivity C-reactive protein (hs-CRP), nitric oxid, and fibrinogen. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Women with PCOS had significantly higher fasting insulin, HOMA-IR, and luteinizing hormone (LH) levels than healthy controls (P P P CONCLUSION: Our study revealed that Saudi women with PCOS had a significantly different levels of plasma markers of cardiovascular disease compared with normal controls. Therefore, clinicians who manage women with PCOS should follow up on these markers to reduce the risk of cardiovascular disease.

Anti-Atherogenic Activity of Polyphenol-Rich Extract from Bee Pollen

PubMed Central

Rzepecka-Stojko, Anna; Stojko, Jerzy; Buszman, Ewa

2017-01-01

The aim of this study was to determine the effect of polyphenol-rich ethanol extract of bee pollen (EEP) on atherosclerosis induced by a high-fat diet in ApoE-knockout mice. EEP was given with feed in two doses of 0.1 and 1 g/kg body mass (BM). The studies have been conducted in a period of 16 weeks. The following factors were estimated: total cholesterol (TC), oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE) and angiotensin II (ANG II) in the 5th, 10th, 12th, 14th, and 16th week of the experiment. In the last, i.e., 16th week of the studies the development of coronary artery disease (CAD) was also estimated histopathologically. Supplementing diet with EEP resulted in decreasing TC level. EEP reduced oxidative stress by lowering the levels of ox-LDL, ADMA, ANG II and ACE. EEP protected coronary arteries by significantly limiting the development of atherosclerosis (the dose of 0.1 g/kg BM) or completely preventing its occurrence (the dose of 1 g/kg BM). The obtained results demonstrate that EEP may be useful as a potential anti-atherogenic agent. PMID:29258230

[The importance of regulation of endogenous methylarginine concentrations in clinical practice].

PubMed

Kopieczna-Grzebieniak, Ewa; Goss, Małgorzata

2005-01-01

Endogenous methylarginines, the catabolism products of proteins containing post-translationally methylated arginine residues, are the modulators of arginine metabolism. Endogenous methylarginines compete with arginine about cationic aminoacid transporter and some of them, e.g. asymmetric dimethylarginine (ADMA) and N-mono-methylarginine (MMA), are competitive inhibitors of nitric oxide synthases. The changes of arginine metabolism, induced by these methylarginines, may have serious consequences, because arginine is the precursor of cell-signalling molecules such as NO, agmatine, glutamate and gamma-aminobutyric acid (GABA) and the regulatory molecules polyamines. ADMA has also prooxidant properties and increases endothelial adhesiveness for monocytes. Asymmetric methyl-arginines induce endothelial dysfunction, which may be reversed by L-arginine supplementation, what is defined as "arginine paradox". The increased plasma concentration of asymmetric methylarginines is induced by hypercholesterolemic or hyperhomocysteinemic diets and by rich sodium chloride intake. The high level of plasma asymmetric methyl-arginines accompanies atherosclerosis, hypertension, chronic renal failure, diabetes, insulin resistence, hyperthyreosis, schizophrenia and sclerosis multiplex. The causes of increased concentration ADMA and MMA in these diseases are just now discovered. The hope in the future is the modulation of methylarginines concentration by regulation of expression and activities of enzymes taking part in the metabolism of these substances, particularly of dimethyl-arginine dimethyl-aminotransferase. The main aim of the present study is to pay attention to possibility of the modulation of asymmetric methyl-arginines concentration, what may be a new way of synthase nitric oxide activity regulation in vivo and may be useful in future therapy of patologies in which synthesis of NO is troubled.

Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in Tertiary Hospital in Indonesia.

PubMed

Soewondo, Pradana; Suyono, Slamet; Sastrosuwignyo, Mpu Kanoko; Harahap, Alida R; Sutrisna, Bambang; Makmun, Lukman H

2017-01-01

to evaluate the role of clinical characteristics, functional markers of vasodilation, inflammatory response, and atherosclerosis in predicting wound healing in diabetic foot ulcer. a cohort study (February - October 2010) was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia. Each subject underwent at least two variable measurements, i.e. during inflammatory phase and proliferation phase. The studied variables were clinical characteristics, complete peripheral blood count (CBC) and differential count, levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG), marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin-1/ET-1, and flow-mediated dilation/FMD of brachial artery), and marker of vascular calcification (osteoprotegerin/OPG). median of time achieving 50% granulation tissue in our study was 21 days. There were nine factors that contribute in the development of 50% granulation tissue, i.e. family history of diabetes mellitus (DM), previous history of wound, wound area, duration of existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and OPG. There were three out of the nine factors that significantly correlated with wound healing, i.e. wound area, OPG levels, and simvastatin medications. in acute diabetic foot ulcers, wound area and OPG levels had positive correlation with wound healing, whereas simvastatin medications had negative correlation with wound healing.

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmetaj-Shala, B., E-mail: b.ahmetaj@imperial.ac.uk; Tesfai, A.; Constantinou, C.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are amongst the most commonly used medications and produce their anti-inflammatory and analgesic benefits by blocking cyclooxygenase (COX)-2. These drugs also have the potential to prevent and treat cancer and some members of the class including ibuprofen can produce anti-platelet effects. Despite their utility, all NSAIDs are associated with increased risk of cardiovascular side effects which our recent work suggests could be mediated by increased levels of the endogenous NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) leading to reduced endothelial NOS activity and associated endothelial cell dysfunction. ADMA is a cardiotoxic hormone and biomarkermore » of cardiovascular risk whose effects can be prevented by L-arginine. The ibuprofen salt, ibuprofen arginate (Spididol{sup ®}) was created to increase drug solubility but we have previously established that it not only effectively blocks COX-2 but also provides an arginine source able to reverse the effects of ADMA in vitro and in vivo. Here we have gone on to explore whether the formulation of ibuprofen with arginine influences the potency and efficacy of the parent molecule using a range of simple in vitro assays designed to test the effects of NSAIDs on (i) platelet aggregation and (iii) colon cancer cell killing. Our findings demonstrate that ibuprofen arginate retains these key functional effects of NSAIDs with similar or increased potency compared to ibuprofen sodium, further illustrating the potential of ibuprofen arginate as an efficacious drug with the possibility of improved cardiovascular safety. - Highlights: • Arginine salts of ibuprofen have improved solubility and deliver arginine. • They retain full anti-inflammatory, anti-cancer and anti-platelet activity. • Arginine formulations may provide a safer but still efficacious NSAID therapy.« less

Deletion of admB gene encoding a fungal ADAM affects cell wall construction in Aspergillus oryzae.

PubMed

Kobayashi, Takuji; Maeda, Hiroshi; Takeuchi, Michio; Yamagata, Youhei

2017-05-01

Mammals possess a unique signaling system based on the proteolytic mechanism of a disintegrin and metalloproteinases (ADAMs) on the cell surface. We found two genes encoding ADAMs in Aspergillus oryzae and named them admA and admB. We produced admA and admB deletion strains to elucidate their biological function and clarify whether fungal ADAMs play a similar role as in mammals. The ∆admA∆admB and ∆admB strains were sensitive to cell wall-perturbing agents, congo red, and calcofluor white. Moreover, the two strains showed significantly increased weights of total alkali-soluble fractions from the mycelial cell wall compared to the control strain. Furthermore, ∆admB showed MpkA phosphorylation at lower concentration of congo red stimulation than the control strain. However, the MpkA phosphorylation level was not different between ∆admB and the control strain without the stimulation. The results indicated that A. oryzae AdmB involved in the cell wall integrity without going through the MpkA pathway.

HPLC-MS/MS investigation of biochemical markers for the disclosure of erythropoietin abuse in sports

NASA Astrophysics Data System (ADS)

Appolonova, S. A.; Dikunets, M. A.; Rodchenkov, G. M.

2009-04-01

The polypeptide hormone erythropoietin (EPO), which is a forbidden doping drug, was determined by high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). The hypothesis about the influence of EPO on the asymmetric dimethylarginine (ADMA)-dimethylargininedime-thylaminohydrolase (DDAH)-NO-synthase system was verified. Changes in this system can serve as indirect biochemical markers of the presence of the forbidden EPO drug in the organism. In the test group, the concentrations of biochemical markers varied from 10 to 40 μg/ml for ADMA and symmetrical DMA (SDMA) and from 0.5 to 10 μg/ml for arginine and citrulline. A single intravenous administration of r-HuEPO (Epocrin, 2000 ME/day) for two volunteers reliably increased ADMA, SDMA, arginine, and citrulline concentrations to 40-270 μg/ml, 40-240μg/ml, 10-60 μg/ml, and 12-140 μg/ml, respectively, with respect to the reference values. The simultaneous increase in arginine, methylarginines, and citrulline contents could be an indirect marker of EPO abuse. The method is recommended for fast screening analysis.

Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation

PubMed Central

El-Hattab, Ayman W.; Hsu, Jean W.; Emrick, Lisa T.; Wong, Lee-Jun C.; Craigen, William J.; Jahoor, Farook; Scaglia, Fernando

2014-01-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism. PMID:22325939

The effect of diet and exercise on markers of endothelial function in overweight and obese women with polycystic ovary syndrome.

PubMed

Thomson, R L; Brinkworth, G D; Noakes, M; Clifton, P M; Norman, R J; Buckley, J D

2012-07-01

Women with polycystic ovary syndrome (PCOS) present with vascular abnormalities, including elevated markers of endothelial dysfunction. There is limited evidence for the effect of lifestyle modification and weight loss on these markers. The aim of this study was to determine if 20 weeks of a high-protein energy-restricted diet with or without exercise in women with PCOS could improve endothelial function. This is a secondary analysis of a subset of 50 overweight/obese women with PCOS (age: 30.3 ± 6.3 years; BMI: 36.5 ± 5.7 kg/m(2)) from a previous study. Participants were randomly assigned by computer generation to one of three 20-week interventions: diet only (DO; n = 14, ≈ 6000 kJ/day), diet and aerobic exercise (DA; n = 16, ≈ 6000 kJ/day and five walking sessions/week) and diet and combined aerobic-resistance exercise (DC; n = 20, ≈ 6000 kJ/day, three walking and two strength sessions/week). At Weeks 0 and 20, weight, markers of endothelial function [vascular cell adhesion molecule-1 (sVCAM-1), inter-cellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1) and asymmetric dimethylarginine (ADMA)], insulin resistance and hormonal profile were assessed. All three treatments resulted in significant weight loss (DO 7.9 ± 1.2%, DA 11.0 ± 1.6%, DC 8.8 ± 1.1; P < 0.001 for time; P = 0.6 time × treatment). sVCAM-1, sICAM-1 and PAI-1 levels decreased with weight loss (P≤ 0.01), with no differences between treatments (P ≥ 0.4). ADMA levels did not change significantly (P = 0.06). Testosterone, sex hormone-binding globulin and the free androgen index (FAI) and insulin resistance also improved (P < 0.001) with no differences between treatments (P ≥ 0.2). Reductions in sVCAM-1 were correlated to reductions in testosterone (r = 0.32, P = 0.03) and FAI (r = 0.33, P = 0.02) as well as weight loss (r= 0.44, P = 0.002). Weight loss was also associated with reductions in sICAM-1 (r= 0.37, P = 0.008). Exercise training provided no additional benefit to following a high-protein, hypocaloric diet on markers of endothelial function in overweight/obese women with PCOS.

Diminished Global Arginine Bioavailability and Increased Arginine Catabolism as Metabolic Profile of Increased Cardiovascular Risk

PubMed Central

Tang, W. H. Wilson; Wang, Zeneng; Cho, Leslie; Brennan, Danielle M.; Hazen, Stanley L.

2009-01-01

Objective We hypothesized that an integrated assessment of arginine with its catabolic products may better predict cardiovascular risks than arginine levels alone. Background Arginine is the sole nitrogen source for nitric oxide (NO) synthesis. The major catabolic products of arginine are ornithine and citrulline. Methods Plasma levels of free arginine, ornithine, citrulline and the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) were measured using LC/MS/MS. We examined the relationship of global arginine bioavailability ratio (GABR, defined as arginine/[ornithine+citrulline]) vs. arginine and its catabolic metabolites to prevalence of coronary artery disease (CAD) and incidence of major adverse cardiovascular events (MACE = death, myocardial infarction, stroke) over a 3-year follow-up in 1,010 subjects undergoing elective cardiac catheterization. Results Patients with CAD had significantly lower GABR [median(IQR); 1.06(0.75, 1.31) versus 1.27(0.96, 1.73), p<0.001] and arginine levels [mean: 68 ±20 μM versus 74 ±24 μM, p<0.001) than those without CAD. After adjusting for Framingham risk score, C-reactive protein, and renal function, lower GABR (but not arginine levels) and higher citrulline levels remained significantly associated with both prevalence of CAD [adjusted odds-ratio (OR) 3.93, p<0.001 and 5.98, p<0.001, respectively] and 3-year risk for incidence of MACE [adjusted Hazard ratio (HR) 1.98, p=0.025 and 2.40, p=0.01, respectively], and remained significant after adjusting for ADMA. Conclusions GABR may serve as a more comprehensive concept of reduced NO synthetic capacity compared to systemic arginine levels. Diminished GABR and high citrulline levels are associated with both development of atherosclerotic CAD and heightened long-term risk for major adverse cardiac events. PMID:19477356

A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS.

PubMed

Wiśniewski, Jerzy; Fleszar, Mariusz G; Piechowicz, Joanna; Krzystek-Korpacka, Małgorzata; Chachaj, Angelika; Szuba, Andrzej; Lorenc-Kukula, Katarzyna; Masłowski, Leszek; Witkiewicz, Wojciech; Gamian, Andrzej

2017-11-01

Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l-arginine to l-citrulline. l-Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse-phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R 2  = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and precision (1.92-11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l-arginine and l-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline. Copyright © 2017 John Wiley & Sons, Ltd.

Gatekeeping versus Promiscuity in the Early Stages of the Andrimid Biosynthetic Assembly Line

PubMed Central

Magarvey, Nathan A.; Fortin, Pascal D.; Thomas, Paul M.; Kelleher, Neil L.; Walsh, Christopher T.

2009-01-01

The antibiotic andrimid, a nanomolar inhibitor of bacterial acetyl coenzyme A carboxylase, is generated on an unusual polyketide/nonribosomal pep-tide enzyme assembly line in that all thiolation (T) domains/small-molecule building stations are on separate proteins. In addition, a transglutaminase homologue is used to condense andrimid building blocks together on the andrimid assembly line. The first two modules of the andrimid assembly line yields an octatrienoyl-β-Phe-thioester tethered to the AdmI T domain, with amide bond formation carried out by a free-standing transglutaminase homologue AdmF. Analysis of the aminomutase AdmH reveals its specific conversion from l-Phe to (S)-β-Phe, which in turn is activated by AdmJ and ATP to form (S)-β-Phe-aminoacyl-AMP. AdmJ then transfers the (S)-β-Phe moiety to one of the free-standing T domains, AdmI, but not AdmA, which instead gets loaded with an octatrienoyl group by other enzymes. AdmF, the amide synthase, will accept a variety of acyl groups in place of the octatrienoyl donor if presented on either AdmA or AdmI. AdmF will also use either stereoisomer of phenylalanine or β-Phe when presented on AdmA and AdmI, but not when placed on noncognate T domains. Further, we show the polyketide synthase proteins responsible for the polyunsaturated acyl cap can be bypassed in vitro with N-acetylcysteamine as a low-molecular-weight acyl donor to AdmF and also in vivo in an Escherichia coli strain bearing the andrimid biosynthetic gene cluster with a knockout in admA. PMID:18652473

Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency.

PubMed

Nagasaka, Hironori; Yorifuji, Tohru; Egawa, Hiroto; Inui, Ayano; Fujisawa, Tomoo; Komatsu, Haruki; Tsukahara, Hirokazu; Uemoto, Shinji; Inomata, Yukihiro

2013-07-01

Urea cycle deficient patients with prominent hyperammonemic often exhibit abnormal production of nitric oxide (NO), which reduces vascular tone, along with amino acid abnormalities. However, information related to the metabolic changes in heterozygotes of ornithine transcarbamylase deficiency (OTCD) lacking overt hyperammonemia is quite limited. We examined vascular mediators and amino acids in non-hyperammonemic heterozygotes. Twenty-four heterozygous OTCD adult females without hyperammonemic bouts, defined as non-hyperammonemic carriers, were enrolled. We measured blood amino acids constituting urea cycle and nitric oxide (NO) cycle. Blood concentrations of nitrate/nitrite (NOx) as stable NO-metabolites, asymmetric dimethylarginine (ADMA) inhibiting NO synthesis, and endothelin-1 (ET-1) raising vascular tone were also determined. NOx concentrations were significantly lower in non-hyperammonemic carriers (p < 0.01). However, ADMA and ET-1 levels in this group were comparable to those in the age-matched control group. Arginine and citrulline levels were also significantly lower in non-hyperammonemic carriers than in controls (p < 0.01). Of the 24 non-hyperammonemic carriers, 10 often developed headaches. Their daily NOx and arginine levels were significantly lower than those in headache-free carriers (p < 0.05). In three carriers receiving oral l-arginine, blood NOx concentrations were significantly higher. In two of those three, the occurrence of headaches was decreased. These results suggest that NO cycle coupling with the urea cycle is altered substantially even in non-hyperammonemic OTCD carriers, predisposing them to headaches. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: An experimental and theoretical approach.

PubMed

Salmas, Ramin Ekhteiari; Gulhan, Mehmet Fuat; Durdagi, Serdar; Sahna, Engin; Abdullah, Huda I; Selamoglu, Zeliha

2017-08-01

The objective of this study was to evaluate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE; active compound in propolis), and pollen on biochemical oxidative stress biomarkers in rat kidney tissue inhibited by N ω -nitro-L-arginine methyl ester (L-NAME). The biomarkers evaluated were paraoxonase (PON1), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), and nuclear factor kappa B (NF-κB). TAS levels and PON1 activity were significantly decreased in kidney tissue samples in the L-NAME-treated group (P < 0.05). The levels of TAS and PONI were higher in the L-NAME plus propolis, CAPE, and pollen groups compared with the L-NAME-treated group. TOS, ADMA, and NF-κB levels were significantly increased in the kidney tissue samples of the L-NAME-treated group (P < 0.05). However, these parameters were significantly lower in the L-NAME plus propolis, CAPE, and pollen groups (P < 0.05) compared with rats administered L-NAME alone (P < 0.05). Furthermore, the binding energy of CAPE within catalytic domain of glutathione reductase (GR) enzyme as well as its inhibitory mechanism was determined using molecular modeling approaches. In conclusion, experimental and theoretical data suggested that oxidative alterations occurring in the kidney tissue of chronic hypertensive rats may be prevented via active compound of propolis, CAPE administration. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

PubMed

Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Bayat, Zeynep; Aras, Bekir; Metineren, Mehmet Huseyin; Yucel, Mehmet; Simsek, Hasan

2016-02-01

Renal ischemia-reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-ɣ (PPAR-ɣ), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF-κB, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR-ɣ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects. © 2016 John Wiley & Sons Australia, Ltd.

The effects of Ramadan fasting on endothelial function in patients with cardiovascular diseases.

PubMed

Yousefi, B; Faghfoori, Z; Samadi, N; Karami, H; Ahmadi, Y; Badalzadeh, R; Shafiei-Irannejad, V; Majidinia, M; Ghavimi, H; Jabbarpour, M

2014-07-01

Endothelial dysfunction, which can be manifested by loss of nitric oxide bioavailability, is an increasingly recognized cause of cardiovascular diseases. Previous studies showed that diets affect endothelial function and modify cardiovascular risks. This study aimed to assess the effects of Ramadan fasting, as a diet intervention, on endothelial function. The study population consisted of 21 male patients (mean age: 52±9 years) with cardiovascular risks (coronary artery disease, cerebrovascular or peripheral arterial diseases). The biochemical variables in serum of patients were measured 2 days before and after Ramadan fasting. The levels of asymmetric dimethylarginine (ADMA) and vascular endothelial growth factor (VEGF) were evaluated using the enzyme-linked immunosorbent assay. Nitric oxide (NO) and Malondialdehyde (MDA) levels were measured by the Griess and thiobarbituric acid reaction substances assay, respectively. NO levels in patients after Ramadan fasting were significantly higher compared with the baseline value (85.1±11.54 vs 75.8±10.7 μmol/l) (P<0.05). Post-Ramadan levels of ADMA decreased significantly in comparison with pre-Ramadan levels (802.6±60.9 vs 837.6±51.0 nmol/l) (P<0.05). In addition, the levels of VEGF and MDA changed during Ramadan fasting, but these changes were not statistically significant (228.1±27.1 vs 222.7±22.9 pg/ml and 3.2±0.7 vs 3.6±1.1 μmol/l, respectively). Ramadan fasting may have beneficial effects on endothelial function and can modulate cardiovascular risks. Further studies are needed to confirm the clinical significance of Ramadan fasting on cardiovascular health.

In Vitro Investigation of Crosstalk between Fatty Acid and Polyketide Synthases in the Andrimid Biosynthetic Assembly Line.

PubMed

Ishikawa, Fumihiro; Sugimoto, Hiroyasu; Kakeya, Hideaki

2016-11-17

Andrimid (Adm) synthase, which belongs to the type II system of enzymes, produces Adm in Pantoea agglomerans. The adm biosynthetic gene cluster lacks canonical acyltransferases (ATs) to load the malonyl group to acyl carrier proteins (ACPs), thus suggesting that a malonyl-CoA ACP transacylase (MCAT) from the fatty acid synthase (FAS) complex provides the essential AT activity in Adm biosynthesis. Here we report that an MCAT is essential for catalysis of the transacylation of malonate from malonyl-CoA to AdmA polyketide synthase (PKS) ACP in vitro. Catalytic self-malonylation of AdmA (PKS ACP) was not observed in reactions without MCAT, although many type II PKS ACPs are capable of catalyzing self-acylation. This lack of self-malonylation was explained by amino acid sequence analysis of the AdmA PKS ACP and the type II PKS ACPs. The results show that MCAT from the organism's FAS complex can provide the missing AT activity in trans, thus suggesting a protein-protein interaction between the fatty acid and polyketide synthases in the Adm assembly line. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of the Separation of NDA-Derivatized Methylarginines by Capillary and Microchip Electrophoresis

PubMed Central

Linz, Thomas H.; Snyder, Christa M.; Lunte, Susan M.

2013-01-01

The methylated arginines (MAs) monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) have been shown to be independent predictors of cardiovascular disease. This article describes progress regarding the development of an analytical method capable of rapidly analyzing MAs using capillary electrophoresis (CE) and microchip electrophoresis (MCE) with laser-induced fluorescence (LIF) detection. Several parameters including buffer composition and separation voltage were optimized to achieve an ideal separation. The analytes of interest were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) to produce fluorescent 1-cyanobenz[f]isoindole (CBI) derivatives and then subjected to CE analysis. Baseline resolution of SDMA, ADMA, MMA, and arginine was achieved in less than 8 min. The limits of detection for SDMA, ADMA, MMA, and arginine were determined to be 15, 20, 25, and 5 nM, respectively, which are well below the expected plasma concentrations. The CE separation method was then transferred to a glass MCE device with LIF detection. MAs were baseline resolved in 3 min on-chip using a 14 cm separation channel with detection limits of approximately 10 nM for each species. To the best of the authors’ knowledge, this is the first report of the separation of MAs by MCE. PMID:22357605

Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

PubMed

El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

2012-04-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of the transdermal low-level laser therapy on endothelial function.

PubMed

Szymczyszyn, Alicja; Doroszko, Adrian; Szahidewicz-Krupska, Ewa; Rola, Piotr; Gutherc, Radosław; Jasiczek, Jakub; Mazur, Grzegorz; Derkacz, Arkadiusz

2016-09-01

The effect of low-level laser therapy (LLLT) on the cardiovascular system is not fully established. Since the endothelium is an important endocrine element, establishing the mechanisms of LLLT action is an important issue.The aim of the study was to evaluate the effect of transdermal LLLT on endothelial function.In this study, healthy volunteers (n = 40, age = 20-40 years) were enrolled. N = 30 (14 female, 16 male, mean age 30 ± 5 years) constituted the laser-irradiated group (LG). The remaining 10 subjects (6 women, 4 men, mean age 28 ± 5 years) constituted the control group (CG). Participants were subjected to LLLT once a day for three consecutive days. Blood for biochemical assessments was drawn before the first irradiation and 24 h after the last session. In the LG, transdermal illumination of radial artery was conducted (a semiconductor laser λ = 808 nm, irradiation 50 mW, energy density 1.6 W/cm(2) and a dose 20 J/day, a total dose of 60 J). Biochemical parameters (reflecting angiogenesis: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiostatin; antioxidative status: glutathione (GSH) and the nitric oxide metabolic pathway: symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA) and L-arginine) were assessed. In the LG, a significant increase in GSH levels and considerable decrease in angiostatin concentration following the LLLT were observed. No significant differences in levels of the VEGF, FGF, SDMA, ADMA were observed.LLLT modifies vascular endothelial function by increasing its antioxidant and angiogenic potential. We found no significant differences in levels of the nitric oxide pathway metabolites within 24 h following the LLLT irradiation.

Supplementation of a γ-tocopherol-rich mixture of tocopherols in healthy men protects against vascular endothelial dysfunction induced by postprandial hyperglycemia.

PubMed

Mah, Eunice; Noh, Sang K; Ballard, Kevin D; Park, Hea Jin; Volek, Jeff S; Bruno, Richard S

2013-01-01

Postprandial hyperglycemia induces oxidative stress responses, impairs vascular endothelial function (VEF) and increases the risk of cardiovascular disease. We hypothesized that the antioxidant and anti-inflammatory activities of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) would protect against vascular dysfunction that is otherwise caused by postprandial hyperglycemia by decreasing oxidative stress and proinflammatory responses, and improving nitric oxide (NO•) homeostasis. In a randomized, crossover study, healthy men (n=15; 21.8 ± 0.8 years) completed a fasting oral glucose challenge (75 g) with or without prior supplementation of γ-TmT (5 days). Brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine and asymmetric dimethylarginine (ADMA) were measured at regular intervals during a 3-h postprandial period. Supplementation of γ-TmT increased (P<.05) plasma γ-T by threefold and γ-carboxyethyl-hydroxychroman by more than ninefold without affecting α-T, glucose, arginine or ADMA. Baseline FMD, MDA, arginine and ADMA were unaffected by γ-TmT (P>.05). Postprandial FMD decreased 30%-44% (P<.05) following glucose ingestion, but was maintained with γ-TmT. Supplementation of γ-TmT also attenuated postprandial increases in MDA that occurred following glucose ingestion. Plasma arginine decreased (P<.05) in both trials to a similar extent regardless of γ-TmT supplementation. However, the ratio of ADMA/arginine increased time-dependently in both trials (P<.05), but to a lesser extent following γ-TmT supplementation (P<.05). Inflammatory proteins were unaffected by glucose ingestion or γ-TmT. Collectively, these findings support that short-term supplementation of γ-TmT maintains VEF during postprandial hyperglycemia possibly by attenuating lipid peroxidation and disruptions in NO• homeostasis, independent of inflammation. Published by Elsevier Inc.

Simultaneous ablation of prmt-1 and prmt-5 abolishes asymmetric and symmetric arginine dimethylations in Caenorhabditis elegans.

PubMed

Hirota, Keiko; Shigekawa, Chihiro; Araoi, Sho; Sha, Liang; Inagawa, Takayuki; Kanou, Akihiko; Kako, Koichiro; Daitoku, Hiroaki; Fukamizu, Akiyoshi

2017-06-01

Protein arginine methyltransferases (PRMTs) catalyze the transfer of a methyl group from S-adenosylmethionine to arginine residues and are classified into two types: type I producing asymmetric dimethylarginine (ADMA) and type II producing symmetric dimethylarginine (SDMA). PRMTs have been shown to regulate many cellular processes, including signal transduction, transcriptional regulation and RNA processing. Since the loss-of-function mutation of PRMT1 and PRMT5, each of which is the predominant type I and II, respectively, causes embryonic lethality in mice, their physiological significance at the whole-body level remains largely unknown. Here, we show the morphological and functional phenotypes of single or double null alleles of prmt-1 and prmt-5 in Caenorhabditis elegans. The prmt-1;prmt-5 double mutants are viable, and exhibit short body length and small brood size compared to N2 and each of the single mutants. The liquid chromatography-tandem mass spectrometry analysis demonstrated that the levels of ADMA and SDMA were abolished in the prmt-1;prmt-5 double mutants. Both prmt-1 and prmt-5 were required for resistance to heat and oxidative stresses, whereas prmt-5 is not involved in lifespan regulation even when prmt-1 is ablated. This mutant strain would be a useful model animal for investigating the role of asymmetric and symmetric arginine dimethylation in vivo. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

INF-β1b therapy modulates L-arginine and nitric oxide metabolism in patients with relapse remittent multiple sclerosis.

PubMed

Stojanovic, Ivana; Vojinovic, Slobodan; Ljubisavljevic, Srdjan; Pavlovic, Radmila; Basic, Jelena; Pavlovic, Dusica; Ilic, Andjelka; Cvetkovic, Tatjana; Stukalov, Maja

2012-12-15

The scope of this study is the examination of NO(2)+NO(3), 3-nitrotyrosine (3-NT), S-nitrosothiols (RSNO), arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethyl-L-arginine concentrations in plasma of MS patients during interferon-β1b therapy. The study population included 15 (12 women, 3 men) untreated MS patients and 12 (10 women, 2 men) interferon-β1b treated MS patients with clinically definite relapsing MS (McDonalds criteria) for at least 1 year and a baseline EDSS score of 1.0 to 3.5 inclusive. Patients were treated with 250 μg IU interferon-β1b s.c. every second day during 30 months. The disease course was evaluated using correlations between baseline EDSS score and relapse rates in both groups. During interferon-β1b treatment, EDSS scores in treated patients were decreased compared to untreated ones - after 18 and 30 months (p<0.05). In interferon-β1b treated MS patients, NO(2)+NO(3), 3-NT and RSNO plasma concentrations were significantly lower (p<0.05), while arginase activity, ADMA and SDMA levels were significantly increased (p<0.05) during the therapy, compared to the baseline levels in treated patients. The investigated parameters may be the new biomarkers, providing information for the therapeutic approach and valuable in clinical monitoring. Copyright © 2012 Elsevier B.V. All rights reserved.

Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

PubMed

Bassi, Roberto; Niewczas, Monika A; Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D'Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and Angiotensin-converting Enzyme Inhibitor

PubMed Central

Bar, Anna; Olkowicz, Mariola; Tyrankiewicz, Urszula; Kus, Edyta; Jasinski, Krzysztof; Smolenski, Ryszard T.; Skorka, Tomasz; Chlopicki, Stefan

2017-01-01

Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR-/-) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1–7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio. Endothelial function and permeability were evaluated in the brachiocephalic artery (BCA) in 4-month-old ApoE/LDLR-/- mice that were non-treated or treated for 1 month or 2 months with either MNA (100 mg/kg/day) or perindopril (10 mg/kg/day). The 3D IntraGate®FLASH sequence was used for evaluation of BCA volume changes following acetylcholine (Ach) administration, and for relaxation time (T1) mapping around BCA to assess endothelial permeability using an intravascular contrast agent. Activity of ACE/Ang II and ACE2/Ang-(1–7) pathways as well as metabolites of L-arginine/ADMA pathway were measured using liquid chromatography/mass spectrometry-based methods. In non-treated 6-month-old ApoE/LDLR-/- mice, Ach induced a vasoconstriction in BCA that amounted to –7.2%. 2-month treatment with either MNA or perindopril resulted in the reversal of impaired Ach-induced response to vasodilatation (4.5 and 5.5%, respectively) and a decrease in endothelial permeability (by about 60% for MNA-, as well as perindopril-treated mice). Improvement of endothelial function by MNA and perindopril was in both cases associated with the activation of ACE2/Ang-(1–7) and the inhibition of ACE/Ang II axes as evidenced by an approximately twofold increase in Ang-(1–9) and Ang-(1–7) and a proportional decrease in Ang II and its active metabolites. Finally, MNA and perindopril treatment resulted in an increase in L-arginine/ADMA ratio by 107% (MNA) and 140% (perindopril), as compared to non-treated mice. Functional and biochemical endothelial profiling in ApoE/LDLR-/- mice in vivo revealed that 2-month treatment with MNA (100 mg/kg/day) displayed a similar profile of vasoprotective effect as 2-month treatment with perindopril (10 mg/kg/day): i.e., the improvement in endothelial function that was associated with the beneficial changes in ACE/Ang II-ACE2/Ang (1–7) balance and in L-arginine/ADMA ratio in plasma. PMID:28443021

Amniotic Fluid Arginine from Gestational Weeks 13 to 15 Is a Predictor of Birth Weight, Length, and Head Circumference.

PubMed

Bjørke-Jenssen, Astrid; Ueland, Per Magne; Bjørke-Monsen, Anne-Lise

2017-12-14

Arginine is a constituent of proteins and a precursor for polyamines and nitric oxide, and is essential for placentation, angiogenesis, and growth. Maternal plasma arginine concentrations are found to be lower in pregnancies complicated by fetal growth restriction, and arginine supplementation in later pregnancy is reported to increase birth weight. We measured arginine and the metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in the amniotic fluid obtained in pregnancy weeks 13 to 15 from 363 pregnancies with a documented normal outcome and related the concentrations to birth weight, length, and head circumference. Arginine was higher in the amniotic fluid from female (mean 40.8 (SD 10.6) µmol/L) compared to male fetuses (37.4 (SD 11.2) µmol/L, p = 0.003). Despite the gender difference, arginine in the amniotic fluid from gestational weeks 13-15 was the strongest predictor for birth weight, length, and head circumference. ADMA was a strong predictor for birth weight and length, SDMA for birth weight, while Arg/ADMA and Arg/SDMA only predicted head circumference in multiple linear regression models. Due to increased arginine demands, pregnancy is considered a state of relative arginine deficiency. Our findings reflect the importance of a good maternal arginine status in early pregnancy, an observation that should be evaluated in an intervention study.

Impaired Arginine Metabolism Coupled to a Defective Redox Conduit Contributes to Low Plasma Nitric Oxide in Polycystic Ovary Syndrome.

PubMed

Krishna, Meera B; Joseph, Annu; Thomas, Philip Litto; Dsilva, Belinda; Pillai, Sathy M; Laloraya, Malini

2017-01-01

Though oxidative stress is associated with Polycystic Ovary Syndrome (PCOS), the status of nitric oxide is still unclear. Nitric Oxide (NO) plays pivotal roles in many physiological functions which are compromised in PCOS. Our recent study reveals lowered T-regulatory cells (Tregs) in PCOS, and Treg generation is known to be regulated by NO levels. However concrete evidences are lacking on mechanisms modulating NO levels under PCOS. This is a retrospective case-control cohort study, comprised of PCOS women (N=29) and normal menstruating women as controls (N=20). We analysed NOx (nitrite+nitrate) and hydrogen peroxide (H2O2) concentrations, transcript levels of endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and arginine modulators, hydrogen peroxide regulators in the cohort. PCOS women showed reduced plasma NOx(nitrate+nitrite) and H2O2 compared to controls. We report reduction in transcript levels of iNOS/NOS2 and eNOS/NOS3 in PCOS peripheral blood. The transcripts involved in arginine bioavailability: Argininosuccinate lyase (ASL), Solute Carrier Family1, member 7 (SLC7A1) and Arginase 1 (ARG1) and Asymmetric Dimethyl Arginine (ADMA) metabolism: Protein arginine methyltransferase 1 (PRMT1) and Dimethylarginine dimethylaminohydrolase 2 (DDAH2) also showed differential expression. H2O2 concentration in PCOS women was also found to be reduced. The reduction can be attributed to increase in catalase levels as a consequence of the body's effort to alleviate the oxidative burden in the system. Our study advocates that PCOS women have lowered NO due to reduced iNOS/eNOS expression, low H2O2, high ADMA synthesis and reduced arginine bioavailability. An in-depth analysis of redox biology of PCOS to open up potential therapeutic strategies is highly recommended. © 2017 The Author(s). Published by S. Karger AG, Basel.

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

PubMed Central

Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D’Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Background Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. Methods To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. Results LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. Conclusions We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function. PMID:28052095

Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway

PubMed Central

Feng, Jun; Chen, Hua-Wen; Pi, Li-Juan; Wang, Jin; Zhan, Da-Qian

2017-01-01

The study aimed to investigate the protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats (SHRs) through the Cys-C/Wnt signaling pathway. Thirty SHRs were randomly divided into cardiac hypertrophy, low- and high-dose tanshinone IIA groups. Ten Wistar-Kyoto rats were selected as control group. The systolic blood pressure (SBP), heart weight (HW), left ventricular weight (LVW) and body weight (BW) of all rats were recorded. HE staining and qRT-PCR were applied to observe the morphology of myocardial tissue and mRNA expressions of COL1A1 and COL3A1. ELISA and Western blotting were used to measure the serum asymmetric dimethylarginine (ADMA), nitric oxide (NO) and cardiac troponin I (cTnI) levels, and the expressions of the Cys-C/Wnt signaling pathway-related proteins, eNOS and Nox4. Compared with the cardiac hypertrophy group, the SBP, HW/BW, LVW/BW, swelling degree of myocardial cells, COL1A1 and COL3A1 mRNA expressions, serum cTnI and ADMA levels, and the Cys-C/Wnt signaling pathway-related proteins and Nox4 expressions in the low- and high-dose tanshinone IIA groups were decreased, but the endothelial NO synthase (eNOS), phosphorylated eNOS (Ser1177) and NO expressions were increased. No significant difference was found between the low- and high-dose tanshinone IIA groups. Our study indicated a protective effect of tanshinone IIA against cardiac hypertrophy in SHRs through inhibiting the Cys-C/Wnt signaling pathway. PMID:28053285

Nitric oxide activity in platelets of dengue haemorrhagic fever patients: the apparent paradoxical role of ADMA and l-NMMA.

PubMed

Matsuura, Cristiane; Moraes, Thalyta L; Barbosa, Julia B; Moss, Monique B; Siqueira, Mariana A S; Mann, Giovanni E; Neto, Miguel Lemos; Brunini, Tatiana M C; Mendes-Ribeiro, Antonio Claudio

2012-03-01

Dengue haemorrhagic fever (DHF) is a prevalent acute disease that occurs in patients infected by an arbovirus in tropical and subtropical regions. We have previously shown increased intraplatelet nitric oxide (NO) production in patients with dengue fever associated with reduced platelet aggregation. In this study, l-arginine transport as well as expression and activity of nitric oxide synthase (NOS) isoforms in the presence or absence of l-arginine analogues were examined in 23 DHF patients. l-arginine transport and NOS activity in platelets were increased in patients with DHF compared with controls. However, platelet endothelial NOS (eNOS) and inducible (iNOS) protein levels did not differ between healthy controls and DHF patients. Endogenous or exogenous analogues did not inhibit platelet NOS activity from DHF patients. In contrast, endogenous l-arginine analogues [N(G)-monomethyl-l-arginine (l-NMMA) and asymmetric dimethylarginine (ADMA)] inhibited NOS activity in platelets from healthy subjects. These results show the first evidence that the intraplatelet l-arginine-NO pathway is activated in DHF patients. The lack of inhibition of NO formation in vitro by all l-arginine analogues tested in DHF platelets may suggest another mechanism by which NOS activity can be regulated. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Detection and quantification of α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid: a metabolite of asymmetric dimethylarginine.

PubMed

Martens-Lobenhoffer, Jens; Rodionov, Roman N; Drust, Andreas; Bode-Böger, Stefanie M

2011-12-15

Nitric oxide is an ubiquitary cell signaling substance. Its enzymatic production rate by nitric oxide synthase is regulated by the concentrations of the substrate L-arginine and the competitive inhibitor asymmetric dimethylarginine (ADMA). A newly recognized elimination pathway for ADMA is the transamination to α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid (DMGV) by the enzyme alanine-glyoxylate aminotransferase 2 (AGXT2). This pathway has been proven to be relevant for nitric oxide regulation, but up to now no method exists for the determination of DMGV in biological fluids. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of DMGV. D(6)-DMGV was used as internal standard. Samples were purified online by column switching, and separation was achieved on a porous graphitic carbon column. The calibration was linear over ranges of 10 to 200 nmol/L for plasma and 0.1 to 20 μmol/L for urine. The intra- and interday accuracies and precisions in plasma and urine were better than 10%. In plasma samples, DMGV was present in concentrations between 19.1 and 77.5 nmol/L. In urine samples, concentrations between 0.0114 and 1.03 μmol/mmol creatinine were found. This method can be used as a tool for the scientific investigation of the ADMA conversion to DMGV via the enzyme AGXT2. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of Febuxostat on the Endothelial Dysfunction in Hemodialysis Patients: A Randomized, Placebo-Controlled, Double-Blinded Study.

PubMed

Alshahawey, Mona; Shahin, Sara Mahmoud; Elsaid, Tamer Wahid; Sabri, Nagwa Ali

2017-01-01

Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study. Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups. Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns. © 2017 S. Karger AG, Basel.

Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats.

PubMed

Martínez, Ana Cristina; Stankevicius, Edgaras; Jakobsen, Preben; Simonsen, Ulf

2006-05-01

The present study was designed to explore whether there are any effects on neurogenic responses in penile small arteries during the development of hypertension in a one-kidney, one-clip (1K1C) model, a non-renin-dependent model of renovascular hypertension. Five weeks after surgery, male Sprague-Dawley rats were given vehicle, bendroflumethiazide (7.5 mg/kg/day), or L-arginine (2 g/kg/day) in their drinking water for five weeks. Experiments were performed on penile small artery rings (150-200 microm) mounted on microvascular myographs for electrical field stimulation (EFS), and erectile tissue was processed for immunohistochemistry. Maximal neurogenic contractions were unmodified in penile preparations. Relaxations induced by EFS were reduced in the presence of ADMA. In 1K1C rats, neurogenic vasorelaxation mediated by nitric oxide (NO) was unaltered, while relaxation resistant to NO synthase inhibition was blunted. L-arginine and bendroflumethiazide lowered blood pressure in 1K1C rats, but vasodilation was still blunted in the penile arteries. Immunoreactivity for factor VIII and neuronal NO synthase was unaltered in penile arteries from 1K1C animals. Endothelium-dependent vasorelaxation evoked by acetylcholine was also blunted in preparations from 1K1C rats, while exogenous NO relaxation was unaffected. Plasma concentrations and urinary excretion of ADMA did not differ among the experimental animals. Our findings indicate that the reduced release of a non-NO vasodilatory neurotransmitter accounts for the impaired neurogenic vasodilation of the penile arteries. Although ADMA inhibits penile vasorelaxation, it is unlikely to affect erectile function in 1K1C rats.

Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors.

PubMed

Miralbell, Júlia; López-Cancio, Elena; López-Oloriz, Jorge; Arenillas, Juan Francisco; Barrios, Maite; Soriano-Raya, Juan José; Galán, Amparo; Cáceres, Cynthia; Alzamora, Maite; Pera, Guillem; Toran, Pere; Dávalos, Antoni; Mataró, Maria

2013-01-01

Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages. Copyright © 2013 S. Karger AG, Basel.

Effects of DHA-enriched fish oil on monocyte/macrophage activation marker sCD163, asymmetric dimethyl arginine, and insulin resistance in type 2 diabetic patients.

PubMed

Toupchian, Omid; Sotoudeh, Gity; Mansoori, Anahita; Nasli-Esfahani, Ensieh; Djalali, Mahmoud; Keshavarz, Seyyed Ali; Koohdani, Fariba

2016-01-01

The beneficial effects of n-3 polyunsaturated fatty acids on reducing cardiovascular risks are well documented. However, the relative effect on some markers of macrophage activation and vascular function is unclear. The primary objective of this study was to investigate the effects of docosahexaenoic acid (DHA)-enriched fish oil on the marker of monocyte/macrophage activation factor soluble CD163, asymmetric dimethyl arginine (ADMA), and insulin resistance in type 2 diabetic patients. In this double-blind randomized controlled trial, 72 type 2 diabetic patients with an age between 30-70 years and body mass index (BMI) of 18.5 to 40 kg/m(2) were randomly assigned to receive 2.4-g DHA-enriched fish oil or placebo per day for 8 weeks. Anthropometric measurements, biochemical, and body composition analyses were assessed at baseline and end of study. Analysis of covariance (ANCOVA) was conducted by controlling for possible confounders to assess between-group differences. Serum levels of sCD163, triglycerides, waist circumference (WC), and weight to height ratio (WHtR) decreased significantly in the fish oil group when compared with the control group. Serum ADMA concentration decreased in the fish oil group with no significant between-group differences. Controlling for confounders revealed that the differences observed in sCD163, triglycerides, WC, and WHtR remained statistically significant. Short-time fish oil supplementation decreased serum sCD163, triglycerides levels, WC, and WHtR in T2DM patients. Because of the positive relationship between sCD163 levels and some T2DM and obesity-related complications, it seems that DHA can be considered as a key intervention in obesity and T2DM. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.

PubMed

Cortés, Berenice; Núñez, Isabel; Cofán, Montserrat; Gilabert, Rosa; Pérez-Heras, Ana; Casals, Elena; Deulofeu, Ramón; Ros, Emilio

2006-10-17

We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.

The Modular Instrumentation Family: Defense and Industry Applications

DTIC Science & Technology

2015-02-01

commercial industry systems. The author can be contacted at gerome.q.banks.civ@mail.mil. Boeing 747 undergoing cargo hold vulnerability testing at Aberdeen...state and local governments, allied foreign governments and commercial entities. Conse- quently, ADMAS models are designed for various types of

Acellular dermal matrix seeded with autologous gingival fibroblasts for the treatment of gingival recession: a proof-of-concept study.

PubMed

Jhaveri, Hiral M; Chavan, Mahesh S; Tomar, Geetanjali B; Deshmukh, Vijay L; Wani, Mohan R; Miller, Preston D

2010-04-01

One of the most common esthetic concerns associated with periodontal tissues is gingival recession. There are multiple periodontal plastic surgery approaches documented in the literature for the treatment of such defects. With the tremendous advances being made in periodontal science and technology, tissue engineering could be considered among the latest exciting techniques for recession management. In this split-mouth, controlled, double-masked clinical case series, 20 sites from 10 patients with Miller Class I or II recessions affecting canines or premolars in the maxillary arch were selected. One tooth in each patient was randomized to receive either a subepithelial connective tissue graft (SCTG) (control group) or an acellular dermal matrix allograft (ADMA) seeded with autologous gingival fibroblasts (test group) under a coronally positioned flap. Clinical parameters, including recession depth, probing depth, clinical attachment level, width of keratinized tissue, attached gingiva, and plaque scores, were recorded by a calibrated examiner at baseline and 3 and 6 months. The inflammation of grafted sites was scored, and the healing time was calculated. The final esthetic outcome of treated sites was assessed by the root coverage esthetic score at the end of 6 months. There were no significant differences between test and control sites for all measured clinical parameters. However, the test sites demonstrated less inflammation in the early postoperative period. Within the limits of this case series, the results indicate that an ADMA seeded with autologous gingival fibroblasts by tissue-engineering technology may be explored as a substitute to an SCTG for the treatment of Miller Class I and II recession defects.

Obesity, lipid profiles and oxidative stress in children after liver transplantation.

PubMed

Czubkowski, Piotr; Wierzbicka, Aldona; Pawłowska, Joanna; Jankowska, Irena; Socha, Piotr

2017-01-01

In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx). We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results. At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85 th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95 th and >85 Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a). Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.

Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy.

PubMed

Haghikia, A; Podewski, E; Libhaber, E; Labidi, S; Fischer, D; Roentgen, P; Tsikas, D; Jordan, J; Lichtinghagen, R; von Kaisenberg, C S; Struman, I; Bovy, N; Sliwa, K; Bauersachs, J; Hilfiker-Kleiner, Denise

2013-07-01

Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.

Atomic Engineering of Superconductors by Design

DTIC Science & Technology

2014-10-23

Kumah, J. H. Ngai, E. D. Specht , D. A. Arena, F. J. Walker, C. H. Ahn. Phase diagram of compressively strained nickelate thin films, Applied Physics...1940 (2014)10.1002/adma.201304256). 3. A. S. Disa, D. P. Kumah, J. H. Ngai, E. D. Specht , D. A. Arena, F. J. Walker, C. H. Ahn, Phase diagram of

Effects of prior aerobic exercise on sitting-induced vascular dysfunction in healthy men.

PubMed

Ballard, Kevin D; Duguid, Robert M; Berry, Craig W; Dey, Priyankar; Bruno, Richard S; Ward, Rose Marie; Timmerman, Kyle L

2017-12-01

Acute aerobic exercise prevents sitting-induced impairment of flow-mediated dilation (FMD). Further, evidence suggests that sitting-induced impairment of FMD occurs via an oxidative stress-dependent mechanism that disrupts endothelial function. We hypothesized that acute aerobic exercise would prevent impairment of femoral artery FMD by limiting oxidative stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric oxide (NO) status. In a randomized, cross-over study, healthy men (n = 11; 21.2 ± 1.9 years) completed two 3 h sitting trials that were preceded by 45 min of either quiet rest (REST) or a single bout of continuous treadmill exercise (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)] were assessed at baseline, 1 h following EX (or REST) (0 h), and at 1 h intervals during 3 h of uninterrupted sitting. Data were analyzed using repeated measures ANOVA. During REST, femoral artery FMD declined from baseline (2.6 ± 1.8%) at 1, 2, and 3 h of sitting and resting shear rate decreased at 3 h. In contrast, when sitting was preceded by EX, femoral artery FMD (2.7 ± 2.0%) and resting shear rate responses were unaffected. No between trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or SDMA. Prior aerobic exercise prevented the decline in femoral artery FMD that is otherwise induced by prolonged sitting independent of changes in oxidative stress, ET-1, and NO status.

Febuxostat attenuates paroxysmal atrial fibrillation-induced regional endothelial dysfunction.

PubMed

Li, YanGuang; Chen, FuKun; Deng, Long; Lin, Kun; Shi, Xiangmin; Zhaoliang, Shan; Wang, YuTang

2017-01-01

Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear. We assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO). Eighteen male New Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or FX+pacing (FP) groups. Group P and group FP received rapid atrial pacing (RAP). Group FP was administered febuxostat (FX) for 7days before RAP. Post-procedure, blood samples were collected from the LA, right atrium (RA) and peripheral circulation. Tissues from the LA and RA were obtained. Endothelial dysfunction (thrombomodulin [TM], von Willebrand factor [VWF], asymmetric dimethylarginine [ADMA]), and indirect thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1.2]) and oxidative stress in atrial tissue (xanthine oxidase [XO], superoxide dismutase [SOD], malondialdehyde [MDA]) were measured using an Enzyme-linked immunosorbent assay. Atrial endothelial expression of TM and VWF was measured by histology/western blotting. Endothelial dysfunction (TM, VWF, ADMA), TAT generation and oxidative stress (XO, SOD, MDA) in group P were more significant compared with that in group S (p<0.05, respectively). In group P, all of these changes occurred to a greater extent in the LA compared with those in the RA or peripheral circulation. In group FP, FX attenuated endothelial dysfunction and reduced TAT levels by inhibition of XO-mediated oxidative stress. PAF can lead to endothelial dysfunction and TAT generation by XO-mediated oxidative stress. The LA is more susceptible to these effects. FX can attenuate these changes by inhibition XO and XO-mediated oxidative stress. Copyright © 2016. Published by Elsevier Ltd.

Opposite Associations of Plasma Homoarginine and Ornithine with Arginine in Healthy Children and Adolescents

PubMed Central

JaŸwińska-Kozuba, Aleksandra; Martens-Lobenhoffer, Jens; Kruszelnicka, Olga; Rycaj, Jarosław; Chyrchel, Bernadeta; Surdacki, Andrzej; Bode-Böger, Stefanie M.

2013-01-01

Homoarginine, a non-proteinogenic amino acid, is formed when lysine replaces ornithine in reactions catalyzed by hepatic urea cycle enzymes or lysine substitutes for glycine as a substrate of renal arginine:glycine amidinotransferase. Decreased circulating homoarginine and elevated ornithine, a downstream product of arginase, predict adverse cardiovascular outcome. Our aim was to investigate correlates of plasma homoarginine and ornithine and their relations with carotid vascular structure in 40 healthy children and adolescents aged 3–18 years without coexistent diseases or subclinical carotid atherosclerosis. Homoarginine, ornithine, arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry with stable isotope-labeled internal standards. Intima-media thickness (IMT) and extra-medial thickness (EMT) of common carotid arteries were estimated by B-mode ultrasound. Homoarginine correlated with arginine (r = 0.43, p = 0.005), age (r = 0.42, p = 0.007) and, weakly, with an increased arginine-to-ornithine ratio, a putative measure of lower arginase activity (r = 0.31, p = 0.048). Ornithine correlated inversely with arginine (r = −0.64, p < 0.001). IMT, EMT or their sum were unrelated to any of the biochemical parameters (p > 0.12). Thus, opposite associations of plasma homoarginine and ornithine with arginine may partially result from possible involvement of arginase, an enzyme controlling homoarginine degradation and ornithine synthesis from arginine. Age-dependency of homoarginine levels can reflect developmental changes in homoarginine metabolism. However, neither homoarginine nor ornithine appears to be associated with carotid vascular structure in healthy children and adolescents. PMID:24192823

Metabolomic Analysis of the Secretome of Human Embryonic Stem Cells Following Methyl Parathion and Methyl Paraoxon Exposure. Phase 3. LC-MS-MS Structural Confirmation

DTIC Science & Technology

2014-01-01

attention deficit - hyperactivity disorder ( ADHD ) in their offspring. The...17 ACRONYMS AND ABBREVIATIONS ADHD attention deficit - hyperactivity disorder ADMA asymmetric dimethylarginine APG Aberdeen Proving...Wright, R.O.; Weisskopf, M.G. Attention - Deficit / Hyperactivity Disorder and Urinary Metabololites or Organophosphate Pesticides. Pediatrics

Methotrexate, blood pressure and markers of arterial function in patients with rheumatoid arthritis: a repeated cross-sectional study

PubMed Central

Mangoni, Arduino A.; Baghdadi, Leena R.; Shanahan, E. Michael; Wiese, Michael D.; Tommasi, Sara; Elliot, David; Woodman, Richard J.

2017-01-01

Background: Methotrexate (MTX) treatment in rheumatoid arthritis (RA) has been associated with lower cardiovascular risk compared to other disease-modifying antirheumatic drugs (DMARDs). We sought to identify whether the MTX-associated cardioprotection involves changes in blood pressure (BP) and/or arterial function. Methods: Clinic and 24-hour peripheral and central systolic and diastolic BP (SBP and DBP), augmentation index (AIx), pulse wave velocity (PWV) and plasma asymmetric dimethylarginine (ADMA) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 56, age 61 ± 13 years, 70% females) or other DMARDs (non-MTX group, n = 30, age 63 ± 12 years, 76% females). Measurements were performed at baseline and after 8 months. Results: After adjusting for visit, age, gender, body mass index, folic acid use and 28-joint disease activity score, the MTX group had significantly lower clinic peripheral SBP (−7.7 mmHg, 95% CI −13.2 to −2.3, p = 0.006) and DBP (−6.1 mmHg, 95% CI −9.8 to −2.4, p = 0.001) and clinic central SBP (−7.8 mmHg, 95% CI −13.1 to −2.6, p = 0.003) and DBP (−5.4 mmHg, 95% CI −9.1 to −1.6, p = 0.005) versus the non-MTX group. Furthermore, the MTX group had significantly lower 24-hour peripheral and central SBP and DBP and PWV versus the non-MTX group (p < 0.01 for all comparisons). By contrast, there were no significant between-group differences in AIx and ADMA. Conclusions: RA patients on MTX treatment had significantly lower clinic and 24-hour peripheral and central BP compared to those who did not take MTX. The lower BP with MTX may be related to differences in PWV, but not in AIx or ADMA concentrations. Further longitudinal studies including randomized controlled trials are warranted to confirm these findings, to identify other possible mechanisms responsible for the effects of MTX on BP and PWV, and to establish whether these effects might account for the reduced cardiovascular risk with MTX. PMID:28932292

DNA Transport in Nanoparticle Porous-Wall Nanochannels

DTIC Science & Technology

2015-08-04

Fabricated by Interferometric Lithography, Advanced Materials, (01 2011): 147. doi: 10.1002/adma.201001856 Anthony L. Garcia, Youn-Jin Oh, Gabriel ...Albuquerque NM 87131 Gabriel P. Lopez University of New Mexico 1 University of New Mexico Albuquerque NM 87131 Fabrication of Enclosed Nanochannels using...University of New Mexico Albuquerque NM 87131 Y N Gabriel P. Lopez University of New Mexico 1 University of New Mexico Albuquerque NM 87131 Dimiter N

Fabrication and characterization of a chemically oxidized-nanostructured porous silicon based biosensor implementing orienting protein A.

PubMed

Naveas, Nelson; Hernandez-Montelongo, Jacobo; Pulido, Ruth; Torres-Costa, Vicente; Villanueva-Guerrero, Raúl; Predestinación García Ruiz, Josefa; Manso-Silván, Miguel

2014-03-01

Nanostructured porous silicon (PSi) elicits as a very attractive material for future biosensing systems due to its high surface area, biocompatibility and well-established fabrication methods. In order to engineer its performance as a biosensor transducer platform, the density of immunoglobulins properly immobilized and oriented onto the surface needs to be optimized. In this work we fabricated and characterized a novel biosensing system focusing on the improvement of the biofunctionalization cascade. The system consists on a chemically oxidized PSi platform derivatized with 3-aminopropyltriethoxysilane (APTS) that is coupled to Staphylococcus protein A (SpA). The chemical oxidation has previously demonstrated to enhance the biofunctionalization process and here "by implementing SpA" a molecularly oriented immunosensor is achieved. The biosensor system is characterized in terms of its chemical composition, wettability and optical reflectance. Finally, this system is successfully exploited to develop a biosensor for detecting asymmetric dimethylarginine (ADMA), an endogenous molecule involved in cardiovascular diseases. Therefore, this work is relevant from the point of view of design and optimization of the biomolecular immobilization cascade on PSi surfaces with the added value of contribution to the development of new assays for detecting ADMA with a view on prevention of cardiovascular diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors.

PubMed

Anyfanti, Panagiota; Triantafyllou, Areti; Gkaliagkousi, Eugenia; Triantafyllou, Georgios; Koletsos, Nikolaos; Chatzimichailidou, Sophia; Panagopoulos, Panagiotis; Botis, Ioannis; Aslanidis, Spyros; Douma, Stella

2017-06-01

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima-media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.

Epitaxial Growth of Molecular Crystals on van der Waals Substrates for High-Performance Organic Electronics

DTIC Science & Technology

2014-01-01

Taniguchi Advanced Materials Laboratory National Institute for Materials Science 1–1 Namiki, Tsukuba , 305–0044 , Japan Prof. J. Hone Department...of Mechanical Engineering Columbia University New York , NY , 10027 , USA DOI : 10.1002/adma.201304973 The growth of high-quality organic...vdW heterostructures, combined with recent progress on large-area growth of layered materials , [ 6,7 ] provides new opportunities for the scalable

Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction.

PubMed

Hoel, Hedda; Hove-Skovsgaard, Malene; Hov, Johannes R; Gaardbo, Julie Christine; Holm, Kristian; Kummen, Martin; Rudi, Knut; Nwosu, Felix; Valeur, Jørgen; Gelpi, Marco; Seljeflot, Ingebjørg; Ueland, Per Magne; Gerstoft, Jan; Ullum, Henrik; Aukrust, Pål; Nielsen, Susanne Dam; Trøseid, Marius

2018-04-30

HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (β = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.

MS³ fragmentation patterns of monomethylarginine species and the quantification of all methylarginine species in yeast using MRM³.

PubMed

Lakowski, Ted M; Szeitz, András; Pak, Magnolia L; Thomas, Dylan; Vhuiyan, Mynol I; Kotthaus, Joscha; Clement, Bernd; Frankel, Adam

2013-03-27

Protein arginine methylation is one of the epigenetic modifications to proteins that is studied in yeast and is known to be involved in a number of human diseases. All eukaryotes produce Nη-monomethylarginine (ηMMA), asymmetric Nη1, Nη1-dimethylarginine (aDMA), and most produce symmetric Nη1, Nη2-dimethylarginine (sDMA) on proteins, but only yeast produce Nδ-monomethylarginine (δMMA). It has proven difficult to differentiate among all of these methylarginines using mass spectrometry. Accordingly, we demonstrated that the two forms of MMA have indistinguishable primary product ion spectra. However, the secondary product ion spectra of δMMA and ηMMA exhibited distinct patterns of ions. Using incorporation of deuterated methyl-groups in yeast, we determined which secondary product ions were methylated and their structures. Utilizing distinct secondary product ions, a triple quadrupole multiple reaction monitoring cubed (MRM(3)) assay was developed to measure δMMA, ηMMA, sDMA and aDMA derived from hydrolyzed protein. As a proof-of-concept, δMMA and ηMMA were measured using the MRM(3) method in wild type and mutant strains of Saccharomyces cerevisiae and compared to the total MMA measured using an existing assay. The MRM(3) assay represents the only method to directly quantify δMMA and the only method to simultaneously quantify all yeast methylarginines. Copyright © 2013 Elsevier B.V. All rights reserved.

Exploring Electrical and Magnetic Resonances from Coherently Correlated Long-Lived Radical Pairs towards Development of Negative Refractive-Index Materials

DTIC Science & Technology

2015-01-03

Dissociation in Perovskite Solar Cells Yu-Che Hsiao, Ting Wu, Mingxing Li, and Bin Hu Advanced Materials, DOI: 10.1002/adma.201405946, 2015 2...Electrode Interface and Donor/Acceptor Interface via Charge Dissociation in Organic Solar Cells at Device-Operating Condition Ting Wu, Yu-Che Hsiao...exchange energy at donor:acceptor interfaces in organic solar cells Mingxing Li, Hongfeng Wang, Lei He, Huidong Zang, Hengxing Xu, and Bin Hu Appl

A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine.

PubMed

Neri, Monica; Frustaci, Alessandra; Milic, Mirta; Valdiglesias, Vanessa; Fini, Massimo; Bonassi, Stefano; Barbanti, Piero

2015-09-01

Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels. © International Headache Society 2015.

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase.

PubMed

Debler, Erik W; Jain, Kanishk; Warmack, Rebeccah A; Feng, You; Clarke, Steven G; Blobel, Günter; Stavropoulos, Pete

2016-02-23

Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-l-homocysteine (AdoHcy) at 2.8 Å resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and β-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and β-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs.

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Debler, Erik W.; Jain, Kanishk; Warmack, Rebeccah A.

Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-L-homocysteine (AdoHcy) at 2.8 Å resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and β-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and β-barrel domains is stabilized by the dimerization arm ofmore » the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs.« less

Performance of the primary mirror center-of-curvature optical metrology system during cryogenic testing of the JWST Pathfinder telescope

NASA Astrophysics Data System (ADS)

Hadaway, James B.; Wells, Conrad; Olczak, Gene; Waldman, Mark; Whitman, Tony; Cosentino, Joseph; Connolly, Mark; Chaney, David; Telfer, Randal

2016-07-01

The James Webb Space Telescope (JWST) primary mirror (PM) is 6.6 m in diameter and consists of 18 hexagonal segments, each 1.5 m point-to-point. Each segment has a six degree-of-freedom hexapod actuation system and a radius of-curvature (RoC) actuation system. The full telescope will be tested at its cryogenic operating temperature at Johnson Space Center. This testing will include center-of-curvature measurements of the PM, using the Center-of-Curvature Optical Assembly (COCOA) and the Absolute Distance Meter Assembly (ADMA). The COCOA includes an interferometer, a reflective null, an interferometer-null calibration system, coarse and fine alignment systems, and two displacement measuring interferometer systems. A multiple-wavelength interferometer (MWIF) is used for alignment and phasing of the PM segments. The ADMA is used to measure, and set, the spacing between the PM and the focus of the COCOA null (i.e. the PM center-of-curvature) for determination of the ROC. The performance of these metrology systems was assessed during two cryogenic tests at JSC. This testing was performed using the JWST Pathfinder telescope, consisting mostly of engineering development and spare hardware. The Pathfinder PM consists of two spare segments. These tests provided the opportunity to assess how well the center-of-curvature optical metrology hardware, along with the software and procedures, performed using real JWST telescope hardware. This paper will describe the test setup, the testing performed, and the resulting metrology system performance. The knowledge gained and the lessons learned during this testing will be of great benefit to the accurate and efficient cryogenic testing of the JWST flight telescope.

Performance of the Primary Mirror Center-of-curvature Optical Metrology System During Cryogenic Testing of the JWST Pathfinder Telescope

NASA Technical Reports Server (NTRS)

Hadaway, James B.; Wells, Conrad; Olczak, Gene; Waldman, Mark; Whitman, Tony; Cosentino, Joseph; Connolly, Mark; Chaney, David; Telfer, Randal

2016-01-01

The James Webb Space Telescope (JWST) primary mirror (PM) is 6.6 m in diameter and consists of 18 hexagonal segments, each 1.5 m point-to-point. Each segment has a six degree-of-freedom hexapod actuation system and a radius-of-curvature (RoC) actuation system. The full telescope will be tested at its cryogenic operating temperature at Johnson Space Center. This testing will include center-of-curvature measurements of the PM, using the Center-of-Curvature Optical Assembly (COCOA) and the Absolute Distance Meter Assembly (ADMA). The COCOA includes an interferometer, a reflective null, an interferometer-null calibration system, coarse & fine alignment systems, and two displacement measuring interferometer systems. A multiple-wavelength interferometer (MWIF) is used for alignment & phasing of the PM segments. The ADMA is used to measure, and set, the spacing between the PM and the focus of the COCOA null (i.e. the PM center-of-curvature) for determination of the ROC. The performance of these metrology systems was assessed during two cryogenic tests at JSC. This testing was performed using the JWST Pathfinder telescope, consisting mostly of engineering development & spare hardware. The Pathfinder PM consists of two spare segments. These tests provided the opportunity to assess how well the center-of-curvature optical metrology hardware, along with the software & procedures, performed using real JWST telescope hardware. This paper will describe the test setup, the testing performed, and the resulting metrology system performance. The knowledge gained and the lessons learned during this testing will be of great benefit to the accurate & efficient cryogenic testing of the JWST flight telescope.

Arginine methylation enhances the RNA chaperone activity of the West Nile virus host factor AUF1 p45.

PubMed

Friedrich, Susann; Schmidt, Tobias; Schierhorn, Angelika; Lilie, Hauke; Szczepankiewicz, Grit; Bergs, Sandra; Liebert, Uwe G; Golbik, Ralph P; Behrens, Sven-Erik

2016-10-01

A prerequisite for the intracellular replication process of the Flavivirus West Nile virus (WNV) is the cyclization of the viral RNA genome, which enables the viral replicase to initiate RNA synthesis. Our earlier studies indicated that the p45 isoform of the cellular AU-rich element binding protein 1 (AUF1) has an RNA chaperone activity, which supports RNA cyclization and viral RNA synthesis by destabilizing a stem structure at the WNV RNA's 3'-end. Here we show that in mammalian cells, AUF1 p45 is consistently modified by arginine methylation of its C terminus. By a combination of different experimental approaches, we can demonstrate that the methyltransferase PRMT1 is necessary and sufficient for AUF1 p45 methylation and that PRMT1 is required for efficient WNV replication. Interestingly, in comparison to the nonmethylated AUF1 p45, the methylated AUF1 p45(aDMA) exhibits a significantly increased affinity to the WNV RNA termini. Further data also revealed that the RNA chaperone activity of AUF1 p45(aDMA) is improved and the methylated protein stimulates viral RNA synthesis considerably more efficiently than the nonmethylated AUF1 p45. In addition to its destabilizing RNA chaperone activity, we identified an RNA annealing activity of AUF1 p45, which is not affected by methylation. Arginine methylation of AUF1 p45 thus represents a specific determinant of its RNA chaperone activity while functioning as a WNV host factor. Our data suggest that the methylation modifies the conformation of AUF1 p45 and in this way affects its RNA binding and restructuring activities. © 2016 Friedrich et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

The effects of proton pump inhibitor on hepatic vascular responsiveness and hemodynamics in cirrhotic rats.

PubMed

Hsin, I-Fang; Hsu, Shao-Jung; Chuang, Chiao-Lin; Huo, Teh-Ia; Huang, Hui-Chun; Lee, Fa-Yauh; Ho, Hsin-Ling; Chang, Shu-Yu; Lee, Shou-Dong

2018-05-17

Liver cirrhosis is associated with increased intrahepatic resistance due to hepatic fibrosis and exaggerated vasoconstriction. Recent studies have indicated that proton pump inhibitors (PPIs), in addition to acid suppression, modulate vasoactive substances and vasoresponsiveness. PPIs are frequently prescribed in patients with cirrhosis due to a higher prevalence of peptic ulcers, however other impacts are unknown. Liver cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). On the 29th day after BDL and after hemodynamic measurements, the intrahepatic vascular responsiveness to high concentrations of endothelin-1 (ET-1) was evaluated after preincubation with (1) Krebs solution (vehicle), (2) esomeprazole (30 μM), or (3) esomeprazole plus N ω -nitro l-arginine (NNA, a non-selective NO synthase (NOS) inhibitor, 10 -4  M). After perfusion, the hepatic protein expressions of endothelial NOS (eNOS), inducible NOS (iNOS), cyclooxygenase (COX)-1, COX-2, endothelin-1, DDAH-1 (dimethylarginine dimethylaminohydrolase-1, ADMA inhibitor), DDAH-2, ADMA (asymmetrical dimethyl arginine, NOS inhibitor) were evaluated. In the chronic model, the BDL rats received (1) vehicle; or (2) esomeprazole (3.6 mg/kg/day, oral gavage) from the 1st to 28th day after BDL. On the 29th day and after hemodynamic measurements, plasma liver biochemistry and liver fibrosis were evaluated. Esomeprazole did not affect hepatic ET-1 vasoresponsiveness. The hepatic protein expressions of the aforementioned factors were not significantly different among the groups. There were no significant differences in hemodynamics, liver biochemistry and hepatic fibrosis after chronic esomeprazole administration. PPIs did not affect hepatic vasoresponsiveness or the release of vasoactive substances. Furthermore, they did not influence hemodynamics, liver biochemistry or severity of hepatic fibrosis in the cirrhotic rats. Copyright © 2018. Published by Elsevier Taiwan LLC.

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase

PubMed Central

Debler, Erik W.; Jain, Kanishk; Warmack, Rebeccah A.; Feng, You; Clarke, Steven G.; Blobel, Günter; Stavropoulos, Pete

2016-01-01

Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-l-homocysteine (AdoHcy) at 2.8 Å resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and β-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and β-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs. PMID:26858449

Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2 pathway.

PubMed

Zhou, Ru; Xu, Qingbin; Xu, Yehua; Xiong, Aiqin; Wang, Yang; Ma, Ping

2016-12-01

Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI 2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A 2 (cPLA 2 ), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA 2 . And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI 2 pathway. Copyright © 2016. Published by Elsevier Masson SAS.

Performance of the Primary Mirror Center-of-Curvature Optical Metrology System during Cryogenic Testing of the JWST Pathfinder Telescope

NASA Technical Reports Server (NTRS)

Hadaway, James B.; Wells, Conrad; Olczak, Gene; Waldman, Mark; Whitman, Tony; Cosentino, Joseph; Connolly, Mark; Chaney, David; Telfer, Randal

2016-01-01

The JWST primary mirror consists of 18 1.5 m hexagonal segments, each with 6-DoF and RoC adjustment. The telescope will be tested at its cryogenic operating temperature at Johnson Space Center. The testing will include center-of-curvature measurements of the PM, using the Center-of-Curvature Optical Assembly (COCOA) and the Absolute Distance Meter Assembly (ADMA). The performance of these metrology systems, including hardware, software, procedures, was assessed during two cryogenic tests at JSC, using the JWST Pathfinder telescope. This paper describes the test setup, the testing performed, and the resulting metrology system performance.

Oral supplementation with L‐homoarginine in young volunteers

PubMed Central

Atzler, Dorothee; Schönhoff, Mirjam; Cordts, Kathrin; Ortland, Imke; Hoppe, Julia; Hummel, Friedhelm C.; Gerloff, Christian; Jaehde, Ulrich; Jagodzinski, Annika; Böger, Rainer H.; Choe, Chi‐un

2016-01-01

Aims Low blood concentrations of the naturally occurring amino acid L‐homoarginine (L‐hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L‐hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L‐hArg supplementation. Methods In a double‐blind, randomized, placebo‐controlled crossover study, 20 young volunteers received 125 mg L‐hArg once daily for 4 weeks. Kinetic parameters (C max, T max and AUC0‐24h) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L‐arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow‐mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF). Results One hour after ingestion (T max), L‐hArg increased the baseline L‐hArg plasma concentration (2.87 ± 0.91 μmol l−1, mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17.3 ± 4.97 [14.9; 19.6] μmol l−1 (C max), after single and multiple doses, respectively. Once‐only and 4 weeks of supplementation resulted in AUCs0‐24h of 63.5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] μmol l−1*h, for single and multiple doses, respectively. Routine laboratory parameters, L‐arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L‐hArg supplementation compared to baseline. Conclusion Once daily orally applied 125 mg L‐hArg raises plasma L‐hArg four‐ and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers. PMID:27434056

DDAH1 deficiency attenuates endothelial cell cycle progression and angiogenesis.

PubMed

Zhang, Ping; Xu, Xin; Hu, Xinli; Wang, Huan; Fassett, John; Huo, Yuqing; Chen, Yingjie; Bache, Robert J

2013-01-01

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase (NOS). ADMA is eliminated largely by the action of dimethylarginine dimethylaminohydrolase1 (DDAH1). Decreased DDAH activity is found in several pathological conditions and is associated with increased risk of vascular disease. Overexpression of DDAH1 has been shown to augment endothelial proliferation and angiogenesis. To better understand the mechanism by which DDAH1 influences endothelial proliferation, this study examined the effect of DDAH1 deficiency on cell cycle progression and the expression of some cell cycle master regulatory proteins. DDAH1 KO decreased in vivo Matrigel angiogenesis and depressed endothelial repair in a mouse model of carotid artery wire injury. DDAH1 deficiency decreased VEGF expression in HUVEC and increased NF1 expression in both HUVEC and DDAH1 KO mice. The expression of active Ras could overcome the decreased VEGF expression caused by the DDAH1 depletion. The addition of VEGF and knockdown NF1 could both restore proliferation in cells with DDAH1 depletion. Flow cytometry analysis revealed that DDAH1 sRNAi knockdown in HUVEC caused G1 and G2/M arrest that was associated with decreased expression of CDC2, CDC25C, cyclin D1 and cyclin E. MEF cells from DDAH1 KO mice also demonstrated G2/M arrest that was associated with decreased cyclin D1 expression and Akt activity. Our findings indicate that DDAH1 exerts effects on cyclin D1 and cyclin E expression through multiple mechanisms, including VEGF, the NO/cGMP/PKG pathway, the Ras/PI3K/Akt pathway, and NF1 expression. Loss of DDAH1 effects on these pathways results in impaired endothelial cell proliferation and decreased angiogenesis. The findings provide background information that may be useful in the development of therapeutic strategies to manipulate DDAH1 expression in cardiovascular diseases or tumor angiogenesis.

DDAH1 Deficiency Attenuates Endothelial Cell Cycle Progression and Angiogenesis

PubMed Central

Zhang, Ping; Xu, Xin; Hu, Xinli; Wang, Huan; Fassett, John; Huo, Yuqing; Chen, Yingjie; Bache, Robert J.

2013-01-01

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase (NOS). ADMA is eliminated largely by the action of dimethylarginine dimethylaminohydrolase1 (DDAH1). Decreased DDAH activity is found in several pathological conditions and is associated with increased risk of vascular disease. Overexpression of DDAH1 has been shown to augment endothelial proliferation and angiogenesis. To better understand the mechanism by which DDAH1 influences endothelial proliferation, this study examined the effect of DDAH1 deficiency on cell cycle progression and the expression of some cell cycle master regulatory proteins. DDAH1 KO decreased in vivo Matrigel angiogenesis and depressed endothelial repair in a mouse model of carotid artery wire injury. DDAH1 deficiency decreased VEGF expression in HUVEC and increased NF1 expression in both HUVEC and DDAH1 KO mice. The expression of active Ras could overcome the decreased VEGF expression caused by the DDAH1 depletion. The addition of VEGF and knockdown NF1 could both restore proliferation in cells with DDAH1 depletion. Flow cytometry analysis revealed that DDAH1 sRNAi knockdown in HUVEC caused G1 and G2/M arrest that was associated with decreased expression of CDC2, CDC25C, cyclin D1 and cyclin E. MEF cells from DDAH1 KO mice also demonstrated G2/M arrest that was associated with decreased cyclin D1 expression and Akt activity. Our findings indicate that DDAH1 exerts effects on cyclin D1 and cyclin E expression through multiple mechanisms, including VEGF, the NO/cGMP/PKG pathway, the Ras/PI3K/Akt pathway, and NF1 expression. Loss of DDAH1 effects on these pathways results in impaired endothelial cell proliferation and decreased angiogenesis. The findings provide background information that may be useful in the development of therapeutic strategies to manipulate DDAH1 expression in cardiovascular diseases or tumor angiogenesis. PMID:24260221

Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.

PubMed

Ayoubian, Hiresh; Fröhlich, Thomas; Pogodski, Dagmar; Flatley, Andrew; Kremmer, Elisabeth; Schepers, Aloys; Feederle, Regina; Arnold, Georg J; Grässer, Friedrich A

2017-08-01

The Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a cellular SDMA-containing protein that interacts with SMN. Accordingly, a monoclonal antibody (mAb) specific for the SDMA-modified RG repeat of EBNA2 also binds to SMD3. With the novel mAb 19D4 we now show that EBNA2 contains mono-methylated arginine (MMA) residues within the RG repeat. Using 19D4, we immune-precipitated and analysed by mass spectrometry cellular proteins in EBV-transformed B-cells that feature MMA motifs that are similar to the one in EBNA2. Among the cellular proteins identified, we confirmed by immunoprecipitation and/or Western blot analyses Aly/REF, Coilin, DDX5, FXR1, HNRNPK, LSM4, MRE11, NRIP, nucleolin, PRPF8, RBM26, SMD1 (SNRDP1) and THRAP3 proteins that are either known to contain MMA residues or feature RG repeat sequences that probably serve as methylation substrates. The identified proteins are involved in splicing, tumorigenesis, transcriptional activation, DNA stability and RNA processing or export. Furthermore, we found that several proteins involved in energy metabolism are associated with MMA-modified proteins. Interestingly, the viral EBNA1 protein that features methylated RG repeat motifs also reacted with the antibodies. Our results indicate that the region between aa 34-52 of EBNA1 contains ADMA or SDMA residues, while the region between aa 328-377 mainly contains MMA residues.

Photodynamic effect of curcumin on Vibrio parahaemolyticus.

PubMed

Wu, Juan; Mou, Haijin; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

2016-09-01

Vibrio parahaemolyticus (V. parahaemolyticus) is currently a major cause of bacterial diarrhoea associated with seafood consumption. The objective of this study was to determine the inactivation effect of curcumin-mediated photodynamic action on V. parahaemolyticus. First of all, V. parahaemolyticus suspended in PBS buffer was irradiated by a visible light from a LED light source with an energy density of 3.6J/cm(2). Colony forming units (CFU) were counted and the viability of V. parahaemolyticus cells was calculated after treatment. Singlet oxygen ((1)O2) production after photodynamic action of curcumin was evaluated using 9,10-Anthracenediyl-bis (methylene) dimalonic acid (ADMA). Bacterial outer membrane protein was extracted and analyzed using electrophoresis SDS-PAGE. DNA and RNA of V. parahaemolyticus were also extracted and analyzed using agarose gel electrophoresis after photodynamic treatment. Finally, the efficacy of photodynamic action of curcumin was preliminarily evaluated in the decontamination of V. parahaemolyticus in oyster. Results showed that the viability of V. parahaemolyticus was significantly decreased to non-detectable levels over 6.5-log reductions with the curcumin concentration of 10 and 20μM. Photodynamic action of curcumin significantly increased the singlet oxygen level with the curcumin concentration of 10μM. Notable damage was found to bacterial outer membrane proteins and genetic materials after photodynamic treatment. Photodynamic action of curcumin reduced the number of V. parahaemolyticus contaminating in oyster to non-detectable level. Our findings demonstrated that photodynamic action of curcumin could be a potentially good method to inactivate Vibrio parahaemolyticus contaminating in oyster. Copyright © 2016 Elsevier B.V. All rights reserved.

Factors determining extreme brain natriuretic peptide elevation.

PubMed

Guglin, Maya; Hourani, Rayan; Pitta, Sridevi

2007-01-01

Brain natriuretic peptide (BNP) level is elevated in heart failure and reflects its severity. It is unknown why some patients have extremely high BNP levels. The authors retrospectively reviewed data on 179 consecutive patients whose BNP levels fell within one of several predetermined ranges: mild elevation, 500 to 1000 pg/mL (n=82); moderate elevation, 2000 to 3000 pg/mL (n=48); and high elevation, 4000 to 20,000 pg/mL (n=49). The statistical analysis was conducted with the unpaired t test and Pearson's correlation coefficient. Adjustments were made for age, sex, and serum creatinine level. Patients with moderate BNP elevation were more symptomatic and had more advanced structural and hemodynamic changes than did patients with lower BNP elevation. Characteristics of the high BNP level group did not differ from those of the moderate BNP level group. Serum creatinine level correlated with BNP level, but neither age nor sex did. High BNP level (4000-20,000 pg/mL) is determined more by renal dysfunction than by the severity of heart failure.

Mean Cancer Mortality Rates in Low Versus High Elevation Counties in Texas

PubMed Central

Hart, John

2010-01-01

There is controversy as to whether low levels of radiation (i.e., < 5 rem) pose a health risk. This brief inquiry compares archived cancer mortality data in counties having relatively low (0–250 feet above sea level), medium (500–1000 feet above sea level), and high (3000+ feet above sea level) elevations also having corresponding greater natural background levels of radiation respectively. Cancer mortality was found to be lowest in the high elevation counties (mean = 58.2) followed by low elevation counties (67.5) and then medium elevation counties (70.4). Statistically significant differences were found between low –high elevations (p = 0.003), and medium – high elevations (p = 0.010), but not between low and medium elevations (p = 0.5). More rigorous research, with an accounting of confounding variables, is indicated. PMID:21191484

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

PubMed

Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

2015-01-01

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Effects of elevated CO2 levels on root morphological traits and Cd uptakes of two Lolium species under Cd stress*

PubMed Central

Jia, Yan; Tang, Shi-rong; Ju, Xue-hai; Shu, Li-na; Tu, Shu-xing; Feng, Ren-wei; Giusti, Lorenzino

2011-01-01

This study was conducted to investigate the combined effects of elevated CO2 levels and cadmium (Cd) on the root morphological traits and Cd accumulation in Lolium multiflorum Lam. and Lolium perenne L. exposed to two CO2 levels (360 and 1000 μl/L) and three Cd levels (0, 4, and 16 mg/L) under hydroponic conditions. The results show that elevated levels of CO2 increased shoot biomass more, compared to root biomass, but decreased Cd concentrations in all plant tissues. Cd exposure caused toxicity to both Lolium species, as shown by the restrictions of the root morphological parameters including root length, surface area, volume, and tip numbers. These parameters were significantly higher under elevated levels of CO2 than under ambient CO2, especially for the number of fine roots. The increases in magnitudes of those parameters triggered by elevated levels of CO2 under Cd stress were more than those under non-Cd stress, suggesting an ameliorated Cd stress under elevated levels of CO2. The total Cd uptake per pot, calculated on the basis of biomass, was significantly greater under elevated levels of CO2 than under ambient CO2. Ameliorated Cd toxicity, decreased Cd concentration, and altered root morphological traits in both Lolium species under elevated levels of CO2 may have implications in food safety and phytoremediation. PMID:21462388

Lead poisoning in United States-bound refugee children: Thailand-Burma border, 2009.

PubMed

Mitchell, Tarissa; Jentes, Emily; Ortega, Luis; Scalia Sucosky, Marissa; Jefferies, Taran; Bajcevic, Predrag; Parr, Valentina; Jones, Warren; Brown, Mary Jean; Painter, John

2012-02-01

Elevated blood lead levels lead to permanent neurocognitive sequelae in children. Resettled refugee children in the United States are considered at high risk for elevated blood lead levels, but the prevalence of and risk factors for elevated blood lead levels before resettlement have not been described. Blood samples from children aged 6 months to 14 years from refugee camps in Thailand were tested for lead and hemoglobin. Sixty-seven children with elevated blood lead levels (venous ≥10 µg/dL) or undetectable (capillary <3.3 µg/dL) blood lead levels participated in a case-control study. Of 642 children, 33 (5.1%) had elevated blood lead levels. Children aged <2 years had the highest prevalence (14.5%). Among children aged <2 years included in a case-control study, elevated blood lead levels risk factors included hemoglobin <10 g/dL, exposure to car batteries, and taking traditional medicines. The prevalence of elevated blood lead levels among tested US-bound Burmese refugee children was higher than the current US prevalence, and was especially high among children <2 years old. Refugee children may arrive in the United States with elevated blood lead levels. A population-specific understanding of preexisting lead exposures can enhance postarrival lead-poisoning prevention efforts, based on Centers for Disease Control and Prevention recommendations for resettled refugee children, and can lead to remediation efforts overseas.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Flowering responses of insect-pollinated plants to elevated CO{sub 2} levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cushman, J.H.; Koch, G.W.; Chiariello, N.R.

1995-06-01

Elevated atmospheric CO{sub 2} concentrations have been predicted or shown to substantially influence plants, communities and ecosystems in a variety of ways. Here, we examined the effects of elevated CO{sub 2} levels on the timing and magnitude of flowering for two insect-pollinated annual plant species in a serpentine grassland. We focused on Lasthenia californica and Linanthus parviflorus and addressed three questions: (1) Do elevated CO{sub 2} levels influence flowering phenologies and is this species specific? (2) Do elevated CO{sub 2} levels affect flower production and is this due to altered numbers of individuals, flowers per plant, or both? and (3)more » Are effects on flowering due to elevated CO{sub 2} levels per se or changes in environmental conditions associated with methods used to manipulate CO{sub 2} levels? To address these questions, we used the ecosystem experiment at Stanford University`s Jasper Ridge Biological Preserve (San Mateo Co., CA). This system consists of 20 open-topped chambers - half receiving ambient CO{sub 2} (360 ppm) and half receiving elevated CO{sub 2} (720 ppm) - and 10 untreated plots serving as chamber controls. Results from the 1994 season demonstrated that there were species-specific responses to elevated CO{sub 2} levels and the field chambers. For Lasthenia californica, elevated CO{sub 2} per se did not affect relative abundance, inflorescence production, or phenology, but chambers did significantly increase inflorescence production and extend the duration of flowering. For Linanthus parviflorus, elevated CO{sub 2} levels significantly increased relative abundance and flower production, and extended the flowering period slightly, while the chambers significantly decreased flower production early in the season and increased it later in the season.« less

Wetland Accretion Rate Model of Ecosystem Resilience (WARMER) and its application to habitat sustainability for endangered species in the San Francisco Estuary

USGS Publications Warehouse

Swanson, Kathleen M.; Drexler, Judith Z.; Schoellhamer, David H.; Thorne, Karen M.; Casazza, Michael L.; Overton, Cory T.; Callaway, John C.; Takekawa, John Y.

2014-01-01

Salt marsh faunas are constrained by specific habitat requirements for marsh elevation relative to sea level and tidal range. As sea level rises, changes in relative elevation of the marsh plain will have differing impacts on the availability of habitat for marsh obligate species. The Wetland Accretion Rate Model for Ecosystem Resilience (WARMER) is a 1-D model of elevation that incorporates both biological and physical processes of vertical marsh accretion. Here, we use WARMER to evaluate changes in marsh surface elevation and the impact of these elevation changes on marsh habitat for specific species of concern. Model results were compared to elevation-based habitat criteria developed for marsh vegetation, the endangered California clapper rail (Rallus longirostris obsoletus), and the endangered salt marsh harvest mouse (Reithrodontomys raviventris) to determine the response of marsh habitat for each species to predicted >1-m sea-level rise by 2100. Feedback between vertical accretion mechanisms and elevation reduced the effect of initial elevation in the modeled scenarios. Elevation decreased nonlinearly with larger changes in elevation during the latter half of the century when the rate of sea-level rise increased. Model scenarios indicated that changes in elevation will degrade habitat quality within salt marshes in the San Francisco Estuary, and degradation will accelerate in the latter half of the century as the rate of sea-level rise accelerates. A sensitivity analysis of the model results showed that inorganic sediment accumulation and the rate of sea-level rise had the greatest influence over salt marsh sustainability.

Elevated Blood Lead Levels in Children Associated With the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response.

PubMed

Hanna-Attisha, Mona; LaChance, Jenny; Sadler, Richard Casey; Champney Schnepp, Allison

2016-02-01

We analyzed differences in pediatric elevated blood lead level incidence before and after Flint, Michigan, introduced a more corrosive water source into an aging water system without adequate corrosion control. We reviewed blood lead levels for children younger than 5 years before (2013) and after (2015) water source change in Greater Flint, Michigan. We assessed the percentage of elevated blood lead levels in both time periods, and identified geographical locations through spatial analysis. Incidence of elevated blood lead levels increased from 2.4% to 4.9% (P < .05) after water source change, and neighborhoods with the highest water lead levels experienced a 6.6% increase. No significant change was seen outside the city. Geospatial analysis identified disadvantaged neighborhoods as having the greatest elevated blood lead level increases and informed response prioritization during the now-declared public health emergency. The percentage of children with elevated blood lead levels increased after water source change, particularly in socioeconomically disadvantaged neighborhoods. Water is a growing source of childhood lead exposure because of aging infrastructure.

Elevated Blood Lead Levels in Children Associated With the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response

PubMed Central

LaChance, Jenny; Sadler, Richard Casey; Champney Schnepp, Allison

2016-01-01

Objectives. We analyzed differences in pediatric elevated blood lead level incidence before and after Flint, Michigan, introduced a more corrosive water source into an aging water system without adequate corrosion control. Methods. We reviewed blood lead levels for children younger than 5 years before (2013) and after (2015) water source change in Greater Flint, Michigan. We assessed the percentage of elevated blood lead levels in both time periods, and identified geographical locations through spatial analysis. Results. Incidence of elevated blood lead levels increased from 2.4% to 4.9% (P < .05) after water source change, and neighborhoods with the highest water lead levels experienced a 6.6% increase. No significant change was seen outside the city. Geospatial analysis identified disadvantaged neighborhoods as having the greatest elevated blood lead level increases and informed response prioritization during the now-declared public health emergency. Conclusions. The percentage of children with elevated blood lead levels increased after water source change, particularly in socioeconomically disadvantaged neighborhoods. Water is a growing source of childhood lead exposure because of aging infrastructure. PMID:26691115

Small-scale topography modulates elevational α-, β- and γ-diversity of Andean leaf beetles.

PubMed

Thormann, Birthe; Ahrens, Dirk; Espinosa, Carlos Iván; Armijos, Diego Marín; Wagner, Thomas; Wägele, Johann W; Peters, Marcell K

2018-05-01

Elevational diversity gradients are typically studied without considering the complex small-scale topography of large mountains, which generates habitats of strongly different environmental conditions within the same elevational zones. Here we analyzed the importance of small-scale topography for elevational diversity patterns of hyperdiverse tropical leaf beetles (Coleoptera: Chrysomelidae). We compared patterns of elevational diversity and species composition of beetles in two types of forests (on mountain ridges and in valleys) and analyzed whether differences in the rate of species turnover among forest habitats lead to shifts in patterns of elevational diversity when scaling up from the local study site to the elevational belt level. We sampled beetle assemblages at 36 sites in the Podocarpus National Park, Ecuador, which were equally distributed over two forest habitats and three elevational levels. DNA barcoding and Poisson tree processes modelling were used to delimitate putative species. On average, local leaf beetle diversity showed a clear hump-shaped pattern. However, only diversity in forests on mountain ridges peaked at mid-elevation, while beetle diversity in valleys was similarly high at low- and mid-elevation and only declined at highest elevations. A higher turnover of species assemblages at lower than at mid-elevations caused a shift from a hump-shaped diversity pattern found at the local level to a low-elevation plateau pattern (with similar species numbers at low and mid-elevation) at the elevational belt level. Our study reveals an important role of small-scale topography and spatial scale for the inference on gradients of elevational species diversity.

Mortality associated with bilirubin levels in insurance applicants.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2009-01-01

Determine the relationship between bilirubin levels with and without other liver function test (LFT) elevations and relative mortality in life insurance applicants. By use of the Social Security Death Master File mortality was determined in 1,905,664 insurance applicants for whom blood samples were submitted to the Clinical Reference Laboratory. There were 50,174 deaths observed in this study population. Results were stratified by 3 age/sex groups: females, age <60; males, age <60; and all, age 60+. The median follow-up was 12 years. Relative mortality increased as bilirubin decreased below bilirubin levels seen for the middle 50% of the population. The known association of smoking with lower bilirubin values explained only part of the additional elevated risk at low bilirubin levels. In the absence of other LFT elevations, relative mortality remained unchanged as bilirubin increased beyond levels seen for the middle 50% of the population. When a bilirubin elevation was combined with other LFT elevations, mortality further increased only at the highest elevations of other LFTs, seen only in <2.5% of applicants. Isolated elevations of bilirubin in this healthy screening population were not associated with excess mortality but values below the midpoint were. Other investigations have suggested a cardiovascular cause may underlie the excess mortality associated with low bilirubin. In association with other LFT elevations, bilirubin elevation further increases the mortality risk only at the highest elevations of other LFTs.

Modeling tidal marsh distribution with sea-level rise: evaluating the role of vegetation, sediment, and upland habitat in marsh resiliency.

PubMed

Schile, Lisa M; Callaway, John C; Morris, James T; Stralberg, Diana; Parker, V Thomas; Kelly, Maggi

2014-01-01

Tidal marshes maintain elevation relative to sea level through accumulation of mineral and organic matter, yet this dynamic accumulation feedback mechanism has not been modeled widely in the context of accelerated sea-level rise. Uncertainties exist about tidal marsh resiliency to accelerated sea-level rise, reduced sediment supply, reduced plant productivity under increased inundation, and limited upland habitat for marsh migration. We examined marsh resiliency under these uncertainties using the Marsh Equilibrium Model, a mechanistic, elevation-based soil cohort model, using a rich data set of plant productivity and physical properties from sites across the estuarine salinity gradient. Four tidal marshes were chosen along this gradient: two islands and two with adjacent uplands. Varying century sea-level rise (52, 100, 165, 180 cm) and suspended sediment concentrations (100%, 50%, and 25% of current concentrations), we simulated marsh accretion across vegetated elevations for 100 years, applying the results to high spatial resolution digital elevation models to quantify potential changes in marsh distributions. At low rates of sea-level rise and mid-high sediment concentrations, all marshes maintained vegetated elevations indicative of mid/high marsh habitat. With century sea-level rise at 100 and 165 cm, marshes shifted to low marsh elevations; mid/high marsh elevations were found only in former uplands. At the highest century sea-level rise and lowest sediment concentrations, the island marshes became dominated by mudflat elevations. Under the same sediment concentrations, low salinity brackish marshes containing highly productive vegetation had slower elevation loss compared to more saline sites with lower productivity. A similar trend was documented when comparing against a marsh accretion model that did not model vegetation feedbacks. Elevation predictions using the Marsh Equilibrium Model highlight the importance of including vegetation responses to sea-level rise. These results also emphasize the importance of adjacent uplands for long-term marsh survival and incorporating such areas in conservation planning efforts.

Application of Geographic Information System Methods to Identify Areas Yielding Water that will be Replaced by Water from the Colorado River in the Vidal and Chemehuevi Areas, California, and the Mohave Mesa Area, Arizona

USGS Publications Warehouse

Spangler, Lawrence E.; Angeroth, Cory E.; Walton, Sarah J.

2008-01-01

Relations between the elevation of the static water level in wells and the elevation of the accounting surface within the Colorado River aquifer in the vicinity of Vidal, California, the Chemehuevi Indian Reservation, California, and on Mohave Mesa, Arizona, were used to determine which wells outside the flood plain of the Colorado River are presumed to yield water that will be replaced by water from the Colorado River. Wells that have a static water-level elevation equal to or below the elevation of the accounting surface are presumed to yield water that will be replaced by water from the Colorado River. Geographic Information System (GIS) interpolation tools were used to produce maps of areas where water levels are above, below, and near (within ? 0.84 foot) the accounting surface. Calculated water-level elevations and interpolated accounting-surface elevations were determined for 33 wells in the vicinity of Vidal, 16 wells in the Chemehuevi area, and 35 wells on Mohave Mesa. Water-level measurements generally were taken in the last 10 years with steel and electrical tapes accurate to within hundredths of a foot. A Differential Global Positioning System (DGPS) was used to determine land-surface elevations to within an operational accuracy of ? 0.43 foot, resulting in calculated water-level elevations having a 95-percent confidence interval of ? 0.84 foot. In the Vidal area, differences in elevation between the accounting surface and measured water levels range from -2.7 feet below to as much as 17.6 feet above the accounting surface. Relative differences between the elevation of the water level and the elevation of the accounting surface decrease from west to east and from north to south. In the Chemehuevi area, differences in elevation range from -3.7 feet below to as much as 8.7 feet above the accounting surface, which is established at 449.6 feet in the vicinity of Lake Havasu. In all of the Mohave Mesa area, the water-level elevation is near or below the elevation of the accounting surface. Differences in elevation between water levels and the accounting surface range from -0.2 to -11.3 feet, with most values exceeding -7.0 feet. In general, the ArcGIS Triangulated Irregular Network (TIN) Contour and Natural Neighbor tools reasonably represent areas where the elevation of water levels in wells is above, below, and near (within ? 0.84 foot) the elevation of the accounting surface in the Vidal and Chemehuevi study areas and accurately delineate areas around outlying wells and where anomalies exist. The TIN Contour tool provides a strict linear interpolation while the Natural Neighbor tool provides a smoothed interpolation. Using the default options in ArcGIS, the Inverse Distance Weighted (IDW) and Spline tools also reasonably represent areas above, below, and near the accounting surface in the Vidal and Chemehuevi areas. However, spatial extent of and boundaries between areas above, below, and near the accounting surface vary among the GIS methods, which results largely from the fundamentally different mathematical approaches used by these tools. The limited number and spatial distribution of wells in comparison to the size of the areas, and the locations and relative differences in elevation between water levels and the accounting surface of wells with anomalous water levels also influence the contouring by each of these methods. Qualitatively, the Natural Neighbor tool appears to provide the best representation of the difference between water-level and accounting-surface elevations in the study areas, on the basis of available well data.

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China

PubMed Central

Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Background and Objective Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Methods Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels(≥14ng/L) and patients with normal hs-cTnT levels (<14ng/L). Results The final analysis involved 84 patients (31 males; mean age, 61.6±12.2years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Conclusion Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies. PMID:26849554

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (<14 ng/L). The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates

PubMed Central

Zahrieh, David; Young, Sean G.; Oleson, Jacob; Ryckman, Kelli K.; Wels, Brian; Simmons, Donald L.; Saftlas, Audrey

2017-01-01

Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1–3 days of birth among Iowa newborns, linked with the area of mother’s residence at the time of birth, we examine the spatial patterns of elevated (>5 μg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 μg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 μg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact. PMID:28520816

Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus.

PubMed

Frank, Marlies; Finsterer, Josef

2012-01-01

To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation.

Elevated CO2 levels affects the concentrations of copper and cadmium in crops grown in soil contaminated with heavy metals under fully open-air field conditions.

PubMed

Guo, Hongyan; Zhu, Jianguo; Zhou, Hui; Sun, Yuanyuan; Yin, Ying; Pei, Daping; Ji, Rong; Wu, Jichun; Wang, Xiaorong

2011-08-15

Elevated CO(2) levels and the increase in heavy metals in soils through pollution are serious problems worldwide. Whether elevated CO(2) levels will affect plants grown in heavy-metal-polluted soil and thereby influence food quality and safety is not clear. Using a free-air CO(2) enrichment (FACE) system, we investigated the impacts of elevated atmospheric CO(2) on the concentrations of copper (Cu) or cadmium (Cd) in rice and wheat grown in soil with different concentrations of the metals in the soil. In the two-year study, elevated CO(2) levels led to lower Cu concentrations and higher Cd concentrations in shoots and grain of both rice and wheat grown in the respective contaminated soil. Elevated CO(2) levels slightly but significantly lowered the pH of the soil and led to changes in Cu and Cd fractionation in the soil. Our study indicates that elevated CO(2) alters the distribution of contaminant elements in soil and plants, thereby probably affecting food quality and safety.

Elevation trends and shrink-swell response of wetland soils to flooding and drying

USGS Publications Warehouse

Cahoon, Donald R.; Perez, Brian C.; Segura, Bradley D.; Lynch, James C.

2011-01-01

Given the potential for a projected acceleration in sea-level rise to impact wetland sustainability over the next century, a better understanding is needed of climate-related drivers that influence the processes controlling wetland elevation. Changes in local hydrology and groundwater conditions can cause short-term perturbations to marsh elevation trends through shrink—swell of marsh soils. To better understand the magnitude of these perturbations and their impacts on marsh elevation trends, we measured vertical accretion and elevation dynamics in microtidal marshes in Texas and Louisiana during and after the extreme drought conditions that existed there from 1998 to 2000. In a Louisiana marsh, elevation was controlled by subsurface hydrologic fluxes occurring below the root zone but above the 4 m depth (i.e., the base of the surface elevation table benchmark) that were related to regional drought and local meteorological conditions, with marsh elevation tracking water level variations closely. In Texas, a rapid decline in marsh elevation was related to severe drought conditions, which lowered local groundwater levels. Unfragmented marshes experienced smaller water level drawdowns and more rapid marsh elevation recovery than fragmented marshes. It appears that extended drawdowns lead to increased substrate consolidation making it less resilient to respond to future favorable conditions. Overall, changes in water storage lead to rapid and large short-term impacts on marsh elevation that are as much as five times greater than the long-term elevation trend, indicating the importance of long-term, high-resolution elevation data sets to understand the prolonged effects of water deficits on marsh elevation change.

[Prevalence of Elevated Lipoprotein (a) Levels in Patients < 60 Years of Age with Retinal Vein Occlusion].

PubMed

Kuhli-Hattenbach, C; Hellstern, P; Miesbach, W; Kohnen, T; Hattenbach, L-O

2018-01-01

The potential impact of elevated Lipoprotein (a) [Lp(a)] levels on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. In a retrospective case-control study, thrombophilia data of 106 young patients (< 60 years at the time of the RVO or a previous thromboembolic event) with RVO and 76 healthy subjects were evaluated. Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients (29.2 %) than among controls (9.2 %; p = 0.0009). Lp(a) levels were found to be significantly (p = 0.012) different between patients and controls. Moreover, we found that an unusual personal or family history of thromboembolism was a strong predictor of elevated Lp(a) (p = 0.03). We observed a significant correlation between elevated Lp(a) and other coagulation disorders (p = 0.005). Multivariate analysis showed that elevated lipoprotein(a) levels (OR: 3.5; p = 0.003) were an independent risk factor for the development of RVO. Elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a). Georg Thieme Verlag KG Stuttgart · New York.

Selenium and mercury have a synergistic negative effect on fish reproduction.

PubMed

Penglase, S; Hamre, K; Ellingsen, S

2014-04-01

Selenium (Se) can reduce the negative impacts of mercury (Hg) toxicity on growth and survival, but little is known about how these two elements interact in reproduction. In the following study we explored the effects of organic Hg and Se on the growth, survival and reproduction of female zebrafish (Danio rerio). Fish were fed one of four diets from 73 until 226 dpf in a 2 × 2 factorial design, using selenomethionine (SeMet) and methylmercury (MeHg) as the Se and Hg sources, respectively. Each diet contained Se at either requirement (0.7 mg Se/kg DM) or elevated levels (10 mg Se/kgDM), and Hg at either low (0.05 mg Hg/kg DM) or elevated (12 mg Hg/kg DM) levels. Between 151 and 206 dpf the female fish were pairwise crossed against untreated male fish and the mating success, fecundity, embryo survival, and subsequent overall reproductive success were measured. Elevated dietary Se reduced Hg levels in both the adult fish and their eggs. Elevated dietary Hg and Se increased egg Se levels to a greater extent than when dietary Se was elevated alone. At elevated maternal intake levels, egg concentrations of Se and Hg reflected the maternal dietary levels and not the body burdens of the adult fish. Elevated dietary Hg reduced the growth and survival of female fish, but these effects were largely prevented with elevated dietary Se. Elevated dietary Se alone did not affect fish growth or survival. Compared to other treatments, elevated dietary Hg alone increased both mating and overall reproductive success with <100 days of exposure, but decreased these parameters with >100 days exposure. Elevated dietary Se decreased fecundity, embryo survival, and overall reproductive success. The combination of elevated Se and Hg had a synergistic negative effect on all aspects of fish reproduction compared to those groups fed elevated levels of either Se or Hg. Overall the data demonstrate that while increased dietary Se may reduce adverse effects of Hg on the growth and survival in adult fish, it can negatively affect fish reproductive potential, and the effect on reproduction is enhanced in the presence of elevated Hg. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum biochemical markers in lung cancer.

PubMed Central

Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.

1978-01-01

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672

High-Intensity Targeted Screening for Elevated Blood Lead Levels Among Children in 2 Inner-City Chicago Communities

PubMed Central

Dignam, Timothy A.; Evens, Anne; Eduardo, Eduard; Ramirez, Shokufeh M.; Caldwell, Kathleen L.; Kilpatrick, Nikki; Noonan, Gary P.; Flanders, W. Dana; Meyer, Pamela A.; McGeehin, Michael A.

2004-01-01

Objectives. We assessed the prevalence of elevated blood lead levels (≥ 10 micrograms of lead per deciliter of blood), risk factors, and previous blood lead testing among children in 2 high-risk Chicago, Ill, communities. Methods. Through high-intensity targeted screening, blood lead levels were tested and risks were assessed among a representative sample of children aged 1 to 5 years who were at risk for lead exposure. Results. Of the 539 children who were tested, 27% had elevated blood lead levels, and 61% had never been tested previously. Elevated blood lead levels were associated with chipped exterior house paint. Conclusions. Most of the children who lived in these communities—where the prevalence for elevated blood lead levels among children was 12 times higher than the national prevalence—were not tested for lead poisoning. Our findings highlight the need for targeted community outreach that includes testing blood lead levels in accordance with the American Academy of Pediatrics’ recommendations. PMID:15514235

Effects of Elevated CO2 on Levels of Primary Metabolites and Transcripts of Genes Encoding Respiratory Enzymes and Their Diurnal Patterns in Arabidopsis thaliana: Possible Relationships with Respiratory Rates

PubMed Central

Watanabe, Chihiro K.; Sato, Shigeru; Yanagisawa, Shuichi; Uesono, Yukifumi; Terashima, Ichiro; Noguchi, Ko

2014-01-01

Elevated CO2 affects plant growth and photosynthesis, which results in changes in plant respiration. However, the mechanisms underlying the responses of plant respiration to elevated CO2 are poorly understood. In this study, we measured diurnal changes in the transcript levels of genes encoding respiratory enzymes, the maximal activities of the enzymes and primary metabolite levels in shoots of Arabidopsis thaliana grown under moderate or elevated CO2 conditions (390 or 780 parts per million by volume CO2, respectively). We examined the relationships between these changes and respiratory rates. Under elevated CO2, the transcript levels of several genes encoding respiratory enzymes increased at the end of the light period, but these increases did not result in changes in the maximal activities of the corresponding enzymes. The levels of some primary metabolites such as starch and sugar phosphates increased under elevated CO2, particularly at the end of the light period. The O2 uptake rate at the end of the dark period was higher under elevated CO2 than under moderate CO2, but higher under moderate CO2 than under elevated CO2 at the end of the light period. These results indicate that the changes in O2 uptake rates are not directly related to changes in maximal enzyme activities and primary metabolite levels. Instead, elevated CO2 may affect anabolic processes that consume respiratory ATP, thereby affecting O2 uptake rates. PMID:24319073

A comparison of bat activity at low and high elevations in the Black Hills of western Washington

USGS Publications Warehouse

Erickson, J.; Adams, Michael J.

2003-01-01

We examined the differences in activity patterns and community structure of bats between low (<150 m) and high ( ! 575 m) elevation sites in two habitats of the Capitol State Forest, Washington. Total bat activity averaged four times higher at low elevation sites than at high elevation sites. Feeding activity was almost 20 times higher at low elevation sites. However, the non-myotis group had similar activity levels at high and low elevation, whereas myotis group activity decreased at higher elevations. Different levels of activity between elevations could be the result of differences in insect availability, climatic conditions, and morphology of the bat species.

Elevated CO2 enhances biological contributions to elevation change in coastal wetlands by offsetting stressors associated with sea-level rise

USGS Publications Warehouse

Cherry, J.A.; McKee, K.L.; Grace, J.B.

2009-01-01

1. Sea-level rise, one indirect consequence of increasing atmospheric CO2, poses a major challenge to long-term stability of coastal wetlands. An important question is whether direct effects of elevated CO 2 on the capacity of marsh plants to accrete organic material and to maintain surface elevations outweigh indirect negative effects of stressors associated with sea-level rise (salinity and flooding). 2. In this study, we used a mesocosm approach to examine potential direct and indirect effects of atmospheric CO2 concentration, salinity and flooding on elevation change in a brackish marsh community dominated by a C3 species, Schoenoplectus americanus, and a C4 grass, Spartina patens. This experimental design permitted identification of mechanisms and their role in controlling elevation change, and the development of models that can be tested in the field. 3. To test hypotheses related to CO2 and sea-level rise, we used conventional anova procedures in conjunction with structural equation modelling (SEM). SEM explained 78% of the variability in elevation change and showed the direct, positive effect of S. americanus production on elevation. The SEM indicated that C3 plant response was influenced by interactive effects between CO2 and salinity on plant growth, not a direct CO2 fertilization effect. Elevated CO2 ameliorated negative effects of salinity on S. americanus and enhanced biomass contribution to elevation. 4. The positive relationship between S. americanus production and elevation change can be explained by shoot-base expansion under elevated CO 2 conditions, which led to vertical soil displacement. While the response of this species may differ under other environmental conditions, shoot-base expansion and the general contribution of C3 plant production to elevation change may be an important mechanism contributing to soil expansion and elevation gain in other coastal wetlands. 5. Synthesis. Our results revealed previously unrecognized interactions and mechanisms contributing to marsh elevation change, including amelioration of salt stress by elevated CO2 and the importance of plant production and shoot-base expansion for elevation gain. Identification of biological processes contributing to elevation change is an important first step in developing comprehensive models that permit more accurate predictions of whether coastal marshes will persist with continued sea-level rise or become submerged. ?? 2008 The Authors.

Is elevated creatinine a reliable marker for methanol toxicity in nitromethane-containing model fuel ingestions in children?

PubMed

Padmanabhan, Pradeep; Spiller, Henry A; Ross, Mitchell P; Bosse, George M

2011-01-01

In the absence of a rapid serum methanol level estimation, it is difficult to assess the risk from unintentional childhood ingestion of model fuels containing methanol and nitromethane (MFNM). Previous reports have documented false elevations of serum creatinine from the nitromethane in these fuels, suggesting its utility as a readily available marker of significant methanol ingestion. We performed a 2-year retrospective chart review of cases of ingestion of MFNM in children, with both a methanol level and measured creatinine level. Seven children, ages 19 months to 3 years, ingested MFNM. All seven children were seen in a hospital and had measured methanol and creatinine levels. All blood samples for methanol and creatinine were drawn within 3 hours of ingestion with methanol estimation delayed up to 24 hours. Creatinine ranged from 0.39 (0.034 mmol/l) to 10.7 mg/dl (0.95 mmol/l). All methanol levels were <10 mg/dl (0.31 mmol/l) or reported as negative. Fomepizole was initiated empirically in two patients due to delay in obtaining methanol analysis results. Transient elevations of creatinine occurred in five of the seven children. Blood urea nitrogen was within normal limits, and there was no history of renal impairment in these children, suggesting the elevated creatinine was mostly related to nitromethane ingestion. No child had a significantly elevated methanol level. Elevated creatinine level, as measured by Jaffe colorimetric method, is not a reliable marker for elevated methanol levels after unintentional ingestion of MFNM.

Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study.

PubMed

Gaillard, Romy; Eilers, Paul H C; Yassine, Siham; Hofman, Albert; Steegers, Eric A P; Jaddoe, Vincent W V

2014-05-01

To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy. In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals. Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7). In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications. © 2014 John Wiley & Sons Ltd.

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

PubMed

Rozen, Todd; Swidan, Sahar Z

2007-01-01

To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

The role of elevated serum procalcitonin in neuroendocrine neoplasms of digestive system.

PubMed

Chen, Luohai; Zhang, Yu; Lin, Yuan; Deng, Langhui; Feng, Shiting; Chen, Minhu; Chen, Jie

2017-12-01

Elevated serum procalcitonin (PCT) was reported in patients with certain type of neuroendocrine neoplasms (NENs). The aim of this study was to assess the role of elevated serum PCT in NENs from digestive system. Serum PCT and serum CgA level were measured in 155 patients with NENs from digestive system. Elevated serum PCT was found in 63 patients (40.6%). Grade 3 disease was a significant factor associated with elevated serum PCT (OR, 9.24; 95%CI, 3.04-28.08; P<0.001). Serum PCT level was significantly decreased after treatment both in patients with stable disease (P=0.003) and patients with partial remission (P=0.001). In these patients, serum PCT level significantly increased again at the time of progression disease (P=0.001). Elevated serum PCT was a significant factor of worse survival (HR, 2.86; 95%CI, 1.36-6.03; P=0.006). Compared with patients with normal serum PCT and CgA level, patients with either PCT or CgA elevated and patients with both PCT and CgA elevated had progressively worse survival. Additionally, PCT expression in tumor cells was found in 24.0% of patients but did not correlate with other clinicopathological factors, including serum PCT. Serum PCT is elevated in part of patients with NENs of digestive system, especially in patients with grade 3 disease. Serum PCT level can help evaluate treatment response and its elevation indicates poor prognosis. Combination of serum PCT and CgA can improve outcome prediction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

PubMed Central

Liu, Chi-Ming; Tung, Tao-Hsin; Liu, Jorn-Hon; Chen, Victor Tze-Kai; Lin, Ching-Heng; Hsu, Chung-Te; Chou, Pesus

2005-01-01

AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study. PMID:15786537

Surface elevation dynamics in a regenerating mangrove forest at Homebush Bay, Australia

USGS Publications Warehouse

Rogers, K.; Saintilan, N.; Cahoon, D.

2005-01-01

Following the dieback of an interior portion of a mangrove forest at Homebush Bay, Australia, surface elevation tables and feldspar marker horizons were installed in the impacted, intermediate and control forest to measure vertical accretion, elevation change, and shallow subsidence. The objectives of the study were to determine current vertical accretion and elevation change rates as a guide to understanding mangrove dieback, ascertain the factors controlling surface elevation change, and investigate the sustainability of the mangrove forest under estimated sea-level rise conditions. The study demonstrates that the influences on surface dynamics are more complex than soil accretion and soil autocompaction alone. During strong vegetative regrowth in the impacted forest, surface elevation increase exceeded vertical accretion apparently as a result of belowground biomass production. In addition, surface elevation in all forest zones was correlated with total monthly rainfall during a severe El Ni?o event, highlighting the importance of rainfall to groundwater recharge and surface elevation. Surface elevation increase for all zones exceeded the 85-year sea level trend for Sydney Harbour. Since mean sea-level also decreased during the El Ni?o event, the decrease in surface elevation did not translate to an increase in inundation frequency or influence the sustainability of the mangrove forest. These findings indicate that subsurface soil processes such as organic matter accumulation and groundwater flux can significantly influence mangrove surface elevation, and contribute to the long-term sustainability of mangrove systems under a scenario of rising sea levels.

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

PubMed

Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

2017-12-01

Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

Compositional Analysis of Asymmetric and Symmetric Dimethylated H3R2 Using Liquid Chromatography-Tandem Mass Spectrometry-Based Targeted Proteomics.

PubMed

Xu, Qingqing; Xu, Feifei; Liu, Liang; Chen, Yun

2016-09-06

Protein arginine methylation is one of the common post-translational modifications in cellular processes. To date, two isomeric forms of dimethylated arginine have been identified: asymmetric N(G),N(G)-dimethylarginine (aDMA), and symmetric N(G),N'(G)-dimethylarginine (sDMA). Evidence indicated that these isomers can coexist and have different or even opposite functions, with aDMA and sDMA forms of arginine 2 on histone H3 (i.e., H3R2me2a and H3R2me2s) being an example. Thus, specific detection and quantification of each isomeric form is important. Current methods are capable of predicting and detecting thousands of methylarginine sites in proteins, whereas differentiation and stoichiometric measurement of dimethylated protein isomers are still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics has emerged as a promising technique for site-specific quantification of protein methylation using enzymatic peptides as surrogates of target proteins. However, it should be pointed out that a routine targeted proteomics strategy cannot easily distinguish sDMA- and aDMA-containing surrogate peptides due to their common nature. The estimated amount should be considered as the sum of both arginine dimethylated isomers. In this study, compositional analysis based on a linear algebra algorithm as an add-on to targeted proteomics was employed to quantify H3R2me2a and H3R2me2s (i.e., surrogate peptides of AR(me2a)TK(me1/2)QT and AR(me2s)TK(me1/2)QT). To achieve this simultaneous quantification, a targeted proteomics assay was developed and validated for each isomer first. With the slope and intercept of their calibration curves for each multiple reaction monitoring (MRM) transition, linear algebraic equations were derived. Using a series of mock mixtures consisting of isomers in varying concentrations, the reliability of the method was confirmed. Finally, the H3R2 dimethylation status was analyzed in normal MCF-10A cells, parental drug-sensitive MCF-7/WT cancer cells, and drug-resistant MCF-7/ADR cancer cells. Dimethylated H3R2 was also monitored in MCF-7/WT cells with the treatment of doxorubicin (DOX) for confirmation.

Leveling

USGS Publications Warehouse

1966-01-01

Geodetic leveling by the U.S. Geological Survey provides a framework of accurate elevations for topographic mapping. Elevations are referred to the Sea Level Datum of 1929. Lines of leveling may be run either with automatic or with precise spirit levels, by either the center-wire or the three-wire method. For future use, the surveys are monumented with bench marks, using standard metal tablets or other marking devices. The elevations are adjusted by least squares or other suitable method and are published in lists of control.

Factors Associated With Elevated Blood Lead Levels in Children.

PubMed

Chaudhary, Sakshi; Firdaus, Uzma; Ali, Syed Manazir; Mahdi, Abbas Ali

2018-01-15

To determine the prevalence and correlates of elevated blood lead level in children (6-144 months) of Aligarh. A hospital-based cross-sectional study was conducted. Venous blood was obtained for lead estimation and a structured questionnaire was filled. A total of 260 children were enrolled. The prevalence of elevated blood lead level was 44.2%, seen mostly in children below 5 years of age. Old and deteriorating wall paints at home was found to be significantly associated with elevated levels. Lead-based house paints are potential source of lead exposure. Meticulous renovation and painting of the walls with safe paints is desirable.

Elevated ground-level O(3) changes the diversity of anoxygenic purple phototrophic bacteria in paddy field.

PubMed

Feng, Youzhi; Lin, Xiangui; Yu, Yongchang; Zhu, Jianguo

2011-11-01

The knowledge of the impact of elevated ground-level O(3) below ground the agro-ecosystem is limited. A field experiment in China Ozone Free-Air Concentration Enrichment (FACE-O(3)) facility on a rice-wheat rotation system was carried out to investigate responses of anoxygenic phototrophic purple bacteria (AnPPB) to elevated ground-level O(3). AnPPB community structures and sizes in paddy soil were monitored by molecular approaches including PCR-DGGE and real-time quantitative PCR based upon the pufM gene on three typical rice growth stages. Repetitive sequence-based PCR (rep-PCR) in combination with culture-reliant method was conducted to reveal changes in genotypic diversity. Elevated ground-level O(3) statistically reduce AnPPB abundance and percentage in total bacterial community in flooded rice soil via decreasing their genotypic diversity and metabolic versatility. Concomitantly, their community composition changed after rice anthesis stage under elevated ground-level O(3). Our results from AnPPB potential responses imply that continuously elevated ground-level O(3) in the future would eventually harm the health of paddy ecosystem through negative effect on soil microorganisms.

Inside the covered hopper car loading dock at railroad level, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Inside the covered hopper car loading dock at railroad level, looking east from the 1945 elevator into the 1913 elevator, control for the railroad car puller in background - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

Light Levels, Refractive Development, and Myopia – a Speculative Review

PubMed Central

Norton, Thomas T.; Siegwart, John T.

2013-01-01

Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia. We propose a model in which the ambient illuminance levels produce a continuum of effects on normal refractive development and the response to myopiagenic stimuli such that low light levels favor myopia development and elevated levels are protective. Among possible mechanisms, elevation of retinal dopamine activity seems the most likely. Inputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs) at elevated light levels may be involved, providing additional activation of retinal dopaminergic pathways. PMID:23680160

4th level of 1913 elevator indicating sacking scale, part of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4th level of 1913 elevator indicating sacking scale, part of the bagging system and nate to the sewing machine. Discharge spout for the grain bin to the left - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW SHOWS VERTICAL LADDER AND CAGE ALONG ELEVATOR SHAFT. - U.S. Naval Base, Pearl Harbor, Signal Tower, Corner of Seventh Street & Avenue D east of Drydock No. 1, Pearl City, Honolulu County, HI

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study.

PubMed

Chen, Yimin; Zhao, Ying; Feng, Linmin; Zhang, Jie; Zhang, Juanwen; Feng, Guofang

2016-04-27

Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population. A cross-sectional study was performed with 7,755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome. Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides. These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.

Estimating relative sea-level rise and submergence potential at a coastal wetland

USGS Publications Warehouse

Cahoon, Donald R.

2015-01-01

A tide gauge records a combined signal of the vertical change (positive or negative) in the level of both the sea and the land to which the gauge is affixed; or relative sea-level change, which is typically referred to as relative sea-level rise (RSLR). Complicating this situation, coastal wetlands exhibit dynamic surface elevation change (both positive and negative), as revealed by surface elevation table (SET) measurements, that is not recorded at tide gauges. Because the usefulness of RSLR is in the ability to tie the change in sea level to the local topography, it is important that RSLR be calculated at a wetland that reflects these local dynamic surface elevation changes in order to better estimate wetland submergence potential. A rationale is described for calculating wetland RSLR (RSLRwet) by subtracting the SET wetland elevation change from the tide gauge RSLR. The calculation is possible because the SET and tide gauge independently measure vertical land motion in different portions of the substrate. For 89 wetlands where RSLRwet was evaluated, wetland elevation change differed significantly from zero for 80 % of them, indicating that RSLRwet at these wetlands differed from the local tide gauge RSLR. When compared to tide gauge RSLR, about 39 % of wetlands experienced an elevation rate surplus and 58 % an elevation rate deficit (i.e., sea level becoming lower and higher, respectively, relative to the wetland surface). These proportions were consistent across saltmarsh, mangrove, and freshwater wetland types. Comparison of wetland elevation change and RSLR is confounded by high levels of temporal and spatial variability, and would be improved by co-locating tide gauge and SET stations near each other and obtaining long-term records for both.

Prevalence of hepatitis A viral RNA and antibodies among Chinese blood donors.

PubMed

Sun, P; Su, N; Lin, F Z; Ma, L; Wang, H J; Rong, X; Dai, Y D; Li, J; Jian, Z W; Tang, L H; Xiao, W; Li, C Q

2015-12-09

Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.

Testosterone and Haemosporidian Parasites Along a Tropical Elevational Gradient in Rufous-Collared Sparrows (Zonotrichia capensis).

PubMed

Escallón, Camilo; Weinstein, Nicole M; Tallant, James A; Wojtenek, Winfried; Rodríguez-Saltos, Carlos A; Bonaccorso, Elisa; Moore, Ignacio T

2016-10-01

Elevation has been proposed as a dominant ecological variable shaping life history traits and subsequently their underlying hormonal mechanisms. In an earlier meta-analysis of tropical birds, elevation was positively related to testosterone levels. Furthermore, parasitism by avian haemosporidians should vary with elevation as environmental conditions affect vector abundance, and while testosterone is needed for breeding, it is hypothesized to be immunosuppressive and thus could exacerbate haemosporidian infection. Our objective in this study was to examine the relationships between elevation, testosterone levels, and parasitism by avian haemosporidians. We surveyed breeding male rufous-collared sparrows (Zonotrichia capensis) across a wide elevational range along the equator. We measured baseline testosterone levels, haemosporidian infection at four elevations spanning the species' natural range in the Ecuadorian Andes (600, 1500, 2100, 3300 m). Testosterone levels from breeding males were not related to elevation, but there was high intrapopulation variability. Testosterone levels were not related to the probability of parasitism, but our results from one population suggested that the likelihood of being infected by haemosporidian parasites was greater when in breeding condition. In conclusion, even though there is variation in life history strategies among the studied populations, wider divergence in seasonality and life history traits would probably be needed to detect an effect of elevation on testosterone if one exists. Additionally, our results show that variation in testosterone is not related to infection risk of haemosporidians, thus other factors that take a toll on energetic resources, such as reproduction, should be looked at more closely. © 2016 Wiley Periodicals, Inc.

75 FR 31342 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... referenced ground [caret] Communities affected elevation Elevation in meters (MSL) Effective Modified... Level, rounded to the nearest 0.1 meter. ** BFEs to be changed include the listed downstream and... ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ** BFEs to be changed include the...

Will fluctuations in salt marsh–mangrove dominance alter vulnerability of a subtropical wetland to sea‐level rise?

USGS Publications Warehouse

Mckee, Karen L.; Vervaeke, William

2018-01-01

To avoid submergence during sea-level rise, coastal wetlands build soil surfaces vertically through accumulation of inorganic sediment and organic matter. At climatic boundaries where mangroves are expanding and replacing salt marsh, wetland capacity to respond to sea-level rise may change. To compare how well mangroves and salt marshes accommodate sea-level rise, we conducted a manipulative field experiment in a subtropical plant community in the subsiding Mississippi River Delta. Experimental plots were established in spatially equivalent positions along creek banks in monospecific stands of Spartina alterniflora (smooth cordgrass) or Avicennia germinans (black mangrove) and in mixed stands containing both species. To examine the effect of disturbance on elevation dynamics, vegetation in half of the plots was subjected to freezing (mangrove) or wrack burial (salt marsh), which caused shoot mortality. Vertical soil development was monitored for 6 years with the surface elevation table-marker horizon system. Comparison of land movement with relative sea-level rise showed that this plant community was experiencing an elevation deficit (i.e., sea level was rising faster than the wetland was building vertically) and was relying on elevation capital (i.e., relative position in the tidal frame) to survive. Although Avicennia plots had more elevation capital, suggesting longer survival, than Spartina or mixed plots, vegetation type had no effect on rates of accretion, vertical movement in root and sub-root zones, or net elevation change. Thus, these salt marsh and mangrove assemblages were accreting sediment and building vertically at equivalent rates. Small-scale disturbance of the plant canopy also had no effect on elevation trajectories—contrary to work in peat-forming wetlands showing elevation responses to changes in plant productivity. The findings indicate that in this deltaic setting with strong physical influences controlling elevation (sediment accretion, subsidence), mangrove replacement of salt marsh, with or without disturbance, will not necessarily alter vulnerability to sea-level rise.

Contrasting Decadal-Scale Changes in Elevation and ...

EPA Pesticide Factsheets

Northeastern US salt marshes face multiple co-stressors, including accelerating rates of relative sea level rise (RSLR), elevated nutrient inputs, and low sediment supplies. In order to evaluate how marsh surface elevations respond to such factors, we used surface elevation tables (SETs) and surface elevation pins to measure changes in marsh surface elevation in two eastern Long Island Sound salt marshes, Barn Island and Mamacoke marshes. We compare marsh elevation change at these two systems with recent rates of RSLR and find evidence of differences between the two sites; Barn Island is maintaining its historic rate of elevation gain (2.3 ± 0.24 mm year−1 from 2003 to 2013) and is no longer keeping pace with RSLR, while Mamacoke shows evidence of a recent increase in rates (4.2 ± 0.52 mm year−1 from 1994 to 2014) to maintain its elevation relative to sea level. In addition to data on short-term elevation responses at these marshes, both sites have unusually long and detailed data on historic vegetation species composition extending back more than half a century. Over this study period, vegetation patterns track elevation change relative to sea levels, with the Barn Island plant community shifting towards those plants that are found at lower elevations and the Mamacoke vegetation patterns showing little change in plant composition. We hypothesize that the apparent contrasting trend in marsh elevation at the sites is due to differences in sediment a

LC-QTOF-MS-based targeted metabolomics of arginine-creatine metabolic pathway-related compounds in plasma: application to identify potential biomarkers in pediatric chronic kidney disease.

PubMed

Benito, Sandra; Sánchez, Alicia; Unceta, Nora; Andrade, Fernando; Aldámiz-Echevarria, Luis; Goicolea, M Aránzazu; Barrio, Ramón J

2016-01-01

Chronic kidney disease (CKD) is a major epidemiologic problem which causes several disturbances in adults and in pediatrics. Despite being a worldwide public health problem, information available for CKD in the pediatric population is scarce. For that reason, an ion-pair reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method has been developed and validated in order to analyze 16 amino acids, amino acid derivatives, and analogous compounds related to the arginine-creatine metabolic pathway that are suspicious of being increased or decreased in plasma from patients with CKD. The analytical method involved the addition of dithiothreitol, a reducing agent which reduces disulfide and thus giving total aminothiol concentration, as well as a simple precipitation of plasma proteins. Moreover, despite amino acids being usually derivatized to improve their retention time and to enhance their signal, for this method, an ion-pairing reagent was used, thus avoiding the need for derivatization. Subsequently, analysis of plasma from pediatric patients suffering from CKD and control pediatrics was carried out. As a result, glycine, citrulline, creatinine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were significantly increased in patients with CKD, regardless of their creatinine level, whereas in addition to these compounds dimethylglycine was also increased when CKD patients had plasma creatinine concentrations above 12 μg mL(-1), thus all are suggested as potential biomarkers for renal impairment.

eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation.

PubMed

Karbach, Susanne; Wenzel, Philip; Waisman, Ari; Munzel, Thomas; Daiber, Andreas

2014-01-01

Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the "kindling radical" hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthase (eNOS) by different mechanisms involving so-called "redox switches". The oxidative depletion of tetrahydrobiopterin (BH4), oxidative disruption of the dimeric eNOS complex, S-glutathionylation and adverse phosphorylation as well as RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) will be discussed. But also new concepts of eNOS uncoupling and state of the art detection of this process will be described. Another part of this review article will address pharmaceutical interventions preventing or reversing eNOS uncoupling and thereby normalize vascular function in a given disease setting. We finally turn our attention to the inflammatory mechanisms that are also involved in the development of endothelial dysfunction and cardiovascular disease. Inflammatory cell and cytokine profiles as well as their interactions, which are among the kindling mechanisms for the development of vascular dysfunction will be discussed on the basis of the current literature.

75 FR 31368 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... referenced ground [caret] Communities affected elevation Elevation in meters (MSL) Effective Modified Santa.... Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ** BFEs to be... Vertical Datum. Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter...

77 FR 21476 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Randolph County... Vertical Datum. Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter.... [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Beebe Maps are available for...

77 FR 7540 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Sebastian County... Level, rounded to the nearest 0.1 meter. ADDRESSES City of Fort Smith Maps are available for inspection.... [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Rolling Fork Maps are...

MONOTERPENE LEVELS IN NEEDLES OF DOUGLAS-FIR EXPOSED TO ELEVATED CO2 AND TEMPERATURE

EPA Science Inventory

Levels of monoterpenes in current year needles of douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings were measured at the conclusion of four years of exposure to ambient or elevated CO2 (+ 179 mmol.mol-1), and ambient or elevated temperature (+ 3.5 C). Eleven monoterpen...

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

PubMed

Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

Bee (Hymenoptera: Apoidea) Diversity and Sampling Methodology in a Midwestern USA Deciduous Forest.

PubMed

McCravy, Kenneth W; Ruholl, Jared D

2017-08-04

Forests provide potentially important bee habitat, but little research has been done on forest bee diversity and the relative effectiveness of bee sampling methods in this environment. Bee diversity and sampling methodology were studied in an Illinois, USA upland oak-hickory forest using elevated and ground-level pan traps, malaise traps, and vane traps. 854 bees and 55 bee species were collected. Elevated pan traps collected the greatest number of bees (473), but ground-level pan traps collected greater species diversity (based on Simpson's diversity index) than did elevated pan traps. Elevated and ground-level pan traps collected the greatest bee species richness, with 43 and 39 species, respectively. An estimated sample size increase of over 18-fold would be required to approach minimum asymptotic richness using ground-level pan traps. Among pan trap colors/elevations, elevated yellow pan traps collected the greatest number of bees (266) but the lowest diversity. Malaise traps were relatively ineffective, collecting only 17 bees. Vane traps collected relatively low species richness (14 species), and Chao1 and abundance coverage estimators suggested that minimum asymptotic species richness was approached for that method. Bee species composition differed significantly between elevated pan traps, ground-level pan traps, and vane traps. Indicator species were significantly associated with each of these trap types, as well as with particular pan trap colors/elevations. These results indicate that Midwestern deciduous forests provide important bee habitat, and that the performance of common bee sampling methods varies substantially in this environment.

Elevator ride comfort monitoring and evaluation using smartphones

NASA Astrophysics Data System (ADS)

Zhang, Yang; Sun, Xiaowei; Zhao, Xuefeng; Su, Wensheng

2018-05-01

With rapid urbanization, the demand for elevators is increasing, and their level of safety and ride comfort under vibrating conditions has also aroused interest. It is therefore essential to monitor the ride comfort level of elevators. The traditional method for such monitoring depends significantly on regular professional inspections, and requires expensive equipment and professional skill. With this regard, a new method for elevator ride comfort monitoring using a smartphone is demonstrated herein in detail. A variety of high-precision sensors are installed in a smartphone with strong data processing and telecommunication capabilities. A series of validation tests were designed and completed, and the international organization for standardization ISO2631-1997 was applied to evaluate the level of elevator ride comfort. Experimental results indicate that the proposed method is stable and reliable, its precision meets the engineering requirements, and the elevator ride comfort level can be accurately monitored under various situations. The method is very economical and convenient, and provides the possibility for the public to participate in elevator ride comfort monitoring. In addition, the method can both provide a wide range of data support and eliminate data errors to a certain extent.

Neighborhood Screening in Communities Throughout the Nation for Children with Elevated Blood Lead Levels

PubMed Central

Anderson, Dudley G.; Clark, John L.

1974-01-01

From the spring of 1971 to September 1973, neighborhood surveys were conducted in 58 communities throughout the nation to determine whether children with confirmed elevated blood lead levels could be identified. Another purpose of these screenings was to assist communities in identifying children with elevated blood lead levels and thereby demonstrate to community officials that such children do exist in communities screened. The children screened were not a random sample. In those communities where the initial elevated blood levels were confirmed all but seven had one or more children requiring followup and/or treatment. Of those children screened, black children had an elevated rate about three times as great as nonblack children. With few exceptions, the homes in the neighborhoods had at least one interior surface with sufficient quantities of lead paint to be dangerous if the paint were ingested. PMID:4831146

Sound-localization experiments with barn owls in virtual space: influence of broadband interaural level different on head-turning behavior.

PubMed

Poganiatz, I; Wagner, H

2001-04-01

Interaural level differences play an important role for elevational sound localization in barn owls. The changes of this cue with sound location are complex and frequency dependent. We exploited the opportunities offered by the virtual space technique to investigate the behavioral relevance of the overall interaural level difference by fixing this parameter in virtual stimuli to a constant value or introducing additional broadband level differences to normal virtual stimuli. Frequency-specific monaural cues in the stimuli were not manipulated. We observed an influence of the broadband interaural level differences on elevational, but not on azimuthal sound localization. Since results obtained with our manipulations explained only part of the variance in elevational turning angle, we conclude that frequency-specific cues are also important. The behavioral consequences of changes of the overall interaural level difference in a virtual sound depended on the combined interaural time difference contained in the stimulus, indicating an indirect influence of temporal cues on elevational sound localization as well. Thus, elevational sound localization is influenced by a combination of many spatial cues including frequency-dependent and temporal features.

Co-ingestion of methanol and nitromethane: using falsely elevated creatinine as indicator for methanol antidote use.

PubMed

Leonard, Charlene P; Akhtar, Javed

2007-07-01

To report a case of co-ingestion of methanol and nitromethane in a child in order to heighten the awareness of false elevation of serum creatinine from nitromethane ingestion. Case report. Pediatric intensive care unit. A 4-yr-old previously healthy girl ingested an unknown quantity of "Blue Thunder" model-engine fuel, which consisted of methanol and nitromethane. The patient was treated with fomepizole for methanol ingestion using elevated creatinine level as a reason for treatment. The patient was asymptomatic but her creatinine level increased ten-fold (from 0.4 mg/dL to 4 mg/dL) within 6 hrs. Blood urea nitrogen, anion gap, and osmolar gap remained within normal limits. When the serum creatinine level was measured with enzymatic method instead of Jaffe's method, a normal creatinine level was obtained. The falsely elevated creatinine level was due to nitromethane. The falsely elevated serum creatinine levels due to nitromethane ingestion can lead to unnecessary therapeutic interventions. We intend to heighten awareness of this potential misstep by reporting this case.

Elevated blood pressure, race/ethnicity, and C-reactive protein levels in children and adolescents.

PubMed

Lande, Marc B; Pearson, Thomas A; Vermilion, Roger P; Auinger, Peggy; Fernandez, Isabel D

2008-12-01

Adult hypertension is independently associated with elevated C-reactive protein levels, after controlling for obesity and other cardiovascular risk factors. The objective of this study was to determine, with a nationally representative sample of children, whether the relationship between elevated blood pressure and C-reactive protein levels may be evident before adulthood. Cross-sectional data for children 8 to 17 years of age who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 were analyzed. Bivariate analyses compared children with C-reactive protein levels of >3 mg/L versus or=95th percentile and 1.3% had diastolic blood pressure of >or=95th percentile. Children with C-reactive protein levels of >3 mg/L had higher systolic blood pressure, compared with children with C-reactive protein levels of or=95th percentile was independently associated with C-reactive protein levels in boys but not girls. Subset analyses according to race/ethnicity demonstrated that the independent association of elevated systolic blood pressure with C-reactive protein levels was largely limited to black boys. These data indicate that there is interplay between race/ethnicity, elevated systolic blood pressure, obesity, and inflammation in children, a finding that has potential implications for disparities in cardiovascular disease later in life.

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

PubMed

Larrieta-Carrasco, Elena; Flores, Yvonne N; Macías-Kauffer, Luis R; Ramírez-Palacios, Paula; Quiterio, Manuel; Ramírez-Salazar, Eric G; León-Mimila, Paola; Rivera-Paredez, Berenice; Cabrera-Álvarez, Guillermo; Canizales-Quinteros, Samuel; Zhang, Zuo-Feng; López-Pérez, Tania V; Salmerón, Jorge; Velázquez-Cruz, Rafael

2018-02-01

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9-12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1-4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypsographic demography: The distribution of human population by altitude

PubMed Central

Cohen, Joel E.; Small, Christopher

1998-01-01

The global distribution of the human population by elevation is quantified here. As of 1994, an estimated 1.88 × 109 people, or 33.5% of the world’s population, lived within 100 vertical meters of sea level, but only 15.6% of all inhabited land lies below 100 m elevation. The median person lived at an elevation of 194 m above sea level. Numbers of people decreased faster than exponentially with increasing elevation. The integrated population density (IPD, the number of people divided by the land area) within 100 vertical meters of sea level was significantly larger than that of any other range of elevations and represented far more people. A significant percentage of the low-elevation population lived at moderate population densities rather than at the highest densities of central large cities. Assessments of coastal hazards that focus only on large cities may substantially underestimate the number of people who could be affected. PMID:9826643

Familial aggregation of circulating C-reactive protein in polycystic ovary syndrome.

PubMed

Sasidevi, Arunachalam; Vellanki, Priyathama; Kunselman, Allen R; Raja-Khan, Nazia; Dunaif, Andrea; Legro, Richard S

2013-03-01

What is the heritability of C-reactive protein (CRP) levels in women with polycystic ovary syndrome (PCOS) and their first-degree relatives? Women with PCOS and their siblings are more likely to have elevated CRP levels when both of their parents have elevated CRP. This PCOS family-based study indicates that CRP levels are likely a heritable trait. Previous studies have established that an elevated blood level of CRP is variably present in women with PCOS, and may be present independent of metabolic status. A familial based phenotyping study consisting of 81 families comprised of PCOS patients and their first-degree relatives for 305 subjects. Study conducted at an academic health center. An elevated CRP level was defined as >28.6 nmol/l. To account for familial clustering, generalized estimating equations with a logit link were used to model the association between elevated CRP levels in patients with PCOS and their siblings with their parental group (A = neither parent with elevated CRP; B = one parent with elevated CRP; C= both parents with elevated CRP), adjusting for gender, age and BMI of the offspring. We did additional heritability analyses by using a variance component estimation method for CRP levels, adjusting for sex, age and BMI. We observed elevated CRP levels in 94% of the offspring in group C, 45% in group B and 10% in group A after adjusting for age, gender and BMI of the offspring. The median BMI of the offspring in group A, B and C were 30.0, 28.7 and 31.2 kg/m², respectively. Heritability estimates of CRP levels ranged from 0.75 to 0.83 and remained significant after excluding for type 2 diabetes mellitus. Our small sample size increases the possibility of a type 1 error. This is a single report in an adequately powered but limited sample size study identifying the strong heritability of CRP levels. Replication in other large family cohorts is necessary. These findings support the concept that there is an increased cardiovascular disease risk profile in families of women with PCOS. This research was supported by National Institutes of Health grants U54HD-034449 and P50 HD044405 (A.D.). Priyathama Vellanki is supported in part by NIH/NIDDK Training Grant T32 DK007169.

Consideration of vertical uncertainty in elevation-based sea-level rise assessments: Mobile Bay, Alabama case study

USGS Publications Warehouse

Gesch, Dean B.

2013-01-01

The accuracy with which coastal topography has been mapped directly affects the reliability and usefulness of elevationbased sea-level rise vulnerability assessments. Recent research has shown that the qualities of the elevation data must be well understood to properly model potential impacts. The cumulative vertical uncertainty has contributions from elevation data error, water level data uncertainties, and vertical datum and transformation uncertainties. The concepts of minimum sealevel rise increment and minimum planning timeline, important parameters for an elevation-based sea-level rise assessment, are used in recognition of the inherent vertical uncertainty of the underlying data. These concepts were applied to conduct a sea-level rise vulnerability assessment of the Mobile Bay, Alabama, region based on high-quality lidar-derived elevation data. The results that detail the area and associated resources (land cover, population, and infrastructure) vulnerable to a 1.18-m sea-level rise by the year 2100 are reported as a range of values (at the 95% confidence level) to account for the vertical uncertainty in the base data. Examination of the tabulated statistics about land cover, population, and infrastructure in the minimum and maximum vulnerable areas shows that these resources are not uniformly distributed throughout the overall vulnerable zone. The methods demonstrated in the Mobile Bay analysis provide an example of how to consider and properly account for vertical uncertainty in elevation-based sea-level rise vulnerability assessments, and the advantages of doing so.

Tidal Marshes across a Chesapeake Bay Subestuary Are Not Keeping up with Sea-Level Rise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beckett, Leah H.; Baldwin, Andrew H.; Kearney, Michael S.

Sea-level rise is a major factor in wetland loss worldwide, and inmuch of Chesapeake Bay (USA) the rate of sea-level rise is higher than the current global rate of 3.2 mmyr -1 due to regional subsidence.Marshes along estuarine salinity gradients differ in vegetation composition, productivity, decomposition pathways, and sediment dynamics, andmay exhibit different responses to sea-level rise. Coastal marshes persist by building vertically at rates at or exceeding regional sea-level rise. In one of the first studies to examine elevation dynamics across an estuarine salinity gradient, we installed 15 surface elevation tables (SET) and accretion marker-horizon plots (MH) in tidalmore » freshwater, oligohaline, and brackish marshes across a Chesapeake Bay subestuary. Over the course of four years, wetlands across the subestuary decreased 1.8 ± 2.7 mmyr -1 in elevation on average, at least 5 mmyr -1 below that needed to keep pace with global sea-level rise. Elevation change rates did not significantly differ among themarshes studied, and ranged from-9.8 ± 6.9 to 4.5 ± 4.3 mmyr -1. Surface accretion of depositedmineral and organic matter was uniformly high across the estuary (~9–15 mmyr -1), indicating that elevation loss was not due to lack of accretionary input. Position in the estuary and associated salinity regime were not related to elevation change or surface matter accretion. In conclusion, previous studies have focused on surface elevation change inmarshes of uniformsalinity (e.g., salt marshes); however, our findings highlight the need for elevation studies inmarshes of all salinity regimes and different geomorphic positions, and warn that brackish, oligohaline, and freshwater tidal wetlands may be at similarly high risk of submergence in some estuaries.« less

Tidal Marshes across a Chesapeake Bay Subestuary Are Not Keeping up with Sea-Level Rise

PubMed Central

Beckett, Leah H.; Baldwin, Andrew H.; Kearney, Michael S.

2016-01-01

Sea-level rise is a major factor in wetland loss worldwide, and in much of Chesapeake Bay (USA) the rate of sea-level rise is higher than the current global rate of 3.2 mm yr-1 due to regional subsidence. Marshes along estuarine salinity gradients differ in vegetation composition, productivity, decomposition pathways, and sediment dynamics, and may exhibit different responses to sea-level rise. Coastal marshes persist by building vertically at rates at or exceeding regional sea-level rise. In one of the first studies to examine elevation dynamics across an estuarine salinity gradient, we installed 15 surface elevation tables (SET) and accretion marker-horizon plots (MH) in tidal freshwater, oligohaline, and brackish marshes across a Chesapeake Bay subestuary. Over the course of four years, wetlands across the subestuary decreased 1.8 ± 2.7 mm yr-1 in elevation on average, at least 5 mm yr-1 below that needed to keep pace with global sea-level rise. Elevation change rates did not significantly differ among the marshes studied, and ranged from -9.8 ± 6.9 to 4.5 ± 4.3 mm yr-1. Surface accretion of deposited mineral and organic matter was uniformly high across the estuary (~9–15 mm yr-1), indicating that elevation loss was not due to lack of accretionary input. Position in the estuary and associated salinity regime were not related to elevation change or surface matter accretion. Previous studies have focused on surface elevation change in marshes of uniform salinity (e.g., salt marshes); however, our findings highlight the need for elevation studies in marshes of all salinity regimes and different geomorphic positions, and warn that brackish, oligohaline, and freshwater tidal wetlands may be at similarly high risk of submergence in some estuaries. PMID:27467784

Tidal Marshes across a Chesapeake Bay Subestuary Are Not Keeping up with Sea-Level Rise

DOE PAGES

Beckett, Leah H.; Baldwin, Andrew H.; Kearney, Michael S.; ...

2016-07-28

Sea-level rise is a major factor in wetland loss worldwide, and inmuch of Chesapeake Bay (USA) the rate of sea-level rise is higher than the current global rate of 3.2 mmyr -1 due to regional subsidence.Marshes along estuarine salinity gradients differ in vegetation composition, productivity, decomposition pathways, and sediment dynamics, andmay exhibit different responses to sea-level rise. Coastal marshes persist by building vertically at rates at or exceeding regional sea-level rise. In one of the first studies to examine elevation dynamics across an estuarine salinity gradient, we installed 15 surface elevation tables (SET) and accretion marker-horizon plots (MH) in tidalmore » freshwater, oligohaline, and brackish marshes across a Chesapeake Bay subestuary. Over the course of four years, wetlands across the subestuary decreased 1.8 ± 2.7 mmyr -1 in elevation on average, at least 5 mmyr -1 below that needed to keep pace with global sea-level rise. Elevation change rates did not significantly differ among themarshes studied, and ranged from-9.8 ± 6.9 to 4.5 ± 4.3 mmyr -1. Surface accretion of depositedmineral and organic matter was uniformly high across the estuary (~9–15 mmyr -1), indicating that elevation loss was not due to lack of accretionary input. Position in the estuary and associated salinity regime were not related to elevation change or surface matter accretion. In conclusion, previous studies have focused on surface elevation change inmarshes of uniformsalinity (e.g., salt marshes); however, our findings highlight the need for elevation studies inmarshes of all salinity regimes and different geomorphic positions, and warn that brackish, oligohaline, and freshwater tidal wetlands may be at similarly high risk of submergence in some estuaries.« less

Feed intake and behavior of dairy goats when offered an elevated feed bunk.

PubMed

Neave, Heather W; von Keyserlingk, Marina A G; Weary, Daniel M; Zobel, Gosia

2018-04-01

Goats are browsers and select vegetation at various heights when foraging. On commercial farms, dairy goats are typically fed from low-level feed bunks. The objective of this study was to determine how feed intake and feeding behavior vary when goats are offered feed at variable heights, with the potential of evaluating the benefits of offering an elevated feeder to dairy goats. Thirteen Saanen X dairy goats were housed in a home pen with a lying area of wood shavings, where they were pre-exposed for 24 d to 3 feeder heights designed to result in differences in head height while feeding: floor level (head lowered relative to body), head level (head level relative to body), and elevated level (head and neck angled upward). Nine groups of 3 goats each were randomly selected and housed for 24 h in a test pen identical to the home pen except that it contained 1 of each of the 3 feeder heights. Each feeder contained ad libitum chopped alfalfa silage and a top-dressed corn-based supplement, refreshed twice daily. Refusals from inside and under each feeder were weighed to calculate intake. Feed intake increased with increasing feeder height (mean ± SE; 0.18, 0.29, and 0.34 ± 0.04 kg of DM/goat for floor-level, head-level, and elevated-level feeders, respectively). Total feeding time did not vary with feeder height, but feeding rate tended to be faster at the elevated-level feeder (14.5 ± 2.1 g of DM/min) compared with head-level (9.2 ± 2.3 g of DM/min) and floor-level (8.9 ± 2.1 g of DM/min) feeders. Goats visited the floor-level feeder (36.4 ± 8.4 visits/goat) less than the head-level (79.4 ± 8.4 visits/goat) and elevated-level (74.8 ± 8.4 visits/goat) feeders. The number of displacements per minute of feeding time (physical removal of another goat from the feeding place) was greater at the elevated-level feeder (0.46 ± 0.06 displacements/min) compared with the floor-level feeder (0.23 ± 0.06 displacements/min) and tended to differ from the head-level feeder (0.27 ± 0.06 displacements/min). We conclude that goats eat more from an elevated feeder and compete more to access this feeder. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

PubMed

Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

2008-08-01

It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Endocrine antecedents of polycystic ovary syndrome (PCOS) in fetal and infant prenatally androgenized female rhesus monkeys

PubMed Central

Abbott, David H; Barnett, Deborah K; Levine, Jon E; Padmanabhan, Vasantha; Dumesic, Daniel A; Jacoris, Steve; Tarantal, Alice F

2008-01-01

Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits in adult female rhesus monkeys. Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily subcutaneous injections of 15 mg testosterone propionate (TP) and six received injections of oil vehicle (controls) from 40 through 80 days of gestation (term 165 [range: ±10] days), and all fetuses were delivered by Cesarean-section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels mostly normalized, while serum androstenedione levels in PA infants were elevated. TP injections did not increase estrogen levels in the dams, PA fetuses and infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally-induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants, and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood. PMID:18385445

Effect of sulfonylureas administered centrally on the blood glucose level in immobilization stress model.

PubMed

Sharma, Naveen; Sim, Yun-Beom; Park, Soo-Hyun; Lim, Su-Min; Kim, Sung-Su; Jung, Jun-Sub; Hong, Jae-Seung; Suh, Hong-Won

2015-05-01

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Evaluation of a childhood lead questionnaire in predicting elevated blood lead levels in a rural community.

PubMed

Muñiz, Marco A; Dundas, Robert; Mahoney, Martin C

2003-01-01

The accuracy of a lead screening questionnaire in predicting elevated blood lead levels was examined in a pediatric practice in a rural part of New York state. A retrospective chart review was used to collect data on children ages 9 to 24 months who presented for well-child visits. Children with both questionnaire and lead level results available in the chart were included in the study (n = 171). The mean blood lead level among all children was 1.6 microg/dl (median = 2.0 microg/dl, range 0 to 24 microg/dl). Four children (2.3%) had elevated lead levels (greater than 10 microg/dl), with levels for two of these children being greater than 20 microg/dl. Although our lead screening questionnaire was expanded from the standard 1991 CDC questionnaire by the inclusion of six additional items, it was not especially useful in predicting elevated blood lead levels above 10 microg/dl. However, the questionnaire exhibited some utility in predicting marked elevations in blood lead levels (over 20 microg/dl). Although results in other geographic areas might differ, the lead questionnaire may have value by enhancing parents' awareness of potential lead hazards in their children's environment and may prove to be more useful in areas of high risk to lead exposure.

Elevated voltage level I.sub.DDQ failure testing of integrated circuits

DOEpatents

Righter, Alan W.

1996-01-01

Burn in testing of static CMOS IC's is eliminated by I.sub.DDQ testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip.

Impact of elevated levels of atmospheric CO2 and herbivory on flavonoids of soybean (Glycine max Linnaeus).

PubMed

O'Neill, Bridget F; Zangerl, Arthur R; Dermody, Orla; Bilgin, Damla D; Casteel, Clare L; Zavala, Jorge A; DeLucia, Evan H; Berenbaum, May R

2010-01-01

Atmospheric levels of carbon dioxide (CO2) have been increasing steadily over the last century. Plants grown under elevated CO2 conditions experience physiological changes, particularly in phytochemical content, that can influence their suitability as food for insects. Flavonoids are important plant defense compounds and antioxidants that can have a large effect on leaf palatability and herbivore longevity. In this study, flavonoid content was examined in foliage of soybean (Glycine max Linnaeus) grown under ambient and elevated levels of CO2 and subjected to damage by herbivores in three feeding guilds: leaf skeletonizer (Popillia japonica Newman), leaf chewer (Vanessa cardui Linnaeus), and phloem feeder (Aphis glycines Matsumura). Flavonoid content also was examined in foliage of soybean grown under ambient and elevated levels of O3 and subjected to damage by the leaf skeletonizer P. japonica. The presence of the isoflavones genistein and daidzein and the flavonols quercetin and kaempferol was confirmed in all plants examined, as were their glycosides. All compounds significantly increased in concentration as the growing season progressed. Concentrations of quercetin glycosides were higher in plants grown under elevated levels of CO2. The majority of compounds in foliage were induced in response to leaf skeletonization damage but remained unchanged in response to non-skeletonizing feeding or phloem-feeding. Most compounds increased in concentration in plants grown under elevated levels of O3. Insects feeding on G. max foliage growing under elevated levels of CO2 may derive additional antioxidant benefits from their host plants as a consequence of the change in ratios of flavonoid classes. This nutritional benefit could lead to increased herbivore longevity and increased damage to soybean (and perhaps other crop plants) in the future.

Is moral elevation an approach-oriented emotion?

PubMed Central

Van de Vyver, Julie; Abrams, Dominic

2017-01-01

Abstract Two studies were designed to test whether moral elevation should be conceptualized as an approach-oriented emotion. The studies examined the relationship between moral elevation and the behavioral activation and inhibition systems. Study 1 (N = 80) showed that individual differences in moral elevation were associated with individual differences in behavioral activation but not inhibition. Study 2 (N = 78) showed that an elevation-inducing video promoted equally high levels of approach orientation as an anger-inducing video and significantly higher levels of approach orientation than a control video. Furthermore, the elevation-inducing stimulus (vs. the control condition) significantly promoted prosocial motivation and this effect was sequentially mediated by feelings of moral elevation followed by an approach-oriented state. Overall the results show unambiguous support for the proposal that moral elevation is an approach-oriented emotion. Applied and theoretical implications are discussed. PMID:28191027

The Encoding of Sound Source Elevation in the Human Auditory Cortex.

PubMed

Trapeau, Régis; Schönwiesner, Marc

2018-03-28

Spatial hearing is a crucial capacity of the auditory system. While the encoding of horizontal sound direction has been extensively studied, very little is known about the representation of vertical sound direction in the auditory cortex. Using high-resolution fMRI, we measured voxelwise sound elevation tuning curves in human auditory cortex and show that sound elevation is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. We changed the ear shape of participants (male and female) with silicone molds for several days. This manipulation reduced or abolished the ability to discriminate sound elevation and flattened cortical tuning curves. Tuning curves recovered their original shape as participants adapted to the modified ears and regained elevation perception over time. These findings suggest that the elevation tuning observed in low-level auditory cortex did not arise from the physical features of the stimuli but is contingent on experience with spectral cues and covaries with the change in perception. One explanation for this observation may be that the tuning in low-level auditory cortex underlies the subjective perception of sound elevation. SIGNIFICANCE STATEMENT This study addresses two fundamental questions about the brain representation of sensory stimuli: how the vertical spatial axis of auditory space is represented in the auditory cortex and whether low-level sensory cortex represents physical stimulus features or subjective perceptual attributes. Using high-resolution fMRI, we show that vertical sound direction is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. In addition, we demonstrate that the shape of these tuning functions is contingent on experience with spectral cues and covaries with the change in perception, which may indicate that the tuning functions in low-level auditory cortex underlie the perceived elevation of a sound source. Copyright © 2018 the authors 0270-6474/18/383252-13$15.00/0.

Functional role of long-lived flowers in preventing pollen limitation in a high elevation outcrossing species

PubMed Central

Pacheco, Diego Andrés; Dudley, Leah S

2017-01-01

Abstract Low pollinator visitation in harsh environments may lead to pollen limitation which can threaten population persistence. Consequently, avoidance of pollen limitation is expected in outcrossing species subjected to habitually low pollinator service. The elevational decline in visitation rates on many high mountains provides an outstanding opportunity for addressing this question. According to a recent meta-analysis, levels of pollen limitation in alpine and lowland species do not differ. If parallel trends are manifested among populations of alpine species with wide elevational ranges, how do their uppermost populations contend with lower visitation? We investigated visitation rates and pollen limitation in high Andean Rhodolirium montanum. We test the hypothesis that lower visitation rates at high elevations are compensated for by the possession of long-lived flowers. Visitation rates decreased markedly over elevation as temperature decreased. Pollen limitation was absent at the low elevation site but did occur at the high elevation site. While initiation of stigmatic pollen deposition at high elevations was not delayed, rates of pollen arrival were lower, and cessation of pollination, as reflected by realized flower longevity, occurred later in the flower lifespan. Comparison of the elevational visitation decline and levels of pollen limitation indicates that flower longevity partially compensates for the lower visitation rates at high elevation. The functional role of flower longevity, however, was strongly masked by qualitative pollen limitation arising from higher abortion levels attributable to transference of genetically low-quality pollen in large clones. Stronger clonal growth at high elevations could counterbalance the negative fitness consequences of residual pollen limitation due to low visitation rates and/or difficult establishment under colder conditions. Visitation rates on the lower part of the elevational range greatly exceeded community rates recorded several decades ago when the planet was cooler. Current pollen limitation for some species in some habitats might underestimate historical levels. PMID:29225762

Base (100-year) flood elevations for selected sites in Marion County, Missouri

USGS Publications Warehouse

Southard, Rodney E.; Wilson, Gary L.

1998-01-01

The primary requirement for community participation in the National Flood Insurance Program is the adoption and enforcement of floodplain management requirements that minimize the potential for flood damages to new construction and avoid aggravating existing flooding conditions. This report provides base flood elevations (BFE) for a 100-year recurrence flood for use in the management and regulation of 14 flood-hazard areas designated by the Federal Emergency Management Agency as approximate Zone A areas in Marion County, Missouri. The one-dimensional surface-water flow model, HEC-RAS, was used to compute the base (100-year) flood elevations for the 14 Zone A sites. The 14 sites were located at U.S., State, or County road crossings and the base flood elevation was determined at the upstream side of each crossing. The base (100-year) flood elevations for BFE 1, 2, and 3 on the South Fork North River near Monroe City, Missouri, are 627.7, 579.2, and 545.9 feet above sea level. The base (100-year) flood elevations for BFE 4, 5, 6, and 7 on the main stem of the North River near or at Philadelphia and Palmyra, Missouri, are 560.5, 539.7, 504.2, and 494.4 feet above sea level. BFE 8 is located on Big Branch near Philadelphia, a tributary to the North River, and the base (100-year) flood elevation at this site is 530.5 feet above sea level. One site (BFE 9) is located on the South River near Monroe City, Missouri. The base (100-year) flood elevation at this site is 619.1 feet above sea level. Site BFE 10 is located on Bear Creek near Hannibal, Missouri, and the base (100-year) elevation is 565.5 feet above sea level. The four remaining sites (BFE 11, 12, 13, and 14) are located on the South Fabius River near Philadelphia and Palmyra, Missouri. The base (100-year) flood elevations for BFE 11, 12, 13, and 14 are 591.2, 578.4, 538.7, and 506.9 feet above sea level.

Effect of high altitude on blood glucose meter performance.

PubMed

Fink, Kenneth S; Christensen, Dale B; Ellsworth, Allan

2002-01-01

Participation in high-altitude wilderness activities may expose persons to extreme environmental conditions, and for those with diabetes mellitus, euglycemia is important to ensure safe travel. We conducted a field assessment of the precision and accuracy of seven commonly used blood glucose meters while mountaineering on Mount Rainier, located in Washington State (elevation 14,410 ft). At various elevations each climber-subject used the randomly assigned device to measure the glucose level of capillary blood and three different concentrations of standardized control solutions, and a venous sample was also collected for later glucose analysis. Ordinary least squares regression was used to assess the effect of elevation and of other environmental potential covariates on the precision and accuracy of blood glucose meters. Elevation affects glucometer precision (p = 0.08), but becomes less significant (p = 0.21) when adjusted for temperature and relative humidity. The overall effect of elevation was to underestimate glucose levels by approximately 1-2% (unadjusted) for each 1,000 ft gain in elevation. Blood glucose meter accuracy was affected by elevation (p = 0.03), temperature (p < 0.01), and relative humidity (p = 0.04) after adjustment for the other variables. The interaction between elevation and relative humidity had a meaningful but not statistically significant effect on accuracy (p = 0.07). Thus, elevation, temperature, and relative humidity affect blood glucose meter performance, and elevated glucose levels are more greatly underestimated at higher elevations. Further research will help to identify which blood glucose meters are best suited for specific environments.

Processes contributing to resilience of coastal wetlands to sea-level rise

USGS Publications Warehouse

Stagg, Camille L.; Krauss, Ken W.; Cahoon, Donald R.; Cormier, Nicole; Conner, William H.; Swarzenski, Christopher M.

2016-01-01

The objectives of this study were to identify processes that contribute to resilience of coastal wetlands subject to rising sea levels and to determine whether the relative contribution of these processes varies across different wetland community types. We assessed the resilience of wetlands to sea-level rise along a transitional gradient from tidal freshwater forested wetland (TFFW) to marsh by measuring processes controlling wetland elevation. We found that, over 5 years of measurement, TFFWs were resilient, although some marginally, and oligohaline marshes exhibited robust resilience to sea-level rise. We identified fundamental differences in how resilience is maintained across wetland community types, which have important implications for management activities that aim to restore or conserve resilient systems. We showed that the relative importance of surface and subsurface processes in controlling wetland surface elevation change differed between TFFWs and oligohaline marshes. The marshes had significantly higher rates of surface accretion than the TFFWs, and in the marshes, surface accretion was the primary contributor to elevation change. In contrast, elevation change in TFFWs was more heavily influenced by subsurface processes, such as root zone expansion or compaction, which played an important role in determining resilience of TFFWs to rising sea level. When root zone contributions were removed statistically from comparisons between relative sea-level rise and surface elevation change, sites that previously had elevation rate deficits showed a surplus. Therefore, assessments of wetland resilience that do not include subsurface processes will likely misjudge vulnerability to sea-level rise.

A comparison and evaluation between ICESat/GLAS altimetry and mean sea level in Thailand

NASA Astrophysics Data System (ADS)

Naksen, Didsaphan; Yang, Dong Kai

2015-10-01

Surface elevation is one of the importance information for GIS. Usually surface elevation can acquired from many sources such as satellite imageries, aerial photograph, SAR data or LiDAR by photogrammetry, remote sensing methodology. However the most trust information describe the actual surface elevation is Leveling from terrestrial survey. Leveling is giving the highest accuracy but in the other hand is also long period process spending a lot of budget and resources, moreover the LiDAR technology is new era to measure surface elevation. ICESat/GLAS is spaceborne LiDAR platform, a scientific satellite lunched by NASA in 2003. The study area was located at the middle part of Thailand between 12. ° - 14° North and 98° -100° East Latitude and Longitude. The main idea is to compare and evaluate about elevation between ICESat/GLAS Altimetry and mean sea level of Thailand. Data are collected from various sources, including the ICESat/GLAS altimetry data product from NASA, mean sea level from Royal Thai Survey Department (RTSD). For methodology, is to transform ICESat GLA14 from TOPX/Poseidon-Jason ellipsoid to WGS84 ellipsoid. In addition, ICESat/GLAS altimetry that extracted form centroid of laser footprint and mean sea level were compared and evaluated by 1st Layer National Vertical Reference Network. The result is shown that generally the range of elevation between ICESat/GLAS and mean sea level is wildly from 0. 8 to 25 meters in study area.

Levels at gaging stations

USGS Publications Warehouse

Kenney, Terry A.

2010-01-01

Operational procedures at U.S. Geological Survey gaging stations include periodic leveling checks to ensure that gages are accurately set to the established gage datum. Differential leveling techniques are used to determine elevations for reference marks, reference points, all gages, and the water surface. The techniques presented in this manual provide guidance on instruments and methods that ensure gaging-station levels are run to both a high precision and accuracy. Levels are run at gaging stations whenever differences in gage readings are unresolved, stations may have been damaged, or according to a pre-determined frequency. Engineer's levels, both optical levels and electronic digital levels, are commonly used for gaging-station levels. Collimation tests should be run at least once a week for any week that levels are run, and the absolute value of the collimation error cannot exceed 0.003 foot/100 feet (ft). An acceptable set of gaging-station levels consists of a minimum of two foresights, each from a different instrument height, taken on at least two independent reference marks, all reference points, all gages, and the water surface. The initial instrument height is determined from another independent reference mark, known as the origin, or base reference mark. The absolute value of the closure error of a leveling circuit must be less than or equal to ft, where n is the total number of instrument setups, and may not exceed |0.015| ft regardless of the number of instrument setups. Closure error for a leveling circuit is distributed by instrument setup and adjusted elevations are determined. Side shots in a level circuit are assessed by examining the differences between the adjusted first and second elevations for each objective point in the circuit. The absolute value of these differences must be less than or equal to 0.005 ft. Final elevations for objective points are determined by averaging the valid adjusted first and second elevations. If final elevations indicate that the reference gage is off by |0.015| ft or more, it must be reset.

Effects of different carbon dioxide and LED lighting levels on the anti-oxidative capabilities of Gynura bicolor DC

NASA Astrophysics Data System (ADS)

Ren, Jin; Guo, Shuangsheng; Xu, Chunlan; Yang, Chengjia; Ai, Weidang; Tang, Yongkang; Qin, Lifeng

2014-01-01

Gynura bicolor DC is not only an edible plant but also a kind of traditional Chinese herbal medicine. G. bicolor DC grown in controlled environmental chambers under 3 CO2 concentrations [450 (ambient), 1500 (elevated), 8000 (super-elevated) μmol mol-1] and 3 LED lighting conditions [white (WL), 85% red + 15% blue (RB15), 70% red + 30% blue (RB30) ] were investigated to reveal plausible antioxidant anabolic responses to CO2 enrichment and LED light quality. Under ambient and elevated CO2 levels, blue light increasing from 15% to 30% was conducive to the accumulation of anthocyanins and total flavonoids, and the antioxidant activity of extract was also increased, but plant biomass was decreased. These results demonstrated that the reinforcement of blue light could induce more antioxidant of secondary metabolites, but depress the effective growth of G. bicolor DC under ambient and elevated CO2 levels. In addition, compared with the ambient and elevated CO2 levels, the increased anthocyanins, total flavonoids contents and antioxidant enzyme activities of G. bicolor DC under super-elevated CO2 level could serve as important components of antioxidative defense mechanism against CO2 stress. Hence, G. bicolor DC might have higher tolerance to CO2 stress.

The magnitude of elevated maternal serum human chorionic gonadotropin and pregnancy complications.

PubMed

Sharony, Reuven; Zipper, Oren; Amichay, Keren; Wiser, Amir; Kidron, Debora; Biron-Shental, Tal; Maymon, Ron

2017-07-01

This study assessed the correlation between the magnitude of the elevation in maternal serum human chorionic gonadotropin (MShCG) levels and pregnancy complications. Among 80,716 screened pregnancies, 120 with moderately elevated MShCG (3.00-5.99 MoM) were compared to 84 with extremely elevated MShCG >6.00 MoM. A control series of 120 women with normal MShCG (<3.00 MoM) were matched. Rates of intrauterine growth restriction, preterm labour, antepartum foetal death (APFD), pre-eclampsia, and placental abruption were analysed. We found that the study group had more adverse outcomes than the control group (73/204 [36%] vs. 18/120 [15%]; p < .0001). The rate was higher in the extremely elevated group than in the moderately elevated group (43/84 [51%] vs. 30/120 [25%]; p < .0001). All 12 cases of APFD (14%) occurred among the extremely elevated series. In conclusion, adverse pregnancy outcomes are more common in women with extremely elevated MShCG. The patients should receive counselling regarding this trend and undergo close pregnancy monitoring. Impact statement • What is already known on this subject?In addition to its contribution to Down syndrome (DS) screening, maternal serum human chorionic gonadotropin (MShCG) levels are a marker for pregnancy complications such as intrauterine growth restriction (IUGR), preterm labour (PTL), antepartum fatal death (APFD), pre-eclampsia (PE), placental abruption (PA) and fetal malformations with or without chromosomal aberrations. • What the results of this study add? We found that in the presence of elevated MShCG levels, the incidence of IUGR and PTL increased. PE increased clinically, but statistical significance was seen only when MShCG was extremely elevated (≥ 6.00 MoM). APFD and PA were associated with very high MShCG levels only. • What the implications are of these findings for clinical practice and/or further research? Women with high MShCG levels should be counselled. In case of very high levels (≥ 6.00 MoM), the risk of APFD and PA should be discussed. The pregnancy should be monitored for IUGR, PTL and PE. In view of the limited number of enrolled patients with very high levels of MShCG, the experience of other institutions is needed to corroborate these findings.

Heat shock response and mammal adaptation to high elevation (hypoxia).

PubMed

Wang, Xiaolin; Xu, Cunshuan; Wang, Xiujie; Wang, Dongjie; Wang, Qingshang; Zhang, Baochen

2006-10-01

The mammal's high elevation (hypoxia) adaptation was studied by using the immunological and the molecular biological methods to understand the significance of Hsp (hypoxia) adaptation in the organic high elevation, through the mammal heat shock response. (1) From high elevation to low elevation (natural hypoxia): Western blot and conventional RT-PCR and real-time fluorescence quota PCR were adopted. Expression difference of heat shock protein of 70 (Hsp70) and natural expression of brain tissue of Hsp70 gene was determined in the cardiac muscle tissue among the different elevation mammals (yak). (2) From low elevation to high elevation (hypoxia induction): The mammals (domestic rabbits) from the low elevation were sent directly to the areas with different high elevations like 2300, 3300 and 5000 m above sea level to be raised for a period of 3 weeks before being slaughtered and the genetic inductive expression of the brain tissue of Hsp70 was determined with RT-PCR. The result indicated that all of the mammals at different elevations possessed their heat shock response gene. Hsp70 of the high elevation mammal rose abruptly under stress and might be induced to come into being by high elevation (hypoxia). The speedy synthesis of Hsp70 in the process of heat shock response is suitable to maintain the cells' normal physiological functions under stress. The Hsp70 has its threshold value. The altitude of 5000 m above sea level is the best condition for the heat shock response, and it starts to reduce when the altitude is over 6000 m above sea level. The Hsp70 production quantity and the cell hypoxia bearing capacity have their direct ratio.

The 3D Elevation Program: summary for Missouri

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Montana

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The new 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Louisiana

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Tennessee

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for New York

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

3D Elevation Program: summary for Vermont

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Maryland

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Ohio

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation's natural and constructed features.

The 3D Elevation Program: summary for Indiana

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation's natural and constructed features.

The 3D Elevation Program: summary for Maine

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Kentucky

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Oregon

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for North Dakota

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Florida

USGS Publications Warehouse

Carswell, William J.

2013-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The new 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the OMB Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

3D Elevation Program: summary for Nebraska

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Alabama

USGS Publications Warehouse

Carswell, William J.

2013-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The new 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A-16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

[Effects of silicon supply on diurnal variations of physiological properties at rice heading stage under elevated UV-B radiation].

PubMed

Wu, Lei; Lou, Yun-sheng; Meng, Yan; Wang, Wei-qing; Cui, He-yang

2015-01-01

A pot experiment was conducted to investigate the effects of silicon (Si) supply on diurnal variations of photosynthesis and transpiration-related physiological parameters at rice heading stage under elevated UV-B radiation. The experiment was designed with two UV-B radiation levels, i.e. ambient UV-B. (ambient, A) and elevated UV-B (elevated by 20%, E), and four Si supply levels, i.e. Sio (control, 0 kg SiO2 . hm-2), Si, (sodium silicate, 100 kg SiO2 . hm-2), Si2 (sodium silicate, 200 kg SiO2 . hm2), Si3 (slag fertilizer, 200 kg SiO2 . hm-2). The results showed that, compared with ambient UV-B radiation, elevated UV-B radiation decreased the net photosynthesis rate (Pn) , intercellular CO2 concentration (Ci), transpiration rate (Tr), stomatal conductivity (gs) and water use efficiency (WUE) by 11.3%, 5.5%, 10.4%, 20.3% and 6.3%, respectively, in the treatment without Si supply (Si, level), and decreased the above parameters by 3.8%-5.5%, 0.7%-4.8%, 4.0%-8.7%, 7.4%-20.2% and 0.7%-5.9% in the treatments with Si supply (Si1, Si2 and Si3 levels) , respectively. Namely, elevated UV-B radiation decreased the photosynthesis and transpiration-related physiological parameters, but silicon supply could obviously mitigate the depressive effects of elevated UV-B radiation. Under elevated UV-B radiation, compared with control (Si0 level), silicon supply increased Pn, Ci, gs and WUE by 16.9%-28.0%, 3.5%-14.3%, 16.8% - 38.7% and 29.0% - 51.2%, respectively, but decreased Tr by 1.9% - 10.8% in the treatments with Si supply (Si1 , Si2 and Si3 levels). That is, silicon supply could mitigate the depressive effects of elevated UV-B radiation through significantly increasingnP., CigsgK and WUE, but decreasing T,. However, the difference existed in ameliorating the depressive effects of elevated UV-B radiation on diurnal variations of physiological parameters among the treatments of silicon supply, with the sequence of Si3>Si2>1i >Si0. This study suggested that fertilizing slag was helpful not only in recycling industrial wastes, but also in effectively mitigating the depressive effects of elevated UV-B radiation on photosynthesis and transpiration in rice production.

Sea level and turbidity controls on mangrove soil surface elevation change

USGS Publications Warehouse

Lovelock, Catherine E.; Fernanda Adame, Maria; Bennion, Vicki; Hayes, Matthew; Reef, Ruth; Santini, Nadia; Cahoon, Donald R.

2015-01-01

Increases in sea level are a threat to seaward fringing mangrove forests if levels of inundation exceed the physiological tolerance of the trees; however, tidal wetlands can keep pace with sea level rise if soil surface elevations can increase at the same pace as sea level rise. Sediment accretion on the soil surface and belowground production of roots are proposed to increase with increasing sea level, enabling intertidal habitats to maintain their position relative to mean sea level, but there are few tests of these predictions in mangrove forests. Here we used variation in sea level and the availability of sediments caused by seasonal and inter-annual variation in the intensity of La Nina-El Nino to assess the effects of increasing sea level on surface elevation gains and contributing processes (accretion on the surface, subsidence and root growth) in mangrove forests. We found that soil surface elevation increased with mean sea level (which varied over 250 mm during the study) and with turbidity at sites where fine sediment in the water column is abundant. In contrast, where sediments were sandy, rates of surface elevation gain were high, but not significantly related to variation in turbidity, and were likely to be influenced by other factors that deliver sand to the mangrove forest. Root growth was not linked to soil surface elevation gains, although it was associated with reduced shallow subsidence, and therefore may contribute to the capacity of mangroves to keep pace with sea level rise. Our results indicate both surface (sedimentation) and subsurface (root growth) processes can influence mangrove capacity to keep pace with sea level rise within the same geographic location, and that current models of tidal marsh responses to sea level rise capture the major feature of the response of mangroves where fine, but not coarse, sediments are abundant.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

Molecular theory for self assembling mixtures of patchy colloids and colloids with spherically symmetric attractions: The single patch case

NASA Astrophysics Data System (ADS)

Marshall, Bennett D.; Chapman, Walter G.

2013-09-01

In this work we develop a new theory to model self assembling mixtures of single patch colloids and colloids with spherically symmetric attractions. In the development of the theory we restrict the interactions such that there are short ranged attractions between patchy and spherically symmetric colloids, but patchy colloids do not attract patchy colloids and spherically symmetric colloids do not attract spherically symmetric colloids. This results in the temperature, density, and composition dependent reversible self assembly of the mixture into colloidal star molecules. This type of mixture has been recently synthesized by grafting of complimentary single stranded DNA [L. Feng, R. Dreyfus, R. Sha, N. C. Seeman, and P. M. Chaikin, Adv. Mater. 25(20), 2779-2783 (2013)], 10.1002/adma.201204864. As a quantitative test of the theory, we perform new monte carlo simulations to study the self assembly of these mixtures; theory and simulation are found to be in excellent agreement.

Anatomy of a Nanoscale Conduction Channel Reveals the Mechanism of a High-Performance Memristor

NASA Astrophysics Data System (ADS)

Miao, Feng; Strachan, John Paul; Yang, J. Joshua; Yi, Wei; Goldfarb, Ilan; Zhang, M.-X.; Torrezan, Antonio C.; Eschbach, Peter; Kelley, Ronald D.; Medeiros-Ribeiro, Gilberto; Williams, R. Stanley

2012-02-01

Two major challenges for resistance memory devices (memristors) based on conductivity changes in oxide materials are better performance and understanding of the microscopic picture of the switching. After researchers' relentless pursuit for years, tantalum oxide-based memristors have rapidly risen to be the top candidate, showing fast speed, high endurance and excellent scalability. While the microscopic picture of these devices remains obscure, by employing a precise method for locating and directly visualizing the conduction channel, here we observed a nanoscale channel consisting of an amorphous Ta(O) solid solution surrounded by crystalline Ta2O5. Structural and chemical analyses of the channel combined with temperature dependent transport measurements revealed a unique resistance switching mechanism: the modulation of the channel elemental composition, and thus the conductivity, by the cooperative influence of drift, diffusion and thermophoresis, which seem to enable the high switching performance observed. (Miao*, Strachan*, Yang* et al., Advanced Materials. DOI: 10.1002/adma201103379 (2011))

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.

PubMed

Hu, Lizhi; Mauro, Theodora M; Dang, Erle; Man, George; Zhang, Jing; Lee, Dale; Wang, Gang; Feingold, Kenneth R; Elias, Peter M; Man, Mao-Qiang

2017-06-01

Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Supplemental and highly-elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects

PubMed Central

McCary, Christine A.; Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2011-01-01

We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with antigen and supplemental tocopherols in a first phase of treatment followed by a 4 week clearance phase and then the mice received a second phase of antigen and tocopherol treatments. The pro-inflammatory effects of supplemental levels of γ-tocopherol in phase 1 were only partially reversed by supplemental α-tocopherol in phase 2 but were completely reversed by raising α-tocopherol levels 10-fold in phase 2. When γ-tocopherol levels were increased 10-fold (highly-elevated tocopherol) so that the lung tissue γ-tocopherol levels were equal to the lung tissue levels of supplemental α-tocopherol, γ-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly-elevated levels of γ-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly-elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of antigen challenge without tocopherols. In summary, the pro-inflammatory effects of supplemental γ-tocopherol on lung inflammation were partially reversed by supplemental levels of α-tocopherol but were completely reversed by highly-elevated-levels of α-tocopherol. Also, highly-elevated levels of γ-tocopherol were inhibitory and reversible in lung lavage but, importantly, were pro-inflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature. PMID:21317387

Elevated voltage level I{sub DDQ} failure testing of integrated circuits

DOEpatents

Righter, A.W.

1996-05-21

Burn in testing of static CMOS IC`s is eliminated by I{sub DDQ} testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip. 4 figs.

Prevalence and predictors of alanine aminotransferase elevation among normal weight, overweight and obese youth in Mexico.

PubMed

Purcell, Maura; Flores, Yvonne N; Zhang, Zuo-Feng; Denova-Gutiérrez, Edgar; Salmeron, Jorge

2013-09-01

This study aimed to determine the prevalence of and risk factors associated with elevated alanine aminotransferase (ALT) levels among a sample of normal weight, overweight and obese youth from two urban populations in Central Mexico. Baseline data from 1262 youth aged 8-19 years who participated in the Mexican Health Worker Cohort Study from March 2004 to April 2006 were reviewed, including 680 girls and 582 boys, with a total of 83 participants with elevated ALT level (>40 U/L). Information was obtained from self-administered questionnaires, anthropometric results and clinical measurements. Associations of interest were examined using multivariate logistic regression models. A total of 3.8% of girls and 9.8% of boys had elevated ALT levels. Elevated ALT was observed in 28.9% of the obese and 14.2% of the overweight participants. Metabolic syndrome (MS) occurred in 6.1% of the study population and those with MS had a high percentage of elevated ALT (14.5% of girls and 40.0% of boys, respectively). Abdominal obesity and insulin resistance were also associated with a greater risk of elevated ALT. Obesity and certain metabolic risk factors are important predictors for elevated ALT. Screening for ALT levels in obese youth could help to identify those at risk and reduce the possibility of future liver diseases. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

NASA Technical Reports Server (NTRS)

Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

1997-01-01

We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

Assessing coastal wetland vulnerability to sea-level rise along the northern Gulf of Mexico coast: Gaps and opportunities for developing a coordinated regional sampling network

PubMed Central

Griffith, Kereen T.; Larriviere, Jack C.; Feher, Laura C.; Cahoon, Donald R.; Enwright, Nicholas M.; Oster, David A.; Tirpak, John M.; Woodrey, Mark S.; Collini, Renee C.; Baustian, Joseph J.; Breithaupt, Joshua L.; Cherry, Julia A.; Conrad, Jeremy R.; Cormier, Nicole; Coronado-Molina, Carlos A.; Donoghue, Joseph F.; Graham, Sean A.; Harper, Jennifer W.; Hester, Mark W.; Howard, Rebecca J.; Krauss, Ken W.; Kroes, Daniel E.; Lane, Robert R.; McKee, Karen L.; Mendelssohn, Irving A.; Middleton, Beth A.; Moon, Jena A.; Piazza, Sarai C.; Rankin, Nicole M.; Sklar, Fred H.; Steyer, Greg D.; Swanson, Kathleen M.; Swarzenski, Christopher M.; Vervaeke, William C.; Willis, Jonathan M.; Wilson, K. Van

2017-01-01

Coastal wetland responses to sea-level rise are greatly influenced by biogeomorphic processes that affect wetland surface elevation. Small changes in elevation relative to sea level can lead to comparatively large changes in ecosystem structure, function, and stability. The surface elevation table-marker horizon (SET-MH) approach is being used globally to quantify the relative contributions of processes affecting wetland elevation change. Historically, SET-MH measurements have been obtained at local scales to address site-specific research questions. However, in the face of accelerated sea-level rise, there is an increasing need for elevation change network data that can be incorporated into regional ecological models and vulnerability assessments. In particular, there is a need for long-term, high-temporal resolution data that are strategically distributed across ecologically-relevant abiotic gradients. Here, we quantify the distribution of SET-MH stations along the northern Gulf of Mexico coast (USA) across political boundaries (states), wetland habitats, and ecologically-relevant abiotic gradients (i.e., gradients in temperature, precipitation, elevation, and relative sea-level rise). Our analyses identify areas with high SET-MH station densities as well as areas with notable gaps. Salt marshes, intermediate elevations, and colder areas with high rainfall have a high number of stations, while salt flat ecosystems, certain elevation zones, the mangrove-marsh ecotone, and hypersaline coastal areas with low rainfall have fewer stations. Due to rapid rates of wetland loss and relative sea-level rise, the state of Louisiana has the most extensive SET-MH station network in the region, and we provide several recent examples where data from Louisiana’s network have been used to assess and compare wetland vulnerability to sea-level rise. Our findings represent the first attempt to examine spatial gaps in SET-MH coverage across abiotic gradients. Our analyses can be used to transform a broadly disseminated and unplanned collection of SET-MH stations into a coordinated and strategic regional network. This regional network would provide data for predicting and preparing for the responses of coastal wetlands to accelerated sea-level rise and other aspects of global change. PMID:28902904

Assessing coastal wetland vulnerability to sea-level rise along the northern Gulf of Mexico coast: Gaps and opportunities for developing a coordinated regional sampling network

USGS Publications Warehouse

Osland, Michael J.; Griffith, Kereen T.; Larriviere, Jack C.; Feher, Laura C.; Cahoon, Donald R.; Enwright, Nicholas M.; Oster, David A.; Tirpak, John M.; Woodrey, Mark S.; Collini, Renee C.; Baustian, Joseph J.; Breithaupt, Joshua L.; Cherry, Julia A; Conrad, Jeremy R.; Cormier, Nicole; Coronado-Molina, Carlos A.; Donoghue, Joseph F.; Graham, Sean A.; Harper, Jennifer W.; Hester, Mark W.; Howard, Rebecca J.; Krauss, Ken W.; Kroes, Daniel; Lane, Robert R.; Mckee, Karen L.; Mendelssohn, Irving A.; Middleton, Beth A.; Moon, Jena A.; Piazza, Sarai; Rankin, Nicole M.; Sklar, Fred H.; Steyer, Gregory D.; Swanson, Kathleen M.; Swarzenski, Christopher M.; Vervaeke, William; Willis, Jonathan M; Van Wilson, K.

2017-01-01

Coastal wetland responses to sea-level rise are greatly influenced by biogeomorphic processes that affect wetland surface elevation. Small changes in elevation relative to sea level can lead to comparatively large changes in ecosystem structure, function, and stability. The surface elevation table-marker horizon (SET-MH) approach is being used globally to quantify the relative contributions of processes affecting wetland elevation change. Historically, SET-MH measurements have been obtained at local scales to address site-specific research questions. However, in the face of accelerated sea-level rise, there is an increasing need for elevation change network data that can be incorporated into regional ecological models and vulnerability assessments. In particular, there is a need for long-term, high-temporal resolution data that are strategically distributed across ecologically-relevant abiotic gradients. Here, we quantify the distribution of SET-MH stations along the northern Gulf of Mexico coast (USA) across political boundaries (states), wetland habitats, and ecologically-relevant abiotic gradients (i.e., gradients in temperature, precipitation, elevation, and relative sea-level rise). Our analyses identify areas with high SET-MH station densities as well as areas with notable gaps. Salt marshes, intermediate elevations, and colder areas with high rainfall have a high number of stations, while salt flat ecosystems, certain elevation zones, the mangrove-marsh ecotone, and hypersaline coastal areas with low rainfall have fewer stations. Due to rapid rates of wetland loss and relative sea-level rise, the state of Louisiana has the most extensive SET-MH station network in the region, and we provide several recent examples where data from Louisiana’s network have been used to assess and compare wetland vulnerability to sea-level rise. Our findings represent the first attempt to examine spatial gaps in SET-MH coverage across abiotic gradients. Our analyses can be used to transform a broadly disseminated and unplanned collection of SET-MH stations into a coordinated and strategic regional network. This regional network would provide data for predicting and preparing for the responses of coastal wetlands to accelerated sea-level rise and other aspects of global change.

Assessing coastal wetland vulnerability to sea-level rise along the northern Gulf of Mexico coast: Gaps and opportunities for developing a coordinated regional sampling network.

PubMed

Osland, Michael J; Griffith, Kereen T; Larriviere, Jack C; Feher, Laura C; Cahoon, Donald R; Enwright, Nicholas M; Oster, David A; Tirpak, John M; Woodrey, Mark S; Collini, Renee C; Baustian, Joseph J; Breithaupt, Joshua L; Cherry, Julia A; Conrad, Jeremy R; Cormier, Nicole; Coronado-Molina, Carlos A; Donoghue, Joseph F; Graham, Sean A; Harper, Jennifer W; Hester, Mark W; Howard, Rebecca J; Krauss, Ken W; Kroes, Daniel E; Lane, Robert R; McKee, Karen L; Mendelssohn, Irving A; Middleton, Beth A; Moon, Jena A; Piazza, Sarai C; Rankin, Nicole M; Sklar, Fred H; Steyer, Greg D; Swanson, Kathleen M; Swarzenski, Christopher M; Vervaeke, William C; Willis, Jonathan M; Wilson, K Van

2017-01-01

Coastal wetland responses to sea-level rise are greatly influenced by biogeomorphic processes that affect wetland surface elevation. Small changes in elevation relative to sea level can lead to comparatively large changes in ecosystem structure, function, and stability. The surface elevation table-marker horizon (SET-MH) approach is being used globally to quantify the relative contributions of processes affecting wetland elevation change. Historically, SET-MH measurements have been obtained at local scales to address site-specific research questions. However, in the face of accelerated sea-level rise, there is an increasing need for elevation change network data that can be incorporated into regional ecological models and vulnerability assessments. In particular, there is a need for long-term, high-temporal resolution data that are strategically distributed across ecologically-relevant abiotic gradients. Here, we quantify the distribution of SET-MH stations along the northern Gulf of Mexico coast (USA) across political boundaries (states), wetland habitats, and ecologically-relevant abiotic gradients (i.e., gradients in temperature, precipitation, elevation, and relative sea-level rise). Our analyses identify areas with high SET-MH station densities as well as areas with notable gaps. Salt marshes, intermediate elevations, and colder areas with high rainfall have a high number of stations, while salt flat ecosystems, certain elevation zones, the mangrove-marsh ecotone, and hypersaline coastal areas with low rainfall have fewer stations. Due to rapid rates of wetland loss and relative sea-level rise, the state of Louisiana has the most extensive SET-MH station network in the region, and we provide several recent examples where data from Louisiana's network have been used to assess and compare wetland vulnerability to sea-level rise. Our findings represent the first attempt to examine spatial gaps in SET-MH coverage across abiotic gradients. Our analyses can be used to transform a broadly disseminated and unplanned collection of SET-MH stations into a coordinated and strategic regional network. This regional network would provide data for predicting and preparing for the responses of coastal wetlands to accelerated sea-level rise and other aspects of global change.

Using blood cytokine measures to define high inflammatory biotype of schizophrenia and schizoaffective disorder.

PubMed

Boerrigter, Danny; Weickert, Thomas W; Lenroot, Rhoshel; O'Donnell, Maryanne; Galletly, Cherrie; Liu, Dennis; Burgess, Martin; Cadiz, Roxanne; Jacomb, Isabella; Catts, Vibeke S; Fillman, Stu G; Weickert, Cynthia Shannon

2017-09-18

Increases in pro-inflammatory cytokines are found in the brain and blood of people with schizophrenia. However, increased cytokines are not evident in all people with schizophrenia, but are found in a subset. The cytokine changes that best define this subset, termed the "elevated inflammatory biotype", are still being identified. Using quantitative RT-PCR, we measured five cytokine mRNAs (IL-1β, IL-2 IL-6, IL-8 and IL-18) from peripheral blood of healthy controls and of people with schizophrenia or schizoaffective disorder (n = 165). We used a cluster analysis of the transcript levels to define those with low and those with elevated levels of cytokine expression. From the same cohort, eight cytokine proteins (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IFNγ and TNFα) were measured in serum and plasma using a Luminex Magpix-based assay. We compared peripheral mRNA and protein levels across diagnostic groups and between those with low and elevated levels of cytokine expression according to our transcription-based cluster analysis. We found an overall decrease in the anti-inflammatory IL-2 mRNA (p = 0.006) and an increase in three serum cytokines, IL-6 (p = 0.010), IL-8 (p = 0.024) and TNFα (p < 0.001) in people with schizophrenia compared to healthy controls. A greater percentage of people with schizophrenia (48%) were categorised into the elevated inflammatory biotype compared to healthy controls (33%). The magnitude of increase in IL-1β, IL-6, IL-8 and IL-10 mRNAs in people in the elevated inflammation biotype ranged from 100 to 220% of those in the non-elevated inflammatory biotype and was comparable between control and schizophrenia groups. Blood cytokine protein levels did not correlate with cytokine mRNA levels, and plasma levels of only two cytokines distinguished the elevated and low inflammatory biotypes, with IL-1β significantly increased in the elevated cytokine control group and IL-8 significantly increased in the elevated cytokine schizophrenia group. Our results confirm that individuals with schizophrenia are more likely to have elevated levels of inflammation compared to controls. We suggest that efforts to define inflammatory status based on peripheral measures need to consider both mRNA and protein measures as each have distinct advantages and disadvantages and can yield different results.

Three Gorges Dam: Impact of Water Level Changes on the Density of Schistosome-Transmitting Snail Oncomelania hupensis in Dongting Lake Area, China

PubMed Central

Wu, Jin-Yi; Zhou, Yi-Biao; Chen, Yue; Liang, Song; Li, Lin-Han; Zheng, Sheng-Bang; Zhu, Shao-ping; Ren, Guang-Hui; Song, Xiu-Xia; Jiang, Qing-Wu

2015-01-01

Background Schistosomiasis remains an important public health issue in China and worldwide. Oncomelania hupensis is the unique intermediate host of schistosoma japonicum, and its change influences the distribution of S. japonica. The Three Gorges Dam (TGD) has substantially changed the ecology and environment in the Dongting Lake region. This study investigated the impact of water level and elevation on the survival and habitat of the snails. Methods Data were collected for 16 bottomlands around 4 hydrological stations, which included water, density of living snails (form the Anxiang Station for Schistosomiasis Control) and elevation (from Google Earth). Based on the elevation, sixteen bottomlands were divided into 3 groups. ARIMA models were built to predict the density of living snails in different elevation areas. Results Before closure of TGD, 7 out of 9 years had a water level beyond the warning level at least once at Anxiang hydrological station, compared with only 3 out of 10 years after closure of TGD. There were two severe droughts that happened in 2006 and 2011, with much fewer number of flooding per year compared with other study years. Overall, there was a correlation between water level changing and density of living snails variation in all the elevations areas. The density of living snails in all elevations areas was decreasing after the TGD was built. The relationship between number of flooding per year and the density of living snails was more pronounced in the medium and high elevation areas; the density of living snails kept decreasing from 2003 to 2014. In low elevation area however, the density of living snails decreased after 2003 first and turned to increase after 2011. Our ARIMA prediction models indicated that the snails would not disappear in the Dongting Lake region in the next 7 years. In the low elevation area, the density of living snails would increase slightly, and then stabilize after the year 2017. In the medium elevation region, the change of the density of living snails would be more obvious and would increase till the year 2020. In the high elevation area, the density of living snails would remain stable after the year 2015. Conclusion The TGD influenced water levels and reduced the risk of flooding and the density of living snails in the study region. Based on our prediction models, the density of living snails in all elevations tends to be stabilized. Control of S. japonica would continue to be an important task in the study area in the coming decade. PMID:26114956

The role of surface and subsurface processes in keeping pace with sea level rise in intertidal wetlands of Moreton Bay, Queensland, Australia

USGS Publications Warehouse

Lovelock, Catherine E.; Bennion, Vicki; Grinham, Alistair; Cahoon, Donald R.

2011-01-01

Increases in the elevation of the soil surfaces of mangroves and salt marshes are key to the maintenance of these habitats with accelerating sea level rise. Understanding the processes that give rise to increases in soil surface elevation provides science for management of landscapes for sustainable coastal wetlands. Here, we tested whether the soil surface elevation of mangroves and salt marshes in Moreton Bay is keeping up with local rates of sea level rise (2.358 mm y-1) and whether accretion on the soil surface was the most important process for keeping up with sea level rise. We found variability in surface elevation gains, with sandy areas in the eastern bay having the highest surface elevation gains in both mangrove and salt marsh (5.9 and 1.9 mm y-1) whereas in the muddier western bay rates of surface elevation gain were lower (1.4 and -0.3 mm y-1 in mangrove and salt marsh, respectively). Both sides of the bay had similar rates of surface accretion (~7–9 mm y-1 in the mangrove and 1–3 mm y-1 in the salt marsh), but mangrove soils in the western bay were subsiding at a rate of approximately 8 mm y-1, possibly due to compaction of organic sediments. Over the study surface elevation increments were sensitive to position in the intertidal zone (higher when lower in the intertidal) and also to variation in mean sea level (higher at high sea level). Although surface accretion was the most important process for keeping up with sea level rise in the eastern bay, subsidence largely negated gains made through surface accretion in the western bay indicating a high vulnerability to sea level rise in these forests.

High serum selenium levels are associated with impaired fasting glucose and elevated fasting serum glucose in Linyi, China.

PubMed

Li, Zhe; Li, Xia; Ju, Wen; Wu, Guanrui; Yang, Xiaomei; Fu, Xiaofeng; Gao, Xibao

2018-01-01

The relationship between selenium level and impaired fasting glucose or elevated fasting serum glucose remains controversial. This study aimed to evaluate these associations in China. This observational population study adopted a cluster sampling approach to enroll participants. Baseline information on selenium categories was tested using one-way analysis of variance and Kruskal-Wallis equality-of-populations rank tests. Multivariable logistic regression was used to investigate the association between serum selenium level and impaired fasting glucose or elevated fasting serum glucose. The mean serum selenium concentration was 121.5μg/L which in a relatively high baseline Se status. Differences were observed among individuals with normal, impaired fasting glucose and elevated fasting serum glucose levels in their basic information, physical examination results and laboratory findings. After adjusting for their basic information, physical examination results and laboratory findings, compared with the low-selenium group, the high-selenium groups (124.9-143.9 and above 143.9μg/L) had ORs for elevated fasting serum glucose of 2.31 (1.37-3.90) and 2.67 (1.59-4.48), respectively (both P<0.05). A sex-difference was observed, and a significant association between selenium levels and impaired fasting glucose was observed for males but not for females. The findings of this observational study suggest that relatively high selenium levels might be positively associated with elevated fasting serum glucose and relatively high selenium levels might be positively associated with impaired fasting glucose in men. Copyright © 2017 Elsevier GmbH. All rights reserved.

The 3D Elevation Program: summary for Connecticut

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Mississippi

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Georgia

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Iowa

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Oklahoma

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment (NEEA; Dewberry, 2011) evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Kansas

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Nevada

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Illinois

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Colorado

USGS Publications Warehouse

Carswell, William J.

2013-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Utah

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Delaware

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Massachusetts

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for West Virginia

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for South Carolina

USGS Publications Warehouse

Carswell, William

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for North Carolina

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment (NEEA; Dewberry, 2011) evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the use community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for South Dakota

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment (NEEA; Dewberry, 2011) evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 ifsar data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The new 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: Summary for New Jersey

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Washington

USGS Publications Warehouse

Carswell, William J.

2013-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for New Mexico

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 (table 1) for the conterminous United States and quality level 5 ifsar data (table 1) for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Wyoming

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Arizona

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for New Hampshire

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Pennsylvania

USGS Publications Warehouse

Carswell, William J.

2015-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

The 3D Elevation Program: summary for Arkansas

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios.The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation’s natural and constructed features.

Elevated serum uric acid levels are associated with endothelial dysfunction in HIV patients receiving highly-active antiretroviral therapy.

PubMed

Pirro, Matteo; Bianconi, Vanessa; Schiaroli, Elisabetta; Francisci, Daniela; Mannarino, Massimo R; Bagaglia, Francesco; Sahebkar, Amirhossein; Merriman, Tony; Baldelli, Franco

2018-05-01

Elevated serum uric acid (SUA) levels may be associated with endothelial dysfunction. Increased rates of metabolic syndrome (MS) and elevated SUA levels were described in human immunodeficiency virus (HIV) infected patients. We investigated whether SUA levels are associated with endothelial dysfunction in HIV positive patients receiving highly-active antiretroviral therapy (HAART) irrespective of MS. In this cross-sectional study of 250 HIV positive patients receiving stable HAART, we evaluated the relationship between MS, SUA levels and endothelial function. SUA levels and brachial artery flow-mediated dilation (bFMD) were measured. The relationship between logarithmic (LG)-transformed SUA levels and bFMD was evaluated after correction for MS. MS was detected in 28.4% of patients and elevated SUA levels (≥6 mg/dL) in 25.2%. MS was associated with higher LG-SUA levels (age-, gender- and glomerular filtration rate-adjusted beta = 0.204, p = 0.001). The crude linear association between LG-SUA levels and LG-bFMD (beta = -0.166, p = 0.008) was abolished after correction for MS (beta = -0.089, p = 0.172). When SUA levels were used as a categorical variable (≥6 mg/dL or <6 mg/dL and SUA quartiles, respectively), the association between LG-SUA levels and LG-bFMD remained significant after adjustment for MS (beta = -0.142, p = 0.022 and beta = -0.163, p = 0.010, respectively). MS significantly affects SUA levels in HAART-treated HIV infected patients. The negative association between SUA and bFMD is independent of MS only for elevated SUA levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Vertical accretion and shallow subsidence in a mangrove forest of southwestern Florida, U.S.A

USGS Publications Warehouse

Cahoon, D.R.; Lynch, J.C.

1997-01-01

Simultaneous measurements of vertical accretion from artificial soil marker horizons and soil elevation change from sedimentation-erosion table (SET) plots were used to evaluate the processes related to soil building in range, basin, and overwash mangrove forests located in a low-energy lagoon which recieves minor inputs of terregenous sediments. Vertical accretion measures reflect the contribution of surficial sedimentation (sediment deposition and surface root growth). Measures of elevation change reflect not only the contributions of vertical accretion but also those of subsurface processes such as compaction, decomposition and shrink-swell. The two measures were used to calculate amounts of shallow subsidence (accretion minus elevation change) in each mangrove forest. The three forest types represent different accretionary envrionments. The basin forest was located behind a natural berm. Hydroperiod here was controlled primarily by rainfall rather than tidal exchange, although the basin flooded during extreme tidal events. Soil accretion here occurred primarily by autochthonous organic matter inputs, and elevation was controlled by accretion and shrink-swell of the substrate apparently related to cycles of flooding-drying and/or root growth-decomposition. This hydrologically-restricted forest did not experience an accretion or elevation deficit relative to sea-level rise. The tidally dominated fringe and overwash island forests accreted through mineral sediment inputs bound in place by plant roots. Filamentous turf algae played an important role in stabilizing loose muds in the fringe forest where erosion was prevalent. Elevation in these high-energy environments was controlled not only by accretion but also by erosion and/or shallow subsidence. The rate of shallow subsidence was consistently 3-4 mm y-1 in the fringe and overwash island forests but was negligible in the basin forest. Hence, the vertical development of mangrove soils was influenced by both surface and subsurface processes and the procces controlling soil elevation differed among forest types. The mangrove ecosystem at Rookery Bay has remained stable as sea level has risen during the past 70 years. Yet, lead-210 accretion data suggest a substantial accretion deficit has occurred in the past century (accretion was 10-20 cm < sea-level rise from 1930 to 1990) in the fringe and island forests at Rookery Bay. In contrast, our measures of elevation change mostly equalled the estimates of sea-level rise and shallow subsidence. These data suggest that (1) vertical accretion in this system is driven by local sea-level rise and shallow subsidence, and (2) the mangrove forests are mostly keeping pace with sea-level rise. Thus, the vulnerability of this mangrove ecosystem to sea-level rise is best described in terms of an elevation deficit (elevation change minus sea-level rise) based on annual measures rather than an accretion deficit (accretion minus sea-level rise) based on decadal measures.

Elevated-CO2 Response of Stomata and Its Dependence on Environmental Factors

PubMed Central

Xu, Zhenzhu; Jiang, Yanling; Jia, Bingrui; Zhou, Guangsheng

2016-01-01

Stomata control the flow of gases between plants and the atmosphere. This review is centered on stomatal responses to elevated CO2 concentration and considers other key environmental factors and underlying mechanisms at multiple levels. First, an outline of general responses in stomatal conductance under elevated CO2 is presented. Second, stomatal density response, its development, and the trade-off with leaf growth under elevated CO2 conditions are depicted. Third, the molecular mechanism regulating guard cell movement at elevated CO2 is suggested. Finally, the interactive effects of elevated CO2 with other factors critical to stomatal behavior are reviewed. It may be useful to better understand how stomata respond to elevated CO2 levels while considering other key environmental factors and mechanisms, including molecular mechanism, biochemical processes, and ecophysiological regulation. This understanding may provide profound new insights into how plants cope with climate change. PMID:27242858

Prostaglandins E and F in endocrine diarrheagenic syndromes.

PubMed Central

Jaffe, B M; Condon, S

1976-01-01

The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea. PMID:189708

Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, M.D.; Cohen, A.S.

1979-01-01

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. Highmore » SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease.« less

Behavioral and modeling studies of sound localization in cats: effects of stimulus level and duration

PubMed Central

Ruhland, Janet L.; Yin, Tom C. T.; Tollin, Daniel J.

2013-01-01

Sound localization accuracy in elevation can be affected by sound spectrum alteration. Correspondingly, any stimulus manipulation that causes a change in the peripheral representation of the spectrum may degrade localization ability in elevation. The present study examined the influence of sound duration and level on localization performance in cats with the head unrestrained. Two cats were trained using operant conditioning to indicate the apparent location of a sound via gaze shift, which was measured with a search-coil technique. Overall, neither sound level nor duration had a notable effect on localization accuracy in azimuth, except at near-threshold levels. In contrast, localization accuracy in elevation improved as sound duration increased, and sound level also had a large effect on localization in elevation. For short-duration noise, the performance peaked at intermediate levels and deteriorated at low and high levels; for long-duration noise, this “negative level effect” at high levels was not observed. Simulations based on an auditory nerve model were used to explain the above observations and to test several hypotheses. Our results indicated that neither the flatness of sound spectrum (before the sound reaches the inner ear) nor the peripheral adaptation influences spectral coding at the periphery for localization in elevation, whereas neural computation that relies on “multiple looks” of the spectral analysis is critical in explaining the effect of sound duration, but not level. The release of negative level effect observed for long-duration sound could not be explained at the periphery and, therefore, is likely a result of processing at higher centers. PMID:23657278

77 FR 6980 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Nowata County... Sea Level, rounded to the nearest 0.1 meter. ADDRESSES Unincorporated Areas of Nowata County Maps are... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified St. Lucie County...

77 FR 3625 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... feet above ground [caret] Elevation in meters (MSL) Modified City of Baltimore, Maryland Docket No... Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Baltimore Maps are available for... Depth in feet Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified...

Adult cystic fibrosis: postprandial response of gut regulatory peptides.

PubMed

Allen, J M; Penketh, A R; Adrian, T E; Lee, Y C; Sarson, D L; Hodson, M E; Batten, J C; Bloom, S R

1983-12-01

Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.

Simulation of Sub-Drains Performance Using Visual MODFLOW for Slope Water Seepage Problem

NASA Astrophysics Data System (ADS)

Baharuddin, M. F. T.; Tajudin, S. A. A.; Abidin, M. H. Z.; Yusoff, N. A.

2016-07-01

Numerical simulation technique was used for investigating water seepage problem at the Botanic Park Kuala Lumpur. A proposed sub-drains installation in problematic site location was simulated using Modular Three-Dimensional Finite Difference Groundwater Flow (MODFLOW) software. The results of simulation heads during transient condition showed that heads in between 43 m (water seepage occurred at level 2) until 45 m (water seepage occurred at level 4) which heads measurement are referred to mean sea level. However, elevations measurements for level 2 showed the values between 41 to 42 m from mean sea level and elevations for level 4 between 42 to 45 m from mean sea level. These results indicated an increase in heads for level 2 and level 4 between 1 to 2 m when compared to elevations slope at the level 2 and level 4. The head increases surpass the elevation level of the slope area that causing water seepage at level 2 and level 4. In order to overcome this problems, the heads level need to be decrease to 1 until 2 m by using two options of sub-drain dimension size. Sub-drain with the dimension of 0.0750 m (diameter), 0.10 m (length) and using 4.90 m spacing was the best method to use as it was able to decrease the heads to the required levels of 1 to 2 m.

The vulnerability of Indo-Pacific mangrove forests to sea-level rise

USGS Publications Warehouse

Lovelock, Catherine E.; Cahoon, Donald R.; Friess, Daniel A.; Guntenspergen, Glenn R.; Krauss, Ken W.; Reef, Ruth; Rogers, Kerrylee; Saunders, Megan L.; Sidik, Frida; Swales, Andrew; Saintilan, Neil; Thuyen, Le Xuan; Triet, Tran

2015-01-01

Sea-level rise can threaten the long-term sustainability of coastal communities and valuable ecosystems such as coral reefs, salt marshes and mangroves. Mangrove forests have the capacity to keep pace with sea-level rise and to avoid inundation through vertical accretion of sediments, which allows them to maintain wetland soil elevations suitable for plant growth. The Indo-Pacific region holds most of the world’s mangrove forests, but sediment delivery in this region is declining, owing to anthropogenic activities such as damming of rivers. This decline is of particular concern because the Indo-Pacific region is expected to have variable, but high, rates of future sea-level rise. Here we analyse recent trends in mangrove surface elevation changes across the Indo-Pacific region using data from a network of surface elevation table instruments. We find that sediment availability can enable mangrove forests to maintain rates of soil-surface elevation gain that match or exceed that of sea-level rise, but for 69 per cent of our study sites the current rate of sea-level rise exceeded the soil surface elevation gain. We also present a model based on our field data, which suggests that mangrove forests at sites with low tidal range and low sediment supply could be submerged as early as 2070.

The vulnerability of Indo-Pacific mangrove forests to sea-level rise.

PubMed

Lovelock, Catherine E; Cahoon, Donald R; Friess, Daniel A; Guntenspergen, Glenn R; Krauss, Ken W; Reef, Ruth; Rogers, Kerrylee; Saunders, Megan L; Sidik, Frida; Swales, Andrew; Saintilan, Neil; Thuyen, Le Xuan; Triet, Tran

2015-10-22

Sea-level rise can threaten the long-term sustainability of coastal communities and valuable ecosystems such as coral reefs, salt marshes and mangroves. Mangrove forests have the capacity to keep pace with sea-level rise and to avoid inundation through vertical accretion of sediments, which allows them to maintain wetland soil elevations suitable for plant growth. The Indo-Pacific region holds most of the world's mangrove forests, but sediment delivery in this region is declining, owing to anthropogenic activities such as damming of rivers. This decline is of particular concern because the Indo-Pacific region is expected to have variable, but high, rates of future sea-level rise. Here we analyse recent trends in mangrove surface elevation changes across the Indo-Pacific region using data from a network of surface elevation table instruments. We find that sediment availability can enable mangrove forests to maintain rates of soil-surface elevation gain that match or exceed that of sea-level rise, but for 69 per cent of our study sites the current rate of sea-level rise exceeded the soil surface elevation gain. We also present a model based on our field data, which suggests that mangrove forests at sites with low tidal range and low sediment supply could be submerged as early as 2070.

Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Harris, J.; Halloran, B. P.; Morey-Holton, E.

1994-01-01

Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.

Analysis of lidar elevation data for improved identification and delineation of lands vulnerable to sea-level rise

USGS Publications Warehouse

Gesch, Dean B.

2009-01-01

The importance of sea-level rise in shaping coastal landscapes is well recognized within the earth science community, but as with many natural hazards, communicating the risks associated with sea-level rise remains a challenge. Topography is a key parameter that influences many of the processes involved in coastal change, and thus, up-to-date, high-resolution, high-accuracy elevation data are required to model the coastal environment. Maps of areas subject to potential inundation have great utility to planners and managers concerned with the effects of sea-level rise. However, most of the maps produced to date are simplistic representations derived from older, coarse elevation data. In the last several years, vast amounts of high quality elevation data derived from lidar have become available. Because of their high vertical accuracy and spatial resolution, these lidar data are an excellent source of up-to-date information from which to improve identification and delineation of vulnerable lands. Four elevation datasets of varying resolution and accuracy were processed to demonstrate that the improved quality of lidar data leads to more precise delineation of coastal lands vulnerable to inundation. A key component of the comparison was to calculate and account for the vertical uncertainty of the elevation datasets. This comparison shows that lidar allows for a much more detailed delineation of the potential inundation zone when compared to other types of elevation models. It also shows how the certainty of the delineation of lands vulnerable to a given sea-level rise scenario is much improved when derived from higher resolution lidar data.

[Effects of silicon supply on rice growth and methane emission from paddy soil under elevated UV-B radiation].

PubMed

Meng, Yan; Lou, Yun-sheng; Wu, Lei; Cui, He-yang; Wang, Wei-qing

2015-01-01

A pot experiment was conducted to investigate the effects of silicon supply on rice growth and methane (CH4) emission in paddy field under elevated UV-B radiation. The experiment was designed with two UV-B radiation levels, i.e. ambient UV-B (ambient, A) and elevated UV-B radiation (elevated by 20%, E) ; with four silicon supply levels, i.e., Si0 (control, without silicon), Si2 (as sodium silicate, 100 kg SiO2 . hm-2), Si2 (as sodium silicate, 200 kg SiO2 hm-2) and Si3 (as slag fertilizer, 200 kg SiO2 . hm-2). The results indicated that, silicon supply obviously alleviated the depressive effect of elevated UV-B radiation on rice growth, and increased the tiller numbers, chlorophyll content, and shoot and root dry masses. Silicon supply promoted rice growth, which increased with the silicon supply level (sodium silicate). Slag fertilizer was better than*sodium silicate in promoting rice growth. CH4 flux and accumulated CH4emission were obviously increased by elevated UV-B radiation, but significantly decreased by silicon application. CH4 emission was reduced with increasing the silicon supply level. Under the same silicon supply level, slag fertilizer was better than sodium silicate in inhibiting CH4 flux and accumulated CH4 emission. This research suggested that fertilizing slag in rice production was helpful not only in utilizing industrial wastes, but also in significantly mitigating CH4 emissions in rice paddy under elevated UV-B radiation.

Amyotrophic lateral sclerosis (ALS), a novel rare cause of elevated plasma troponin T levels.

PubMed

Von Lueder, Thomas G; Melsom, Morten Nissen; Atar, Dan; Agewall, Stefan

2011-01-01

In this article, we report on a patient with chronic and modestly elevated plasma troponin T (TnT) levels and frequent hospitalizations following the first admission until his death one year later. The patient was initially admitted for dyspnea and discharged from hospital with a diagnosis of non-ST elevation acute myocardial infarction (AMI). Coronary angiography and echocardiography were normal, but the patient received the (false) diagnosis of AMI at two further admissions, based purely on elevated TnT. Shortly thereafter, severe respiratory failure with restrictive-type spirometry pattern became the predominant clinical symptom, with constantly elevated TnT levels at frequent re-admissions. Due to inconsistent follow-up by primarily junior and non-specialist staff at a number of different wards, pulmonary function tests and previous smoking history were mis-interpreted as typical of chronic obstructive pulmonary disease (COPD). The patient received standard COPD treatment without any improvement. After a year of gradually worsening respiratory failure and repeated hospitalizations, thorough assessment by a pulmonologist and neurologist established the final diagnosis of amyotrophic lateral sclerosis (ALS). The patient died shortly thereafter. While progressive respiratory failure is well-known to determine morbidity and mortality in patients with ALS, chronically elevated TnT levels in the absence of coronary artery disease have, to our best knowledge, not been described so far. We suggest that chronic myocardial hypoxia due to ALS-related hypoxic respiratory failure was the most likely underlying etiology for the elevated TnT levels seen here but other mechanism such as immune-mediated myocardial injury cannot be excluded.

Correlation of serum metal ion levels with pathological changes of ARMD in failed metal-on-metal-hip-resurfacing arthroplasties.

PubMed

Grammatopoulos, George; Munemoto, Mitsuru; Pollalis, Athanasios; Athanasou, Nicholas A

2017-08-01

Metal-on-metal-hip-resurfacing arthroplasties (MoMHRAs) have been associated with an increased failure rates due to an adverse-response-to-metal-debris (ARMD) associated with a spectrum of pathological features. Serum levels of cobalt (Co) and chromium (Cr) are used to assess MoMHRAs, with regard to ARMD, but it is not certain whether ion levels correlate with pathological changes in periprosthetic tissues. Serum Co and Cr levels were correlated with histological findings in 38 revised MoMHRAs (29 pseudotumour cases and 9 non-pseudotumour cases revised for pain). The extent of necrosis and macrophage infiltrate as well as the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response was assessed semi-quantitatively; the prosthesis linear wear rate (PLWR) was also determined in ten cases. Cr levels were elevated in 82% and Co levels elevated in 53% of cases; the PLWR correlated with Cr level (rho = 0.8, p = 0.006). Tissue necrosis and macrophage infiltration were noted in all, most of which also exhibited significant ALVAL. Although a discrete correlation was not seen between Co and/or Cr ion levels and the extent of necrosis, degree of macrophage infiltration, or ALVAL score, it was noted that cases with acceptable metal ions levels had high ALVAL score. Histological features of both innate and adaptive immune response to metal wear are seen in periprosthetic tissues in cases with both elevated and non-elevated metal ion levels. MoMHRA failures with acceptable ion levels exhibited a pronounced ALVAL response. Although metal ion levels are elevated in most cases of MoMHRA failure due to ARMD, the finding of a normal metal ion level does not exclude this diagnosis.

Network global navigation satellite system survey to harmonize water-surface elevation data for the Rainy River Basin

USGS Publications Warehouse

Ziegeweid, Jeffrey R.; Silliker, R. Jason; Densmore, Brenda K.; Krahulik, Justin

2016-08-15

Continuously recording water-level streamgages in Rainy Lake and Namakan Reservoir are used to regulate water levels according to rule curves established in 2000 by the International Joint Commission; however, water levels at streamgages were referenced to a variety of vertical datums, confounding efforts to model the flow of water through the system, regulate water levels during periods of high inflow, and evaluate the effectiveness of the rule curves. In October 2014, the U.S. Geological Survey, Natural Resources Canada, International Joint Commission, and National Park Service began a joint field study with the goal of obtaining precise elevations referenced to a uniform vertical datum for all reference marks used to set water levels at streamgages throughout Rainy Lake and Namakan Reservoir. This report was prepared by the U.S. Geological Survey in cooperation with Natural Resources Canada, International Joint Commission, and National Park Service.Three field crews deployed Global Navigation Satellite System receivers statically over 16 reference marks colocated with active and discontinued water-level streamgages throughout Rainy River, Rainy Lake, Namakan Reservoir, and select tributaries of Rainy Lake and Namakan Reservoir. A Global Navigation Satellite System receiver also was deployed statically over a National Geodetic Survey cooperative base network control station for use as a quality-control reference mark. Satellite data were collected simultaneously during a 5-day period and processed independently by the U.S. Geological Survey and Natural Resources Canada to obtain accurate positioning and elevations for the 17 surveyed reference marks. Processed satellite data were used to convert published water levels to elevations above sea level referenced to the Canadian Geodetic Vertical Datum of 2013 in order to compare water-surface elevations referenced to a uniform vertical datum throughout the study area. In this report, an “offset” refers to the correction applied to published data from a particular streamgage to produce elevation data referenced to a specified vertical datum.Offsets were applied to water-level data from surveyed streamgages to further evaluate the accuracy and utility of updated reference mark elevations presented in this report. Daily mean water levels from active streamgages surveyed in this study were converted to water-surface elevations referenced to the Canadian Geodetic Vertical Datum of 2013. Graphical comparisons of water-surface elevations for streamgages in Namakan Reservoir, Rainy Lake, and selected rivers are presented (referencing the Canadian Geodetic Vertical Datum of 2013). Offsets presented in this report can be used in the evaluation of rule curves and in flood damage curves that fully assess the benefits of one regulation approach over another. In addition, offsets may be used to calibrate hydraulic models developed for four narrows that connect lakes of Namakan Reservoir, refine digital elevation models, and support modeling studies designed to assess the effects of rule curves on aquatic vegetation, benthic invertebrates, northern pike, and walleye.

Caribbean mangroves adjust to rising sea level through biotic controls on change in soil elevation

USGS Publications Warehouse

McKee, K.L.; Cahoon, D.R.; Feller, Ilka C.

2007-01-01

Aim The long-term stability of coastal ecosystems such as mangroves and salt marshes depends upon the maintenance of soil elevations within the intertidal habitat as sea level changes. We examined the rates and processes of peat formation by mangroves of the Caribbean Region to better understand biological controls on habitat stability. Location Mangrove-dominated islands on the Caribbean coasts of Belize, Honduras and Panama were selected as study sites. Methods Biological processes controlling mangrove peat formation were manipulated (in Belize) by the addition of nutrients (nitrogen or phosphorus) to Rhizophora mangle (red mangrove), and the effects on the dynamics of soil elevation were determined over a 3-year period using rod surface elevation tables (RSET) and marker horizons. Peat composition and geological accretion rates were determined at all sites using radiocarbon-dated cores. Results The addition of nutrients to mangroves caused significant changes in rates of mangrove root accumulation, which influenced both the rate and direction of change in elevation. Areas with low root input lost elevation and those with high rates gained elevation. These findings were consistent with peat analyses at multiple Caribbean sites showing that deposits (up to 10 m in depth) were composed primarily of mangrove root matter. Comparison of radiocarbon-dated cores at the study sites with a sea-level curve for the western Atlantic indicated a tight coupling between peat building in Caribbean mangroves and sea-level rise over the Holocene. Main conclusions Mangroves common to the Caribbean region have adjusted to changing sea level mainly through subsurface accumulation of refractory mangrove roots. Without root and other organic inputs, submergence of these tidal forests is inevitable due to peat decomposition, physical compaction and eustatic sea-level rise. These findings have relevance for predicting the effects of sea-level rise and biophysical processes on tropical mangrove ecosystems.

Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.

PubMed

Kegeles, Lawrence S; Mao, Xiangling; Stanford, Arielle D; Girgis, Ragy; Ojeil, Najate; Xu, Xiaoyan; Gil, Roberto; Slifstein, Mark; Abi-Dargham, Anissa; Lisanby, Sarah H; Shungu, Dikoma C

2012-05-01

Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. Case-control study. Inpatient psychiatric research unit and associated outpatient clinic. Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.

In-vitro Wound Healing Effect of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor from Plant.

PubMed

Karna, Sandeep

2017-01-01

Prostaglandins (PGs) have short existence in vivo because they are rapidly metabolized by NAD + -dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) to 15-ketoprostaglandins. Inhibition of 15-PGDH causes elevated level of PGE 2 in cellular system. It will be valuable for the therapeutic management of diseases requiring elevated PGE 2 levels, like wound healing. Ninety-eight plant samples were screened for the discovery of potent 15-PGDH inhibitor. Among them, top five plant extracts as potent 15-PGDH inhibitor were chosen to determine PGE 2 release from HaCaT (Keratinocyte cell line) cell line. Finally, top 15-PGDH inhibitor was selected to evaluate in vitro wound healing effect on HaCaT scratch model. The inhibitory activity for 15-PGDH inhibitors was evaluated using fluorescence spectrophotometer by measuring the formation of NADH at 468 nm following excitation at 340 nm. Cell viability assay and PGE 2 release was evaluated in HaCaT cell line after treatment of 15-PGDH inhibitors. Scratches were made using sterile 200 μL on HaCaT cell and wound-healing effect was evaluated after treatment of 15-PGDH inhibitor. 15-PGDH inhibitors elevated PGE 2 levels in concentration-dependent manner. Ethanol extract of Artocarpus heterophyllus (EEAH), the most potent 15-PGDH inhibitor (IC 50 = 0.62 µg/mL) with least cytotoxicity (IC 50 = 670 µg/ml), elevated both intracellular and extracellular PGE 2 levels. EEAH facilitated in-vitro wound healing in a HaCaT (Keratinocyte cell line) scratch model. EEAH might apply to treat dermal wounds by elevating PGE 2 levels via COX-1 induction and 15-PGDH inhibition. Biological inactivation of 15-PGDH causes elevated level of PGE 2 which will be useful for the management of disease that requires elevated level of PGE 2 . Abbreviations used: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase, COX: Cyclooxygenase, DTT: Dithiothreitol, DMEM: Dulbecco's modified Eagle's media, EEAH: Ethanol extract of Artocarpus heterophyllus, MRP4: Multidrug resistance 4, PGs: Prostaglandins, PGT: Prostaglandin transporter, SDS: Sodium dodecylsulfate.

Long-term moderate elevation of corticosterone facilitates avian food-caching behaviour and enhances spatial memory.

PubMed

Pravosudov, Vladimir V

2003-12-22

It is widely assumed that chronic stress and corresponding chronic elevations of glucocorticoid levels have deleterious effects on animals' brain functions such as learning and memory. Some animals, however, appear to maintain moderately elevated levels of glucocorticoids over long periods of time under natural energetically demanding conditions, and it is not clear whether such chronic but moderate elevations may be adaptive. I implanted wild-caught food-caching mountain chickadees (Poecile gambeli), which rely at least in part on spatial memory to find their caches, with 90-day continuous time-release corticosterone pellets designed to approximately double the baseline corticosterone levels. Corticosterone-implanted birds cached and consumed significantly more food and showed more efficient cache recovery and superior spatial memory performance compared with placebo-implanted birds. Thus, contrary to prevailing assumptions, long-term moderate elevations of corticosterone appear to enhance spatial memory in food-caching mountain chickadees. These results suggest that moderate chronic elevation of corticosterone may serve as an adaptation to unpredictable environments by facilitating feeding and food-caching behaviour and by improving cache-retrieval efficiency in food-caching birds.

Tidal marsh plant responses to elevated CO2 , nitrogen fertilization, and sea level rise.

PubMed

Adam Langley, J; Mozdzer, Thomas J; Shepard, Katherine A; Hagerty, Shannon B; Patrick Megonigal, J

2013-05-01

Elevated CO2 and nitrogen (N) addition directly affect plant productivity and the mechanisms that allow tidal marshes to maintain a constant elevation relative to sea level, but it remains unknown how these global change drivers modify marsh plant response to sea level rise. Here we manipulated factorial combinations of CO2 concentration (two levels), N availability (two levels) and relative sea level (six levels) using in situ mesocosms containing a tidal marsh community composed of a sedge, Schoenoplectus americanus, and a grass, Spartina patens. Our objective is to determine, if elevated CO2 and N alter the growth and persistence of these plants in coastal ecosystems facing rising sea levels. After two growing seasons, we found that N addition enhanced plant growth particularly at sea levels where plants were most stressed by flooding (114% stimulation in the + 10 cm treatment), and N effects were generally larger in combination with elevated CO2 (288% stimulation). N fertilization shifted the optimal productivity of S. patens to a higher sea level, but did not confer S. patens an enhanced ability to tolerate sea level rise. S. americanus responded strongly to N only in the higher sea level treatments that excluded S. patens. Interestingly, addition of N, which has been suggested to accelerate marsh loss, may afford some marsh plants, such as the widespread sedge, S. americanus, the enhanced ability to tolerate inundation. However, if chronic N pollution reduces the availability of propagules of S. americanus or other flood-tolerant species on the landscape scale, this shift in species dominance could render tidal marshes more susceptible to marsh collapse. © 2013 Blackwell Publishing Ltd.

Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

PubMed

Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

2014-07-01

Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. © 2014 by the Society for the Study of Reproduction, Inc.

Gestational Exposure to Elevated Testosterone Levels Induces Hypertension via Heightened Vascular Angiotensin II Type 1 Receptor Signaling in Rats1

PubMed Central

Chinnathambi, Vijayakumar; More, Amar S.; Hankins, Gary D.; Yallampalli, Chandra; Sathishkumar, Kunju

2014-01-01

ABSTRACT Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. PMID:24855104

Boosted food web productivity through ocean acidification collapses under warming.

PubMed

Goldenberg, Silvan U; Nagelkerken, Ivan; Ferreira, Camilo M; Ullah, Hadayet; Connell, Sean D

2017-10-01

Future climate is forecast to drive bottom-up (resource driven) and top-down (consumer driven) change to food web dynamics and community structure. Yet, our predictive understanding of these changes is hampered by an over-reliance on simplified laboratory systems centred on single trophic levels. Using a large mesocosm experiment, we reveal how future ocean acidification and warming modify trophic linkages across a three-level food web: that is, primary (algae), secondary (herbivorous invertebrates) and tertiary (predatory fish) producers. Both elevated CO 2 and elevated temperature boosted primary production. Under elevated CO 2 , the enhanced bottom-up forcing propagated through all trophic levels. Elevated temperature, however, negated the benefits of elevated CO 2 by stalling secondary production. This imbalance caused secondary producer populations to decline as elevated temperature drove predators to consume their prey more rapidly in the face of higher metabolic demand. Our findings demonstrate how anthropogenic CO 2 can function as a resource that boosts productivity throughout food webs, and how warming can reverse this effect by acting as a stressor to trophic interactions. Understanding the shifting balance between the propagation of resource enrichment and its consumption across trophic levels provides a predictive understanding of future dynamics of stability and collapse in food webs and fisheries production. © 2017 John Wiley & Sons Ltd.

Spontaneous normalization of anti-tissue transglutaminase antibody levels is common in children with type 1 diabetes mellitus.

PubMed

Waisbourd-Zinman, Orith; Hojsak, Iva; Rosenbach, Yoram; Mozer-Glassberg, Yael; Shalitin, Shlomit; Phillip, Moshe; Shamir, Raanan

2012-05-01

The prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5-10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up. This study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors. The files of all children diagnosed with type 1 diabetes mellitus from 2003-2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized. Forty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements. Physicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

Cardiac troponin increases among marathon runners in the Perth Marathon: the Troponin in Marathons (TRIM) study.

PubMed

Hubble, Kelley M; Fatovich, Daniel M; Grasko, Jonathon M; Vasikaran, Samuel D

2009-01-19

To determine the prevalence of elevated troponin levels after a marathon, and test for an association with reduced renal clearance. Prospective observational study of entrants running the full (42 km) 2007 Perth Marathon, Western Australia. Elevated troponin levels (> or = 0.1 microg/L) after the race; pre- and post-race survey data, and biochemical parameters. 27% of runners (92/346) enrolled in the study, of whom 88 (96%) completed it. Most were men (71%; 65/92); mean age was 43.1 years (SD, 9.8 years; range, 25-64 years) and mean body mass index (BMI) was 24.1 kg/m(2). Raised troponin levels were seen in 32% of participants (28/88), the highest being 1.4 microg/L. The strongest predictor for developing elevated troponin levels was a decrease in weight (odds ratio [OR], 2.15; 95% CI, 1.27-3.65). Creatinine increase was also associated with elevated troponin levels (OR, 1.03; 95% CI, 1.01-1.06), but pre-race estimated glomerular filtration rate, age, sex, BMI, training factors, marathon experience and race time were not. Most runners (99%; 87/88) had elevated levels of ischaemia-modified albumin after the race. Troponin level increases were common among marathon finishers. The strongest predictors were weight loss and an increase in creatinine levels, suggesting that reduced renal clearance is an associated factor. Further study is needed to determine the clinical significance of these findings, and to understand the mechanism.

Contrasting Decadal-Scale Changes in Elevation and Vegetation in Two Long Island Sound Salt Marshes

EPA Science Inventory

Northeastern US salt marshes face multiple co-stressors, including accelerating rates of relative sea level rise (RSLR), elevated nutrient inputs, and low sediment supplies. In order to evaluate how marsh surface elevations respond to such factors, we used surface elevation table...

Transcriptional profiling reveals elevated CO2 and elevated O3 alter resistance of soybean (Glycine max) to Japanese beetles (Popillia japonica).

PubMed

Casteel, Clare L; O'Neill, Bridget F; Zavala, Jorge A; Bilgin, Damla D; Berenbaum, May R; Delucia, Evan H

2008-04-01

The accumulation of CO2 and O3 in the troposphere alters phytochemistry which in turn influences the interactions between plants and insects. Using microarray analysis of field-grown soybean (Glycine max), we found that the number of transcripts in the leaves affected by herbivory by Japanese beetles (Popillia japonica) was greater when plants were grown under elevated CO2, elevated O3 and the combination of elevated CO2 plus elevated O3 than when grown in ambient atmosphere. The effect of herbivory on transcription diminished strongly with time (<1% of genes were affected by herbivory after 3 weeks), and elevated CO2 interacted more strongly with herbivory than elevated O3. The majority of transcripts affected by elevated O3 were related to antioxidant metabolism. Constitutive levels and the induction by herbivory of key transcripts associated with defence and hormone signalling were down-regulated under elevated CO2; 1-aminocyclopropane-1-carboxylate (ACC) synthase, lipoxygenase (LOX), allene oxide synthase (AOS), allene oxide cyclase (AOC), chalcone synthase (CHS), polyphenol oxidase (PPO) and cysteine protease inhibitor (CystPI) were lower in abundance compared with levels under ambient conditions. By suppressing the ability to mount an effective defence, elevated CO2 may decrease resistance of soybean to herbivory.

Adenosine triphosphate and diphosphoglycerate levels in red blood cells from patients with Down's syndrome.

PubMed

Knull, H R; Bronstein, W W; Porter, P J

1978-09-15

The levels of ATP and ATP plus DPG were significantly elevated in erythrocytes from Down's syndrome patients when compared to erythrocytes from age matched controls. The hemoglobin content and hematocrit values were significantly reduced. The resultant tendency towards anemia probably explains the elevation in metabolite levels.

Relationship between elevated triglyceride levels with the increase of HOMA-IR and HOMA-β in healthy children and adolescents with normal weight.

PubMed

Simental-Mendía, Luis E; Castañeda-Chacón, Argelia; Rodriguez-Morán, Martha; Aradillas-García, Celia; Guerrero-Romero, Fernando

2015-05-01

To test the hypothesis that mildly elevated triglyceride levels are associated with the increase of homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) indices in healthy children and adolescents with normal weight, we conducted a cross-sectional population study. Based on fasting triglyceride levels, participants were allocated into groups with and without triglyceride levels ≥1.2 mmol/L. Normal weight was defined by body mass index between the 15th and 85th percentiles, for age and gender. Insulin resistance and insulin secretion were estimated using HOMA-IR and HOMA-β indices. A total of 1660 children and adolescents were enrolled, of them 327 (19.7%) with mildly elevated triglycerides. The multivariate linear regression analysis showed that mildly elevated triglyceride levels in children were associated with HOMA-IR (β = 0.214, p < 0.001), HOMA-β (β = 0.139, p = 0.001), systolic (β = 0.094, p = 0.01), and diastolic blood pressure (β = 0.102, p = 0.007), whereas in adolescents, HOMA-IR (β = 0.267, p < 0.001) and HOMA-β (β = 0.154, p < 0.001), but not systolic (β = 0.029, p = 0.38) and diastolic blood pressure (β = 0.015, p = 0.642), showed association with mildly elevated triglycerides. Mildly elevated triglyceride levels are associated with increased HOMA-IR and HOMA-β indices in healthy children and adolescents with normal weight.

Clinical implications in the prevalence and associated cardiovascular factors of elevated serum alanine aminotransferase levels among elderly agricultural and fishing population in Taipei, Taiwan: experience at a teaching hospital.

PubMed

Chen, Yu-Fen; Hu, Yi-Chun; Shen, Hsi-Che; Chang, Hui-Te; Tung, Tao-Hsin

2014-01-01

To discuss the prevalence and associated factors related to an elevated serum alanine aminotransferase (ALT) level among the elderly agricultural and fishing population. A total of 6542 (3989 males and 2553 females) healthy adults voluntarily admitted to a teaching hospital for a physical checkup in 2010 in Taipei, Taiwan. Fasting blood samples were drawn via venipuncture, and clinical nurses interviewed the study participants using a structured questionnaire from. The overall prevalence of an elevated serum ALT level was 18.2% and revealed a statistically significant decrease with increasing age (P < 0.001). The men exhibited a higher prevalence than the women (19.7% vs 15.9%; P < 0.001). Male sex; younger age; and presence of obesity, hypertension, hyperuricemia, and hypoalbuminemia were significantly associated with an elevated serum ALT level. Sex-related differences were also revealed. For the men, type 2 diabetes (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02-1.57), hypercholesterolemia (OR, 1.78; 95% CI, 1.22-2.83), hypertriglyceridemia (OR, 1.32; 95% CI, 1.04-1.73), and low high-density lipoprotein (OR, 1.26; 95% CI, 1.05-1.51) were significantly related to an elevated serum ALT level, but this was not so for the women. The disparity of ALT in age groups was revealed. Several sex-related differences were indicated pertaining to the prevalence of an elevated serum ALT level among elderly specific occupational population.

Salt marsh persistence is threatened by predicted sea-level rise

NASA Astrophysics Data System (ADS)

Crosby, Sarah C.; Sax, Dov F.; Palmer, Megan E.; Booth, Harriet S.; Deegan, Linda A.; Bertness, Mark D.; Leslie, Heather M.

2016-11-01

Salt marshes buffer coastlines and provide critical ecosystem services from storm protection to food provision. Worldwide, these ecosystems are in danger of disappearing if they cannot increase elevation at rates that match sea-level rise. However, the magnitude of loss to be expected is not known. A synthesis of existing records of salt marsh elevation change was conducted in order to consider the likelihood of their future persistence. This analysis indicates that many salt marshes did not keep pace with sea-level rise in the past century and kept pace even less well over the past two decades. Salt marshes experiencing higher local sea-level rise rates were less likely to be keeping pace. These results suggest that sea-level rise will overwhelm most salt marshes' capacity to maintain elevation. Under the most optimistic IPCC emissions pathway, 60% of the salt marshes studied will be gaining elevation at a rate insufficient to keep pace with sea-level rise by 2100. Without mitigation of greenhouse gas emissions this potential loss could exceed 90%, which will have substantial ecological, economic, and human health consequences.

Serum pro-gastrin-releasing peptide (31-98) in benign prostatic hyperplasia and prostatic carcinoma.

PubMed

Nagakawa, Osamu; Furuya, Yuzo; Fujiuchi, Yasuyoshi; Fuse, Hideki

2002-09-01

To clarify whether serum levels of pro-gastrin-releasing peptide (ProGRP) (31-98) could be a useful marker in patients with prostatic carcinoma. GRP is produced and secreted by prostatic neuroendocrine cells. Serum levels of ProGRP(31-98) were measured by enzyme-linked immunosorbent assay in 20 patients with benign prostatic hyperplasia and 107 patients with prostatic carcinoma. The mean serum levels of ProGRP(31-98) in patients with distant metastasis and hormone-resistant prostate cancer were significantly elevated compared with those in patients with organ-confined disease. Significantly elevated levels of ProGRP(31-98) were detected in 9 patients with prostatic carcinoma before any treatment. During hormone-resistant prostate cancer progression, ProGRP(31-98) levels were elevated in 9 patients (23%). Of the 9 patients with Stage D3 and elevated serum ProGRP, 4 had a normal serum prostate-specific antigen level. ProGRP may be a potential tumor marker for prostate cancer. Additional studies in large groups of patients are needed to define the clinical value of ProGRP.

Leptin Elevation as a Risk Factor for Slipped Capital Femoral Epiphysis Independent of Obesity Status.

PubMed

Halverson, Schuyler J; Warhoover, Tracy; Mencio, Gregory A; Lovejoy, Steven A; Martus, Jeffrey E; Schoenecker, Jonathan G

2017-05-17

Slipped capital femoral epiphysis (SCFE) is strongly associated with childhood obesity, yet the prevalence of obesity is orders of magnitude greater than the prevalence of SCFE. Therefore, it is hypothesized that obesity is not, by itself, a sufficient condition for SCFE, but rather one component of a multifactorial process requiring preexisting physeal pathology. Leptin elevation is seen to varying degrees in patients with obesity, and as leptin has been shown to cause physeal pathology similar to the changes seen in SCFE, we propose that leptin may be a factor distinguishing between patients with SCFE and equally obese children without hip abnormalities. Serum leptin levels were obtained from 40 patients with SCFE and 30 control patients with approximate body mass index (BMI) matching. BMI percentiles were calculated according to Centers for Disease Control and Prevention population data by patient age and sex. Patients were compared by demographic characteristics, leptin levels, odds of leptin elevation, and odds of SCFE. The odds of developing SCFE was increased by an odds ratio of 4.9 (95% confidence interval [CI], 1.31 to 18.48; p < 0.02) in patients with elevated leptin levels, regardless of obesity status, sex, and race. When grouping patients by their obesity status, non-obese patients with SCFE showed elevated median leptin levels at 5.8 ng/mL compared with non-obese controls at 1.7 ng/mL (p = 0.006). Similarly, obese patients with SCFE showed elevated median leptin levels at 17.9 ng/mL compared with equally obese controls at 10.5 ng/mL (p = 0.039). Serum leptin levels increased in association with obesity (p < 0.001), with an increase in leptin of 0.17 ng/mL (95% CI, 0.07 to 0.27 ng/mL) per BMI percentile point. To our knowledge, this study is the first to clinically demonstrate an association between elevated serum leptin levels and SCFE, regardless of BMI. This adds to existing literature suggesting that SCFE is a multifactorial process and that leptin levels may have profound physiological effects on the development of various disease states. Despite a strong association with adiposity, leptin levels vary between patients of equal BMI and may be a vital resource in prognostication of future obesity-related comorbidities. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surviving at high elevations: an inter- and intra-specific analysis in a mountain bird community.

PubMed

Bastianelli, G; Tavecchia, G; Meléndez, L; Seoane, J; Obeso, J R; Laiolo, P

2017-06-01

Elevation represents an important selection agent on self-maintenance traits and correlated life histories in birds, but no study has analysed whether life-history variation along this environmental cline is consistent among and within species. In a sympatric community of passerines, we analysed how the average adult survival of 25 open-habitat species varied with their elevational distribution and how adult survival varied with elevation at the intra-specific level. For such purpose, we estimated intra-specific variation in adult survival in two mountainous species, the Water pipit (Anthus spinoletta) and the Northern wheatear (Oenanthe oenanthe) in NW Spain, by means of capture-recapture analyses. At the inter-specific level, high-elevation species showed higher survival values than low elevation ones, likely because a greater allocation to self-maintenance permits species to persist in alpine environments. At the intra-specific level, the magnitude of survival variation was lower by far. Nevertheless, Water pipit survival slightly decreased at high elevations, while the proportion of transient birds increased. In contrast, no such relationships were found in the Northern wheatear. Intra-specific analyses suggest that living at high elevation may be costly, such as for the Water pipit in our case study. Therefore, it seems that a species can persist with viable populations in uplands, where extrinsic mortality is high, by increasing the investment in self-maintenance and prospecting behaviours.

B Lymphocyte Stimulator Levels in Systemic Lupus Erythematosus: Higher Circulating Levels in African American Patients and Increased Production after Influenza Vaccination in Patients with Low Baseline Levels

PubMed Central

Ritterhouse, Lauren L.; Crowe, Sherry R.; Niewold, Timothy B.; Merrill, Joan T.; Roberts, Virginia C.; Dedeke, Amy B.; Neas, Barbara R.; Thompson, Linda F.; Guthridge, Joel M.; James, Judith A.

2011-01-01

Objective Examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels. Clinical and serologic features of SLE that are associated with elevated BLyS levels will also be investigated. Methods Clinical history, disease activity measurements and blood specimens were collected from sixty SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum IFN-α activity, 25-hydroxyvitamin D, and humoral responses to influenza vaccination. Results Thirty percent of SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than European American patients (p=0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (p=0.863), and BLyS levels increased post-vaccination only in the subset of patients in the lowest quartile of BLyS levels (p=0.0003). Elevated BLyS levels were associated with increased disease activity as measured by SLEDAI, PGA, and SLAM in European Americans (p=0.035, p=0.016, p=0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nRNP (p=0.0003) and decreased 25(OH)D (p=0.018). Serum IFN-α activity was a significant predictor of elevated BLyS in a multivariate analysis (p=0.002). Conclusion African American SLE patients have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination. PMID:22127709

Predictors of backrest elevation in critical care.

PubMed

Grap, Mary Jo; Munro, Cindy L; Bryant, Sandra; Ashtiani, Brooke

2003-04-01

Low backrest and supine positions are associated with increased mortality and ventilator associated pneumonia (VAP). Data are not available across ICU settings about the level of backrest position used and its relationship to enteral feeding and hemodynamic status. The purpose of this descriptive study was to document the level of backrest elevation and position and identify factors associated with and predict positioning in a medical, surgical and neuroscience intensive care unit. Data were collected randomly in each unit over a 6-week period, resulting in 506 observations for170 patients. Backrest elevation was determined by electronic bed read-out or bed frame elevation gauge. BP, HR and enteral feeding status were retrieved from the medical record. Results showed that mean backrest elevation was 19.2 degrees and 70% of subjects were supine. No difference in backrest elevation among units was found. Significant correlations between backrest elevation and systolic BP (r=0.15, P=0.006); and backrest and diastolic BP (r=0.13, P=0.02) were found. There was no difference in backrest elevation between patients being fed and not being fed. Differences in backrest elevation for intubated versus nonintubated patients approached significance (P=0.07) with intubated patients at lower backrest elevations. In summary, use of higher backrest elevations (>30 degrees ) is minimal, is not related to feeding and minimally related to hemodynamic status. Strategies to meet published recommendations for backrest elevation (30-45 degrees ) must include repeated feedback about nurse's use of backrest elevation and estimates of elevation.

Glycosylation-related genes in NS0 cells are insensitive to moderately elevated ammonium concentrations

PubMed Central

Brodsky, Arthur Nathan; Caldwell, Mary; Bae, Sooneon; Harcum, Sarah W.

2014-01-01

NS0 and Chinese hamster ovary (CHO) cell lines are used to produce recombinant proteins for human therapeutics; however, ammonium accumulation can negatively impact cell growth, recombinant protein production, and protein glycosylation. To improve product quality and decrease costs, the relationship between ammonium and protein glycosylation needs to be elucidated. While ammonium has been shown to adversely affect glycosylation-related gene expression in CHO cells, NS0 studies have not been performed. Therefore, this study sought to determine if glycosylation in NS0 cells were ammonium-sensitive at the gene expression level. Using a DNA microarray that contained mouse glycosylation-related and housekeeping genes, the of these genes was analysed in response to various culture conditions – elevated ammonium, elevated salt, and elevated ammonium with proline. Surprisingly, no significant differences in gene expression levels were observed between the control and these conditions. Further, the elevated ammonium cultures were analysed using real-time quantitative reverse transcriptase PCR (qRT-PCR) for key glycosylation genes, and the qRT-PCR results corroborated the DNA microarray results, demonstrating that NS0 cells are ammonium-insensitive at the gene expression level. Since NS0 are known to have elevated nucleotide sugar pools under ammonium stress, and none of the genes directly responsible for these metabolic pools were changed, consequently cellular control at the translational or substrate-level must be responsible for the universally observed decreased glycosylation quality under elevated ammonium. PMID:25062658

10. WEST ELEVATION OF SHOWROOM ADDITION WITH ACCESS DOORS TO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. WEST ELEVATION OF SHOWROOM ADDITION WITH ACCESS DOORS TO SHOP ON LOWER LEVEL. NOTE BOW SECTION OF OLD DORY BOAT USED AS STEP INTO LOWER LEVEL. - Lowell's Boat Shop, 459 Main Street, Amesbury, Essex County, MA

Changes in wetland sediment elevation following major storms: implications for estimating trends in relative sea-level rise

USGS Publications Warehouse

Cahoon, D.R.

2003-01-01

Hurricanes can be important agents of geomorphic change in coastal marshes and mangrove forests. Hurricanes can cause large-scale redistribution of sediments within the coastal environment resulting in sedimentation, erosion, disruption of vegetated substrates, or some combination of these processes in coastal wetlands. It has been proposed that such sediment pulsing events are important at maintaining wetland sediment elevations in sediment-poor settings with high rates of relative sea-level rise, such as the Mississippi River Delta. But do these pulsing events result in a net gain in sediment elevation even when substantial amounts of sediment are deposited? Clearly sediment erosion and scour would result in a loss of elevation. But will a substantial sediment deposit on poorly consolidated sediments always result in a net gain in elevation? If the wetland vegetation is killed by wind, tidal surge, or the introduction of saline water, will there be a collapse of sediment elevation in the absence of root production and ongoing decomposition of root matter? During the past decade several wetlands where my colleagues and I have monitored sedimentation and elevation change have been struck by one to several hurricanes. This paper describes the range of sediment elevation responses to hurricane strikes, the suggested mechanisms driving those responses, the implications for estimating long-term trends in relative sea-level rise, and future research needs for improving our understanding of the role that major storms play in wetland sediment elevation dynamics. For many wetlands the change in sediment elevation was directly proportional to the amount of sediment deposited by the storm. But surprisingly, there was a loss of elevation in some wetlands with substantial sediment deposits. In these wetlands, the impact of the storm was either direct (sedimentation and compaction) or indirect (vegetation death), and the effect on sediment elevation was either permanent or temporary. For example, 2 cm of sediment deposited by Hurricane Andrew on a healthy salt marsh in south Louisiana had a direct and positive effect on sediment elevation. But in a deteriorated salt marsh a 3 cm thick sediment deposit was associated with a permanent loss in elevation (we have monitored this site for 10 years). The apparent mechanism driving elevation loss was compaction of the weakened substrate by the weight of the sediment deposit, the storm surge waters, or both. Clearly, storm-related sediment pulses are not going to save this marsh from becoming submerged by rising sea level. A temporary loss in elevation, as much as 2 cm, was observed in a North Carolina salt marsh with a highly organic substrate after each of 3 successive hurricanes even when sediment was deposited. The loss in elevation was apparently related to degassing of the chronically flooded substrate while the rebound in elevation was apparently related to a temporary drawdown of marsh water levels. Interestingly, sediment elevation increased after Hurricane Dennis in 1999, although the increase was less than the thickness of the sediment deposit. Further research is required to determine the mechanisms driving storm-related elevation change (i.e., compaction and expansion) in this marsh. There were two marshes where the gain in sediment elevation was greater than the thickness of the sediment deposit, but the effect was short-lived. In a high salt marsh in southern California, we hypothesize that the temporary spike in elevation was related to the flushing of salts from the hypersaline soils, which enhanced root growth that led to an increase in elevation. In a marsh with a highly organic substrate in north Florida, temporary increases in elevation (as much as 2 cm) greater than the thickness of the sediment deposit were apparently related to groundwater fluxes, which may have been influenced by enhanced runoff from storm rainfall. Lastly, Hurricane Mitch

Curiosity Rover Martian Mission, Exaggerated Cross Section

NASA Image and Video Library

2016-12-13

This graphic depicts aspects of the driving distance, elevation, geological units and time intervals of NASA's Curiosity Mars rover mission, as of late 2016. The vertical dimension is exaggerated 14-fold compared with the horizontal dimension, for presentation-screen proportions. As of early December 2016, Curiosity had driven 9.3 miles (15 kilometers) since its August 2012 landing on the floor of Gale Crater near the base of Mount Sharp. It had climbed 541 feet (165 meters) in elevation. Elevation values shown on the vertical scale of this chart denote meters below an established zero-elevation level on Mars, which lacks a planetary "sea level." Because Curiosity is below the zero elevation, the numbers are negative. http://photojournal.jpl.nasa.gov/catalog/PIA21145

The Effects of Elevated pCO2, Hypoxia and Temperature on ...

EPA Pesticide Factsheets

Estuarine fish are acclimated to living in an environment with rapid and frequent changes in temperature, salinity, pH, and dissolved oxygen (DO) levels; the physiology of these organisms is well suited to cope with extreme thermal, hypercapnic, and hypoxic stress. While the adverse effects of low dissolved oxygen levels on estuarine fish has been well-documented, the interaction between low DO and elevated pCO2 is not well understood. There is some evidence that low DO and elevated pCO2 interact antagonistically, however little information exists on how projected changes of pCO2 levels in near-shore waters may affect estuarine species, and how these changes may specifically interact with dissolved oxygen and temperature. We explored the survivability of 7-day post fertilization sheepshead minnow, Cyprinodon variegatus, using short term exposure to the combined effects of elevated pCO2 (~1300 µatm; IPCC RCP 8.5) and low dissolved oxygen levels (~2 mg/L). Additionally, we determined if the susceptibility of these fish to elevated pCO2 and low DO was influenced by increases in temperature from 27.5°C to 35°C. Results from this study and future studies will be used to identify estuarine species and lifestages sensitive to the combined effects of elevated pCO2 and low dissolved oxygen. This project was created in order to better understand the interactive effects of projected pCO2 levels and hypoxia in estuarine organisms. This work is currently focused on the se

Thyroid hormone elevations during acute psychiatric illness: relationship to severity and distinction from hyperthyroidism.

PubMed

Roca, R P; Blackman, M R; Ackerley, M B; Harman, S M; Gregerman, R I

1990-01-01

Acute psychiatric illness may be accompanied by transient hyperthyroxinemia. The mechanism of this phenomenon was examined by determining the role of thyrotropin (TSH) in the genesis of this state. Serial measurements of TSH, thyroxine (T4), free T4 index (FT4I), triiodothyronine (T3), and free T3 index (FT3I) were performed in 45 acutely hospitalized patients with major psychiatric disorders. Twenty-two (49%) patients exhibited significant elevations (greater than or equal to 2 SD above mean value of controls) of one or more thyroid hormone (or index) levels. Among depressed patients with elevated FT4I, TSH was higher (p less than .05) on the day of the peak FT4I than on the day of the FT4I nadir. There were significant positive correlations between psychiatric symptom severity and levels of FT4I among both depressed (p less than .01) and schizophrenic (p less than .025) patients. These data show that elevations of T4, FT4I, T3, and FT3I are common among psychiatric inpatients, especially early in their hospitalization, and that levels of thyroid hormones are correlated with severity of psychiatric symptomatology. TSH is higher early in the acute phase of illness and is not suppressed in the face of elevated thyroid hormone levels, a finding that distinguishes this phenomenon from ordinary hyperthyroidism. Elevations of peripheral thyroid hormone levels, particularly among depressed patients, may result from a centrally-mediated hypersecretion of TSH.

Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

PubMed Central

Brady, Roscoe O; McCarthy, Julie M; Prescot, Andrew P; Jensen, J Eric; Cooper, Alissa J; Cohen, Bruce M; Renshaw, Perry F; Ongür, Dost

2017-01-01

Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition. PMID:23634979

Improving yield potential in crops under elevated CO2: Integrating the photosynthetic and nitrogen utilization efficiencies

PubMed Central

Kant, Surya; Seneweera, Saman; Rodin, Joakim; Materne, Michael; Burch, David; Rothstein, Steven J.; Spangenberg, German

2012-01-01

Increasing crop productivity to meet burgeoning human food demand is challenging under changing environmental conditions. Since industrial revolution atmospheric CO2 levels have linearly increased. Developing crop varieties with increased utilization of CO2 for photosynthesis is an urgent requirement to cope with the irreversible rise of atmospheric CO2 and achieve higher food production. The primary effects of elevated CO2 levels in most crop plants, particularly C3 plants, include increased biomass accumulation, although initial stimulation of net photosynthesis rate is only temporal and plants fail to sustain the maximal stimulation, a phenomenon known as photosynthesis acclimation. Despite this acclimation, grain yield is known to marginally increase under elevated CO2. The yield potential of C3 crops is limited by their capacity to exploit sufficient carbon. The “C fertilization” through elevated CO2 levels could potentially be used for substantial yield increase. Rubisco is the rate-limiting enzyme in photosynthesis and its activity is largely affected by atmospheric CO2 and nitrogen availability. In addition, maintenance of the C/N ratio is pivotal for various growth and development processes in plants governing yield and seed quality. For maximizing the benefits of elevated CO2, raising plant nitrogen pools will be necessary as part of maintaining an optimal C/N balance. In this review, we discuss potential causes for the stagnation in yield increases under elevated CO2 levels and explore possibilities to overcome this limitation by improved photosynthetic capacity and enhanced nitrogen use efficiency. Opportunities of engineering nitrogen uptake, assimilatory, and responsive genes are also discussed that could ensure optimal nitrogen allocation toward expanding source and sink tissues. This might avert photosynthetic acclimation partially or completely and drive for improved crop production under elevated CO2 levels. PMID:22833749

Improving yield potential in crops under elevated CO(2): Integrating the photosynthetic and nitrogen utilization efficiencies.

PubMed

Kant, Surya; Seneweera, Saman; Rodin, Joakim; Materne, Michael; Burch, David; Rothstein, Steven J; Spangenberg, German

2012-01-01

Increasing crop productivity to meet burgeoning human food demand is challenging under changing environmental conditions. Since industrial revolution atmospheric CO(2) levels have linearly increased. Developing crop varieties with increased utilization of CO(2) for photosynthesis is an urgent requirement to cope with the irreversible rise of atmospheric CO(2) and achieve higher food production. The primary effects of elevated CO(2) levels in most crop plants, particularly C(3) plants, include increased biomass accumulation, although initial stimulation of net photosynthesis rate is only temporal and plants fail to sustain the maximal stimulation, a phenomenon known as photosynthesis acclimation. Despite this acclimation, grain yield is known to marginally increase under elevated CO(2). The yield potential of C(3) crops is limited by their capacity to exploit sufficient carbon. The "C fertilization" through elevated CO(2) levels could potentially be used for substantial yield increase. Rubisco is the rate-limiting enzyme in photosynthesis and its activity is largely affected by atmospheric CO(2) and nitrogen availability. In addition, maintenance of the C/N ratio is pivotal for various growth and development processes in plants governing yield and seed quality. For maximizing the benefits of elevated CO(2), raising plant nitrogen pools will be necessary as part of maintaining an optimal C/N balance. In this review, we discuss potential causes for the stagnation in yield increases under elevated CO(2) levels and explore possibilities to overcome this limitation by improved photosynthetic capacity and enhanced nitrogen use efficiency. Opportunities of engineering nitrogen uptake, assimilatory, and responsive genes are also discussed that could ensure optimal nitrogen allocation toward expanding source and sink tissues. This might avert photosynthetic acclimation partially or completely and drive for improved crop production under elevated CO(2) levels.

Evaluating optimal superficial limb perfusion at different angles using non-invasive micro-lightguide spectrophotometry.

PubMed

Darmanin, Geraldine; Jaggard, Matthew; Hettiaratchy, Shehan; Nanchahal, Jagdeep; Jain, Abhilash

2013-06-01

It is common practice to elevate the limbs postoperatively to reduce oedema and hence optimise perfusion and facilitate rehabilitation. However, elevation may be counterproductive as it reduces the mean perfusion pressure. There are no clear data on the optimal position of the limbs even in normal subjects. The optimal position of limbs was investigated in 25 healthy subjects using a non-invasive micro-lightguide spectrophotometry system "O2C", which indirectly measures skin and superficial tissue perfusion through blood flow, oxygen saturation and relative haemoglobin concentration. We found a reduction in skin and superficial tissue blood flow of 17% (p=0.0001) on arm elevation (180° shoulder flexion) as compared to heart level and an increase in skin and superficial tissue blood flow of 25% (p=0.02) on forearm elevation of 45°. Lower limb skin and superficial tissue blood flow decreased by 15% (p=0.004) on elevation to 47 cm and by 70% on dependency (p=0.0001) compared to heart level. However, on elevation of the lower limb there was also a 28% reduction in superficial venous pooling (p=0.0001) compared to heart level. In the normal limb, the position for optimal superficial perfusion of the upper limb is with the arm placed at heart level and forearm at 45°. In the lower limb the optimal position for superficial perfusion would be at heart level. However, some degree of elevation may be useful if there is an element of venous congestion. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Importance of measuring lactate levels in children with sepsis.

PubMed

Anil, Nisha

2017-10-10

Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Serum metal levels after minimally invasive repair of pectus excavatum.

PubMed

Cundy, Thomas P; Kirby, Christopher P

2012-08-01

Metal implants may wear and corrode, resulting in systemic dissemination of metallic debris that is measurable in serum. Concern exists regarding adverse health effects related to implant-derived debris. Minimally invasive repair of pectus excavatum (MIRPE) is a popular technique in which a stainless steel substernal bar is implanted to achieve deformity correction. Serum metal levels have not previously been investigated after MIRPE. Serum chromium, molybdenum, and nickel levels were measured in this cross-sectional study of 11 children implanted with pectus bars after MIRPE. Samples were analyzed using high-resolution inductively coupled plasma mass spectrometry. Median serum chromium and nickel values were elevated 3.3-fold (P = .0003) and 2.3-fold (P = .25), respectively, compared with age-matched controls. Serum chromium and nickel levels were abnormally elevated in 6 (55%) of 11 and 5 (45%) of 11, respectively. In patients whom postexplantation metal levels were measured, previously elevated levels were lowered. Serum chromium levels in children after MIRPE are comparable with adult cohorts with hip arthroplasty implants measured 1-year postoperatively. No acute metal toxicity was observed. Abnormally elevated levels of serum metal levels are measurable in children implanted with pectus bars. These findings warrant further investigation to assess the biocompatibility of this surgical implant in children. Copyright © 2012 Elsevier Inc. All rights reserved.

Ecogeomorphology of Spartina patens-dominated tidal marshes: Soil organic matter accumulation, marsh elevation dynamics, and disturbance

USGS Publications Warehouse

Cahoon, D.R.; Ford, M.A.; Hensel, P.F.; Fagherazzi, Sergio; Marani, Marco; Blum, Linda K.

2004-01-01

Marsh soil development and vertical accretion in Spartina patens (Aiton) Muhl.-dominated tidal marshes is largely dependent on soil organic matter accumulation from root-rhizome production and litter deposition. Yet there are few quantitative data sets on belowground production and the relationship between soil organic matter accumulation and soil elevation dynamics for this marsh type. Spartina patens marshes are subject to numerous stressors, including sea-level rise, water level manipulations (i.e., flooding and draining) by impoundments, and prescribed burning. These stressors could influence long-term marsh sustainability by their effect on root production, soil organic matter accumulation, and soil elevation dynamics. In this review, we summarize current knowledge on the interactions among vegetative production, soil organic matter accumulation and marsh elevation dynamics, or the ecogeomorphology, of Spartina patens-dominated tidal marshes. Additional studies are needed of belowground production/decomposition and soil elevation change (measured simultaneously) to better understand the links among soil organic matter accumulation, soil elevation change, and disturbance in this marsh type. From a management perspective, we need to better understand the impacts of disturbance stressors, both lethal and sub-lethal, and the interactive effect of multiple stressors on soil elevation dynamics in order to develop better management practices to safeguard marsh sustainability as sea level rises.

Photosynthetic Performance of the Red Alga Pyropia haitanensis During Emersion, With Special Reference to Effects of Solar UV Radiation, Dehydration and Elevated CO2 Concentration.

PubMed

Xu, Juntian; Gao, Kunshan

2015-11-01

Macroalgae distributed in intertidal zones experience a series of environmental changes, such as periodical desiccation associated with tidal cycles, increasing CO2 concentration and solar UVB (280-315 nm) irradiance in the context of climate change. We investigated how the economic red macroalga, Pyropia haitanensis, perform its photosynthesis under elevated atmospheric CO2 concentration and in the presence of solar UV radiation (280-400 nm) during emersion. Our results showed that the elevated CO2 (800 ppmv) significantly increased the photosynthetic carbon fixation rate of P. haitanensis by about 100% when the alga was dehydrated. Solar UV radiation had insignificant effects on the net photosynthesis without desiccation stress and under low levels of sunlight, but significantly inhibited it with increased levels of desiccation and sunlight intensity, to the highest extent at the highest levels of water loss and solar radiation. Presence of UV radiation and the elevated CO2 acted synergistically to cause higher inhibition of the photosynthetic carbon fixation, which exacerbated at higher levels of desiccation and sunlight. While P. haitanensis can benefit from increasing atmospheric CO2 concentration during emersion under low and moderate levels of solar radiation, combined effects of elevated CO2 and UV radiation acted synergistically to reduce its photosynthesis under high solar radiation levels during noon periods. © 2015 The American Society of Photobiology.

Experimental tooth pain elevates substance P and matrix metalloproteinase-8 levels in human gingival crevice fluid.

PubMed

Avellán, Nina-Li; Sorsa, Timo; Tervahartiala, Taina; Forster, Clemens; Kemppainen, Pentti

2008-02-01

Tooth pain can induce a neurogenic inflammatory reaction in gingiva in association with local elevations of matrix metalloproteinase (MMP)-8, which is considered the major tissue destructive protease in gingival crevice fluid (GCF). The pro-inflammatory neuropeptides released by sensory nerves coordinate the activities of the immuno-effector cells and may influence the secretion of MMP-8. With this background, we studied whether experimental tooth pain can trigger changes in GCF levels of the neuropeptide substance P (SP) and MMP-8. The GCF SP levels of stimulated and non-stimulated teeth were analyzed for SP using a competitive enzyme immunoassay (EIA). The GCF MMP-8 levels were determined by quantitative immunofluorometric assay (IFMA). Painful stimulation of the upper central incisor caused significant elevations in GCF SP and MMP-8 levels of the stimulated tooth. At the same time, the GCF SP and MMP-8 levels of non-stimulated control teeth were unchanged. These data indicate that experimental tooth pain can induce local elevations of SP and MMP-8 levels in GCF simultaneously. This supports the possibility of a local neurogenic spread of inflammatory reactions from intrapulpal to surrounding periodontal tissues.

Decreased C-reactive protein levels in Alzheimer disease.

PubMed

O'Bryant, Sid E; Waring, Stephen C; Hobson, Valerie; Hall, James R; Moore, Carol B; Bottiglieri, Teodoro; Massman, Paul; Diaz-Arrastia, Ramon

2010-03-01

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histopathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 +/- 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 +/- 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 microg/mL) versus controls (4.9 microg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD.

Decreased C-Reactive Protein Levels in Alzheimer Disease

PubMed Central

O’Bryant, Sid E.; Waring, Stephen C.; Hobson, Valerie; Hall, James R.; Moore, Carol B.; Bottiglieri, Teodoro; Massman, Paul; Diaz-Arrastia, Ramon

2011-01-01

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histo-pathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 ± 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 ± 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 µg/mL) versus controls (4.9 µg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD. PMID:19933496

Factors associated with positive direct antiglobulin tests in pretransfusion patients: a case-control study.

PubMed

Toy, P T; Chin, C A; Reid, M E; Burns, M A

1985-01-01

During routine pretransfusion testing, the presence of IgG on patient red cells is suggested by a positive autocontrol and confirmed by a positive direct antiglobulin test (DAT) using monospecific anti-IgG sera. Most IgG on patient red cells detected in this manner are of unknown etiology. We recently showed an association between elevated serum globulin levels and positive DAT with unreactive eluate in patients with acquired immunodeficiency syndrome (AIDS). In the present study, we wished to determine whether elevated serum globulin levels contribute to some of the positive DAT encountered in pretransfusion testing of patients without AIDS. 76 patients with positive DAT were compared with 90 controls without IgG detected on their red cells during pretransfusion testing. The rate of elevated serum globulin levels was 75% in positive DAT cases versus 29% in controls (p less than 0.001); the odds ratio was 7.6. Elevated blood urea nitrogen levels occurred in 42% of cases versus 19% of controls (p less than 0.025); the odds ratio was 3.1. Cases and controls were not significantly different with regard to age, sex, race, quinidine usage, or hyperalimentation. Elevated serum globulin and blood urea nitrogen levels are significantly associated with a positive DAT with unreactive eluate in pretransfusion patients.

Passive radiation shielding considerations for the proposed space elevator

NASA Astrophysics Data System (ADS)

Jorgensen, A. M.; Patamia, S. E.; Gassend, B.

2007-02-01

The Earth's natural van Allen radiation belts present a serious hazard to space travel in general, and to travel on the space elevator in particular. The average radiation level is sufficiently high that it can cause radiation sickness, and perhaps death, for humans spending more than a brief period of time in the belts without shielding. The exact dose and the level of the related hazard depends on the type or radiation, the intensity of the radiation, the length of exposure, and on any shielding introduced. For the space elevator the radiation concern is particularly critical since it passes through the most intense regions of the radiation belts. The only humans who have ever traveled through the radiation belts have been the Apollo astronauts. They received radiation doses up to approximately 1 rem over a time interval less than an hour. A vehicle climbing the space elevator travels approximately 200 times slower than the moon rockets did, which would result in an extremely high dose up to approximately 200 rem under similar conditions, in a timespan of a few days. Technological systems on the space elevator, which spend prolonged periods of time in the radiation belts, may also be affected by the high radiation levels. In this paper we will give an overview of the radiation belts in terms relevant to space elevator studies. We will then compute the expected radiation doses, and evaluate the required level of shielding. We concentrate on passive shielding using aluminum, but also look briefly at active shielding using magnetic fields. We also look at the effect of moving the space elevator anchor point and increasing the speed of the climber. Each of these mitigation mechanisms will result in a performance decrease, cost increase, and technical complications for the space elevator.

The 3D Elevation Program: summary for Puerto Rico

USGS Publications Warehouse

Carswell, William J.

2016-02-03

Elevation data are essential to a broad range of applications, including forest resources management, wildlife and habitat management, scientific research, national security, recreation, and many others. For the Commonwealth of Puerto Rico, elevation data are critical for flood risk management, landslide mitigation, natural resources conservation, sea level rise and subsidence, coastal zone management, infrastructure and construction management, and other business uses. Today, high-density light detection and ranging (lidar) data are the primary sources for deriving elevation models and other datasets. Federal, State, Tribal, U.S. territorial, and local agencies work in partnership to (1) replace data that are older and of lower quality and (2) provide coverage where publicly accessible data do not exist. A joint goal of State and Federal partners is to acquire consistent, statewide coverage to support existing and emerging applications enabled by lidar data.The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States, Hawaii, and selected U.S. territories, and quality level 5 interferometric synthetic aperture radar (IfSAR) data for Alaska, all with a 6- to 10-year acquisition cycle, provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey (USGS), the Office of Management and Budget Circular A‒16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other three-dimensional (3D) representations of the Nation’s natural and constructed features.

Elevated serum erythropoietin in a patient with polycythaemia vera presenting with Budd-Chiari syndrome

PubMed Central

Jones, Catherine; Levy, Yair; Tong, Alex W

2014-01-01

Polycythaemia vera (PV) is a clonal disorder of bone marrow stem cells characterised by erythrocytosis. Diagnosis of PV requires exclusion of secondary causes of polycythaemia. It has been held that an elevated erythropoietin (Epo) level strongly indicates secondary erythrocytosis and excludes PV diagnosis, to the extent that the reduced serum Epo level is currently listed as a minor criterion in the WHO classification scheme for PV. However, patients with PV who co-present with Budd-Chiari syndrome have been documented with elevated serum Epo levels. For these patients, identification of the Janus kinase 2 (JAK2) V617F point mutation along with the transient nature of the Epo elevation provides certainty of PV diagnosis, as illustrated by the proband. In this case report, the patient's positive response to cytoreductive therapy (hydroxyurea 500 mg daily) and phlebotomy (750 mL over three phlebotomies) further supports validity of PV diagnosis with elevated Epo. The patient remains on rivaroxaban (Xarelto) for treatment of her portal vein thrombosis. PMID:25452296

The 3D Elevation Program: summary for Michigan

USGS Publications Warehouse

Carswell, William J.

2014-01-01

The National Enhanced Elevation Assessment evaluated multiple elevation data acquisition options to determine the optimal data quality and data replacement cycle relative to cost to meet the identified requirements of the user community. The evaluation demonstrated that lidar acquisition at quality level 2 for the conterminous United States and quality level 5 interferometric synthetic aperture radar (ifsar) data for Alaska with a 6- to 10-year acquisition cycle provided the highest benefit/cost ratios. The 3D Elevation Program (3DEP) initiative selected an 8-year acquisition cycle for the respective quality levels. 3DEP, managed by the U.S. Geological Survey, the Office of Management and Budget Circular A–16 lead agency for terrestrial elevation data, responds to the growing need for high-quality topographic data and a wide range of other 3D representations of the Nation's natural and constructed features. The Michigan Statewide Authoritative Imagery and Lidar (MiSAIL) program provides statewide lidar coordination with local, State, and national groups in support of 3DEP for Michigan.

Medical management of lead-exposed workers: results of physician interviews in New Jersey.

PubMed

Roché, L M; Gerwel, B; Ramaprasad, R; Udasin, I G

1995-02-01

Between July 1990 and April 1992, a questionnaire was administered to the physicians who saw 62 individuals with a blood lead (PbB) level equal to or higher than 2.40 mumol/liter with occupational inorganic lead exposure, to ascertain the medical management of workers with elevated PbB levels. Most of the 62 cases were seen by their personal physician (50%) or a private physician under contract with the company for which the patient worked (40%). Only eight (13%) patients were seen by a physician in a medical specialty assumed to include training relevant to occupational lead exposure. Fifteen percent of the patients' physicians reported taking no action for the elevated PbB level. Twenty-nine percent did not report retesting the patient (all should have been retested). Twenty-one percent of the 62 patients' physicians reported informing no one, including the patient, of the elevated PbB level. The majority of the physicians did not know the answer or declined to answer a question about what PbB level would prompt them to take six follow-up actions. The results of the physician interviews indicate that medical follow-up on workers with elevated PbB levels may not be adequate to prevent lead poisoning of the workers and their co-workers. Recommendations include methods to increase physician and employer knowledge of the medical management of workers with elevated PbB levels and to increase employer compliance with OSHA standards regarding medical surveillance of lead-exposed workers.

Chromium ion release from stainless steel pediatric scoliosis instrumentation.

PubMed

Cundy, Thomas P; Delaney, Christopher L; Rackham, Matthew D; Antoniou, Georgia; Oakley, Andrew P; Freeman, Brian J C; Sutherland, Leanne M; Cundy, Peter J

2010-04-20

Case-control study. To determine whether serum metal ion levels and erythrocyte chromium levels in adolescents with stainless steel spinal instrumentation are elevated when compared with 2 control groups. Instrumented spinal arthrodesis is a common procedure to correct scoliosis. The long-term consequences of retained implants are unclear. Possible toxic effects related to raised metal ion levels have been reported in the literature. Thirty patients who underwent posterior spinal arthrodesis with stainless steel instrumentation for scoliosis (group 1) were included. Minimum postoperative duration was 3 years. Serum chromium, molybdenum, iron, and ferritin levels were measured. Participants with elevated above normal serum chromium levels (n = 11) also underwent erythrocyte chromium analysis. Comparisons were made with 2 control groups; 10 individuals with scoliosis with no spinal surgery (group 2) and 10 volunteers without scoliosis (group 3). All control group participants underwent serum and erythrocyte analysis. Elevated above normal serum chromium levels were demonstrated in 11 of 30 (37%) group 1 participants. Elevated serum chromium levels were demonstrated in 0 of 10 participants (0%) in group 2 and 1 of 10 (10%) in group 3. There was a statistically significant elevation in serum chromium levels between group 1 and group 2 participants (P = 0.001). There was no significant association between groups 1, 2, and 3 for serum molybdenum, iron, and ferritin levels. Erythrocyte chromium measurements were considered within the normal range for all participants tested (n = 31). Raised serum chromium levels were detected in 37% of patients following instrumented spinal arthrodesis for correction of scoliosis. This new finding has relatively unknown health implications but potential mutagenic, teratogenic and carcinogenic sequelae. This is especially concerning with most scoliosis patients being adolescent females with their reproductive years ahead.

47 CFR 24.53 - Calculation of height above average terrain (HAAT).

Code of Federal Regulations, 2012 CFR

2012-10-01

... height above mean sea level. (b) Average terrain elevation shall be calculated using elevation data from... Digital Chart of the World (DCW) may be used. (c) Radial average terrain elevation is calculated as the...

47 CFR 24.53 - Calculation of height above average terrain (HAAT).

Code of Federal Regulations, 2011 CFR

2011-10-01

... height above mean sea level. (b) Average terrain elevation shall be calculated using elevation data from... Digital Chart of the World (DCW) may be used. (c) Radial average terrain elevation is calculated as the...

47 CFR 24.53 - Calculation of height above average terrain (HAAT).

Code of Federal Regulations, 2010 CFR

2010-10-01

... height above mean sea level. (b) Average terrain elevation shall be calculated using elevation data from... Digital Chart of the World (DCW) may be used. (c) Radial average terrain elevation is calculated as the...

47 CFR 24.53 - Calculation of height above average terrain (HAAT).

Code of Federal Regulations, 2014 CFR

2014-10-01

... height above mean sea level. (b) Average terrain elevation shall be calculated using elevation data from... Digital Chart of the World (DCW) may be used. (c) Radial average terrain elevation is calculated as the...

47 CFR 24.53 - Calculation of height above average terrain (HAAT).

Code of Federal Regulations, 2013 CFR

2013-10-01

... height above mean sea level. (b) Average terrain elevation shall be calculated using elevation data from... Digital Chart of the World (DCW) may be used. (c) Radial average terrain elevation is calculated as the...

Elevated carbon dioxide increases salicylic acid in Glycine max.

PubMed

Casteel, Clare L; Segal, Lauren M; Niziolek, Olivia K; Berenbaum, May R; DeLucia, Evan H

2012-12-01

Concentrations of carbon dioxide (CO(2)) are increasing in the atmosphere, affecting soybean (Glycine max L.) phytohormone signaling and herbivore resistance. Whether the impact of elevated CO(2) on phytohormones and induced defenses is a generalized response within this species is an open question. We examined jasmonic acid (JA) and salicylic acid (SA) under ambient and elevated CO(2) concentrations with and without Japanese beetle (Popillia japonica Newman) damage and artificial damage across six soybean cultivars (HS93-4118, Pana, IA 3010, Loda, LN97-15076, and Dwight). Elevated CO(2) reduced constitutive levels of JA and related transcripts in some but not all soybean cultivars. In contrast to the variation in JA, constitutive levels of salicylic were increased universally among soybean cultivars grown under elevated CO(2). Variation in hormonal signaling may underpin observed variation in the response of insect herbivores and pathogens to plants grown under elevated CO(2).

Increased urinary levels of tissue polypeptide specific antigen (TPS) in alcoholics.

PubMed

Barros, Paula; Gonzalez-Quintela, Arturo; Mella, Carmen; Perez, Luis-Fernando

2006-01-01

Urinary levels of tissue polypeptide specific antigen (TPS, cytokeratin-18) have been proposed as a marker of urothelial malignancies. Previous studies have shown that serum TPS levels are elevated in alcoholics. This study was designed to determine whether alcoholics had elevated urinary TPS levels as well. Serum and urinary TPS levels were determined in 24 alcoholics and 15 healthy controls by means of a commercial chemiluminiscent immunoassay. Serum TPS levels were higher in alcoholics than in controls (median 332 U/L, range 51-21241 U/L versus median 17 U/L, range 15-65 U/L, respectively, p<0.001). Urinary TPS levels were also higher in alcoholics than in controls (median 244 U/L, range 22-1267 U/L versus median 66.5 U/L, range 15-600 U/L, respectively, p=0.001). Urinary TPS levels were correlated with serum TPS levels in alcoholics. Urinary TPS levels are elevated in alcoholics. Consequently, the specificity of urinary TPS as a tumor marker may be limited in alcoholics.

Effects of ambient and elevated CO2 on growth, chlorophyll fluorescence, photosynthetic pigments, antioxidants, and secondary metabolites of Catharanthus roseus (L.) G Don. grown under three different soil N levels.

PubMed

Singh, Aradhana; Agrawal, Madhoolika

2015-03-01

Catharanthus roseus L. plants were grown under ambient (375 ± 30 ppm) and elevated (560 ± 25 ppm) concentrations of atmospheric CO2 at different rates of N supply (without supplemental N, 0 kg N ha(-1); recommended N, 50 kg N ha(-1); and double recommended N, 100 kg N ha(-1)) in open top chambers under field condition. Elevated CO2 significantly increased photosynthetic pigments, photosynthetic efficiency, and organic carbon content in leaves at recommended (RN) and double recommended N (DRN), while significantly decreased total nitrogen content in without supplemental N (WSN). Activities of superoxide dismutase, catalase, and ascorbate peroxidase were declined, while glutathione reductase, peroxidase, and phenylalanine-ammonia lyase were stimulated under elevated CO2. However, the responses of the above enzymes were modified with different rates of N supply. Elevated CO2 significantly reduced superoxide production rate, hydrogen peroxide, and malondialdehyde contents in RN and DRN. Compared with ambient, total alkaloids content increased maximally at recommended level of N, while total phenolics in WSN under elevated CO2. Elevated CO2 stimulated growth of plants by increasing plant height and numbers of branches and leaves, and the magnitude of increment were maximum in DRN. The study suggests that elevated CO2 has positively affected plants by increasing growth and alkaloids production and reducing the level of oxidative stress. However, the positive effects of elevated CO2 were comparatively lesser in plants grown under limited N availability than in moderate and higher N availability. Furthermore, the excess N supply in DRN has stimulated the growth but not the alkaloids production under elevated CO2.

Response of tundra ecosystems to elevated atmospheric carbon dioxide. [Annual report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oechel, W.C.; Grulke, N.E.

1988-12-31

Our past research shows that arctic tussock tundra responds to elevated atmospheric CO{sub 2} with marked increases in net ecosystem carbon flux and photosynthetic rates. However, at ambient temperatures and nutrient availabilities, homeostatic adjustments result in net ecosystem flux rates dropping to those found a contemporary CO{sub 2} levels within three years. Evidence for ecosystem-level acclimation in the first season of elevated CO{sub 2} exposure was found in 1987. Photosynthetic rates of Eriophorum vaginatum, the dominant species, adjusts to elevated CO{sub 2} within three weeks. Past research also indicates other changes potentially important to ecosystem structure and function. Elevated CO{submore » 2} treatment apparently delays senescence and increases the period of positive photosynthetic activity. Recent results from the 1987 field season verify the results obtained in the 1983--1986 field seasons: Elevated CO{sub 2} resulted in increased ecosystem-level flux rates. Regressions fitted to the seasonal flux rates indicate an apparent 10 d extension of positive CO{sub 2} uptake reflecting a delay of the onset of plant dormancy. This delay in senescence could increase the frost sensitivity of the system. Major end points proposed for this research include the effects of elevated CO{sub 2} and the interaction of elevated atmospheric CO{sub 2} with elevated soil temperature and increased nutrient availability on: (1) Net ecosystem CO{sub 2} flux; (2) Net photosynthetic rates; (3) Patterns and resource controls on homeostatic adjustment in the above processes to elevated CO{sub 2}; (4) Plant-nutrient status, litter quality, and forage quality; (5) Soil-nutrient status; (6) Plant-growth pattern and shoot demography.« less

Abnormal maternal serum alpha fetoprotein and pregnancy outcome.

PubMed

Zarzour, S J; Gabert, H A; Diket, A L; St Amant, M; Miller, J M

1998-01-01

The objective was to assess the occurrence of miscarriages, low birth weight, and karyotype abnormalities found with low and elevated maternal serum alpha-fetoprotein (MSAFP) among women who had genetic amniocentesis performed. A retrospective study of 2,159 women who had MSAFP analysis prior to amniocentesis was conducted. Pregnancy outcomes were obtained from record review and physicians follow-up. Limits of MSAFP used in analysis were <0.5 adjusted multiples of the median (MOM) (lower levels) and >2.0 MOM (upper levels). Autosomal trisomy was found in 1.6% with low, 0.9% normal, and 0.6% with elevated MSAFP values. Sex chromosome abnormalities were present only in patients with normal MSAFP, [45X (n = 6), 47XXY (n = 2), 69XXX]. Of five open neural tube defects, four had elevated MSAFP and one had a normal value. Omphalocele was identified in four patients, two with normal and two with elevated MSAFP. Gastroschisis was found in one low and one elevated MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) values did not correlate with MSAFP values. Patients with low MSAFP levels had a greater prevalence of abnormal karyotype (19 of 249, prevalence = 0.076) than patients with an elevated MSAFP level (2 or 166, prevalence = 0.012 OR (odds ratio) = 0.20 (P value = 0.024) when unadjusted for maternal age, and OR = 0.09 (P value = 0.001) when adjusted for maternal age. Spontaneous abortion occurred more often in patients with elevated (4 of 166, or 4%) than normal or low (20 of 1948, or 1%) values of MSAFP (odds ratio 4.32, P = 0.020 when adjusted for maternal age). Birth weight below 2,500 g was present less frequently with low or normal MSAFP (136 of 1,760, or 7.7%) than in elevated MSAFP (21 of 144 or 14.6%) (odds ratio 2.04, P = 0.005, unadjusted; and odds ratio = 2.32, P = 0.003, adjusted for maternal age). Female fetuses were present more often with low MSAFP (136 of 249, or 55%) than elevated levels 43% (71 of 164, or 43%; P = 0.024). We conclude that patients undergoing genetic amniocentesis with MSAFP <.5 MOM are less likely to miscarry, deliver a low birth weight newborn, or have a male infant than patients with MSAFP levels >2.0 MOM.

Tumor necrosis factor and interleukin-6 levels in hypertensive patients with and without left ventricular hypertrophy.

PubMed

Leibowitz, David; Planer, David; Ben-Ivgi, Fanny; Weiss, A Teddy; Bursztyn, Michael

2005-01-01

The objective of this prospective study was to examine the association between serum levels of TNF (tumor-necrosis factor) and IL-6 (interleukin-6) and left ventricular mass in hypertensive patients. Hypertensive patients currently receiving medical therapy were eligible. All subjects underwent echocardiography with measurements of left ventricular (LV) mass and ejection fraction (EF) and had serum levels of TNF and IL-6 measured by ELISA immunoassay. 35 subjects (20F, 15M; mean age 56.4 +/- 10.5 yrs) were studied. 19 patients (54%) had elevated LV mass. Of these patients, 6 (32%) had detectable serum TNF levels and 1 (7%) had detectable IL-6 levels, (p = NS). Hypertensive patients with elevated LV mass do not consistently exhibit elevated cytokine levels when compared to those with normal LV mass.

Ocean acidification affects prey detection by a predatory reef fish.

PubMed

Cripps, Ingrid L; Munday, Philip L; McCormick, Mark I

2011-01-01

Changes in olfactory-mediated behaviour caused by elevated CO(2) levels in the ocean could affect recruitment to reef fish populations because larval fish become more vulnerable to predation. However, it is currently unclear how elevated CO(2) will impact the other key part of the predator-prey interaction--the predators. We investigated the effects of elevated CO(2) and reduced pH on olfactory preferences, activity levels and feeding behaviour of a common coral reef meso-predator, the brown dottyback (Pseudochromis fuscus). Predators were exposed to either current-day CO(2) levels or one of two elevated CO(2) levels (∼600 µatm or ∼950 µatm) that may occur by 2100 according to climate change predictions. Exposure to elevated CO(2) and reduced pH caused a shift from preference to avoidance of the smell of injured prey, with CO(2) treated predators spending approximately 20% less time in a water stream containing prey odour compared with controls. Furthermore, activity levels of fish was higher in the high CO(2) treatment and feeding activity was lower for fish in the mid CO(2) treatment; indicating that future conditions may potentially reduce the ability of the fish to respond rapidly to fluctuations in food availability. Elevated activity levels of predators in the high CO(2) treatment, however, may compensate for reduced olfactory ability, as greater movement facilitated visual detection of food. Our findings show that, at least for the species tested to date, both parties in the predator-prey relationship may be affected by ocean acidification. Although impairment of olfactory-mediated behaviour of predators might reduce the risk of predation for larval fishes, the magnitude of the observed effects of elevated CO(2) acidification appear to be more dramatic for prey compared to predators. Thus, it is unlikely that the altered behaviour of predators is sufficient to fully compensate for the effects of ocean acidification on prey mortality.

National Enhanced Elevation Assessment at a glance

USGS Publications Warehouse

Snyder, Gregory I.

2012-01-01

Elevation data are essential for hazards mitigation, conservation, infrastructure development, national security, and many other applications. Under the leadership of the U.S. Geological Survey and the member States of the National Digital Elevation Program (NDEP), Federal agencies, State agencies, and others work together to acquire high-quality elevation data for the United States and its territories. New elevation data are acquired using modern technology to replace elevation data that are, on average, more than 30 years old. Through the efforts of the NDEP, a project-by-project data acquisition approach resulted in improved, publicly available data for 28 percent of the conterminous United States and 15 percent of Alaska over the past 15 years. Although the program operates efficiently, the rate of data collection and the typical project specifications are currently insufficient to address the needs of government, the private sector, and other organizations. The National Enhanced Elevation Assessment was conducted to (1) document national-level requirements for improved elevation data, (2) estimate the benefits and costs of meeting those requirements, and (3) evaluate multiple national-level program-implementation scenarios. The assessment was sponsored by the NDEP's member agencies. The study participants came from 34 Federal agencies, agencies from all 50 States, selected local government and Tribal offices, and private and not-for-profit organizations. A total of 602 mission-critical activities were identified that need significantly more accurate data than are currently available. The results of the assessment indicate that a national-level enhanced-elevation-data program has the potential to generate from $1.2 billion to $13 billion in new benefits annually.

DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF ELEVATOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF ELEVATOR SHOWING THE DOUBLED COLUMN FOR THE BUILDING EXPANSION JOINT AT COLUMN LINE AA-18. - Offutt Air Force Base, Glenn L. Martin-Nebraska Bomber Plant, Building D, Peacekeeper Drive, Bellevue, Sarpy County, NE

Acceleration levels on board the Space Station and a tethered elevator for micro and variable-gravity applications

NASA Technical Reports Server (NTRS)

Lorenzini, E. C.; Cosmo, M.; Vetrella, S.; Moccia, A.

1988-01-01

This paper investigates the dynamics and acceleration levels of a new tethered system for micro and variable-gravity applications. The system consists of two platforms tethered on opposite sides to the Space Station. A fourth platform, the elevator, is placed in between the Space Station and the upper platform. Variable-g levels on board the elevator are obtained by moving this facility along the upper tether, while micro-g experiments are carried out on board the Space Station. By controlling the length of the lower tether the position of the system CM can be maintained on board the Space Station despite variations of the station's distribution of mass. The paper illustrates the mathematical model, the environmental perturbations and the control techniques which have been adopted for the simulation and control of the system dynamics. Two sets of results from two different simulation runs are shown. The first set shows the system dynamics and the acceleration spectra on board the Space Station and the elevator during station-keeping. The second set of results demonstrates the capability of the elevator to attain a preselected g-level.

[Clinical significance of peak body temperature, white blood cell count, and C-reactive protein level in febrile episodes among geriatric inpatients].

PubMed

Ikematsu, H; Nabeshima, A; Yamaga, S; Yamaji, K; Kakuda, K; Ueno, K; Hayashi, J; Shirai, T; Hara, H; Kashiwagi, S

1997-06-01

To investigate the clinical implication of peak body temperature, peripheral blood white blood cell (WBC) count, and serum C-reactive protein (CRP) level in febrile symptoms among geriatric hospitalized patients, they were analyzed in 968 febrile episodes obtained from 433 hospitalized patients in the referred hospital. Episodes of one day duration were most frequent (41.6%). WBC count was elevated over 8000/microliters in 475 episodes (49.1%) and CRP exceeded 1.0 mg/dl in 770 episodes (79.5%). Frequency of WBC elevation decreased and frequency of CRP elevation increased according to the time course. The mean value of CRP increased significantly according to the time course. The frequency of WBC count increase and CRP elevation and their averages correlated to the peak body temperature. The peak body temperature displayed the most striking correlation to the length of febrile episodes among three clinical indicators, peak body temperature, WBC count, and CRP level. These results indicate that the elevation of WBC count and/or CRP level is frequent in geriatric patients with febrile symptoms. Peak body temperature may serve as a clinical indicator of the severy of the febrile disease occurring in geriatric patients.

tRNA and Its Activation Targets as Biomarkers and Regulators of Breast Cancer

DTIC Science & Technology

2013-09-01

linked tRNA misregulation to cancer. We have previously reported that tRNA levels are significantly elevated in breast cancer and multiple myeloma ...significantly elevated in breast cancer and multiple myeloma cells. To further investigate the cellular and physiological effects of tRNA overexpression, we...tRNA levels are elevated in breast cancer and multiple myeloma cell lines (Pavon-Eternod et al. 2009; Zhou et al. 2009). Though abnormal RNA polymerase

[Changes of serum aminotransferase in children with obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Zhenjiang; Duo, Likun

2013-08-01

Obstructive sleep apnea hypopnea syndrome (OSAHS) and non-alcoholic fatty liver disease (NAFLD) are both strongly associated with obesity. Whether OSAHS is an independent risk factor for liver injury or not is uncertain. To assess the hypothesis that OSAHS is associated with liver injury independent of obesity. One hundred and thirty children with OSAHS and 77 children with primary snoring(PS) were enrolled. Polysomnography was performed. Body mass index (BMI), liver function tests, serum lipids, fasting plasma glucose (FPG), and insulin (INS) were measured. Seventeen children of OSAHS had elevated serum aminotransferase levels,while only 2 children of non-OSAHS had elevated serum aminotransferase in healthy control group (chi2 = 5.18, P < 0.05; OR = 5.64 CI 1.27-24.97). Fifteen children of obese had elevated serum aminotransferase levels, while only 4 children had elevated serum aminotransferase in non-obese group (chi2 = 4.58, P < 0.05; (OR = 1.97 CI 1.06-3.67). Seventy cases of obese children, 15 cases of elevated aminotransferase levels (21.4%), namely fatty liver patients, of these children, 14 had OSAHS (93.3%). In contrast, OSAHS was present in only 67.3% of obese children without elevated aminotransferase. OSAHS may be a risk factor for liver injury independent of obesity; Increased liver enzyme levels are frequently found in obese snoring children, particularly among those with OSAHS.

Mediation of a corticosterone-induced reproductive conflict.

PubMed

Love, Oliver P; Breuner, Creagh W; Vézina, François; Williams, Tony D

2004-06-01

Current research in birds suggests that a conflict should exist during reproduction for the role of the glucocorticoid corticosterone (CORT). While elevated levels have been correlated with the increased energetic demand of raising offspring, elevated CORT levels have traditionally been implicated in reproductive abandonment. We examined the relationship between CORT and nest desertion in breeding wild female European starlings (Sturnus vulgaris) incorporating analyses of both total circulating levels and 'free', unbound CORT through analysis of corticosteroid-binding globulin (CBG). Free baseline CORT levels of nest-abandoning birds were significantly higher than nonabandoning birds within each stage, with chick-rearing birds exhibiting the highest free baseline CORT levels, while concurrently remaining the most resistant stage to nest desertion. Elevated free baseline CORT levels in chick-rearing birds were not due to increased total CORT secretion, but rather to a decrease in CBG levels. Overall, our results suggest that CORT and CBG interact to play a role in mediating the increased energetic demand of offspring, while minimizing the chances of nest desertion, thereby alleviating any potential behavioral conflict for CORT during reproduction. Furthermore, these results demonstrate that the traditional view of the role of CORT during reproduction is much more complex than previously appreciated. Together with mounting evidence, we suggest that elevated corticosteroid levels are an inherent and necessary part of reproduction in nonmammalian tetrapods.

Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

PubMed Central

Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

2012-01-01

Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

Effects of simultaneously elevated temperature and CO2 levels on Nicotiana benthamiana and its infection by different positive-sense RNA viruses are cumulative and virus type-specific.

PubMed

Del Toro, Francisco J; Rakhshandehroo, Farshad; Larruy, Beatriz; Aguilar, Emmanuel; Tenllado, Francisco; Canto, Tomás

2017-11-01

We have studied how simultaneously elevated temperature and CO 2 levels [climate change-related conditions (CCC) of 30°C, 970 parts-per-million (ppm) of CO 2 vs. standard conditions (SC) of 25°C, ~ 405ppm CO 2 ] affect physiochemical properties of Nicotiana benthamiana leaves, and also its infection by several positive-sense RNA viruses. In previous works we had studied effects of elevated temperature, CO 2 levels separately. Under CCC, leaves of healthy plants almost doubled their area relative to SC but contained less protein/unit-of-area, similarly to what we had found under conditions of elevated CO 2 alone. CCC also affected the sizes/numbers of different foliar cell types differently. Under CCC, infection outcomes in titers and symptoms were virus type-specific, broadly similar to those observed under elevated temperature alone. Under either condition, infections did not significantly alter the protein content of leaf discs. Therefore, effects of elevated temperature and CO 2 combined on properties of the pathosystems studied were overall cumulative. Copyright © 2017 Elsevier Inc. All rights reserved.

False elevation of carboxyhemoglobin: case report.

PubMed

Mehrotra, Shruti; Edmonds, Marcia; Lim, Rodrick K

2011-02-01

Carbon monoxide toxicity in infants and children, like adults, produce nonspecific symptoms with normal vital signs necessitating the serum measurement of carboxyhemoglobin (COHb). In infants, the COHb may be falsely elevated. Our goal was to report a case of suspected carbon monoxide toxicity in an infant and the likely cause of the falsely elevated serum COHb. A previously healthy 3-month-old girl presented to the pediatric emergency department (ED) with smoke inhalation from a defective furnace. She was asymptomatic. On examination, she was alert, with Glasgow Coma Scale of 15 and normal vital signs. Cardiorespiratory and neurological examinations were completely normal. Because of concern regarding carbon monoxide poisoning, she was treated with normobaric oxygen therapy. Initial and subsequent serum COHb levels were persistently elevated, despite treatment and the infant appearing clinically well. As such, she had a prolonged stay in the ED. Further investigations found that fetal hemoglobin interferes with the spectrophotometric method used to analyze serum COHb levels. Carboxyhemoglobin serum level, in infants, may be falsely elevated due to the fetal hemoglobin interfering with standard methods of analysis. Knowledge of the false elevation using standard spectrophotometric methods of COHb in clinically well-appearing infants can decrease unnecessary oxygen therapy and monitoring time in the ED.

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

PubMed

Reading, Stephanie R; Porter, Kimberly R; Hsu, Jin-Wen Y; Wallner, Lauren P; Loo, Ronald K; Jacobsen, Steven J

2016-10-01

To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA. Copyright © 2016. Published by Elsevier Inc.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

PubMed

Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p < 0.001). Serum NO(x) were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO(x) level defined as mean +/- 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Uric Acid Level and Elevated Blood Pressure in U.S. Adolescents

PubMed Central

Loeffler, Lauren F.; Navas-Acien, Ana; Brady, Tammy M.; Miller, Edgar R.; Fadrowski, Jeffrey J.

2012-01-01

Uric acid is associated with cardiovascular disease (CVD) and CVD risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of U.S. adolescents, a population with a relatively low prevalence of CVD and CVD risk factors. Among 6,036 adolescents 12-17 years of age examined in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) the mean age was 14.5 years, 17% were obese (body mass index [BMI] ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity and BMI percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex and height, for each 0.1 mg/dL increase in uric acid level was 1.38 (95% confidence interval [CI], 1.16 to 1.65). Compared to <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI, 1.38 to 3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy U.S. adolescents. Additional prospective studies and clinical trials are needed to determine if uric acid is merely a marker in a complex metabolic pathway, or causal of hypertension and thus a potential screening and therapeutic target. PMID:22353609

Incidence of elevated lipoprotein (a) levels in a large cohort of patients with cardiovascular disease.

PubMed

van Buuren, Frank; Horstkotte, Dieter; Knabbe, Cornelius; Hinse, Dennis; Mellwig, Klaus Peter

2017-03-01

Recently it has been demonstrated that elevated lipoprotein (a) (LPA) levels are associated with an increased risk of cardiovascular disease across multiple ethnic groups. However, there is only scanty data about the incidence of elevated LPA levels in different patient cohorts. As a consequence, we aimed to examine whether patients with elevated LPA levels might be seen more often in a cardiovascular center in comparison to the general population. We reviewed LPA concentrations of 52,898 consecutive patients who were admitted to our hospital between January 2004 and December 2014. We subdivided them into different groups according to their LPA levels. Data was compared to available information in medical literature. 26.4% of the patients had LPA levels >30 mg/dl which is in line with the data from literature. Mean level of LPA concentration in our study was twice as high in comparison to the general population (25.8% vs. 13.3%). 4.6% had LPA levels >98 mg/dl (general population <0.3%). In patients admitted to a cardiovascular center the proportion of LPA >30 mg/dl is comparable to the general population but mean levels over all are twice as high and the proportion of patients with LPA levels of >98 mg/dl is extremely higher.

Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

PubMed

Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

2007-02-01

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

The Algorithm Theoretical Basis Document for the Derivation of Range and Range Distributions from Laser Pulse Waveform Analysis for Surface Elevations, Roughness, Slope, and Vegetation Heights

NASA Technical Reports Server (NTRS)

Brenner, Anita C.; Zwally, H. Jay; Bentley, Charles R.; Csatho, Bea M.; Harding, David J.; Hofton, Michelle A.; Minster, Jean-Bernard; Roberts, LeeAnne; Saba, Jack L.; Thomas, Robert H.;

Retrieving improved multi-temporal CryoSat elevations over ice caps and glaciers - a case study of Barnes ice cap

NASA Astrophysics Data System (ADS)

Nilsson, Johan; Burgess, David

2014-05-01

The CryoSat mission was launched in 2010 to observe the Earth's cryosphere. In contrast to previous satellite radar altimeters, this mission is expected to monitor the elevation of small ice caps and glaciers, which according to the IPCC will be the largest contributor to 21st century sea level rise. To date the ESA CryoSat SARiN level-2 (L2) elevation product is not yet fully optimized for use over these types of glaciated regions, as its processed with a more universal algorithm. Thus the aim of this study is to demonstrate that with the use of improved processing CryoSat SARiN data can be used for more accurate topography mapping and elevation change detection for ice caps and glaciers. To demonstrate this, elevations and elevation changes over Barnes ice cap, located on Baffin Island in the Canadian Arctic, have been estimated from available data from the years 2010-2013. ESA's CryoSat level-1b (L1b) SARiN baseline "B" data product was used and processed in-house to estimate surface elevations. The resulting product is referred to as DTU-L2. The processing focused on improving the retracker, reducing phase noise and correcting phase ambiguities. The accuracy of the DTU-L2 and the ESA-L2 product was determined by comparing the measured elevations against NASA's IceBridge Airborne Topographic Mapper (ATM) elevations from May 2011. The resulting difference in accuracy was determined by comparing their associated errors. From the multi-temporal measurements spanning the period 2010-2013, elevation changes where estimated and compared to ICESat derived changes from 2003-2009. The result of the study shows good agreement between the NASA measured ATM elevations and the DTU-L2 data. It also shows that the pattern of elevation change is similar to that derived from ICESat data. The accuracy of the DTU-L2 estimated elevations is on average several factors higher compared to the ESA-L2 elevation product. These preliminary results demonstrates that CryoSat elevation data, using improved processing, can be used for accurate topographic mapping and elevation change detection on ice caps and glaciers. Future work would entail extending this processing to other regions of this type to support these results.

Effects of Elevated Atmospheric Carbon Dioxide and Tropospheric Ozone on Phytochemical Composition of Trembling Aspen ( Populus tremuloides ) and Paper Birch ( Betula papyrifera ).

PubMed

Couture, John J; Meehan, Timothy D; Rubert-Nason, Kennedy F; Lindroth, Richard L

2017-01-01

Anthropogenic activities are altering levels of atmospheric carbon dioxide (CO 2 ) and tropospheric ozone (O 3 ). These changes can alter phytochemistry, and in turn, influence ecosystem processes. We assessed the individual and combined effects of elevated CO 2 and O 3 on the phytochemical composition of two tree species common to early successional, northern temperate forests. Trembling aspen (Populus tremuloides) and paper birch (Betula papyrifera) were grown at the Aspen FACE (Free-Air Carbon dioxide and ozone Enrichment) facility under four combinations of ambient and elevated CO 2 and O 3 . We measured, over three years (2006-08), the effects of CO 2 and O 3 on a suite of foliar traits known to influence forest functioning. Elevated CO 2 had minimal effect on foliar nitrogen and carbohydrate levels in either tree species, and increased synthesis of condensed tannins and fiber in aspen, but not birch. Elevated O 3 decreased nitrogen levels in both tree species and increased production of sugar, condensed tannins, fiber, and lignin in aspen, but not birch. The magnitude of responses to elevated CO 2 and O 3 varied seasonally for both tree species. When co-occurring, CO 2 offset most of the changes in foliar chemistry expressed under elevated O 3 alone. Our results suggest that levels of CO 2 and O 3 predicted for the mid-twenty-first century will alter the foliar chemistry of northern temperate forests with likely consequences for forest community and ecosystem dynamics.

Longitudinal association of obesity, metabolic syndrome and diabetes with risk of elevated aminotransferase levels in a cohort of Mexican health workers.

PubMed

Flores, Yvonne N; Auslander, Allyn; Crespi, Catherine M; Rodriguez, Michael; Zhang, Zuo-Feng; Durazo, Francisco; Salmerón, Jorge

2016-05-01

In Mexico, chronic liver disease have been increasingly found along with the rapidly growing prevalence of obesity, diabetes and metabolic syndrome (MS). We aimed to investigate the longitudinal association between these three factors and risk of elevated alanine aminotransferase (ALT) levels (>40 U/L), a marker for liver damage, in a cohort of Mexican adults. Data were obtained from two separate waves of the Mexican Health Worker Cohort Study: Wave 1 (2004-2006) and Wave 2 (2011-2013). Unconditional logistic regression models were employed to determine the cross-sectional and longitudinal association between these risk factors and elevated ALT levels. The prevalence of elevated ALT was significantly higher among men, individuals aged under 60 years, those who were overweight or obese, diabetic, with MS or heavy/binge drinkers. The longitudinal results indicated that weight gain between waves that resulted in a change in body mass index, along with remaining overweight or obese, were significantly associated with an increased risk of elevated ALT levels. A significantly increased risk of developing elevated ALT was also observed among those who acquired diabetes or MS from Wave 1 to Wave 2. Weight gain and acquiring diabetes or MS are associated with a significant risk of having elevated ALT. These results, within the context of the rapid increase in global obesity rates, call urgently for programs to help to prevent chronic liver disease. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Chronic treatment with fibrates elevates superoxide dismutase in adult mouse brain microvessels

PubMed Central

Wang, Guangming; Liu, Xiaowei; Guo, Qingmin; Namura, Shobu

2010-01-01

Fibrates are activators of peroxisome proliferator-activated receptor (PPAR) α. Pretreatment with fibrates has been shown to protect brain against ischemia in mice. We hypothesized that fibrates elevate superoxide dismutase (SOD) levels in the brain microvessels (BMV). BMV were isolated from male C57BL/6 and PPARα null mice that had been treated with fenofibrate or gemfibrozil for 7 days. To examine the effect of discontinuation of fenofibrate, another animal group treated with fenofibrate was examined on post-discontinuation day 3 (D-3). To examine whether SOD elevations attenuate oxidative stress in the ischemic brain, separate animals treated with fenofibrate for 7 days were subjected to 60 minutes focal ischemia on post-discontinuation day 0 (D-0) or D-3. Fenofibrate (30 mg/kg) increased mRNA levels of all three isoforms of SOD and activity level in BMV on D-0 but these effects were not detected on D-3. The elevations were not detected in PPARα null mice. SOD levels were also elevated by gemfibrozil (30 mg/kg). Fenofibrate significantly reduced superoxide production and protein oxidation in the ischemic brain at 30 minutes after reperfusion. Fenofibrate reduced infarct size measured at 24 hours after reperfusion on D-0; however, the infarct reduction was not seen when ischemia was induced on D-3. These findings suggest that fibrates elevate SOD in BMV through PPARα, which contributes to the infarct reduction, at least in part. Further studies are needed to establish the link between the SOD elevations and the brain protection by fibrates against ischemia. PMID:20813100

Association of anemia, child and family characteristics with elevated blood lead concentrations in preschool children from Montevideo, Uruguay.

PubMed

Queirolo, Elena I; Ettinger, Adrienne S; Stoltzfus, Rebecca J; Kordas, Katarzyna

2010-01-01

Elevated blood lead levels (BPbs) have been identified in Uruguayan children in the La Teja neighborhood of Montevideo, but the extent of lead exposure in other city areas is unknown. Sources and predictors of exposure also remain understudied in this population. In 2007, the authors screened lead and hemoglobin levels in capillary blood of 222 preschool children from several areas of Montevideo, Uruguay, and identified predictors of elevated BPbs. Mean BPb was 9.0 +/- 6.0 microg/dL and 32.9% of children had levels >or= 10microg/dL. Mean hemoglobin level was 10.5 +/- 1.5 g/dL, with 44.1% having levels <10.5g/dL. Older child age, hemoglobin <10.5g/dL, and putting fingers/toys in the mouth were associated with higher BPbs. Young maternal age, less education, father's job with potential risk of lead exposure, and fewer family possessions were also associated with higher BPbs. Pediatric lead exposure is a public health problem in Uruguay, with children experiencing elevated BPbs at a young age.

Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib.

PubMed

Chen, Fengsheng; Luo, Xi; Zhang, Jinbiao; Lu, Yang; Luo, Rongcheng

2010-09-01

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients' clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.

Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

McPherson, Stuart; Henderson, Elsbeth; Burt, Alastair D; Day, Christopher P; Anstee, Quentin M

2014-05-01

A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features. Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy. 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, p<0.001). Overall, 55 (19%) patients had advanced liver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (p<0.001). Serum IgA, age, platelets, AST/ALT ratio and BMI were all independently with advanced fibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87). The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hurricane Rita surge data, southwestern Louisiana and southeastern Texas, September to November 2005

USGS Publications Warehouse

McGee, Benton D.; Goree, Burl B.; Tollett, Roland W.; Woodward, Brenda K.; Kress, Wade H.

2006-01-01

Pressure transducers and high-water marks were used to document the inland water levels related to storm surge generated by Hurricane Rita in southwestern Louisiana and southeastern Texas. On September 22-23, 2005, an experimental monitoring network consisting of 47 pressure transducers (sensors) was deployed at 33 sites over an area of about 4,000 square miles to record the timing, extent, and magnitude of inland hurricane storm surge and coastal flooding. Sensors were programmed to record date and time, temperature, and barometric or water pressure. Water pressure was corrected for changes in barometric pressure and salinity. Elevation surveys using global-positioning systems and differential levels were used to relate all storm-surge water-level data, reference marks, benchmarks, sensor measuring points, and high-water marks to the North American Vertical Datum of 1988 (NAVD 88). The resulting data indicated that storm-surge water levels over 14 feet above NAVD 88 occurred at three locations and rates of water-level rise greater than 5 feet per hour occurred at three locations near the Louisiana coast. Quality-assurance measures were used to assess the variability and accuracy of the water-level data recorded by the sensors. Water-level data from sensors were similar to data from co-located sensors, permanent U.S. Geological Survey streamgages, and water-surface elevations performed by field staff. Water-level data from sensors at selected locations were compared to corresponding high-water mark elevations. In general, the water-level data from sensors were similar to elevations of high quality high-water marks, while reporting consistently higher than elevations of lesser quality high-water marks.

Soluble tumor necrosis factor receptor-I in preterm infants with chorioamnionitis.

PubMed

Sato, Miho; Nishimaki, Shigeru; An, Hiromi; Shima, Yoshio; Naruto, Takuya; Sugai, Toshiyuki; Iwasaki, Shiho; Seki, Kazuo; Imagawa, Tomoyuki; Mori, Masaaki; Yokota, Shumpei

2009-04-01

The aim of our study was (i) to determine whether chorioamnionitis (CAM) is associated with an elevated soluble tumor necrosis factor receptor I (sTNFR-I) level and (ii) to examine the time course of the concentration of sTNFR-I in preterm infants after birth. We measured sTNFR-I levels in the cord blood of 112 preterm infants (gestational age < or =34 weeks), and those in peripheral blood of 30 preterm infants on days 7, 14, 21 and 28. The median value for the sTNFR-I was significantly elevated in 33 infants with CAM at stage 3 (4618 pg/mL) compared with the 52 infants without CAM (2866 pg/mL), or the 13 infants with CAM at stage 1 (3638 pg/mL) and the 14 infants at stage 2 (3242 pg/mL). The severity of CAM is an independent factor for the elevation of cord blood sTNFR-I. The sTNFR-I level on day 0 was significantly higher in eight infants with CAM at stage 3 than in the 22 infants without CAM or with CAM at stage 1 and 2; however there were no significant differences on days 7, 14, 21 and 28. The serum level of sTNFR-I showed a significant gradual decline with time. We suggest that there is an association between elevated sTNFR-I levels in cord blood and maternal CAM, and this elevation may reflect the fetal inflammation. However the elevation of sTNFR-I could not persist postnatally for a long time.

Rising atmospheric CO2 concentration may imply higher risk of Fusarium mycotoxin contamination of wheat grains.

PubMed

Bencze, Szilvia; Puskás, Katalin; Vida, Gyula; Karsai, Ildikó; Balla, Krisztina; Komáromi, Judit; Veisz, Ottó

2017-08-01

Increasing atmospheric CO 2 concentration not only has a direct impact on plants but also affects plant-pathogen interactions. Due to economic and health-related problems, special concern was given thus in the present work to the effect of elevated CO 2 (750 μmol mol -1 ) level on the Fusarium culmorum infection and mycotoxin contamination of wheat. Despite the fact that disease severity was found to be not or little affected by elevated CO 2 in most varieties, as the spread of Fusarium increased only in one variety, spike grain number and/or grain weight decreased significantly at elevated CO 2 in all the varieties, indicating that Fusarium infection generally had a more dramatic impact on the grain yield at elevated CO 2 than at the ambient level. Likewise, grain deoxynivalenol (DON) content was usually considerably higher at elevated CO 2 than at the ambient level in the single-floret inoculation treatment, suggesting that the toxin content is not in direct relation to the level of Fusarium infection. In the whole-spike inoculation, DON production did not change, decreased or increased depending on the variety × experiment interaction. Cooler (18 °C) conditions delayed rachis penetration while 20 °C maximum temperature caused striking increases in the mycotoxin contents, resulting in extremely high DON values and also in a dramatic triggering of the grain zearalenone contamination at elevated CO 2 . The results indicate that future environmental conditions, such as rising CO 2 levels, may increase the threat of grain mycotoxin contamination.

In-vitro Wound Healing Effect of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor from Plant

PubMed Central

Karna, Sandeep

2017-01-01

Background: Prostaglandins (PGs) have short existence in vivo because they are rapidly metabolized by NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) to 15-ketoprostaglandins. Inhibition of 15-PGDH causes elevated level of PGE2 in cellular system. It will be valuable for the therapeutic management of diseases requiring elevated PGE2 levels, like wound healing. Objective: Ninety-eight plant samples were screened for the discovery of potent 15-PGDH inhibitor. Among them, top five plant extracts as potent 15-PGDH inhibitor were chosen to determine PGE2 release from HaCaT (Keratinocyte cell line) cell line. Finally, top 15-PGDH inhibitor was selected to evaluate in vitro wound healing effect on HaCaT scratch model. Method: The inhibitory activity for 15-PGDH inhibitors was evaluated using fluorescence spectrophotometer by measuring the formation of NADH at 468 nm following excitation at 340 nm. Cell viability assay and PGE2 release was evaluated in HaCaT cell line after treatment of 15-PGDH inhibitors. Scratches were made using sterile 200 μL on HaCaT cell and wound-healing effect was evaluated after treatment of 15-PGDH inhibitor. Results: 15-PGDH inhibitors elevated PGE2 levels in concentration-dependent manner. Ethanol extract of Artocarpus heterophyllus (EEAH), the most potent 15-PGDH inhibitor (IC50 = 0.62 µg/mL) with least cytotoxicity (IC50 = 670 µg/ml), elevated both intracellular and extracellular PGE2 levels. EEAH facilitated in-vitro wound healing in a HaCaT (Keratinocyte cell line) scratch model. Conclusion: EEAH might apply to treat dermal wounds by elevating PGE2 levels via COX-1 induction and 15-PGDH inhibition. SUMMARY Biological inactivation of 15-PGDH causes elevated level of PGE2 which will be useful for the management of disease that requires elevated level of PGE2. Abbreviations used: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase, COX: Cyclooxygenase, DTT: Dithiothreitol, DMEM: Dulbecco's modified Eagle's media, EEAH: Ethanol extract of Artocarpus heterophyllus, MRP4: Multidrug resistance 4, PGs: Prostaglandins, PGT: Prostaglandin transporter, SDS: Sodium dodecylsulfate PMID:28479736

A control system formulation of the mechanism that controls the secretions of serum group hormone in humans during sleep

NASA Technical Reports Server (NTRS)

Howard, J. C.; Young, D. R.

1975-01-01

Plasma growth hormone concentrations during sleep were determined experimentally. An elevated level of plasma growth hormone was observed during the initial phase of sleep and remained elevated for approximately 3 hr before returning to the steady-state level. Moreover, subsequent to a prolonged interruption of sleep, of the order of 2-3 hr, an elevated level of plasma growth hormone was again observed during the initial phase of resumed sleep. A control system formulation of the mechanism that controls the secretions of serum growth hormone in humans was used to account for the growth hormone responses observed.

Elevation of branched-chain amino acid levels in diabetes and NAFL and changes with antidiabetic drug treatment.

PubMed

Iwasa, Motoh; Ishihara, Tomoaki; Mifuji-Moroka, Rumi; Fujita, Naoki; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Iwata, Kazuko; Kaito, Masahiko; Takei, Yoshiyuki

2015-01-01

Diabetes mellitus (DM), non-alcoholic fatty liver (NAFL), and obesity are associated with elevated branched-chain amino acid (BCAA) levels, but the mechanism and significance of this has not been elucidated. Eighty-four subjects were enrolled including 43 with DM. Serum BCAA levels were positively correlated with waist-hip ratio and ALT. Serum BCAA levels in subjects with DM were higher than non-DM and those in subjects with NAFL were also higher than non-NAFL. Treatment with pioglitazone and alogliptin (19 of 43 DM subjects) improved serum haemoglobin A1c and decreased BCAA levels. The decrease in BCAAs with improved glucose metabolism suggests that abnormal glucose metabolism is also a factor in elevated BCAA levels. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes

PubMed Central

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.

PubMed

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.

Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

PubMed

Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

2014-09-01

MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. © 2014 Wiley Periodicals, Inc.

Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

PubMed

Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

2018-05-07

Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

PubMed

Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D

2000-07-01

We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.

75 FR 23595 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

...] Elevation in meters (MSL) Modified Crittenden County, Arkansas, and Incorporated Areas Docket No.: FEMA-B... Sea Level, rounded to the nearest 0.1 meter. ADDRESSES Unincorporated Areas of Crittenden County... feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Grand...

SAFETY AND SECURITY BUILDING, TRA614. ELEVATIONS. SECTIONS. TWO ROOF LEVELS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SAFETY AND SECURITY BUILDING, TRA-614. ELEVATIONS. SECTIONS. TWO ROOF LEVELS. BLAW-KNOX 3150-814-2, 3/1950. INL INDEX NO. 531-0614-00-098-100703, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

Lead exposure and the 2010 achievement test scores of children in New York counties

PubMed Central

2012-01-01

Background Lead is toxic to cognitive and behavioral functioning in children even at levels well below those producing physical symptoms. Continuing efforts in the U.S. since about the 1970s to reduce lead exposure in children have dramatically reduced the incidence of elevated blood lead levels (with elevated levels defined by the current U.S. Centers for Disease Control threshold of 10 μg/dl). The current study examines how much lead toxicity continues to impair the academic achievement of children of New York State, using 2010 test data. Methods This study relies on three sets of data published for the 57 New York counties outside New York City: school achievement data from the New York State Department of Education, data on incidence of elevated blood lead levels from the New York State Department of Health, and data on income from the U.S. Census Bureau. We studied third grade and eighth grade test scores in English Language Arts and mathematics. Using the county as the unit of analysis, we computed bivariate correlations and regression coefficients, with percent of children achieving at the lowest reported level as the dependent variable and the percent of preschoolers in the county with elevated blood lead levels as the independent variable. Then we repeated those analyses using partial correlations to control for possible confounding effects of family income, and using multiple regressions with income included. Results The bivariate correlations between incidence of elevated lead and number of children in the lowest achievement group ranged between 0.38 and 0.47. The partial correlations ranged from 0.29 to 0.40. The regression coefficients, both bivariate and partial (both estimating the increase in percent of children in the lowest achievement group for every percent increase in the children with elevated blood lead levels), ranged from 0.52 to 1.31. All regression coefficients, when rounded to the nearest integer, were approximately 1. Thus, when the percent of children showing elevated lead increases by one percent, the percent of children in the lowest achievement group, according to the regression equations generated, also increases by about one percent. All associations were significant at the 0.05 level. Conclusion Despite public health advances, and despite the imprecision of measures, an association between the incidence of elevated blood lead and achievement in New York counties is still apparent, not attributable to confounding by income. Efforts to reduce lead exposure should persist with vigor. PMID:22269775

Elevated troponin I levels in acute liver failure: is myocardial injury an integral part of acute liver failure?

PubMed

Parekh, Nimisha K; Hynan, Linda S; De Lemos, James; Lee, William M

2007-06-01

Although rare instances of cardiac injury or arrhythmias have been reported in acute liver failure (ALF), overall, the heart is considered to be spared in this condition. Troponin I, a sensitive and specific marker of myocardial injury, may be elevated in patients with sepsis and acute stroke without underlying acute coronary syndrome, indicating unrecognized cardiac injury in these settings. We sought to determine whether subclinical cardiac injury might also occur in acute liver failure. Serum troponin I levels were measured in 187 patients enrolled in the US Acute Liver Failure Study Group registry, and correlated with clinical variables and outcomes. Diagnoses were representative of the larger group of >1000 patients thus far enrolled and included 80 with acetaminophen-related injury, 26 with viral hepatitis, 19 with ischemic injury, and 62 others. Overall, 74% of patients had elevated troponin I levels (>0.1 ng/ml). Patients with elevated troponin I levels were more likely to have advanced hepatic coma (grades III or IV) or to die (for troponin I levels >0.1 ng/ml, odds ratio 3.88 and 4.69 for advanced coma or death, respectively). In acute liver failure, subclinical myocardial injury appears to occur more commonly than has been recognized, and its pathogenesis in the context of acute liver failure is unclear. Elevated troponin levels are associated with a significant increase in morbidity and mortality. Measurement of troponin I levels may be helpful in patients with acute liver failure, to detect unrecognized myocardial damage and as a marker of unfavorable outcome.

Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice

PubMed Central

Niewiadomski, Julie; Zhou, James Q.; Roman, Heather B.; Liu, Xiaojing; Hirschberger, Lawrence L.; Locasale, Jason W.; Stipanuk, Martha H.

2016-01-01

To gain further insights into the effect of elevated cysteine levels on energy metabolism and the possible mechanisms by which cysteine may have these effects, we conducted studies in cysteine dioxygenase (Cdo1)–null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression holds in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggested impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2S production and impairments in energy metabolism suggest that H2S signaling could be involved. PMID:26995761

Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice.

PubMed

Niewiadomski, Julie; Zhou, James Q; Roman, Heather B; Liu, Xiaojing; Hirschberger, Lawrence L; Locasale, Jason W; Stipanuk, Martha H

2016-01-01

To gain further insights into the effects of elevated cysteine levels on energy metabolism and the possible mechanisms underlying these effects, we conducted studies in cysteine dioxygenase (Cdo1)-null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression are also seen in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggests impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2 S production and impairments in energy metabolism suggest that H2 S signaling could be involved. © 2016 New York Academy of Sciences.

Elevated levels of insulin-like growth factor (IGF)-I in serum rescue the severe growth retardation of IGF-I null mice.

PubMed

Wu, Yingjie; Sun, Hui; Yakar, Shoshana; LeRoith, Derek

2009-09-01

IGF-I plays a vital role in growth and development and acts in an endocrine and an autocrine/paracrine fashion. The purpose of the current study was to clarify whether elevated levels of IGF-I in serum can rescue the severe growth retardation and organ development and function of igf-I null mice. To address that, we overexpressed a rat igf-I transgene specifically in the liver of igf-I null mice. We found that in the total absence of tissue IGF-I, elevated levels of IGF-I in serum can support normal body size at puberty and after puberty but are insufficient to fully support the female reproductive system (evident by irregular estrous cycle, impaired development of ovarian corpus luteum, reduced number of uterine glands and endometrial hypoplasia, all leading to decreased number of pregnancies and litter size). We conclude that most autocrine/paracrine actions of IGF-I that determine organ growth and function can be compensated by elevated levels of endocrine IGF-I. However, in mice, full compensatory responses are evident later in development, suggesting that autocrine/paracrine IGF-I is critical for neonatal development. Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I.

Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer.

PubMed

Norris, Alixanna M; Woodruff, R D; D'Agostino, Ralph B; Clodfelter, Jill E; Scarpinato, Karin Drotschmann

2007-02-01

Defects in mismatch repair (MMR) proteins have been identified in various types of cancer. However, an association with prostate cancer has been controversial. Defective MMR results in genome instability with detrimental consequences that significantly contribute to tumorigenesis. This study determined alterations in key MMR protein levels in prostate cancer with the goal to identify prognostic markers. Prostatectomy samples were immunohistochemically stained and the relative presence or absence of key proteins MSH2, MLH1, and PMS2 determined. Cancer tissue of distinct grades was compared with the normal surrounding tissue. Microsatellite instability (MSI) in altered tissues was determined according to NCI guidelines. In contrast to reports that associate a lack of individual MMR proteins with tumorigenesis, a significant increase in PMS2 levels was identified in PIN lesions and prostate cancer tissue. This elevation in PMS2 was independent of changes in levels in its heterodimeric partner, MLH1. Prostate tumors with elevated levels of PMS2 were genetically unstable, which was corrected by MLH1 co-elevation. This is the first documentation of detrimental consequences associated with the increase in a MMR protein in human cancer. This study recognizes PMS2 elevation as a prognostic marker in pre-neoplastic and prostate cancer lesions. This result has significant implications for future diagnostic and treatment measures. (c) 2006 Wiley-Liss, Inc.

76 FR 1093 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Stephenson County.../Wisconsin +782 State boundary. Yellow Creek Approximately 400 feet +814 Unincorporated Areas of downstream... Sea Level, rounded to the nearest 0.1 meter. ADDRESSES City of Freeport Maps are available for...

Evidence of high-elevation amplification versus Arctic amplification

NASA Astrophysics Data System (ADS)

Wang, Qixiang; Fan, Xiaohui; Wang, Mengben

2016-01-01

Elevation-dependent warming in high-elevation regions and Arctic amplification are of tremendous interest to many scientists who are engaged in studies in climate change. Here, using annual mean temperatures from 2781 global stations for the 1961-2010 period, we find that the warming for the world’s high-elevation stations (>500 m above sea level) is clearly stronger than their low-elevation counterparts; and the high-elevation amplification consists of not only an altitudinal amplification but also a latitudinal amplification. The warming for the high-elevation stations is linearly proportional to the temperature lapse rates along altitudinal and latitudinal gradients, as a result of the functional shape of Stefan-Boltzmann law in both vertical and latitudinal directions. In contrast, neither altitudinal amplification nor latitudinal amplification is found within the Arctic region despite its greater warming than lower latitudes. Further analysis shows that the Arctic amplification is an integrated part of the latitudinal amplification trend for the low-elevation stations (≤500 m above sea level) across the entire low- to high-latitude Northern Hemisphere, also a result of the mathematical shape of Stefan-Boltzmann law but only in latitudinal direction.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

USGS Publications Warehouse

Langley, J.A.; McKee, K.L.; Cahoon, D.R.; Cherry, J.A.; Megonigala, J.P.

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise.

PubMed

Langley, J Adam; McKee, Karen L; Cahoon, Donald R; Cherry, Julia A; Megonigal, J Patrick

2009-04-14

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO(2) concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO(2)] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO(2) (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr(-1) in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO(2) effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO(2), may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

PubMed Central

Langley, J. Adam; McKee, Karen L.; Cahoon, Donald R.; Cherry, Julia A.; Megonigal, J. Patrick

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1 in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas. PMID:19325121

Evidence of high-elevation amplification versus Arctic amplification

PubMed Central

Wang, Qixiang; Fan, Xiaohui; Wang, Mengben

2016-01-01

Elevation-dependent warming in high-elevation regions and Arctic amplification are of tremendous interest to many scientists who are engaged in studies in climate change. Here, using annual mean temperatures from 2781 global stations for the 1961–2010 period, we find that the warming for the world’s high-elevation stations (>500 m above sea level) is clearly stronger than their low-elevation counterparts; and the high-elevation amplification consists of not only an altitudinal amplification but also a latitudinal amplification. The warming for the high-elevation stations is linearly proportional to the temperature lapse rates along altitudinal and latitudinal gradients, as a result of the functional shape of Stefan-Boltzmann law in both vertical and latitudinal directions. In contrast, neither altitudinal amplification nor latitudinal amplification is found within the Arctic region despite its greater warming than lower latitudes. Further analysis shows that the Arctic amplification is an integrated part of the latitudinal amplification trend for the low-elevation stations (≤500 m above sea level) across the entire low- to high-latitude Northern Hemisphere, also a result of the mathematical shape of Stefan-Boltzmann law but only in latitudinal direction. PMID:26753547

Brassinosteroid signaling-dependent root responses to prolonged elevated ambient temperature.

PubMed

Martins, Sara; Montiel-Jorda, Alvaro; Cayrel, Anne; Huguet, Stéphanie; Roux, Christine Paysant-Le; Ljung, Karin; Vert, Grégory

2017-08-21

Due to their sessile nature, plants have to cope with and adjust to their fluctuating environment. Temperature elevation stimulates the growth of Arabidopsis aerial parts. This process is mediated by increased biosynthesis of the growth-promoting hormone auxin. How plant roots respond to elevated ambient temperature is however still elusive. Here we present strong evidence that temperature elevation impinges on brassinosteroid hormone signaling to alter root growth. We show that elevated temperature leads to increased root elongation, independently of auxin or factors known to drive temperature-mediated shoot growth. We further demonstrate that brassinosteroid signaling regulates root responses to elevated ambient temperature. Increased growth temperature specifically impacts on the level of the brassinosteroid receptor BRI1 to downregulate brassinosteroid signaling and mediate root elongation. Our results establish that BRI1 integrates temperature and brassinosteroid signaling to regulate root growth upon long-term changes in environmental conditions associated with global warming.Moderate heat stimulates the growth of Arabidopsis shoots in an auxin-dependent manner. Here, Martins et al. show that elevated ambient temperature modifies root growth by reducing the BRI1 brassinosteroid-receptor protein level and downregulating brassinosteroid signaling.

Growth habit and leaf economics determine gas exchange responses to high elevation in an evergreen tree, a deciduous shrub and a herbaceous annual

PubMed Central

Shi, Zuomin; Haworth, Matthew; Feng, Qiuhong; Cheng, Ruimei; Centritto, Mauro

2015-01-01

Plant growth at high elevations necessitates physiological and morphological plasticity to enable photosynthesis (A) under conditions of reduced temperature, increased radiation and the lower partial pressure of atmospheric gases, in particular carbon dioxide (pCO2). Previous studies have observed a wide range of responses to elevation in plant species depending on their adaptation to temperature, elevational range and growth habit. Here, we investigated the effect of an increase in elevation from 2500 to 3500 m above sea level (a.s.l.) on three montane species with contrasting growth habits and leaf economic strategies. While all of the species showed identical increases in foliar δ13C, dark respiration and nitrogen concentration with elevation, contrasting leaf gas exchange and photosynthetic responses were observed between species with different leaf economic strategies. The deciduous shrub Salix atopantha and annual herb Rumex dentatus exhibited increased stomatal (Gs) and mesophyll (Gm) conductance and enhanced photosynthetic capacity at the higher elevation. However, evergreen Quercus spinosa displayed reduced conductance to CO2 that coincided with lower levels of photosynthetic carbon fixation at 3500 m a.s.l. The lower Gs and Gm values of evergreen species at higher elevations currently constrains their rates of A. Future rises in the atmospheric concentration of CO2 ([CO2]) will likely predominantly affect evergreen species with lower specific leaf areas (SLAs) and levels of Gm rather than deciduous species with higher SLA and Gm values. We argue that climate change may affect plant species that compose high-elevation ecosystems differently depending on phenotypic plasticity and adaptive traits affecting leaf economics, as rising [CO2] is likely to benefit evergreen species with thick sclerophyllous leaves. PMID:26433706

Carbon balance, partitioning and photosynthetic acclimation in fruit-bearing grapevine (Vitis vinifera L. cv. Tempranillo) grown under simulated climate change (elevated CO2, elevated temperature and moderate drought) scenarios in temperature gradient greenhouses.

PubMed

Salazar-Parra, Carolina; Aranjuelo, Iker; Pascual, Inmaculada; Erice, Gorka; Sanz-Sáez, Álvaro; Aguirreolea, Jone; Sánchez-Díaz, Manuel; Irigoyen, Juan José; Araus, José Luis; Morales, Fermín

2015-02-01

Although plant performance under elevated CO2 has been extensively studied in the past little is known about photosynthetic performance changing simultaneously CO2, water availability and temperature conditions. Moreover, despite of its relevancy in crop responsiveness to elevated CO2 conditions, plant level C balance is a topic that, comparatively, has received little attention. In order to test responsiveness of grapevine photosynthetic apparatus to predicted climate change conditions, grapevine (Vitis vinifera L. cv. Tempranillo) fruit-bearing cuttings were exposed to different CO2 (elevated, 700ppm vs. ambient, ca. 400ppm), temperature (ambient vs. elevated, ambient +4°C) and irrigation levels (partial vs. full irrigation). Carbon balance was followed monitoring net photosynthesis (AN, C gain), respiration (RD) and photorespiration (RL) (C losses). Modification of environment (13)C isotopic composition (δ(13)C) under elevated CO2 (from -10.30 to -24.93‰) enabled the further characterization of C partitioning into roots, cuttings, shoots, petioles, leaves, rachides and berries. Irrespective of irrigation level and temperature, exposure to elevated CO2 induced photosynthetic acclimation of plants. C/N imbalance reflected the inability of plants grown at 700ppm CO2 to develop strong C sinks. Partitioning of labeled C to storage organs (main stem and roots) did not avoid accumulation of labeled photoassimilates in leaves, affecting negatively Rubisco carboxylation activity. The study also revealed that, after 20 days of treatment, no oxidative damage to chlorophylls or carotenoids was observed, suggesting a protective role of CO2 either at current or elevated temperatures against the adverse effect of water stress. Copyright © 2014 Elsevier GmbH. All rights reserved.

Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Ito, Takanori; Maeda, Atsuyuki; Kaneoka, Yuji; Kagebayashi, Chiaki; Satomura, Shinji

2014-06-01

We investigated changes in highly sensitive lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre- and postoperatively was compared, and recurrence-free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence-free and overall survival rates of patients in whom hsAFP-L3 became elevated postoperatively despite normal preoperative hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP-L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3 identifies patients with poor prognosis despite the normalization of AFP and DCP. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Analytical investigation of the dynamics of tethered constellations in Earth orbit, phase 2

NASA Technical Reports Server (NTRS)

Lorenzini, Enrico C.

1987-01-01

A control law was developed to control the elevator during short-distance maneuvers along the tether of a 4-mass tethered system. This control law (called retarded exponential or RE) was analyzed parametrically in order to assess which control parameters provide a good dynamic response and a smooth time history of the acceleration on board the elevator. The short-distance maneuver under investigation consists of a slow crawling of the elevator over the distance of 10 m that represents a typical maneuver for fine tuning the acceleration level on board the elevator. The contribution of aerodynamic and thermal perturbations upon acceleration levels was also evaluated and acceleration levels obtained when such pertubations are taken into account were compared to those obtained by neglecting the thermal and aerodynamic forces. In addition, the preparation of a tether simulation questionnaire is illustrated. Analytic solutions to be compared to numerical cases and simulator test cases are also discussed.

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

PubMed

Davies, S F; Rohrbach, M S; Thelen, V; Kuritsky, J; Gruninger, R; Simpson, M L; DeRemee, R A

1984-03-01

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

Water Resources Data, Florida, Water Year 2003, Volume 3B: Southwest Florida Ground Water

USGS Publications Warehouse

Kane, Richard L.; Fletcher, William L.; Lane, Susan L.

2004-01-01

Water resources data for the 2003 water year in Florida consist of continuous or daily discharges for 385 streams, periodic discharge for 13 streams, continuous daily stage for 255 streams, periodic stage for 13 streams, peak stage for 36 streams and peak discharge for 36 streams, continuous or daily elevations for 13 lakes, periodic elevations for 46 lakes; continuous ground-water levels for 441 wells, periodic ground-water levels for 1,227 wells, and quality-of-water data for 133 surface-water sites and 308 wells. The data for Southwest Florida include records of stage, discharge, and water quality of streams; stage, contents, water quality of lakes and reservoirs, and water levels and water quality of ground-water wells. Volume 3B contains records for continuous ground-water elevations for 128 wells; periodic ground-water elevations at 31 wells; miscellaneous ground-water elevations at 405 wells; and water quality at 32 ground-water sites. These data represent the national Water Data System records collected by the U.S. Geological Survey and cooperating local, state, and federal agencies in Florida.

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE-/- Mice.

PubMed

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A; Moore-Carrasco, Rodrigo

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE-/- mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE-/- mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice.

Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, Henrik; Barth, Stephanie; Palermo, Richard D.

The Epstein-Barr virus (EBV) growth-transforms B-lymphocytes. The virus-encoded nuclear antigen 2 (EBNA2) is essential for transformation and activates gene expression by association with DNA-bound transcription factors such as RBPJkappa (CSL/CBF1). We have previously shown that EBNA2 contains symmetrically dimethylated Arginine (sDMA) residues. Deletion of the RG-repeat results in a reduced ability of the virus to immortalise B-cells. We now show that the RG repeat also contains asymmetrically dimethylated Arginines (aDMA) but neither non-methylated (NMA) Arginines nor citrulline residues. We demonstrate that only aDMA-containing EBNA2 is found in a complex with DNA-bound RBPJkappa in vitro and preferentially associates with the EBNA2-responsivemore » EBV C, LMP1 and LMP2A promoters in vivo. Inhibition of methylation in EBV-infected cells results in reduced expression of the EBNA2-regulated viral gene LMP1, providing additional evidence that methylation is a prerequisite for DNA-binding by EBNA2 via association with the transcription factor RBPJkappa.« less

Arginine analogues incorporating carboxylate bioisosteric functions are micromolar inhibitors of human recombinant DDAH-1.

PubMed

Tommasi, Sara; Zanato, Chiara; Lewis, Benjamin C; Nair, Pramod C; Dall'Angelo, Sergio; Zanda, Matteo; Mangoni, Arduino A

2015-12-14

Dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme involved in the metabolism of asymmetric dimethylarginine (ADMA) and N-monomethyl arginine (NMMA), which are endogenous inhibitors of the nitric oxide synthase (NOS) family of enzymes. Two isoforms of DDAH have been identified in humans, DDAH-1 and DDAH-2. DDAH-1 inhibition represents a promising strategy to limit the overproduction of NO in pathological states without affecting the homeostatic role of this important messenger molecule. Here we describe the design and synthesis of 12 novel DDAH-1 inhibitors and report their derived kinetic parameters, IC50 and Ki. Arginine analogue 10a, characterized by an acylsulfonamide isosteric replacement of the carboxylate, showed a 13-fold greater inhibitory potential relative to the known DDAH-1 inhibitor, L-257. Compound 10a was utilized to study the putative binding interactions of human DDAH-1 inhibition using molecular dynamics simulations. The latter suggests that several stabilizing interactions occur in the DDAH-1 active-site, providing structural insights for the enhanced inhibitory potential demonstrated by in vitro inhibition studies.

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE−/− Mice

PubMed Central

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A.

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE−/− mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE−/− mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice. PMID:26075004

Role of proton magnetic resonance spectroscopy in the diagnosis of gliomatosis cerebri: a unique pattern of normal choline but elevated Myo-inositol metabolite levels.

PubMed

Mohana-Borges, Aurea V R; Imbesi, Steven G; Dietrich, Rosalind; Alksne, John; Amjadi, Darius K

2004-01-01

A patient with histologically proven gliomatosis cerebri presented with a normal choline level but a markedly abnormal elevated myo-inositol level on magnetic resonance (MR) spectroscopy. We describe the case presentation, imaging findings (in particular, the unique MR spectroscopic pattern), and their significance regarding the diagnosis of this relatively rare neoplasm.

Prevalence of high HbA1c levels in Brazilian adolescents: The Study of Cardiovascular Risk in Adolescents.

PubMed

de Cássia Lima Fernandes, Rita; Teló, Gabriela H; Cureau, Felipe V; Barufaldi, Laura A; Kuschnir, Maria Cristina C; Schaan, Beatriz D; Szklo, Moyses; Bloch, Katia V

2017-03-01

To evaluate the prevalence of elevated glycated haemoglobin (HbA1c) levels in a population of adolescents participating in the Study of Cardiovascular Risk in Adolescents. This is a school-based cross-sectional study based on a complex sample of adolescents 12-17years old representative at the national and macro-regional levels and for each Brazilian state capital. Blood was collected in schools and then evaluated in a single laboratory. HbA1c levels were considered elevated if ⩾5.7% (39mmol/mol) and were analyzed according to sex, age, macro-region, type of school, skin color, and nutritional status. Data from 37,804 adolescents were analyzed. The mean level of HbA1c was 5.4% (95%CI 5.4-5.4) (36mmol/mol [95%CI 36-36]), and 20.5% (95%CI 19.1-22.0) of adolescents presented values ⩾5.7% (⩾39mmol/mol). Among males, 23.6% (95%CI 21.8-25.6) showed elevated HbA1c levels compared to 17.5% (95%CI 15.9-19.2) observed in females. The prevalence of elevated levels of HbA1c was higher in adolescents with black skin color (27.6%; 95%CI 23.2-32.4) vs. white skin color (16.9%; 95%CI 15.4-18.5), and higher in those who studied in public schools (21.6%; 95%CI 20.0-23.4) vs. private schools (16.7%; 95%CI 14.7-19.0). Among obese adolescents, 29.7% (95%CI 25.4-34.3) had elevated levels of HbA1c, compared to 19.3% (95%CI 18.0-20.7) in normal weight students and 19.7% (95%CI 17.1-22.6) in overweight adolescents. Obese male adolescents of lower socioeconomic status had a higher prevalence of elevated HbA1c levels. Our findings highlight the importance of focusing on this high risk group for interventions to prevent diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Suppressing the Morning Rise in Cortisol Impairs Free Recall

ERIC Educational Resources Information Center

Rimmele, Ulrike; Meier, Flurina; Lange, Tanja; Born, Jan

2010-01-01

Elevated glucocorticoid levels impair memory retrieval. We investigated whether retrieval under naturally elevated glucocorticoid levels, i.e., during the morning rise in cortisol can be improved by suppressing cortisol. In a crossover study 16 men retrieved emotional and neutral texts and pictures (learned 3 d earlier) 30 min after morning…

ANALYSIS OF LOW-LEVEL PESTICIDES FROM HIGH-ELEVATION LAKE WATERS BY LARGE VOLUME INJECTION GCMS

EPA Science Inventory

This paper describes the method development for the determination of ultra-low level pesticides from high-elevation lake waters by large-volume injection programmable temperature vaporizer (LVI-PTV) GC/MS. This analytical method is developed as a subtask of a larger study, backgr...

4th level of 1945 warehouse indicating drag conveyor. From here ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4th level of 1945 warehouse indicating drag conveyor. From here screenings were pumped from the elevator leg to this conveyor. The grains were ground, then conveyed back down to the first floor for bagging. - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

Circulating Galectin-3 Levels Are Persistently Elevated After Heart Transplantation and Are Associated With Renal Dysfunction.

PubMed

Grupper, Avishay; Nativi-Nicolau, Jose; Maleszewski, Joseph J; Geske, Jennifer R; Kremers, Walter K; Edwards, Brooks S; Kushwaha, Sudhir S; Pereira, Naveen L

2016-11-01

This study evaluated changes in serum levels of galectin (Gal)-3 before and after heart transplantation (HTx) and assessed the role of pre-HTx Gal-3 as a biomarker for post-HTx outcomes. Gal-3 is a novel biomarker that reflects cardiac remodeling and fibrosis. Elevated serum Gal-3 levels are associated with poor prognosis in heart failure patients. Whether Gal-3 levels change following HTx and the significance of post-HTx outcomes are unknown. Serum Gal-3 levels were measured in 62 patients at 118 days (Interquartile Range [IQR]: 23 to 798 days) before and 365 days (IQR: 54 to 767 days) post HTx. Cardiac tissue taken during routine post-HTx endomyocardial biopsy was evaluated to assess the correlation between tissue Gal-3 staining and serum Gal-3 levels and with the presence of myocardial hypertrophy and fibrosis. Serum Gal-3 levels remained significantly elevated (>17.8 ng/ml) in 35 patients (56%) post HTx. There was a significant inverse correlation between Gal-3 levels and glomerular filtration rate measured before and after HTx (p > 0.005). There was no association between Gal-3 serum level and Gal-3 staining of myocardial tissue or with the presence of myocyte hypertrophy and interstitial fibrosis post HTx. Elevated pre-HTx Gal-3 levels were associated with reduced post-HTx exercise capacity, but this association was not significant after adjustment for age, body mass index, and glomerular filtration rate. This is the first study to demonstrate the fact that Gal-3 levels remain elevated in the majority of patients despite HTx and is associated with renal dysfunction. Our findings suggest Gal-3 is a systemic rather than cardiac-specific biomarker. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

76 FR 50920 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

... Depth in feet Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified... above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. ADDRESSES Unincorporated Areas... Unincorporated Areas of downstream of Main Butler County. Street. Approximately 400 feet + 958 upstream of Main...

76 FR 39305 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Franklin County... Level, rounded to the nearest 0.1 meter. ADDRESSES Unincorporated Areas of Franklin County Maps are....1 meter. ADDRESSES City of Spring Valley Maps are available for inspection at City Hall, 215 North...

76 FR 62329 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

...] Communities affected elevation * * Elevation in meters (MSL) Effective Modified Anne Arundel County, Maryland... + 8 + 10 Unincorporated Areas of Crain Highway. Anne Arundel County. Approximately 400 feet None + 105... American Vertical Datum. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. * * BFEs to be changed...

76 FR 39800 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

... referenced ground [caret] Communities affected elevation ** Elevation in meters (MSL) Effective Modified.... Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1 meter. [[Page 39802... Unincorporated Areas Logsboro Road. of Edgecombe County. Approximately 400 feet +91 +90 downstream of the...