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Sample records for ace inhibitor acei

  1. ACE-I Inhibitory Activity from Phaseolus lunatus and Phaseolus vulgaris Peptide Fractions Obtained by Ultrafiltration.

    PubMed

    Betancur-Ancona, David; Dávila-Ortiz, Gloria; Chel-Guerrero, Luis Antonio; Torruco-Uco, Juan Gabriel

    2015-11-01

    The involvement of angiotensin-I-converting enzyme (ACE-I) as one of the mechanisms controlling blood pressure is being studied to find alternative means of control of hypertension on human beings. On the market there are synthetic drugs that can control it, but these can cause undesirable health side effects. In this work was assessed the fractionation by ultrafiltration of the Lima bean (Phaseolus lunatus) and Jamapa bean (Phaseolus vulgaris), protein hydrolysates obtained with Alcalase(®) and Flavourzyme(®) on ACE-I inhibitory activity. Four membranes of different molecular cutoffs (10, 5, 3, and 1 kDa) were used. Fractions that had a higher inhibitory activity in both legumes were denominated as E (<1 kDa) with IC50 of 30.3 and 51.8 μg/mL values for the P. lunatus with Alcalase and Flavourzyme, respectively, and for the Phaseolus vulgaris with Alcalase and Flavourzyme with about 63.8 and 65.8 μg/mL values, respectively. The amino acid composition of these fractions showed residues in essential amino acids, which make a good source of energy and amino acids. On the other hand, the presence of hydrophobic amino acids such as V and P is a determining factor in the ACE-I inhibitor effect. The results suggest the possibility of obtaining and utilizing these peptide fractions in the development and innovation of a functional product that helps with treatment and/or prevention of hypertension. PMID:26061663

  2. Homologs of the Acinetobacter baumannii AceI Transporter Represent a New Family of Bacterial Multidrug Efflux Systems

    PubMed Central

    Liu, Qi; Henderson, Peter J. F.

    2015-01-01

    ABSTRACT Multidrug efflux systems are a major cause of resistance to antimicrobials in bacteria, including those pathogenic to humans, animals, and plants. These proteins are ubiquitous in these pathogens, and five families of bacterial multidrug efflux systems have been identified to date. By using transcriptomic and biochemical analyses, we recently identified the novel AceI (Acinetobacter chlorhexidine efflux) protein from Acinetobacter baumannii that conferred resistance to the biocide chlorhexidine, via an active efflux mechanism. Proteins homologous to AceI are encoded in the genomes of many other bacterial species and are particularly prominent within proteobacterial lineages. In this study, we expressed 23 homologs of AceI and examined their resistance and/or transport profiles. MIC analyses demonstrated that, like AceI, many of the homologs conferred resistance to chlorhexidine. Many of the AceI homologs conferred resistance to additional biocides, including benzalkonium, dequalinium, proflavine, and acriflavine. We conducted fluorimetric transport assays using the AceI homolog from Vibrio parahaemolyticus and confirmed that resistance to both proflavine and acriflavine was mediated by an active efflux mechanism. These results show that this group of AceI homologs represent a new family of bacterial multidrug efflux pumps, which we have designated the proteobacterial antimicrobial compound efflux (PACE) family of transport proteins. PMID:25670776

  3. Occurrence and fate of ACE-inhibitor peptides in cheeses and in their digestates following in vitro static gastrointestinal digestion.

    PubMed

    Stuknytė, Milda; Cattaneo, Stefano; Masotti, Fabio; De Noni, Ivano

    2015-02-01

    The occurrence of the casein-derived angiotensin converting enzyme-inhibitor (ACE-I) peptides VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP and HLPLP were investigated in 12 different cheese samples by Ultra Performance Liquid Chromatography/High-Resolution Mass Spectrometry. The total amount of ACE-I peptides was in the range 0.87-331mgkg(-1). VPP and IPP largely prevailed in almost all cheeses. Following in vitro static gastrointestinal digestion of Cheddar, Gorgonzola, Maasdam and Grana Padano cheeses, type and amount of ACE-I peptides changed, and only VPP, IPP, HLPLP and LHLPLP were detected in the intestinal digestates. The results evidenced that the degree of proteolysis itself cannot be regarded as a promoting or hindering factor for ACE-I peptide release during cheese digestion. Moreover, the data indicated that the ACE-I potential of cheeses cannot be inferred based on the type and amount of ACE-I peptides present in undigested samples. PMID:25172679

  4. ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

    PubMed Central

    Curtis, R. Mason; Felder, Sarah; Borici-Mazi, Rozita; Ball, Ian

    2016-01-01

    Introduction Upper airway angioedema is a life-threatening emergency department (ED) presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE) is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity. Methods We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012. Results Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257) of cases. The most common identifiable etiology was AAE (33.1%, n=85), with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54), corticosteroids (50.6%, n=43) and ranitidine (31.8%, n=27). Epinephrine was administered in 21.2% (n=18) of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7%) and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration. Conclusion AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management. PMID:27330660

  5. Inequity of access to ACE inhibitors in Swedish heart failure patients: a register-based study

    PubMed Central

    Lindahl, Bertil; Hanning, Marianne; Westerling, Ragnar

    2016-01-01

    Background Several international studies suggest inequity in access to evidence-based heart failure (HF) care. Specifically, studies of ACE inhibitors (ACEIs) point to reduced ACEI access related to female sex, old age and socioeconomic position. Thus far, most studies have either been rather small, lacking diagnostic data, or lacking the possibility to account for several individual-based sociodemographic factors. Our aim was to investigate differences, which could reflect inequity in access to ACEIs based on sex, age, socioeconomic status or immigration status in Swedish patients with HF. Methods Individually linked register data for all Swedish adults hospitalised for HF in 2005–2010 (n=93 258) were analysed by multivariate regression models to assess the independent risk of female sex, high age, low employment status, low income level, low educational level or foreign country of birth, associated with lack of an ACEI dispensation within 1 year of hospitalisation. Adjustment for possible confounding was made for age, comorbidity, Angiotensin receptor blocker therapy, period and follow-up time. Results Analysis revealed an adjusted OR for no ACEI dispensation for women of 1.31 (95% CI 1.27 to 1.35); for the oldest patients of 2.71 (95% CI 2.53 to 2.91); and for unemployed patients of 1.59 (95% CI 1.46 to 1.73). Conclusions Access to ACEI treatment was reduced in women, older patients and unemployed patients. We conclude that access to ACEIs is inequitable among Swedish patients with HF. Future studies should include clinical data, as well as mortality outcomes in different groups. PMID:26261264

  6. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    PubMed

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. PMID:26617077

  7. ACE Inhibitor Delapril Prevents Ca(2+)-Dependent Blunting of IK1 and Ventricular Arrhythmia in Ischemic Heart Disease.

    PubMed

    Thireau, J; Zalvidea, S; Meschin, P; Pasquie, J-L; Aimond, F; Richard, S

    2015-01-01

    Angiotensin-converting enzyme inhibitors (ACE-I) improve clinical outcome in patients with myocardial infarction (MI) and chronic heart failure. We investigated potential anti-arrhythmic (AA) benefits in a mouse model of ischemic HF. We hypothesized that normalization of diastolic calcium (Ca(2+)) by ACE-I may prevent Ca(2+)-dependent reduction of inward rectifying K(+) current (IK1) and occurrence of arrhythmias after MI. Mice were randomly assigned to three groups: Sham, MI, and MI-D (6 weeks of treatment with ACE-I delapril started 24h after MI). Electrophysiological analyses showed that delapril attenuates MI-induced prolongations of electrocardiogram parameters (QRS complex, QT, QTc intervals) and conduction time from His bundle to ventricular activation. Delapril improved the sympatho-vagal balance (LF/HF) and reduced atrio-ventricular blocks and ventricular arrhythmia. Investigations in cardiomyocytes showed that delapril prevented the decrease of IK1 measured by patch-clamp technique. IK1 reduction was related to intracellular Ca(2+) overload. This reduction was not observed when intracellular free-Ca(2+) was maintained low. Conversely, increasing intracellular free-Ca(2+) in Sham following application of SERCA2a inhibitor thapsigargin reduced IK1. Thapsigargin had no effect in MI animals and abolished the benefits of delapril on IK1 in MI-D mice. Delapril prevented both the prolongation of action potential late repolarization and the depolarization of resting membrane potential, two phenomena known to trigger abnormal electrical activities, promoted by MI. In conclusion, early chronic therapy with delapril after MI prevented Ca(2+)-dependent reduction of IK1. This mechanism may significantly contribute to the antiarrhythmic benefits of ACE-I in patients at risk for sudden cardiac death. PMID:26321755

  8. ACE inhibitors can induce circulating antibodies directed to antigens of the superficial epidermal cells.

    PubMed

    Cozzani, Emanuele; Rosa, Gian Marco; Drosera, Massimo; Intra, Chiara; Barsotti, Antonio; Parodi, Aurora

    2011-07-01

    Drug-induced pemphigus has been reported in patients receiving angiotensin-converting enzyme inhibitors. The aim of this work was to study a group of hypertensive patients without skin diseases treated with angiotensin-converting enzyme (ACE) Inhibitors (I), to verify the presence of serum circulating anti-antibodies. The indirect immunofluorescence showed that 33 sera (52.38%) presented autoantibodies directed to an antigen of the cytoplasm of the superficial epidermal keratinocytes. Two of the 33 positive sera had antibodies to Dsg1 and/or 3 in ELISA. Immunoblot analyses were negative. All the 48 control sera were found to have no circulating antibodies using the three assays. Our results would confirm that ACEI drugs may trigger the production of circulating autoantibodies also in patients without clinical manifestations of pemphigus. PMID:20563876

  9. Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity.

    PubMed

    Taddei, Stefano; Bortolotto, L

    2016-10-01

    Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling. PMID:27260014

  10. ACE inhibition in the treatment of children after renal transplantation.

    PubMed

    Arbeiter, Klaus; Pichler, Andrea; Stemberger, Regina; Mueller, Thomas; Ruffingshofer, Dagmar; Vargha, Regina; Balzar, Egon; Aufricht, Christoph

    2004-02-01

    Currently, there are no data available on long-term effects of angiotensin-converting enzyme inhibitors (ACE-I) on graft function in children after renal transplantation. We therefore analyzed all children who were transplanted at our institution between 1989 and 1998 and followed for at least 2 years. Those treated with ACE-I, mainly because of failure of other antihypertensive medications, were compared to those without ACE-I. The ACE-I-treated children ( n=19) showed significantly better blood pressure control during the 1st year of follow-up ( p<0.05). In children with chronic allograft dysfunction ( n=8), treatment with ACE-I stabilized graft function, with improvement in creatinine clearance in 50% ( p<0.01). Serum potassium and hemoglobin levels remained stable. One patient discontinued ACE-I because of renal artery stenosis. Taken together, ACE-I were effective and safe in the treatment of hypertension in children following renal transplantation. Children with chronic allograft dysfunction experienced a stabilizing effect on graft function. PMID:14673630

  11. ACE inhibitor potentiation of bradykinin-induced venoconstriction

    PubMed Central

    Hecker, Markus; Blaukat, Andree; Bara, Agnieszka T; Müller-Esterl, Werner; Busse, Rudi

    1997-01-01

    Angiotensin-converting enzyme (ACE) inhibitors exert their cardiovascular effects not only by preventing the formation of angiotensin II (AII), but also by promoting the accumulation of bradykinin in or at the vessel wall. In addition, certain ACE inhibitors have been shown to augment the vasodilator response to bradykinin, presumably by an interaction at the level of the B2 receptor. We have investigated whether this is a specific effect of the ACE inhibitor class of compounds in isolated endothelium-denuded segments of the rabbit jugular vein where bradykinin elicits a constrictor response which is exclusively mediated by activation of the B2 receptor. Moexiprilat and ramiprilat (⩽ 3 nM) enhanced the constrictor response to bradykinin three to four fold. Captopril and enalaprilat were less active by approximately one and quinaprilat by two orders of magnitude. Moexiprilat and ramiprilat, on the other hand, had no effect on the constrictor response to AII or the dilator response to acetylcholine. The bradykinin-potentiating effect of the ACE inhibitors was not mimicked by inhibitors of amino-, carboxy-, metallo- or serine peptidases or the synthetic ACE substrate, hippuryl-L-histidyl-L-leucine, at a concentration which almost abolished the residual ACE activity in the vessel wall. In contrast, angiotensin-(1–7) (10 μM), an angiotensin I metabolite, significantly enhanced the constrictor response to bradykinin. Ramiprilat did not alter the binding of [3H]-bradykinin to a membrane fraction prepared from endothelium-denuded rabbit jugular veins or to cultured fibroblasts, and there was no ACE inhibitor-sensitive, bradykinin-induced cleavage of the B2 receptor in cultured endothelial cells. These findings demonstrate that ACE inhibitors selectively potentiate the B2 receptor-mediated vascular effects of bradykinin. Their relative efficacy appears to be independent of their ACE-inhibiting properties and might be related to differences in molecule structure

  12. ACE Inhibitor and Angiotensin Receptor-II Antagonist Prescribing and Hospital Admissions with Acute Kidney Injury: A Longitudinal Ecological Study

    PubMed Central

    Tomlinson, Laurie A.; Abel, Gary A.; Chaudhry, Afzal N.; Tomson, Charles R.; Wilkinson, Ian B.; Roland, Martin O.; Payne, Rupert A.

    2013-01-01

    Background ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. Methods and Findings English NHS prescribing data for ACE-I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540-1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. Conclusion In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level

  13. [Trials with ACE-inhibitors in acute myocardial infarction].

    PubMed

    Dalla Volta, S

    1994-12-01

    In acute myocardial infarction, the results of the trials with ACE-inhibitors have not been always good, in contrast with what has been observed in chronic heart failure. The comparison of these compounds with the placebo has demonstrated lack of reduction of mortality in the study CONSENSUS II, favorable results on the survival as first endpoint and on the secondary endpoints, as reinfarction, heart failure and stroke in the studies SOLVD, AIRE, GISSI 3, ISIS 4, and uncertain (interim report) results in the Chinese study. Nevertheless, the analysis of the recruitment of the patients with acute infarction and the way these patients have been treated seem to be the most important cause of the conflicting results. ACE-inhibitors have proved no efficacy in acute myocardial infarction without signs of left ventricular failure (CONSENSUS II), have worsened the clinical picture and the mortality in patients in shock or with severe heart failure in the acute phase. On the reverse, in presence of mild to moderate left ventricular dysfunction and failure, the use of ACE-inhibitors has been followed by reduction of mortality in the early (AIRE, GISSI 3, ISIS 4), medium term (GISSI 3) and long-term follow-up (up to 4 years in the AIRE study). In parallel with the reduction of the primary endpoint, also secondary endpoints have been favorably influenced by the different ACE-inhibitors. No differences have been observed among the different class of compounds. ACE-inhibitors seem, therefore, to have a clear indication in acute myocardial infarction with mild or moderate signs and symptoms of heart failure. PMID:7634258

  14. ACE

    NASA Technical Reports Server (NTRS)

    Lumia, R.

    1999-01-01

    This document describes the progress made during the fourth year of the Center for Autonomous Control Engineering (ACE). We currently support 30 graduate students, 52 undergraduate students, 9 faculty members, and 4 staff members. Progress will be divided into two categories. The first category explores progress for ACE in general. The second describes the results of each specific project supported within ACE.

  15. ACE Inhibitor and Angiotensin Receptor Blocker Use and Mortality in Patients with Chronic Kidney Disease

    PubMed Central

    Molnar, Miklos Z; Kalantar-Zadeh, Kamyar; Lott, Evan H; Lu, Jun Ling; Malakauskas, Sandra M; Ma, Jennie Z; Quarles, Darryl L; Kovesdy, Csaba P

    2014-01-01

    Objective To assess the association between ACEI/ARB use and mortality in CKD patients. Background There is insufficient evidence about the association of angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) with mortality in chronic kidney disease (CKD) patients. Methods A logistic regression analysis was used to calculate the propensity of ACEI/ARB initiation in 141,413 US veterans with non-dialysis CKD previously unexposed to ACEI/ARB treatment. We examined the association of ACEI/ARB administration with all-cause mortality in patients matched by propensity scores, using the Kaplan-Meier method and Cox models in “intention-to-treat” analyses, and in generalized linear models with binary outcomes and inverse probability treatment weighing (IPTW) in “as-treated” analyses. Results The mean±SD age of the patients at baseline was 75±10 years, 8% of patients were black, and 22% were diabetic. ACEI/ARB administration was associated with significantly lower risk of mortality both in the intention-to-treat analysis (HR=0.81; 95%CI: 0.78-0.84, p<0.001) and in the as-treated analysis with IPTW (OR=0.37; 95%CI: 0.34-0.41, p<0.001). The association of ACEI/ARB treatment with lower risk of mortality was present in all examined subgroups. Conclusions In this large contemporary cohort of non-dialysis dependent CKD patients, ACEI/ARB administration was associated with greater survival. PMID:24269363

  16. Characterization of angiotensin converting enzyme (ACE) in the testis and assessment of the in vivo effects of the ACE inhibitor perindopril

    SciTech Connect

    Jackson, B.; Cubela, R.B.; Sakaguchi, K.; Johnston, C.I.

    1988-07-01

    Angiotensin converting enzyme (ACE) was characterized by radioligand studies utilizing the potent ACE inhibitor 351A, a derivative of lisinopril. Ligand binding characteristics were similar for ACE derived from testis, lung, and kidney, despite known differences in structure between ACe from these sources. This observation suggests that the ACE active enzymatic site is similar in different tissues. The effect of the orally active ACE inhibitor perindopril was studied ex vivo in tissues of the rat after oral gavage. Radioligand bound to tissue ACE was reduced after perindopril treatment, in tissue homogenates of lung and kidney, but not testis. Autoradiographs of radioligand binding to tissue sections obtained ex vivo after oral perindopril showed inhibition of ACE in the aorta, lung, and kidney, but did not reveal any inhibition of ACE in the testis. ACE in small vessels of the testis was inhibited as in the aorta, while at the same time testicular ACE was unaffected. ACE in rat testis appears to have a similar enzymatic binding site to ACE from the lung and kidney. Perindopril inhibited ACE in the lung and kidney but did not affect ACE in the testis, suggesting the drug is limited in testicular penetration by the blood-testis barrier. This may explain the lack of any reports of adverse effects of ACE inhibitors on testicular function.

  17. Multifactorial Model and Treatment Approaches of Refractory Hypotension in a Patient Who Took an ACE Inhibitor the Day of Surgery

    PubMed Central

    Srivastava, Karan; Sacher, Vikas Y.; Nelson, Craig T.; Lew, John I.

    2013-01-01

    In the field of anesthesiology, there is wide debate on discontinuing angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy the day of noncardiac surgery. Although there have been many studies attributing perioperative hypotension to same-day ACEI and ARB use, there are many additional variables that play a role in perioperative hypotension. Additionally, restoring blood pressure in these patients presents a unique challenge to anesthesiologists. A case report is presented in which a patient took her ACEI the day of surgery and developed refractory hypotension during surgery. The evidence of ACEI use on the day of surgery and development of hypotension is reviewed, and additional variables that contributed to this hypotensive episode are discussed. Lastly, current challenges in restoring blood pressure are presented, and a basic model on treatment approaches for refractory hypotension in the setting of perioperative ACEI use is proposed. PMID:23662213

  18. Comparison of the Efficacy and Safety of Different ACE Inhibitors in Patients With Chronic Heart Failure

    PubMed Central

    Sun, WeiPing; Zhang, HaiBin; Guo, JinCheng; Zhang, XueKun; Zhang, LiXin; Li, ChunLei; Zhang, Ling

    2016-01-01

    Abstract Heart failure is a public health problem and a great economic burden for patients and healthcare systems. Suppression of the renin–angiotensin system (RAS) by angiotensin-converting enzyme (ACE)-inhibitors remains the mainstay of treatment for heart failure. However, the abundance of ACE inhibitors makes it difficult for doctors to choose. We performed this network meta-analysis of ACEIs in patients with heart failure in order to address this area of uncertainty. We searched PubMed, Embase, CENTRAL, and Medline. Any randomized controlled trial evaluating the efficacy and safety of captopril, enalapril, lisinopril, ramipril, or trandolapril or combined interventions of 2 or more of these drugs. Two reviewers extracted the data and made the quality assessment. At first, we used Stata software (version 12.0, StataCorp, College Station, TX) to make traditional pairwise meta-analyses for studies that directly compared different interventions. Then, network meta-analysis was performed using WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK). A total of 29 studies were included. Lisinopril was associated with a higher rate of all-cause mortality compared with placebo (odds ratio 65.9, 95% credible interval 1.91 to 239.6) or ramipril (14.65, 1.23 to 49.5). Enalapril significantly reduced systolic blood pressure when compared with placebo (standardized mean differences −0.6, 95% credible interval −1.03 to −0.18). Both captopril (odds ratio 76.2, 95% credible interval 1.56 to 149.3) and enalapril (274.4, 2.4 to 512.9) were associated with a higher incidence of cough compared to placebo. Some important outcomes such as rehospitalization and cardiac death were not included. The sample size and the number of studies were limited, especially for ramipril. Our results suggest that enalapril might be the best option when considering factors such as increased ejection fraction, stroke volume, and decreased mean arterial pressure. However, enalapril was

  19. Can ACE inhibitors and angiotensin receptor blockers be detrimental in CKD patients?

    PubMed

    Onuigbo, Macaulay A C

    2011-01-01

    Current epidemiological data from the USA, Europe, Asia and the Indian subcontinent, Africa, the Far East, South America, the Middle East and Eastern Europe all point to the increasing incidence of renal failure encompassing acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD). While the explanations for these worldwide epidemics remain speculative, it must be acknowledged that these increases in AKI, CKD and ESRD, happening worldwide, have occurred despite the universal application of strategies of renoprotection over the last 2 decades, more especially the widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We note that many of the published large renin-angiotensin-aldosterone system (RAAS) blockade randomized controlled trials, upon which current evidence-based practice for the increasing use of ACEIs and ARBs for renoprotection derived from, have strong deficiencies that have been highlighted over the years. From reports in the literature, there is an increasing association of exacerbations of renal failure with ACEIs and ARBs, more so in the older hypertensive patient, >65 years old. The biological plausibility for ACEI and ARB to protect the kidneys against a background of potential multiple pathogenetic pathways to account for CKD progression appears to be not very defensible. We reviewed the literature along these lines and submit that ACEIs and ARBs often cause unrecognized significant worsening renal failure in CKD patients, sometimes irreversible, and that more caution is required regarding their use, especially in the older hypertensive patients, with likely ischemic hypertensive nephropathy. Given the increasing association of concomitant RAAS blockade with worsening renal failure following exposure to iodinated contrast, during acute illness, in the perioperative period and following lower bowel preparations prior to colonoscopy, we submit that, preferably

  20. Effect of ace inhibitors and TMOF on growth, development, and trypsin activity of larval Spodoptera littoralis.

    PubMed

    Lemeire, Els; Borovsky, Dov; Van Camp, John; Smagghe, Guy

    2008-12-01

    Angiotensin converting enzyme (ACE) is a zinc metallopeptidase capable of cleaving dipeptide or dipeptideamide moieties at the C-terminal end of peptides. ACE is present in the hemolymph and reproductive tissues of insects. The presence of ACE in the hemolymph and its broad substrate specificity suggests an important role in processing of bioactive peptides. This study reports the effects of ACE inhibitors on larval growth in the cotton leafworm Spodoptera littoralis. Feeding ACE inhibitors ad lib decreased the growth rate, inhibited ACE activity in the larval hemolymph, and down-regulated trypsin activity in the larval gut. These results indicate that S. littoralis ACE may influence trypsin biosynthesis in the larval gut by interacting with a trypsin-modulating oostatic factor (TMOF). Injecting third instar larvae with a combination of Aea-TMOF and the ACE inhibitor captopril, down-regulated trypsin biosynthesis in the larval gut indicating that an Aea-TMOF gut receptor analogue could be present. Injecting captopril and enalapril into newly molted fifth instar larvae stopped larval feeding and decreased weight gain. Together, these results indicate that ACE inhibitors are efficacious in stunting larval growth and ACE plays an important role in larval growth and development. PMID:18949805

  1. Risk-benefit ratio of angiotensin antagonists versus ACE inhibitors in end-stage renal disease.

    PubMed

    Sica, D A; Gehr, T W; Fernandez, A

    2000-05-01

    The effective treatment of hypertension is an extremely important consideration in patients with end-stage renal disease (ESRD). Virtually any drug class--with the possible exception of diuretics--can be used to treat hypertension in the patient with ESRD. Despite there being such a wide range of treatment options, drugs which interrupt the renin-angiotensin axis are generally suggested as agents of choice in this population, even though the evidence in support of their preferential use is quite scanty. ACE inhibitors, and more recently angiotensin antagonists, are the 2 drug classes most commonly employed to alter renin-angiotensin axis activity and therefore produce blood pressure control. ACE inhibitor use in patients with ESRD can sometimes prove an exacting proposition. ACE inhibitors are variably dialysed, with compounds such as catopril, enalapril, lisinopril and perindopril undergoing substantial cross-dialyser clearance during a standard dialysis session. This phenomenon makes the selection of a dose and the timing of administration for an ACE inhibitor a complex issue in patients with ESRD. Furthermore, ACE inhibitors are recognised as having a range of nonpressor effects that are pertinent to patients with ESRD. Such effects include their ability to decrease thirst drive and to decrease erythropoiesis. In addition, ACE inhibitors have a unique adverse effect profile. As is the case with their use in patients without renal failure, use of ACE inhibitors in patients with ESRD can be accompanied by cough and less frequently by angioneurotic oedema. In the ESRD population, ACE inhibitor use is also accompanied by so-called anaphylactoid dialyser reactions. Angiotensin antagonists are similar to ACE inhibitors in their mechanism of blood pressure lowering. Angiotensin antagonists are not dialysable and therefore can be distinguished from a number of the ACE inhibitors. In addition, the adverse effect profile for angiotensin antagonists is remarkably bland

  2. Different effects of thiol and nonthiol ace inhibitors on copper-induced lipid and protein oxidative modification.

    PubMed

    Fernandes, A C; Filipe, P M; Freitas, J P; Manso, C F

    1996-01-01

    Differences among angiotensin-converting enzyme inhibitors (ACEI) in scavenging reactive oxygen species were described and mainly attributed to the presence or absence of a thiol group. Plasma constituents and red cells are known targets for oxidative damage. Transition metals, like copper, are well known catalizers of free radical generation. In the present study we compared the abilities of captopril (a thiol ACEI), enalaprilat, and lisinopril (two nonthiol ACEI) for inhibiting copper-induced thiobarbituric acid reactive substances (TBARS) formation and fluorescence generation in whole human plasma and low-density lipoprotein. The effects of those ACEI on copper/hydrogen peroxide-induced fluorescence development and electrophoretic mobility modification in albumin and on copper-induced TBARS formation and hemolysis in human red cells were also compared. Captopril was more effective than the two nonthiol ACEI in inhibiting plasma and LDL lipid peroxidation, but it was ineffective in inhibiting the albumin oxidative modification that was moderately inhibited by enalaprilat and lisinopril. On the contrary, the inhibitory effects of the three ACEI on copper-induced lipid peroxidation and hemolysis in red cell suspensions were more uniform. This as yet unreported red cell protective effect may deserve pharmacological evaluation. Our results show that captopril is a more effective antioxidant than the nonthiol ACEI in some systems. However, the nonthiol ACEI also have the ability to partially protect some targets against oxidative damage. These observations suggest that the presence of a thiol group in the ACEI structure is not the only determinant for the antioxidant properties. PMID:8904291

  3. Angiotensin-I-Converting Enzyme (ACE) Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry

    PubMed Central

    Wijesekara, Isuru; Kim, Se-Kwon

    2010-01-01

    Hypertension or high blood pressure is one of the major independent risk factors for cardiovascular diseases. Angiotensin-I-converting enzyme (EC 3.4.15.1; ACE) plays an important physiological role in regulation of blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor. Therefore, the inhibition of ACE activity is a major target in the prevention of hypertension. Recently, the search for natural ACE inhibitors as alternatives to synthetic drugs is of great interest to prevent several side effects and a number of novel compounds such as bioactive peptides, chitooligosaccharide derivatives (COS) and phlorotannins have been derived from marine organisms as potential ACE inhibitors. These inhibitory derivatives can be developed as nutraceuticals and pharmaceuticals with potential to prevent hypertension. Hence, the aim of this review is to discuss the marine-derived ACE inhibitors and their future prospects as novel therapeutic drug candidates for treat hypertension. PMID:20479968

  4. Use of Ophiocordyceps sinensis (syn. Cordyceps sinensis) combined with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) versus ACEI/ARB alone in the treatment of diabetic kidney disease: a meta-analysis.

    PubMed

    Luo, Ying; Yang, Shi-kun; Zhou, Xun; Wang, Ming; Tang, Dan; Liu, Fu-you; Sun, Lin; Xiao, Li

    2015-05-01

    Ophiocordyceps sinensis (O. sinensis; syn. Cordyceps sinensis) has been used in clinical therapy for diabetic kidney disease (DKD) for more than 15 years. O. sinensis is a household name in china and it is available even in supermarket. However, the precise role of O. sinensis has not been fully elucidated with meta-analysis. The aim of this study was to review existing evidence on the effectiveness of O. sinensis for the treatment of DKD. We identified 60 trials involving 4288 participants. Overall, O. sinensis combined with ACEI/ARB had a better effect when compared to ACEI/ARB alone on 24 h UP (MD = -0.23 g/d, 95% CI: - 0.28 to -0.19, p < 0.00001), UAER (MD = -19.71 μg/min, 95% CI: -22.76 to -16.66, p < 0.00001), MAU (MD = -45.09 mg/d, 95% CI: -55.68 to -34.50, p < 0.00001), BUN (MD = -0.70 mmol/L, 95% CI: -1.02 to -0.39, p < 0.0001), SCr (MD = -8.37 μmol/L, 95% CI: -12.41 to -4.32, p < 0.0001), CRP (MD = -1.32 mg/L; 95% CI: -1.78 to -0.86; p < 0.00001), TG (MD = -0.51 mmol/L; 95% CI: -0.69 to -0.34, p < 0.00001), TC (MD = -0.64 mmol/L; 95% CI: -0.91 to -0.37, p < 0.00001), and SBP (MD = -2.01 mmHg; 95% CI: -3.45 to -0.58, p = 0.006). However, no effects were found for DBP, FBG, and HbA1C. This meta-analysis suggested that use of O. sinensis combined with ACEI/ARB may have a more beneficial effect on the proteinuria, inflammatory, dyslipidemia status as compared to ACEI/ARB alone in DKD III-IV stage patients, while there is no evidence that O. sinensis could improve the hyperglycemia status. However, with regard to low-quality and significant heterogeneity of included trials, to further verify the current results from this meta-analysis, long-term and well-designed RCTs with high-quality study are warranted to ascertain the long-term efficacy of O. sinensis. PMID:25682973

  5. An angiotensin-converting enzyme (ACE) polymorphism may mitigate the effects of angiotensin-pathway medications on posttraumatic stress symptoms.

    PubMed

    Nylocks, K M; Michopoulos, V; Rothbaum, A O; Almli, L; Gillespie, C F; Wingo, A; Schwartz, A C; Habib, L; Gamwell, K L; Marvar, P J; Bradley, B; Ressler, K J

    2015-06-01

    Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and fear responses. Common antihypertensive medication classes of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) have been associated with lower PTSD symptoms. Here we examine the rs4311 SNP in the ACE gene, previously implicated in panic attacks, in the relationship between ACE-I/ARB medications and PTSD symptoms. Participants were recruited from outpatient wait rooms between 2006 and March 2014 (n=  803). We examined the interaction between rs4311 genotype and the presence of blood pressure medication on PTSD symptoms and diagnosis. PTSD symptoms were lower in individuals taking ACE-Is or ARBs (N = 776). The rs4311 was associated with PTSD symptoms and diagnosis (N = 3803), as the T-carriers at the rs4311 SNP had significantly greater likelihood of a PTSD diagnosis. Lastly, the rs4311 genotype modified the effect of ACE-Is or ARBs on PTSD symptoms (N = 443; F1,443 = 4.41, P < 0.05). Individuals with the CC rs4311 genotype showed lower PTSD symptoms in the presence of ACE-Is or ARBs. In contrast, T- carriers showed the opposite, such that the presence of ACE-Is or ARBs was associated with higher PTSD symptoms. These data suggest that the renin-angiotensin system may be important in PTSD, as ACE-I/ARB usage associates with lower symptoms. Furthermore, we provide genetic evidence that some individuals are comparatively more benefitted by ACE-Is/ARBs in PTSD treatment. Future research should examine the mechanisms by which ACE-Is/ARBs affect PTSD symptoms such that pharmaco-genetically informed interventions may be used to treat PTSD. PMID:25921615

  6. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span.

    PubMed

    Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

    2016-02-01

    Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabditis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

  7. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span

    PubMed Central

    Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

    2016-01-01

    Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabdtitis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

  8. Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3 enzymes catabolizing bradykinin.

    PubMed

    Beaudouin, E; Defendi, F; Picaud, J; Drouet, C; Ponard, D; Moneret-Vautrin, D A

    2014-05-01

    New concepts of idiopathic and iatrogenic angioedema underline the role of bradykinin, and the importance of catabolizing enzymes. A case is described of Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced angioedema, where AO attacks decreased after the withdrawal of lisinopril but resolved only after the withdrawal of sitagliptin, an inhibitor of dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased down to 17%, 42%, 64% of median references values, and remained low one year after the interruption of these drugs: 56%, 28% and 50%, respectively. The combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP IV inhibitor. The fact that this triple deficiency remained latent before and after the treatment indicates that searching for latent enzyme deficiencies should be carried out when there is intention to treat with a combination of drugs interfering with the bradykinin metabolism. PMID:24853572

  9. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

    PubMed

    Mosley, J D; Shaffer, C M; Van Driest, S L; Weeke, P E; Wells, Q S; Karnes, J H; Velez Edwards, D R; Wei, W-Q; Teixeira, P L; Bastarache, L; Crawford, D C; Li, R; Manolio, T A; Bottinger, E P; McCarty, C A; Linneman, J G; Brilliant, M H; Pacheco, J A; Thompson, W; Chisholm, R L; Jarvik, G P; Crosslin, D R; Carrell, D S; Baldwin, E; Ralston, J; Larson, E B; Grafton, J; Scrol, A; Jouni, H; Kullo, I J; Tromp, G; Borthwick, K M; Kuivaniemi, H; Carey, D J; Ritchie, M D; Bradford, Y; Verma, S S; Chute, C G; Veluchamy, A; Siddiqui, M K; Palmer, C N A; Doney, A; MahmoudPour, S H; Maitland-van der Zee, A H; Morris, A D; Denny, J C; Roden, D M

    2016-06-01

    The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk. PMID:26169577

  10. Exercise-induced ventricular arrhythmias in congestive heart failure and role of ACE inhibitors.

    PubMed

    Hasija, P K; Karloopia, S D; Shahi, B N; Chauhan, S S

    1998-02-01

    Ventricular arrhythmias are considered to be related to left ventricular (LV) dysfunction. ACE inhibitors though improve LV function their beneficial role on exercise-induced ventricular arrhythmias is not established. To study the effects of ACE inhibitors on exercise capacity vis-a-vis their role on exercise-induced ventricular arrhythmias, 25 patients of congestive heart failure (CHF) of various etiologies in NYHA Class II and III were subjected to a prospective randomised controlled trial. The control group comprising of 12 patients received conventional treatment (digitalis and diuretics) and the test group was given enalapril/captopril in addition as tolerated. They were followed up for 3 months. Exercise testing on treadmill and monitoring of clinical and biochemical parameters were done at the beginning and end of study in all cases. Ventricular arrhythmias observed during exercise and post-exercise for 10 minutes was analysed using Lown's grading for frequency and severity of ventricular arrhythmia. The mean exercise duration showed significant improvement on ACE inhibitor as compared to the control group (p < 0.05) however there was no significant change in the grades of arrhythmia. Serum electrolytes and other bio-chemical parameter were within normal range. It is concluded that effect of ACE inhibitor on improving functional capacity in CHF is independent of it's any effect on exercise-induced ventricular arrhythmias. PMID:11273109

  11. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

    PubMed Central

    Mosley, J D; Shaffer, C M; Van Driest, S L; Weeke, P E; Wells, Q S; Karnes, J H; Velez Edwards, D R; Wei, W-Q; Teixeira, P L; Bastarache, L; Crawford, D C; Li, R; Manolio, T A; Bottinger, E P; McCarty, C A; Linneman, J G; Brilliant, M H; Pacheco, J A; Thompson, W; Chisholm, R L; Jarvik, G P; Crosslin, D R; Carrell, D S; Baldwin, E; Ralston, J; Larson, E B; Grafton, J; Scrol, A; Jouni, H; Kullo, I J; Tromp, G; Borthwick, K M; Kuivaniemi, H; Carey, D J; Ritchie, M D; Bradford, Y; Verma, S S; Chute, C G; Veluchamy, A; Siddiqui, M K; Palmer, C N A; Doney, A; MahmoudPour, S H; Maitland-van der Zee, A H; Morris, A D; Denny, J C; Roden, D M

    2016-01-01

    The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2–1.4), P=1.0 × 10−8). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01–1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01–1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15–1.32), P=1.9 × 10−9). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk. PMID:26169577

  12. Acute abdomen due to intestinal angioedema induced by ACE inhibitors: not so rare?

    PubMed

    Dobbels, P; Van Overbeke, L; Vanbeckevoort, D; Hiele, M

    2009-01-01

    During the last 5 years we identified 7 patients with a history of episodic acute abdominal pain and subobstruction due to intestinal angioedema secondary to the use of Angiotensin Converting Enzyme (ACE) inhibitors. These cases were all diagnosed in one gastroenterology department. This is thereby the largest single centre case series of ACE inhibitor-induced angioedema that has been published until now. Our findings suggest that this syndrome is far more frequent than international literature would let us believe. We also describe one of the first male cases diagnosed with this entity for which there is a significant female predominance. In the presence of an appropriate history and suggestive findings on CT scan, this diagnosis can relatively easily be made if one is sufficiently intent on it. An appropriate diagnosis can save these patients a lot of unnecessary diagnostic procedures and discomfort. PMID:20163043

  13. Investigation of interaction studies of cefpirome with ACE-inhibitors in various buffers

    NASA Astrophysics Data System (ADS)

    Nawaz, Muhammad; Arayne, Muhammad Saeed; Sultana, Najma; Abbas, Hira Fatima

    2015-02-01

    This work describes a RP-HPLC method for the determination and interaction studies of cefpirome with ACE-inhibitors (captopril, enalapril and lisinopril) in various buffers. The separation and interaction of cefpirome with ACE-inhibitors was achieved on a Purospher Star, C18 (5 μm, 250 × 4.6 mm) column. Mobile phase consisted of methanol: water (80:20, v/v, pH 3.3); however, for the separation of lisinopril, it was modified to methanol-water (40:60, v/v, pH 3.3) and pumped at a flow rate of 1 mL min-1. In all cases, UV detection was performed at 225 nm. Interactions were carried out in physiological pH i.e., pH 1 (simulated gastric juice), 4 (simulated full stomach), 7.4 (blood pH) and 9 (simulated GI), drug contents were analyzed by reverse phase high performance liquid chromatography. Method was found linear in the concentration range of 1.0-50.0 μg mL-1 with correlation coefficient (r2) of 0.999. Precision (RSD%) was less than 2.0%, indicating good precision of the method and accuracy was 98.0-100.0%. Furthermore, cefpirome-ACE-inhibitors' complexes were also synthesized and results were elucidated on the basis of FT-IR, and 1H NMR. The interaction results show that these interactions are pH dependent and for the co-administration of cefpirome and ACE-inhibitors, a proper interval should be given.

  14. Application of quantitative NMR for purity determination of standard ACE inhibitors.

    PubMed

    Shen, Shi; Yang, Xing; Shi, Yaqin

    2015-10-10

    This study investigated the accuracy of the quantitative NMR method for purity determination of ACE inhibitors reference standards and the discovery of two pairs of new diastereoisomers. Six types of ACE inhibitors, imidapril hydrochloride, benazepril hydrochloride, lisinopril, enalapril maleate, quinapril hydrochloride, and captopril were quantificated and validated for the qNMR method by discussing factors that affect parameters of the qNMR experiment, internal standards, integration, pH-effect, and uncertainty. The results were compared with data obtained by the mass balance method. The study found that maleic acid influenced the quantification of captopril in deuteroxide because of a chemical reaction. The mixtures of the reaction products were isolated by HPLC and structurally elucidated by NMR as two pairs of new diastereoisomers, 1-[(2S,4R)-thio-2-methylpropionyl-5-d-ethanedicarboxylicacid]-L-proline and 1-[(2S,4S)-thio-2-methylpropionyl-5-d-ethanedicarboxylicacid]-L-proline. The results showed that the accuracy and precision of quantitative (1)H NMR spectroscopy satisfied the requirements for quantitative analysis of chemical reference standards and provided a simple, rapid, and reliable method for purity determination of ACE inhibitors systematically. PMID:26070161

  15. Binding of ACE-inhibitors to in vitro and patient-derived amyloid-β fibril models

    NASA Astrophysics Data System (ADS)

    Bhavaraju, Manikanthan; Phillips, Malachi; Bowman, Deborah; Aceves-Hernandez, Juan M.; Hansmann, Ulrich H. E.

    2016-01-01

    Currently, no drugs exist that can prevent or reverse Alzheimer's disease, a neurodegenerative disease associated with the presence, in the brain, of plaques that are composed of β-amyloid (Aβ) peptides. Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors, a set of drugs used to treat hypertension, may inhibit amyloid formation in vitro. In the present study, we investigate through computer simulations the binding of ACE inhibitors to patient-derived Aβ fibrils and contrast it with that of ACE inhibitors binding to in vitro generated fibrils. The binding affinities of the ACE inhibitors are compared with that of Congo red, a dye that is used to identify amyloid structures and that is known to be a weak inhibitor of Aβ aggregation. We find that ACE inhibitors have a lower binding affinity to the patient-derived fibrils than to in vitro generated ones. For patient-derived fibrils, their binding affinities are even lower than that of Congo red. Our observations raise doubts on the hypothesis that these drugs inhibit fibril formation in Alzheimer patients by interacting directly with the amyloids.

  16. The binding of metal ions and angiotensin converting enzyme (ACE) inhibitor by 13C NMR

    NASA Astrophysics Data System (ADS)

    Sakamoto, Yohko; Sakamoto, Yuko; Ishii, Tomoko; Ohmoto, Taichi

    1991-06-01

    Enalaprilat (MK-422, 1- [ N- [1 (S)-carboxy-3-phenylpropyl]- L-alanyl]- L-proline (1)) and Lisinopril (MK521, N- N- [ (s)-l-carboxy-3- phenylpropyl]- L-lysyl- L-proline, (2)) exhibit the capacity to act as a chelate, unidentate or bridge towards metal ions in aqueous solution, as determined by 13C NMR. By adding metal ions, in the series of Zn 2+, Ni 2+, Pb 2+, Pd 2+ and Cd 2+, the active site of the ACE inhibitor was well defined. MK-521 was more influenced by nuclei that were distant from the active site than MK-422.

  17. ACE inhibitors

    MedlinePlus

    ... Clinical Cardiology; American Heart Association Council on Nutrition, Physical Activity, and Metabolism; American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research. State of the science: promoting self-care in persons with heart failure: ...

  18. ACE inhibitors

    MedlinePlus

    ... your dose helps. But sometimes your doctor will switch you to a different medication. Do not lower ... American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation . 2013 Oct 15; ...

  19. Comparison of the Efficacy and Safety of Different ACE Inhibitors in Patients With Chronic Heart Failure: A PRISMA-Compliant Network Meta-Analysis.

    PubMed

    Sun, WeiPing; Zhang, HaiBin; Guo, JinCheng; Zhang, XueKun; Zhang, LiXin; Li, ChunLei; Zhang, Ling

    2016-02-01

    Heart failure is a public health problem and a great economic burden for patients and healthcare systems. Suppression of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE)-inhibitors remains the mainstay of treatment for heart failure. However, the abundance of ACE inhibitors makes it difficult for doctors to choose.We performed this network meta-analysis of ACEIs in patients with heart failure in order to address this area of uncertainty.We searched PubMed, Embase, CENTRAL, and Medline.Any randomized controlled trial evaluating the efficacy and safety of captopril, enalapril, lisinopril, ramipril, or trandolapril or combined interventions of 2 or more of these drugs.Two reviewers extracted the data and made the quality assessment. At first, we used Stata software (version 12.0, StataCorp, College Station, TX) to make traditional pairwise meta-analyses for studies that directly compared different interventions. Then, network meta-analysis was performed using WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).A total of 29 studies were included. Lisinopril was associated with a higher rate of all-cause mortality compared with placebo (odds ratio 65.9, 95% credible interval 1.91 to 239.6) or ramipril (14.65, 1.23 to 49.5). Enalapril significantly reduced systolic blood pressure when compared with placebo (standardized mean differences -0.6, 95% credible interval -1.03 to -0.18). Both captopril (odds ratio 76.2, 95% credible interval 1.56 to 149.3) and enalapril (274.4, 2.4 to 512.9) were associated with a higher incidence of cough compared to placebo.Some important outcomes such as rehospitalization and cardiac death were not included. The sample size and the number of studies were limited, especially for ramipril.Our results suggest that enalapril might be the best option when considering factors such as increased ejection fraction, stroke volume, and decreased mean arterial pressure. However, enalapril was associated with the

  20. [The new drug is much more effective than ACE inhibitors in chronic heart failure].

    PubMed

    Sr, Jiří Widimský

    2015-02-01

    PARADIGM-HF study observed clinical outcomes after treatment by new drug LCZ696 or enalapril in patients with systolic chronic heart failure. It was randomized double-blind trial with LCZ696 (200 mg twice a day) and enalapril (10 mg twice a day). 8442 patients were enrolled with NYHA class II or III and left ventricular ejection fiction of 40% or less. Study drugs were added to other recommended medication. The trial was prematurely terminated after median follow-up of 27 months. The primary endpoint of the study was a combination of cardiovascular mortality and the first hospitalization for heart failure. LCZ696 drug, an inhibitor of angiotensin receptor and neprilysin (Arnie), has led to a reduction in the primary composite target by 20% (p <0.001). The treatment has decreased cardiovascular mortality by 20%, p <0.001 and hospitalization for worsening heart failure by 21%, p <0.001. LCZ696 has also decreased total mortality by 16%, p <0.001. The use of LCZ696 has been accompanied by frequent symptomatic hypotension and hypotension with a decrease in systolic blood pressure below 90 mm Hg, however, LCZ696 was less often associated with an increase in serum creatinine and serum potassium than enalapril. In addition, cough has occurred less frequently after LCZ696 than after enalapril. Discontinuation of therapy occurred in 746 patients (17.8%) treated with LCZ696 and in 833 patients (19.8%) treated with enalapril (19.8%) (p = 0.02). PARADIGM-HF study has also shown superiority of LCZ696 compared to ACE inhibitors in stable outpatients with chronic systolic heart failure NYHA stages II and III. Therefore, LCZ696 is more effective than ACE inhibitors (and angiotensin receptor blockers). Moreover, it is well tolerated. LCZ696 seems to replace the ACE inhibitors in mentioned patients. The authors also discuss the results of the first randomized study PARAMOUNT investigating LCZ696 efficacy in patients with chronic heart failure and good left ventricular ejection

  1. Angiotensin-converting enzyme gene insertion/deletion, not bradykinin B2 receptor -58T/C gene polymorphism, associated with angiotensin-converting enzyme inhibitor-related cough in Chinese female patients with non-insulin-dependent diabetes mellitus.

    PubMed

    Lee, Y J; Tsai, J C

    2001-11-01

    To investigate the genetic susceptibility associated with cough related to angiotensin-converting enzyme inhibitor (ACEI) therapy in patients with type 2 diabetes, 189 non-insulin-dependent diabetes mellitus (NIDDM) patients with proteinuria or hypertension treated with perindopril were studied. Cough was considered to be present if the patients had been bothered by a cough during treatment and if they had had related symptoms for at least 2 weeks without an identifiable cause. Polymerase chain reaction (PCR) coupled with single-strand conformation polymorphism (SSCP) was used to detect polymorphisms of ACE and bradykinin B2-receptor genes. After 8 weeks of treatment, 49.2% (93 of 189) of our NIDDM patients were found to be suffering from ACEI-related cough. ACEI-related cough was mainly associated with female patients, with 71.7% (76 of 106) of female and only 20.5% (17 of 83) of male patients experiencing cough after ACEI treatment. There was a significant association of ACE II genotype with ACEI-related cough. The genotype frequencies were 58.2% for II, 47.8% for ID, and 16.7% for DD in patients with ACEI-associated cough and 41.8% for II, 52.2% for ID, and 83.3% for DD in subjects without ACEI-associated cough (chi(2) = 10.268; df = 2, P =.006). As female patients made up the majority of the subjects suffering from ACEI-related cough, we further analyzed the association of ACE I/D genotype with ACEI-related cough separately by sex. Male patients with ACEI-related cough were not associated with ACE I/D genotype distribution, while female patients were strongly associated with ACE I/D genotype polymorphism (chi(2) = 16.12; df = 2; P <.001). There was no association between the bradykinin B2 receptor gene -58T/C polymorphism with ACEI-related cough. In conclusion, our results indicate that Chinese diabetic female subjects are susceptible to ACEI-related cough, and this susceptibility may be genetically predetermined. PMID:11699055

  2. Choice of ACE inhibitor combinations in hypertensive patients with type 2 diabetes: update after recent clinical trials

    PubMed Central

    Reboldi, Gianpaolo; Gentile, Giorgio; Angeli, Fabio; Verdecchia, Paolo

    2009-01-01

    The diabetes epidemic continues to grow unabated, with a staggering toll in micro- and macrovascular complications, disability, and death. Diabetes causes a two- to fourfold increase in the risk of cardiovascular disease, and represents the first cause of dialysis treatment both in the UK and the US. Concomitant hypertension doubles total mortality and stroke risk, triples the risk of coronary heart disease and significantly hastens the progression of microvascular complications, including diabetic nephropathy. Therefore, blood pressure reduction is of particular importance in preventing cardiovascular and renal outcomes. Successful antihypertensive treatment will often require a combination therapy, either with separate drugs or with fixed-dose combinations. Angiotensin converting enzyme (ACE) inhibitor plus diuretic combination therapy improves blood pressure control, counterbalances renin-angiotensin system activation due to diuretic therapy and reduces the risk of electrolyte alterations, obtaining at the same time synergistic antiproteinuric effects. ACE inhibitor plus calcium channel blocker provides a significant additive effect on blood pressure reduction, may have favorable metabolic effects and synergistically reduce proteinuria and the rate of decline in glomerular filtration rate, as evidenced by the GUARD trial. Finally, the recently published ACCOMPLISH trial showed that an ACE inhibitor/calcium channel blocker combination may be particularly useful in reducing cardiovascular outcomes in high-risk patients. The present review will focus on different ACE inhibitor combinations in the treatment of patients with type 2 diabetes mellitus and hypertension, in the light of recent clinical trials, including GUARD and ACCOMPLISH. PMID:19475778

  3. A role for the extracellular matrix component hyaluronan in kidney dysfunction during ACE-inhibitor fetopathy.

    PubMed

    Hansell, P; Palm, F

    2015-04-01

    Despite data showing that inhibitors of the renin-angiotensin system increase the risks of fetal morbidity and dysfunctionality later in life, their use during pregnancy has increased. The fetopathy induced by angiotensin converting enzyme (ACE) inhibitors is characterized by anuria, hypotension and growth restriction, but can also be associated with pulmonary hypoplasia. In the kidney, this fetopathy includes atrophy of the medulla, reduced number of glomeruli, developmental lesions of tubules and vessels, tubulointerstitial inflammation and extracellular matrix accumulation. Although angiotensin II (Ang II) inhibition during nephrogenesis interferes with normal growth and development, this review will focus on effects of the heavily accumulated matrix component hyaluronan (HA). An important mechanism of HA accumulation during nephrogenesis is disruption of its normal reduction as a consequence of lack of Ang II activation of hyaluronidase. Hyaluronan has very large water-attracting properties and is pro-inflammatory when fragmented. The ensuing inflammation and interstitial oedema affect kidney function. Hyaluronan is colocalized with CD44 overexpression and infiltrating immune cells. These properties make HA a plausible contributor to the observed structural and functional kidney defects associated with the fetopathy. Available data support an involvement of HA in kidney dysfunction of the foetus and during adulthood due to the physico-chemical characteristics of HA. No clinical treatment for HA accumulation exists. Treatment with the HA-degrading enzyme hyaluronidase and an HA synthesis inhibitor has been tested successfully in experimental models in the kidney, heart and pancreas. Reduced HA accumulation to reduce interstitial oedema and inflammation may improve organ function, but this concept needs to be tested in a controlled study before causal relationships can be established. PMID:25600777

  4. Preclinical development and characterization of an intravenous dosage form for the ACE inhibitor RS-10029.

    PubMed

    Visor, G C; Lin, L H; Henry, P; Singer, L

    1989-01-01

    Preclinical development of an intravenous dosage form for the ACE inhibitor RS-10029 involved the formulation and characterization of the drug's chemical/physical stability in two prototype formulations (injectable solution and lyophilized powder). Included in these studies were quantitative evaluations of various processing and administration parameters (membrane qualification, terminal sterilization, compatibility/delivery of the drug with typical infusion fluids and administration sets) on finished product integrity and quality. Analytical methodology used in these studies consisted primarily of a stability specific HPLC assay and a light obscuration based sensor (HIAC) for particulate matter analysis. Results of these studies indicate that the drug is relatively stable at ambient temperature and under accelerated storage conditions (predicted T90 at 25 degrees C greater than 2 yr, and T90 at 50 degrees C greater than 2 mo). However, the ability of the product to withstand a full terminal sterilization cycle is limited, and therefore other approaches toward sterile processing were examined. With regard to the stability and compatibility of the drug in a variety of fluids and devices there appears to be no overt limitations in its use for either bolus or infusion delivery. PMID:2600732

  5. Cardiovascular risk reduction by reversing endothelial dysfunction:ARBs, ACE inhibitors, or both? Expectations from The ONTARGET Trial Programme

    PubMed Central

    Ruilope, Luis Miguel; Redón, Josep; Schmieder, Roland

    2007-01-01

    Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008. PMID:17583170

  6. Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay

    PubMed Central

    2013-01-01

    Background and purpose of the study Angiotensin converting enzyme (ACE) inhibitors plays a critical role in treating hypertension. The purpose of the present investigation was to evaluate ACE inhibition activity of 50 Iranian medicinal plants using an in vitro assay. Methods The ACE activity was evaluated by determining the hydrolysis rate of substrate, hippuryl-L-histidyl-L-leucine (HHL), using reverse phase high performance liquid chromatography (RP-HPLC). Total phenolic content and antioxidant activity were determined by Folin-Ciocalteu colorimetric method and DPPH radical scavenging assay respectively. Results Six extracts revealed > 50% ACE inhibition activity at 330 μg/ml concentration. They were Berberis integerrima Bunge. (Berberidaceae) (88.2 ± 1.7%), Crataegus microphylla C. Koch (Rosaceae) (80.9 ± 1.3%), Nymphaea alba L. (Nymphaeaceae) (66.3 ± 1.2%), Onopordon acanthium L. (Asteraceae) (80.2 ± 2.0%), Quercus infectoria G. Olivier. (Fagaceae) (93.9 ± 2.5%) and Rubus sp. (Rosaceae) (51.3 ± 1.0%). Q. infectoria possessed the highest total phenolic content with 7410 ± 101 mg gallic acid/100 g dry plant. Antioxidant activity of Q. infectoria (IC50 value 1.7 ± 0.03 μg/ml) was more than that of BHT (IC50 value of 10.3 ± 0.15 μg/ml) and Trolox (IC50 value of 3.2 ± 0.06 μg/ml) as the positive controls. Conclusions In this study, we introduced six medicinal plants with ACE inhibition activity. Despite the high ACE inhibition and antioxidant activity of Q. infectoria, due to its tannin content (tannins interfere in ACE activity), another plant, O. acanthium, which also had high ACE inhibition and antioxidant activity, but contained no tannin, could be utilized in further studies for isolation of active compounds. PMID:24359711

  7. Angioedema of the lips and tongue induced by angiotensin-converting enzyme inhibitor. A report of two cases.

    PubMed

    Stevenson, Helen A; Steele, John C; Field, E Anne; Darroch, Campbell J

    2004-01-01

    The following case reports describe the clinical presentation, diagnosis and management of two patients who attended Liverpool University Dental Hospital with rapidly increasing swelling of the lips and tongue. Both patients were suffering from angioedema and were taking an angiotension-converting enzyme (ACE) inhibitor (ACEI). A provisional diagnosis of ACEI-induced angioedema was made. An intramuscular injection of chlorpheniramine maleate was given to both patients and they were immediately transferred to the local accident and emergency department. These cases illustrate the potential role of the general dental practitioner in the early recognition and management of this potentially life-threatening condition. PMID:14768205

  8. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

    PubMed Central

    Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

    2015-01-01

    Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID:26540279

  9. Anti-Resorptive Activity of Anti-Hypertensive Agent ACEi in Older Men

    NASA Technical Reports Server (NTRS)

    Rianon, Nahid; Edwards, BeJier; Nhonthachit, Phetsamong; Messick, Amanda; Gagel, Robert; Smith, Scott M.

    2016-01-01

    Hypertension (HTN) is associated with bone loss due to activation of the renin- angiotensin system (RAS) which in turn affects bone turnover. Animal studies have shown decreased bone resorption (up to 19%) and increased bone mass (up to 2%) following treatment with RAStargeted antihypertensive medications (e.g., angiotensin converting enzyme inhibitors, ACEi). Cross-sectional human studies have documented greater femoral neck BMD in older hypertensive men and women treated with ACEi compared to those not-treated with ACEi (nor other RAS-targeted medications). These findings raise the potential for ACEi use in preventing, or at a minimum slowing bone loss due to age or even microgravity. Based on this, we conducted a cohort study to investigate if ACEi treatment would decrease bone resorption in humans. We investigated changes in serum CTX and P1NP in 10 hypertensive men (45 years or older) treated with (N=5) without (N=5) exposure to ACEi for 3-months. Lisinopril was the ACEi used, and dose was adjusted as deemed appropriate by the attending physicians. Participants did not have any known skeletal health problem and were not exposed to any bisphosphonates or hydrochlorothiazides. A small sample size prevented detailed statistical analysis and hence, we present a preliminary descriptive report of our findings. Participants' age was 57+/-7 years (mean +/-SD), baseline body mass index was 27+/-5 kg/sq m, serum concentration of 25-hydroxyvitamin D was 66+/-17 nmol/L and parathyroid hormone was 30+/-13 pg/ml. After Lisinopril treatment, men demonstrated a 10% decrease in the bone resorption marker C-terminal telopeptide (CTX) and 5% decrease in formation marker procollagen type 1 amino-terminal pro-peptide (P1NP). On the contrary, serum CTX increased 41% and P1NP increased 10% in those who were not treated with ACEi. This is the first human study to report reduction in bone resorptive activity following ACEi treatment for hypertension in older men. Our results indicates

  10. Help Strengthen ACEI's Voice for Children Worldwide

    ERIC Educational Resources Information Center

    Odland, Jerry

    2005-01-01

    The Association for Childhood Education International (ACEI) is among the oldest professional education organizations in the world and the only international organization of its kind that focuses on the development of the whole child from birth through early adolescence. Given the current sad state of world affairs and the plight of millions of…

  11. On Standardized Testing: An ACEI Position Paper

    ERIC Educational Resources Information Center

    Solley, Bobbie A.

    2007-01-01

    Following the whirlwind standards movement of the 1980s, the beginning of the 1990s ushered in an overwhelming interest in and use of testing to document students' progress. In 1991, the Association for Childhood Education International (ACEI) issued its second position paper calling for a moratorium on standardized testing in the early years of…

  12. West Tennessee ACEI 2006 Fall Conference

    ERIC Educational Resources Information Center

    Clifford, Anna; Hailey, Beth

    2007-01-01

    This article presents the West Tennessee ACEI 2006 Fall Conference held at Union University in Jackson, Tennessee on October 14, 2006. The conference theme, Turning the Pages: A Focus on Children's Literature, was emphasized throughout the day. During the conference, the early childhood classroom teachers, preservice teachers, and administrators…

  13. [Liver damage in a patient treated with a vitamin K antagonist, a statin and an ACE inhibitor].

    PubMed

    Bruggisser, M; Terraciano, L; Rätz Bravo, A; Haschke, M

    2010-10-20

    We report the case of a 71-year-old male patient who presented at the emergency room with episodes of epistaxis and jaundice. The patient was on therapy with phenprocoumon, atorvastatin and perindopril. Findings on admission included prominent elevation of transaminases and bilirubin and a high INR due to impaired liver function and oral anticoagulation. After exclusion of other causes like viral or autoimmune hepatitis and after having obtained a liver biopsy, a diagnosis of drug induced liver damage (DILI) was made. Epidemiology, pathophysiology and clinical signs of DILI are discussed with a special focus on coumarines, statins and ACE-inhibitors. PMID:20960395

  14. EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy – rationale and design of the EARLY hypertension registry

    PubMed Central

    2013-01-01

    Background Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. Methods/Design The “Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy” (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. Conclusions The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice. PMID:23819631

  15. Ace inhibitor therapy for heart failure in patients with impaired renal function: a review of the literature.

    PubMed

    Valika, Ali A; Gheorghiade, Mihai

    2013-03-01

    Heart failure syndromes are often associated with multi-organ dysfunction, and concomitant liver, renal, and neurologic involvement is very common. Neuro-hormonal antagonism plays a key role in the management of this syndrome, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are one of the cornerstones of therapy. Cardiorenal physiology is becoming more recognized in these patients with advanced heart failure, and the role of neuro-hormonal blockade in this setting is vaguely defined in the literature. Often, angiotensin-converting enzyme inhibitors are decreased or even withheld in these circumstances. The purpose of this article is to review the role and pathophysiology of ace inhibition and angiotensin receptor blockade in patients with acute and chronic heart failure syndromes and concomitant cardiorenal physiology. PMID:22213014

  16. Identification of a new angiotensin-converting enzyme (ACE) inhibitor from Thai edible plants.

    PubMed

    Simaratanamongkol, Arunee; Umehara, Kaoru; Noguchi, Hiroshi; Panichayupakaranant, Pharkphoom

    2014-12-15

    Eight Thai edible plants were tested for their inhibitory activity against an angiotensin-converting enzyme (ACE) using an in vitro assay. The methanol extract of Apium graveolens exhibited significant ACE inhibitory activity with an IC50 value of 1.7 mg/ml, and was then subjected to an isolation procedure that resulted in identification of a pure active constituent, junipediol A 8-O-β-d-glucoside (1-β-d-glucosyloxy-2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol) (1), which had good ACE inhibitory activity with an IC50 value of 76 μg/ml. Another eight known compounds, isofraxidin-β-d-glucoside (2), roseoside (3), apigenin-7-O-β-d-glucoside (4), luteolin-7-O-β-d-glucoside (5), icariside D2 (6), apiin (7), chrysoeriol-7-O-β-d-apiosylglucoside (8), and 11,21-dioxo-3 β,15 α,24-trihydroxyurs-12-ene-24-O-β-d-glucopyranoside (9) were also identified. Although each of these five constituents (2-6) isolated from the same fraction as 1 showed no activity at concentrations of 500 μM, together, when each was present at 300 μg/ml, they enhanced the inhibitory activity of 500 μM of 1 from 64% to 81%. PMID:25038653

  17. Refill Adherence in Relation to Substitution and the Use of Multiple Medications: A Nationwide Population Based Study on New ACE-Inhibitor Users

    PubMed Central

    Jönsson, Anna K.; Lesén, Eva; Mårdby, Ann-Charlotte; Sundell, Karolina Andersson

    2016-01-01

    Objective Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden. Study Design and Setting New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. Results The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. Conclusion The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications. PMID:27192203

  18. The effects of drug market regulation on pharmaceutical prices in Europe: overview and evidence from the market of ACE inhibitors

    PubMed Central

    2011-01-01

    This study provides an overview of policy measures targeting pharmaceutical expenditure in Europe and analyses their impact on originator pharmaceutical prices. Panel data methods are used to examine the market of ACE Inhibitors in six European countries (Denmark, France, Germany, Netherlands, Sweden, United Kingdom) over period 1991-2006. We find that although some measures are effective in reducing originator prices, others appear to have an insignificant effect. Results suggest that supply side measures such as mandatory generic substitution, regressive pharmacy mark-ups and claw-backs are effective in reducing pharmaceuticals prices. Results are not as strong for demand side measures. Profit controls and the use of cost-effectiveness analysis appear to have a negative effect on prices, while results on reference pricing are inconclusive. Findings also indicate that, although originator prices are not immediately affected by generic entry, they may be influenced by changes in generic prices post patent expiry. PMID:22828053

  19. The ACE inhibitor ( sup 3 H)SQ29,852 identifies a high affinity recognition site located in the human temporal cortex

    SciTech Connect

    Barnes, N.M.; Costall, B.; Egli, P.; Horovitz, Z.P.; Ironside, J.W.; Naylor, R.J.; Williams, T.J. )

    1990-07-01

    The angiotensin converting enzyme (ACE) inhibitor ({sup 3}H)SQ29,852 identified a single high affinity recognition site (defined by 10.0 microM captopril) in the human temporal cortex (pKD 8.62 +/- 0.03; Bmax 248 +/- 24 fmol mg-1 protein, mean +/- S.E.M., n = 4). ACE inhibitors and thiorphan competed to a similar level for the ({sup 3}H)SQ29,852 binding site in the human temporal cortex with a rank order of affinity (pKi values mean +/- S.E.M., n = 3), lisinopril (9.49 +/- 0.02), captopril (9.16 +/- 0.08), SQ29,852 (8.58 +/- 0.04), epicaptopril (7.09 +/- 0.08), fosinopril (7.08 +/- 0.05) and thiorphan (6.40 +/- 0.04). Since this rank order of affinity is similar to the affinity of these compounds to inhibit brain ACE activity it is concluded that ({sup 3}H)SQ29,852 selectively labels the inhibitor recognition site of ACE in the human temporal cortex.

  20. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition.

    PubMed

    Gonzalez-Villalobos, Romer A; Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C; Katsurada, Akemi; Kim, Catherine; Upchurch, G M; Prieto, Minolfa C; Kobori, Hiroyuki; Navar, L Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT(1)R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9-12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng x kg(-1) x min(-1) for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 +/- 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 +/- 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 +/- 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 +/- 0.07, P < 0.05) or in combination with ANG II (0.80 +/- 0.07, P < 0.05). AT(1)R protein (by WB) was increased by ANG II (1.27 +/- 0.06, P < 0.05) and ACEi (1.17 +/- 0.06, P < 0.05) but not ANG II + ACEi [1.15 +/- 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 +/- 0.23, P < 0.05) and ACEi (1.57 +/- 0.15, P < 0.05), but not ANG II + ACEi (1.10 +/- 0.15, NS). No significant changes were observed in AGT, ACE, or AT(1)R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT(1)R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  1. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

    PubMed Central

    Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C.; Katsurada, Akemi; Kim, Catherine; Upchurch, G. M.; Prieto, Minolfa C.; Kobori, Hiroyuki; Navar, L. Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  2. Scleroderma renal crisis during intravenous cyclophosphamide pulse therapy for complicated interstitial lung disease was successfully treated with angiotensin converting enzyme inhibitor and plasma exchange

    PubMed Central

    Nagamura, Norihiro; Kin, Seikon

    2016-01-01

    ABSTRACT Systemic sclerosis (SSc) is a multiorgan disorder involving the skin, heart, lungs, kidneys, and intestines. Progressive interstitial lung disease (ILD) is a serious complication in SSc patients, and cyclophosphamide (CYC) is the only recommended therapy for this condition;1) however, its clinical effectiveness is not sufficient. Scleroderma renal crisis (SRC) is a rare complication, characterized by acute renal failure and progressive hypertension. Angiotensin-converting-enzyme inhibitor (ACE-i) is a widely accepted therapy for SRC. We report an SSc patient with SRC and progressive ILD who underwent treatment with CYC and successful treatment with ACE-i and plasma exchange (PE). SRC and ILD are significant contributors to morbidity and mortality among SSc patients, and the therapy for these disorders is of great interest to rheumatologists. This study presents the possibility of favorable effects of PE for SSc-associated ILD and SRC. PMID:27578917

  3. Scleroderma renal crisis during intravenous cyclophosphamide pulse therapy for complicated interstitial lung disease was successfully treated with angiotensin converting enzyme inhibitor and plasma exchange.

    PubMed

    Nagamura, Norihiro; Kin, Seikon

    2016-08-01

    Systemic sclerosis (SSc) is a multiorgan disorder involving the skin, heart, lungs, kidneys, and intestines. Progressive interstitial lung disease (ILD) is a serious complication in SSc patients, and cyclophosphamide (CYC) is the only recommended therapy for this condition;(1)) however, its clinical effectiveness is not sufficient. Scleroderma renal crisis (SRC) is a rare complication, characterized by acute renal failure and progressive hypertension. Angiotensin-converting-enzyme inhibitor (ACE-i) is a widely accepted therapy for SRC. We report an SSc patient with SRC and progressive ILD who underwent treatment with CYC and successful treatment with ACE-i and plasma exchange (PE). SRC and ILD are significant contributors to morbidity and mortality among SSc patients, and the therapy for these disorders is of great interest to rheumatologists. This study presents the possibility of favorable effects of PE for SSc-associated ILD and SRC. PMID:27578917

  4. Cardiorespiratory effects of continuous i.v. administration of the ACE inhibitor enalaprilat in the critically ill.

    PubMed Central

    Boldt, J; Müller, M; Heesen, M; Härter, K; Hempelmann, G

    1995-01-01

    1. Cardiorespiratory effects of long-term, continuous i.v. administration of the ACE inhibitor enalaprilat were studied. 2. Forty-five consecutive critically patients suffering from trauma or postoperative complications were randomly separated into three groups (15 patients in each group) receiving either 0.25 mg h-1 or 0.50 mg h-1 enalaprilat, respectively, or saline solution as placebo (= control group). The infusion was continued for 5 days. 3. Haemodynamic and respiratory parameters were intensively monitored on admission to the intensive care unit (= 'baseline' values) and daily during the next 5 days. 4. Mean arterial blood pressure (MAP) decreased significantly only in the enalaprilat-treated patients, whereas heart rate (HR) remained unchanged in these patients. 5. Pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressure (PAP) were decreased by enalaprilat (0.50 mg h-1: PAP (mean +/- s.d.) decreased from 28.0 +/- 4.1 to 24.0 +/- 3.0 mm Hg) and remained significantly lower than in the control group. In the untreated control group, cardiac index (CI), oxygen consumption (VO2I) and oxygen delivery (DO2I) significantly decreased, which was blunted by enalaprilat infusion. Oxygen extraction (O2-extr) increased in both enalaprilat groups (0.25 mg h-1: from 26.1 +/- 5.5 to 30.4 +/- 4.0%; 0.50 mg h-1: 25.2 +/- 5.6 to 30.9 +/- 4.4%) and decreased in the control patients. 6. Right ventricular haemodynamics improved by enalaprilat infusion (0.50 mg h-1: RVEF increased from 40.0 +/- 3.5 to 45.5 +/- 4.0%). Lactate plasma concentrations decreased in the group with 0.50 mg h-1 enalaprilat (from 1.9 +/- 1.0 to 1.3 +/- 0.3 mg dl-1) and increased in the control patients. 7. Continuous infusion of the ACE inhibitor enalaprilat exerted beneficial cardiorespiratory effects in the critically ill. The widespread common risk of altered perfusion with decreased CI, DO2, VO2, O2-extr and increased lactate concentration was blunted by enalaprilat infusion. 8. Although

  5. Risk of Hospitalized Gastrointestinal Bleeding in Persons Randomized to Diuretic, ACE-Inhibitor, or Calcium-Channel Blocker in ALLHAT

    PubMed Central

    Phillips, William; Piller, Linda B.; Williamson, Jeff D.; Whittle, Jeffrey; Jafri, Syed Z.A.; Ford, Charles E.; Einhorn, Paula T.; Oparil, Suzanne; Furberg, Curt D.; Grimm, Richard H.; Alderman, Michael H.; Davis, Barry R.; Probstfield, Jeffrey L.

    2013-01-01

    Calcium channel-blockers (CCB) are an important class of medication useful in the treatment of hypertension. Several observational studies have suggested an association between CCB therapy and gastrointestinal hemorrhage. Using administrative databases, we re-examined in a post-hoc analysis whether the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants randomized to the calcium-channel blocker amlodipine had a greater risk of hospitalized gastrointestinal bleeding (a pre-specified outcome) compared to those randomized to the diuretic chlorthalidone or the ACE-inhibitor lisinopril. Participants randomized to chlorthalidone did not have a reduced risk for gastrointestinal bleeding hospitalizations compared to participants randomized to amlodipine (HR, 1.09, 95% CI 0.92-1.28). Those randomized to lisinopril were at increased risk of gastrointestinal bleeding compared those randomized to chlorthalidone (HR, 1.16; 95% CI, 1.00-1.36). In a post-hoc comparison, participants assigned lisinopril therapy had a higher risk of hospitalized gastrointestinal hemorrhage (HR,1.27, 95% CI 1.06-1.51) versus those assigned to amlodipine. In-study use of atenolol prior to first gastrointestinal hemorrhage was related to a lower incidence of GI bleeding (HR, 0.69; 95% CI, 0.57-0.83). In conclusion, hypertensive patients on amlodipine do not have an increased risk of GI bleeding hospitalizations compared to those on either chlorthalidone or lisinopril. PMID:24283598

  6. Life-threatening angio-oedema after the first dose of an ACE inhibitor-not an anaphylactic reaction.

    PubMed

    Krogh Nielsen, Troels; Bygum, Anette; Rye Rasmussen, Eva

    2016-01-01

    We present a case of a 60-year-old Caucasian woman, with no prior history of swellings, who was admitted to a hospital due to life-threatening angio-oedema. She had, the previous day, been prescribed an ACE inhibitor for her essential hypertension. She had taken one tablet at night-time, and awoke in the morning with a swollen face progressing to involve the tongue and throat within a few hours. On arrival at her doctor's office, her voice had altered. Corticosteroids and antihistamine were administered while awaiting an ambulance. Arriving at the emergency department, she had dyspnoea due to increasingly severe angio-oedema of the upper airways. Neither adrenaline inhalations, intravenously administrated corticosteroids, atropine nor furosemide were effective and the patient soon become bradycardic. A tracheotomy was performed and the patient was placed on a ventilator. She eventually made a full recovery. It was concluded that she had suffered from life-threatening angio-oedema due to her new medication. PMID:27229746

  7. One-year effectiveness and safety of open-label losartan/hydrochlorothiazide combination therapy in Japanese patients with hypertension uncontrolled with ARBs or ACE inhibitors.

    PubMed

    Kita, Toshihiro; Yokota, Naoto; Ichiki, Yoshinari; Ayabe, Takao; Etoh, Takuma; Tamaki, Noboru; Kato, Johji; Eto, Tanenao; Kitamura, Kazuo

    2010-04-01

    The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan. PMID:20075934

  8. Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease

    PubMed Central

    Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

    2016-01-01

    Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. PMID:27546928

  9. Renoprotective effects of combined SGLT2 and ACE inhibitor therapy in diabetic Dahl S rats

    PubMed Central

    Kojima, Naoki; Williams, Jan M; Slaughter, Tiffani N; Kato, Sota; Takahashi, Teisuke; Miyata, Noriyuki; Roman, Richard J

    2015-01-01

    This study examined whether control of hyperglycemia with a new SGLT2 inhibitor, luseogliflozin, given alone or in combination with lisinopril could prevent the development of renal injury in diabetic Dahl salt-sensitive (Dahl S) rats treated with streptozotocin (Dahl-STZ). Blood glucose levels increased from normoglycemic to hyperglycemic levels after treatment of STZ in Dahl S rats. Chronic treatment of Dahl-STZ rats with luseogliflozin (10 mg/kg/day) increased the fractional excretion of glucose and normalized blood glucose and HbA1c levels. Lisinopril (20 mg/kg/day) reduced blood pressure from 145 ± 9 to 120 ± 5 mmHg in Dahl-STZ rats, while luseogliflozin had no effect on blood pressure. Combination therapy reduced blood pressure more than that seen in the rats treated with luseogliflozin or lisinopril alone. Dahl-STZ rats exhibited hyperfiltration, mesangial matrix expansion, severe progressive proteinuria, focal glomerulosclerosis and interstitial fibrosis. Control of hyperglycemia with luseogliflozin reduced the degree of hyperfiltration and renal injury but had no effect on blood pressure or the development of proteinuria. Treatment with lisinopril reduced hyperfiltration, proteinuria and renal injury in Dahl-STZ rats. Combination therapy afforded greater renoprotection than administration of either drug alone. These results suggest that long-term control of hyperglycemia with luseogliflozin, especially in combination with lisinopril to lower blood pressure, attenuates the development of renal injury in this rat model of advanced diabetic nephropathy. PMID:26169541

  10. Ventricular dilatation in the absence of ACE inhibitors: influence of haemodynamic and neurohormonal variables following myocardial infarction

    PubMed Central

    Walsh, J; Batin, P; Hawkins, M; McEntegart, D; Cowley, A

    1999-01-01

    Objective—To examine the relation between patterns of ventricular remodelling and haemodynamic and neurohormonal variables, at rest and during symptom limited exercise, in the year following acute myocardial infarction in patients not receiving angiotensin converting enzyme (ACE) inhibitors.
Design—A prospective observational study.
Patients—65 patients recruited following hospital admission with a transmural anterior myocardial infarction.
Methods—Central haemodynamics and neurohormonal activation at rest and during symptom limited treadmill exercise were measured at baseline before hospital discharge, one month later, and at three monthly intervals thereafter. Patients were classified according to individual patterns of change in left ventricular end diastolic volumes at rest, assessed at each visit using transthoracic echocardiography.
Results—In most patients (n = 43, 66%) ventricular volumes were unchanged or reduced. Mean (SEM) treadmill exercise capacity and peak exercise cardiac index increased at month 12 by 200 (24) seconds (p < 0.001 v baseline) and by 0.8 (0.4) l/min/m2 (p<0.05 v baseline), respectively, in this group. In patients with limited ventricular dilatation (n = 11, 17%) exercise capacity increased by 259 (52) seconds (p < 0.001 v baseline) and peak exercise cardiac index improved by 0.8 (0.7) l/min/m2 (NS). In the remaining 11 patients with progressive left ventricular dilatation, exercise capacity increased by 308 (53) seconds (p< 0.001 v baseline) and peak exercise cardiac index similarly improved by 1.3 (0.7) l/min/m2 (NS). There were trends towards increased atrial natriuretic factor (ANF) secretion at rest and at peak exercise in this group.
Conclusions—Ventricular dilatation after acute myocardial infarction is a heterogeneous process that is progressive in only a minority of patients. Compensatory mechanisms, including ANF release, appear capable of maintaining and improving exercise capacity in

  11. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

    PubMed Central

    Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles “Del” and “4G”. The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-γ and TNF-α contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations

  12. The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats.

    PubMed

    Rakusan, K; Cicutti, N; Maurin, A; Guez, D; Schiavi, P

    2000-03-01

    Angiotensin II is considered to have angiogenic properties. Nevertheless, several authors reported an increase in coronary capillary density after treatment with ACE inhibitors. The aim of the present study was to evaluate the effect of treatment with low doses of ACE inhibitor perindopril, low doses of the diuretic indapamide, or a combination of the two on microvascular structure in hearts from stroke-prone spontaneously hypertensive rats (SHR-sp). Young adult male SHR treated with indapamide (0.24 mg/kg/day), perindopril (0.76 mg/kg/day), or both were compared with untreated animals after 8 or 14 weeks of treatment. Survival of SHR-sp was significantly increased after treatment. Only perindopril alone or in combination with indapamide significantly decreased blood pressure and cardiac mass. Treatment also significantly increased capillary and myocyte densities but arteriolar density tended to decrease. External and internal diameters significantly increased in treated animals while arteriolar thickness remained the same. Thus, thickness in vessels of the same size was the greatest in untreated animals, followed by indapamide- and perindopril-treated rats with the thinnest walls in rats with combined treatment, and the treatment resulted in a significant increase in the lumen to wall ratio. Capillary and arteriolar growth responses in treated animals seem to indicate that the two are independently regulated processes. Treatment with indapamide alone at this dosage did not significantly influence most responses but in combination with perindopril it strengthened the effect of perindopril. PMID:10684730

  13. Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro-Junior, Ernesto Lopes; Zoccal, Karina Furlani; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Peigneur, Steve; Vriens, Kim; Thevissen, Karin; Cammue, Bruno Philippe Angelo; Júnior, Ronaldo Bragança Martins; Arruda, Eurico; Faccioli, Lúcia Helena; Tytgat, Jan; Arantes, Eliane Candiani

    2016-08-01

    The present study purifies two T. serrulatus non-disulfide-bridged peptides (NDBPs), named venom peptides 7.2 (RLRSKG) and 8 (KIWRS) and details their synthesis and biological activity, comparing to the synthetic venom peptide 7.1 (RLRSKGKK), previously identified. The synthetic replicate peptides were subjected to a range of biological assays: hemolytic, antifungal, antiviral, electrophysiological, immunological and angiotensin-converting enzyme (ACE) inhibition activities. All venom peptides neither showed to be cytolytic nor demonstrated significant antifungal or antiviral activities. Interestingly, peptides were able to modulate macrophages' responses, increasing IL-6 production. The three venom peptides also demonstrated potential to inhibit ACE in the following order: 7.2>7.1>8. The ACE inhibition activity was unexpected, since peptides that display this function are usually proline-rich peptides. In attempt to understand the origin of such small peptides, we discovered that the isolated peptides 7.2 and 8 are fragments of the same molecule, named Pape peptide precursor. Furthermore, the study discusses that Pape fragments could be originated from a post-splitting mechanism resulting from metalloserrulases and other proteinases cleavage, which can be seen as a clever mechanism used by the scorpion to enlarge its repertoire of venom components. Scorpion venom remains as an interesting source of bioactive proteins and this study advances our knowledge about three NDBPs and their biological activities. PMID:27221550

  14. Banning Corporal Punishment of Children: An ACEI Position Paper

    ERIC Educational Resources Information Center

    Paintal, Sureshrani

    2007-01-01

    Childhood is a unique and critical stage of life. All children share the same basic needs for safety, health, nurturance, and dignity. The Association for Childhood Education International (ACEI) is committed to supporting children's development; respecting individual differences; helping children learn to live and work cooperatively; and…

  15. Effect of chronic treatment with the vasopeptidase inhibitor AVE 7688 and ramipril on endothelial function in atherogenic diet rabbits.

    PubMed

    Weckler, Nadine; Leitzbach, Daniela; Kalinowski, Leszek; Malinski, Tadeusz; Busch, Andreas E; Linz, Wolfgang; Kalinowski, Ludmila

    2003-09-01

    Cardiovascular disease is the major cause of death in Western nations, although improved possibilities regarding diagnosis and therapy now exist. Endothelial dysfunction is triggered by cardiovascular risk factors such as hypercholesterolaemia, hypertension, adiposity and smoking, contributing to the common endpoint of atherosclerosis. This study examined the pharmacological effects of angiotensin-converting enzyme (ACE) and combined ACE-neutral endopeptidase (NEP) (vasopeptidase) inhibitors on endothelial dysfunction in the model of hyperlipidaemic rabbits. The focus of the study was to assess endothelial function after treatment with the ACE-NEP inhibitor AVE 7688 (30 mg/kg/day) in comparison to the ACE inhibitor (ACE-I) ramipril (1 mg/kg/day). Different parameters, such as endothelial function, blood pressure (BP), expansion of plaques, endothelial nitric oxide (NO) and superoxide (O2-) release and plasma levels of various lipidaemic parameters were analysed. Control groups consisted of one group fed only with normal diet, one group fed only with atherogenic diet and the direct control group fed with varied diets (six weeks atherogenic diet followed by 12 weeks normal diet). Since for the treatment of atherosclerosis, a change in feeding is absolutely necessary, in the present study, at the start of the treatments with AVE 7688 and ramipril, the rabbits food was changed to a normal diet. At the end of the study, mean arterial blood pressure (MAP) was measured in the anaesthetised animals. The values in standard, atherogenic and varied diet-fed rabbits were around 73 2 mmHg. Angiotensin I (Ang I) given intravenous (i.v.) induced a strong increase in MAP of about 20%. In both the treated groups Ang I-induced BP increase was inhibited. In contrast, i.v. bradykinin led to a strong reduction in MAP in both the treated groups of around 50%. Six weeks feeding with an atherogenic diet in the rabbits induced an enduring endothelial dysfunction despite the food

  16. Release of angiotensin converting enzyme-inhibitor peptides during in vitro gastrointestinal digestion of Parmigiano Reggiano PDO cheese and their absorption through an in vitro model of intestinal epithelium.

    PubMed

    Basiricò, L; Catalani, E; Morera, P; Cattaneo, S; Stuknytė, M; Bernabucci, U; De Noni, I; Nardone, A

    2015-11-01

    The occurrence of 8 bovine casein-derived peptides (VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP, and HLPLP) reported as angiotensin converting enzyme-inhibitors (ACE-I) was investigated in the 3-kDa ultrafiltered water-soluble extract (WSE) of Parmigiano Reggiano (PR) cheese samples by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry via an electrospray ionization source. Only VPP, IPP, LHLPLP, and HLPLP were revealed in the WSE, and their total amount was in the range of 8.46 to 21.55 mg/kg of cheese. Following in vitro static gastrointestinal digestion, the same ACE-I peptides along with the newly formed AYFYPEL and AYFYPE were found in the 3 kDa WSE of PR digestates. Digestates presented high amounts (1,880-3,053 mg/kg) of LHLPLP, whereas the remaining peptides accounted for 69.24 to 82.82 mg/kg. The half-maximal inhibitory concentration (IC50) values decreased from 7.92 ± 2.08 in undigested cheese to 3.20 ± 1.69 after in vitro gastrointestinal digestion. The 3-kDa WSE of digested cheeses were used to study the transport of the 8 ACE-I peptides across the monolayers of the Caco-2 cell culture grown on a semipermeable membrane of the transwells. After 1h of incubation, 649.20 ± 148.85 mg/kg of LHLPLP remained in the apical compartment, whereas VPP, IPP, AYFYPEL, AYFYPE, and HLPLP accounted in total for less than 36.78 mg/kg. On average, 0.6% of LHLPLP initially present in the digestates added to the apical compartment were transported intact to the basolateral chamber after the same incubation time. Higher transport rate (2.9%) was ascertained for the peptide HLPLP. No other intact ACE-I peptides were revealed in the basolateral compartment. For the first time, these results demonstrated that the ACE-I peptides HLPLP and LHLPLP present in the in vitro digestates of PR cheese are partially absorbed through an in vitro model of human intestinal epithelium. PMID:26364103

  17. Twenty years after ACEIs and ARBs: emerging treatment strategies for diabetic nephropathy.

    PubMed

    Johnson, Stacy A; Spurney, Robert F

    2015-11-15

    Diabetic nephropathy (DN) is a serious complication of both type 1 and type 2 diabetes mellitus. The disease is now the most common cause of end-stage kidney disease (ESKD) in developed countries, and both the incidence and prevalence of diabetes mellitus is increasing worldwide. Current treatments are directed at controlling hyperglycemia and hypertension, as well as blockade of the renin angiotensin system with angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers. Despite these therapies, DN progresses to ESKD in many patients. As a result, much interest is focused on developing new therapies. It has been over two decades since ACEIs were shown to have beneficial effects in DN independent of their blood pressure-lowering actions. Since that time, our understanding of disease mechanisms in DN has evolved. In this review, we summarize major cell signaling pathways implicated in the pathogenesis of diabetic kidney disease, as well as emerging treatment strategies. The goal is to identify promising targets that might be translated into therapies for the treatment of patients with diabetic kidney disease. PMID:26336162

  18. ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity

    PubMed Central

    Porritt, Michelle J; Chen, Michelle; Rewell, Sarah S J; Dean, Rachael G; Burrell, Louise M; Howells, David W

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR. PMID:20407464

  19. Effects of bradykinin B2 receptor antagonism on the hypotensive effects of ACE inhibition.

    PubMed Central

    Bouaziz, H; Joulin, Y; Safar, M; Benetos, A

    1994-01-01

    1. The aim of this study was to determine the participation of endogenous bradykinin (BK) in the antihypertensive effects of the angiotensin converting enzyme inhibitor (ACEI), perindoprilat, in the spontaneously hypertensive rat (SHR) on different salt diets. 2. Conscious SHRs receiving either a low or a high NaCl diet were used in order to evaluate the respective roles of angiotensin II suppression and bradykinin stimulation in the acute hypotensive effects of perindoprilat. Two different B2 receptor antagonists (B 4146 and Hoe 140) were used after bolus administration of 7 mg kg-1 of the ACEI, perindoprilat. In separate animals, Hoe 140 was administered before the injection of perindoprilat. In other experiments, the effects of Hoe 140 on the hypotensive effects of the calcium antagonist, nicardipine, were tested. 3. The different NaCl diets had no effect on baseline blood pressure. Hoe 140 injection before ACE inhibition did not modify blood pressure. Perindoprilat caused more marked hypotension in the low salt-fed rats than in the high salt animals (P < 0.01). Administration of Hoe 140 or B4146 after perindoprilat significantly reduced the antihypertensive effects of perindoprilat in the different groups, but this effect was more pronounced in high salt-fed rats. However, in SHRs receiving Hoe 140 before perindoprilat, the antihypertensive effect of perindoprilat was completely abolished in both high or low salt diet rats. In separate experiments we confirmed that Hoe 140 did not affect the hypotensive efficacy of the calcium antagonist, nicardipine. 4. Our study shows that inhibition of endogenous bradykinin degradation participates in the acute antihypertensive effects of perindoprilat in SHRs. The role of bradykinin is more pronounced following exposure to a high salt diet i.e., when the renin-angiotensin system is suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7858859

  20. ACE blood test

    MedlinePlus

    ... to help diagnose and monitor a disorder called sarcoidosis . People with sarcoidosis may have their ACE level tested regularly to ... normal ACE level may be a sign of sarcoidosis. ACE levels may rise or fall as sarcoidosis ...

  1. [Comparative evaluation of the influence of sulfhydryl and phosphate ACE inhibitors on thrombocyte aggregation in patients suffering from atrerial hypertension with metabolic syndrome].

    PubMed

    Simonenko, V B; Medvedev, I N; Tolmachev, V V

    2007-01-01

    The purpose of the study was to compare the influence of two ACE inhibitors--captopril, a sulfhydryl one, and fozinopril, a phosphate one--on the aggregation activity of thrombocytes in patients suffering from arterial hypertension (AH) with metabolic syndrome (MS). Sixty-nine patients suffering from AH with MS were examined; 36 patients were administered captopril during 16 weeks, while 33 patients were treated with fozinopril during the same period of time. Changes in anthropometric parameters, blood lipid spectrum, lipid peroxidation in blood plasma and thrombocytes, and the antioxidative protection of liquid part of blood and platelets, as well as the aggregation activity of thrombocytes were assessed. The data received were processed using Student criterion and system multifactor analysis. The study shows that the use of fozinopril in patients with AH and metabolic syndrome attenuates peroxidation syndrome and optimizes thrombocyte aggregation. Prolonged fozinopril application will stabilize the achieved effect. Captopril did not have a positive effect on the parameters under study. In conclusion, fozinopril should be applied in combination with non-drug means to lower body weight in patients suffering from AH with MS. PMID:17564032

  2. An International, Web-Based, Prospective Cohort Study to Determine Whether the Use of ACE Inhibitors prior to the Onset of Scleroderma Renal Crisis Is Associated with Worse Outcomes—Methodology and Preliminary Results

    PubMed Central

    Hudson, Marie; Baron, Murray; Lo, Ernest; Weinfeld, Joanna; Furst, Daniel E.; Khanna, Dinesh

    2010-01-01

    Background. To describe the methodology of a study designed to determine whether systemic sclerosis (SSc) patients with incident scleroderma renal crisis (SRC) on angiotensin converting enzyme (ACE) inhibitors prior to the onset of SRC have worse outcomes. Methods. Prospective, international cohort study of SRC subjects identified through an ongoing web-based survey. Every second Friday afternoon, an e-mail was sent to 589 participating physicians to identify new cases of SRC. Death or dialysis at one year after the onset of SRC will be compared in patients exposed or not to ACE inhibitors prior to the onset of SRC. Results. Fifteen months after the start of the survey, we had identified 76 incident cases of SRC. Of these, 66 (87%) had a hypertensive SRC and 10 (13%) a normotensive SRC. Twenty-two percent (22%) of the patients were on an ACE inhibitor immediately prior to the onset of the SRC. To date, we have collected one-year follow-up data on approximately 1/3 of the cohort. Of these, over 50% have died or remain on dialysis at one year. Conclusion. An international, web-based cohort study design is a feasible method of recruiting a substantial number of patients to study an infrequent vascular manifestation of SSc. PMID:20936135

  3. Pharmacology of a phosphorus-containing novel angiotensin converting enzyme inhibitor, SQ 29 852 in anesthetized dogs.

    PubMed

    Ohara, N; Yokota, S; Konishi, C; Shukunobe, K; Ono, H

    1991-12-01

    The effects of (S)-1[6-amino-2[[hydrozy(4- phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29 852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI), which is synthesized aiming an ACEI with long-lasting activity and with few side effects, were studied using anesthetized dogs. SQ 29 852 was equipotent with captopril to modify blood pressure response of the animals to angiotensin I (Ang I) and bradykinin (Bdk). An intravenous infusion of SQ 29 852 at 0.1 mg/kg/min for 30 min caused a remarkable hypotension without reflex tachycardia in open-chest dogs. In these animals cardiac contractility (dP/dtmax of left ventricular pressure) appeared to be reduced by SQ 29 852 without any changes in right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP) and aortic blood flow (AoF, cardiac output). In sodium-restricted dogs, the hypotension and renal vasodilation by SQ 29 852 (at 0.01, 0.1, and 1 mg/kg, i.v.) were slightly pronounced compared with animals fed with normal diet. It is demonstrated from these results that SQ 29 852 has comparable potency with captopril to inhibit angiotensin converting enzyme (ACE) activity and as common a pharmacological profile as ACEI. SQ 29 852 may be a favorable antihypertensive agent, if its long-lasting activity and few side effects are confirmed. PMID:1812274

  4. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    PubMed Central

    Benter, Ibrahim F.; Babiker, Fawzi; Al-Rashdan, Ibrahim; Yousif, Mariam; Akhtar, Saghir

    2013-01-01

    Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving −dP/dt (a measure of diastolic function) when administered to diabetic hearts after ischemia. PMID:24066305

  5. An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice

    PubMed Central

    Zhou, Guangyu; Johansson, Ulrika; Peng, Xiao-Rong; Bamberg, Krister; Huang, Yufeng

    2016-01-01

    Although blockade of the renin-angiotensin-system (RAS) has become standard therapy for diabetic nephropathy (DN), decline in kidney function towards end-stage renal disease is seen in many patients. Elevated plasma aldosterone often accompanies RAS blockade by a phenomenon known as “aldosterone escape” and activates the mineralocorticoid receptor (MR). We therefore examined whether addition of the MR antagonist eplerenone to an ACEI would enhance the efficacy in slowing the progression of DN. Untreated uninephrectomized diabetic db/db mice developed progressive albuminuria and glomerulosclerosis between weeks 18 and 22, associated with decreased number of podocytes and increased renal expression of fibrotic markers. The therapeutic effect of eplerenone at 100 mg/kg BW/d on albuminuria, podocyte injury and renal fibrosis was similar to that of enalapril given alone at maximally effective doses. Adding eplerenone to enalapril resulted in further reduction in these measurements. Renal expressions of TNF-α, MCP-1, Nox2 and p47phox and renal TBARS levels, markers of inflammation and oxidative stress, were increased during disease progression in diabetic mice, which were reduced by eplerenone or enalapril given alone and further reduced by the two drugs given in combination. However, there were no treatment related effects on plasma K+. Our results suggest that eplerenone is effective in slowing the progression of DN in db/db mice and that the effect is additive to an ACEI. The addition of an MR antagonist void of effects on plasma K+ to an ACEI may offer additional renoprotection in progressive DN via blocking the effects of aldosterone due to escape or diabetes-induction. PMID:27186263

  6. Reduction of Mean Arterial Pressure and Proteinuria by the Effect of ACEIs (Lisinopril) in Kurdish Hypertensive Patients in Hawler City

    PubMed Central

    A.I., Muslih

    2012-01-01

    The angiotensin converting enzyme inhibitors (ACEIs) are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in some cases as the drugs of first choice. The renin-angiotensin system is activated in response to hypotension, decreased sodium concentration in the distal tubule, decreased blood volume and in renal sympathetic nerve stimulation. This study examines the effects of angiotensin converting enzyme inhibitor (Lisinopril) on blood pressure (BP) 131±2.4 and proteinuria 0.198±0.005 in Kurd hypertensive patients, mean arterial blood pressure and proteinuria excretion were measured weekly along the period of 12 weeks. Lisinopril significantly reduced mean arterial blood pressure, and attenuated proteinuria level in patients subjected to this study in lisinopril 10mg dose dependent manner (p<0.05, n=24). In conclusion, lisinopril is of beneficial of renoprotection and in lowering BP PMID:22980373

  7. The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

    NASA Astrophysics Data System (ADS)

    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

    Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular

  8. Tryptic amaranth glutelin digests induce endothelial nitric oxide production through inhibition of ACE: antihypertensive role of amaranth peptides.

    PubMed

    de la Rosa, A P Barba; Montoya, A Barba; Martínez-Cuevas, Pedro; Hernández-Ledesma, B; León-Galván, M F; De León-Rodríguez, A; González, C

    2010-09-15

    Amaranth seed proteins have a better balance of essential amino acids than cereals and legumes. In addition, the tryptic hydrolysis of amaranth proteins generates, among other peptides, angiotensin converting enzyme (ACE) inhibitory (ACEi) peptides. ACE converts angiotensin I (Ang I) into Ang II, but is also responsible for the degradation of bradykinin (BK). In contrast to Ang II, BK stimulates vasodilation modulated through endothelial nitric oxide (NO) production. The aim of the present study was to characterize the ACEi activity of amaranth trypsin-digested glutelins (TDGs) and their ability to induce endothelial NO production. An IC(50) value of 200microgml(-1) was measured for TDG inhibition of ACE. TDGs stimulated endothelial NO production in coronary endothelial cells (CEC) by 52% compared to control. The effects of TDGs were comparable to those of BK and Captopril, both used as positive controls of NO production. Consistent with these effects, TDGs induced, in a dose-dependent manner, endothelial NO-dependent vasodilation in isolated rat aortic rings. These results suggest that TDGs induce endothelial NO production and consequent vasodilation through their ACEi activity. Amaranth TDGs have a high potential as a nutraceutical food in prevention of cardiovascular diseases. Further molecular, cellular and physiological studies are currently under way and the results may contribute to a better understanding and control of cardiovascular disorders. PMID:20435155

  9. Marketing ACE in Victoria.

    ERIC Educational Resources Information Center

    2001

    This publication presents options raised through various forums for marketing adult and community education (ACE) in Victoria, Australia, and suggested strategies. After an introduction (chapter 1), chapters 2 and 3 provide a broad view of the current situation for marketing ACE. Chapter 2 discusses general issues in the current position--ACE…

  10. Investigation of the energy barrier to the rotation of amide CN bonds in ACE inhibitors by NMR, dynamic HPLC and DFT.

    PubMed

    Bouabdallah, S; Ben Dhia, M T; Driss, M R; Touil, S

    2016-09-01

    The isomerizations of Enalapril, Perindopril, Enalaprilat and Lisinopril have been investigated using NMR spectroscopic, dynamic chromatographic, unified equation and DFT theoretical calculations. The thermodynamic parameters (ΔH, ΔS and ΔG) were determined by varying the temperature in the NMR experiments. At the coalescence temperature, we can evaluate the isomerization barrier to the rotation (ΔG(≠)) around the amide bond. Using dynamics chromatography and an unified equation introduced by Trap, we can determine isomerization rate constants and Gibbs activation energies. Molecular mechanics calculations also provided evidence for the presence of low energy conformers for the ACE due to restricted amide rotation. With the value of barriers (ΔE) between them of the order of (20kJmol(-1)), which is in agreement with the dynamic NMR results and DFT calculations. PMID:27344631

  11. ACE blood test

    MedlinePlus

    Serum angiotensin-converting enzyme; SACE ... Chernecky CC, Berger BJ. Angiotensin-converting enzyme (ACE) - blood. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures . 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:138-139.

  12. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules.

    PubMed

    Das, Undurti N

    2008-01-01

    Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites: gamma-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and other products such as prostaglandins E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, protectins including neuroprotectin D1 (NPD1) prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-gamma ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of omega-3 and omega-6 fatty acids and the

  13. [Direct renin inhibitor aliskiren in the treatment of cardiovascular and renal diseases].

    PubMed

    Horký, Karel

    2010-02-01

    The role of renin-angiotensin-aldosterone system (RAAS) in regulating the volume and composition of extracellular fluid, blood pressure (BP) as well as onset and progression of cardiovascular and renal diseases has been studied for more than 150 years. The compounds that block the vital stages of the RAAS cascade, such as ACE-inhibitors (ACEI), AT1-receptor blockers (ARB) and aldosterone receptor antagonists, importantly extended our treatment options. However, the positive therapeutic effects of these compounds also have certain negative consequences. Administration of ACEIs and ARBs interrupts physiological feedback for renal renin release and leads to reactive elevation of circulating active renin and greater production of angiotensin I and angiotensin II with subsequent return of aldosterone secretion to the pre-treatment levels ('escape' phenomenon). These possible adverse effects of the intermediary products of incomplete RAAS blockade leading to organ complications have facilitated the efforts to develop compounds blocking the initial stages of renin-angiotensin cascade--i.e. direct renin blockers. After several years of unsuccessful attempts, the recent years have seen development of the first non-peptide, orally long-term effective renin inhibitor, aliskiren fumarate. In monotherapy or in combination with other antihypertensives (hydrochlorothiazide, ARB, ACEI), aliskiren reduces BP in a dose-dependent manner (75-600 mg/den). Aliskiren reduces plasma renin activity (PRA) and neutralises hydrochlorothiazide-induced RAAS activation. Once daily administration of the drug leads to longer than 24-hour activity and its prolonged blocking effects on the kidneys are the basis for its renoprotectivity. In addition to the significant antihypertensive effect, clinical studies also showed a range of organoprotective properties in patients with left ventricle hypertrophy (ALLAY study), heart failure (ALOFT study) and diabetic nephropathy (AVOID study). Similar to other

  14. Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 signaling

    PubMed Central

    Xiao, Liang; Haack, Karla K. V.

    2013-01-01

    Brain ANG II plays an important role in modulating sympathetic function and homeostasis. The generation and degradation of ANG II are carried out, to a large extent, through the angiotensin-converting enzyme (ACE) and ACE2, respectively. In disease states, such as hypertension and chronic heart failure, central expression of ACE is upregulated and ACE2 is decreased in central sympathoregulatory neurons. In this study, we determined the expression of ACE and ACE2 in response to ANG II in a neuronal cell culture and the subsequent signaling mechanism(s) involved. A mouse catecholaminergic neuronal cell line (CATH.a) was treated with ANG II (30, 100, and 300 nM) for 24 h, and protein expression was determined by Western blot analysis. ANG II induced a significant dose-dependent increase in ACE and decrease in ACE2 mRNA and protein expression in CATH.a neurons. This effect was abolished by pretreatment of the cells with the p38 MAPK inhibitor SB-203580 (10 μM) 30 min before administration of ANG II or the ERK1/2 inhibitor U-0126 (10 μM). These data suggest that ANG II increases ACE and attenuates ACE2 expression in neurons via the ANG II type 1 receptor, p38 MAPK, and ERK1/2 signaling pathways. PMID:23535237

  15. ACES--Today and Tomorrow.

    ERIC Educational Resources Information Center

    Hackney, Harold

    1991-01-01

    Presents text of Presidential Address delivered March 24, 1991, at the Association for Counselor Education and Supervision (ACES) luncheon, part of the American Association for Counseling and Development Convention held in Reno, Nevada. Comments on past, present, and future of ACES, particularly on future challenges and role of ACES. (ABL)

  16. Effects of a novel ACE inhibitor, 3-(3-thienyl)-l-alanyl-ornithyl-proline, on endothelial vasodilation and hepatotoxicity in l-NAME-induced hypertensive rats

    PubMed Central

    Seth, Mahesh Kumar; Hussain, M Ejaz; Pasha, Santosh; Fahim, Mohammad

    2016-01-01

    Nitric oxide (NO) is a widespread biological mediator involved in many physiological and pathological processes, eg, in the regulation of vascular tone and hypertension. Chronic inhibition of NO synthase by NG-nitro-l-arginine methyl ester (l-NAME) hydrochloride results in the development of hypertension accompanied by an increase in vascular responsiveness to adrenergic stimuli. Recently, we developed a novel sulfur-containing angiotensin-converting enzyme inhibitor: 3-(3-thienyl)-l-alanyl-ornithyl-proline (TOP). Our previous studies indicated a superior nature of the molecule as an antihypertensive agent in spontaneously hypertensive rats (showing the involvement of renin–angiotensin–aldosterone system) in comparison to captopril. The aim of the present study was to investigate the effect of TOP on NO pathway in l-NAME-induced hypertensive rats, and captopril was included as the standard treatment group. Treatment with both TOP (20 mg/kg) and captopril (40 mg/kg) prevented the development of hypertension in l-NAME model, but TOP showed better restoration of NO and normal levels of angiotensin-converting enzyme. In addition, in vitro vasorelaxation assay showed an improvement in endothelium-dependent vasodilation in both the cases. Further, the biochemical (malondialdehyde, alanine aminotransferase, and aspartate aminotransferase) and the histopathological effects of TOP on rat liver tissues revealed a protective nature of TOP in comparison to captopril in the l-NAME model. In conclusion, TOP at 50% lesser dose than captopril was found to be better in the l-NAME model. PMID:27143859

  17. An ACE diagnosis.

    PubMed

    Nasher, Omar; Gupta, Anindya

    2013-01-01

    Gaucher's disease is not commonly considered in the differential diagnosis of adult patients with hepatosplenomegaly and increased serum ACE. A 19-year-old girl presented with recurrent epigastric and left hypochondrial pain over a period of 9 years, associated with episodes of nausea and diarrhoea. She was extensively investigated and found to have splenomegaly and raised serum ACE. A screen for haematological disorders was negative. She reported an insect bite during an overseas holiday preceding her symptoms. She was therefore also screened for infectious causes of hepatosplenomegaly but without success. Later on in life, she reported joint pain and discomfort. Sarcoidosis was thought to be the putative cause on more than one occasion. However, the presence of splenomegaly and her relatively young age, led the rheumatologist to the correct diagnosis. PMID:23417380

  18. An ACE diagnosis

    PubMed Central

    Nasher, Omar; Gupta, Anindya

    2013-01-01

    Gaucher's disease is not commonly considered in the differential diagnosis of adult patients with hepatosplenomegaly and increased serum ACE. A 19-year-old girl presented with recurrent epigastric and left hypochondrial pain over a period of 9 years, associated with episodes of nausea and diarrhoea. She was extensively investigated and found to have splenomegaly and raised serum ACE. A screen for haematological disorders was negative. She reported an insect bite during an overseas holiday preceding her symptoms. She was therefore also screened for infectious causes of hepatosplenomegaly but without success. Later on in life, she reported joint pain and discomfort. Sarcoidosis was thought to be the putative cause on more than one occasion. However, the presence of splenomegaly and her relatively young age, led the rheumatologist to the correct diagnosis. PMID:23417380

  19. Strong suppression of the renin-angiotensin system has a renal-protective effect in hypertensive patients: high-dose ARB with ACE inhibitor (Hawaii) study.

    PubMed

    Ohishi, Mitsuru; Takeya, Yasushi; Tatara, Yuji; Yamamoto, Koichi; Onishi, Miyuki; Maekawa, Yoshihiro; Kamide, Kei; Rakugi, Hiromi

    2010-11-01

    The principal means for reducing proteinuria in patients with chronic kidney disease are strong blockade of the renin-angiotensin system and strict regulation of blood pressure (BP). This study compared the efficacy of the maximum permissible doses of two common angiotensin receptor blockers (ARBs), namely valsartan (maximum dose=160 mg per day) and olmesartan (maximum dose=40 mg per day). We also investigated whether a high-dose ARB or the combination of an angiotensin-converting enzyme inhibitor with a high-dose ARB would be more renal protective. We recruited 87 poorly controlled hypertensive patients. In the first study, 50 patients without proteinuria were switched from valsartan (160 mg per day) to olmesartan (40 mg per day) for 4 months. In the second study, 37 patients with proteinuria were randomized to either switch from valsartan 160 mg per day to 40 mg per day olmesartan (n=19; Olm-G) or addition of 2.5-10 mg per day imidapril (stepped up by 2.5 mg per month) to valsartan at 160 mg per day (n=18; Imi-G). After 4 months, the BP level decreased (first study) from 157/88 mm Hg to 145/82 mm Hg (P<0.001) and (second study) from 149/86 mm Hg to 135/77 mm Hg and 145/82 mm Hg for Olm-G and Imi-G, respectively. Furthermore, in the second study, urinary protein/creatinine excretion was reduced from 2.0±1.8 g g⁻¹ to 0.8±0.8 g g⁻¹ (P=0.0242) in Olm-G and from 1.4±1.3 g g⁻¹ to 0.9±1.0 g g⁻¹ (P=0.0398) in Imi-G. The significance persisted after adjustment for BP or other risk factors. Our results suggested that the maximum dose of olmesartan was more effective than that of valsartan and comparable with the combination of valsartan and imidapril for reducing BP and proteinuria in poorly controlled hypertensive patients. PMID:20703230

  20. Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study

    PubMed Central

    Di, P; Bucca, V; Scalzo, S; Cannizzaro, S; Giubilato, A; Paterna, S

    1999-01-01

    (141) pg/ml; AII 12.77 (4.79) v 12.65 (4.71) pg/ml) or 10 days after admission (NA 283 (93) v 277 (98) pg/ml; AII 5.31 (2.25) v 6.09 (3.31) pg/ml). However, patients in group C had higher plasma concentrations of AII (14.79 (5.7) pg/ml on the third day and 7.98 (4.92) pg/ml on the 10th day) than patients in either group A or B (p = 0.006). After 90 days following treatment, group B (captopril plus losartan) patients had a smaller ESV than patients in group A (captopril) and group C (losartan).
CONCLUSION—The data suggest that the combination of captopril plus losartan is feasible in the early treatment of acute myocardial infarction patients, and it appears that this combination has more effect on ESV than captopril alone in the short term.


Keywords: acute myocardial infarction; angiotensin converting enzyme inhibitors; captopril; losartan PMID:10336919

  1. The Pharmacogenetic Footprint of ACE Inhibition: A Population-Based Metabolomics Study.

    PubMed

    Altmaier, Elisabeth; Menni, Cristina; Heier, Margit; Meisinger, Christa; Thorand, Barbara; Quell, Jan; Kobl, Michael; Römisch-Margl, Werner; Valdes, Ana M; Mangino, Massimo; Waldenberger, Melanie; Strauch, Konstantin; Illig, Thomas; Adamski, Jerzy; Spector, Tim; Gieger, Christian; Suhre, Karsten; Kastenmüller, Gabi

    2016-01-01

    Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them-and perhaps also the other dipeptides-as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity. PMID:27120469

  2. The Pharmacogenetic Footprint of ACE Inhibition: A Population-Based Metabolomics Study

    PubMed Central

    Altmaier, Elisabeth; Menni, Cristina; Heier, Margit; Meisinger, Christa; Thorand, Barbara; Quell, Jan; Kobl, Michael; Römisch-Margl, Werner; Valdes, Ana M.; Mangino, Massimo; Waldenberger, Melanie; Strauch, Konstantin; Illig, Thomas; Adamski, Jerzy; Spector, Tim; Gieger, Christian; Suhre, Karsten; Kastenmüller, Gabi

    2016-01-01

    Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them—and perhaps also the other dipeptides—as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity. PMID:27120469

  3. Angiotensin-Receptor Blocker, Angiotensin-Converting Enzyme Inhibitor, and Risks of Atrial Fibrillation

    PubMed Central

    Hsieh, Yu-Cheng; Hung, Chen-Ying; Li, Cheng-Hung; Liao, Ying-Chieh; Huang, Jin-Long; Lin, Ching-Heng; Wu, Tsu-Juey

    2016-01-01

    Abstract Both angiotensin-receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have protective effects against atrial fibrillation (AF). The differences between ARB and ACEI in their effects on the primary prevention of AF remain unclear. This study compared ARB and ACEI in combined antihypertensive medications for reducing the risk of AF in patients with hypertension, and determined which was better for AF prevention in a nationwide cohort study. Patients aged ≥55 years and with a history of hypertension were identified from Taiwan National Health Insurance Research Database. Medical records of 25,075 patients were obtained, and included 6205 who used ARB, 8034 who used ACEI, and 10,836 nonusers (no ARB or ACEI) in their antihypertensive regimen. Cox regression models were applied to estimate the hazard ratio (HR) for new-onset AF. During an average of 7.7 years’ follow-up, 1619 patients developed new-onset AF. Both ARB (adjusted HR: 0.51, 95% CI 0.44–0.58, P < 0.001) and ACEI (adjusted HR: 0.53, 95% CI 0.47–0.59, P < 0.001) reduced the risk of AF compared to nonusers. Subgroup analysis showed that ARB and ACEI were equally effective in preventing new-onset AF regardless of age, gender, the presence of heart failure, diabetes, and vascular disease, except for those with prior stroke or transient ischemic attack (TIA). ARB prevents new-onset AF better than ACEI in patients with a history of stroke or TIA (log-rank P = 0.012). Both ARB and ACEI reduce new-onset AF in patients with hypertension. ARB prevents AF better than ACEI in patients with a history of prior stroke or TIA. PMID:27196491

  4. ACEE composite structures technology

    NASA Technical Reports Server (NTRS)

    Klotzsche, M. (Compiler)

    1984-01-01

    The NASA Aircraft Energy Efficiency (ACEE) Composite Primary Aircraft Structures Program has made significant progress in the development of technology for advanced composites in commercial aircraft. Commercial airframe manufacturers have demonstrated technology readiness and cost effectiveness of advanced composites for secondary and medium primary components and have initiated a concerted program to develop the data base required for efficient application to safety-of-flight wing and fuselage structures. Oral presentations were compiled into five papers. Topics addressed include: damage tolerance and failsafe testing of composite vertical stabilizer; optimization of composite multi-row bolted joints; large wing joint demonstation components; and joints and cutouts in fuselage structure.

  5. Possible involvement of ATP-dependent K-channel related mechanisms in the antihypertensive and cough suppressant effects of the novel ACE inhibitor (2S, 3aS, 7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D-glutamyl)octahydro-1H- indole-2-carboxylic acid.

    PubMed

    Nagata, S; Takeyama, K; Hosoki, K; Karasawa, T

    1997-06-01

    The antihypertensive and cough suppressant mechanisms of DU-1777 ((2S,3aS,7aS)-1-(N2-nicotinoyl-L-lsyl-gamma-D-glutamyl )octahydro-1H-indole-2 -carboxylic acid, CAS 116662-73-8), a new long-acting angiotensin-1-converting enzyme (ACE) inhibitor, were investigated in vivo and in vitro. The antihypertensive effects of DU-1777 at 10 mg/kg p.o. and cromakalim at 0.3 mg/kg p.o. were partially (about 60%) or fully antagonized by glibenclamide at 10 mg/kg i.v. in 2-kidney, 1-clip renal hypertensive rats (2K-1C RHR). The antihypertensive effects of a Ca blocker (nifedipine) and other ACE inhibitors (captopril, alacepril, enalapril, lisinopril, imidapril and quanapril) were not antagonized by glibenclamide. In deoxycorticosterone acetate-salt hypertensive rats (DOCA-HR), the antihypertensive effects of DU-1777 at 3-30 mg/kg p.o. were fully antagonized by glibenclamide. However, in vitro, DU-1777 (10(-6)-10(-3) mol/l) did not affect aortic ring contractions induced by high K (30 mmol/l). In guinea pig, citric acid induced cough was increased by ACE inhibitors, captopril, alacepril, enalapril and lisinopril (10 and 30 mg/kg p.o.). DU-1777 had a tendency to decrease citric acid induced cough and the effect was antagonized by glibenclamide. These results suggest that while DU-1777 itself does not open ATP-dependent K channel, it indirectly produces these effects through unknown mechanisms in vivo. Moreover, these effects contributed to the antihypertensive effect in DOCA-HR and cough suppressant effect in guinea pigs. PMID:9239450

  6. Role of homocysteinylation of ACE in endothelial dysfunction of arteries

    PubMed Central

    Huang, An; Pinto, John T.; Froogh, Ghezal; Kandhi, Sharath; Qin, Jun; Wolin, Michael S.; Hintze, Thomas H.

    2014-01-01

    The direct impact of de novo synthesis of homocysteine (Hcy) and its reactive metabolites, Hcy-S-S-Hcy and Hcy thiolactone (HCTL), on vascular function has not been fully elucidated. We hypothesized that Hcy synthesized within endothelial cells affects activity of angiotensin-converting enzyme (ACE) by direct homocysteinylation of its amino- and/or sulfhydryl moieties. This covalent modification enhances ACE reactivity toward angiotensin II (ANG II)-NADPH oxidase-superoxide-dependent endothelial dysfunction. Mesenteric and coronary arteries isolated from normal rats were incubated for 3 days with or without exogenous methionine (Met, 0.1–0.3 mM), a precursor to Hcy. Incubation of arteries in Met-free media resulted in time-dependent decreases in vascular Hcy formation. By contrast, vessels incubated with Met produced Hcy in a dose-dependent manner. There was a notably greater de novo synthesis of Hcy from endothelial than from smooth muscle cells. Enhanced levels of Hcy production significantly impaired shear stress-induced dilation and release of nitric oxide, events that are associated with elevated production of vascular superoxide. Each of these processes was attenuated by ANG II type I receptor blocker or ACE and NADPH oxidase inhibitors. In addition, in vitro exposure of purified ACE to Hcy-S-S-Hcy/HCTL resulted in formation of homocysteinylated ACE and an enhanced ACE activity. The enhanced ACE activity was confirmed in isolated coronary and mesenteric arteries that had been exposed directly to Hcy-S-S-Hcy/HCTL or after Met incubation. In conclusion, vasculature-derived Hcy initiates endothelial dysfunction that, in part, may be mediated by ANG II-dependent activation of NADPH oxidase in association with homocysteinylation of ACE. PMID:25416191

  7. National Survey of ACE Programs.

    ERIC Educational Resources Information Center

    Constantino, Ernesto A.

    In 1987-88, a national survey was conducted to determine the adult/continuing education (ACE) policies and practices of large, urban community colleges. Questionnaires were mailed to ACE deans at 74 colleges, requesting information about program characteristics, funding sources, personnel, curriculum review, and marketing and publicity. Study…

  8. Angiotensin-Receptor Blocker, Angiotensin-Converting Enzyme Inhibitor, and Risks of Atrial Fibrillation: A Nationwide Cohort Study.

    PubMed

    Hsieh, Yu-Cheng; Hung, Chen-Ying; Li, Cheng-Hung; Liao, Ying-Chieh; Huang, Jin-Long; Lin, Ching-Heng; Wu, Tsu-Juey

    2016-05-01

    Both angiotensin-receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have protective effects against atrial fibrillation (AF). The differences between ARB and ACEI in their effects on the primary prevention of AF remain unclear. This study compared ARB and ACEI in combined antihypertensive medications for reducing the risk of AF in patients with hypertension, and determined which was better for AF prevention in a nationwide cohort study.Patients aged ≥55 years and with a history of hypertension were identified from Taiwan National Health Insurance Research Database. Medical records of 25,075 patients were obtained, and included 6205 who used ARB, 8034 who used ACEI, and 10,836 nonusers (no ARB or ACEI) in their antihypertensive regimen. Cox regression models were applied to estimate the hazard ratio (HR) for new-onset AF.During an average of 7.7 years' follow-up, 1619 patients developed new-onset AF. Both ARB (adjusted HR: 0.51, 95% CI 0.44-0.58, P < 0.001) and ACEI (adjusted HR: 0.53, 95% CI 0.47-0.59, P < 0.001) reduced the risk of AF compared to nonusers. Subgroup analysis showed that ARB and ACEI were equally effective in preventing new-onset AF regardless of age, gender, the presence of heart failure, diabetes, and vascular disease, except for those with prior stroke or transient ischemic attack (TIA). ARB prevents new-onset AF better than ACEI in patients with a history of stroke or TIA (log-rank P = 0.012).Both ARB and ACEI reduce new-onset AF in patients with hypertension. ARB prevents AF better than ACEI in patients with a history of prior stroke or TIA. PMID:27196491

  9. Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis

    PubMed Central

    de Carvalho, Sara Santos; Simões e Silva, Ana Cristina; Sabino, Adriano de Paula; Evangelista, Fernanda Cristina Gontijo; Gomes, Karina Braga; Dusse, Luci Maria SantAna; Rios, Danyelle Romana Alves

    2016-01-01

    Background There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms. Methods The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03. Results Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele. Conclusion ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the

  10. Inhibitors

    MedlinePlus

    ... Community Counts Blood Safety Inhibitors Articles & Key Findings Free Materials Videos Starting the Conversation Playing it Safe A Look at Hemophilia Joint Range of Motion My Story Links to Other Websites ...

  11. ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis.

    PubMed

    Simões E Silva, Ana Cristina; Teixeira, Mauro Martins

    2016-05-01

    The Renin Angiotensin System (RAS) is a pivotal physiological regulator of heart and kidney homeostasis, but also plays an important role in the pathophysiology of heart and kidney diseases. Recently, new components of the RAS have been discovered, including angiotensin converting enzyme 2 (ACE2), Angiotensin(Ang)-(1-7), Mas receptor, Ang-(1-9) and Alamandine. These new components of RAS are formed by the hydrolysis of Ang I and Ang II and, in general, counteract the effects of Ang II. In experimental models of heart and renal diseases, Ang-(1-7), Ang-(1-9) and Alamandine produced vasodilation, inhibition of cell growth, anti-thrombotic, anti-inflammatory and anti-fibrotic effects. Recent pharmacological strategies have been proposed to potentiate the effects or to enhance the formation of Ang-(1-7) and Ang-(1-9), including ACE2 activators, Ang-(1-7) in hydroxypropyl β-cyclodextrin, cyclized form of Ang-(1-7) and nonpeptide synthetic Mas receptor agonists. Here, we review the role and effects of ACE2, ACE2 activators, Ang-(1-7) and synthetic Mas receptor agonists in the control of inflammation and fibrosis in cardiovascular and renal diseases and as counter-regulators of the ACE-Ang II-AT1 axis. We briefly comment on the therapeutic potential of the novel members of RAS, Ang-(1-9) and alamandine, and the interactions between classical RAS inhibitors and new players in heart and kidney diseases. PMID:26995300

  12. Persistent change in cardiac fibroblast physiology after transient ACE inhibition.

    PubMed

    D'Souza, K M; Biwer, L A; Madhavpeddi, L; Ramaiah, P; Shahid, W; Hale, T M

    2015-10-01

    Transient angiotensin-converting enzyme (ACE) inhibition induces persistent changes that protect against future nitric oxide synthase (NOS) inhibitor-induced cardiac fibrosis and inflammation. Given the role of fibroblasts in mediating these effects, the present study investigates whether prior ACE inhibition produced persistent changes in cardiac fibroblast physiology. Adult male spontaneously hypertensive rats (SHRs) were treated with vehicle (C+L) or the ACE inhibitor, enalapril (E+L) for 2 wk followed by a 2-wk washout period and a subsequent 7-day challenge with the NOS inhibitor N(ω)-nitro-l-arginine methyl ester. A third set of untreated SHRs served as controls. At the end of the study period, cardiac fibroblasts were isolated from control, C+L, and E+L left ventricles to assess proliferation rate, collagen expression, and chemokine release in vitro. After 7 days of NOS inhibition, there were areas of myocardial injury but no significant change in collagen deposition in E+L and C+L hearts in vivo. In vitro, cardiac fibroblasts isolated from C+L but not E+L hearts were hyperproliferative, demonstrated increased collagen type I gene expression, and an elevated secretion of the macrophage-recruiting chemokines monocyte chemoattractant protein-1 and granulocyte macrophage-colony stimulating factor. These findings demonstrate that in vivo N(ω)-nitro-l-arginine methyl ester treatment produces phenotypic changes in fibroblasts that persist in vitro. Moreover, this is the first demonstration that transient ACE inhibition can produce a persistent modification of the cardiac fibroblast phenotype to one that is less inflammatory and fibrogenic. It may be that the cardioprotective effects of ACE inhibition are related in part to beneficial changes in cardiac fibroblast physiology. PMID:26371174

  13. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock in Patients with Severe Systolic Heart Failure (From the GRADE Multicenter Study)

    PubMed Central

    AlJaroudi, Wael A.; Refaat, Marwan M.; Habib, Robert H.; Al-Shaar, Laila; Singh, Madhurmeet; Gutmann, Rebecca; Bloom, Heather L.; Dudley, Samuel C.; Ellinor, Patrick T.; Saba, Samir F.; Shalaby, Alaa A.; Weiss, Raul; McNamara, Dennis M.; Halder, Indrani; London, Barry

    2015-01-01

    Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. While angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events (GRADE) study which included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no ACEi/ARB was physician dependent. There were 1509 patients (mean age [SD] 63[12] years, 80% male, mean [SD] EF 21% [6%]) with 1213 (80%) on ACEi/ARB, and 296 (20%) not on ACEi/ARB. We identified 574 propensity matched patients (287 in each group). After a mean (SD) of 2.5(1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3 and 5 years in the matched cohort (7.7%, 16.7%, 18.5% vs. 13.2%, 27.5%, and 32.0% (RR= 0.61[0.43–0.86], p =0.005). Among patients with GFR >60 and 30–60 ml/min/1.73m2, those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock as compared to those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73m2, and with neutral effect among those GFR <30 ml/min/1.73m2. PMID:25682436

  14. Angiotensin-converting enzyme inhibitors-induced angioedema treated by C1 esterase inhibitor concentrate (Berinert®): about one case and review of the therapeutic arsenal

    PubMed Central

    Lipski, Samuel Michael; Casimir, Georges; Vanlommel, Martine; Jeanmaire, Mathieu; Dolhen, Pierre

    2015-01-01

    Key Clinical Message C1 esterase inhibitor (Berinert®) is generally used to treat severe attack of hereditary angioedema. We describe here the case of a patient who presented with a severe angioedema induced by angiotensin-converting enzyme inhibitors (ACEIs) endangering her life. It could be successfully treated with that medicine. PMID:25767713

  15. Angiotensin-converting enzyme inhibitors-induced angioedema treated by C1 esterase inhibitor concentrate (Berinert®): about one case and review of the therapeutic arsenal.

    PubMed

    Lipski, Samuel Michael; Casimir, Georges; Vanlommel, Martine; Jeanmaire, Mathieu; Dolhen, Pierre

    2015-02-01

    C1 esterase inhibitor (Berinert®) is generally used to treat severe attack of hereditary angioedema. We describe here the case of a patient who presented with a severe angioedema induced by angiotensin-converting enzyme inhibitors (ACEIs) endangering her life. It could be successfully treated with that medicine. PMID:25767713

  16. ACE to Ulysses Coherences

    NASA Astrophysics Data System (ADS)

    Thomson, D. J.; Maclennan, C. G.; Lanzerotti, L. J.

    2006-12-01

    The EPAM charged particle instrument on ACE is the backup for the HISCALE instrument on Ulysses making the two ideally suited for spatial coherence studies over large heliosphere distances. Fluxes of low-energy ( ~50 - 200 keV) electrons are detected in eight spatial sectors on both spacecraft. A spherical harmonic description of the particle flux as a function of time using only the l=0 and l=1 degree coefficients describes most of the observed flux. Here we concentrate on the three l=1 coefficients for the 60--100 kev electrons.Between the two spacecraft these result in nine coherence estimates that are all typically moderately coherent, but the fact that the different coefficients at each spacecraft are also coherent with each other makes interpretation difficult. To avoid this difficulty we estimated the canonical coherences between the two groups of three series. This, in effect, chooses an optimum coordinate system at each spacecraft and for each frequency and estimates the coherence in this frame. Using one--minute data, we find that the canonical coherences are generally larger at high frequencies (3 mHz and above) than they are at low frequencies. This appears to be generally true and does not depend particularly on time, range, etc. However, if the data segment is chosen too long, say > 30 days with 1--minute sampling, the coherence at high frequencies drops. This may be because the spatial and temporal features of the mode are confounded, or possibly because the solar modes p--modes are known to change frequency with solar activity, so do not appear coherent on long blocks.The coherences are not smooth functions of frequency, but have a bimodal distribution particularly in the 100 μHz to 5 mHz range. Classifying the data at frequencies where the canonical coherences are high in terms of apparent polarization and orientation, we note two major families of modes that appear to be organized by the Parker spiral. The magnetic field data on the two

  17. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis

    PubMed Central

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-01-01

    Abstract Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB. We conducted a nested case–control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates. From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78–0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66–0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine. In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  18. Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery

    PubMed Central

    Coca, Steven G.; Garg, Amit X.; Swaminathan, Madhav; Garwood, Susan; Hong, Kwangik; Thiessen-Philbrook, Heather; Passik, Cary; Koyner, Jay L.; Parikh, Chirag R.; Jai, Raman; Jeevanandam, Valluvan; Akhter, Shahab; Devarajan, Prasad; Bennett, Michael; Edelsteinm, Charles; Patel, Uptal; Chu, Michael; Goldbach, Martin; Guo, Lin Ruo; McKenzie, Neil; Myers, Mary Lee; Novick, Richard; Quantz, Mac; Zappitelli, Michael; Dewar, Michael; Darr, Umer; Hashim, Sabet; Elefteriades, John; Geirsson, Arnar

    2013-01-01

    Background Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to ‘functional’ postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for ‘structural’ AKI, measured with new urinary biomarkers, is unknown. Methods The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: ‘none’ (no exposure prior to surgery), ‘held’ (on chronic ACEi/ARB but held on the morning of surgery) or ‘continued’ (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were ‘functional’ AKI based upon changes in pre- to postoperative serum creatinine, and ‘structural AKI’, based upon peak postoperative levels of four urinary biomarkers of kidney injury. Results Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein). Conclusions Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted. PMID:24081864

  19. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in women of childbearing age: risks versus benefits.

    PubMed

    Pucci, Mark; Sarween, Nadia; Knox, Ellen; Lipkin, Graham; Martin, Una

    2015-03-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective and widely used antihypertensive drugs. Exposure to these agents is known to be harmful to the fetus in the second and third trimesters of pregnancy. Concerns have also been raised about the risk of congenital malformations if ACEIs or ARBs are taken during the first trimester of pregnancy. The evidence to date, however, is conflicting and observed malformations may be due to confounders such as undiagnosed diabetes or maternal obesity, other antihypertensive medications or the hypertension itself. Nonetheless, in women who become pregnant while taking an ACEI or ARB, the drug should be stopped as soon as possible. In women with chronic kidney disease and proteinuria, it may be appropriate to continue taking an ACEI or ARB until the pregnancy is confirmed because of the significant benefit to their kidney function and the lower fertility rate in these patients. PMID:25612630

  20. Isolation, Purification and Molecular Mechanism of a Peanut Protein-Derived ACE-Inhibitory Peptide

    PubMed Central

    Shi, Aimin; Liu, Hongzhi; Liu, Li; Hu, Hui; Wang, Qiang; Adhikari, Benu

    2014-01-01

    Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of peanut peptides using molecular simulation. The aim of this study was to obtain ACE inhibiting peptide from peanut protein and provide insight on the molecular mechanism of its ACE inhibiting action. Peanut peptides having ACE inhibitory activity were isolated through enzymatic hydrolysis and ultrafiltration. Further chromatographic fractionation was conducted to isolate a more potent peanut peptide and its antihypertensive activity was analyzed through in vitro ACE inhibitory tests and in vivo animal experiments. MALDI-TOF/TOF-MS was used to identify its amino acid sequence. Mechanism of ACE inhibition of P8 was analyzed using molecular docking and molecular dynamics simulation. A peanut peptide (P8) having Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence was obtained which had the highest ACE inhibiting activity of 85.77% (half maximal inhibitory concentration (IC50): 0.0052 mg/ml). This peanut peptide is a competitive inhibitor and show significant short term (12 h) and long term (28 days) antihypertensive activity. Dynamic tests illustrated that P8 can be successfully docked into the active pocket of ACE and can be combined with several amino acid residues. Hydrogen bond, electrostatic bond and Pi-bond were found to be the three main interaction contributing to the structural stability of ACE-peptide complex. In addition, zinc atom could form metal-carboxylic coordination bond with Tyr, Met residues of P8, resulting into its high ACE inhibiting activity. Our finding indicated that the peanut peptide (P8) having a Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence can be a promising candidate for functional foods and prescription drug aimed at control of hypertension. PMID:25347076

  1. Angiotensinogen (AGT) M235T, AGT T174M and Angiotensin-1-Converting Enzyme (ACE) I/D Gene Polymorphisms in Essential Hypertension: Effects on Ramipril Efficacy

    PubMed Central

    Kolovou, Vana; Lagou, Evangelia; Mihas, Constantinos; Vasiliki, Giannakopoulou; Katsiki, Niki; Kollia, Aikaterini; Triposkiadis, Filippos; Degiannis, Dimitris; Mavrogeni, Sophie; Kolovou, Genovefa

    2015-01-01

    Background: Hypertension, one of the most important risk factors for premature cardiovascular disease, is a major worldwide public health problem. Angiotensin-1-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms are thought to be associated with primary hypertension. In the present study, we examined the frequency of these gene polymorphisms in an adult population with and without essential hypertension. Furthermore, we evaluated the effect of ACE and AGT gene polymorphisms on ramipril treatment efficacy in the hypertensive patients. Methods: A total of 166 adults (83 hypertensives and 83 normotensives) were involved in the study and genotyped for AGTM235T (rs699), AGTT174M (rs4762) and ACEI/D (rs1799752) gene polymorphisms. Results: The genotype and allele distribution of the AGTM235T variant significantly differed between hypertensives and normotensives [odds ratio (OR) = 1.57% (T vs M allele), 95% confidence intervals (CIs): 1.01 - 2.44; p=0.045 for hypertensives]. However, none of the 3 studied Simple Nucleotide Polymorphisms were associated with the blood pressure-lowering response to ramipril. Conclusion: These results suggest that AGTM235T gene polymorphism is associated with essential hypertension. However, none of the AGTM235T, AGTT174M and ACEI/D gene polymorphisms influenced ramipril effectiveness. PMID:27006715

  2. Preparation and antihypertensive activity of peptides from Porphyra yezoensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research was to develop an antihypertensive peptide, an efficient angiotensin converting enzyme (ACE) inhibitor (ACEI), from Porphyra yezoensis. Seven commercial enzymes were screened and then enzymatic hydrolysis conditions were optimised. The results showed that alcalase was the most effectiv...

  3. Advanced Collaborative Emissions Study (ACES)

    SciTech Connect

    Greenbaum, Daniel; Costantini, Maria; Van Erp, Annemoon; Shaikh, Rashid; Bailey, Brent; Tennant, Chris; Khalek, Imad; Mauderly, Joe; McDonald, Jacob; Zielinska, Barbara; Bemis, Jeffrey; Storey, John; Hallberg, Lance; Clark, Nigel

    2013-12-31

    The objective of the Advanced Collaborative Emissions Study (ACES) was to determine before widespread commercial deployment whether or not the new, energy-efficient, heavy duty diesel engines (2007 and 2010 EPA Emissions Standards Compliant) may generate anticipated toxic emissions that could adversely affect the environment and human health. ACES was planned to take place in three phases. In Phase 1, extensive emissions characterization of four production-intent prototype engine and control systems designed to meet 2007 standards for nitrogen oxides (NOx) and particulate matter (PM) was conducted at an existing emissions characterization facility: Southwest Research Institute (SwRI). One of the tested engines was selected (at random, after careful comparison of results) for health testing in Phase 3. In Phase 2, extensive emission characterization of three production-intent prototype engine and control systems meeting the 2010 standards (including more advanced NOx controls to meet the more stringent 2010 NOx standards) was conducted at the same test facility. In Phase 3, one engine/aftertreatment system selected from Phase 1 was further characterized during health effects studies (at an existing inhalation toxicology laboratory: Lovelace Respiratory Research Institute, [LRRI]) to form the basis of the ACES safety assessment. The Department of Energy (DOE) award provided funding for emissions characterization in Phases 1 and 2 as well as exposure characterization in Phase 3. The main health analyses in Phase 3 were funded separately and are not reported here.

  4. β-blockers and Angiotensin Converting Enzyme Inhibitors: Comparison of Effects on Aortic Growth in Pediatric Patients with Marfan Syndrome

    PubMed Central

    Phomakay, Venusa; Huett, Wilson G.; Gossett, Jeffrey M.; Tang, Xinyu; Bornemeier, Renee A.; Collins, R. Thomas

    2015-01-01

    Objectives Angiotensin converting enzyme inhibitors (ACEI) have been shown to decrease AGV in Marfan syndrome (MFS). We sought to compare the effect of β-blockers and ACEI on aortic growth velocity (AGV) in MFS. Study design We reviewed retrospectively all data from all patients with MFS seen at Arkansas Children’s Hospital between January 1, 1976 and January 1, 2013. Generalized least squares were used to evaluate AGV over time as a function of age, medication group, and the interaction between the two. A mixed model was used to compare AGV between medication groups as a function of age, medication group (none, β-blocker, ACEI), and the interaction between the two. Results A total of 67 patients with confirmed MFS were identified (34/67, 51% female). Mean age at first encounter was 13 ± 10 years, with mean follow-up of 7.6 ± 5.8 years. There were 839 patient encounters with a median of 10 (range 2–42) encounters per patient. AGV was nearly normal in the β-blocker group, and was less than either the ACEI or untreated groups. The AGV was higher than normal in ACEI and untreated groups (p<0.001 for both). Conclusions β-blocker therapy results in near-normalization of AGV in MFS. ACEI did not decrease AGV in a clinically significant manner. PMID:25109242

  5. Targeted in-vivo computed tomography (CT) imaging of tissue ACE using concentrated lisinopril-capped gold nanoparticle solutions

    NASA Astrophysics Data System (ADS)

    Daniel, Marie-Christine; Aras, Omer; Smith, Mark F.; Nan, Anjan; Fleiter, Thorsten

    2010-04-01

    The development of cardiac and pulmonary fibrosis have been associated with overexpression of angiotensin-converting enzyme (ACE). Moreover, ACE inhibitors, such as lisinopril, have shown a benificial effect for patients diagnosed with heart failure or systemic hypertension. Thus targeted imaging of the ACE is of crucial importance for monitoring of the tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-capped gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. Concentrated solutions of these modified gold nanoparticles, with a diameter around 16 nm, showed high contrast in CT imaging. These new targeted imaging agents were thus used for in vivo imaging on rat models.

  6. ACE VET Linkages: Provider, Student and Industry Views.

    ERIC Educational Resources Information Center

    Saunders, John

    In recent years, Australia's system of adult and community education (ACE) has broadened to include vocational learning as well as the hobby, enrichment, and personal development traditionally provided by ACE in the past. A study examined the views of ACE providers, ACE students, and industry organizations regarding ACE vocational education and…

  7. Angiotensin-converting enzyme inhibitors in veterinary medicine.

    PubMed

    Lefebvre, H P; Brown, S A; Chetboul, V; King, J N; Pouchelon, J-L; Toutain, P L

    2007-01-01

    Angiotensin-converting enzyme (ACE) inhibitors represent one of the most commonly used categories of drugs in canine and feline medicine. ACE inhibitors currently approved for use in veterinary medicine are benazepril, enalapril, imidapril and ramipril. They are all pro-drugs administered by oral route. A physiologically based model taking into account the saturable binding to ACE has been developed for pharmacokinetic analysis. The bioavailability of the active compounds from their respective pro-drug is low. The active metabolites are eliminated by renal, hepatorenal or biliary excretion, according to the drug. The elimination half-life of the free fraction of the active compounds is very short (ranging from approximately 10 min to 2 h). ACE inhibitors are generally well tolerated. Benazepril, enalapril, imidapril and ramipril are approved for dogs with chronic heart failure (CHF). The efficacy of ACE inhibitors has been convincingly demonstrated in dogs with CHF, especially in those with chronic valvular disease. In such clinical settings, ACE inhibitors improve hemodynamics and clinical signs, and increase survival time. In cats with cardiovascular disease, little information is available except for reports of some benefit in cats with hypertrophic cardiomyopathy in two non-controlled investigations. ACE inhibitors have also a mild to moderate hypotensive effect. There is also evidence to recommend ACE inhibitors in dogs and cats with chronic renal failure (CRF). They decrease the glomerular capillary pressure, have antiproteinuric effects, tend to delay the progression of CRF and to limit the extent of renal lesions. PMID:17506720

  8. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study.

    PubMed

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-05-01

    Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78-0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66-0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  9. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    SciTech Connect

    Wang, Hongmei; Liao, Zhongxing; Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O'Reilly, Michael; Gold, Kathryn A.; Gomez, Daniel R.

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  10. Transdermal delivery of Angiotensin Converting Enzyme inhibitors.

    PubMed

    Helal, Fouad; Lane, Majella E

    2014-09-01

    The Angiotensin Converting Enzyme (ACE) inhibitor class of drugs has been in clinical use since the 1970s for the management of all grades of heart failure, hypertension, diabetic nephropathy and prophylaxis of cardiovascular events. Because of the advantages associated with transdermal delivery compared with oral delivery many researchers have investigated the skin as a portal for administration of ACE inhibitors. This review summarises the various studies reported in the literature describing the development and evaluation of transdermal formulations of ACE inhibitors. Captopril, enalapril maleate, lisinopril dihydrate, perindopril erbumine and trandolapril are the most studied in connection with transdermal preparations. The methodologies reported are considered critically and the limitations of the various skin models used are also highlighted. Finally, opportunities for novel transdermal preparations of ACE inhibitor drugs are discussed with an emphasis on rational formulation design. PMID:24657822

  11. ACE program/UNIX user manual

    SciTech Connect

    Feng-Berman, S.K.

    1993-01-12

    This report the following: How to use the ace program ; Introduction to the ace program; Online command; Define a macro file; Macro commands; Counters and MCA; Counters usage; Counters database; Feedback Counter Database; MCA functions and macro command; X window Interclient Communication; and How to get around in UNIX

  12. ACE program/UNIX user manual

    SciTech Connect

    Feng-Berman, S.K.

    1993-01-12

    This report the following: How to use the ace program?; Introduction to the ace program; Online command; Define a macro file; Macro commands; Counters and MCA; Counters usage; Counters database; Feedback Counter Database; MCA functions and macro command; X window Interclient Communication; and How to get around in UNIX?

  13. Mega clinical trials which have shaped the RAS intervention clinical practice.

    PubMed

    Düsing, Rainer

    2016-06-01

    Following extensive clinical research, drugs affecting the renin-angiotensin system have been used for the treatment of patients with congestive heart failure, myocardial infarction, hypertension, diabetic nephropathy, chronic renal failure and for reducing the risk of developing major cardiovascular (CV) events. This review examines all mega trials (those involving >1000 patients) and smaller pivotal trials involving angiotensin-converting enzyme inhibitors (ACE-Is; 25 mega trials) and angiotensin receptor blockers (ARBs; 27 mega trials) to provide perspective on the huge database of evidence that has accumulated on the use of these drugs. Our review demonstrates that ACE-Is and ARBs are generally as effective as conventional therapies in the treatment of hypertension, but offer additional cardioprotective benefits in patients with heart failure, and in those who have experienced myocardial infarction. Also, both ACE-Is and ARBs are capable of renal protection in addition to their blood-pressure-lowering effects. Although ACE-Is and ARBs provide major benefits to CV patients, doubts remain over the concept of blood-pressure-independent CV protection offered by both classes of drugs. ACE-Is and ARBs appear to be equally effective with respect to morbidity and mortality endpoints, but ARBs are better tolerated. Considering the available evidence, the combined use of an ACE-I and ARB should be avoided and full doses of either ACE-I or ARB should be aimed for as evidence suggests they provide a greater prognostic benefit. PMID:27271312

  14. CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors.

    PubMed

    Wang, X; Wang, G; Shi, J; Aa, J; Comas, R; Liang, Y; Zhu, H-J

    2016-06-01

    The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs. PMID:26076923

  15. [Psychotropic effects of angiotensin-converting enzyme inhibitors: what are the arguments?].

    PubMed

    Mesure, G; Fallet, A; Chevalier, J F

    1995-01-01

    The authors report a case of acute mania induced by perindopril (Coversyl) in a 57 year old man with no prior history of mental illness. This Angiotensin-Converting Enzyme Inhibitor (ACEI) had been introduced eight days prior to the first signs of excitation, in order to treat recently diagnosed arterial hypertension. Without proof of reintroduction, and on the basis of clinical observations, the attribution appears plausible. Similar observations have been made for other molecules in this class of medication, such as captopril (Lopril). A review of literature regroups recent data concerning psychotropic effects of ACEIs. Several reports claim that captopril clearly acts as an antidepressant. Studies on the mood or the quality of life of treated hypertensive patients show ACEIs to have an euphoric-type positive effect compared to other anti-hypertensive treatments. Captopril and perindopril also act like potential antidepressants in experimental models of antidepression. Furthermore, pharmacologic data confirm that the most lipophilic ACEIs penetrate the central nervous system and argue in favor of the role of these molecules in activating central opioides. As these data provide evidence of mood swing in some patients, but also of an overall benefit in hypertensive populations, the clinical importance of the antidepressant effect of ACEIs needs further investigations. PMID:8529571

  16. Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

    PubMed Central

    2012-01-01

    Background A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. Methods Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. Results The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (

  17. Advanced control evaluation for structures (ACES) programs

    NASA Technical Reports Server (NTRS)

    Pearson, Jerome; Waites, Henry

    1988-01-01

    The ACES programs are a series of past, present, and future activities at the Marshall Space Flight Center (MSFC) Ground facility for Large Space Structure Control Verification (GF/LSSCV). The main objectives of the ACES programs are to implement control techniques on a series of complex dynamical systems, to determine the control/structure interaction for the control techniques, and to provide a national facility in which dynamics and control verification can be effected. The focus is on these objectives and how they are implemented under various engineering and economic constraints. Future plans that will be effected in upcoming ACES programs are considered.

  18. Impact of Angiotensin Converting Enzyme Inhibitor versus Angiotensin Receptor Blocker on Incidence of New-Onset Diabetes Mellitus in Asians

    PubMed Central

    Park, Ji Young; Choi, Byoung Geol; Choi, Se Yeon; Choi, Jae Woong; Ryu, Sung Kee; Lee, Se Jin; Kim, Seunghwan; Noh, Yung-Kyun; Akkala, Raghavender Goud; Li, Hu; Ali, Jabar; Kim, Ji Bak; Lee, Sunki; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Jin Won; Kim, Eung Ju; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo

    2016-01-01

    Purpose Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are associated with a decreased incidence of new-onset diabetes mellitus (NODM). The aim of this study was to compare the protective effect of ACEI versus ARBs on NODM in an Asian population. Materials and Methods We investigated a total of 2817 patients who did not have diabetes mellitus from January 2004 to September 2009. To adjust for potential confounders, a propensity score matched (PSM) analysis was performed using a logistic regression model. The primary end-point was the cumulative incidence of NODM, which was defined as having a fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%. Multivariable cox-regression analysis was performed to determine the impact of ACEI versus ARB on the incidence of NODM. Results Mean follow-up duration was 1839±1019 days in all groups before baseline adjustment and 1864±1034 days in the PSM group. After PSM (C-statistics=0.731), a total 1024 patients (ACEI group, n=512 and ARB group, n=512) were enrolled for analysis and baseline characteristics were well balanced. After PSM, the cumulative incidence of NODM at 3 years was lower in the ACEI group than the ARB group (2.1% vs. 5.0%, p=0.012). In multivariate analysis, ACEI vs. ARB was an independent predictor of the lower incidence for NODM (odd ratio 0.37, confidence interval 0.17-0.79, p=0.010). Conclusion In the present study, compared with ARB, chronic ACEI administration appeared to be associated with a lower incidence of NODM in a series of Asian cardiovascular patients. PMID:26632399

  19. Spermidine Derivatives in Lulo (Solanum quitoense Lam.) Fruit: Sensory (Taste) versus Biofunctional (ACE-Inhibition) Properties.

    PubMed

    Forero, Diana Paola; Masatani, Chieko; Fujimoto, Yoshinori; Coy-Barrera, Ericsson; Peterson, Devin G; Osorio, Coralia

    2016-07-01

    The bitterness in lulo (Solanum quitoense Lam.) fruit is increased during processing (juicing or drying). To identify the bitter-active compounds, the ethanolic fruit pulp extract was subjected to RP-18 solid-phase extraction, and then sensory-guided fractionated by HPLC. Two spermidine derivatives, N(1),N(4),N(8)-tris(dihydrocaffeoyl)spermidine and N(1),N(8)-bis(dihydrocaffeoyl)spermidine, were isolated and their structures confirmed by analysis of their HPLC-ESI/MS and (1)H and (13)C NMR data. The N(1),N(4),N(8)-tris(dihydrocaffeoyl)spermidine was synthesized and used as an authentic sample to unequivocally confirm the structure of this compound and to quantitate it in both fresh and dried fruit. In silico analyses demonstrated that spermidine derivatives identified in lulo pulp exhibited a strong ACE-I (angiotensin I-converting enzyme) inhibitory activity. Subsequently, these results were confirmed by in vitro analyses and showed the potential use of lulo fruit pulp as an ingredient of functional foods related to the prevention of blood hypertension. PMID:27292771

  20. FIRE_ACE_ER2_MAS

    Atmospheric Science Data Center

    2015-10-28

    ... First ISCCP Regional Experiment (FIRE) Arctic Cloud Experiment (ACE) NASA ER-2 Moderate Resolution Imaging ... SSFR Location:  Northern Alaska Arctic Ocean Spatial Coverage:  Fairbanks, Alaska and the surrounding ...

  1. Cell cycle dependence of ACE-2 explains downregulation in idiopathic pulmonary fibrosis.

    PubMed

    Uhal, Bruce D; Dang, MyTrang; Dang, Vinh; Llatos, Roger; Cano, Esteban; Abdul-Hafez, Amal; Markey, Jonathan; Piasecki, Christopher C; Molina-Molina, Maria

    2013-07-01

    Alveolar epithelial type II cells, a major source of angiotensin-converting enzyme (ACE)-2 in the adult lung, are normally quiescent but actively proliferate in lung fibrosis and downregulate this protective enzyme. It was, therefore, hypothesised that ACE-2 expression might be related to cell cycle progression. To test this hypothesis, ACE-2 mRNA levels, protein levels and enzymatic activity were examined in fibrotic human lungs and in the alveolar epithelial cell lines A549 and MLE-12 studied at postconfluent (quiescent) versus subconfluent (proliferating) densities. ACE-2 mRNA, immunoreactive protein and enzymatic activity were all high in quiescent cells, but were severely downregulated or absent in actively proliferating cells. Upregulation of the enzyme in cells that were progressing to quiescence was completely inhibited by the transcription blocker actinomycin D or by SP600125, an inhibitor of c-Jun N-terminal kinase (JNK). In lung biopsy specimens obtained from patients with idiopathic pulmonary fibrosis, immunoreactive enzyme was absent in alveolar epithelia that were positive for proliferation markers, but was robustly expressed in alveolar epithelia devoid of proliferation markers. These data explain the loss of ACE-2 in lung fibrosis and demonstrate cell cycle-dependent regulation of this protective enzyme by a JNK-mediated transcriptional mechanism. PMID:23100504

  2. General relativistic observables for the ACES experiment

    NASA Astrophysics Data System (ADS)

    Turyshev, Slava G.; Yu, Nan; Toth, Viktor T.

    2016-02-01

    We develop a high-precision model for relativistic observables of the Atomic Clock Ensemble in Space (ACES) experiment on the International Space Station (ISS). We develop all relativistic coordinate transformations that are needed to describe the motion of ACES in Earth orbit and to compute observable quantities. We analyze the accuracy of the required model as it applies to the proper-to-coordinate time transformations, light-time equation, and spacecraft equations of motion. We consider various sources of nongravitational noise and their effects on ACES. We estimate the accuracy of orbit reconstruction that is needed to satisfy the ACES science objectives. Based on our analysis, we derive models for the relativistic observables of ACES, which also account for the contribution of atmospheric drag on the clock rate. We include the Earth's oblateness coefficient J2 and the effects of major nongravitational forces on the orbit of the ISS. We demonstrate that the ACES reference frame is pseudoinertial at the level of accuracy required by the experiment. We construct a Doppler-canceled science observable representing the gravitational redshift. We derive accuracy requirements for ISS navigation. The improved model is accurate up to <1 ps and ˜4 ×1 0-17 for time and frequency transfers, correspondingly. These limits are determined by the higher-order harmonics in Earth's gravitational potential.

  3. The Aerosol/Cloud/Ecosystems Mission (ACE)

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark

    2008-01-01

    The goals and measurement strategy of the Aerosol/Cloud/Ecosystems Mission (ACE) are described. ACE will help to answer fundamental science questions associated with aerosols, clouds, air quality and global ocean ecosystems. Specifically, the goals of ACE are: 1) to quantify aerosol-cloud interactions and to assess the impact of aerosols on the hydrological cycle and 2) determine Ocean Carbon Cycling and other ocean biological processes. It is expected that ACE will: narrow the uncertainty in aerosol-cloud-precipitation interaction and quantify the role of aerosols in climate change; measure the ocean ecosystem changes and precisely quantify ocean carbon uptake; and, improve air quality forecasting by determining the height and type of aerosols being transported long distances. Overviews are provided of the aerosol-cloud community measurement strategy, aerosol and cloud observations over South Asia, and ocean biology research goals. Instruments used in the measurement strategy of the ACE mission are also highlighted, including: multi-beam lidar, multiwavelength high spectra resolution lidar, the ocean color instrument (ORCA)--a spectroradiometer for ocean remote sensing, dual frequency cloud radar and high- and low-frequency micron-wave radiometer. Future steps for the ACE mission include refining measurement requirements and carrying out additional instrument and payload studies.

  4. An Unusual Case of Angiotensin-Converting-Enzyme Inhibitor-Related Penile Angioedema with Evolution to the Oropharynx

    PubMed Central

    Wagner, Jonathan G.; Bench, Elias M.; Plantmason, Lee

    2015-01-01

    A 52-year-old African American male with a long history of poorly controlled hypertension presented to the emergency department (ED) with two days of genital edema and pain. During ED work-up, the patient developed sudden onset of non-pitting, non-pruritic, and non-urticarial upper lip edema. Review of his antihypertensive medication list revealed that he normally took benazepril, highly suggestive of a diagnosis of angiotensin-converting-enzyme inhibitor-related angioedema (ACEI-RA). We present the first reported case of penile ACEI-RA that progressed to involve the oropharynx. The ED management of the condition and some of the newer treatment options available for ACEI-RA is also briefly discussed. PMID:26759679

  5. Regional Aerosol Optical Depth Characteristics from Satellite Observations: ACE-1, TARFOX and ACE-2 Results

    NASA Technical Reports Server (NTRS)

    Durkee, P. A.; Nielsen, K. E.; Smith, P. J.; Russell, P. B.; Schmid, B.; Livingston, J. M.; Holben, B. N.; Tomasi, C.; Vitale, V.; Collins, D.

    1999-01-01

    Analysis of the aerosol properties during 3 recent international field campaigns ACE-1, TARFOX and ACE-2 are described using satellite retrievals from NOAA AVHRR data. Validation of the satellite retrieval procedure is performed with airborne, shipboard, and land-based sunphotometry during ACE-2. The intercomparison between satellite and surface optical depths has a correlation coefficient of 0.93 for 630 nm wavelength and 0.92 for 860 nm wavelength, The standard error of estimate is 0.025 for 630 nm wavelength and 0.023 for 860 nm wavelength. Regional aerosol properties are examined in composite analysis of aerosol optical properties from the ACE-1, TARFOX and ACE-2 regions. ACE-1 and ACE-2 regions have strong modes in the distribution of optical depth around 0.1, but the ACE-2 tails toward higher values yielding an average of 0.16 consistent with pollution and dust aerosol intrusions. The TARFOX region has a noticeable mode of 0.2, but has significant spread of aerosol optical depth values consistent with the varied continental aerosol constituents off the eastern North American Coast.

  6. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study).

    PubMed

    AlJaroudi, Wael A; Refaat, Marwan M; Habib, Robert H; Al-Shaar, Laila; Singh, Madhurmeet; Gutmann, Rebecca; Bloom, Heather L; Dudley, Samuel C; Ellinor, Patrick T; Saba, Samir F; Shalaby, Alaa A; Weiss, Raul; McNamara, Dennis M; Halder, Indrani; London, Barry

    2015-04-01

    Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2). PMID:25682436

  7. Angiotensin II-inhibition: effect on Alzheimer’s pathology in the aged triple transgenic mouse

    PubMed Central

    Ferrington, Linda; Palmer, Laura E.; Love, Seth; Horsburgh, Karen J; Kelly, Paul AT; Kehoe, Patrick G

    2012-01-01

    Reducing excessive accumulation of amyloid-β (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies, and inhibition of angiotensin-converting enzyme (ACE) may delay onset or progression of AD. The effects of an ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Aβ and tau pathology in a triple transgenic (3xTGAD) mouse model of AD were investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6 months. Mean arterial blood pressure (MABP) was measured periodically and mice were assessed behaviourally. Aβ, phospho-tau, amyloid precursor protein (APP) and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3 months in the ACE-I group and at 3 months in the ARB group, compared to vehicle. Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze, nor were Aβ, tau immunolabelling or APP levels altered. ACE-I significantly reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not affect Aβ or phospho-tau accumulation in brains of aged 3xTGAD mice. PMID:22611468

  8. Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

    PubMed Central

    Huang, Rong-Shuang; Cheng, Yi-Ming; Zeng, Xiao-Xi; Kim, Sehee; Fu, Ping

    2016-01-01

    Background: Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD. Methods: Publications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted. Results: Based on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.52–1.33) and cardiovascular events (RR = 0.58; 95% CI: 0.21–1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = −1.28 mmHg; 95% CI: −3.18 to −0.62), proteinuria (standard mean difference = −0.55; 95% CI: −1.41 to −0.30), GFR (WMD = −0.32 ml/min; 95% CI: −1.53 to −0.89), and occurrence of adverse events (RR = 1.05; 95% CI: 0.72–1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = −4.46 mmHg; 95% CI: −6.95 to −1.97), compared with ACEI/ARB monotherapy. Conclusion: ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy. PMID:26904991

  9. Angiotensin converting enzyme inhibitors as oxygen free radical scavengers.

    PubMed

    Mira, M L; Silva, M M; Queiroz, M J; Manso, C F

    1993-01-01

    The authors have compared the ability of two non-SH-containing angiotensin converting enzyme (ACE) inhibitors (enalaprilat and lisinopril) with an -SH containing ACE inhibitor (captopril) to scavenge the hydroxyl radical (.OH). All three compounds were able to scavenge .OH radicals generated in free solution at approximately diffusion-controlled rates (10(10) M-1 s-1) as established by the deoxyribose assay in the presence of EDTA. The compounds also inhibited deoxyribose degradation in reaction mixtures which did not contain EDTA but not so effectively. This later findings also suggests that they have some degree of metal-binding capability. Chemiluminescence assays of oxidation of hypoxanthine by xanthine oxidase in the presence of luminol, confirm that the three ACE inhibitors are oxygen free radical scavengers. Our results indicate that the presence of a sulphydryl group in the chemical structure of ACE inhibitors is not relevant for their oxygen free radical scavenging ability. PMID:8244086

  10. Inhibition of ACE Retards Tau Hyperphosphorylation and Signs of Neuronal Degeneration in Aged Rats Subjected to Chronic Mild Stress

    PubMed Central

    AbdAlla, Said; el Hakim, Ahmed; Abdelbaset, Ahmed; Elfaramawy, Yasser; Quitterer, Ursula

    2015-01-01

    With increasing life expectancy, Alzheimer's disease (AD) and other types of age-associated dementia are on the rise worldwide. Treatment approaches for dementia are insufficient and novel therapies are not readily available. In this context repurposing of established drugs appears attractive. A well-established class of cardiovascular drugs, which targets the angiotensin II system, is such a candidate, which currently undergoes a paradigm shift with regard to the potential benefit for treatment of neurodegenerative symptoms. In search for additional evidence, we subjected aged rats to chronic unpredictable mild stress, which is known to enhance the development of AD-related neuropathological features. We report here that four weeks of chronic mild stress induced a strong upregulation of the hippocampal angiotensin-converting enzyme (Ace) at gene expression and protein level. Concomitantly, tau protein hyperphosphorylation developed. Signs of neurodegeneration were detected by the significant downregulation of neuronal structure proteins such as microtubule-associated protein 2 (Map2) and synuclein-gamma (Sncg). Ace was involved in neurodegenerative symptoms because treatment with the brain-penetrating ACE inhibitor, captopril, retarded tau hyperphosphorylation and signs of neurodegeneration. Moreover, ACE inhibitor treatment could counteract glutamate neurotoxicity by preventing the downregulation of glutamate decarboxylase 2 (Gad2). Taken together, ACE inhibition targets neurodegeneration triggered by environmental stress. PMID:26697495

  11. Remarks on KERMA Factors in ACE files

    NASA Astrophysics Data System (ADS)

    Konno, C.; Ochiai, K.; Takakura, K.; Sato, S.

    2014-04-01

    Some neutron KERMA factors in ACE files are negative and extremely large if nuclear data libraries do not keep energy-balance. The status of neutron KERMA factors in the official ACE file of ENDF/B-VII.1 is examined. As a result, it is found out that neutron KERMA factors of nuclei more than 200 in ENDF/B-VII.1 have some problems. Effects of the inadequate KERMA factor are also investigated, which are large for neutron heat while those are small for total (neutron + gamma) heat. Users who use only neutron KERMA factors should check if the factors are adequate or not before they use the factors.

  12. Renal ACE immunohistochemical localization in NIDDM patients with nephropathy.

    PubMed

    Mizuiri, S; Yoshikawa, H; Tanegashima, M; Miyagi, M; Kobayashi, M; Sakai, K; Hayashi, I; Aikawa, A; Ohara, T; Hasegawa, A

    1998-02-01

    A role of renal angiotensin-converting enzyme (ACE) in diabetic nephropathy has been suggested. Immunohistochemical localization of ACE was studied in 20 non-insulin-dependent diabetes mellitus patients with diabetic nephropathy and 17 healthy kidney transplant donors, with ACE gene insertion/deletion (I/D) polymorphism also examined in the latter. Immunohistochemical studies indicated that ACE staining was significantly (P < 0.01) enhanced in glomeruli and slightly decreased in proximal tubules in diabetic patients. Glomeruli positive for ACE immunostaining were observed in 23.5% of the healthy subjects and in 80% of the diabetic patients. All patients with nodular lesions had ACE-positive glomeruli and showed significantly (P < 0.01) more intense glomerular ACE immunostaining than patients without nodular lesions. Among healthy controls, subjects with the DD genotype had ACE-positive glomeruli more frequently and tended to show slightly increased intensity on proximal tubule ACE immunostaining compared with subjects with other genotypes. These observations suggest that increased ACE localization in glomeruli is likely to be one of the factors in the increased renin-angiotensin system activity in glomeruli in patients with diabetic nephropathy. There is a possibility that ACE gene I/D polymorphism may be related to renal ACE immunohistochemical localization. PMID:9469501

  13. Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy

    PubMed Central

    Saleem, Saba; Azam, Aisha; Maqsood, Sundus Ijaz; Muslim, Irfan; Bashir, Shaheena; Fazal, Nosheen; Riaz, Moeen; Ali, Syeda Hafiza Benish; Niazi, Muhammad Khizar; Ishaq, Mazhar; Waheed, Nadia Khalida; Qamar, Raheel; Azam, Maleeha

    2015-01-01

    In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR). PMID:26658948

  14. Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy.

    PubMed

    Saleem, Saba; Azam, Aisha; Maqsood, Sundus Ijaz; Muslim, Irfan; Bashir, Shaheena; Fazal, Nosheen; Riaz, Moeen; Ali, Syeda Hafiza Benish; Niazi, Muhammad Khizar; Ishaq, Mazhar; Waheed, Nadia Khalida; Qamar, Raheel; Azam, Maleeha

    2015-01-01

    In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04-3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098-4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR). PMID:26658948

  15. Advanced Colloids Experiment (ACE-T1)

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ron; Brown, Dan; Eustace, John

    2015-01-01

    Increment 45 - 46 Science Symposium presentation of Advanced Colloids Experiment (ACE-T1) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

  16. Advanced Colloids Experiment (ACE-H-2)

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ron; Chmiel, Alan J.; Eustace, John; LaBarbera, Melissa

    2015-01-01

    Increment 43 - 44 Science Symposium presentation of Advanced Colloids Experiment (ACE-H-2) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

  17. Developing Communities: Serving ACE through Tertiary Education

    ERIC Educational Resources Information Center

    Sofo, Francesco

    2011-01-01

    Purpose: The purpose of this paper is to review the focus and practice of Adult and Community Education (ACE) as well as its conceptualization and delivery and to suggest parameters for an approach based on excellence, a balanced scorecard and performance to meet community needs. Design/methodology/approach: The review examines key aspects of the…

  18. Ace the Verbal on the SAT

    ERIC Educational Resources Information Center

    Meierding, Loren

    2005-01-01

    Many students are not accepted in to certain colleges and universities because of low SAT scores. Loren Meierding has written Ace the Verbal on the SAT to help students with minimal preparation do well by improving their vocabulary and use better techniques for finding the answers to the questions. This book provides strategies needed to score…

  19. Renoprotective effects of renin–angiotensin system inhibitor combined with calcium channel blocker or diuretic in hypertensive patients

    PubMed Central

    Cheng, Yiming; Huang, Rongshuang; Kim, Sehee; Zhao, Yuliang; Li, Yi; Fu, Ping

    2016-01-01

    Abstract Objectives: To conduct a meta-analysis of studies comparing the renoprotective effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) combined with either calcium channel blocker (CCB) or diuretic, but not both, in hypertensive patients. Data sources: Pubmed, Embase, Medline, and Cochrane databases were searched to identify randomized controlled trials (RCTs) of blood pressure lowering treatments in patients with hypertension. Study selection: RCTs comparing the renoprotective effects of ACEI/ARB plus CCB with ACEI/ARB plus diuretic in hypertensive patients, with at least one of the following reported outcomes: urinary protein, estimated glomerular filtration rate/creatinine clearance (eGFR/CrCl), or serum creatinine. Results: Based on 14 RCTs with 18,125 patients, statistically significant benefits were found in ACEI/ARB plus CCB for maintaining eGFR/CrCl (standardized mean difference [SMD] = 0.36; 95% confidence interval [CI]: 0.20–0.53; P < 0.001), serum creatinine reduction (mean difference [MD] = −0.05 mg/dL; 95% CI: −0.07 to −0.03; P < 0.001). However, no statistical differences were found between the 2 therapeutic strategies in terms of urinary protein (MD = 7.48%; 95% CI: –6.13% to 21.08%; P = 0.28; I2 = 92%). Conclusions: This meta-analysis concluded that ACEI/ARB plus CCB have a stronger effect on the maintenance of renal function in patients with hypertension than ACEI/ARB plus diuretic. PMID:27428210

  20. Angiotensin-Converting Enzyme Inhibitor Use and Major Cardiovascular Outcomes in Type 2 Diabetes Mellitus Treated With the Dipeptidyl Peptidase 4 Inhibitor Alogliptin.

    PubMed

    White, William B; Wilson, Craig A; Bakris, George L; Bergenstal, Richard M; Cannon, Christopher P; Cushman, William C; Heller, Simon K; Mehta, Cyrus R; Nissen, Steven E; Zannad, Faiez; Kupfer, Stuart

    2016-09-01

    Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors. PMID:27480840

  1. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination

    PubMed Central

    Cagnoni, Francesca; Njwe, Christian Achiri Ngu; Zaninelli, Augusto; Ricci, Alessandra Rossi; Daffra, Diletta; D’Ospina, Antonio; Preti, Paola; Destro, Maurizio

    2010-01-01

    The renin–angiotensin–aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination. PMID:20730071

  2. [A Case of Life-Threatening Angioedema Occurred During Prolonged Angiotensin-Converting Enzyme Inhibitor Treatment].

    PubMed

    Nakamura, Rintaro; Nihei, Shun-Ichi; Arai, Hideaki; Nagata, Keiji; Isa, Yasuki; Harayama, Nobuya; Aibara, Keiji; Kamochi, Msayuki

    2016-03-01

    Although angiotensin-converting enzyme (ACE) inhibitors are widely used as the first choice drug for treating hypertension, we have only a superficial understanding of their relationship to angioedema. We report a case of life-threatening angioedema. The case was a 60-year-old man who had been taking an ACE inhibitor for hypertension for 11 years. He visited his home doctor for dyspnea, and tongue and neck swelling. He was transported to our hospital because of the possibility of airway obstruction. On admission, his tongue and neck swelling became more severe. We performed an intubation using an endoscope and started airway management. We also stopped his ACE inhibitor. The severe tongue and neck swelling improved gradually and he was extubated on day 3. On the fifth day he was discharged. We diagnosed angioedema caused by an ACE inhibitor. Although the risk of airway obstruction with ACE inhibitors is acknowledged, we have only a superficial understanding of how prolonged ACE inhibitor treatment induces angioedema. So we should consider angioedema in cases of taking ACE inhibitors, especially in cases of prolonged treatment. PMID:26972946

  3. Synthesis and biological studies of highly concentrated lisinopril-capped gold nanoparticles for CT tracking of angiotensin converting enzyme (ACE)

    NASA Astrophysics Data System (ADS)

    Ghann, William E.; Aras, Omer; Fleiter, Thorsten; Daniel, Marie-Christine

    2011-05-01

    For patients with a history of heart attack or stroke, the prevention of another cardiovascular or cerebrovascular event is crucial. The development of cardiac and pulmonary fibrosis has been associated with overexpression of tissue angiotensin-converting enzyme (ACE). Recently, gold nanoparticles (GNPs) have shown great potential as X-ray computed tomography (CT) contrast agents. Since lisinopril is an ACE inhibitor, it has been used as coating on GNPs for targeted imaging of tissue ACE in prevention of fibrosis. Herein, lisinopril-capped gold nanoparticles (LIS-GNPs) were synthesized up to a concentration of 55 mgAu/mL. Their contrast was measured using CT and the results were compared to Omnipaque, a commonly used iodine-based contrast agent. The targeting ability of these LIS-GNPs was also assessed.

  4. Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

    SciTech Connect

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio

    2013-12-06

    Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

  5. Pollen Count and Presentation of Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema

    PubMed Central

    Straka, Brittany; Nian, Hui; Sloan, Chantel; Byrd, James Brian; Woodard-Grice, Alencia; Yu, Chang; Stone, Elizabeth; Steven, Gary; Hartert, Tina; Teo, Koon K.; Pare, Guillaume; McCarty, Catherine A.; Brown, Nancy J.

    2014-01-01

    BACKGROUND The incidence of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema is increased in patients with seasonal allergies. OBJECTIVE We tested the hypothesis that patients with ACE inhibitor-associated angioedema present during months when pollen counts are increased. METHODS Cohort analysis examined the month of presentation of ACE inhibitor-associated angioedema and pollen counts in the ambulatory and hospital setting. Patients with ACE inhibitor-associated angioedema were ascertained through (1) an observational study of patients presenting to Vanderbilt University Medical Center, (2) patients presenting to the Marshfield Clinic and participating in the Marshfield Clinic Personalized Medicine Research Project, and (3) patients enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE inhibitor-associated angioedema, population exposure to ACE inhibitor by date, and local pollen counts by date. RESULTS At Vanderbilt, the rate of angioedema was significantly associated with tree pollen months (P = .01 from χ2 test). When separate analyses were conducted in patients with a history of seasonal allergies and patients without, the rate of ACE inhibitor-associated angioedema was increased during tree pollen months only in patients with a history of seasonal allergies (P = .002). In Marshfield, the rate of angioedema was significantly associated with ragweed pollen months (P = .025). In ONTARGET, a positive trend was observed between the ACE inhibitor-associated angioedema rate and grass season, although it was not statistically significant (P = .057). CONCLUSIONS Patients with ACE inhibitor-associated angioedema are more likely to present with this adverse drug event during months when pollen counts are increased. PMID:24565618

  6. ACES-PHARAO : Microwave link data processing

    NASA Astrophysics Data System (ADS)

    Meynadier, F.; Delva, P.; Le Poncin-Lafitte, C.; Laurent, P.; Wolf, P.

    2011-12-01

    The Atomic Clocks Ensemble in Space (PHARAO-ACES mission, te{Salomon2007}), which will be installed on board the International Space Station , uses a dedicated two-way microwave link in order to compare the timescale generated on board with those provided by many ground stations disseminated on the Earth. Phase accuracy and stability of this long range link will have a key role in the success of the PHARAO-ACES experiment. The SYRTE is heavily involved in the design and the development of the data processing software : from theoretical modelling and numerical simulations to the development of a software prototype. Our team is working on a wide range of problems that need to be solved in order to achieve high accuracy in (almost) real time. In this poster we present some key aspects of the measurement, as well as the current status of the software's development.

  7. Regulation of alveolar epithelial cell survival by the ACE-2/angiotensin 1-7/Mas axis.

    PubMed

    Uhal, Bruce D; Li, Xiaopeng; Xue, Anita; Gao, Xu; Abdul-Hafez, Amal

    2011-09-01

    Earlier work from this laboratory demonstrated that apoptosis of alveolar epithelial cells (AECs) requires autocrine generation of angiotensin (ANG) II. More recent studies showed that angiotensin converting enzyme-2 (ACE-2), which degrades ANGII to form ANG1-7, is protective but severely downregulated in human and experimental lung fibrosis. Here it was theorized that ACE-2 and its product ANG1-7 might therefore regulate AEC apoptosis. To evaluate this hypothesis, the AEC cell line MLE-12 and primary cultures of rat AECs were exposed to the profibrotic apoptosis inducers ANGII or bleomycin (Bleo). Markers of apoptosis (caspase-9 or -3 activation and nuclear fragmentation), steady-state ANGII and ANG1-7, and JNK phosphorylation were measured thereafter. In the absence of Bleo, inhibition of ACE-2 by small interfering RNA or by a competitive inhibitor (DX600 peptide) caused a reciprocal increase in autocrine ANGII and corresponding decrease in ANG1-7 in cell culture media (both P < 0.05) and, moreover, induced AEC apoptosis. At baseline (without inhibitor), ANG1-7 in culture media was 10-fold higher than ANGII (P < 0.01). Addition of purified ANGII or bleomycin-induced caspase activation, nuclear fragmentation, and JNK phosphorylation in cultured AECs. However, preincubation with ANG1-7 (0.1 μM) prevented JNK phosphorylation and apoptosis. Moreover, pretreatment with A779, a specific blocker of the ANG1-7 receptor mas, prevented ANG1-7 blockade of JNK phosphorylation, caspase activation, and nuclear fragmentation. These data demonstrate that ACE-2 regulates AEC survival by balancing the proapoptotic ANGII and its antiapoptotic degradation product ANG1-7. They also suggest that ANG1-7 inhibits AEC apoptosis through the ANG1-7 receptor mas. PMID:21665960

  8. Human Recombinant ACE2 Reduces the Progression of Diabetic Nephropathy

    PubMed Central

    Oudit, Gavin Y.; Liu, George C.; Zhong, JiuChang; Basu, Ratnadeep; Chow, Fung L.; Zhou, Joyce; Loibner, Hans; Janzek, Evelyne; Schuster, Manfred; Penninger, Josef M.; Herzenberg, Andrew M.; Kassiri, Zamaneh; Scholey, James W.

    2010-01-01

    OBJECTIVE Diabetic nephropathy is one of the most common causes of end-stage renal failure. Inhibition of ACE2 function accelerates diabetic kidney injury, whereas renal ACE2 is downregulated in diabetic nephropathy. We examined the ability of human recombinant ACE2 (hrACE2) to slow the progression of diabetic kidney injury. RESEARCH DESIGN AND METHODS Male 12-week-old diabetic Akita mice (Ins2WT/C96Y) and control C57BL/6J mice (Ins2WT/WT) were injected daily with placebo or with rhACE2 (2 mg/kg, i.p.) for 4 weeks. Albumin excretion, gene expression, histomorphometry, NADPH oxidase activity, and peptide levels were examined. The effect of hrACE2 on high glucose and angiotensin II (ANG II)–induced changes was also examined in cultured mesangial cells. RESULTS Treatment with hrACE2 increased plasma ACE2 activity, normalized blood pressure, and reduced the urinary albumin excretion in Akita Ins2WT/C96Y mice in association with a decreased glomerular mesangial matrix expansion and normalization of increased α-smooth muscle actin and collagen III expression. Human recombinant ACE2 increased ANG 1–7 levels, lowered ANG II levels, and reduced NADPH oxidase activity. mRNA levels for p47phox and NOX2 and protein levels for protein kinase Cα (PKCα) and PKCβ1 were also normalized by treatment with hrACE2. In vitro, hrACE2 attenuated both high glucose and ANG II–induced oxidative stress and NADPH oxidase activity. CONCLUSIONS Treatment with hrACE2 attenuates diabetic kidney injury in the Akita mouse in association with a reduction in blood pressure and a decrease in NADPH oxidase activity. In vitro studies show that the protective effect of hrACE2 is due to reduction in ANG II and an increase in ANG 1–7 signaling. PMID:19934006

  9. Prevention of atrial fibrillation with renin-angiotensin system inhibitors on essential hypertensive patients: a meta-analysis of randomized controlled trials

    PubMed Central

    Zhao, Di; Wang, Ze-Mu; Wang, Lian-Sheng

    2015-01-01

    Abstract We aimed to investigate the effectiveness and safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on preventing atrial fibrillation in essential hypertensive patients. Systematic literature retrieval was carried out to obtain randomized controlled trials on the effects of ACEI/ARBs on essential hypertensive patients before December, 2013. Data extraction and quality evaluation were performed. Meta-analysis was performed by Review Manager 5.2.3. Ten high quality studies (11 articles) with a total of 42,892 patients (20,491 patients in the ACEI/ARBs group and 22,401 patients in the β-blocker or the calcium antagonist group) met the inclusion criteria and were included in the meta-analysis. The results showed that ACEI/ARBs reduced the incidence of atrial fibrillation (AF) recurrence compared to calcium antagonists (RR = 0.48; 95%CI, 0.40-0.58; P<0.00001) or β-blockers (RR = 0.39; 95%CI, 0.20-0.74; P = 0.005) in long-term follow-up, respectively. Furthermore, ACEI/ARBs reduced the incidence of congestive heart failure (RR = 0.86; 95%CI, 0.77-0.96; P = 0.007). However, no significant effects were observed on the incidence of new AF, cardiac death, myocardial infarction, and stroke. Our results suggest that ACEI/ARBs may reduce the incidence of AF recurrence and congestive heart failure, with fewer serious adverse effects. PMID:26668582

  10. Cardiovascular risk reduction in hypertension: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers. Where are we up to?

    PubMed

    Sindone, A; Erlich, J; Lee, C; Newman, H; Suranyi, M; Roger, S D

    2016-03-01

    Previously, management of hypertension has concentrated on lowering elevated blood pressure. However, the target has shifted to reducing absolute cardiovascular (CV) risk. It is estimated that two in three Australian adults have three or more CV risk factors at the same time. Moderate reductions in several risk factors can, therefore, be more effective than major reductions in one. When managing hypertension, therapy should be focused on medications with the strongest evidence for CV event reduction, substituting alternatives only when a primary choice is not appropriate. Hypertension management guidelines categorise angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) interchangeably as first-line treatments in uncomplicated hypertension. These medications have different mechanisms of action and quite different evidence bases. They are not interchangeable and their prescription should be based on clinical evidence. Despite this, currently ARB prescriptions are increasing at a higher rate than those for ACEI and other antihypertensive classes. Evidence that ACEI therapy prevents CV events and death, in patients with coronary artery disease or multiple CV risk factors, emerged from the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) trials respectively. The consistent benefit has been demonstrated in meta-analyses. The clinical trial data for ARB are less consistent, particularly regarding CV outcomes and mortality benefit. The evidence supports the use of ACEI (Class 1a) compared with ARB despite current prescribing trends. PMID:26968600

  11. Cognitive enhancing effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on learning and memory

    PubMed Central

    Nade, V. S.; Kawale, L. A.; Valte, K. D.; Shendye, N. V.

    2015-01-01

    Objective: The present study was designed to investigate cognitive enhancing property of angiotensin-converting enzymes inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in rats. Materials and Methods: The elevated plus maze (EPM), passive avoidance test (PAT), and water maze test (WMT) were used to assess cognitive enhancing activity in young and aged rats. Ramipril (10 mg/kg, p.o.), perindopril (10 mg/kg, i.p), losartan (20 mg/kg, i.p), and valsartan (20 mg/kg, p.o) were administered to assess their effect on learning and memory. Scopolamine (1 mg/kg, i.p) was used to impair cognitive function. Piracetam (200 mg/kg, i.p) was used as reference drug. Results: All the treatments significantly attenuated amnesia induced by aging and scopolamine. In EPM, aged and scopolamine-treated rats showed an increase in transfer latency (TL) whereas, ACEI and ARBs showed a significant decrease in TL. Treatment with ACEI and ARBs significantly increased step down latencies and decreased latency to reach the platform in target quadrant in young, aged and scopolamine-treated animals in PAT and WMT, respectively. The treatments inhibited acetylcholinesterase (AChE) enzyme in the brain. Similarly, all the treatments attenuated scopolamine-induced lipid peroxidation and normalize antioxidant enzymes. Conclusion: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV. PMID:26069362

  12. The solar array is installed on ACE in SAEF-2

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Applied Physics Laboratory engineers and technicians from Johns Hopkins University assist in leveling and orienting the Advanced Composition Explorer (ACE) as it is seated on a platform for solar array installation in KSC's Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory has six high-resolution particle detection sensors and three monitoring instruments. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA.

  13. An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK).

    PubMed Central

    Kiru, Gaia; Bicknell, Colin; Falaschetti, Emanuela; Powell, Janet; Poulter, Neil

    2016-01-01

    BACKGROUND Although data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases. OBJECTIVES (1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters. DESIGN A three-arm, multicentre, single-blind, randomised placebo-controlled trial. SETTING Fourteen hospitals in England. PARTICIPANTS Men or women aged ≥ 55 years with an AAA of 3.0-5.4 cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria. INTERVENTIONS Patients were randomised to receive 10 mg of perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily or placebo daily. MAIN OUTCOME MEASURES The primary outcome was AAA diameter growth using external measurements in the longitudinal plane, which in-trial studies suggested was the preferred measure. Secondary outcome measures included AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the threshold for intervention (5.5 cm) or referral for surgery, tolerance of study medication (measured by compliance, adverse events and quality of life) and a comparison of the repeatability of measures of internal and external AAA diameter. Patients were followed up every 3-6 months over 2 years. RESULTS In total, 227 patients were recruited and randomised into the three groups, which were generally well matched at baseline. Multilevel modelling was used to determine the maximum likelihood estimates for AAA diameter growth. No significant differences in the estimates of annual growth were apparent [1.68 (standard error 0.02) mm, 1.77 (0.02) mm and 1.81 (0.02) mm in the

  14. Multiphysics Applications of ACE3P

    SciTech Connect

    K.H. Lee, C. Ko, Z. Li, C.-K. Ng, L. Xiao, G. Cheng, H. Wang

    2012-07-01

    The TEM3P module of ACE3P, a parallel finite-element electromagnetic code suite from SLAC, focuses on the multiphysics simulation capabilities, including thermal and mechanical analysis for accelerator applications. In this pa- per, thermal analysis of coupler feedthroughs to supercon- ducting rf (SRF) cavities will be presented. For the realistic simulation, internal boundary condition is implemented to capture RF heating effects on the surface shared by a di- electric and a conductor. The multiphysics simulation with TEM3P matched the measurement within 0.4%.

  15. Acute Kidney Injury in Elderly Patients With Chronic Kidney Disease: Do Angiotensin-Converting Enzyme Inhibitors Carry a Risk?

    PubMed

    Chaumont, Martin; Pourcelet, Aline; van Nuffelen, Marc; Racapé, Judith; Leeman, Marc; Hougardy, Jean-Michel

    2016-06-01

    In contrast to angiotensin receptor blockers (ARBs), mainly excreted by the liver, the dosage of angiotensin-converting enzyme (ACE) inhibitors, cleared by the kidney, must be adapted to account for renal clearance in patients with chronic kidney disease (CKD) to avoid acute kidney injury (AKI). Community-acquired AKI and the use of ACE inhibitors or ARBs in the emergency department were retrospectively assessed in 324 patients with baseline stage 3 or higher CKD. After stepwise regression analysis, the use of ACE inhibitors (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.1; P=.02) and the presence of dehydration (OR, 30.8; 95% CI, 3.9-239.1) were associated with AKI. A total of 45% of patients using ACE inhibitors experienced overdosing, which causes most of the excess risk of AKI. These results suggest that dosage adjustment of ACE inhibitors to renal function or substitution of ACE inhibitors with ARBs could reduce the incidence of AKI. Moreover, ACE inhibitors and ARBs should be stopped in cases of dehydration. PMID:27080620

  16. Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome.

    PubMed

    Neidert, Marian C; Schmidt, Tobias; Mitova, Tatyana; Fierstra, Jorn; Bellut, David; Regli, Luca; Burkhardt, Jan-Karl; Bozinov, Oliver

    2016-06-01

    The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics. Out of 203 patients (58 females, mean age 73.2years), 53 (26%) patients were on ACE inhibitors before their presentation with cSDH. Median initial hematoma volume in individuals with ACE inhibitors (179.2±standard error of the mean [SEM] 13.0ml) was significantly higher compared to patients without ACE inhibitors (140.4±SEM 6.2ml; p=0.007). There was an increased probability of surgical reintervention in the ACE inhibitor group (12/53, 23% versus 19/153, 12%; p=0.079), especially in patients older than 80years (6/23, 26% versus 3/45, 7%; p=0.026). ACE inhibitors are associated with higher hematoma volume in patients with cSDH and with a higher frequency of recurrences requiring surgery (especially in the very old). We hypothesize that these effects are due to ACE inhibitor induced bradykinin elevation causing increased vascular permeability of the highly vascularized neomembranes in cSDH. PMID:26898577

  17. Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei.

    PubMed

    Khalesi, Mohammadreza; Jahanbani, Raheleh; Riveros-Galan, David; Sheikh-Hassani, Vahid; Sheikh-Zeinoddin, Mahmoud; Sahihi, Mehdi; Winterburn, James; Derdelinckx, Guy; Moosavi-Movahedi, Ali Akbar

    2016-10-01

    There are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01-0.40mg/mL) were determined. The results show that for HFBII concentrations of 0.04mg/mL and upwards the protein significantly reduced the presence of ABTS(+) radicals in the medium, the IC50 value found to be 0.13mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry. PMID:27211298

  18. Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes

    PubMed Central

    Miners, Scott; Ashby, Emma; Baig, Shabnam; Harrison, Rachel; Tayler, Hannah; Speedy, Elizabeth; Prince, Jonathan A; Love, Seth; Kehoe, Patrick G

    2009-01-01

    Angiotensin-converting enzyme (ACE) has been implicated in Alzheimer's disease (AD): ACE1 variations influence plasma ACE and risk of AD, and ACE is increased in AD brain. We measured frontal ACE level and activity in 89 AD and 51 control brains, and post-mortem CSF from 101 cases and 19 controls. Neuron-specific enolase (NSE) level and Braak stage were used to indicate neuronal preservation and disease progression. We genotyped the common ACE insertion/deletion polymorphism, rs4343, rs1800764 and rs4921. ACE activity was elevated in AD and correlated with Braak stage. Crude ACE levels were unchanged but adjustment for NSE suggested increased neuronal ACE production with Braak stage. Exposing SH-SY-5Y neurons to oligomeric Aβ1-42 increased ACE level and activity, suggesting Aβ may upregulate ACE in AD. In CSF, ACE level but not activity was reduced in AD. ACE1 genotype did not predict ACE level or activity in brain or CSF. ACE activity and neuronal production increase in AD brain, possibly in response to Aβ. Peripheral measurements do not reflect ACE activity in the brain. PMID:19956428

  19. ACE: A Collaborative School Consultation Program for Secondary School Teachers

    ERIC Educational Resources Information Center

    Couture, Caroline; Massé, Line

    2014-01-01

    This article presents a description of ACE (Accompagnement collaboratif des enseignants (Collaborative teacher accompaniment)), a new program designed to guide secondary school teachers in integrating students with behavioral problems in their classrooms. ACE proposes collaborative accompaniment inspired by behavioral and mental health…

  20. An Inclusive ACE. Broadening Participation in Adult and Community Education.

    ERIC Educational Resources Information Center

    Alt, Merilyn; Beatty, Dianne

    A project identified strategies to increase participation by community members who traditionally have not used adult and community education (ACE) in Australia. Methodology included a focus group, literature research, and interviews with 70 people. Government-supported ACE was seen as having a broad role in supporting lifelong learning. ACE…

  1. ACE and AGTR1 polymorphisms in elite rhythmic gymnastics.

    PubMed

    Di Cagno, Alessandra; Sapere, Nadia; Piazza, Marina; Aquino, Giovanna; Iuliano, Enzo; Intrieri, Mariano; Calcagno, Giuseppe

    2013-02-01

    In the angiotensin-converting enzyme (ACE) gene, Alu deletion, in intron 16, is associated with higher concentrations of ACE serum activity and this may be associated with elite sprint and power performance. The Alu insertion is associated with lower ACE levels and this could lead to endurance performance. Moreover, recent studies have identified a single-nucleotide polymorphism of the angiotensin type 1 receptor gene AGTR1, which seems to be related to ACE activity. The aim of this study was to examine the involvement of the ACE and the AGTR1 gene polymorphisms in 28 Italian elite rhythmic gymnasts (age range 21 ± 7.6 years), and compare them to 23 middle level rhythmic gymnasts (age range 17 ± 10.9 years). The ACE D allele was significantly more frequent in elite athletes than in the control population (χ(2)=4.07, p=0.04). Comparisons between the middle level and elite athletes revealed significant differences (p<0.0001) for the ACE DD genotype (OR=6.48, 95% confidence interval=1.48-28.34), which was more frequent in elite athletes. There were no significant differences in the AGTR1 A/C genotype or allele distributions between the middle level and elite athletes. In conclusion, the ACE D allele genotype could be a contributing factor to high-performance rhythmic gymnastics that should be considered in athlete development and could help to identify which skills should be trained for talent promotion. PMID:23145508

  2. ENALAPRIL: PHARMACOKINETIC/DYNAMIC INFERENCES FOR COMPARATIVE DEVELOPMENTAL TOXICITY

    EPA Science Inventory

    Enalapril is an antihypertensive drug of the class of angiotensin-converting enzyme inhibitors (ACEI) used in pregnancy for treatment of pre-existing or pregnancy-induced hypertension. The use of ACE inhibitors (drugs that act directly on the renin-angiotensin system) during the ...

  3. The solar array is installed on ACE in SAEF-2

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Applied Physics Laboratory engineers and technicians from Johns Hopkins University install solar array panels on the Advanced Composition Explorer (ACE) in KSC's Spacecraft Assembly and Encapsulation Facility-II. The panel on which they are working is identical to the panel (one of four) seen in the foreground on the ACE spacecraft. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low- energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA.

  4. Desert Dust Layers Over Polluted Marine Boundary Layers: ACE-2 Measurements and ACE-Asia Plans

    NASA Technical Reports Server (NTRS)

    Russell, Philip B.; Schmid, B.; Livingston, J. M.; Redemann, J.; Bergstrom, R. W.; Condon, Estelle P. (Technical Monitor)

    2000-01-01

    Aerosols in ACE-Asia are expected to have some commonalties with those in ACE-2, along with important differences. Among the commonalities are occurrences of desert dust layers over polluted marine boundary layers. Differences include the nature of the dust (yellowish in the East Asia desert outflow, vs. reddish-brown in the Sahara Outflow measured in ACE-2) and the composition of boundary-layer aerosols (e.g., more absorbing, soot and organic aerosol in-the Asian plume, caused by coal and biomass burning, with limited controls). In this paper we present ACE-2 measurements and analyses as a guide to our plans for ACE-2 Asia. The measurements include: (1) Vertical profiles of aerosol optical depth and extinction (380-1558 nm), and of water vapor column and concentration, from the surface through the elevated desert dust, measured by the 14-channel Ames Airborne Tracking Sunphotometer (AATS-14); (2) Comparisons of airborne and shipborne sunphotometer optical depths to satellite-retrieved values, with and without desert dust; (3) Comparisons between airborne Sunphotometer optical depth and extinction spectra and those derived from coincident airborne in situ measurements of aerosol size distribution, scattering and absorption; (4) Comparisons between size distributions measured in situ and retrieved from sunphotometer optical depth spectra; (5) Comparisons between aerosol single scattering albedo values obtained by several techniques, using various combinations of measurements of backscatter, extinction, size distribution, scattering, absorption, and radiative flux. We show how analyses of these data can be used to address questions important to ACE-Asia, such as: (1) How do dust and other absorbing aerosols affect the accuracy of satellite optical depth retrievals? How important are asphericity effects? (2) How important are supermicron dust and seasalt aerosols to overall aerosol optical depth and radiative forcing? How well are these aerosols sampled by aircraft

  5. Effect of Beta Blockers and Renin-Angiotensin System Inhibitors on Survival in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

    PubMed

    Lee, Pil Hyung; Park, Gyung-Min; Kim, Young-Hak; Yun, Sung-Cheol; Chang, Mineok; Roh, Jae-Hyung; Yoon, Sung-Han; Ahn, Jung-Min; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung

    2016-03-01

    Because it remains uncertain whether β-blockers (BBs) and/or renin-angiotensin system inhibitors benefit a broad population of acute myocardial infarction (AMI) patients, we sought to evaluate the effectiveness of these drugs in improving survival for post-AMI patients who underwent a percutaneous coronary intervention (PCI).From the nationwide data of the South Korea National Health Insurance, 33,390 patients with a diagnosis of AMI who underwent a PCI between 2009 and 2013 and survived at least 30 days were included in this study. We evaluated the risk of all-cause death for patients treated with both BB and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor antagonist (ARB) (n = 16,280), only BB (n = 3683), and only ACEI/ARB (n = 9849), with the drug-untreated patients (n = 3578) as the reference.Over a median follow-up of 2.4 years, although treated patients displayed a trend toward improved survival, there were no significant differences in the adjusted risk of all-cause death when patients were treated with both drugs (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.70-1.06, P = 0.154), BB (HR 0.88, 95% CI 0.68-1.14, P = 0.325), or ACEI/ARB (HR 0.84, 95% CI 0.68-1.04, P = 0.111). No additional benefit was found for the combination therapy compared with either isolated BB (HR 0.98, 95% CI 0.80-1.21, P = 0.856) or ACEI/ARB (HR 1.03, 95% CI 0.89-1.19, P = 0.727) therapy.Treatment with BB and/or ACEI/ARB has limited effect on survival in unselected nonfatal AMI patients who undergo PCI. PMID:26962802

  6. Angioedema in the emergency department: the impact of angiotensin-converting enzyme inhibitors.

    PubMed

    Pigman, E C; Scott, J L

    1993-07-01

    Angiotensin-converting enzyme (ACE) inhibitors have been reported to cause angioedema. The purpose of this study was to establish what proportion of patients who present to the emergency department (ED) with angioedema were concomitantly taking any of the ACE inhibitors and to show how this group differed in presentation and response to treatment from the larger population of patients with non-ACE inhibitor-related angioedema. An 8-year retrospective chart review of all patients with the diagnosis of angioedema observed from January 1, 1984 to December 31, 1991 was undertaken in the ED of an urban teaching hospital. Forty-nine patients ranging from 12 to 88 years of age with symptoms and physical examination that was consistent with the diagnosis of angioedema were entered onto the study. Twelve cases of ACE inhibitor-related angioedema were identified, all occurring in the last 4 years of the review, and when compared with the non-ACE inhibitor-related group were older (mean age, 63.3 vs 43.0 years), had less of an allergic history (0% vs 49%; P = .013), but demonstrated the same severity of symptoms and response to medical therapy. No case required an artificial or surgical airway. ACE inhibitor related angioedema is becoming a common type of angioedema observed in this ED. These patients are older and free of other allergic disease and respond well to traditional therapy. PMID:8216515

  7. A novel angiotensin-І converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study.

    PubMed

    Wu, Qiongying; Jia, Junqiang; Yan, Hui; Du, Jinjuan; Gui, Zhongzheng

    2015-06-01

    Silkworm pupa (Bombyx mori) protein was hydrolyzed using gastrointestinal endopeptidases (pepsin, trypsin and α-chymotrypsin). Then, the hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and RP-HPLC. A novel ACE inhibitory peptide, Ala-Ser-Leu, with the IC50 value of 102.15μM, was identified by IT-MS/MS. This is the first report of Ala-Ser-Leu from natural protein. Lineweaver-Burk plots suggest that the peptide is a competitive inhibitor against ACE. The molecular docking studies revealed that the ACE inhibition of Ala-Ser-Leu is mainly attributed to forming very strong hydrogen bonds with the S1 pocket (Ala354) and the S2 pocket (Gln281 and His353). The results indicate that silkworm pupa (B. mori) protein or its gastrointestinal protease hydrolysate could be used as a functional ingredient in auxiliary therapeutic foods against hypertension. PMID:25111373

  8. The solar array is installed on ACE in SAEF-2

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Applied Physics Laboratory engineers and technicians from Johns Hopkins University assist in guiding the Advanced Composition Explorer (ACE) as it is hoisted over a platform for solar array installation in KSC's Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will contribute to the understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA.

  9. The solar array is installed on ACE in SAEF-2

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Applied Physics Laboratory Engineer Cliff Willey (kneeling) and Engineering Assistant Jim Hutcheson from Johns Hopkins University install solar array panels on the Advanced Composition Explorer (ACE) in KSC's Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA.

  10. Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment

    PubMed Central

    Paschos, Paschalis; Tziomalos, Konstantinos

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in Western countries. Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far. Emerging evidence, mainly from animal studies, suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) as a potentially useful therapeutic approach. However, data from human studies are limited and contradictory. In addition, there are few randomized controlled trials (RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies, pilot prospective studies and post hoc analyses of clinical trials. Accordingly, more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD. PMID:23355909

  11. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Terms of Major Cardiovascular Disease Outcomes in Elderly Patients

    PubMed Central

    Chien, Shu-Chen; Ou, Shuo-Ming; Shih, Chia-Jen; Chao, Pei-Wen; Li, Szu-Yuan; Lee, Yi-Jung; Kuo, Shu-Chen; Wang, Shuu-Jiun; Chen, Tzeng-Ji; Tarng, Der-Cherng; Chu, Hsi; Chen, Yung-Tai

    2015-01-01

    Abstract Renin and aldosterone activity levels are low in elderly patients, raising concerns about the benefits and risks of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARB) use. However, data from direct comparisons of the effects of ACEIs on ARBs in the elderly population remain inconclusive. In this nationwide study, all patients aged ≥ 70 years were retrieved from the Taiwan National Health Insurance database for the period 2000 to 2009 and were followed up until the end of 2010. The ARB cohort (12,347 patients who continuously used ARBs for ≥ 90 days) was matched to ACEI cohort using high-dimensional propensity score (hdPS). Intention-to-treat (ITT) and as-treated (AT) analyses were conducted. In the ITT analysis, after considering death as a competing risk, the ACEI cohort had similar risks of myocardial infarction (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.79–1.06), ischemic stroke (HR 0.98, 95% CI 0.90–1.07), and heart failure (HR 0.93, 95% CI 0.83–1.04) compared with the ARB cohort. No difference in adverse effects, such as acute kidney injury (HR 0.99, 95% CI 0.89–1.09) and hyperkalemia (HR 1.02, 95% CI 0.87–1.20), was observed between cohorts. AT analysis produced similar results to those of ITT analysis. We were unable to demonstrate a survival difference between cohorts (HR 1.03, 95% CI 0.88–1.21) after considering drug discontinuation as a competing risk in AT analysis. Our study supports the notion that ACEI and ARB users have similar risks of major adverse cardiovascular events (MACE), even in elderly populations. PMID:26512568

  12. Climate-active Trace Gases from ACE Satellite Observations

    NASA Astrophysics Data System (ADS)

    Bernath, P. F.; Brown, A.; Harrison, J.; Chipperfield, M.; Boone, C.; Wilson, C.; Walker, K. A.

    2011-12-01

    ACE (also known as SCISAT) is making a comprehensive set of simultaneous measurements of more than 30 trace gases, thin clouds, aerosols and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) gives ACE coverage of tropical, mid-latitudes and polar regions. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4400 cm-1) is measuring the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. Launched by NASA in August 2003 for a nominal two-year mission, ACE performance remains excellent after 8 years in orbit. Volume mixing ratio (VMR) profiles of sixteen halogenated trace gases are routinely retrieved from ACE-FTS atmospheric spectra: CCl4, CF4, CCl3F (CFC-11), CCl2F2 (CFC-12), C2Cl3F3 (CFC-113), CH3Cl, ClONO2, COF2, COCl2, COClF, CHF2Cl (HCFC-22), CH3CCl2F (HCFC-141b), CH3CClF2 (HCFC-142b), HCl, HF and SF6. ACE also provides VMR profiles for CH4, N2O and OCS; HCFC-23 (CHF3) is a recent research product. ACE-FTS measurements were compared to surface measurements made by the AGAGE network and output from the SLIMCAT three-dimensional (3-D) chemical transport model, which is constrained by similar surface data. ACE-FTS measurements of CFCs (and HCl) show declining trends which agree with both AGAGE and SLIMCAT values. The concentrations of HCFCs are increasing with ACE-FTS, SLIMCAT and AGAGE all showing positive trends. These results illustrate the success of the Montreal Protocol in reducing ozone depleting substances. The replacement of CFCs with HCFCs has led to an increase in the VMR of HF in the stratosphere. As chlorine containing compounds continue to be phased out and replaced by fluorine-containing molecules, it is likely that total atmospheric fluorine will continue increasing in the near future. These species are all powerful greenhouse gases. ACE provides near global VMR

  13. Inhibitors of angiotensin-converting enzyme modulate mitosis and gene expression in pancreatic cancer cells

    SciTech Connect

    Reddy, M.K.; Baskaran, K.; Molteni, A.

    1995-12-01

    The angiotensin-converting enzyme (ACE) inhibitor captopril inhibits mitosis in several cell types that contain ACE and renin activity. In the present study, we evaluated the effect of the ACE inhibitors captopril and CGS 13945 (10{sup {minus}8} to 10{sup {minus}2}M) on proliferation and gene expression in hamster pancreatic duct carcinoma cells in culture. These cells lack renin and ACE activity. Both ACE inhibitors produced a dose-dependent reduction in tumor cell proliferation within 24 hr. Captopril at a concentration of 0.36 mM and CGS 13945 at 150 {mu}M decreased cellular growth rate to approximately half that of the control. Neither drug influenced the viability or the cell cycle distribution of the tumor cells. Slot blot analysis of mRNA for four genes, proliferation associated cell nuclear antigen (PCNA), K-ras, protein kinase C-{Beta} (PKC-{Beta}) and carbonic anhydrase II (CA II) was performed. Both ACE inhibitors increased K-ras expression by a factor of 2, and had no effect on CA II mRNA levels. Captopril also lowered PCNA by 40% and CGS 13945 lowered PKC-{Beta} gene expression to 30% of the control level. The data demonstrate that ACE inhibitors exhibit antimitotic activity and differential gene modulation in hamster pancreatic duct carcinoma cells. The absence of renin and ACE activity in these cells suggests that the antimitotic action of captopril and CGS 13945 is independent of renin-angiotensin regulation. The growth inhibition may occur through downregulation of growth-related gene expression. 27 refs., 5 figs.

  14. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    PubMed Central

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  15. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema.

    PubMed

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  16. Baseline characteristics and treatment of patients in Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

    PubMed Central

    McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jianjian; Lefkowitz, Martin; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

    2014-01-01

    Aim To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin–angiotensin–aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction. Methods Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction. Results The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886–3221 pg/mL). Conclusion PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction. PMID:24828035

  17. Contemplating Synergistic Algorithms for the NASA ACE Mission

    NASA Technical Reports Server (NTRS)

    Mace, Gerald G.; Starr, David O.; Marchand, Roger; Ackerman, Steven A.; Platnick, Steven E.; Fridlind, Ann; Cooper, Steven; Vane, Deborah G.; Stephens, Graeme L.

    2013-01-01

    ACE is a proposed Tier 2 NASA Decadal Survey mission that will focus on clouds, aerosols, and precipitation as well as ocean ecosystems. The primary objective of the clouds component of this mission is to advance our ability to predict changes to the Earth's hydrological cycle and energy balance in response to climate forcings by generating observational constraints on future science questions, especially those associated with the effects of aerosol on clouds and precipitation. ACE will continue and extend the measurement heritage that began with the A-Train and that will continue through Earthcare. ACE planning efforts have identified several data streams that can contribute significantly to characterizing the properties of clouds and precipitation and the physical processes that force these properties. These include dual frequency Doppler radar, high spectral resolution lidar, polarimetric visible imagers, passive microwave and submillimeter wave radiometry. While all these data streams are technologically feasible, their total cost is substantial and likely prohibitive. It is, therefore, necessary to critically evaluate their contributions to the ACE science goals. We have begun developing algorithms to explore this trade space. Specifically, we will describe our early exploratory algorithms that take as input the set of potential ACE-like data streams and evaluate critically to what extent each data stream influences the error in a specific cloud quantity retrieval.

  18. Advanced Colloids Experiment (ACE) Science Overview

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ronald J.; Chiaramonte, Francis P.; Luna, Unique J.; Chaiken, Paul M.; Hollingsworth, Andrew; Secanna, Stefano; Weitz, David; Lu, Peter; Yodh, Arjun; Yunker, Peter; Lohr, Matthew; Gratale, Matthew; Lynch, Matthew; Kodger, Thomas; Piazza, Roberto; Buzzaccaro, Stefano; Cipelletti, Luca; Schall, Peter; Veen, Sandra; Wegdam, Gerhard; Lee, Chand-Soo; Choi, Chang-Hyung; Paul, Anna-Lisa; Ferl, Robert J.; Cohen, Jacob

    2013-01-01

    accessible with the availability of the Light Microscopy Module (LMM) on ISS. To meet these goals, the ACE experiment is being built-up in stages, with the availability of confocal microscopy being the ultimate objective. Supported by NASAs Physical Sciences Research Program, ESAESTEC, and the authors respective governments.

  19. [Job satisfaction among the professionals of AceS Baixo Vouga II].

    PubMed

    Santana, Silvina; Cerdeira, José

    2011-12-01

    Job satisfaction is a measure of quality of life at work and is related to emotional states. The interest for this theme is increasing and, in the last years, many studies have attempted to demonstrate its relation with professional performance. Primary care professionals are in the first line of the Serviço Nacional de Saúde (SNS). Therefore, it is necessary that they feel satisfaction with their jobs, in order to perform the tasks with the quality required. Several factors seem to have impact in the satisfaction of these professionals, such as payment, promotion, recognition from supervisors and peers, physical conditions at work and available resources, opportunities for personal development, among others. Insatisfaction may lead to absentism and in the limit to job quit. The main objective of this work is to study job satisfaction among the professionals working at the health centers of ACeS Baixo Vouga II, namely, the relationship between job characteristics and job satisfaction and between job characteristics and considering job quit as a serious option. All the professionals working in the four health centers were inquired. Results show that job characteristics are defined by six dimensions: leadership and supervision, task characteristics and autonomy, payment, personal and professional development and promotion, peers and relations inside the organization and work environment. Globally, payment and opportunities for personal and professional development and promotion are perceived at low level by all the professional groups. Results also show that there are differences by gender and professional groups regarding job satisfaction and the will to quit job. Considering the specificity of the tasks performed by these professionals, measures should be taken in order to improve job satisfaction in the Portuguese health centers. PMID:22849951

  20. The ACE2/Ang-(1-7)/Mas Axis Regulates the Development of Pancreatic Endocrine Cells in Mouse Embryos

    PubMed Central

    Wang, Lin; Liang, Juan; Leung, Po Sing

    2015-01-01

    Angiotensin-converting enzyme 2 (ACE2), its product Angiotensin-(1-7) [Ang-(1-7)], and Ang-(1-7) receptor Mas, have been shown to regulate organogenesis during embryonic development in various species. However, it is not known whether a local ACE2/Ang-(1-7)/Mas axis is present in the fetal pancreas. It is hypothesized that there is a local ACE2/Ang-(1-7)/Mas axis in the embryonic pancreas in mice that is involved in regulating islet cell development. To address this issue, the endogenous expression profile of axis constituents in embryonic mouse pancreata was examined. Involvement of the ACE2 axis in the regulation of pancreatic development was also examined. The present experiments showed in an in vivo animal model that endogenous expression levels of ACE2 and the Mas receptor were upregulated in mouse pancreata in late embryogenesis, peaking on embryonic day E16.5, when it reached 3 folds compared to that seen at E12.5. Consistently, endogenous expression of Ang-(1-7) also peaked at E16.5. Treatment with the ACE2 inhibitor DX600 did not alter islet development. However, prenatal treatment with A779, a Mas receptor antagonist, reduced the β-cell to α-cell ratio in neonatal islets, impaired islet insulin secretory function, and impaired the pups’ glucose tolerance. In ex vivo pancreas explant cultures, A779 again decreased the β-cell to α-cell ratio, apparently through its effects on β-cell proliferation (reduced proliferation shown with Ki67 staining), and also decreased Insulin and Ngn3 mRNA expression. Furthermore, treatment of explant cultures with Ang-(1-7) increased mRNA levels of Insulin and pancreatic progenitor marker Ngn3, as well as Nox4, the ROS generation enzyme; these stimulatory effects were attenuated by co-treatment with A779, suggesting that Ang-(1-7), via Mas receptor signaling, may promote differentiation of pancreatic progenitors into insulin-producing cells via modulation of reactive oxygen species. These data together suggest that a

  1. Improved ACE-FTS observations of carbon tetrachloride (CCl4)

    NASA Astrophysics Data System (ADS)

    Harrison, Jeremy; Chipperfield, Martyn; Boone, Chris; Bernath, Peter

    2016-04-01

    The Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS), on board the SCISAT satellite, has been recording solar occultation spectra through the Earth's atmosphere since 2004 and continues to take measurements with only minor loss in performance. ACE-FTS time series are available for a range of chlorine 'source' gases, including CCl3F (CFC-11), CCl2F2 (CFC-12), CHF2Cl (HCFC-22), CH3Cl and CCl4. Recently there has been much community interest in carbon tetrachloride (CCl4), a substance regulated by the Montreal Protocol because it leads to the catalytic destruction of stratospheric ozone. Estimated sources and sinks of CCl4 remain inconsistent with observations of its abundance. Satellite observations of CCl4 in the stratosphere are particularly useful in validating stratospheric loss (photolysis) rates; in fact the atmospheric loss of CCl4 is essentially all due to photolysis in the stratosphere. However, the latest ACE-FTS v3.5 CCl4 retrieval is biased high by ˜ 20-30%. A new ACE-FTS retrieval scheme utilising new laboratory spectroscopic measurements of CCl4 and improved microwindow selection has recently been developed. This improves upon the v3.5 retrieval and resolves the issue of the high bias; this new scheme will form the basis for the upcoming v4 processing version of ACE-FTS data. This presentation will outline the improvements made in the retrieval, and a subset of data will be compared with modelled CCl4 distributions from SLIMCAT, a state-of-the-art three-dimensional chemical transport model. The use of ACE-FTS data to evaluate the modelled stratospheric loss rate of CCl4 will also be discussed. The evaluated model, which also includes a treatment of surface soil and ocean sinks, will then be used to quantify current uncertainties in the global budget of CCl4.

  2. Haplotypes extending across ACE are associated with Alzheimer's disease.

    PubMed

    Kehoe, Patrick G; Katzov, Hagit; Feuk, Lars; Bennet, Anna M; Johansson, Boo; Wiman, Björn; de Faire, Ulf; Cairns, Nigel J; Wilcock, Gordon K; Brookes, Anthony J; Blennow, Kaj; Prince, Jonathan A

    2003-04-15

    Numerous genes have been implicated in Alzheimer's disease (AD), but, with the exception of a demonstrated association with the epsilon 4 allele of APOE, findings have not been consistently replicated across populations. One of the most widely studied is the gene for angiotensin I converting enzyme (ACE ). A meta-analysis of published data on a common Alu indel polymorphism in ACE was performed which indicated highly significant association of the insertion allele with AD (OR 1.30; 95% CI 1.19 - 1.41; P=4 x 10(-8)). To further explore the influence of ACE on AD, several single-nucleotide polymorphisms (SNPs) were genotyped in five independent populations represented by over 3100 individuals. Analyses based upon single markers and haplotypes revealed strong evidence of association in case-control models and also in a model examining the influence of variation in ACE upon cerebrospinal fluid levels of amyloid beta42 peptide (Abeta42). The most significant evidence for association with AD was found for an SNP, A-262T, located in the ACE promoter (OR 1.64; 95% CI 1.33 -1.94; P=2 x 10(-5)). Estimates of population attributable risk for the common allele of this SNP suggest that it, or an allele in tight linkage disequilibrium (LD) with it, may contribute to as much as 35% of AD in the general population. Results support a model whereby decreased ACE activity may influence AD susceptibility by a mechanism involving beta-amyloid metabolism. PMID:12668609

  3. Performance Enhancement of the Automated Concrete Evaluation System (ACES)

    SciTech Connect

    Baumgart,C.W.; Cave,S.P.; Linder,K.E.

    2002-02-14

    The objective of this proposed research is to improve and expand the detection and analysis capabilities of the automated, concrete evaluation (ACE) system. MoDOT and Honeywell jointly developed this system. The focus of this proposed research will be on the following: Coordination of concrete imaging efforts with other states, Validation and testing of the ACE system on a broad range of concrete samples, and Identification and development of software and hardware enhancements. These enhancements will meet the needs of diverse users in the field of concrete materials, construction, and research.

  4. Defective intestinal amino acid absorption in Ace2 null mice.

    PubMed

    Singer, Dustin; Camargo, Simone M R; Ramadan, Tamara; Schäfer, Matthias; Mariotta, Luca; Herzog, Brigitte; Huggel, Katja; Wolfer, David; Werner, Sabine; Penninger, Josef M; Verrey, François

    2012-09-15

    Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low-niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since Ace2 is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a severalfold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low-protein/low-niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low-niacin with a low-protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms, such as photosensitive skin rash or ataxia, were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under a low-protein and low-niacin diet, despite gross amino acid homeostasis alterations

  5. Chronic endothelin-A receptor antagonism is as protective as angiotensin converting enzyme inhibition against cardiac dysfunction in diabetic rats

    PubMed Central

    Wölkart, G; Pang, X; Stessel, H; Kirchengast, M; Brunner, F

    2007-01-01

    Background and purpose: Diabetes mellitus is associated with a specific cardiomyopathy. We compared the cardioprotective effects of an endothelin-A receptor blocker (ETA-RB) with those of an angiotensin-converting enzyme inhibitor (ACE-I) in rats with streptozotocin (STZ)-induced diabetes. Experimental approach: Diabetic rats were left untreated or received either the ETA-RB atrasentan or the ACE-I ramipril (each 3 mg kg−1 per day) orally for 8 weeks. Isolated isovolumic heart function was studied during normoxia and in response to ischaemia-reperfusion. Cardiac fibrosis, tissue oxidative stress and tissue nitric oxide synthase (NOS) activity were determined. Key results: Basal left ventricular systolic contractility was lower in diabetic compared to nondiabetic hearts and ETA-RB or ACE-I treatment significantly antagonised the decline. Following 15 min of no-flow ischaemia, reperfusion systolic function was depressed and left-ventricular end-diastolic pressure (LVEDP) was elevated in diabetic hearts. ETA-RB or ACE-I treatment significantly improved recovery of reperfusion systolic and diastolic function, without differences between groups. Hydroxyproline (an index of tissue fibrosis) and malondialdehyde (a measure of tissue oxidative stress) were elevated at the end of reperfusion in diabetic, compared to nondiabetic hearts. Either treatment reduced hydroxyproline and malondialdehyde to control level. Constitutive NOS activity was similar in nondiabetic and diabetic hearts and unaffected by ETA-RB or ACE-I treatment. Conclusions and implications: These results suggest that in experimental type 1 diabetes ETA-RB is as effective as an ACE-I in ameliorating myocardial functions during normoxia and ischaemia-reperfusion. Combining the two treatments neither afforded additive effects, nor diminished any protection effect seen with either drug. PMID:17572700

  6. 77 FR 48527 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... Automated Commercial Environment (ACE) Simplified Entry: Modification of Participant Selection Criteria and... (NCAP) test concerning the simplified entry functionality in the Automated Commercial Environment (ACE...) National Customs Automation Program (NCAP) test concerning Automated Commercial Environment...

  7. Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter review and an algorithm for airway management.

    PubMed

    Chiu, A G; Newkirk, K A; Davidson, B J; Burningham, A R; Krowiak, E J; Deeb, Z E

    2001-09-01

    Angioedema is a nonpitting edema of which the presentation ranges from benign facial swelling to airway obstruction managed by intubation or tracheotomy. The presentation of this disease is reviewed, and a treatment algorithm based on initial signs and symptoms is proposed for proper airway management. We performed a retrospective review of 108 patients treated in 2 tertiary care centers in the Washington, DC, area over a 5-year period. Ninety-eight patients (90.7%) were African-American, and 81 (75%) were female. Seventy-four patients (68.5%) were taking angiotensin-converting enzyme inhibitors (ACEIs). A classification system was developed based on the location of the edema at initial presentation: 1) isolated facial swelling and oral cavity edema, excluding the floor of the mouth; 2) floor of mouth and/or oropharyngeal edema, and 3) oropharyngeal edema with glottic and/or supraglottic involvement. Fourteen patients (13%) needed airway intervention, 2 of whom underwent a cricothyrotomy after a failed intubation attempt. Eleven (78.6%) were taking ACEIs. The indication for each intubation was massive tongue and floor of mouth edema. The patients were extubated 48 to 72 hours later. No patient demonstrated symptom progression after medical treatment was initiated. Therapy included discontinuation of the ACEI or other inciting agent, a high-humidity face tent, an initial dose of intravenous antihistamines, and a continued course of intravenous steroids. Within 48 hours, most patients had a resolution of their edema. Only cases of significant tongue and oropharyngeal edema took longer than 48 hours to resolve. The ACEIs are a common cause of angioedema. Left untreated, angioedema may progress to involve the oropharynx and supraglottis, resulting in a life-threatening airway compromise. Marked floor of mouth and tongue edema are the indications for airway intervention. An algorithm based on the initial presentation is essential for proper airway and patient management

  8. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases.

    PubMed

    Zhuang, Xiao-Dong; Liao, Li-Zhen; Dong, Xiao-Bian; Hu, Xun; Guo, Yue; Du, Zhi-Min; Liao, Xin-Xue; Wang, Li-Chun

    2016-01-01

    This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice. PMID:26792980

  9. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases

    PubMed Central

    Zhuang, Xiao-dong; Liao, Li-zhen; Dong, Xiao-bian; Hu, Xun; Guo, Yue; Du, Zhi-min; Liao, Xin-xue; Wang, Li-chun

    2016-01-01

    This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice. PMID:26792980

  10. ACES Attitudes: Supervision Competencies and a National Certification Program.

    ERIC Educational Resources Information Center

    Dye, Allen

    A survey was conducted to identify requisite supervisor knowledge and skills and to determine what procedures should be used in establishing a national "approved supervisor" certification program. Subjects surveyed were members of the Association for Counselor Education and Supervision (ACES); all members were invited to participate and some 724…

  11. ACE TECH: The Fourth Year of CTE and Academic Integration

    ERIC Educational Resources Information Center

    Knight, Eileen Quinn; Donahue, John; Knight, Patrick

    2008-01-01

    It only takes an hour or two of roaming the halls of Architecture, Construction and Engineering (ACE) Tech Charter High School to detect an enduring attitude of accomplishment from both the teachers and the students. This atmosphere is intentional. The school, located in Chicago, was created specifically to hone the skills of individuals choosing…

  12. POMB/ACE chemotherapy for mediastinal germ cell tumours.

    PubMed

    Bower, M; Brock, C; Holden, L; Nelstrop, A; Makey, A R; Rustin, G J; Newlands, E S

    1997-05-01

    Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates. PMID:9291802

  13. The Clothes Line. Airing Equity Challenges for ACE.

    ERIC Educational Resources Information Center

    Whyte, Ann

    1991-01-01

    Along with schooling, technical and further education, and higher education, adult and community education (ACE) forms part of the framework of lifelong education. It makes a major contribution to the social justice performance of postsecondary education by catering to adults who cannot gain access to or succeed in mainstream postsecondary…

  14. Linkages between ACE Vocational Provision and Mainstream VET.

    ERIC Educational Resources Information Center

    Saunders, John

    A study investigated linkages between adult community education (ACE) and mainstream vocational education and training (VET) in Australia, which enable people to move between the two sectors in their pursuit of vocational learning, and the ways in which linkages might be improved or new ones developed. The data from the study were derived from 69…

  15. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

    PubMed Central

    McMurray, John J. V.; Packer, Milton; Desai, Akshay S.; Gong, Jim; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.

    2013-01-01

    Aims Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides. Methods Patients with chronic HF, NYHA class II–IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. Perspectives PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF. Trial registration NCT01035255 PMID:23563576

  16. From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension

    PubMed Central

    Patel, Sheila K.; Velkoska, Elena; Freeman, Melanie; Wai, Bryan; Lancefield, Terase F.; Burrell, Louise M.

    2014-01-01

    Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial

  17. ACE2 Decreases Formation and Severity of Angiotensin II-induced Abdominal Aortic Aneurysms

    PubMed Central

    Thatcher, Sean E.; Zhang, Xuan; Howatt, Deborah A.; Yiannikouris, Frederique; Gurley, Susan B.; Ennis, Terri; Curci, John A.; Daugherty, Alan; Cassis, Lisa A.

    2014-01-01

    Objective Angiotensin converting enzyme 2 (ACE2) cleaves angiotensin II (AngII) to form angiotensin-(1-7) (Ang-(1-7)), which generally opposes effects of AngII. AngII infusion into hypercholesterolemic male mice induces formation of abdominal aortic aneurysms (AAAs). This study tests the hypothesis that deficiency of ACE2 promotes AngII-induced AAAs, while ACE2 activation suppresses aneurysm formation. Approach and Results ACE2 protein was detectable by immunostaining in mice and human AAAs. Whole body deficiency of ACE2 significantly increased aortic lumen diameters and external diameters of suprarenal aortas from AngII-infused mice. Conversely, ACE2 deficiency in bone marrow-derived cells had no effect on AngII-induced AAAs. In contrast to AngII-induced AAAs, ACE2 deficiency had no significant effect on external aortic diameters of elastase-induced AAAs. Since ACE2 deficiency promoted AAA formation in AngII-infused mice, we determined if ACE2 activation suppressed AAAs. ACE2 activation by administration of diminazine aceturate (DIZE, 30 mg/kg/day) to Ldlr−/− mice increased kidney ACE2 mRNA abundance and activity and elevated plasma Ang-(1-7) concentrations. Unexpectedly, administration of DIZE significantly reduced total sera cholesterol and VLDL-cholesterol concentrations. Notably, DIZE significantly decreased aortic lumen diameters and aortic external diameters of AngII-infused mice resulting in a marked reduction in AAA incidence (from 73 to 29%). None of these effects of DIZE were observed in the Ace2−/y mice. Conclusions These results demonstrate that ACE2 exerts a modulatory role in AngII-induced AAA formation, and that therapeutic stimulation of ACE2 could be a benefit to reduce AAA expansion and rupture in patients with an activated renin-angiotensin system. PMID:25301841

  18. Parallel Signal Processing and System Simulation using aCe

    NASA Technical Reports Server (NTRS)

    Dorband, John E.; Aburdene, Maurice F.

    2003-01-01

    Recently, networked and cluster computation have become very popular for both signal processing and system simulation. A new language is ideally suited for parallel signal processing applications and system simulation since it allows the programmer to explicitly express the computations that can be performed concurrently. In addition, the new C based parallel language (ace C) for architecture-adaptive programming allows programmers to implement algorithms and system simulation applications on parallel architectures by providing them with the assurance that future parallel architectures will be able to run their applications with a minimum of modification. In this paper, we will focus on some fundamental features of ace C and present a signal processing application (FFT).

  19. ACE infrared spectral atlases of the Earth's atmosphere

    NASA Astrophysics Data System (ADS)

    Hughes, Ryan; Bernath, Peter; Boone, Chris

    2014-11-01

    Five infrared atmospheric atlases are presented using solar occultation spectra from the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) in low earth orbit. The spectral atlases were created for Arctic summer, Arctic winter, mid-latitude summer, mid-latitude winter and the tropics. Each covers the spectral range from 700 to 4400 cm-1 and consists of 31 spectra that span an altitude range of 6-126 km in 4-km altitude intervals. To improve the signal-to-noise ratio, each spectrum in the atlas is an average of at least several hundred individual ACE-FTS limb transmission spectra. Representative plots in pdf format at 10 km (troposphere), 30 km (stratosphere), 70 km (mesosphere), and 110 km (lower thermosphere) are also available.

  20. Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis.

    PubMed

    Raimondi, Sara; Botteri, Edoardo; Munzone, Elisabetta; Cipolla, Carlo; Rotmensz, Nicole; DeCensi, Andrea; Gandini, Sara

    2016-07-01

    Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I(2)  = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted. PMID:26916107

  1. ACES: An Enabling Technology for Next Generation Space Transportation

    NASA Astrophysics Data System (ADS)

    Crocker, Andrew M.; Wuerl, Adam M.; Andrews, Jason E.; Andrews, Dana G.

    2004-02-01

    Andrews Space has developed the ``Alchemist'' Air Collection and Enrichment System (ACES), a dual-mode propulsion system that enables safe, economical launch systems that take off and land horizontally. Alchemist generates liquid oxygen through separation of atmospheric air using the refrigeration capacity of liquid hydrogen. The key benefit of Alchemist is that it minimizes vehicle takeoff weight. All internal and NASA-funded activities have shown that ACES, previously proposed for hypersonic combined cycle RLVs, is a higher payoff, lower-risk technology if LOX generation is performed while the vehicle cruises subsonically. Andrews Space has developed the Alchemist concept from a small system study to viable Next Generation launch system technology, conducting not only feasibility studies but also related hardware tests, and it has planned a detailed risk reduction program which employs an experienced, proven contractor team. Andrews also has participated in preliminary studies of an evolvable Next Generation vehicle architecture-enabled by Alchemist ACES-which could meet civil, military, and commercial space requirements within two decades.

  2. ACE-FTS instrument: activities in preparation for launch

    NASA Astrophysics Data System (ADS)

    Soucy, Marc-Andre; Walker, Kaley A.; Fortin, Serge; Deutsch, Christophe

    2003-11-01

    The Atmospheric Chemistry Experiment (ACE) is the mission selected by the Canadian Space Agency for its next science satellite, SCISAT-1. ACE consists of a suite of instruments in which the primary element is an infrared Fourier Transform Spectrometer (FTS) coupled with an auxiliary 2-channel visible (525 nm) and near infrared imager (1020 nm). A secondary instrument, MAESTRO, provides spectrographic data from the near ultra-violet to the near infrared, including the visible spectral range. In combination the instrument payload covers the spectral range from 0.25 to 13.3 micron. A comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols and temperature will be made by solar occultation from a satellite in low earth orbit. The ACE mission will measure and analyse the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere. A high inclination (74 degrees), low earth orbit (650 km) allows coverage of tropical, mid-latitude and polar regions. This paper presents the instrument-related activities in preparation for launch. In particular, activities related to the integration of instrument to spacecraft are presented as well as tests of the instrument on-board the SciSat-1 bus. Environmental qualification activities at spacecraft-level are described. An overview of the characterization and calibration campaign is presented. Activities for integration and verification at launch site are also covered. The latest status of the spacecraft is also presented.

  3. Pharmacogenetic Risk Stratification in Angiotensin-Converting Enzyme Inhibitor-Treated Patients with Congestive Heart Failure: A Retrospective Cohort Study

    PubMed Central

    Nelveg-Kristensen, Karl Emil; Busk Madsen, Majbritt; Torp-Pedersen, Christian; Køber, Lars; Egfjord, Martin; Berg Rasmussen, Henrik; Riis Hansen, Peter

    2015-01-01

    Background Evidence for pharmacogenetic risk stratification of angiotensin-converting enzyme inhibitor (ACEI) treatment is limited. Therefore, in a cohort of ACEI-treated patients with congestive heart failure (CHF), we investigated the predictive value of two pharmacogenetic scores that previously were found to predict ACEI efficacy in patients with ischemic heart disease and hypertension, respectively. Score A combined single nucleotide polymorphisms (SNPs) of the angiotensin II receptor type 1 gene (rs275651 and rs5182) and the bradykinin receptor B1 gene (rs12050217). Score B combined SNPs of the angiotensin-converting enzyme gene (rs4343) and ABO blood group genes (rs495828 and rs8176746). Methods Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses. Results We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486) and all-cause death (P = 0.515 and P = 0.486) were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79–1.34] and HR 1.11 [95% CI 0.88–1.42]), score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59–1.08] and HR 0.91 [95% CI 0.70–1.20]), score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78–1.32] and HR 0.98 [95% CI 0.77–1.24]), and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75–1.41] and HR 1.05 [95% CI 0.79–1.40]), respectively. Conclusions We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI

  4. Identification of the Major ACE-Inhibitory Peptides Produced by Enzymatic Hydrolysis of a Protein Concentrate from Cuttlefish Wastewater

    PubMed Central

    Rodríguez Amado, Isabel; Vázquez, José Antonio; González, Pilar; Esteban-Fernández, Diego; Carrera, Mónica; Piñeiro, Carmen

    2014-01-01

    The aim of this work was the purification and identification of the major angiotensin converting enzyme (ACE) inhibitory peptides produced by enzymatic hydrolysis of a protein concentrate recovered from a cuttlefish industrial manufacturing effluent. This process consisted on the ultrafiltration of cuttlefish softening wastewater, with a 10 kDa cut-off membrane, followed by the hydrolysis with alcalase of the retained fraction. Alcalase produced ACE inhibitors reaching the highest activity (IC50 = 76.8 ± 15.2 μg mL−1) after 8 h of proteolysis. Sequential ultrafiltration of the 8 h hydrolysate with molecular weight cut-off (MWCO) membranes of 10 and 1 kDa resulted in the increased activity of each permeate, with a final IC50 value of 58.4 ± 4.6 μg mL−1. Permeate containing peptides lower than 1 kDa was separated by reversed-phase high performance liquid chromatography (RP-HPLC). Four fractions (A–D) with potent ACE inhibitory activity were isolated and their main peptides identified using high performance liquid chromatography coupled to an electrospray ion trap Fourier transform ion cyclotron resonance-mass spectrometer (HPLC-ESI-IT-FTICR) followed by comparison with databases and de novo sequencing. The amino acid sequences of the identified peptides contained at least one hydrophobic and/or a proline together with positively charged residues in at least one of the three C-terminal positions. The IC50 values of the fractions ranged from 1.92 to 8.83 μg mL−1, however this study fails to identify which of these peptides are ultimately responsible for the potent antihypertensive activity of these fractions. PMID:24619242

  5. Effect of Beta Blockers and Renin–Angiotensin System Inhibitors on Survival in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Lee, Pil Hyung; Park, Gyung-Min; Kim, Young-Hak; Yun, Sung-Cheol; Chang, Mineok; Roh, Jae-Hyung; Yoon, Sung-Han; Ahn, Jung-Min; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung

    2016-01-01

    Abstract Because it remains uncertain whether β-blockers (BBs) and/or renin–angiotensin system inhibitors benefit a broad population of acute myocardial infarction (AMI) patients, we sought to evaluate the effectiveness of these drugs in improving survival for post-AMI patients who underwent a percutaneous coronary intervention (PCI). From the nationwide data of the South Korea National Health Insurance, 33,390 patients with a diagnosis of AMI who underwent a PCI between 2009 and 2013 and survived at least 30 days were included in this study. We evaluated the risk of all-cause death for patients treated with both BB and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor antagonist (ARB) (n = 16,280), only BB (n = 3683), and only ACEI/ARB (n = 9849), with the drug-untreated patients (n = 3578) as the reference. Over a median follow-up of 2.4 years, although treated patients displayed a trend toward improved survival, there were no significant differences in the adjusted risk of all-cause death when patients were treated with both drugs (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.70–1.06, P = 0.154), BB (HR 0.88, 95% CI 0.68–1.14, P = 0.325), or ACEI/ARB (HR 0.84, 95% CI 0.68–1.04, P = 0.111). No additional benefit was found for the combination therapy compared with either isolated BB (HR 0.98, 95% CI 0.80–1.21, P = 0.856) or ACEI/ARB (HR 1.03, 95% CI 0.89–1.19, P = 0.727) therapy. Treatment with BB and/or ACEI/ARB has limited effect on survival in unselected nonfatal AMI patients who undergo PCI. PMID:26962802

  6. Extension of the ACE solar panels is tested in SAEF-II

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Extension of the solar panels is tested on the Advanced Composition Explorer (ACE) spacecraft in KSC's Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA.

  7. Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study.

    PubMed

    Wieczorek-Surdacka, Ewa; Świerszcz, Jolanta; Surdacki, Andrzej

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10-40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: -4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m² for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman's rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: -1.3 ± 1.0, -4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m², p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD. PMID:26848655

  8. Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

    PubMed Central

    Wieczorek-Surdacka, Ewa; Świerszcz, Jolanta; Surdacki, Andrzej

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD. PMID:26848655

  9. Heavy Ion Temperatures As Observed By ACE/Swics

    NASA Astrophysics Data System (ADS)

    Tracy, P.; Zurbuchen, T.; Raines, J. M.; Shearer, P.; Kasper, J. C.; Gilbert, J. A.; Alterman, B. L.

    2014-12-01

    Heavy ions observed near 1 AU, especially in fast solar wind, tend to have thermal speeds that are approximately equal, indicative of a mass proportional temperature. Additionally, observations near 1 AU have shown a streaming of heavy ions (Z>4) along the magnetic field direction at speeds faster than protons. The differential velocities observed are of the same order but typically less than the Alfven speed. Previous analysis of the behavior of ion thermal velocities with Ulysses-SWICS, focusing on daily average properties of 35 ion species at 5 AU, found only a small systematic trend with respect to q2/m. Utilizing improved data processing techniques, results from the Solar Wind Ion Composition Spectrometer (SWICS) onboard the Advanced Composition Explorer (ACE) shed new light on the thermal properties of the heavy ion population at 1 AU. A clear dependence of heavy ion thermal behavior on q2/m has now been found in the recent ACE-SWICS two hour cadence data set at 1 AU. Examining the thermal velocities of about 70 heavy ion species relative to alpha particles (He2+) shows a distinct trend from equal thermal speed toward equal temperature with increasing q2/m. When examined for solar winds of different collisional ages, the observations indicate the extent of thermal relaxation present in different solar wind types. We explore this collisional dependence with a model for the collisional thermal relaxation of the heavy ions as the solar wind propagates out to 1 AU. This model is used to subtract out the collisional effects seen in the ACE-SWICS data, providing an estimate for the temperature distribution among heavy ions at the corona to be compared to remote sensing observations that have shown that heavy ions are preferentially heated at the corona. We will discuss how this new analysis elucidates the thermal behavior and evolution of heavy ions in the solar wind, along with implications for the upcoming Solar Probe Plus and Solar Orbiter missions.

  10. Helium at Interplanetary Discontinuities: ACE STEREO Observations and Simulations

    NASA Astrophysics Data System (ADS)

    Moebius, E.; Kucharek, H.; Allegrini, F.; Desai, M.; Klecker, B.; Popecki, M.; Farrugia, C.; Galvin, A.; Bochsler, P.; Karrer, R.; Opitz, A.; Simunac, K.

    2007-12-01

    ACE/SEPICA observations showed that, on average, energetic He+ is after H+ and He2+ the third most abundant energetic particle species in the heliosphere. Depending on the type of the energetic population the He+/He2+ ratio can reach unusually high values in the energy range 250 - 800keV/n ratios up to unity. As a major source of energetic He+ interplanetary pickup ions have been identified that are preferentially accelerated at co-rotating interaction regions (CIRs), transient interaction regions (TIRs), and interplanetary traveling shocks. Most recent data from STEREO/PLASTIC in the energy range of 0.2-80keV/Q show clear evidence of abundant He+ at interplanetary discontinuities. Thus PLASTIC extends the energy range into injection region of the source. Furthermore, ACE/ULEIS and ACE/SEPICA measurements showed that very often 3He2+ and He+ are also accelerated simultaneously at CME-driven IP shocks. This is surprising because, these to species originate from different sources. However, this may indicate that the injection, or the acceleration efficiency of the accelerator for different source population may be similar. From observations, however, this cannot be differentiated easily. In numerical simulations this can be done because there is control over species and distribution functions. In a numerical study we applied test particle simulations and multi-dimensional hybrid simulations to address the contribution of source, injection and acceleration efficiency at shocks to the variability of the helium ratio. These, simulations with and without superimposed turbulence in the shock region will be compared with observations.

  11. Recovery of casein-derived peptides with in vitro inhibitory activity of angiotensin converting enzyme (ACE) using aqueous two-phase systems.

    PubMed

    de Souza, Evaldo Cardozo; Coimbra, Jane Sélia Dos Reis; de Oliveira, Eduardo Basílio; Bonomo, Renata Cristina Ferreira

    2014-10-22

    Peptides inhibiting the activity of angiotensin converting enzyme (ACE) were obtained by trypsin-catalyzed hydrolysis of bovine milk casein, performed at 37°C, during 1, 2, 5, 8 and 24h. Results of in vitro inhibitory activity ranged between 13.4% and 78.5%. The highest ACE inhibitory activity was evidenced for hydrolysates obtained after 2h of reaction. Aqueous two-phase systems (ATPS) formed by polyethylene glycol of 1500gmol(-1) (PEG 1500)+sodium phosphate or potassium phosphates were produced and evaluated, in terms of partition coefficients (K) and extraction yields (y), to recovery the casein hydrolysates at room temperature. In ATPS containing sodium phosphate, the peptides showed a slightly greater affinity toward the bottom salt-rich phase (0.1≤K≤0.9; 5.7%≤y≤47%). In the case of ATPS containing potassium phosphates, these molecules showed substantially greater affinity toward the top polymer-rich phase (137≤K≤266; y≥99%). These results point out extraction using PEG 1500/potassium phosphate ATPS is an efficient technique to recover casein hydrolysates containing ACE inhibitors peptides. Outlined data will be helpful in integrating such unit operation to larger scale processes. PMID:25464099

  12. DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression

    PubMed Central

    Zill, Peter; Baghai, Thomas C.; Schüle, Cornelius; Born, Christoph; Früstück, Clemens; Büttner, Andreas; Eisenmenger, Wolfgang; Varallo-Bedarida, Gabriella; Rupprecht, Rainer; Möller, Hans-Jürgen; Bondy, Brigitta

    2012-01-01

    Background The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ∼40%–50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. Materials and Methods The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. Results We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). Conclusion The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders. PMID:22808171

  13. ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC.

    PubMed

    Cheng, Qijian; Zhou, Ling; Zhou, Jianping; Wan, Huanying; Li, Qingyun; Feng, Yun

    2016-09-01

    Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS. We previously reported that ACE2 overexpression may inhibit cell growth and vascular endothelial growth factor (VEGF) production in vitro and in vivo. In the present study, we investigated the effect of ACE2 on tumor-associated angiogen-esis after the development of acquired platinum resistance in non-small cell lung cancer (NSCLC). Four NSCLC cell lines, A549, LLC, A549-DDP and LLC-DDP, were used in vitro, while A549 and A549-DDP cells were used in vivo. A549-DDP and LLC-DDP cells were newly established at our institution as acquired platinum-resistant sublines by culturing the former parent cells in cisplatin (CDDP)-containing conditioned medium for 6 months. These platinum-resistant cells showed significantly higher angiotensin II type 1 receptor (AT1R), ACE and VEGF production and lower ACE2 expression than their corresponding parent cells. We showed that ACE2 overexpression inhibited the production of VEGF in vitro and in vivo compared to their corresponding parent cells. We also found that ACE2 overexpression reduced the expression of AT1R and ACE. Additionally, we confirmed that ACE2 overexpres-sion inhibited cell growth and VEGF production while simultaneously suppressing ACE and AT1R expression in human lung cancer xenografts. Our findings indicate that ACE2 overexpression may potentially suppress angiogenesis in NSCLC after the development of acquired platinum resistance. PMID:27460845

  14. Effects of ACE2 deficiency on physical performance and physiological adaptations of cardiac and skeletal muscle to exercise.

    PubMed

    Motta-Santos, Daisy; Dos Santos, Robson Augusto Souza; Oliveira, Marilene; Qadri, Fatimunnisa; Poglitsch, Marko; Mosienko, Valentina; Kappes Becker, Lenice; Campagnole-Santos, Maria Jose; M Penninger, Joseph; Alenina, Natalia; Bader, Michael

    2016-07-01

    The renin-angiotensin system (RAS) is related to physiological adaptations induced by exercise. Angiotensin-converting enzyme (ACE) 2 is a major regulator of the RAS in tissues, as it metabolizes angiotensin (Ang) II to Ang-(1-7). The aim of this study was to determine the effects of ACE2 deficiency on physical performance and physiological adaptations induced by voluntary running. Physical performance, body composition and plasma angiotensin levels, as well as tissue morphology and gene expression of RAS components in the left ventricle (LV) and skeletal muscle (gastrocnemius), were evaluated in ACE2-deficient (ACE2(-/y)) and wild-type (ACE2(+/y)) mice after 6 weeks of voluntary wheel running. ACE2(-/y) mice run less than ACE2(+/y) mice (19±4.7 vs. 26±12.6 revolutions per day × 100, P<0.01). The ACE2(+/y) group presented a lower fat mass (15±1.1%) and higher muscle mass (76.6±1.6%) after 6 weeks of voluntary running compared with the sedentary control group (fat mass: 18.3±2.1%; muscle mass: 72.7±2.2). However, no change in body composition was observed in ACE2(-/y) mice after exercise. Heart and skeletal muscle hypertrophy was observed only in trained ACE2(+/y) mice. Besides a small decrease in Ang I in ACE2(-/y) mice, plasma levels of angiotensin peptides remained unchanged by exercise or ACE2 deficiency. In the LV of trained animals, AT2 gene expression was higher in ACE2(+/y) compared with ACE2(-/y) mice. ACE2 deficiency leads to an increase in AT1 gene expression in skeletal muscle. ACE expression in soleus was increased in all exercised groups. ACE2 deficiency affects physical performance and impairs cardiac and skeletal muscle adaptations to exercise. PMID:27053009

  15. Postanesthetic Severe Oral Angioedema in Patient's Taking Angiotensin-Converting Enzyme Inhibitor

    PubMed Central

    Marques, Acílio; Retroz-Marques, Carla; Mota, Sara; Cabral, Raquel; Campos, Matos

    2014-01-01

    Angiotensin-converting enzyme (ACE) inhibitors are the leading cause of a drug-induced angioedema. This occurrence is frequently underdiagnosed, but its relapse can be life-threatening. The authors' intention in reporting this clinical case is to sound a warning about reviewing attitudes and surveillance to try to improve patient perioperative safety. PMID:25431681

  16. Treating High Blood Pressure: Is an ACE Inhibitor Drug Right for You?

    MedlinePlus

    ... scientific review by the Oregon Health and Science University-based Drug Effectiveness Review Project. This is a summary of a longer, more detailed report you can find at www.CRBestBuyDrugs.org . Best Buy Generic Name Brand Name A Pills per Average Cost & Strength Day B per Month C Benazepril 20 ...

  17. Uncertainty quantification for accident management using ACE surrogates

    SciTech Connect

    Varuttamaseni, A.; Lee, J. C.; Youngblood, R. W.

    2012-07-01

    The alternating conditional expectation (ACE) regression method is used to generate RELAP5 surrogates which are then used to determine the distribution of the peak clad temperature (PCT) during the loss of feedwater accident coupled with a subsequent initiation of the feed and bleed (F and B) operation in the Zion-1 nuclear power plant. The construction of the surrogates assumes conditional independence relations among key reactor parameters. The choice of parameters to model is based on the macroscopic balance statements governing the behavior of the reactor. The peak clad temperature is calculated based on the independent variables that are known to be important in determining the success of the F and B operation. The relationship between these independent variables and the plant parameters such as coolant pressure and temperature is represented by surrogates that are constructed based on 45 RELAP5 cases. The time-dependent PCT for different values of F and B parameters is calculated by sampling the independent variables from their probability distributions and propagating the information through two layers of surrogates. The results of our analysis show that the ACE surrogates are able to satisfactorily reproduce the behavior of the plant parameters even though a quasi-static assumption is primarily used in their construction. The PCT is found to be lower in cases where the F and B operation is initiated, compared to the case without F and B, regardless of the F and B parameters used. (authors)

  18. Signatures of interchange reconnection: STEREO, ACE and Hinode observations combined

    NASA Astrophysics Data System (ADS)

    Baker, D.; Rouillard, A. P.; van Driel-Gesztelyi, L.; Démoulin, P.; Harra, L. K.; Lavraud, B.; Davies, J. A.; Opitz, A.; Luhmann, J. G.; Sauvaud, J.-A.; Galvin, A. B.

    2009-10-01

    Combining STEREO, ACE and Hinode observations has presented an opportunity to follow a filament eruption and coronal mass ejection (CME) on 17 October 2007 from an active region (AR) inside a coronal hole (CH) into the heliosphere. This particular combination of "open" and closed magnetic topologies provides an ideal scenario for interchange reconnection to take place. With Hinode and STEREO data we were able to identify the emergence time and type of structure seen in the in-situ data four days later. On the 21st, ACE observed in-situ the passage of an ICME with "open" magnetic topology. The magnetic field configuration of the source, a mature AR located inside an equatorial CH, has important implications for the solar and interplanetary signatures of the eruption. We interpret the formation of an "anemone" structure of the erupting AR and the passage in-situ of the ICME being disconnected at one leg, as manifested by uni-directional suprathermal electron flux in the ICME, to be a direct result of interchange reconnection between closed loops of the CME originating from the AR and "open" field lines of the surrounding CH.

  19. ACE: A distributed system to manage large data archives

    NASA Technical Reports Server (NTRS)

    Daily, Mike I.; Allen, Frank W.

    1993-01-01

    Competitive pressures in the oil and gas industry are requiring a much tighter integration of technical data into E and P business processes. The development of new systems to accommodate this business need must comprehend the significant numbers of large, complex data objects which the industry generates. The life cycle of the data objects is a four phase progression from data acquisition, to data processing, through data interpretation, and ending finally with data archival. In order to implement a cost effect system which provides an efficient conversion from data to information and allows effective use of this information, an organization must consider the technical data management requirements in all four phases. A set of technical issues which may differ in each phase must be addressed to insure an overall successful development strategy. The technical issues include standardized data formats and media for data acquisition, data management during processing, plus networks, applications software, and GUI's for interpretation of the processed data. Mass storage hardware and software is required to provide cost effective storage and retrieval during the latter three stages as well as long term archival. Mobil Oil Corporation's Exploration and Producing Technical Center (MEPTEC) has addressed the technical and cost issues of designing, building, and implementing an Advanced Computing Environment (ACE) to support the petroleum E and P function, which is critical to the corporation's continued success. Mobile views ACE as a cost effective solution which can give Mobile a competitive edge as well as a viable technical solution.

  20. ACE2 Global Digital Elevation Model : User Analysis

    NASA Astrophysics Data System (ADS)

    Smith, R. G.; Berry, P. A. M.; Benveniste, J.

    2013-12-01

    Altimeter Corrected Elevations 2 (ACE2), first released in October 2009, is the Global Digital Elevation Model (GDEM) created by fusing the high accuracy of over 100 million altimeter retracked height estimates, derived primarily from the ERS-1 Geodetic Mission, with the high frequency content available within the near-global Shuttle Radar Topography Mission. This novel ACE2 GDEM is freely available at 3”, 9”, 30” and 5' and has been distributed via the web to over 680 subscribers. This paper presents the results of a detailed analysis of geographical distribution of subscribed users, along with fields of study and potential uses. Investigations have also been performed to determine the most popular spatial resolutions and the impact these have on the scope of data downloaded. The analysis has shown that, even though the majority of users have come from Europe and America, a significant number of website hits have been received from South America, Africa and Asia. Registered users also vary widely, from research institutions and major companies down to individual hobbyists looking at data for single projects.

  1. Patients With Newly Diagnosed Hypertension Treated With the Renin Angiotensin Receptor Blocker Azilsartan Medoxomil vs Angiotensin-Converting Enzyme Inhibitors: The Prospective EARLY Registry.

    PubMed

    Schmieder, Roland E; Potthoff, Sebastian A; Bramlage, Peter; Baumgart, Peter; Mahfoud, Felix; Buhck, Hartmut; Ouarrak, Taoufik; Ehmen, Martina; Senges, Jochen; Gitt, Anselm K

    2015-12-01

    For patients with newly diagnosed hypertension, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are usually the first-line therapies. There is, however, no real-life data regarding the relative clinical effectiveness and tolerability of either drug class. The prospective registry, Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY), was conducted to evaluate the effectiveness of the ARB azilsartan medoxomil (AZL-M) vs ACE inhibitors in real-world patients. Of the 1153 patients with newly diagnosed hypertension who were included in the registry, 789 were prescribed AZL-M and 364 were prescribed an ACE inhibitor. After multivariate adjustment, AZL-M was found to provide superior blood pressure reduction and better target blood pressure (<140/90 mm Hg) achievement. The proportion of patients with adverse events was not statistically different between groups. The authors conclude that in newly diagnosed hypertensive patients, AZL-M provides superior blood pressure control with a similar safety profile compared with ACE inhibitors. PMID:26105590

  2. Communications, Navigation, and Surveillance Models in ACES: Design Implementation and Capabilities

    NASA Technical Reports Server (NTRS)

    Kubat, Greg; Vandrei, Don; Satapathy, Goutam; Kumar, Anil; Khanna, Manu

    2006-01-01

    Presentation objectives include: a) Overview of the ACES/CNS System Models Design and Integration; b) Configuration Capabilities available for Models and Simulations using ACES with CNS Modeling; c) Descriptions of recently added, Enhanced CNS Simulation Capabilities; and d) General Concepts Ideas that Utilize CNS Modeling to Enhance Concept Evaluations.

  3. Airspace Concept Evaluation System (ACES), Concept Simulations using Communication, Navigation and Surveillance (CNS) System Models

    NASA Technical Reports Server (NTRS)

    Kubat, Greg; Vandrei, Don

    2006-01-01

    Project Objectives include: a) CNS Model Development; b Design/Integration of baseline set of CNS Models into ACES; c) Implement Enhanced Simulation Capabilities in ACES; d) Design and Integration of Enhanced (2nd set) CNS Models; and e) Continue with CNS Model Integration/Concept evaluations.

  4. A Consolidation of ACE Research, 1990-2000. Review of Research.

    ERIC Educational Resources Information Center

    Golding, Barry; Davies, Merryn; Volkoff, Veronica

    The volume and scope of research into adult and community education (ACE) in Australia have increased significantly over the past decade. Studies designed to map, reevaluate, showcase, and promote ACE have been funded by Australia's federal and state governments and by bodies such as Adult Learning Australia. Practitioner-generated research has…

  5. Formative Evaluation of ACES Program: Findings from Surveys and Interviews Year One, Grades 11 and 12

    ERIC Educational Resources Information Center

    Wolanin, Natalie; Modarresi, Shahpar

    2015-01-01

    The Office of Shared Accountability (OSA) in Montgomery County (Maryland) Public Schools (MCPS) is conducting a multiyear evaluation of the Achieving Collegiate Excellence and Success (ACES) program. The ACES program is a collaboration between MCPS, Montgomery College (MC), and the Universities at Shady Grove (USG) to create a seamless pathway…

  6. Measurements of O3, NO2 and Temperature during the 2004 Canadian Arctic ACE Validation Campaign

    NASA Astrophysics Data System (ADS)

    Kerzenmacher, Tobias E.; Walker, Kaley A.; Strong, Kimberly; Berman, Richard; Bernath, Peter F.; Boone, Chris D.; Drummond, James R.; Fast, Hans; Fraser, Annemarie; MacQuarrie, Keith; Midwinter, Clive; Sung, Keeyoon; McElroy, C. Thomas; Mittermeier, Richard L.; Walker, Jennifer; Wu, Hongjiang

    2005-07-01

    The 2004 Canadian Arctic ACE Validation Campaign was conducted to provide correlative data for validating measurements from the Atmospheric Chemistry Experiment (ACE) satellite mission. These measurements were made at Eureka, Nunavut during polar springtime 2004. Six ground-based instruments were operated during the intensive phase of the campaign and ozonesondes and radiosondes were flown. During this time, ACE-FTS and ACE-MAESTRO were performing solar-occultation measurements over the Canadian Arctic. We report the first comparisons between campaign measurements and those from ACE, focusing on O3, NO2 and temperature. Initial mean O3 profiles from ACE-FTS and ACE-MAESTRO agree to within 20% between 10 and 30 km, and the NO2 profiles agree to within 40% between 17 and 40 km, which is within the standard deviations. The ACE-FTS temperature profiles agree to better than 2.5 K with the radiosonde temperatures from 10 to 32 km and with the lidar temperatures from 17 to 45 km.

  7. ACE expression in monocytes is induced by cytokines, phorbol ester and steroid

    SciTech Connect

    Lazarus, D.; Lanzillo, J.; Fanburg, B. )

    1991-03-15

    Angiotensin converting enzyme (ACE) levels are elevated in the serum and peripheral blood monocytes (PBM) of patients with granulomatous diseases. However, the role of ACE in (Mo) physiology and the regulation of the inflammatory response is not well understood. Since Mo can be stimulated to form giant cells using phorbol esters, glucocorticoids or certain inflammatory cytokines, the authors examined production of ACE protein by normal PBM, a Mo-like cell line, THP-1, and a macrophage-like cell line, U937 following stimulation with these agents. Using a sensitive ELISA assay, they found that in U937 cells, expression of ACE protein increased by 3.4 fold with dexamethasone, 3.7. fold with phorbol 12-myristate acetate (PMA), and 5.8 fold with the two agents combined. The cytokines IL-4 and GM-CSF substantially increased ACE expression, by 7.6 and 7.7 fold respectively, with maximal effect at 0.01 U/ml, while IFN-{gamma} and TNF-{alpha} had little effect. Similar results were found with PBM and THP-1 cells. The combination of dexamethasone and PMA also induced homotypic cluster formation in PBM, suggesting a correlation between cell adhesion and ACE production. The authors conclude that ACE expression in monocytes and macrophages is stimulated by low concentration of glucocorticoids and certain inflammatory cytokines. ACE may participate in the initiation and propagation of granulomatous inflammatory processes.

  8. 76 FR 34246 - Automated Commercial Environment (ACE); Announcement of National Customs Automation Program Test...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-13

    ..., 2003, CBP published a final rule in the Federal Register (68 FR 68140) to effectuate the provisions of... 27, 2006 (71 FR 62922), CBP designated the ACE Truck Manifest System as the approved system for... in which CBP had planned to require the use of ACE. See, 72 FR 53789, September 20, 2007....

  9. SCORE/ACE Counselor Handbook. Service Corps of Retired Executives. Active Corps of Executives.

    ERIC Educational Resources Information Center

    Landsverk, Arvel; And Others

    This counselor handbook is intended to help Service Corps of Retired Executives/Active Corps of Executives (SCORE/ACE) counselors to plan and conduct counseling services more effectively. Included in the introductory section are an overview of the SCORE/ACE counseling program, a discussion of what the counselor does, directions for completing…

  10. Education for 2001 and Beyond: Imperatives and Possibilities. Outcomes from the ACE "Education 2000" International Conference.

    ERIC Educational Resources Information Center

    Unicorn: Journal of the Australian College of Education, 2000

    2000-01-01

    This issue of "Unicorn," the journal of the Australian College of Education (ACE), contains extracts and summaries of 13 presentations given at the international ACE conference, "Education 2000: Priorities for the New Millennium." The papers not only address the five themes of the conference (priorities for learning, priorities for supporting…

  11. Preparing GMAT for Operational Maneuver Planning of the Advanced Composition Explorer (ACE)

    NASA Technical Reports Server (NTRS)

    Qureshi, Rizwan Hamid; Hughes, Steven P.

    2014-01-01

    The General Mission Analysis Tool (GMAT) is an open-source space mission design, analysis and trajectory optimization tool. GMAT is developed by a team of NASA, private industry, public and private contributors. GMAT is designed to model, optimize and estimate spacecraft trajectories in flight regimes ranging from low Earth orbit to lunar applications, interplanetary trajectories and other deep space missions. GMAT has also been flight qualified to support operational maneuver planning for the Advanced Composition Explorer (ACE) mission. ACE was launched in August, 1997 and is orbiting the Sun-Earth L1 libration point. The primary science objective of ACE is to study the composition of both the solar wind and the galactic cosmic rays. Operational orbit determination, maneuver operations and product generation for ACE are conducted by NASA Goddard Space Flight Center (GSFC) Flight Dynamics Facility (FDF). This paper discusses the entire engineering lifecycle and major operational certification milestones that GMAT successfully completed to obtain operational certification for the ACE mission. Operational certification milestones such as gathering of the requirements for ACE operational maneuver planning, gap analysis, test plans and procedures development, system design, pre-shadow operations, training to FDF ACE maneuver planners, shadow operations, Test Readiness Review (TRR) and finally Operational Readiness Review (ORR) are discussed. These efforts have demonstrated that GMAT is flight quality software ready to support ACE mission operations in the FDF.

  12. 77 FR 20835 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... was on trade compliance and the development of the Automated Commercial Environment (ACE), the planned... Portal Accounts and Subsequent Revision Notices: 67 FR 21800 (May 1, 2002); 70 FR 5199 (February 1, 2005); 69 FR 5360 and 69 FR 5362 (February 4, 2004); 69 FR 54302 (September 8, 2004). ACE System of...

  13. Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar) Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

    PubMed Central

    Darewicz, Małgorzata; Borawska, Justyna; Vegarud, Gerd E.; Minkiewicz, Piotr; Iwaniak, Anna

    2014-01-01

    The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE) inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes) and ex vivo digestion (with human gastrointestinal enzymes). Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50%) of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes. PMID:25123137

  14. Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview.

    PubMed

    Zughaib, M E; Sun, J Z; Bolli, R

    1993-01-01

    There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II, ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearrangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in

  15. An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito

    PubMed Central

    Assogba, Benoît S.; Djogbénou, Luc S.; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

    2015-01-01

    Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1R allele), is already present. Furthermore, a duplicated allele (ace-1D) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1D confers less resistance than ace-1R, the high fitness cost associated with ace-1R is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management. PMID:26434951

  16. The effect of saturation of ACE binding sites on the pharmacokinetics of enalaprilat in man.

    PubMed Central

    Wade, J R; Meredith, P A; Hughes, D M; Elliott, H L

    1992-01-01

    1. Eight healthy male volunteers received oral enalapril, 10 mg, in the presence and absence of pretreatment with captopril, 50 mg, twice daily for 5 days. 2. Enalaprilat pharmacokinetics were characterised after both doses of enalapril to investigate the effect of saturating ACE binding sites by pretreatment with captopril. 3. The pharmacokinetics of enalaprilat were best described by a one compartment model with zero order input incorporating saturable binding to plasma and tissue ACE. 4. Values of AUC (0.72 h) for enalaprilat were 419 +/- 97 and 450 +/- 87 ng ml-1 h in the presence and absence of captopril, respectively. The difference was not statistically significant nor were there any other differences in model parameters. 5. Induction of ACE by captopril resulting in an increase in the number of ACE binding sites, may have obscured any effect of captopril on the occupancy of ACE binding sites by enalapril. PMID:1312853

  17. Adolescent parents and their children: a multifaceted approach to prevention of adverse childhood experiences (ACE).

    PubMed

    Mayer, Lynn Milgram; Thursby, Ellen

    2012-01-01

    Childhood experiences can have long-term effects. Research shows that children who undergo adverse childhood experiences (ACE) often have negative health and mental health outcomes later in life. Children of adolescent parents with high ACE Scores are at greater risk of ACE. As such, an intergenerational approach to preventing ACE is proposed in this article, addressing the needs of both the adolescent parent and their children. A review of the literature indicates that a public health perspective can guide the development of a prevention model aimed at reducing the effects of ACE. The current article proposes a universal, multifaceted, and interdisciplinary prevention science model that has two targets: adolescent parents and their children. Schools and early childhood programs can be mobilized to offer community prevention strategies across realms to include the individual, community, provider, coalitions/networks, organizational practices, and policy/legislation. PMID:22970783

  18. Proteasome inhibitors.

    PubMed

    Teicher, Beverly A; Tomaszewski, Joseph E

    2015-07-01

    Proteasome inhibitors have a 20 year history in cancer therapy. The first proteasome inhibitor, bortezomib (Velcade, PS-341), a break-through multiple myeloma treatment, moved rapidly through development from bench in 1994 to first approval in 2003. Bortezomib is a reversible boronic acid inhibitor of the chymotrypsin-like activity of the proteasome. Next generation proteasome inhibitors include carfilzomib and oprozomib which are irreversible epoxyketone proteasome inhibitors; and ixazomib and delanzomib which are reversible boronic acid proteasome inhibitors. Two proteasome inhibitors, bortezomib and carfilzomib are FDA approved drugs and ixazomib and oprozomib are in late stage clinical trials. All of the agents are potent cytotoxics. The disease focus for all the proteasome inhibitors is multiple myeloma. This focus arose from clinical observations made in bortezomib early clinical trials. Later preclinical studies confirmed that multiple myeloma cells were indeed more sensitive to proteasome inhibitors than other tumor cell types. The discovery and development of the proteasome inhibitor class of anticancer agents has progressed through a classic route of serendipity and scientific investigation. These agents are continuing to have a major impact in their treatment of hematologic malignancies and are beginning to be explored as potential treatment agent for non-cancer indications. PMID:25935605

  19. Planning Pathways for Women from Adult Community Education (ACE) to Vocational Education and Training (VET). Project Report.

    ERIC Educational Resources Information Center

    McIntyre, John; Kimberley, Helen

    The formal and informal pathways taken by Australian women from nonaccredited adult community education (ACE) to accredited programs of vocational education and training (VET) were examined in a national survey. Data were collected from a review of the literature on ACE, and telephone interviews with providers of ACE and VET (from a sample limited…

  20. Nine novel angiotensin I-converting enzyme (ACE) inhibitory peptides from cuttlefish (Sepia officinalis) muscle protein hydrolysates and antihypertensive effect of the potent active peptide in spontaneously hypertensive rats.

    PubMed

    Balti, Rafik; Bougatef, Ali; Sila, Assaâd; Guillochon, Didier; Dhulster, Pascal; Nedjar-Arroume, Naima

    2015-03-01

    This study aimed to identify novel ACE inhibitory peptides from the muscle of cuttlefish. Proteins were hydrolyzed and the hydrolysates were then subjected to various types of chromatography to isolate the active peptides. Nine ACE inhibitory peptides were isolated and their molecular masses and amino acid sequences were determined using ESI-MS and ESI-MS/MS, respectively. The structures of the most potent peptides were identified as Val-Glu-Leu-Tyr-Pro, Ala-Phe-Val-Gly-Tyr-Val-Leu-Pro and Glu-Lys-Ser-Tyr-Glu-Leu-Pro. The first peptide displayed the highest ACE inhibitory activity with an IC50 of 5.22μM. Lineweaver-Burk plots suggest that Val-Glu-Leu-Tyr-Pro acts as a non-competitive inhibitor against ACE. Furthermore, antihypertensive effects in spontaneously hypertensive rats (SHR) also revealed that oral administration of Val-Glu-Leu-Tyr-Pro can decrease systolic blood pressure significantly (p<0.01). These results suggest that the Val-Glu-Leu-Tyr-Pro would be a beneficial ingredient for nutraceuticals and pharmaceuticals acting against hypertension and its related diseases. PMID:25306378

  1. Adipocyte-derived lipids increase angiotensin-converting enzyme (ACE) expression and modulate macrophage phenotype.

    PubMed

    Kohlstedt, Karin; Trouvain, Caroline; Namgaladze, Dmitry; Fleming, Ingrid

    2011-03-01

    Human monocytes/macrophages express the angiotensin-converting enzyme (ACE) but nothing is known about its role under physiological conditions. As adipose tissue contains resident macrophages that have been implicated in the generation of insulin resistance in expanding fat mass, we determined whether adipocytes release factors that affect ACE expression and function in monocytes. Incubation of human monocyte-derived macrophages with conditioned medium from freshly isolated human adipocytes (BMI = 25.4 ± 0.96) resulted in a 4-fold increase in ACE expression. The effect was insensitive to denaturation and different proteases but abolished after lipid extraction. mRNA levels of the major histocompatibility complex class II protein increased in parallel with ACE, whereas the expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and cyclooxygenase-2 decreased. As a consequence of the reduction in MCP-1, monocyte recruitment was also attenuated. Moreover, adipocyte-conditioned medium prevented the interferon (IFN)-γ induced formation of TNF-α, IL-6, and MCP-1, all markers of classically-activated (M1 type) macrophages. The decrease in cytokine expression in adipocyte-conditioned medium-treated macrophages was sensitive to ACE silencing by small interfering RNA (siRNA). Accordingly, ACE overexpression in THP-1 cells mimicked the effect of adipocyte-conditioned medium. In both cell types, ACE inhibition failed to affect the changes induced by adipocyte conditioned-medium treatment and ACE overexpression. Thus, the modulation of macrophage polarization by ACE appears to be mediated independently of enzyme activity, probably via intracellular signaling. Interestingly, human macrophage ACE expression was also upregulated by IL-4 and IL-13, which promote the "alternative" activation of macrophages and decreased by LPS and IFN-γ. Mechanistically, adipocyte-conditioned medium stimulated the phosphorylation of

  2. Clouds in the Tropical Lowermost Stratosphere Observed by ACE

    NASA Astrophysics Data System (ADS)

    Sloan, J. J.; Galkina, I.; Sioris, C. E.; Nowlan, C. R.; McElroy, T.; Zou, J.; Hu, J.; Drummond, J. R.; McLinden, C. A.

    2008-12-01

    Evidence for the occurrence of cloud particles in the tropical lowermost stratosphere in the 2004-2007 period is presented. This study is based on measurements by the three Atmospheric Chemistry Experiment (ACE) instruments onboard SCI-SAT. The Vis & NIR Imagers are used to determine the presence of clouds and their top height. The Fourier Transform Spectrometer (FTS) observations are used to determine the size distribution and composition of the aerosols. The FTS has a 4 km field-of-view. Measurements of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (MAESTRO) provide more precise altitude determination of the thermal tropopause and the cloud tops by virtue of its smaller FOV (~1 km). Clouds in the tropical lower stratosphere are a rare occurrence but April 2005 produced a few such cases, consistent with previous observations by OSIRIS. We discuss several individual case studies that demonstrate the presence of large particles (mode radius of ~8 microns) clearly above the tropopause.

  3. Cosmic Ray Helium Intensities over the Solar Cycle from ACE

    NASA Technical Reports Server (NTRS)

    DeNolfo, G. A.; Yanasak, N. E.; Binns, W. R.; Cohen, C. M. S.; Cummings, A. C.; Davis, A. J.; George, J. S.; Hink. P. L.; Israel, M. H.; Lave, K.; Leske, R. A.; Mewaldt, R. A.; Moskalenko, I. V.; Ogliore, R.; Stone, E. C.; Von Rosenvinge, T. T.; Wiedenback, M. E.

    2007-01-01

    Observations of cosmic-ray helium energy spectra provide important constraints on cosmic ray origin and propagation. However, helium intensities measured at Earth are affected by solar modulation, especially below several GeV/nucleon. Observations of helium intensities over a solar cycle are important for understanding how solar modulation affects galactic cosmic ray intensities and for separating the contributions of anomalous and galactic cosmic rays. The Cosmic Ray Isotope Spectrometer (CRIS) on ACE has been measuring cosmic ray isotopes, including helium, since 1997 with high statistical precision. We present helium elemental intensities between approx. 10 to approx. 100 MeV/nucleon from the Solar Isotope Spectrometer (SIS) and CRIS observations over a solar cycle and compare these results with the observations from other satellite and balloon-borne instruments, and with GCR transport and solar modulation models.

  4. Economic evaluation of the Annual Cycle Energy System (ACES). Volume II. Detailed results. Final report

    SciTech Connect

    Not Available

    1980-05-01

    The energy effectiveness and the economic viability of the ACES concept are examined. ACES is studied in a variety of different applications and compared to a number of conventional systems. The different applications are studied in two groups: the class of building into which the ACES is incorporated and the climatic region in which the ACES is located. Buildings investigated include single-family and multi-family residences and a commercial office building. The application of ACES to each of these building types is studied in Minneapolis, Atlanta, and Philadelphia. The economic evaluation of the ACES is based on a comparison of the present worth of the ACES to the present worth of conventional systems; namely, electric resistance heating, electric air conditioning, and electric domestic water heating; air-to-air heat pump and electric domestic water heating; oil-fired furnace, electric air conditioning, and electric domestic water heating; and gas-fired furnace, electric air conditioning, and gas domestic water heating.

  5. Impact of disease states on the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors.

    PubMed

    LeBlanc, Jaclyn M; Dasta, Joseph F; Pruchnicki, Maria C; Schentag, Jerome J

    2006-09-01

    The pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors (ACE) in elderly patients and patients with renal and hepatic impairment were examined, and a role for an AUC/EC50 ratio to guide dosing was evaluated. A Medline and International Pharmaceutical Abstracts search was used to identify human studies and abstracts. Relevant data were evaluated and summarized. Dosing regimens were compared using an AUC/EC50 ratio. Most studies evaluating ACE inhibitors in renal impairment report a strong linear correlation between creatine clearance and drug elimination. AUC and EC50 values for these drugs in elderly subjects appear similar to younger and hypertensive patients. There is increased AUC in some patients with hepatic impairment. Pharmacodynamic data are conflicting. Prolonged ACE inhibition is evident in renal impairment but not necessarily other disease states. ACE inhibitor dosing for hypertension is reasonable based on pharmacokinetics and EC50 values. Further individualization of therapy may improve outcomes, and using the threshold AUC/EC50 ratio may help guide appropriate dosing. PMID:16920891

  6. Developmental expression of ACE2 in the SHR kidney: a role in hypertension?

    PubMed

    Tikellis, C; Cooper, M E; Bialkowski, K; Johnston, C I; Burns, W C; Lew, R A; Smith, A I; Thomas, M C

    2006-07-01

    The abnormal development of the intrarenal renin-angiotensin system (RAS) is thought contribute to adult-onset hypertension in the spontaneously hypertensive rat (SHR). Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with complementary actions to that of ACE. Recent studies have shown that ACE2 expression is reduced in the adult SHR. However, its regulation in pre-hypertensive animals is unknown. In this study, we examine the developmental expression of ACE2 in the rodent kidney and its temporal expression, as it relates to the development of hypertension in the SHR model. Kidneys from SHR and normotensive Wistar Kyoto (WKY) rats (n=8-12/group) at birth, 6 weeks of age, and adulthood (80 days) were examined. Gene expression and activity of ACE2 were determined by real-time reverse transcription-polymerase chain reaction and quenched fluorescence assays, respectively. Renal expression was localized by in situ hybridization and immunohistochemistry. The expression and ACE2 activity are significantly increased in the SHR kidney at birth. With the onset of hypertension, the tubular expression of ACE2 falls in SHR compared to WKY and remains reduced in the adult SHR kidney. Glomerular expression is paradoxically increased in the SHR glomerulus. The overall developmental pattern of ACE2 expression in the SHR kidney is also modified, with declining expression over the course of renal development. The developmental pattern of ACE2 expression in the SHR kidney is altered before the onset of hypertension, consistent with the key role of the RAS in the pathogenesis of adult-onset hypertension. Further research is required to distinguish the contribution of these changes to the development and progression of hypertension in this model. PMID:16710353

  7. Progress on the Multiphysics Capabilities of the Parallel Electromagnetic ACE3P Simulation Suite

    SciTech Connect

    Kononenko, Oleksiy

    2015-03-26

    ACE3P is a 3D parallel simulation suite that is being developed at SLAC National Accelerator Laboratory. Effectively utilizing supercomputer resources, ACE3P has become a key tool for the coupled electromagnetic, thermal and mechanical research and design of particle accelerators. Based on the existing finite-element infrastructure, a massively parallel eigensolver is developed for modal analysis of mechanical structures. It complements a set of the multiphysics tools in ACE3P and, in particular, can be used for the comprehensive study of microphonics in accelerating cavities ensuring the operational reliability of a particle accelerator.

  8. APL workers install CRIS on the Advanced Composition Explorer (ACE) in SAEF-2

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Workers from the Johns Hopkins University's Applied Physics Laboratory (APL) install the Cosmic Ray Isotope Spectrometer (CRIS) on the Advanced Composition Explorer (ACE) spacecraft in KSC's Spacecraft Assembly and Encapsulation Facility-2 (SAEF-2). From left, are Al Sadilek, Marcos Gonzalez and Cliff Willey. CRIS is one of nine instruments on ACE, which will investigate the origin and evolution of solar phenomenon, the formation of the solar corona, solar flares and the acceleration of the solar wind. ACE was developed for NASA by the APL. The spacecraft is scheduled to be launched Aug. 21 aboard a two-stage Delta II 7920-8 rocket from Space Launch Complex 17, Pad A.

  9. Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR: impact of prior transient ACE inhibition.

    PubMed

    Biwer, Lauren A; D'souza, Karen M; Abidali, Ali; Tu, Danni; Siniard, Ashley L; DeBoth, Matthew; Huentelman, Matthew; Hale, Taben M

    2016-01-01

    We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (L-arginine methyl ester, L-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of L-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. L-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during L-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of L-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts. PMID:26490086

  10. ACES: The ASCENDS CarbonHawk Experiment Simulator

    NASA Astrophysics Data System (ADS)

    Obland, M. D.; Prasad, N. S.; Harrison, F. W.; Browell, E. V.; Ismail, S.; Dobler, J. T.; Moore, B.; Zaccheo, T.; Campbell, J.; Chen, S.; Cleckner, C. S.; DiJoseph, M.; Little, A.; Notari, A.; Refaat, T. F.; Rosenbaum, D.; Vanek, M. D.; Bender, J.; Braun, M.; Chavez-Pirson, A.; Neal, M.; Rayner, P. J.; Rosiewicz, A.; Shure, M.; Welch, W.

    2012-12-01

    The ASCENDS CarbonHawk Experiment Simulator (ACES) is a NASA Langley Research Center project funded by NASA's Earth Science Technology Office (ESTO) Instrument Incubator Program (IIP) that seeks to advance technologies critical to measuring atmospheric column carbon dioxide (CO2) mixing ratios in support of the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. The technologies being advanced are: (1) a high bandwidth detector, (2) a multi-aperture telescope assembly, (3) advanced algorithms for cloud and aerosol discrimination, and (4) high-efficiency, multiple-amplifier CO2 and O2 laser transmitters. The instrument architecture will be developed to operate on a high-altitude aircraft and will be directly scalable to meet the ASCENDS mission requirements. These technologies are viewed as critical towards developing an airborne simulator and eventual spaceborne instrument with lower size, mass, and power consumption, and improved performance. The detector effort will improve the existing detector subsystem by increasing its bandwidth to a goal of 5 MHz, reducing its overall mass from 18 lbs to <10 lbs, and stretching the duration of autonomous, service-free operation periods from 4 hrs to >24 hrs. The development goals are to permit higher laser modulation rates, which provides greater flexibility for implementing thin-cloud discrimination algorithms as well as improving range resolution and error reduction, and to enable long flights on a high-altitude unmanned aerial vehicle (UAV). The telescope development consists of a three-telescope design built for the constraints of the Global Hawk aircraft. This task addresses the ability of multiple smaller telescopes to provide equal or greater collection efficiency compared with a single larger telescope with a reduced impact on launch mass and cost. The telescope assembly also integrates fiber-coupled transmit collimators for all of the laser transmitters and fiber-coupled optical

  11. Favourable outcome of scleroderma renal crisis.

    PubMed Central

    Collins, D A; Patel, S; Eastwood, J B; Bourke, B E

    1996-01-01

    Severe hypertension and rapidly progressive acute renal failure is a well recognized complication of scleroderma, often referred to as the renal crisis, and widely thought to cause irreversible deterioration in renal function. With the advent of angiotensin-converting-enzyme inhibitors (ACE-I) the outlook for patients with this condition has dramatically improved. We report here one such patient. Images Figure 1 PMID:8709086

  12. Early genes induction in spontaneously hypertensive rats left ventricle with angiotensin-converting enzyme inhibitors but not hydralazine

    SciTech Connect

    Susic, D.; Aristizabal, D.J.; Prakash, O.; Nunez, E.; Frohlich, E.D.

    1995-12-01

    Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hyralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action. 27 refs., 1 fig., 2 tabs.

  13. The path to an angiotensin receptor antagonist-neprilysin inhibitor in the treatment of heart failure.

    PubMed

    Braunwald, Eugene

    2015-03-17

    The PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial demonstrated that a new angiotensin receptor antagonist-neprilysin inhibitor was superior to an angiotensin-converting enzyme inhibitor in reducing mortality in patients with heart failure and reduced ejection fraction. This paper traces the research path that culminated in the development of this drug. The first phase, elucidation of the renin-angiotensin-aldosterone system, began with Tigerstedt's discovery of renin, followed by isolation of angiotensin, isolation of angiotensin-converting enzyme, and synthesis of its inhibitors and of angiotensin receptor blockers. Phase 2 began with de Bold's discovery of atrial natriuretic peptide, followed by isolation of the enzyme that degrades it (neprilysin) and its inhibitors. Phase 3 consists of blocking both the renin-angiotensin-aldosterone and atrial natriuretic peptide-degrading systems simultaneously. A molecular complex, LCZ696, developed by scientists at Novartis, combines an angiotensin receptor blocker with a neprilysin inhibitor, is well tolerated, and represents an important step in the management of heart failure and reduced ejection fraction. PMID:25766951

  14. Atmospheric Chemistry Experiment (ACE) Measurements of Tropospheric and Stratospheric Chemistry and Long-Term Trends

    NASA Technical Reports Server (NTRS)

    Rinsland, Curtis P.; Bernath, Peter; Boone, Chris; Nassar, Ray

    2007-01-01

    We highlight chemistry and trend measurement results from the Atmospheric Chemistry Experiment (ACE) which is providing precise middle troposphere to the lower thermosphere measurements with a 0.02/cm resolution Fourier transform spectrometer covering 750-4400/cm

  15. ACE2: Angiotensin II/Angiotensin-(1-7) balance in cardiorenal injury

    PubMed Central

    Varagic, Jasmina; Ahmad, Sarfaraz; Nagata, Sayaka; Ferrario, Carlos M.

    2014-01-01

    Our current recognition of the renin-angiotensin system is more convoluted than originally thought due to the discovery of multiple novel enzymes, peptides, and receptors inherent to this interactive biochemical cascade. Over the last decade angiotensin converting enzyme 2 (ACE2) has emerged as a key player in the pathophysiology of hypertension and cardiovascular and renal disease due to its pivotal role in metabolizing vasoconstrictive/hypertrophic/proliferative angiotensin II into favorable angiotensin-(1-7). This review addresses a considerable advancement in research on the role of tissue ACE2 in development and progression of hypertension and cardiorenal injury. We also summarize the results from recent clinical and experimental studies suggesting that serum or urine soluble ACE2 may serve as a novel biomarker or independent risk factor relevant for diagnosis and prognosis of cardiorenal disease. Recent proceedings on novel therapeutic approaches to enhance ACE2/angiotensin-(1-7) axis are also reviewed. PMID:24510672

  16. Beneficial role of D allele in controlling ACE levels: a study among Brahmins of north India.

    PubMed

    Kumari, Shobha; Sharma, Nidhi; Thakur, Sunil; Mondal, Prakash R; Saraswathy, Kallur N

    2016-06-01

    India being a country with vast diversity is expected to have different dietary and life style patterns which in turn may lead to population-specific environmental risk factors. Further, the interaction of these risk factors with the genetic makeup of population makes it either susceptible or resistant to cardiovascular disease. One such candidate gene is angiotensin converting enzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone system pathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associated with various complex diseases. The DD genotype is found to increase ACE levels, which is associated with cardiovascular diseases and decrease in ACE levels are associated with kidney diseases. The aim of this study was to understand the distribution of ACE I/D polymorphism and ACE levels among Brahmins of National Capital Region (NCR) north India, with respect to age and sex ratio distribution. In this study, 136 subjects of which 50 males and 86 females, who were unrelated up to first cousin, aged 25 to70 years were studied. ACE gene was found to be polymorphic with high frequency of heterozygote (ID) followed by II and DD genotypes. The studied population was found to be in Hardy-Weinberg equilibrium with respect to ACE I/D polymorphism (P = 0.55). I allele frequency was found to be higher (0.560) than the D allele (0.44). The median level of ACE was found to be 65.96 ng/mL (48.12-86.24) which is towards lower side of the normal range. ACE levels were found to be increased among individual having either of the homozygotes that is II or DD and higher frequency of heterozygote (ID) is indicative of advantage in the population by maintaining lower ACE levels. The limitation of the present study is low sample size, however, the merit is that the subjects belonged to a Mendalian population with a common gene pool. PMID:27350671

  17. Angiotensin I-Converting Enzyme Inhibitory Peptides of Chia (Salvia hispanica) Produced by Enzymatic Hydrolysis

    PubMed Central

    Segura Campos, Maira Rubi; Peralta González, Fanny; Chel Guerrero, Luis

    2013-01-01

    Synthetic angiotensin I-converting enzyme (ACE-I) inhibitors can have undesirable side effects, while natural inhibitors have no side effects and are potential nutraceuticals. A protein-rich fraction from chia (Salvia hispanica L.) seed was hydrolyzed with an Alcalase-Flavourzyme sequential system and the hydrolysate ultrafiltered through four molecular weight cut-off membranes (1 kDa, 3 kDa, 5 kDa, and 10 kDa). ACE-I inhibitory activity was quantified in the hydrolysate and ultrafiltered fractions. The hydrolysate was extensive (DH = 51.64%) and had 58.46% ACE-inhibitory activity. Inhibition ranged from 53.84% to 69.31% in the five ultrafiltered fractions and was highest in the <1 kDa fraction (69.31%). This fraction's amino acid composition was identified and then it was purified by gel filtration chromatography and ACE-I inhibition measured in the purified fractions. Amino acid composition suggested that hydrophobic residues contributed substantially to chia peptide ACE-I inhibitory strength, probably by blocking angiotensin II production. Inhibitory activity ranged from 48.41% to 62.58% in the purified fractions, but fraction F1 (1.5–2.5 kDa) exhibited the highest inhibition (IC50 = 3.97 μg/mL; 427–455 mL elution volume). The results point out the possibility of obtaining bioactive peptides from chia proteins by means of a controlled protein hydrolysis using Alcalase-Flavourzyme sequentional system. PMID:26904588

  18. Angiotensin I-Converting Enzyme Inhibitory Peptides of Chia (Salvia hispanica) Produced by Enzymatic Hydrolysis.

    PubMed

    Segura Campos, Maira Rubi; Peralta González, Fanny; Chel Guerrero, Luis; Betancur Ancona, David

    2013-01-01

    Synthetic angiotensin I-converting enzyme (ACE-I) inhibitors can have undesirable side effects, while natural inhibitors have no side effects and are potential nutraceuticals. A protein-rich fraction from chia (Salvia hispanica L.) seed was hydrolyzed with an Alcalase-Flavourzyme sequential system and the hydrolysate ultrafiltered through four molecular weight cut-off membranes (1 kDa, 3 kDa, 5 kDa, and 10 kDa). ACE-I inhibitory activity was quantified in the hydrolysate and ultrafiltered fractions. The hydrolysate was extensive (DH = 51.64%) and had 58.46% ACE-inhibitory activity. Inhibition ranged from 53.84% to 69.31% in the five ultrafiltered fractions and was highest in the <1 kDa fraction (69.31%). This fraction's amino acid composition was identified and then it was purified by gel filtration chromatography and ACE-I inhibition measured in the purified fractions. Amino acid composition suggested that hydrophobic residues contributed substantially to chia peptide ACE-I inhibitory strength, probably by blocking angiotensin II production. Inhibitory activity ranged from 48.41% to 62.58% in the purified fractions, but fraction F1 (1.5-2.5 kDa) exhibited the highest inhibition (IC50 = 3.97 μg/mL; 427-455 mL elution volume). The results point out the possibility of obtaining bioactive peptides from chia proteins by means of a controlled protein hydrolysis using Alcalase-Flavourzyme sequentional system. PMID:26904588

  19. Characterization, biomedical and agricultural applications of protease inhibitors: A review.

    PubMed

    Shamsi, Tooba Naz; Parveen, Romana; Fatima, Sadaf

    2016-10-01

    This review describes Protease Inhibitors (PIs) which target or inhibit proteases, protein digesting enzymes. These proteases play a crucial task in many biological events including digestion, blood coagulation, apoptosis etc. Regardless of their crucial roles, they need to be checked regularly by PIs as their excess may possibly damage host organism. On basis of amino acid composition of PIs where Protease-PI enzymatic reactions occur i.e. serine, cysteine, and aspartic acid, they are classified. Nowadays, various PIs are being worked upon to fight various parasitic or viral diseases including malaria, schistosomiasis, colds, flu', dengue etc. They prevent an ongoing process begun by carcinogen exposure by keeping a check on metastasis. They also possess potential to reduce carcinogen-induced, increased levels of gene amplification to almost normal levels. Some PIs can principally be used for treatment of hypertension and congestive heart failure by blocking conversion of angiotensin I to angiotensin II for example Angiotensin-converting enzyme inhibitors (ACEIs). Also PIs target amyloid β-peptide (Aβ) level in brain which is prime responsible for development of Alzheimer's Disease (AD). Also, PIs inhibit enzymatic activity of HIV-1 Protease Receptor (PR) by preventing cleavage events in Gag and Gag-Pol that result in production of non-virulent virus particles. PMID:26955746

  20. CFTR Inhibitors

    PubMed Central

    Verkman, Alan S.; Synder, David; Tradtrantip, Lukmanee; Thiagarajah, Jay R.; Anderson, Marc O.

    2014-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl− channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretory diarrheas, such as cholera, and for cyst expansion in autosomal dominant polycystic kidney disease. High-throughput screening has yielded CFTR inhibitors of the thiazolidinone, glycine hydrazide and quinoxalinedione chemical classes. The glycine hydrazides target the extracellular CFTR pore, whereas the thiazolidinones and quinoxalinediones act at the cytoplasmic surface. These inhibitors have been widely used in cystic fibrosis research to study CFTR function at the cell and organ levels. The most potent CFTR inhibitor has IC50 of approximately 4 nM. Studies in animal models support the development of CFTR inhibitors for antisecretory therapy of enterotoxin-mediated diarrheas and polycystic kidney disease. PMID:23331030

  1. ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension.

    PubMed

    Mendoza-Torres, Evelyn; Oyarzún, Alejandra; Mondaca-Ruff, David; Azocar, Andrés; Castro, Pablo F; Jalil, Jorge E; Chiong, Mario; Lavandero, Sergio; Ocaranza, María Paz

    2015-08-01

    The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling. PMID:26275770

  2. Crosstalk between ACE2 and PLGF regulates vascular permeability during acute lung injury

    PubMed Central

    Wang, Lantao; Li, Yong; Qin, Hao; Xing, Dong; Su, Jie; Hu, Zhenjie

    2016-01-01

    Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI), through antagonizing hydrolyzing angiotensin II (AngII) and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with placental growth factor (PLGF) remain ill-defined. In the current study, we examined the relationship between ACE2 and PLGF in ALI model in mice. We used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of PLGF in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5 µg/kg Visudyne. PLGF pump or soluble Flt-1 (sFlt-1) pump was given to augment or suppress PLGF effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. We found that ACE2 treatment did not alter PLGF levels in lung, but antagonized the effects of PLGF on increases of lung vessel permeability. Ectogenic PLGF abolished the antagonizing effects of ACE2 on the vessel permeability against PLGF. On the other hand, suppression of PLGF signaling mimicked the effects of ACE2 on the vessel permeability against PLGF. The suppression of vessel permeability resulted in improvement of lung function after ALI. Thus, ACE2 may antagonize the PLGF-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI. PMID:27158411

  3. Isolation of angiotensin converting enzyme (ACE) inhibiting triterpenes from Schinus molle.

    PubMed

    Olafsson, K; Jaroszewski, J W; Smitt, U W; Nyman, U

    1997-08-01

    Bioactivity-guided fractionation of extracts of Schinus molle leaves, using an in vitro assay, led to the isolation of ACE-inhibitory steroidal triterpenes of the euphane type, identified by means of NMR spectroscopic methods. One of the triterpenes was isolated as an equilibrium mixture of epimeric aldehydes. The triterpenes showed moderate ACE-inhibitory activity (IC(50) about 250 microM). PMID:17252394

  4. Variation in the ACE, PPARGC1A and PPARA genes in Lithuanian football players.

    PubMed

    Gineviciene, Valentina; Jakaitiene, Audrone; Tubelis, Linas; Kucinskas, Vaidutis

    2014-01-01

    The aim of this study was to determine the impact of ACE (I/D), PPARGC1A (G/A) and PPARA (G/C) polymorphisms on footballers performance among 199 Lithuanian professional footballers and 167 sedentary, healthy men (controls). Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism methods on DNA from leucocytes. Results revealed that the angiotensin-1-coverting enzyme gene (ACE) genotype distribution was significantly different between total football players group (II 23.6%, ID 46.7% and DD 29.6%) and the controls (II 24.6%, ID 29.9% and DD 45.5%; P=0.002). Although investigating PPARGC1A (G/A) and PPARA (G/C) polymorphisms no significant results were obtained in the total football players group, however, significant differences were determined between forwards and controls [PPARGC1A: GG 54.6%, GA 29.5%, AA 15.9% vs. GG 49.7%, GA 44.3% and AA 6.0% (P = 0.044); PPARA: GG 52.3%, GC 40.9%, CC 6.8% vs. GG 72.4%, GC 24.6% and CC 3.0% (P = 0.034)]. In the whole cohort, the odds ratio of the genotype [ACE ID + PPARA GG] being a footballer was 1.69 (95% CI 1.04-2.74), and of [ACE ID + PPARGC1A GG] 1.93 (95% CI 1.10-3.37) and of [ACE II + PPARA GC] 2.83 (95% CI 1.02-7.91) compared to controls. It was revealed that ACE ID genotype together with PPARA GG and PPARGC1A GG as well as ACE II genotype with PPARA GC is probably the 'preferable genotype' for footballers. Summing up, the present study suggests that the ACE, PPARGC1A and PPARA polymorphisms genotypes are associated, separately and in combination, with Lithuanian footballers' performance. PMID:24444220

  5. Helping Students Process a Simulated Death Experience: Integration of an NLN ACE.S Evolving Case Study and the ELNEC Curriculum.

    PubMed

    Kopka, Judith A; Aschenbrenner, Ann P; Reynolds, Mary B

    2016-01-01

    The nursing literature supports the need for end-of-life (EOL) education, but the ability to provide quality clinical experience in this area is limited by the availability of patients and nursing instructors' and preceptors' comfort and expertise in teaching EOL care. Clinical simulation allows faculty to provide the same quality EOL experience to all students. This article discusses an effective teaching strategy integrating End-of-Life Nursing Education Consortium core content with National League for Nursing ACE.S unfolding case studies, clinical simulation, and social media. PMID:27405204

  6. Exercise manual for the Augmented Computer Exercise for Inspection Training (ACE-IT) software

    SciTech Connect

    Dobranich, P.R.; Widney, T.W.; Goolsby, P.T.; Nelson, J.D.; Evanko, D.A.

    1997-09-01

    The on-site inspection provisions in many current and proposed arms control agreements require extensive preparation and training on the part of both the Inspected Party and the Inspection Team. Current training techniques include table-top inspections and practice inspections. The Augmented Computer Exercise for Inspection Training (ACE-IT), an interactive computer training tool, increases the utility of table-top inspections. ACE-IT has been designed to provide training for a hypothetical challenge inspection under the Chemical Weapons Convention (CWC); however, this training tool can be modified for other inspection regimes. Although ACE-IT provides training from notification of an inspection through post-inspection activities, the primary emphasis of ACE-IT is in the inspection itself--particularly with the concept of managed access. ACE-IT also demonstrates how inspection provisions impact compliance determination and the protection of sensitive information. The Exercise Manual supplements the ACE-IT software by providing general information on on-site inspections and detailed information for the CWC challenge inspection exercise. The detailed information includes the pre-inspection briefing, maps, list of sensitive items, medical records, and shipping records.

  7. Aerosol Characterization Data from the Asian Pacific Regional Aerosol Characterization Project (ACE-Asia)

    DOE Data Explorer

    The Aerosol Characterization Experiments (ACE) were designed to increase understanding of how atmospheric aerosol particles affect the Earth's climate system. These experiments integrated in-situ measurements, satellite observations, and models to reduce the uncertainty in calculations of the climate forcing due to aerosol particles and improve the ability of models to predict the influences of aerosols on the Earth's radiation balance. ACE-Asia was the fourth in a series of experiments organized by the International Global Atmospheric Chemistry (IGAC) Program (A Core Project of the International Geosphere Biosphere Program). The Intensive Field Phase for ACE-Asia took place during the spring of 2001 (mid-March through early May) off the coast of China, Japan and Korea. ACE-Asia pursued three specific objectives: 1) Determine the physical, chemical, and radiative properties of the major aerosol types in the Eastern Asia and Northwest Pacific region and investigate the relationships among these properties. 2) Quantify the physical and chemical processes controlling the evolution of the major aerosol types and in particular their physical, chemical, and radiative properties. 3) Develop procedures to extrapolate aerosol properties and processes from local to regional and global scales, and assess the regional direct and indirect radiative forcing by aerosols in the Eastern Asia and Northwest Pacific region [Edited and shortened version of summary at http://data.eol.ucar.edu/codiac/projs?ACE-ASIA]. The Ace-Asia collection contains 174 datasets.

  8. Technical manual for the Augmented Computer Exercise for Inspection Training (ACE-IT) software

    SciTech Connect

    Dobranich, P.R.; Horak, K.E.; Hagan, D.; Evanko, D.; Nelson, J.; Ryder, C.; Hedlund, D.

    1997-09-01

    The on-site inspection provisions in many current and proposed arms control agreements require extensive preparation and training on the part of both the Inspection Teams (inspectors) and Inspected Parties (host). Current training techniques include table-top inspections and practice inspections. The Augmented Computer Exercise for Inspection Training (ACE-IT), an interactive computer training tool, increases the utility of table-top inspections. ACE-IT has been designed to provide training for challenge inspections under the Chemical Weapons Convention (CWC); however, this training tool can be modified for other inspection regimes. Although ACE-IT provides training from notification of an inspection through post-inspection activities, the primary emphasis of ACE-IT is in the inspection itself--particularly with the concept of managed access. ACE-IT also demonstrates how inspection provisions impact compliance determination and the protection of sensitive information. This Technical Manual describes many of the technical aspects of the ACE-IT training software.

  9. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2

    PubMed Central

    Li, Wenhui; Zhang, Chengsheng; Sui, Jianhua; Kuhn, Jens H; Moore, Michael J; Luo, Shiwen; Wong, Swee-Kee; Huang, I-Chueh; Xu, Keming; Vasilieva, Natalya; Murakami, Akikazu; He, Yaqing; Marasco, Wayne A; Guan, Yi; Choe, Hyeryun; Farzan, Michael

    2005-01-01

    Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic. PMID:15791205

  10. ACE insertion/deletion polymorphism and diabetic nephropathy: clinical implications of genetic information.

    PubMed

    Ha, Sung-Kyu

    2014-01-01

    Approximately 20-40% of diabetic patients develop nephropathy which is the leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought to be a marker for functional polymorphism which regulates circulating and tissue ACE activity. While the initial study found a protective effect of the II genotype on the development of nephropathy in IDDM patients, subsequent studies have addressed the role of ACE I/D polymorphism in the development and progression of diabetic nephropathy. RAAS blockers are the first line drugs for the treatment hypertension associated with diabetes and have been widely used in everyday clinical practice for the purpose of reducing proteinuria in patients with various renal diseases. However, the antiproteinuric effect of RAAS blockers is variable and the percentage of reducing proteinuria is in the range of 20-80%. The antiproteinuric effect of RAAS blockers may be related to a number of factors: the type or the dose of RAAS blockers, the duration of therapy, the level of sodium intake, and the type of patient's ACE I/D genotype. Besides the nongenetic factors, drug responses, can be influenced by ACE gene polymorphism. In this review, we discuss the relationship between ACE I/D polymorphism and diabetic nephropathy and therapeutic response of RAAS blockers. PMID:25587546

  11. Hamsters vaccinated with Ace-mep-7 DNA vaccine produced protective immunity against Ancylostoma ceylanicum infection.

    PubMed

    Wiśniewski, Marcin; Jaros, Sławomir; Bąska, Piotr; Cappello, Michael; Długosz, Ewa; Wędrychowicz, Halina

    2016-04-01

    Hookworms are intestinal nematodes that infect up to 740 million people, mostly in tropical and subtropical regions. Adult worms suck blood from damaged vessels in the gut mucosa, digesting hemoglobin using aspartic-, cysteine- and metalloproteases. Targeting aspartic hemoglobinases using drugs or vaccines is therefore a promising approach to ancylostomiasis control. Based on homology to metalloproteases from other hookworm species, we cloned the Ancylostoma ceylanicum metalloprotease 7 cDNA (Ace-mep-7). The corresponding Ace-MEP-7 protein has a predicted molecular mass of 98.8 kDa. The homology to metallopeptidases from other hookworm species and its predicted transmembrane region support the hypothesis that Ace-MEP-7 may be involved in hemoglobin digestion in the hookworm gastrointestinal tract, especially that our analyses show expression of Ace-mep-7 in the adult stage of the parasite. Immunization of Syrian golden hamsters with Ace-mep-7 cDNA resulted in 50% (p < 0.01) intestinal worm burden reduction. Additionally 78% (p < 0.05) egg count reduction in both sexes was observed. These results suggest that immunization with Ace-mep-7 may contribute to reduction in egg count released into the environment during the A. ceylanicum infection. PMID:26795262

  12. Drug Repositioning and Pharmacophore Identification in the Discovery of Hookworm MIF Inhibitors

    SciTech Connect

    Y Cho; J Vermeire; J Merkel; L Leng; X Du; R Bucala; M Cappello; E Lolis

    2011-12-31

    The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new pharmacophores. Hookworms are blood-feeding, intestinal nematode parasites that infect up to 600 million people worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage migration inhibitory factor (rAceMIF) provided partial protection from disease, thus establishing a 'proof-of-concept' for targeting AceMIF to prevent or treat infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF-specific inhibitors. A nonsteroidal anti-inflammatory drug (NSAID), sodium meclofenamate, could be tested in an animal model to assess the therapeutic efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic, exhibited submicromolar inhibition of rAceMIF tautomerase activity. Structure-activity relationships of a pharmacophore based on furosemide included one analog that binds similarly to the active site, yet does not inhibit the Na-K-Cl symporter (NKCC1) responsible for diuretic activity.

  13. GPS Antenna Characterization Experiment (ACE): Receiver Design and Initial Results

    NASA Technical Reports Server (NTRS)

    Martzen, Phillip; Highsmith, Dolan E.; Valdez, Jennifer E.; Parker, Joel J. K.; Moreau, Michael C.

    2015-01-01

    The GPS Antenna Characterization Experiment (ACE) is a research collaboration between Aerospace and NASA Goddard to characterize the gain patterns of the GPS L1 transmit antennas. High altitude GPS observations are collected at a ground station through a transponder-based or "bent-pipe" architecture where the GPS L1 RF spectrum is received at a platform in geosynchronous orbit and relayed to the ground for processing. The focus of this paper is the unique receiver algorithm design and implementation. The high-sensitivity GPS C/A-code receiver uses high fidelity code and carrier estimates and externally supplied GPS message bit data in a batch algorithm with settings for a 0 dB-Hz threshold. The resulting carrier-to-noise measurements are used in a GPS L1 transmit antenna pattern reconstruction. This paper shows initial transmit gain patterns averaged over each block of GPS satellites, including comparisons to available pre-flight gain measurements from the GPS vehicle contractors. These results provide never-before-seen assessments of the full, in-flight transmit gain patterns.

  14. Operation Heli-STAR - Atlanta Communications Experiment (ACE). Volume 9

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Operation Heli-STAR (Helicopter Short-Haul Transportation and Aviation Research) was established and operated in Atlanta, Georgia, during the period of the 1996 Centennial Olympic Games. Heli-STAR had three major thrusts: (1) the establishment and operation of a helicopter-based cargo transportation system, (2) the management of low-altitude air traffic in the airspace of an urban area, and (3) the collection and analysis of research and development data associated with items 1 and 2. Heli-STAR was a cooperative industry/government program that included parcel package shippers and couriers in the Atlanta area, the helicopter industry, aviation electronics manufacturers, the Federal Aviation Administration (FAA), the National Aeronautics and Space Administration (NASA), and support contractors. Several detailed reports have been produced as a result of Operation Heli-STAR. These include four reports on acoustic measurements and associated analyses, and reports on the Heli-STAR tracking data including the data processing and retrieval system, the Heli-STAR cargo simulation, and the community response system. In addition, NASA's Advanced General Aviation Transport Experiments (AGATE) program has produced a report describing the Atlanta Communications Experiment (ACE) which produced the avionics and ground equipment using automatic dependent surveillance-broadcast (ADS-B) technology. This latter report is restricted to organizations belonging to NASA's AGATE industry consortium. A complete list of these reports is shown on the following page.

  15. ACE Observatory Control System - 16 years of remote intercontinental observing

    NASA Astrophysics Data System (ADS)

    Mack, Peter

    2011-03-01

    The ACE Observatory Control System has been used for remote control since 1995. The system was designed for use at isolated observatories with no-one present on the mountain-top. The software provides complete diagnostic feedback to the astronomer and is supplemented by live audio-visual. Accessories include environmental sensors (weather station, all-sky camera, constellation cameras), automated mirror covers and remote power control. This gives the astronomer the same experience as being present at the observatory. The system is installed on 30 telescopes and many of them are used for routine nightly intercontinental observations, such as Taejeon (S. Korea) to Mt. Lemmon (Arizona) and southeast USA to KPNO and CTIO. The system has fully integrated autoguider acquisition and science camera control. We describe the building blocks of the system and the accessories including automated mirror covers, weather station, all sky camera, remote power control and dome control. Future plans are presented for a fully autonomous platform-independent scheduler and robot for use on multiple telescopes.

  16. Oral Delivery of ACE2/Ang-(1–7) Bioencapsulated in Plant Cells Protects against Experimental Uveitis and Autoimmune Uveoretinitis

    PubMed Central

    Shil, Pollob K; Kwon, Kwang-Chul; Zhu, Ping; Verma, Amrisha; Daniell, Henry; Li, Qiuhong

    2014-01-01

    Hyperactivity of the renin-angiotensin system (RAS) resulting in elevated Angiotensin II (Ang II) contributes to all stages of inflammatory responses including ocular inflammation. The discovery of angiotensin-converting enzyme 2 (ACE2) has established a protective axis of RAS involving ACE2/Ang-(1–7)/Mas that counteracts the proinflammatory and hypertrophic effects of the deleterious ACE/AngII/AT1R axis. Here we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS by oral delivery of ACE2 and Ang-(1–7) bioencapsulated in plant cells would confer protection against ocular inflammation. Both ACE2 and Ang-(1–7), fused with the non-toxic cholera toxin subunit B (CTB) were expressed in plant chloroplasts. Increased levels of ACE2 and Ang-(1–7) were observed in circulation and retina after oral administration of CTB-ACE2 and Ang-(1–7) expressing plant cells. Oral feeding of mice with bioencapsulated ACE2/Ang-(1–7) significantly reduced endotoxin-induced uveitis (EIU) in mice. Treatment with bioencapsulated ACE2/Ang-(1–7) also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in experimental autoimmune uveoretinitis (EAU). Thus, enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1–7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for ocular inflammatory diseases. PMID:25228068

  17. Inhibition Mechanism and Model of an Angiotensin I-Converting Enzyme (ACE)-Inhibitory Hexapeptide from Yeast (Saccharomyces cerevisiae)

    PubMed Central

    Ni, He; Li, Lin; Liu, Guang; Hu, Song-Qing

    2012-01-01

    Angiotensin I-converting enzyme (ACE) has an important function in blood pressure regulation. ACE-inhibitory peptides can lower blood pressure by inhibiting ACE activity. Based on the sequence of an ACE-inhibitory hexapeptide (TPTQQS) purified from yeast, enzyme kinetics experiments, isothermal titration calorimetry (ITC), and a docking simulation were performed. The hexapeptide was found to inhibit ACE in a non-competitive manner, as supported by the structural model. The hexapeptide bound to ACE via interactions of the N-terminal Thr1, Thr3, and Gln4 residues with the residues on the lid structure of ACE, and the C-terminal Ser6 attracted the zinc ion, which is vital for ACE catalysis. The displacement of the zinc ion from the active site resulted in the inhibition of ACE activity. The structural model based on the docking simulation was supported by experiments in which the peptide was modified. This study provides a new inhibitory mechanism of ACE by a peptide which broads our knowledge for drug designing against enzyme targets. PMID:22606330

  18. Attenuation of myocardial fibrosis with curcumin is mediated by modulating expression of angiotensin II AT1/AT2 receptors and ACE2 in rats

    PubMed Central

    Pang, Xue-Fen; Zhang, Li-Hui; Bai, Feng; Wang, Ning-Ping; Garner, Ron E; McKallip, Robert J; Zhao, Zhi-Qing

    2015-01-01

    Curcumin is known to improve cardiac function by balancing degradation and synthesis of collagens after myocardial infarction. This study tested the hypothesis that inhibition of myocardial fibrosis by curcumin is associated with modulating expression of angiotensin II (Ang II) receptors and angiotensin-converting enzyme 2 (ACE2). Male Sprague Dawley rats were subjected to Ang II infusion (500 ng/kg/min) using osmotic minipumps for 2 and 4 weeks, respectively, and curcumin (150 mg/kg/day) was fed by gastric gavage during Ang II infusion. Compared to the animals with Ang II infusion, curcumin significantly decreased the mean arterial blood pressure during the course of the observation. The protein level of the Ang II type 1 (AT1) receptor was reduced, and the Ang II type 2 (AT2) receptor was up-regulated, evidenced by an increased ratio of the AT2 receptor over the AT1 receptor in the curcumin group (1.2±0.02%) vs in the Ang II group (0.7±0.03%, P<0.05). These changes were coincident with less locally expressed AT1 receptor and enhanced AT2 receptor in the intracardiac vessels and intermyocardium. Along with these modulations, curcumin significantly decreased the populations of macrophages and alpha smooth muscle actin-expressing myofibroblasts, which were accompanied by reduced expression of transforming growth factor beta 1 and phosphorylated-Smad2/3. Collagen I synthesis was inhibited, and tissue fibrosis was attenuated, as demonstrated by less extensive collagen-rich fibrosis. Furthermore, curcumin increased protein level of ACE2 and enhanced its expression in the intermyocardium relative to the Ang II group. These results suggest that curcumin could be considered as an add-on therapeutic agent in the treatment of fibrosis-derived heart failure patient who is intolerant of ACE inhibitor therapy. PMID:26648693

  19. Current role of neprilysin inhibitors in hypertension and heart failure.

    PubMed

    von Lueder, Thomas G; Atar, Dan; Krum, Henry

    2014-10-01

    Cardiovascular diseases (CVD) continue to represent the major cause of death, morbidity and healthcare expenditure worldwide. Current medical therapy fails to effectively halt disease progression and to reduce adverse clinical outcomes, reflecting incomplete understanding of pathomechanisms as well as the need to expand current pharmacotherapeutic strategies. Hypertension and heart failure, the most important CVD entities, are associated with imbalance in neurohormonal systems activity such as the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system and the endothelin system. Blockade of the RAAS constitutes the most successful pharmacotherapeutic concept in hypertension and heart failure to date. The RAAS-opposing natriuretic peptide system constitutes the body's own BP-lowering system, and mediates a multitude of beneficial actions within cardiovascular tissues. The metallopeptidase neprilysin (NEP) hydrolyzes natriuretic peptides. Conceptually, NEP inhibition would increase salutary natriuretic peptide actions in CVD. However, stand-alone NEP inhibitors (NEPi) lacked efficacy beyond standard pharmacotherapy. Combined blockers of NEP and the endothelin system demonstrated efficacy in preclinical studies but have not been evaluated in clinical trials. A decade ago, omapatrilat and other dual-acting NEPi-ACEi (vasopeptidase-inhibitors) were promising agents for hypertension and heart failure. Despite greater efficacy, development of vasopeptidase-inhibitors was halted due to significant off-target effects in some cohorts, most notably increased frequency of angioedema in hypertensive subjects. Novel angiotensin-receptor-neprilysin-inhibitors (ARNi) seek to fully exploit clinical efficacy of combined RAAS-blockade and NEPi-mediated natriuretic peptide augmentation, and hopefully do so with improved clinical safety. We herein review current knowledge of NEPi as stand-alone and combined pharmacotherapeutic agents in hypertension and heart

  20. Effects of angiotensin converting enzyme inhibitor and angiotensin II receptor antagonist combination on nitric oxide bioavailability and atherosclerotic change in Watanabe heritable hyperlipidemic rabbits.

    PubMed

    Imanishi, Toshio; Kuroi, Akio; Ikejima, Hideyuki; Kobayashi, Katsunobu; Muragaki, Yasuteru; Mochizuki, Seiichi; Goto, Masami; Yoshida, Kiyoshi; Akasaka, Takashi

    2008-03-01

    We investigated the effects of co-administration of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blocker (ARB) on nitric oxide (NO) bioavailability in genetically hyperlipidemic rabbits with our newly developed NO sensor. Plasma NO was measured using the new NO sensor in the abdominal aorta of anesthetized Watanabe heritable hyperlipidemic (WHHL) rabbits. Acetylcholine (ACh)-stimulated (20 microg in 5 min into the aortic arch) NO production was recorded after an 8 week per os pretreatment with 1) vehicle (control), 2) the ACEI enalapril (E: 3 mg/kg/day), 3) the ARB losartan (L: 30 mg/kg/day) and 4) enalapril (1.5 mg/kg/day)+losartan (15 mg/kg/day) (E+L). Intra-aortic infusion of ACh produced an increase in plasma NO concentration, which was significantly greater with all the drug treatments than with the control. E increased ACh-induced NO significantly more than L (by 6.9 nmol/L, and 4.7 nmol/L, respectively). E+L increased ACh-induced NO by 9.5 nmol/L, significantly more than either E or L. Plasma peroxynitrite concentration was 1.2 pmol/mg protein in the control group and significantly less than in the E- and L-group. The lowest peroxynitrite concentration was observed in the E+L group (0.5 pmol/mg protein), which was significantly lower than in the E-group and the L-group. Optical coherence tomography and histology of the thoracic aorta revealed that the plaque area decreased significantly more with the combination than with the monotherapy (p<0.01). In conclusion, the combined treatment with an ACEI and an ARB may have additive protective effects on endothelial function as well as atherosclerotic change. PMID:18497479

  1. Enhancing the ACE control center for the multiple uses of spacecraft integration and test and mission and science operations

    NASA Technical Reports Server (NTRS)

    Snow, Frank; Garrard, Thomas L.; Steck, Jane A.; Maury, Jesse L.

    1996-01-01

    In relation to the mandate to reduce space mission development and operations costs, the advanced composition explorer (ACE) will use a version of the Transportable Payload Operations Control Center (TPOCC) for its mission operations. It was determined during the phase B of the ACE project that a potential existed for substantial savings if the adaptation of the TPOCC for the ACE mission operations could include its adaptation for use as the primary component in the ground support equipment for the integration and testing of the ACE spacecraft, and for use as the basic component in the ACE science center. The implementation of this approach required the enhancement of the TPOCC requirements, changes in the development schedule and changes in the allocation and activities of the personnel responsible for the development of ACE operations. It is discussed how these issues, and the problems that arose, were addressed.

  2. Angiotensin I-Converting Enzyme Inhibitor Activity on Egg Albumen Fermentation

    PubMed Central

    Nahariah, N.; Legowo, A. M.; Abustam, E.; Hintono, A.

    2015-01-01

    Lactobacillus plantarum is used for fermentation of fish products, meat and milk. However, the utilization of these bacteria in egg processing has not been done. This study was designed to evaluate the potential of fermented egg albumen as a functional food that is rich in angiotensin I-converting enzyme inhibitors activity (ACE-inhibitor activity) and is antihypertensive. A completely randomized design was used in this study with six durations of fermentation (6, 12, 18, 24, 30, and 36 h) as treatments. Six hundred eggs obtained from the same chicken farm were used in the experiment as sources of egg albumen. Bacteria L. plantarum FNCC 0027 used in the fermentation was isolated from cow’s milk. The parameters measured were the total bacteria, dissolved protein, pH, total acid and the activity of ACE-inhibitors. The results showed that there were significant effects of fermentation time on the parameters tested. Total bacteria increased significantly during fermentation for 6, 12, 18, and 24 h and then decreased with the increasing time of fermentation to 30 and 36 h. Soluble protein increased significantly during fermentation to 18 h and then subsequently decreased during of fermentation to 24, 30, and 36 h. The pH value decreased markedly during fermentation. The activities of ACE-inhibitor in fermented egg albumen increased during fermentation to 18 h and then decreased with the increasing of the duration of fermentation to 24, 30, and 36 h. The egg albumen which was fermented for 18 h resulted in a functional food that was rich in ACE-inhibitor activity. PMID:25715689

  3. Regulation of Ace2-dependent genes requires components of the PBF complex in Schizosaccharomyces pombe

    PubMed Central

    Suárez, M Belén; Alonso-Nuñez, María Luisa; del Rey, Francisco; McInerny, Christopher J; Vázquez de Aldana, Carlos R

    2015-01-01

    The division cycle of unicellular yeasts is completed with the activation of a cell separation program that results in the dissolution of the septum assembled during cytokinesis between the 2 daughter cells, allowing them to become independent entities. Expression of the eng1+ and agn1+ genes, encoding the hydrolytic enzymes responsible for septum degradation, is activated at the end of each cell cycle by the transcription factor Ace2. Periodic ace2+ expression is regulated by the transcriptional complex PBF (PCB Binding Factor), composed of the forkhead-like proteins Sep1 and Fkh2 and the MADS box-like protein Mbx1. In this report, we show that Ace2-dependent genes contain several combinations of motifs for Ace2 and PBF binding in their promoters. Thus, Ace2, Fkh2 and Sep1 were found to bind in vivo to the eng1+ promoter. Ace2 binding was coincident with maximum level of eng1+ expression, whereas Fkh2 binding was maximal when mRNA levels were low, supporting the notion that they play opposing roles. In addition, we found that the expression of eng1+ and agn1+ was differentially affected by mutations in PBF components. Interestingly, agn1+ was a major target of Mbx1, since its ectopic expression resulted in the suppression of Mbx1 deletion phenotypes. Our results reveal a complex regulation system through which the transcription factors Ace2, Fkh2, Sep1 and Mbx1 in combination control the expression of the genes involved in separation at the end of the cell division cycle. PMID:26237280

  4. The Altus Cumulus Electrification Study (ACES): A UAV-based Investigation of Thunderstorms

    NASA Technical Reports Server (NTRS)

    Blakeslee, Richard; Arnold, James E. (Technical Monitor)

    2001-01-01

    The Altus Cumulus Electrification Study (ACES) is a NASA-sponsored and -led science investigation that utilizes an uninhabited aerial vehicle (UAV) to investigate thunderstorms in the vicinity of the NASA Kennedy Space Center, Florida. As part of NASA's UAV-based science demonstration program, ACES will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES will employ the Altus 11 aircraft, built by General Atomics-Aeronautical Systems, Inc. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high-altitude flight (up to 55,000 feet), the Altus will be flown near, and when possible, above (but never into) thunderstorms for long periods of time, allowing investigations to be conducted over entire storm life cycles. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and (3) provide Lightning Imaging Sensor validation. The ACES payload, already developed and flown on Altus, includes electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. The ACES field campaign will be conducted during July 2002 with a goal of performing 8 to 10 UAV flights. Each flight will require about 4 to 5 hours on station at altitudes from 40,000 ft to 55,000 ft. The ACES team is comprised of scientists from the NASA Marshall Space Flight Center and NASA Goddard Space Flight Centers partnered with General Atomics and IDEA, LLC.

  5. Regulation of Ace2-dependent genes requires components of the PBF complex in Schizosaccharomyces pombe.

    PubMed

    Suárez, M Belén; Alonso-Nuñez, María Luisa; del Rey, Francisco; McInerny, Christopher J; Vázquez de Aldana, Carlos R

    2015-01-01

    The division cycle of unicellular yeasts is completed with the activation of a cell separation program that results in the dissolution of the septum assembled during cytokinesis between the 2 daughter cells, allowing them to become independent entities. Expression of the eng1(+) and agn1(+) genes, encoding the hydrolytic enzymes responsible for septum degradation, is activated at the end of each cell cycle by the transcription factor Ace2. Periodic ace2(+) expression is regulated by the transcriptional complex PBF (PCB Binding Factor), composed of the forkhead-like proteins Sep1 and Fkh2 and the MADS box-like protein Mbx1. In this report, we show that Ace2-dependent genes contain several combinations of motifs for Ace2 and PBF binding in their promoters. Thus, Ace2, Fkh2 and Sep1 were found to bind in vivo to the eng1(+) promoter. Ace2 binding was coincident with maximum level of eng1(+) expression, whereas Fkh2 binding was maximal when mRNA levels were low, supporting the notion that they play opposing roles. In addition, we found that the expression of eng1(+) and agn1(+) was differentially affected by mutations in PBF components. Interestingly, agn1(+) was a major target of Mbx1, since its ectopic expression resulted in the suppression of Mbx1 deletion phenotypes. Our results reveal a complex regulation system through which the transcription factors Ace2, Fkh2, Sep1 and Mbx1 in combination control the expression of the genes involved in separation at the end of the cell division cycle. PMID:26237280

  6. Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

    PubMed Central

    Chung, Chia-Min; Wang, Ruey-Yun; Fann, Cathy S. J.; Chen, Jaw-Wen; Jong, Yuh-Shiun; Jou, Yuh-Shan; Yang, Hsin-Chou; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Pan, Wen-Harn

    2013-01-01

    Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10–16 to <10–33). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3′UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects. PMID:23469169

  7. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

    PubMed

    Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance. PMID:26224885

  8. Ethics and ACEI: Beginning the Conversation

    ERIC Educational Resources Information Center

    Freeman, Nancy

    2004-01-01

    Codes of ethics are one of the important hallmarks of a profession. Along with prolonged training, specialized knowledge, and rites of passage, a code is one of the criteria that sets professionals apart from other workers (Katz & Ward, 1991). Literature describing the current focus on ethics in the workplace invariably describes codes addressing…

  9. High resolution critical habitat mapping and classification of tidal freshwater wetlands in the ACE Basin

    NASA Astrophysics Data System (ADS)

    Strickland, Melissa Anne

    In collaboration with the South Carolina Department of Natural Resources ACE Basin National Estuarine Research Reserve (ACE Basin NERR), the tidal freshwater ecosystems along the South Edisto River in the ACE Basin are being accurately mapped and classified using a LIDAR-Remote Sensing Fusion technique that integrates LAS LIDAR data into texture images and then merges the elevation textures and multispectral imagery for very high resolution mapping. This project discusses the development and refinement of an ArcGIS Toolbox capable of automating protocols and procedures for marsh delineation and microhabitat identification. The result is a high resolution habitat and land use map used for the identification of threatened habitat. Tidal freshwater wetlands are also a critical habitat for colonial wading birds and an accurate assessment of community diversity and acreage of this habitat type in the ACE Basin will support SCDNR's conservation and protection efforts. The maps developed by this study will be used to better monitor the freshwater/saltwater interface and establish a baseline for an ACE NERR monitoring program to track the rates and extent of alterations due to projected environmental stressors. Preliminary ground-truthing in the field will provide information about the accuracy of the mapping tool.

  10. Seasonal comparisons of retrieved temperature and water vapour between ACE-FTS and COSMIC.

    NASA Astrophysics Data System (ADS)

    Olsen, Kevin; Toon, Geoff; Boone, Chris; Strong, Kim

    2015-04-01

    Motivated by the selection of a high-resolution solar occultation Fourier transform spectrometer (FTS) to fly to Mars, we developed new algorithms for retrieving vertical profiles of temperature and pressure from spectra. We present temperature retrieval results from remote sensing spectra collected by the Canadian Space Agency's (CSA) Atmospheric Chemistry Experiment (ACE), which recently celebrated its tenth year in orbit. ACE utilizes a high-resolution (0.02 cm-1) Fourier Transform Spectrometer (FTS) operating between 750-4400 cm-1 in limb-scanning mode using the sun as a light source (solar occultation). We compare our retrieved profiles to those of the ACE Science Team and the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC). COSMIC is a group of six small satellites that use signals from GPS satellites to measure water vapour pressure an temperature via radio occultation. We have collected five sets of zonal and seasonal coincidences with a tight criteria of 150 km and 1 hour. Retrieved H2O profiles from both satellites will also be presented for these data sets. Compared to ACE, we can achieve T differences between 1 and 5 K below 50 km, perform less well between 50 and 100 km. Compared to COSMIC, available below 40 km, we perform similarly, while the ACE retrievals are in close agreement.

  11. Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs

    SciTech Connect

    Pitt, B.R.; Lister, G.; Dawson, C.A.; Linehan, J.H.

    1986-05-01

    Angiotensin-converting enzyme (ACE) activity of the cerebral microcirculation of anesthetized dogs was measured from cerebral venous outflow curves after bolus injection of a synthetic ACE substrate, (/sup 3/H)benzoyl-phenylalanyl-alanylproline ((/sup 3/H)BPAP), into a common carotid artery. Cerebral BPAP metabolism was quantified by measuring the concentration of (/sup 3/H)benzoyl-phenylalanine (the product of BPAP hydrolysis by ACE) in blood samples from the sagittal sinus after occlusion of the lateral sinuses with bone wax. Instantaneous BPAP metabolism in each sample increased as a function of time after injection, suggestive of perfusion heterogeneity, and averaged 59 +/- 4% (n = 8) over a single pass during normoxia and normocapnia. The ratio of Vmax (the maximal rate of cerebral BPAP metabolism) to Km (the concentration at Vmax/2), was calculated from instantaneous outflow curves using a model based on first-order kinetics. Increases in cerebral blood flow during either hypoxia or hypercapnia significantly reduced BPAP metabolism to 33 +/- 3 (n = 7) and 24 +/- 3% (n = 5), respectively; however, Vmax/Km of ACE activity (0.19 +/- 0.03 ml/s) was not affected by either condition. The lack of change in apparent kinetics of ACE activity (i.e., in Vmax/Km) during hypoxia or hypercapnia suggests that recruitment of cerebral capillaries was not a quantitatively significant factor in controlling BPAP metabolism with this degree of either hypoxia or hypercapnia.

  12. [Comparison of salvage chemotherapy regimen ACES with ESHAP for refractory or relapsed malignant lymphoma].

    PubMed

    Imataki, Osamu; Tamai, Yotaro; Kawakami, Kimihiro

    2007-10-01

    Standard salvage chemotherapy for refractory or relapsed malignant lymphoma has not been defined. The efficacy and feasibility of the ACES regimen, consisting of carboplatin at 100 mg/m(2) on day 1 to 4, etoposide at 80 mg/m(2) on day 1 to 4, high-dose Ara-C at 2 g/m(2) on day 5 and methylprednisolone at 500 mg/day for 5 days, for refractory or relapsed lymphoma were retrospectively reviewed in comparison with the ESHAP regimen. The subjects were 29 patients, including 7 aggressive follicular lymphomas, 16 large B cell lymphomas and 6 Hodgkin lymphomas. Characteristics of patients with ESHAP (19 cases) and the ACES (10 cases) group were as follows: male/female ratio, 10/9 and 3/7; median age, 49 (range, 31-72) and 54 (22-65); and initial clinical stage (I and II / III / IV), 5/8/6 and 1/1/8, respectively. Among the 29 patients, complete response was achieved in 68% (13/19) in ESHAP and 40% (4/10) in ACES.Progression-free survival and overall survival were 31.3% and 34.3%, respectively. Hematological toxicity was not significantly different between the two groups, and renal toxicity was significantly higher in ESHAP (52%) than ACES (0%). We concluded that the ACES regimen had a possibility of effective consolidation therapy for the elderly aiming to undergo autologous stem cell transplantation. PMID:17940378

  13. ace-3 plays an important role in phoxim resistance in Caenorhabditis elegans.

    PubMed

    Han, Yan; Song, Shaojuan; Guo, Yaping; Zhang, Jianzhen; Ma, Enbo

    2016-05-01

    Organophosphorus and carbamate are widely used in agricultural production. Caenorhabditis elegans is a model organism that is widely used in various toxicology studies. To understand the effects of two types of commonly used pesticides, phoxim (organophosphorus) and carbaryl (carbamate), we determined the activities of acetylcholinesterases (AChEs) and detected the expression of four ace genes by RT-qPCR in C. elegans following treatment with these pesticides. The results showed that phoxim and carbaryl could reduce acetylcholinesterase activities and up-regulate the ace-3 mRNA expression levels. We also detected the toxic effects of these pesticides on the ace-3 deletion mutant dc-2, and found that some characteristics, including LC50, development, movement, reproduction and lifespan, were reduced in the dc-2 mutant. However, the toxic effects of carbaryl were weaker than those of phoxim. Carbaryl treatment did not significantly affect the LC50, movement ability or lifespan. Interestingly, body and brood size increased with carbaryl treatment at low concentrations. These data showed that both phoxim and carbaryl could inhibit AChE but that the ace-3 was necessary for phoxim detoxification. The LC50 of phoxim and carbaryl in wild type N2 and the ace-3 deletion mutant dc-2. **Higher significant differences (P < 0.01). PMID:26947509

  14. ACE Project ∼ Advocating for Clinical Excellence: Creating Change in the Delivery of Palliative Care

    PubMed Central

    Otis-Green, Shirley; Yang, Eunice; Lynne, Lisa

    2013-01-01

    Background Psychologists, social workers and spiritual care professionals report inadequate preparation to maximize their effectiveness in advocating for institutional reform to meet oncology patients' diverse bio-psychosocial-spiritual and cultural needs. This article provides an overview of the ACE Project, a National Cancer Institute, 5 year, R25-funded transdisciplinary palliative care education program designed to enhance the advocacy and leadership skills of 301 competitively selected psycho-oncology professionals. Methods ACE Project participants identified an institutional goal, refined their goals during the course and received mentorship and support throughout the subsequent year. Participants were invited to return to a Reunion Conference in year five to report on their activities, network and share the results of their change efforts. A subset of 28 ACE Project participants contributed to this OMEGA special issue. Results Participants' goals primarily focused on strategies to improve clinical care through program development and improvements in palliative care education within their institutions. Conclusions The results of this transdisciplinary leadership skills-building program for psycho-oncology professionals affirm the feasibility and perceived need for the program. See the ACE Project website (http://www.cityofhope.org/ace-project ) for additional program information. PMID:23977775

  15. ACE inhibitory activity of pangasius catfish (Pangasius sutchi) skin and bone gelatin hydrolysate.

    PubMed

    Mahmoodani, Fatemeh; Ghassem, Masomeh; Babji, Abdul Salam; Yusop, Salma Mohamad; Khosrokhavar, Roya

    2014-09-01

    Skin and bone gelatins of pangasius catfish (Pangasius sutchi) were hydrolyzed with alcalase to isolate Angiotensin Converting Enzyme (ACE) inhibitory peptides. Samples with the highest degree of hydrolysis (DH) were separated into different fractions with molecular weight cut-off (MWCO) sizes of 10, 3 and 1 kDa, respectively and assayed for ACE inhibitory activity. Skin and bone gelatins had highest DH of 64.87 and 68.48 % after 2 and 1 h incubation, respectively. Results from this study indicated that by decreasing the molecular weight of fractions, ACE inhibitory activity was increased. Therefore, F3 permeates (MWCO < 1 kDa) of skin (IC50 = 3.2 μg/ml) and bone (IC50 = 1.3 μg/ml) gelatins possessed higher ACE inhibitory activity compared to their untreated gelatins and corresponding hydrolyzed fractions. In this study, the major amino acids were Glycine followed by Proline with an increased amount of hydrophobic amino acid content in F3 permeates of skin (4.01 %) and bone (5.79 %) gelatin. Digestion stability against gastrointestinal proteases did not show any remarkable change on ACE inhibition potency of these permeates. It was concluded that alcalase hydrolysis of P. sutchi by-products could be utilized as a part of functional food or ingredients of a formulated drug in order to control high blood pressure. PMID:25190839

  16. Preparation of ACE Inhibitory Peptides from Mytilus coruscus Hydrolysate Using Uniform Design

    PubMed Central

    Wu, Jin-Chao; Cheng, Jie; Shi, Xiao-lai

    2013-01-01

    The angiotensin-I-converting enzyme (ACE) inhibitory peptides from mussel, Mytilus coruscus, were investigated and the variable factors, protease concentration, hydrolysis time, pH, and temperature, were optimized using Uniform Design, a new statistical experimental method. The results proved that the hydrolysate of alkali proteases had high ACE-inhibitory activity, especially the alkali protease E1. Optimization by Uniform Design showed that the best hydrolysis conditions for preparation of ACE-inhibitory peptides from Mytilus coruscus were protease concentration of 36.0 U/mL, hydrolysis time of 2.7 hours, pH 8.2, and Temperature at 59.5°C, respectively. The verification experiments under optimum conditions showed that the ACE-inhibitory activity (91.3%) were agreed closely with the predicted activity of 90.7%. The amino acid composition analysis of Mytilus coruscus ACE-inhibitory peptides proved that it had high percent of lysine, leucine, glycine, aspartic acid, and glutamic acid. PMID:23484103

  17. ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

    PubMed Central

    Lee, Seong-Jong; Han, Jong-Min; Lee, Jin-Seok; Son, Chang-Gue; Im, Hwi-Jin; Jo, Hyun-Kyung; Yoo, Ho-Ryong; Kim, Yoon-Sik; Seol, In-Chan

    2015-01-01

    The medicinal plants Artemisia iwayomogi (A. iwayomogi) and Curcuma longa (C. longa) radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM). In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE) on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group) were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group) were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg) or curcumin (50 mg/kg). Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides), glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα). The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model. PMID:26508977

  18. Overview of Aircraft Operations during ACE-Asia

    NASA Astrophysics Data System (ADS)

    Seinfeld, J. H.; Huebert, B.

    2001-12-01

    The NSF/NCAR C-130 flew 19 flights out of Iwakuni, Japan between March 31 and May 4, 2001, and data were collected on 7 ferry flights crossing the Pacific. Many of the instruments derived their air from low-turbulence inlets, which enabled studies of supermicron particles vs altitude. Several flights sampled two heavy dust outbreaks, where the aerosol mass concentration exceeded 1000 †g/m3. Size-dependent chemical measurements indicated that this dust did not dramatically change the sulfate size distribution (by causing SO2 to convert to sulfate on its alkaline surfaces), since the vast majority of the sulfate was still in a submicron accumulation mode. Similarly, while the scattering in dust was dominated by large particles, the particle absorption was almost exclusively submicron. We found extensive layering, with as many as 6 distinct dust layers (and clean layers between them) in one profile to 6 km. During ACE-Asia research missions were also conducted using a modified De Havilland DHC-6 Twin Otter aircraft operated by the California Institute of Technology and the Center for Interdisciplinary Remotely Piloted Aircraft studies (CIRPAS). A total of 19 research flights were conducted between March 31 and May 1, 2001 from the base of operations at the MCAS Iwakuni, Japan. The sampling area included portions of the Sea of Japan south and east of the Korean Peninsula, the East China Sea between China, Japan and Korea, and the Philippine Sea south of Japan. Collected aerosols were analyzed to determine their chemical composition and physical properties such as size distribution, hygroscopic growth, light scattering and absorption properties. Simultaneous radiative measurements were also made using the 14-channel Ames Airborne Tracking Sunphotometer (AATS-14), which measured solar beam transmission at 14 wavelengths (353-1558 nm), yielding aerosol optical depth (AOD) spectra and column water vapor (CWV). Vertical differentiation in profiles yielded aerosol

  19. Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications.

    PubMed

    Tikoo, Kulbhushan; Patel, Gaurang; Kumar, Sandeep; Karpe, Pinakin Arun; Sanghavi, Maitri; Malek, Vajir; Srinivasan, K

    2015-02-01

    Growing body of evidence points out the crucial role of ACE2 in preventing atherosclerosis. However, data on how atherosclerosis affects ACE2 expression in heart and kidney remains unknown. Atherosclerosis was induced by feeding New Zealand White rabbits with high cholesterol diet (HCD - 2%) for 12 weeks and atorvastatin was administered (5mg/kg/day p.o) in last 3 weeks. ACE2 mRNA and protein expression was assessed by Western blotting and real time PCR. HCD fed rabbits developed atherosclerosis as confirmed by increase in plasma total cholesterol, LDL and triglycerides as well as formation atherosclerotic plaques in arch of aorta. The ACE2 protein but not mRNA expression was reduced in heart and kidney of HCD rabbits. Interestingly, atorvastatin increased the ACE2 protein expression in heart and kidney of HCD rabbits. However, atorvastatin increased ACE2 mRNA in heart but not in kidney of HCD rabbits. Atorvastatin increased the occupancy of histone H3 acetylation (H3-Ac) mark on ACE2 promoter region in heart of HCD rabbits indicating direct or indirect epigenetic up-regulation of ACE2 by atorvastatin. Further, atorvastatin suppressed Ang II-induced contractile responses and enhanced AT2 receptor mediated relaxant responses in atherosclerotic aorta. We propose that atherosclerosis is associated with reduced ACE2 expression in heart and kidney. We also show an unexplored potential of atorvastatin to up-regulate ACE2 via epigenetic histone modifications. Our data suggest a novel way of replenishing ACE2 expression for preventing not only atherosclerosis but also other cardiovascular disorders. PMID:25482567

  20. The Delta II with ACE aboard is prepared for liftoff from Pad 17A, CCAS

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Boeing Delta II expendable launch vehicle carrying the Advanced Composition Explorer (ACE) undergoes final preparations for liftoff in the predawn hours of Aug. 25, 1997, at Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. The first launch attempt on Aug. 24 was scrubbed by Air Force range safety personnel because two commercial fishing vessels were within the Delta's launch danger area. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology.

  1. [Proteasome inhibitor].

    PubMed

    Yagi, Hideo

    2014-06-01

    The ubiquitin-proteasome system plays an essential role in degradation of eukaryotic intracellular protein, including cell cycle regulation, cell growth and proliferation, and survival. Cancer cells generally have higher level of proteasome activity compared with normal cells, suggesting proteasome inhibition could be therapeutic target in oncology. Bortezomib, the first proteasome inhibitor introduced into the clinic, is approved for the treatment of patients with multiple myeloma (MM). Although it was approved as single agent in the relapsed setting, bortezomib is now predominantly used in combination with conventional and novel targeted agents because bortezomib has demonstrated additive and synergistic activity in preclinical studies. Recently, several second-generation proteasome inhibitors, such as carfilzomib and MLN9708, have been developed and entered into clinical trials. These agents were investigated in frontline MM in combination with lenalidomide and low-dose dexamethasone. These studies demonstrated positive efficacy and safety, and it is expected that they will be approved in near future. PMID:25016815

  2. Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease.

    PubMed

    Kehoe, Patrick G; Katzov, Hagit; Andreasen, Niels; Gatz, Maragaret; Wilcock, Gordon K; Cairns, Nigel J; Palmgren, Juni; de Faire, Ulf; Brookes, Anthony J; Pedersen, Nancy L; Blennow, Kaj; Prince, Jonathan A

    2004-04-01

    Studies on the role that genetic variation may play in a complex human disease can be empowered by an assessment of both disease risk in case-control or family models and of quantitative traits that reflect elements of disease etiology. An excellent example of this can be found for the epsilon4 allele of APOE in relation to Alzheimer's disease (AD) for which association with both risk and age-at-onset (AAO) is evident. Following a recent demonstration that variants of the gene encoding angiotensin I converting enzyme ( ACE) contribute to AD risk, we have explored the potential influence of ACE upon AAO in AD. A total of 2861 individuals from three European populations, including six independent AD samples, have been examined in this study. Three single nucleotide polymorphisms (SNPs) previously demonstrated to have maximum effects upon ACE plasma levels and that span the ACE locus were genotyped in these materials. A strong effect upon AAO was observed for marker rs4343 in exon 17 ( P<0.0001), but evidence was also obtained indicating a possible independent effect of marker rs4291 ( P=0.0095) located in the ACE promoter. Effects were consistent with data from previous studies suggesting association with AD in case-control models, whereby alleles demonstrated to confer risk to disease also appear to reduce AAO. Equivalent effects were evident regardless of APOE epsilon4 carrier status and in both males and females. These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology. PMID:14986105

  3. SIGACE Code for Generating High-Temperature ACE Files; Validation and Benchmarking

    SciTech Connect

    Sharma, Amit R.; Ganesan, S.; Trkov, A.

    2005-05-24

    A code named SIGACE has been developed as a tool for MCNP users within the scope of a research contract awarded by the Nuclear Data Section of the International Atomic Energy Agency (IAEA) (Ref: 302-F4-IND-11566 B5-IND-29641). A new recipe has been evolved for generating high-temperature ACE files for use with the MCNP code. Under this scheme the low-temperature ACE file is first converted to an ENDF formatted file using the ACELST code and then Doppler broadened, essentially limited to the data in the resolved resonance region, to any desired higher temperature using SIGMA1. The SIGACE code then generates a high-temperature ACE file for use with the MCNP code. A thinning routine has also been introduced in the SIGACE code for reducing the size of the ACE files. The SIGACE code and the recipe for generating ACE files at higher temperatures has been applied to the SEFOR fast reactor benchmark problem (sodium-cooled fast reactor benchmark described in ENDF-202/BNL-19302, 1974 document). The calculated Doppler coefficient is in good agreement with the experimental value. A similar calculation using ACE files generated directly with the NJOY system also agrees with our SIGACE computed results. The SIGACE code and the recipe is further applied to study the numerical benchmark configuration of selected idealized PWR pin cell configurations with five different fuel enrichments as reported by Mosteller and Eisenhart. The SIGACE code that has been tested with several FENDL/MC files will be available, free of cost, upon request, from the Nuclear Data Section of the IAEA.

  4. Comparison of upper tropospheric carbon monoxide from MOPITT, ACE-FTS, and HIPPO-QCLS

    NASA Astrophysics Data System (ADS)

    Martínez-Alonso, Sara; Deeter, Merritt N.; Worden, Helen M.; Gille, John C.; Emmons, Louisa K.; Pan, Laura L.; Park, Mijeong; Manney, Gloria L.; Bernath, Peter F.; Boone, Chris D.; Walker, Kaley A.; Kolonjari, Felicia; Wofsy, Steven C.; Pittman, Jasna; Daube, Bruce C.

    2014-12-01

    Products from the Measurements Of Pollution In The Troposphere (MOPITT) instrument are regularly validated using in situ airborne measurements. However, few of these measurements reach into the upper troposphere, thus hindering MOPITT validation in that region. Here we evaluate upper tropospheric (~500 hPa to the tropopause) MOPITT CO profiles by comparing them to satellite Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) retrievals and to measurements from the High-performance Instrumented Airborne Platform for Environmental Research Pole to Pole Observations (HIPPO) Quantum Cascade Laser Spectrometer (QCLS). Direct comparison of colocated v5 MOPITT thermal infrared-only retrievals, v3.0 ACE-FTS retrievals, and HIPPO-QCLS measurements shows a slight positive MOPITT CO bias within its 10% accuracy requirement with respect to the other two data sets. Direct comparison of colocated ACE-FTS and HIPPO-QCLS measurements results in a small number of samples due to the large disparity in sampling pattern and density of these data sets. Thus, two additional indirect techniques for comparison of noncoincident data sets have been applied: tracer-tracer (CO-O3) correlation analysis and analysis of profiles in tropopause coordinates. These techniques suggest a negative bias of ACE-FTS with respect to HIPPO-QCLS; this could be caused by differences in resolution (horizontal, vertical) or by deficiencies in the ACE-FTS CO retrievals below ~20 km of altitude, among others. We also investigate the temporal stability of MOPITT and ACE-FTS data, which provide unique global CO records and are thus important in climate analysis. Our results indicate that the relative bias between the two data sets has remained generally stable during the 2004-2010 period.

  5. PAPR reduction in FBMC using an ACE-based linear programming optimization

    NASA Astrophysics Data System (ADS)

    van der Neut, Nuan; Maharaj, Bodhaswar TJ; de Lange, Frederick; González, Gustavo J.; Gregorio, Fernando; Cousseau, Juan

    2014-12-01

    This paper presents four novel techniques for peak-to-average power ratio (PAPR) reduction in filter bank multicarrier (FBMC) modulation systems. The approach extends on current PAPR reduction active constellation extension (ACE) methods, as used in orthogonal frequency division multiplexing (OFDM), to an FBMC implementation as the main contribution. The four techniques introduced can be split up into two: linear programming optimization ACE-based techniques and smart gradient-project (SGP) ACE techniques. The linear programming (LP)-based techniques compensate for the symbol overlaps by utilizing a frame-based approach and provide a theoretical upper bound on achievable performance for the overlapping ACE techniques. The overlapping ACE techniques on the other hand can handle symbol by symbol processing. Furthermore, as a result of FBMC properties, the proposed techniques do not require side information transmission. The PAPR performance of the techniques is shown to match, or in some cases improve, on current PAPR techniques for FBMC. Initial analysis of the computational complexity of the SGP techniques indicates that the complexity issues with PAPR reduction in FBMC implementations can be addressed. The out-of-band interference introduced by the techniques is investigated. As a result, it is shown that the interference can be compensated for, whilst still maintaining decent PAPR performance. Additional results are also provided by means of a study of the PAPR reduction of the proposed techniques at a fixed clipping probability. The bit error rate (BER) degradation is investigated to ensure that the trade-off in terms of BER degradation is not too severe. As illustrated by exhaustive simulations, the SGP ACE-based technique proposed are ideal candidates for practical implementation in systems employing the low-complexity polyphase implementation of FBMC modulators. The methods are shown to offer significant PAPR reduction and increase the feasibility of FBMC as

  6. The Altus Cumulus Electrification Study (ACES): A UAV-Based Science Demonstration

    NASA Technical Reports Server (NTRS)

    Blakeslee, R. J.; Croskey, C. L.; Desch, M. D.; Farrell, W. M.; Goldberg, R. A.; Houser, J. G.; Kim, H. S.; Mach, D. M.; Mitchell, J. D.; Stoneburner, J. C.

    2003-01-01

    The Altus Cumulus Electrification Study (ACES) is an unmanned aerial vehicle (UAV)- based project that investigated thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES was conducted to investigate storm electrical activity and its relationship to storm morphology, and to validate satellite-based lightning measurements. In addition, as part of the NASA sponsored UAV-based science demonstration program, this project provided a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES employed the Altus II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and provide Lightning Imaging Sensor validation. The ACES payload included electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES contributed important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) provided cloud-top perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the Altus was flown near, and when possible, over (but never into) thunderstorms for long periods of time that allowed investigations to be conducted over entire storm life cycles. An innovative real time weather system was used to identify and vector the aircraft to selected thunderstorms and safely fly around these storms, while, at the same time monitor the weather near our base of operations. In addition, concurrent ground-based observations that included radar (Miami and Key West WSRBD, NASA NPOL), satellite imagery, and lightning (NALDN and Los Alamos EDOT) enable the UAV measurements to be more completely

  7. Kidney scintigraphy after ACE inhibition in the diagnosis of renovascular hypertension

    SciTech Connect

    Ghione, S.; Fommei, E.; Palombo, C.; Giaconi, S.; Mantovanelli, A.; Ragazzini, A.; Palla, L.

    1986-01-01

    Suppression of the renin-angiotensin system (RAS) by angiotensin converting enzyme (ACE) inhibition may induce renal failure in patients with bilateral renal artery stenosis. Recent scintigraphic studies with the glomerular tracer technetium-99m-diethylenetriaminepenta-acetate (99m-Tc DTPA) indicate that in patients with unilateral renal artery stenosis, glomerular filtration rate (GFR) may be markedly reduced in the affected kidney after inhibition of ACE. This finding reflects the important role of the RAS in maintaining GFR (by increasing postglomerular resistance) in states of low renal perfusion pressure. Preliminary observations suggest that this scintigraphic test might be useful in the detection of renovascular hypertension.

  8. Comparison of ARAC calculations with surface and airborne measurements for the ACE field trials

    SciTech Connect

    Foster, K.T.; Pobanz, B.

    1996-11-01

    These Atmospheric Collection Equipment (ACE) trials were sponsored by the Air Force Technical Applications Center (AFTAC) for the purpose of investigating specific tracer monitoring methods and equipment. Three different tracers (sulfur hexafluoride and two particulate tracers) were released simultaneously for each experiment. This document provides a brief summary of the sulfur hexafluoride modeling results for three of the remaining four ACE trials (the tracer plume from the fifth trial was not located by the monitoring teams and provided no tracer measurements for model comparison). This summary is followed by a discussion of model results for the two particulate tracers which were co-released with sulfur hexafluoride.

  9. VizieR Online Data Catalog: SP_Ace derived data from stellar spectra (Boeche+, 2016)

    NASA Astrophysics Data System (ADS)

    Boeche, C.; Grebel, E. K.

    2015-11-01

    SP_Ace is a software designed to derive stellar parameters and elemental abundances from stellar spectra. In this tables we report the stellar parameters Teff, logg, [M/H], and chemical abundances [El/H] for ten elements derived with the software SP_Ace from spectra of the ELODIE spectral library (Prugniel et al., 2007, Cat. III/251), the benchmark stars (Jofre et al., 2014, Cat. J/A+A/564/A133), and the S4N library (Allende Prieto et al., 2004, Cat. J/A+A/420/183) degraded to spectral resolution R=12,000 and S/N=100. (3 data files).

  10. Nh and CH in the Ace Satellite Solar Spectrumtitle of your Abstract

    NASA Astrophysics Data System (ADS)

    Bernath, P. F.; Ram, R. S.; Colin, R.

    2010-06-01

    The Canadian ACE (Atmospheric Chemistry Experiment) mission has a high resolution (0.02 cm-1) Fourier transform spectrometer (FTS) in low earth orbit. The primary ACE mission goal is the study ozone chemistry in the stratosphere although it is making a wide range of other measurements, for example, of organic molecules in the troposphere. In the normal operating mode, the ACE-FTS measures a sequence of atmospheric absorption spectra during sunrise and sunset (``solar occultation''). As part of the measurement sequence about 16 high sun exoatmospheric spectra are recorded for each occultation to serve as reference spectra. We have co-added 224782 pure solar spectra to produce the ACE solar atlas in the 750--4400 cm-1 spectral region [Hase et al., JQSRT 111, 521 (2010), see http://www.ace.uwaterloo.ca/solaratlas.html]. The ACE solar spectrum displays prominent vibration-rotation bands of CO, OH, NH and CH, and pure rotational lines of OH and NH. An improved spectroscopic analysis for OH has already been published [Bernath and Colin, JMS 257, 20 (2009)] and we now report on similar work for NH and CH. The vibration-rotation spectra of NH have been reinvestigated using laboratory spectra and infrared solar spectra recorded from orbit by the ACE and ATMOS instruments. In addition to identifying the previously unobserved 6-5 vibration-rotation band in the laboratory spectra, many additional high N rotational lines have been observed. By combining the new observations with the previously published data and recent far infrared data, an improved set of molecular constants and term values have been derived for the NH X^3Σ^- and A^3Π states. Vibration-rotation spectra of the CH X^2Π ground state have also been re-analyzed based on laboratory spectra, the ACE solar spectrum and published data. The previously unobserved 5-4 band has been measured and the other four bands (1-0 to 4-3) have been extended to higher J values. TEXT OF YOUR ABSTRACT

  11. Angiotensin-converting enzyme (ACE-I/D) polymorphism frequency in Brazilian soccer players.

    PubMed

    Coelho, Daniel Barbosa; Pimenta, Eduardo; Rosse, Izinara Cruz; Veneroso, Christiano; Pussieldi, Guilherme; Becker, Lenice Kapes; Carvalho, Maria-Raquel; Silami-Garcia, Emerson

    2016-06-01

    This study aimed to analyze the angiotensin-converting enzyme (ACE-I/D) allelic and genotypic frequencies in Brazilian soccer players of different ages. The study group comprised 353 players from first-division clubs in the under (U)-14, U-15, U-17, U-20, and professional categories. The allelic and genotypic frequencies did not differ significantly in any of the categories between the group of players and the control group. This was the first study of ACE-I/D polymorphism in Brazilian soccer players. PMID:27232187

  12. Adaptive coherence estimator (ACE) for explosive hazard detection using wideband electromagnetic induction (WEMI)

    NASA Astrophysics Data System (ADS)

    Alvey, Brendan; Zare, Alina; Cook, Matthew; Ho, Dominic K. C.

    2016-05-01

    The adaptive coherence estimator (ACE) estimates the squared cosine of the angle between a known target vector and a sample vector in a transformed coordinate space. The space is transformed according to an estimation of the background statistics, which directly effects the performance of the statistic as a target detector. In this paper, the ACE detection statistic is used to detect buried explosive hazards with data from a Wideband Electromagnetic Induction (WEMI) sensor. Target signatures are based on a dictionary defined using a Discrete Spectrum of Relaxation Frequencies (DSRF) model. Results are summarized as a receiver operator curve (ROC) and compared to other leading methods.

  13. Experimental demonstration of a classical approach for flexible structure control - The ACES testbed

    NASA Technical Reports Server (NTRS)

    Wie, Bong

    1991-01-01

    This paper describes the results of an active structural control experiment performed for the Advanced Control Evaluation for Structures (ACES) testbed at NASA-Marshall as part of the NASA Control-Structure Interaction Guest Investigator Program. The experimental results successfully demonstrate the effectiveness of a 'dipole' concept for line-of-sight control of a pointing system mounted on a flexible structure. The simplicity and effectiveness of a classical 'single-loop-at-a-time' approach for the active structural control design for a complex structure, such as the ACES testbed, are demonstrated.

  14. Diabetes and CVD risk during angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment in hypertension: a study of 15 990 patients

    PubMed Central

    Hasvold, L P; Bodegård, J; Thuresson, M; Stålhammar, J; Hammar, N; Sundström, J; Russell, D; Kjeldsen, S E

    2014-01-01

    Differences in clinical effectiveness between angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in the primary treatment of hypertension are unknown. The aim of this retrospective cohort study was to assess the prevention of type 2 diabetes and cardiovascular disease (CVD) in patients treated with ARBs or ACEis. Patients initiated on enalapril or candesartan treatment in 71 Swedish primary care centers between 1999 and 2007 were included. Medical records data were extracted and linked with nationwide hospital discharge and cause of death registers. The 11 725 patients initiated on enalapril and 4265 on candesartan had similar baseline characteristics. During a mean follow-up of 1.84 years, 36 482 patient-years, the risk of new diabetes onset was lower in the candesartan group (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69–0.96, P=0.01) compared with the enalapril group. No difference between the groups was observed in CVD risk (HR 0.99, 95% CI 0.87–1.13, P=0.86). More patients discontinued treatment in the enalapril group (38.1%) vs the candesartan group (27.2%). In a clinical setting, patients initiated on candesartan treatment had a lower risk of new-onset type 2 diabetes and lower rates of drug discontinuation compared with patients initiated on enalapril. No differences in CVD risk were observed. PMID:25211055

  15. Validating the ACE Model for Evaluating Student Performance Using a Teaching-Learning Process Based on Computational Modeling Systems

    ERIC Educational Resources Information Center

    Louzada, Alexandre Neves; Elia, Marcos da Fonseca; Sampaio, Fábio Ferrentini; Vidal, Andre Luiz Pestana

    2014-01-01

    The aim of this work is to adapt and test, in a Brazilian public school, the ACE model proposed by Borkulo for evaluating student performance as a teaching-learning process based on computational modeling systems. The ACE model is based on different types of reasoning involving three dimensions. In addition to adapting the model and introducing…

  16. The Two-Component System GrvRS (EtaRS) Regulates ace Expression in Enterococcus faecalis OG1RF

    PubMed Central

    Singh, Kavindra V.; La Rosa, Sabina Leanti; Cohen, Ana Luisa V.; Murray, Barbara E.

    2014-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. PMID:25385790

  17. Does Education Plus Action Lead to Leadership on Climate? Preliminary Results from the ACE Leadership Development Longitudinal Survey Project

    NASA Astrophysics Data System (ADS)

    Anderson, R. K.; Qusba, L.; Lappe, M.; Flora, J. A.

    2014-12-01

    Through education and leadership development, Alliance for Climate Education (ACE) is building a generation of confident and capable youth driving climate solutions now throughout their lives. In 2011-12, a random sample of 2,800 high school students across the country was surveyed before and after seeing the ACE Assembly on climate science and solutions. The survey showed that the ACE Assembly resulted in a 27% increase in climate science knowledge scores, with 59% of students increasing their intentions to take action on climate and a doubling of the number of students talking to parents and peers about climate change. Students were also compared to the Global Warming's Six Americas classification of Americans' views on climate. Following the ACE Assembly, 60% of students were alarmed or concerned about climate change. Building off these results, in 2014 ACE began to assess the results of its leadership development program that follows the ACE Assembly. The goal of this survey project is to measure ACE's long-term impact on students' college and career pathways, civic engagement and climate action. Preliminary results show that a majority of students in ACE's leadership development program are alarmed about global warming and are having conversations about global warming. A majority of these students also feel confident in their ability to lead a climate-related campaign in their school and community. These students will continue to be surveyed through 2015.

  18. T-lymphocyte induction of human monocyte angiotensin converting enzyme (ACE) is not dependent upon T-lymphocyte proliferation

    SciTech Connect

    Vuk-Pavlovic, Z.; Rohrbach, M.S.

    1986-03-05

    Human peripheral blood monocytes cultured in serum free media for seven days show a basal activity of the ectoenzyme ACE which is augmented 2-3 times by the presence of autologous peripheral blood T-lymphocytes. Since these two cell types are also involved in autologous mixed lymphocyte reaction if serum is present, the authors compared the ability of T-cells to stimulate ACE activity in the presence or absence of proliferation (measured by /sup 3/H-thymidine incorporation). By the seventh day, cultures with 5% AB/sup +/ serum showed significant increase in proliferation but no increase in ACE activity compared to the serum free cultures. Even higher proliferation rate achieved by co-culturing T-lymphocytes with allogeneic monocytes did not increase ACE production; on the contrary, ACE activity remained at the basal level. Monocyte-T-cell co-cultures stimulated with increasing concentrations of ConA or PHA showed dose dependent increases in proliferation but parallel decreases in ACE activity. Addition of soluble antigen (Candida albicans) also enhanced proliferation but not ACE synthesis. They conclude that T-lymphocyte induction of monocyte ACE is a result of cooperation between autologous cells which is not dependent upon T-cell proliferation.

  19. Mentoring Functions within the American Council on Education (ACE) Fellows Leadership Development Program: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Grotrian-Ryan, Sheri A.

    2012-01-01

    The purpose of this study was to examine and better comprehend the concept of mentoring within the American Council on Education (ACE) Fellows Program. This study addressed the functions of mentoring and how they applied to those participating in the ACE Fellows Program--from the Fellows' (or protégés') perspectives. A sequential…

  20. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy.

    PubMed

    Forbes, Josephine M; Thorpe, Suzanne R; Thallas-Bonke, Vicki; Pete, Josefa; Thomas, Merlin C; Deemer, Elizabeth R; Bassal, Sahar; El-Osta, Assam; Long, David M; Panagiotopoulos, Sianna; Jerums, George; Osicka, Tanya M; Cooper, Mark E

    2005-08-01

    Recent studies have identified that first-line renoprotective agents that interrupt the renin-angiotensin system not only reduce BP but also can attenuate advanced glycation end product (AGE) accumulation. This study used in vitro, preclinical, and human approaches to explore the potential effects of these agents on the modulation of the receptor for AGE (RAGE). Bovine aortic endothelial cells that were exposed to the angiotensin-converting enzyme inhibitor (ACEi) ramiprilat in the presence of high glucose demonstrated a significant increase in soluble RAGE (sRAGE) secreted into the medium. In streptozotocin-induced diabetic rats, ramipril treatment (ACEi) at 3 mg/L for 24 wk reduced the accumulation of skin collagen-linked carboxymethyllysine and pentosidine, as well as circulating and renal AGE. Renal gene upregulation of total RAGE (all three splice variants) was observed in ACEi-treated animals. There was a specific increase in the gene expression of the splice variant C-truncated RAGE (sRAGE). There were also increases in sRAGE protein identified within renal cells with ACEi treatment, which showed AGE-binding ability. This was associated with decreases in renal full-length RAGE protein from ACEi-treated rats. Decreases in plasma soluble RAGE that were significantly increased by ACEi treatment were also identified in diabetic rats. Similarly, there was a significant increase in plasma sRAGE in patients who had type 1 diabetes and were treated with the ACEi perindopril. Complexes between sRAGE and carboxymethyllysine were identified in human and rodent diabetic plasma. It is postulated that ACE inhibition reduces the accumulation of AGE in diabetes partly by increasing the production and secretion of sRAGE into plasma. PMID:15930093

  1. Long Term Missions at the Sun-Earth Libration Point L1: ACE, SOHO, and WIND

    NASA Technical Reports Server (NTRS)

    Roberts, Craig E.

    2011-01-01

    Three heliophysics missions -- the Advanced Composition Explorer (ACE), Solar Heliospheric Observatory (SOHO), and the Global Geoscience WIND -- have been orbiting the Sun-Earth interior libration point L1 continuously since 1997, 1996, and 2004, respectively. ACE and WIND (both NASA missions) and SOHO (an ESA-NASA joint mission) are all operated from the NASA Goddard Space Flight Center (GSFC). While ACE and SOHO have been dedicated libration point orbiters since their launches, WIND has had also a remarkable 10-year career flying a deep-space, multiple lunar-flyby trajectory prior to 2004. That era featured 36 targeted lunar flybys with excursions to both L1 and L2 before its final insertion in L1 orbit. A figure depicts the orbits of the three spacecraft, showing projections of the orbits onto the orthographic planes of a solar rotating ecliptic frame of reference. The SOHO orbit is a quasi-periodic halo orbit, where the frequencies of the in-plane and out-of-plane motions are practically equal. Such an orbit is seen to repeat itself with a period of approximately 178 days. For ACE and WIND, the frequencies of the in-plane and out-of-plane motions are unequal, giving rise to the characteristic Lissajous motion. ACE's orbit is of moderately small amplitude, whereas WIND's orbit is a large-amplitude Lissajous of dimensions close to those of the SOHO halo orbit. As motion about the collinear points is inherently unstable, stationkeeping maneuvers are necessary to prevent orbital decay and eventual escape from the L1 region. Though the three spacecraft are dissimilar (SOHO is a 3-axis stabilized Sun pointer, WIND is a spin-stabilized ecliptic pole pointer, and ACE is also spin-stabilized with its spin axis maintained between 4 and 20 degrees of the Sun), the stationkeeping technique for the three is fundamentally the same. The technique consists of correcting the energy of the orbit via a delta-V directed parallel or anti-parallel to the Spacecraft-to-Sun line. SOHO

  2. Perioperative management of patients treated with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a quality improvement audit.

    PubMed

    Vijay, A; Grover, A; Coulson, T G; Myles, P S

    2016-05-01

    Previous studies have shown that patients continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers on the day of surgery are more likely to have significant intraoperative hypotension, higher rates of postoperative acute kidney injury, and lower incidences of postoperative atrial fibrillation. However, many of these studies were prone to bias and confounding, and questions remain over the validity of these outcomes. This observational, before-and-after quality improvement audit aimed to assess the effect of withholding these medications on the morning of surgery. We recruited 323 participants, with 83 (26%) having their preoperative angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) withheld on the day of surgery. There were only very small Spearman rank-order correlations between time since last dose of these medications (rho -0.12, P=0.057) and intraoperative and recovery room intravenous fluid administration (rho -0.11, P=0.042). There was no statistically significant difference between the continued or withheld groups in vasopressor (metaraminol use 3.5 [1.5-8.3] mg versus 3.5 [1.5-8.5] mg, P=0.67) or intravenous fluid administration (1000 ml [800-1500] ml versus 1000 [800-1500] ml, P=0.096), nor rates of postoperative acute kidney injury (13% vs 18%, P=0.25) or atrial fibrillation (15% versus 18%, P=0.71). This audit found no significant differences in measured outcomes between the continued or withheld ACEi/ARB groups. This finding should be interpreted with caution due to the possibility of confounding and an insufficient sample size. However, as the finding is in contrast to many previous studies, future prospective randomised clinical trials are required to answer this important question. PMID:27246933

  3. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice.

    PubMed

    Hung, Yi-Han; Hsieh, Wen-Yeh; Hsieh, Jih-Sheng; Liu, Fon-Chang; Tsai, Chin-Hung; Lu, Li-Che; Huang, Chen-Yi; Wu, Chien-Liang; Lin, Chih-Sheng

    2016-01-01

    Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2(-/-)) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2(-/-) mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2(-/-) mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2(-/-) mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2(-/-) mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury. PMID:27019629

  4. Angiotensin-converting enzyme 2 (ACE2) from raccoon dog can serve as an efficient receptor for the spike protein of severe acute respiratory syndrome coronavirus.

    PubMed

    Xu, Lili; Zhang, Yanfang; Liu, Yun; Chen, Zhiwei; Deng, Hongkui; Ma, Zhongbin; Wang, Hualin; Hu, Zhihong; Deng, Fei

    2009-11-01

    Raccoon dog is one of the suspected intermediate hosts of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, the angiotensin-converting enzyme 2 (ACE2) gene of raccoon dog (rdACE2) was cloned and sequenced. The amino acid sequence of rdACE2 has identities of 99.3, 89.2, 83.9 and 80.4 % to ACE2 proteins from dog, masked palm civet (pcACE2), human (huACE2) and bat, respectively. There are six amino acid changes in rdACE2 compared with huACE2, and four changes compared with pcACE2, within the 18 residues of ACE2 known to make direct contact with the SARS-CoV S protein. A HeLa cell line stably expressing rdACE2 was established; Western blot analyses and an enzyme-activity assay indicated that the cell line expressed ACE2 at a similar level to two previously established cell lines that express ACE2 from human and masked palm civet, respectively. Human immunodeficiency virus-backboned pseudoviruses expressing spike proteins derived from human SARS-CoV or SARS-CoV-like viruses of masked palm civets and raccoon dogs were tested for their entry efficiency into these cell lines. The results showed that rdACE2 is a more efficient receptor for human SARS-CoV, but not for SARS-CoV-like viruses of masked palm civets and raccoon dogs, than huACE2 or pcACE2. This study provides useful data to elucidate the role of raccoon dog in SARS outbreaks. PMID:19625462

  5. ACE2 deficiency reduces β-cell mass and impairs β-cell proliferation in obese C57BL/6 mice.

    PubMed

    Shoemaker, Robin; Yiannikouris, Frederique; Thatcher, Sean; Cassis, Lisa

    2015-10-01

    Drugs that inhibit the renin-angiotensin system (RAS) decrease the onset of type 2 diabetes (T2D). Pancreatic islets express RAS components, including angiotensin-converting enzyme 2 (ACE2), which cleaves angiotensin II (Ang II) to angiotensin-(1-7) [Ang-(1-7)]. Overexpression of ACE2 in pancreas of diabetic mice improved glucose homeostasis. The purpose of this study was to determine if deficiency of endogenous ACE2 contributes to islet dysfunction and T2D. We hypothesized that ACE2 deficiency potentiates the decline in β-cell function and augments the development of diet-induced T2D. Male Ace2(+/y) or Ace2(-/y) mice were fed a low-fat (LF) or high-fat (HF) diet for 1 or 4 mo. A subset of 1-mo HF-fed mice were infused with Sal (Sal), losartan (Los), or Ang-(1-7). At 4 mo, while both genotypes of HF-fed mice developed a similar level of insulin resistance, adaptive hyperinsulinemia was reduced in Ace2(-/y) vs. Ace2(+/y) mice. Similarly, in vivo glucose-stimulated insulin secretion (GSIS) was reduced in 1-mo HF-fed Ace2(-/y) compared with Ace2(+/y) mice, resulting in augmented hyperglycemia. The average islet area was significantly smaller in both LF- and HF-fed Ace2(-/y) vs. Ace2(+/y) mice. Additionally, β-cell mass and proliferation were reduced significantly in HF-fed Ace2(-/y) vs. Ace2(+/y) mice. Neither infusion of Los nor Ang-(1-7) was able to correct impaired in vivo GSIS of HF-fed ACE2-deficient mice. These results demonstrate a critical role for endogenous ACE2 in the adaptive β-cell hyperinsulinemic response to HF feeding through regulation of β-cell proliferation and growth. PMID:26389599

  6. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice

    PubMed Central

    Hung, Yi-Han; Hsieh, Wen-Yeh; Hsieh, Jih-Sheng; Liu, Fon-Chang; Tsai, Chin-Hung; Lu, Li-Che; Huang, Chen-Yi; Wu, Chien-Liang; Lin, Chih-Sheng

    2016-01-01

    Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2-/-) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2-/- mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2-/- mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2-/- mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2-/- mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury. PMID:27019629

  7. Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

    SciTech Connect

    Kharofa, Jordan; Cohen, Eric P.; Tomic, Rade; Xiang Qun; Gore, Elizabeth

    2012-09-01

    Purpose: Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation. Methods and Materials: Patients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors, nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis. Results: A total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose-volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] {<=}37% and mean lung dose {<=}20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade 2 or

  8. Diversity of ace, a gene encoding a microbial surface component recognizing adhesive matrix molecules, from different strains of Enterococcus faecalis and evidence for production of ace during human infections.

    PubMed

    Nallapareddy, S R; Singh, K V; Duh, R W; Weinstock, G M; Murray, B E

    2000-09-01

    Our previous work reported that most Enterococcus faecalis strains adhered to the extracellular matrix proteins collagen types I and IV and laminin after growth at 46 degrees C, but not 37 degrees C, and we subsequently identified an E. faecalis sequence, ace, that encodes a bacterial adhesin similar to the collagen binding protein Cna of Staphylococcus aureus. In this study, we examined the diversity of E. faecalis-specific ace gene sequences among different isolates obtained from various geographic regions as well as from various clinical sources. A comparison of nucleotide and deduced amino acid sequences of Ace from nine E. faecalis strains identified a highly conserved N-terminal A domain, followed by a variable B domain which contains two to five repeats of 47 amino acids in tandem array, preceded by a 20-amino-acid partial repeat. Using 17 other strains collected worldwide, the 5' region of ace that encodes the A domain was sequenced, and these sequences showed > or =97.5% identity. Among the previously reported five amino acids critical for collagen binding by Cna of S. aureus, four were found to be identical in Ace from all strains tested. Polyclonal immune rabbit serum prepared against recombinant Ace A derived from E. faecalis strain OG1RF detected Ace in mutanolysin extracts of seven of nine E. faecalis strains after growth at 46 degrees C; Ace was detected in four different molecular sizes that correspond to the variation in the B repeat region. To determine if there was any evidence to indicate that Ace might be produced under physiological conditions, we quantitatively assayed sera collected from patients with enterococcal infections for the presence of anti-Ace A antibodies. Ninety percent of sera (19 of 21) from patients with E. faecalis endocarditis showed reactivity with titers from 1:32 to >1:1,024; the only 2 sera which lacked antibodies to Ace A had considerably lower titers of antibodies to other E. faecalis antigens as well. Human

  9. Endopeptidase 3.4.24.11 converts N-1-(R,S)carboxy-3-phenylpropyl-Ala-Ala-Phe-p-carboxyanilide into a potent inhibitor of angiotensin-converting enzyme.

    PubMed Central

    Williams, C H; Yamamoto, T; Walsh, D M; Allsop, D

    1993-01-01

    It was reported recently that N-1-(R,S)carboxy-3-phenylpropyl-Ala-Ala-Phe-p-carboxyanilide (CPP-A-A-F-pAB), an inhibitor of endopeptidase 3.4.24.15 (E-24.15), also inhibits angiotensin-converting enzyme (ACE) from rabbit lung. We have found that this compound is without effect on ACE purified from pig kidney, at a concentration some 1000-fold greater than the Ki reported for inhibition of the enzyme from lung. However, preincubation of CPP-A-A-F-pAB with neutral endopeptidase 3.4.24.11 (E-24.11) does result in potent inhibitory effects on ACE. We have shown this to be due to formation of a fragment, CPP-A-A, the structure of which is closely related to ACE inhibitors such as enalaprilat. CPP-A-A was found to be a potent inhibitor of pig ACE. Under the conditions used it had an IC50 value of 1.6 x 10(-8) M, compared with the value obtained for captopril of 7.5 x 10(-10) M. These results have important implications for studies of E-24.15 when using CPP-A-A-F-pAB in vivo or in crude tissue extracts where E-24.11 might also be present. PMID:8379924

  10. Angiotensin-converting Enzyme Inhibitor and Statin Medication Use and Incident Mobility Limitation in Community Older Adults. The Health, Aging and Body Composition Study

    PubMed Central

    Gray, Shelly L.; Boudreau, Robert M.; Newman, Anne B.; Studenski, Stephanie A.; Shorr, Ronald I; Bauer, Douglas C.; Simonsick, Eleanor M.; Hanlon, Joseph T

    2012-01-01

    Objective Angiotensin-converting enzyme (ACE) inhibitors and statin medications have been proposed as potential agents to prevent or delay physical disability; yet limited research has evaluated whether such use in older community dwelling adults is associated with a lower risk of incident mobility limitation. Design Longitudinal cohort study Setting Health, Aging and Body Composition (Health ABC) Participants 3055 participants who were well functioning at baseline (e.g., no mobility limitations). Measurements Summated standardized daily doses (low, medium and high) and duration of ACE inhibitor and statin use was computed. Mobility limitation (two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health status, and health behaviors. Results At baseline, ACE inhibitors and statins were used by 15.2% and 12.9%, respectively and both increased to over 25% by year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.82–1.09) nor statin use (multivariate HR 1.02; 95% CI 0.87–1.17) was associated with a lower risk for mobility limitation. Similar findings were seen in analyses examining dose- and duration-response relationships and sensitivity analyses restricted to those with hypertension. Conclusions These findings indicate that ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively do not lower risk of mobility limitation, an important life quality indicator. PMID:22092102

  11. Adult Competency Education Kit. Basic Skills in Speaking, Math, and Reading for Employment. Part G. ACE Competency Based Job Descriptions: #22--Refrigerator Mechanic; #24--Motorcycle Repairperson.

    ERIC Educational Resources Information Center

    San Mateo County Office of Education, Redwood City, CA. Career Preparation Centers.

    This fourth of fifteen sets of Adult Competency Education (ACE) Competency Based Job Descriptions in the ACE kit contains job descriptions for Refrigerator Mechanic and Motorcycle Repairperson. Each begins with a fact sheet that includes this information: occupational title, D.O.T. code, ACE number, career ladder, D.O.T. general educational…

  12. N-Ace: using solvent accessibility and physicochemical properties to identify protein N-acetylation sites.

    PubMed

    Lee, Tzong-Yi; Hsu, Justin Bo-Kai; Lin, Feng-Mao; Chang, Wen-Chi; Hsu, Po-Chiang; Huang, Hsien-Da

    2010-11-30

    Protein acetylation, which is catalyzed by acetyltransferases, is a type of post-translational modification and crucial to numerous essential biological processes, including transcriptional regulation, apoptosis, and cytokine signaling. As the experimental identification of protein acetylation sites is time consuming and laboratory intensive, several computational approaches have been developed for identifying the candidates of experimental validation. In this work, solvent accessibility and the physicochemical properties of proteins are utilized to identify acetylated alanine, glycine, lysine, methionine, serine, and threonine. A two-stage support vector machine was applied to learn the computational models with combinations of amino acid sequences, and the accessible surface area and physicochemical properties of proteins. The predictive accuracy thus achieved is 5% to 14% higher than that of models trained using only amino acid sequences. Additionally, the substrate specificity of the acetylated site was investigated in detail with reference to the subcellular colocalization of acetyltransferases and acetylated proteins. The proposed method, N-Ace, is evaluated using independent test sets in various acetylated residues and predictive accuracies of 90% were achieved, indicating that the performance of N-Ace is comparable with that of other acetylation prediction methods. N-Ace not only provides a user-friendly input/output interface but also is a creative method for predicting protein acetylation sites. This novel analytical resource is now freely available at http://N-Ace.mbc.NCTU.edu.tw/. PMID:20839302

  13. Purple Computational Environment With Mappings to ACE Requirements for the General Availability User Environment Capabilities

    SciTech Connect

    Barney, B; Shuler, J

    2006-08-21

    Purple is an Advanced Simulation and Computing (ASC) funded massively parallel supercomputer located at Lawrence Livermore National Laboratory (LLNL). The Purple Computational Environment documents the capabilities and the environment provided for the FY06 LLNL Level 1 General Availability Milestone. This document describes specific capabilities, tools, and procedures to support both local and remote users. The model is focused on the needs of the ASC user working in the secure computing environments at Los Alamos National Laboratory, Lawrence Livermore National Laboratory, and Sandia National Laboratories, but also documents needs of the LLNL and Alliance users working in the unclassified environment. Additionally, the Purple Computational Environment maps the provided capabilities to the Trilab ASC Computing Environment (ACE) Version 8.0 requirements. The ACE requirements reflect the high performance computing requirements for the General Availability user environment capabilities of the ASC community. Appendix A lists these requirements and includes a description of ACE requirements met and those requirements that are not met for each section of this document. The Purple Computing Environment, along with the ACE mappings, has been issued and reviewed throughout the Tri-lab community.

  14. A Further Local Participation Study: TAFE and ACE in Melbourne Postcodes. Working Paper.

    ERIC Educational Resources Information Center

    McIntyre, John

    A study analyzed patterns of participation at the local level in adult and community education (ACE) and technical and further education (TAFE) in Melbourne, Australia postcodes. Patterns of participation were hypothesized as being different from those in Sydney, New South Wales, where previous research established the marked differentiation of…

  15. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  16. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  17. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  18. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  19. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  20. ACED IT: A Tool for Improved Ethical and Moral Decision-Making

    ERIC Educational Resources Information Center

    Kreitler, Crystal Mata; Stenmark, Cheryl K.; Rodarte, Allen M.; Piñón DuMond, Rebecca

    2014-01-01

    Numerous examples of unethical organizational decision-making highlighted in the media have led many to question the general moral perception and ethical judgments of individuals. The present study examined two forms of a straightforward ethical decision-making (EDM) tool (ACED IT cognitive map) that could be a relatively simple instrument for…

  1. Antihypertensive effects of silk fibroin hydrolysate by alcalase and purification of an ACE inhibitory dipeptide.

    PubMed

    Zhou, Fengjuan; Xue, Zhaohui; Wang, Jiehua

    2010-06-01

    Silk fibroin, which is normally discarded as an industrial byproduct in clothing plants, was hydrolyzed with alcalase. Angiotensin I converting enzyme (ACE) inhibitory activities of the silk fibroin hydrolysates (SFH) were investigated, and the hydrolysate with hydrolysis degree of 17% exhibited the highest ACE inhibitory activity. At the tested 600 mg/kg.d and 1200 mg/kg x d doses, SFH significantly lowered blood pressure of spontaneously hypertensive rats (SHR) after chronic oral administration. SFH was further purified using consecutive chromatographic methods on Sephadex G-15 column and reverse phase high-performance liquid chromatography (RP-HPLC) on an octadecylsilane column. After its purity was confirmed by analytical RP-HPLC and capillary electrophoresis, one ACE inhibitory dipeptide was isolated, and its molecular mass and amino acid sequence were determined as 238.2 Da and Gly-Tyr, respectively, by LC-ESI/MS. The results of this study suggest that silk fibroin byproducts have the possibility to become an effective source for ACE inhibitory peptides. PMID:20481470

  2. Acute stress and cardiovascular health: is there an ACE gene connection?

    PubMed

    Holman, E Alison

    2012-10-01

    Cardiovascular disorders (CVD) are associated with acute and posttraumatic stress responses, yet biological processes underlying this association are poorly understood. This study examined whether renin-angiotensin-aldosterone system activity, as indicated by a functional single nucleotide polymorphism (SNP) in the angiotensin converting enzyme (ACE) gene, is associated with both CVD and acute stress related to the September 11, 2001 (9/11) terrorist attacks. European-American respondents (N = 527) from a nationally representative longitudinal study of coping following 9/11 provided saliva for genotyping. Respondents had completed health surveys before 9/11 and annually for 3 years after, and acute stress assessments 9 to 23 days after 9/11. Respondents with rs4291 AA or TT genotypes reported high acute stress twice as often as those with the AT genotype. Individuals with the TT genotype were 43% more likely to report increased physician-diagnosed CVD over 3 years following 9/11, when the following variables were included in the model: (a) pre-9/11 CVD, mental health, and non-CVD ailments; (b) cardiac risk factors; (c) ongoing endocrine disorders; and (d) significant demographics. The ACE rs4291 TT genotype, which has been associated with HPA axis hyperactivity and higher levels of serum angiotensin converting enzyme (ACE), predicted acute stress response and reports of physician-diagnosed CVD in a national sample following collective stress. ACE gene function may be associated with both mental and physical health disorders following collective stress. PMID:23055331

  3. Informational webinar for EPA STAR RFA on "Air, Climate and Energy (ACE) Centers: Science Supporting Solutions"

    EPA Science Inventory

    The purpose of this webinar presentation is to discuss the application process and required elements for the Air, Climate and Energy (ACE) Centers: Science Supporting Solutions RFA. EPA is seeking research on the development of sound science to systematically inform policy makers...

  4. ACEE Composite Structures Technology: Review of selected NASA research on composite materials and structures

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The NASA Aircraft Energy Efficiency (ACEE) Composite Primary Aircraft Structures Program was designed to develop technology for advanced composites in commercial aircraft. Research on composite materials, aircraft structures, and aircraft design is presented herein. The following parameters of composite materials were addressed: residual strength, damage tolerance, toughness, tensile strength, impact resistance, buckling, and noise transmission within composite materials structures.

  5. Accounting Early for Life Long Learning: The AcE Project.

    ERIC Educational Resources Information Center

    University Coll. Worcester (England). Centre for Research in Early Childhood Education.

    Building upon the work of the Effective Early Learning (EEL) Project in raising the quality of early learning for young children in the United Kingdom, the 3-year Accounting Early for Life Long Learning Project (AcE Project) focuses on enhancing in 3- to 6-year-olds those attitudes and dispositions that are important to life-long learning. This…

  6. Monoclonal antibodies recognizing the Enterococcus faecalis collagen-binding MSCRAMM Ace: conditional expression and binding analysis.

    PubMed

    Hall, Andrea E; Gorovits, Elena L; Syribeys, Peter J; Domanski, Paul J; Ames, Brenda R; Chang, Cathy Y; Vernachio, John H; Patti, Joseph M; Hutchins, Jeff T

    2007-01-01

    Enterococci are opportunistic pathogens known to cause numerous clinical infections and complications in humans. Adhesin-mediated binding to extracellular matrix (ECM) proteins of the host is thought to be a crucial step in the pathogenesis of these bacterial infections. Adhesin of collagen from Enterococcus faecalis (Ace) is a cell-wall anchored protein of E. faecalis that has been shown to be important for bacterial binding to the ECM. In this report, we characterize the conditions for Ace expression and demonstrate Ace binding to mammalian epithelial and endothelial cells as well as to collagens found in the ECM. To further characterize Ace expression and function, we report the generation of a panel of monoclonal antibodies (mAbs) directed against this important E. faecalis virulence factor. Through the use of multiple in vitro assays, surface plasmon resonance and flow cytometry, we have characterized this panel of mAbs which may prove to be not only beneficial in studies that address the precise biological role of adhesion of E. faecalis, but may also serve as beneficial therapeutic agents against E. faecalis infections. PMID:17521860

  7. Educational Measurement. Fourth Edition. ACE/Praeger Series on Higher Education

    ERIC Educational Resources Information Center

    Brennan, Robert L., Ed.

    2006-01-01

    "Educational Measurement" has been the bible in its field since the first edition was published by ACE in 1951. The importance of this fourth edition of "Educational Measurement" is to extensively update and extend the topics treated in the previous three editions. As such, the fourth edition documents progress in the field and…

  8. Professional Knowledge Formation and Organisational Capacity-Building in ACE: Lessons from the Victorian Research Circles

    ERIC Educational Resources Information Center

    McIntyre, John

    2008-01-01

    The national reform agenda of the Council of Australian Governments challenges community education agencies to contribute to its goals and raises questions about their capacity to do so. It is crucial to define the conditions that are necessary to develop the capability of adult and community education (ACE) organisations to play a broader social…

  9. Stress pathways to health inequalities: Embedding ACEs within social and behavioral contexts

    PubMed Central

    Nurius, Paula S.; Green, Sara; Logan-Greene, Patricia; Longhi, Dario; Song, Chiho

    2014-01-01

    Objective This study addresses whether adverse childhood experiences (ACEs) demonstrate disproportional prevalence across demographic- and health-affecting characteristics, offer significant explanation of adult health outcomes, and show patterned association with illness susceptibility early within and across adulthood when viewed in combination with income and psychosocial resources. Methods Data were derived from a population-based state health survey using stratified random sampling of household adults (n=7,470): ages 18–99 (M=55), 59.9% females, and race/ethnicity, income and education levels representative of the region. We assessed ACEs by aggregating 8 adversity forms, 5 health behaviors and 3 psychosocial resources; and health outcomes (number of chronic conditions, subjective wellness). Results Disproportionality was evident in ACEs levels by demographics, adult SES, health behaviors, and psychosocial resources in expected directions. Stepped multiple regressions of health outcomes demonstrated significant betas and R2 change for each predictor block, revealing cumulative as well as unique explanatory utility. Early onset chronic illness was evident on the basis of ACEs levels. These illnesses were amplified for low income respondents. Prevalence was highest across adulthood for those also reporting low psychosocial assets. Conclusions Findings offer novel insights as to the “long reach” of childhood adversity on health, conditioned by circumstances under which these effects may occur. Health resilience offered by health behaviors and psychosocial resources should shape thinking about preventive and remedial interventions by social work and allied professionals across a range of settings. PMID:27274786

  10. 76 FR 69755 - National Customs Automation Program Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... was on trade compliance and the development of the Automated Commercial Environment (ACE), the planned..., 2008 (73 FR 50337) for more information. These new capabilities include functionality specific to the... published October 20, 2010 (75 FR 64737) for more information. In order to provide the link between...

  11. 75 FR 64737 - Automated Commercial Environment (ACE): Announcement of a National Customs Automation Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... Security Act of 2002 (see 68 FR 68140, December 5, 2003), and the advance data ocean carriers are required... rule, commonly known as 10 + 2 (see 73 FR 71730, November 25, 2008).\\1\\ Currently, this information is... ACE Systems of Record Notice (71 FR 3109), published in the Federal Register on January 19, 2006....

  12. 77 FR 4815 - Ace Info Solutions, Inc., and Information International Associates; Transfer of Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-31

    ...This notice announces that pesticide related information submitted to EPA's Office of Pesticide Programs (OPP) pursuant to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA), including information that may have been claimed as Confidential Business Information (CBI) by the submitter, will be transferred to Ace Info Solutions,......

  13. ACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines.

    PubMed

    Bosnyák, E; Trájer, E; Udvardy, A; Komka, Z; Protzner, A; Kováts, T; Györe, I; Tóth, M; Pucsok, J; Szmodis, M

    2015-12-01

    The aim of the study was to determine the importance of two sport-associated gene polymorphisms, alpha-actinin-3 R577X (ACTN3) and angiotensin-converting enzyme I/D (ACE), among Hungarian athletes in different sports. The examination was carried out only on women (n = 100). Sport-specific groups were formed in order to guarantee the most homogeneous clusters. Human genomic DNA was isolated from blood, and genotyping was performed by polymerase chain reaction. To measure the differences between the participating groups, Chi-squared test was performed using Statistica 9.0 for Windows® (significance level: p < 0.05). In comparing the ACE I/D allele frequencies, significant difference was detected between water polo (I = 61.11%; D = 38.89%) and combat sports (I = 35.71%, D = 64.29%) athletes (p < 0.03). There was no statistical difference when ACE I/D alleles in combat sports and kayaking/rowing (p > 0.05) were compared. A similarity was detectable in the I allele frequencies of the water polo (61.11%) and kayaking/rowing (56.67%) groups. The ACTN3 R/X polymorphism showed no differences in comparison with the sport groups. R allele frequencies were higher in every group compared to the X allele. The potential significance of the ACE I allele in sports of an aerobic nature was not clearly confirmed among Hungarian athletes. PMID:26690037

  14. Expression and biochemical characterisation of recombinant AceA, a bacterial alpha-mannosyltransferase.

    PubMed

    Geremia, R A; Roux, M; Ferreiro, D U; Dauphin-Dubois, R; Lellouch, A C; Ielpi, L

    1999-07-01

    Biosynthesis of repeat-unit polysaccharides and N-linked glycans proceeds by sequential transfer of sugars from the appropriate sugar donor to an activated lipid carrier. The transfer of each sugar is catalysed by a specific glycosyltransferase. The molecular basis of the specificity of sugar addition is not yet well understood, mainly because of the difficulty of isolating these proteins. In this study, the aceA gene product expressed by Acetobacter xylinum, which is involved in the biosynthesis of the exopolysaccharide acetan, was overproduced in Escherichia coli and its function was characterised. The aceA ORF was subcloned into the expression vector pET29 in frame with the S.tag epitope. The recombinant protein was identified, and culture conditions were optimised for production of the soluble protein. The results of test reactions showed that AceA is able to transfer one alpha-mannose residue from GDP-mannose to cellobiose-P-P-lipid to produce alpha-mannose-cellobiose-P-P-lipid. AceA was not able to use free cellobiose as a substrate, indicating that the pyrophosphate-lipid moiety is needed for enzymatic activity. PMID:10485283

  15. Classification of Gaia16ace as type Ia supernova near maximum

    NASA Astrophysics Data System (ADS)

    Piascik, A. S.; Steele, I. A.

    2016-02-01

    We conducted a spectroscopic observation of transient Gaia16ace at 2016-02-11T02:56:31 UT. The transient was discovered by the Gaia Photometric Science survey on 2016-02-03T22:43:39 UT at position RA=13:48:32.33 DEC=-02:03:33.6.

  16. Educational Measurement. Fourth Edition. ACE/Praeger Series on Higher Education

    ERIC Educational Resources Information Center

    Brennan, Robert L., Ed.

    2006-01-01

    "Educational Measurement" has been the bible in its field since the first edition was published by ACE in 1951. The importance of this fourth edition of "Educational Measurement" is to extensively update and extend the topics treated in the previous three editions. As such, the fourth edition documents progress in the field and provides critical…

  17. Review of the ACE-FTS measurements and recent results for the troposphere and UTLS

    NASA Astrophysics Data System (ADS)

    Bernath, Peter

    The ACE satellite mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; and (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE is making a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) gives ACE coverage of tropical, mid-latitudes and polar regions. A high-resolution (0.02 cm-1 ) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4400 cm-1 ) is measuring the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. Aerosols and clouds are being monitored using the extinction of solar radiation at 0.525 and 1.02 microns as measured by two filtered imagers as well as by their infrared spectra. A dual spectrograph called MAESTRO was added to the mission to extend the wavelength coverage to the 280-1000 nm spectral region. The principal investigator for MAESTRO is T. McElroy of the Meteorological Service of Canada. The FTS and imagers have been built by ABB-Bomem in Quebec City, while the satellite bus has been made by Bristol Aerospace in Winnipeg. ACE was selected in the Canadian Space Agency's SCISAT-1 program, and was successfully launched by NASA on August 12, 2003 for a nominal 2-year mission. The first results of ACE have been presented in a special issue of Geophysics Research Letters in 2005 and recently a special issue on ACE validation has been prepared for Atmospheric Chemistry and Physics by K

  18. Automated multi-step purification protocol for Angiotensin-I-Converting-Enzyme (ACE).

    PubMed

    Eisele, Thomas; Stressler, Timo; Kranz, Bertolt; Fischer, Lutz

    2012-12-12

    Highly purified proteins are essential for the investigation of the functional and biochemical properties of proteins. The purification of a protein requires several steps, which are often time-consuming. In our study, the Angiotensin-I-Converting-Enzyme (ACE; EC 3.4.15.1) was solubilised from pig lung without additional detergents, which are commonly used, under mild alkaline conditions in a Tris-HCl buffer (50mM, pH 9.0) for 48h. An automation of the ACE purification was performed using a multi-step protocol in less than 8h, resulting in a purified protein with a specific activity of 37Umg(-1) (purification factor 308) and a yield of 23.6%. The automated ACE purification used an ordinary fast-protein-liquid-chromatography (FPLC) system equipped with two additional switching valves. These switching valves were needed for the buffer stream inversion and for the connection of the Superloop™ used for the protein parking. Automated ACE purification was performed using four combined chromatography steps, including two desalting procedures. The purification methods contained two hydrophobic interaction chromatography steps, a Cibacron 3FG-A chromatography step and a strong anion exchange chromatography step. The purified ACE was characterised by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and native-PAGE. The estimated monomer size of the purified glycosylated ACE was determined to be ∼175kDa by SDS-PAGE, with the dimeric form at ∼330kDa as characterised by a native PAGE using a novel activity staining protocol. For the activity staining, the tripeptide l-Phe-Gly-Gly was used as the substrate. The ACE cleaved the dipeptide Gly-Gly, releasing the l-Phe to be oxidised with l-amino acid oxidase. Combined with peroxidase and o-dianisidine, the generated H(2)O(2) stained a brown coloured band. This automated purification protocol can be easily adapted to be used with other protein purification tasks. PMID:23217308

  19. Angiotensin II-inhibiting drugs have no effect on intraneuronal Aβ or oligomeric Aβ levels in a triple transgenic mouse model of Alzheimer's disease

    PubMed Central

    Ferrington, Linda; Miners, J Scott; Palmer, Laura E; Bond, Susan M; Povey, Joanne E; Kelly, Paul AT; Love, Seth; Horsburgh, Karen J; Kehoe, Patrick G

    2011-01-01

    Background: Reducing the excessive accumulation of amyloid β-protein (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies. Several studies suggest that pharmacological inhibition of angiotensin-converting enzyme (ACE) or its by-product angiotensin II may delay onset or progression of dementia and it has been suggested that this occurs via regulation of Aβ. Intraneuronal oligomeric accumulation of Aβ is postulated to be one of the earliest pathological events. Thus this study investigated the effect of an ACE-inhibitor, captopril, and two angiotensin II receptor blockers (ARBs), eprosartan and valsartan, on intraneuronal Aβ pathology and oligomeric Aβ levels in a triple transgenic (3xTGAD) mouse model of AD. Methods: Male, adult (3-4 month old) 3xTgAD mice (n=39) were randomly assigned to 4 treatment groups: valsartan (0.17g/l), eprosartan (0.8g/l), captopril (5g/l) or normal drinking water and the drugs given ad libitum for 2 months. Mean arterial blood pressure (MABP) was measured at baseline, at 2 weeks and at 2 months when the mice were sacrificed and the brains hemisected for analysis. One hemisphere was processed for Aβ and amyloid precursor protein (APP) immunohistochemistry and the other for biochemical measurement of oligomeric Aβ and APP. ACE activity was measured in the brain and kidney. Results: MABP was significantly reduced at 2 weeks and 2 months in the ACE-I group (p=0.0006) but was unaltered in the ARB groups compared to vehicle. Neither ACE-I nor ARB treatment altered Aβ and APP immunolabelling or the level of Aβ or APP in brain tissue homogenates. Similarly neither ACE-I nor ARB treatment altered ACE activity in either brain or kidney compared to control tissue. Conclusions: ACE-I or ARB administration over 2 months did not affect APP levels or either intraneuronal Aβ or oligomeric Aβ levels in 3xTGAD mice. While ARBs did not alter MABP, captopril did mediate reductions in MABP in the 3xTGAD mice which appeared to

  20. Coronal Sources and In Situ Properties of the Solar Winds Sampled by ACE During 1999 - 2008

    NASA Astrophysics Data System (ADS)

    Fu, Hui; Li, Bo; Li, Xing; Huang, Zhenghua; Mou, Chaozhou; Jiao, Fangran; Xia, Lidong

    2015-05-01

    We identify the coronal sources of the solar winds sampled by the ACE spacecraft during 1999 - 2008 and examine the in situ solar wind properties as a function of wind sources. The standard two-step mapping technique is adopted to establish the photospheric footpoints of the magnetic flux tubes along which the ACE winds flow. The footpoints are then placed in the context of EIT 284 Å images and photospheric magnetograms, allowing us to categorize the sources into four groups: coronal holes (CHs), active regions (ARs), the quiet Sun (QS), and "undefined". This practice also enables us to establish the response to solar activity of the fractions occupied by each type of solar wind, and of their speeds and O7+/O6+ ratios measured in situ. We find that during the maximum phase, the majority of ACE winds originate from ARs. During the declining phase, CHs and ARs are equally important contributors to the ACE solar winds. The QS contribution increases with decreasing solar activity and maximizes in the minimum phase when the QS appears to be the primary supplier of the ACE winds. With decreasing activity, the winds from all sources tend to become cooler, as represented by the increasingly low O7+/O6+ ratios. On the other hand, during each activity phase, the AR winds tend to be the slowest and are associated with the highest O7+/O6+ ratios, while the CH winds correspond to the other extreme, with the QS winds lying in between. Applying the same analysis method to the slow winds alone, here defined as the winds with speeds lower than 500 km s-1, we find basically the same overall behavior, as far as the contributions of individual groups of sources are concerned. This statistical study indicates that QS regions are an important source of the solar wind during the minimum phase.

  1. Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins

    PubMed Central

    Yousr, Marwa; Howell, Nazlin

    2015-01-01

    Protein by-products from the extraction of lecithin from egg yolk can be converted into value-added products, such as bioactive hydrolysates and peptides that have potential health enhancing antioxidant, and antihypertensive properties. In this study, the antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of peptides isolated and purified from egg yolk protein were investigated. Defatted egg yolk was hydrolyzed using pepsin and pancreatin and sequentially fractionated by ultrafiltration, followed by gel filtration to produce egg yolk gel filtration fractions (EYGF). Of these, two fractions, EYGF-23 and EYGF-33, effectively inhibited the peroxides and thiobarbituric acid reactive substance (TBARS) in an oxidizing linoleic acid model system. The antioxidant mechanism involved superoxide anion and hydroxyl radicals scavenging and ferrous chelation. The presence of hydrophobic amino acids such as tyrosine (Y) and tryptophan (W), in sequences identified by LC-MS as WYGPD (EYGF-23) and KLSDW (EYGF-33), contributed to the antioxidant activity and were not significantly different from the synthetic BHA antioxidant. A third fraction (EYGF-56) was also purified from egg yolk protein by gel filtration and exhibited high ACE inhibitory activity (69%) and IC50 value (3.35 mg/mL). The SDNRNQGY peptide (10 mg/mL) had ACE inhibitory activity, which was not significantly different from that of the positive control captopril (0.5 mg/mL). In addition, YPSPV in (EYGF-33) (10 mg/mL) had higher ACE inhibitory activity compared with captopril. These findings indicated a substantial potential for producing valuable peptides with antioxidant and ACE inhibitory activity from egg yolk. PMID:26690134

  2. ACE-II genotype and I allele predicts ischemic stroke among males in south India

    PubMed Central

    Vijayan, Murali; Chinniah, Rathika; Ravi, Padma Malini; Mosses Joseph, Arun Kumar; Vellaiappan, Neethi Arasu; Krishnan, Jeyaram Illiayaraja; Karuppiah, Balakrishnan

    2014-01-01

    Two hundred ischemic stroke patients and 193 age and sex matched healthy controls were studied for the presence of Angiotensin Converting Enzyme Insertion/Deletion (ACE I/D) gene polymorphism. The PCR studies revealed that ACE ‘II’ (OR = 2.055; p = 0.004) genotype and ‘I’ (OR = 1.411; p = 0.018) alleles were significantly associated with IS patients. Gender specific analysis revealed a strong association of ‘II’ (OR = 2.044; p = 0.014) genotype and ‘I’ (OR = 1.531; p = 0.011) allele with male sex. Classification of patients based on TOAST criteria, revealed a significant association for ‘II’ genotype (OR = 1.713; p = 0.043) and ‘I’ (OR = 1.382; p = 0.039) allele in LVD patients only. When the data was stratified based on age and sex, a statistically significant association was observed for ACE ‘II’ genotype (OR = 2.288; p = 0.006) and ‘I’ allele (OR = 1.395; p = 0.054) in IS male patients of > 50 years of age. The ACE ‘D’ allele was found to be increased in controls (OR = 0.709; p = 0.018) than IS patients. Multivariate logistic regression analysis showed that smoking and diabetes were the most powerful independent risk factor in LVD type of stroke. Thus, we presented here an evidence for a strong association of ACE ‘II’ genotype and ‘I’ allele compounded by factors such as smoking and diabetes among south Indian IS patients. PMID:25606450

  3. Modulation of Vascular ACE by Oxidative Stress in Young Syrian Cardiomyopathic Hamsters: Therapeutic Implications.

    PubMed

    Cruz, Nildris; Miranda, Jorge D; Crespo, Maria J

    2016-01-01

    Increased vascular angiotensin-converting enzyme (ACE) activity and oxidative stress are present in young Syrian cardiomyopathic hamsters (SCH) before the clinical manifestation of heart failure (HF). The developmental time-course of these alterations and their potential interactions, however, are still unknown. We evaluated mRNA and protein levels of ACE, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) in the vasculature of SCH from one to four months of age. Total RNA and proteins were quantified with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The role of nitric oxide (NO) on vascular ACE activity was also assessed. ACE mRNA and protein levels were up-regulated in SCH at two months of age compared with controls (CT) (p < 0.05). At this two-month stage, eNOS protein levels were lower in SCH (87%) than in CT (100%) (p < 0.05), although iNOS protein levels increased significantly (482%) compared to CT (100%; p < 0.05). In addition, ACE mRNA expression and activity were modulated by NO at two months of age. Thus, the combination of low eNOS and high iNOS protein levels may underlie vascular renin-angiotensin system (RAS) over-activation. Altogether, these factors may contribute to the development of endothelial dysfunction and vascular hyper-reactivity in the early stages of heart failure, and eventually trigger cardiac deterioration in this animal model of HF. PMID:27420103

  4. Ozone Measurements from the Canadian Arctic Validation of ACE Campaign: 2004 and 2005

    NASA Astrophysics Data System (ADS)

    Walker, K. A.; Strong, K.; Berman, R.; Bernath, P. F.; Boone, C.; Drummond, J. R.; Fast, H.; Fraser, A.; Goutail, F.; Harwood, M.; Kerzenmacher, T. E.; Loewen, P.; Macquarrie, K.; McElroy, C. T.; Midwinter, C.; Mittermeier, R.; Skelton, R.; Strawbridge, K.; Sung, K.; Walker, J.; Wu, H.

    2005-12-01

    Two springtime validation campaigns have been conducted in the Canadian Arctic to provide correlative measurements for validating results from the Atmospheric Chemistry Experiment (ACE) satellite mission. The satellite has two instruments on-board: a high-resolution infrared Fourier Transform Spectrometer (ACE-FTS) and a dual UV-visible-NIR spectrophotometer called MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). The validation campaigns took place at Environment Canada's Arctic Stratospheric Ozone (AStrO) Observatory in Eureka, Nunavut (80 N, 86 W) between February and April in both 2004 and 2005. Seven ground-based instruments were operated during the 2004 campaign: a ground-based adaptation of the ACE-FTS (PARIS - Portable Atmospheric Research Interferometric Spectrometer), a ground-based version of the ACE-MAESTRO, a SunPhotoSpectrometer, a zenith-viewing UV-visible grating spectrometer, a Bomem DA8 Fourier transform spectrometer, a Differential Absorption Lidar and a Brewer spectrophotometer. For the 2005 campaign, a Systeme d'Analyse par Observations Zenithales (SAOZ) instrument and a second Brewer were added to the instrument complement. Also, balloon-borne ozonesonde and radiosonde sensors were flown frequently during both campaigns. This paper will focus on comparisons of ozone measurements made by the ground-based, balloon-borne and satellite-borne instruments during the two ACE Arctic Validation campaigns. Comparisons of both retrieved columns and profiles will be presented. Also, the results from the 2004 and 2005 campaigns will be intercompared to highlight the differences between the two years.

  5. Development of a Robust star identification technique for use in attitude determination of the ACE spacecraft

    NASA Technical Reports Server (NTRS)

    Woodard, Mark; Rohrbaugh, Dave

    1995-01-01

    The Advanced Composition Explorer (ACE) spacecraft is designed to fly in a spin-stabilized attitude. The spacecraft will carry two attitude sensors - a digital fine Sun sensor and a charge coupled device (CCD) star tracker - to allow ground-based determination of the spacecraft attitude and spin rate. Part of the processing that must be performed on the CCD star tracker data is the star identification. Star data received from the spacecraft must be matched with star information in the SKYMAP catalog to determine exactly which stars the sensor is tracking. This information, along with the Sun vector measured by the Sun sensor, is used to determine the spacecraft attitude. Several existing star identification (star ID) systems were examined to determine whether they could be modified for use on the ACE mission. Star ID systems which exist for three-axis stabilized spacecraft tend to be complex in nature and many require fairly good knowledge of the spacecraft attitude, making their use for ACE excessive. Star ID systems used for spinners carrying traditional slit star sensors would have to be modified to model the CCD star tracker. The ACE star ID algorithm must also be robust, in that it will be able to correctly identify stars even though the attitude is not known to a high degree of accuracy, and must be very efficient to allow real-time star identification. The paper presents the star ID algorithm that was developed for ACE. Results from prototype testing are also presented to demonstrate the efficiency, accuracy, and robustness of the algorithm.

  6. Modulation of Vascular ACE by Oxidative Stress in Young Syrian Cardiomyopathic Hamsters: Therapeutic Implications

    PubMed Central

    Cruz, Nildris; Miranda, Jorge D.; Crespo, Maria J.

    2016-01-01

    Increased vascular angiotensin-converting enzyme (ACE) activity and oxidative stress are present in young Syrian cardiomyopathic hamsters (SCH) before the clinical manifestation of heart failure (HF). The developmental time-course of these alterations and their potential interactions, however, are still unknown. We evaluated mRNA and protein levels of ACE, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) in the vasculature of SCH from one to four months of age. Total RNA and proteins were quantified with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The role of nitric oxide (NO) on vascular ACE activity was also assessed. ACE mRNA and protein levels were up-regulated in SCH at two months of age compared with controls (CT) (p < 0.05). At this two-month stage, eNOS protein levels were lower in SCH (87%) than in CT (100%) (p < 0.05), although iNOS protein levels increased significantly (482%) compared to CT (100%; p < 0.05). In addition, ACE mRNA expression and activity were modulated by NO at two months of age. Thus, the combination of low eNOS and high iNOS protein levels may underlie vascular renin-angiotensin system (RAS) over-activation. Altogether, these factors may contribute to the development of endothelial dysfunction and vascular hyper-reactivity in the early stages of heart failure, and eventually trigger cardiac deterioration in this animal model of HF. PMID:27420103

  7. Antihypertensive drugs decrease risk of Alzheimer disease

    PubMed Central

    Xia, Jin; Yao, Wenliang; Furberg, Curt D.; Xue, Qian-Li; Mercado, Carla I.; Fitzpatrick, Annette L.; Fried, Linda P.; Kawas, Claudia H.; Sink, Kaycee M.; Williamson, Jeff D.; DeKosky, Steven T.; Carlson, Michelle C.

    2013-01-01

    Objectives: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI). Methods: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders. Results: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31–0.82), 0.31 in ARB (95% CI 0.14–0.68), 0.50 in ACE-I (95% CI 0.29–0.83), 0.62 in CCB (95% CI 0.35–1.09), and 0.58 in BB (95% CI 0.36–0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20–0.73). Conclusions: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI. PMID:23911756

  8. Autophagy inhibitors.

    PubMed

    Pasquier, Benoit

    2016-03-01

    Autophagy is a lysosome-dependent mechanism of intracellular degradation. The cellular and molecular mechanisms underlying this process are highly complex and involve multiple proteins, including the kinases ULK1 and Vps34. The main function of autophagy is the maintenance of cell survival when modifications occur in the cellular environment. During the past decade, extensive studies have greatly improved our knowledge and autophagy has exploded as a research field. This process is now widely implicated in pathophysiological processes such as cancer, metabolic, and neurodegenerative disorders, making it an attractive target for drug discovery. In this review, we will summarize the different types of inhibitors that affect the autophagy machinery and provide some potential therapeutic perspectives. PMID:26658914

  9. The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample.

    PubMed

    Siciliano, Mattia; Raimo, Simona; Tufano, Dario; Basile, Giuseppe; Grossi, Dario; Santangelo, Franco; Trojano, Luigi; Santangelo, Gabriella

    2016-03-01

    The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes. PMID:26563847

  10. Signal transduction inhibitors in treatment of myelodysplastic syndromes.

    PubMed

    Bachegowda, Lohith; Gligich, Oleg; Mantzaris, Ionnis; Schinke, Carolina; Wyville, Dale; Carrillo, Tatiana; Braunschweig, Ira; Steidl, Ulrich; Verma, Amit

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by ineffective hematopoiesis that results in reduced blood counts. Although MDS can transform into leukemia, most of the morbidity experienced by these patients is due to chronically low blood counts. Conventional cytotoxic agents used to treat MDS have yielded some encouraging results but are characterized by many adverse effects in the predominantly elderly patient population. Targeted interventions aimed at reversing the bone marrow failure and increasing the peripheral blood counts would be advantageous in this cohort of patients. Studies have demonstrated over-activated signaling of myelo-suppressive cytokines such as TGF-β, TNF-α and Interferons in MDS hematopoietic stem cells. Targeting these signaling cascades could be potentially therapeutic in MDS. The p38 MAP kinase pathway, which is constitutively activated in MDS, is an example of cytokine stimulated kinase that promotes aberrant apoptosis of stem and progenitor cells in MDS. ARRY-614 and SCIO-469 are p38 MAPK inhibitors that have been used in clinical trials and have shown activity in a subset of MDS patients. TGF-β signaling has been therapeutically targeted by small molecule inhibitor of the TGF-β receptor kinase, LY-2157299, with encouraging preclinical results. Apart from TGF-β receptor kinase inhibition, members of TGF-β super family and BMP ligands have also been targeted by ligand trap compounds like Sotatercept (ACE-011) and ACE-536. The multikinase inhibitor, ON-01910.Na (Rigosertib) has demonstrated early signs of efficacy in reducing the percentage of leukemic blasts and is in advanced stages of clinical testing. Temsirolimus, Deforolimus and other mTOR inhibitors are being tested in clinical trials and have shown preclinical efficacy in CMML. EGF receptor inhibitors, Erlotinib and Gefitinib have shown efficacy in small trials that may be related to off target effects. Cell cycle regulator inhibitors

  11. Signal transduction inhibitors in treatment of myelodysplastic syndromes

    PubMed Central

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by ineffective hematopoiesis that results in reduced blood counts. Although MDS can transform into leukemia, most of the morbidity experienced by these patients is due to chronically low blood counts. Conventional cytotoxic agents used to treat MDS have yielded some encouraging results but are characterized by many adverse effects in the predominantly elderly patient population. Targeted interventions aimed at reversing the bone marrow failure and increasing the peripheral blood counts would be advantageous in this cohort of patients. Studies have demonstrated over-activated signaling of myelo-suppressive cytokines such as TGF-β, TNF-α and Interferons in MDS hematopoietic stem cells. Targeting these signaling cascades could be potentially therapeutic in MDS. The p38 MAP kinase pathway, which is constitutively activated in MDS, is an example of cytokine stimulated kinase that promotes aberrant apoptosis of stem and progenitor cells in MDS. ARRY-614 and SCIO-469 are p38 MAPK inhibitors that have been used in clinical trials and have shown activity in a subset of MDS patients. TGF-β signaling has been therapeutically targeted by small molecule inhibitor of the TGF-β receptor kinase, LY-2157299, with encouraging preclinical results. Apart from TGF-β receptor kinase inhibition, members of TGF-β super family and BMP ligands have also been targeted by ligand trap compounds like Sotatercept (ACE-011) and ACE-536. The multikinase inhibitor, ON-01910.Na (Rigosertib) has demonstrated early signs of efficacy in reducing the percentage of leukemic blasts and is in advanced stages of clinical testing. Temsirolimus, Deforolimus and other mTOR inhibitors are being tested in clinical trials and have shown preclinical efficacy in CMML. EGF receptor inhibitors, Erlotinib and Gefitinib have shown efficacy in small trials that may be related to off target effects. Cell cycle regulator inhibitors

  12. Long-range safety and protective benefits of angiotensin-converting enzyme inhibitors for hypertension. Do we need more clinical trials?

    PubMed Central

    Sambhi, M P; Gavras, H; Robertson, J I; Smith, W M

    1993-01-01

    Inhibition of the renin-angiotensin system is being applied with considerable success to the treatment of hypertension and heart failure. Angiotensin-converting enzyme (ACE) inhibitors are the only currently available agents that can achieve this objective. In general, the major therapeutic effects of these agents in the treatment of mild to moderate hypertension or of heart failure are exerted on the vascular tissue through inhibition of the renin-angiotensin system and, secondarily, of the sympathetic nervous system. When cardiovascular functional reserve is diminished and autoregulation of regional and systemic blood flow is strained, however, ACE inhibitors may affect other organ functions (heart, kidneys, and possibly brain), hormones other than the renin system, and local tissue humoral systems. The interrelations between the renin-angiotensin system and several other vasoactive systems--including circulating and locally generated tissue hormones and centrally acting neurohormonal factors--are complex and unclear. A better understanding of these mechanisms and interrelations would allow for a more rational therapeutic use of these agents. Unknown also are the clinical effects of prolonged ACE inhibition. Whether the use of ACE inhibitors can provide primary cardiorenal protection requires proof through definitive clinical trials. Images PMID:8460511

  13. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model.

    PubMed

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan

    2016-09-01

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2weeks. 48h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocyte count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. PMID:27343405

  14. A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development.

    PubMed

    Calderón-Noreña, Diana M; González-Novo, Alberto; Orellana-Muñoz, Sara; Gutiérrez-Escribano, Pilar; Arnáiz-Pita, Yolanda; Dueñas-Santero, Encarnación; Suárez, M Belén; Bougnoux, Marie-Elisabeth; Del Rey, Francisco; Sherlock, Gavin; d'Enfert, Christophe; Correa-Bordes, Jaime; de Aldana, Carlos R Vázquez

    2015-04-01

    Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages

  15. A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Candida albicans Hyphal Development

    PubMed Central

    Orellana-Muñoz, Sara; Gutiérrez-Escribano, Pilar; Arnáiz-Pita, Yolanda; Dueñas-Santero, Encarnación; Suárez, M. Belén; Bougnoux, Marie-Elisabeth; del Rey, Francisco; Sherlock, Gavin; d’Enfert, Christophe; Correa-Bordes, Jaime; de Aldana, Carlos R. Vázquez

    2015-01-01

    Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages

  16. Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism.

    PubMed

    Wang, Yu; Shoemaker, Robin; Thatcher, Sean E; Batifoulier-Yiannikouris, Frederique; English, Victoria L; Cassis, Lisa A

    2015-06-15

    We recently demonstrated that female mice are resistant to the development of obesity-induced hypertension through a sex hormone-dependent mechanism that involved adipose angiotensin-converting enzyme 2 (ACE2). In this study, we hypothesized that provision of 17β-estradiol (E2) to ovariectomized (OVX) high-fat (HF)-fed female hypertensive mice would reverse obesity-hypertension through an ACE2-dependent mechanism. Pilot studies defined dose-dependent effects of E2 in OVX female mice on serum E2 concentrations and uterine weights. An E2 dose of 36 μg/ml restored normal serum E2 concentrations and uterine weights. Therefore, HF-fed OVX female Ace2(+/+) and Ace2(-/-) mice were administered vehicle or E2 (36 μg/ml) for 16 wk. E2 administration significantly decreased body weights of HF-fed OVX female Ace2(+/+) and Ace2(-/-) mice of either genotype. At 15 wk, E2 administration decreased systolic blood pressure (SBP) of OVX HF-fed Ace2(+/+) but not Ace2(-/-) females during the light but not the dark cycle. E2-mediated reductions in SBP in Ace2(+/+) females were associated with significant elevations in adipose ACE2 mRNA abundance and activity and reduced plasma ANG II concentrations. In contrast to females, E2 administration had no effect on any parameter quantified in HF-fed male hypertensive mice. In 3T3-L1 adipocytes, E2 promoted ACE2 mRNA abundance through effects at estrogen receptor-α (ERα) and resulted in ERα-mediated binding at the ACE2 promoter. These results demonstrate that E2 administration to OVX females reduces obesity-induced elevations in SBP (light cycle) through an ACE2-dependent mechanism. Beneficial effects of E2 to decrease blood pressure in OVX obese females may result from stimulation of adipose ACE2. PMID:26078188

  17. Alternative therapies for the management of inhibitors.

    PubMed

    Shima, M; Lillicrap, D; Kruse-Jarres, R

    2016-07-01

    The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains a major treatment complication encountered in the treatment of haemophilia. Not all patients with even the same severity and genotype develop inhibitors suggesting an underlying mechanism of tolerance against FVIII- or FIX-related immunity. One mechanism may be central tolerance observed in patients in whom the FVIII mutation enables some production of the protein. The other is a peripheral tolerance mechanism which may be evident in patients with null mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI-1, BAX801) has been developed for the haemostatic treatment of both congenital haemophilia with inhibitor (CHAWI) and acquired haemophilia A (AHA). In 28 subjects with AHA with life-/limb-threatening bleeding, rpFVIII reduced or stopped bleeding in all patients within 24 h. The cross-reactivity of anti-human FVIII antibodies to rpFVIII remains around 30-50%. Recently, new therapeutics based on the quite novel concepts have been developed and clinical studies are ongoing. These are humanized asymmetric antibody mimicking FVIIIa function by maintaining a suitable interaction between FIXa and FX (Emicizumab, ACE910), and small interfering RNAs (siRNA, ALN-AT3) suppress liver production of AT through post-transcriptional gene silencing and a humanized anti-TFPI monoclonal antibody (Concizumab). Their main advantages are longer half-life, subcutaneous applicability and efficacy irrespective of the presence of inhibitors which will make it easier to initiate more effective treatment especially early childhood. PMID:27405674

  18. Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors.

    PubMed

    Douglas, Ross G; Sharma, Rajni K; Masuyer, Geoffrey; Lubbe, Lizelle; Zamora, Ismael; Acharya, K Ravi; Chibale, Kelly; Sturrock, Edward D

    2014-02-01

    ACE (angiotensin-1-converting enzyme) is a zinc metallopeptidase that plays a prominent role in blood pressure regulation and electrolyte homeostasis. ACE consists of two homologous domains that despite similarities of sequence and topology display differences in substrate processing and inhibitor binding. The design of inhibitors that selectively inhibit the N-domain (N-selective) could be useful in treating conditions of tissue injury and fibrosis due to build-up of N-domain-specific substrate Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro). Using a receptor-based SHOP (scaffold hopping) approach with N-selective inhibitor RXP407, a shortlist of scaffolds that consisted of modified RXP407 backbones with novel chemotypes was generated. These scaffolds were selected on the basis of enhanced predicted interaction energies with N-domain residues that differed from their C-domain counterparts. One scaffold was synthesized and inhibitory binding tested using a fluorogenic ACE assay. A molecule incorporating a tetrazole moiety in the P2 position (compound 33RE) displayed potent inhibition (K(i)=11.21±0.74 nM) and was 927-fold more selective for the N-domain than the C-domain. A crystal structure of compound 33RE in complex with the N-domain revealed its mode of binding through aromatic stacking with His388 and a direct hydrogen bond with the hydroxy group of the N-domain specific Tyr369. This work further elucidates the molecular basis for N-domain-selective inhibition and assists in the design of novel N-selective ACE inhibitors that could be employed in treatment of fibrosis disorders. PMID:24015848

  19. Association between ACE polymorphism, cognitive phenotype and APOE E4 allele in a Tunisian population with Alzheimer disease.

    PubMed

    Achouri-Rassas, Afef; Ali, Nadia Ben; Cherif, Aroua; Fray, Saloua; Siala, Hajer; Zakraoui, Nouria Oudiaa; Hadj-Fredj, Sondes; Kechaou, Mariem; Anane, Nadia; Echebi, Slim; Messaoud, Taieb; Belal, Samir

    2016-03-01

    Angiotensin-converting enzyme (ACE) has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the ACE gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), and is generally considered to be a disorder primarily affecting memory. We conducted a case-control study in a sample composed of 85 sporadic AD patients and 90 age- and sex-matched controls to investigate the possible effect of the polymorphism and cognitive profile. Our data revealed an association between the ACE polymorphism and AD risk. There was a significant difference in the ACE allele or genotype frequencies between cases and controls. The D/D genotype showed an increased risk for AD and in the amnestic group and the effect was independent on ApoE genotypes. PMID:26456241

  20. Badhwar-O'Neil 2007 Galactic Cosmic Ray (GCR) Model Using Advanced Composition Explorer (ACE) Measurements for Solar Cycle 23

    NASA Technical Reports Server (NTRS)

    ONeill, P. M.

    2007-01-01

    Advanced Composition Explorer (ACE) satellite measurements of the galactic cosmic ray flux and correlation with the Climax Neutron Monitor count over Solar Cycle 23 are used to update the Badhwar O'Neill Galactic Cosmic Ray (GCR) model.

  1. 75 FR 82010 - AceInfo Solutions and Avaya Government Solutions, Koansys LLC, and Quality Associates Inc...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY AceInfo Solutions and Avaya Government Solutions, Koansys LLC, and Quality Associates Inc... completed their work. List of Subjects Environmental protection, Business and industry, Government...

  2. Intercalibration and Cross-Correlation of Ace and Wind Solar Wind Data

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This report covers activities funded from October 1, 1998 through September 30, 2002. Two yearly status reports have been filed on this grant, and they are included as Appendix 1. The purpose of this grant was to compare ACE and Wind solar wind parameters when the two spacecraft were near to one another and then to use the intercalibrated parameters to carry out scientific investigations. In September, 2001 a request for a one-year, no-cost extension until September 30, 2002 was submitted and approved. The statement of work for that extension included adjustment of ACE densities below wind speeds of 350 km/s, a study of shock normal orientations using travel time delays between the two spacecraft, comparison of density jumps at shocks, and a study of temperature anisotropies and double streaming to see if such features evolved between the spacecraft.

  3. ACE observations of magnetic waves arising from newborn interstellar pickup helium ions

    NASA Astrophysics Data System (ADS)

    Argall, Matthew R.; Fisher, Meghan K.; Joyce, Colin J.; Smith, Charles W.; Isenberg, Philip A.; Vasquez, Bernard J.; Schwadron, Nathan A.; Skoug, Ruth M.

    2015-11-01

    We report low-frequency magnetic waves that were observed by the Advanced Composition Explorer (ACE) spacecraft on day of year 180 of 1999 with characteristics consistent with the predictions of waves excited by newborn interstellar pickup He+ ions. This event was found by examining daily spectrograms of MAG data, a new data product that is now available to the community via the ACE Science Center. The event shown here is one of approximately 20 similar events that will be analyzed in future studies. This event is fairly typical of those we have found so far. The waves exist at spacecraft-frame frequencies between the He+ cyclotron frequency and approximately twice the H+ cyclotron frequency. Fluctuations are transverse to the mean magnetic field, are noncompressive, circularly polarized, have field-aligned minimum variance directions, and are left-hand polarized in the spacecraft frame as predicted by theory. The event lasts for just under 1 h.

  4. Language Comprehension in the Balance: The Robustness of the Action-Compatibility Effect (ACE)

    PubMed Central

    Zwaan, Rolf A.; van der Stoep, Nathan; Guadalupe, Tulio; Bouwmeester, Samantha

    2012-01-01

    How does language comprehension interact with motor activity? We investigated the conditions under which comprehending an action sentence affects people's balance. We performed two experiments to assess whether sentences describing forward or backward movement modulate the lateral movements made by subjects who made sensibility judgments about the sentences. In one experiment subjects were standing on a balance board and in the other they were seated on a balance board that was mounted on a chair. This allowed us to investigate whether the action compatibility effect (ACE) is robust and persists in the face of salient incompatibilities between sentence content and subject movement. Growth-curve analysis of the movement trajectories produced by the subjects in response to the sentences suggests that the ACE is indeed robust. Sentence content influenced movement trajectory despite salient inconsistencies between implied and actual movement. These results are interpreted in the context of the current discussion of embodied, or grounded, language comprehension and meaning representation. PMID:22363580

  5. Systematic Variation in the Spectral Slope of the IMF at ACE

    NASA Astrophysics Data System (ADS)

    Thomson, David J.

    Inferences on turbulence in interplanetary plasmas commonly depend on the slope of the power spectrum. We have studied the slopes of spectra of the interplanetary magnetic field and charged particles from the HISCALE and EPAM detectors on Ulysses and ACE and find that it is systematically nonstationary. As an example, when the spectra are estimated on time blocks varying between three hours and one day, the average slope on the ACE GSE Y component of the IMF is close to -5/3, but fluctuations about this average are not random. Using 1-minute data, the slopes made from three hour data blocks offset by one hour gives a new time series. Solar rotation and its first harmonic are nearly absent in the spectrum of this series, but there are a series of strong peaks that may be convection or gravity modes.

  6. Solar Activity and GCR Particle Flux Variations: Assessment and Modeling with Ulysses and ACE/CRIS

    NASA Astrophysics Data System (ADS)

    Saganti, Premkumar

    Galactic Cosmic Ray (GCR) environment during the current and historically known lower solar minimum condition indicate some of the very high anticipated measurements of particle spectral data. Data from the Ulysses spacecraft in the polar orbit about the sun during the years 2004 and 2008 (about 5 AU) provided proton and alpha particle flux data and showed such anticipated high particle flux variations. Also, ACE/CRIS spacecraft data during the years 2007 and 2009 showed some of the high particle flux measurements of several heavy ions such as oxygen and iron. We present Ulysses and ACE/CRIS measured particle flux data and discuss their high density and variations in the context of the current low solar activity for depicting current space radiation environment.

  7. Time and frequency transfer with a microwave link in the ACES/PHARAO mission

    NASA Astrophysics Data System (ADS)

    Le Poncin-Lafitte, C.; Delva, P.; Meynadier, F.; Guerlin, C.; Wolf, P.; Laurent, P.

    2015-08-01

    The Atomic Clocks Ensemble in Space (ACES/PHARAO mission), which will be installed on board the International Space Station (ISS), uses a dedicated two-way microwave link in order to compare the timescale generated on board with those provided by many ground stations disseminated on the Earth. Phase accuracy and stability of this long range link will have a key role in the success of the ACES/PHARAO experiment. SYRTE laboratory is heavily involved in the design and development of the data processing software: from theoretical modeling and numerical simulations to the development of a software prototype. Our team is working on a wide range of problems that need to be solved in order to achieve high accuracy in (almost) real time. In this article we present some key aspects of the measurement, as well as current status of the software's development.

  8. The Canadian Arctic ACE/OSIRIS Validation Project at PEARL: Validating Satellite Observations Over the High Arctic

    NASA Astrophysics Data System (ADS)

    Walker, Kaley A.; Strong, Kimberly; Fogal, Pierre F.; Drummond, James R.

    2016-04-01

    Ground-based measurements provide critical data for the validation of satellite retrievals of atmospheric trace gases and for the assessment of long-term stability of these measurements. As of February 2016, the Canadian-led Atmospheric Chemistry Experiment (ACE) satellite mission has been making measurements of the Earth's atmosphere for nearly twelve years and Canada's Optical Spectrograph and InfraRed Imager System (OSIRIS) instrument on the Odin satellite has been operating for fourteen years. As ACE and OSIRIS operations have extended beyond their planned two-year missions, there is an ongoing need to validate the trace gas data profiles from the ACE-Fourier Transform Spectrometer (ACE-FTS), the Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (ACE-MAESTRO) and OSIRIS. In particular, validation comparisons are needed during Arctic springtime to understand better the measurements of species involved in stratospheric ozone chemistry. To this end, thirteen Canadian Arctic ACE/OSIRIS Validation Campaigns have been conducted during the spring period (February - April in 2004 - 2016) at the Polar Environment Atmospheric Research Laboratory (PEARL) in Eureka, Nunavut (80N, 86W). For the past decade, these campaigns have been undertaken in collaboration with the Canadian Network for the Detection of Atmospheric Change (CANDAC). The spring period coincides with the most chemically active time of year in the Arctic, as well as a significant number of satellite overpasses. A suite of as many as 12 ground-based instruments, as well as frequent balloon-borne ozonesonde and radiosonde launches, have been used in each campaign. These instruments include: a ground-based version of the ACE-FTS (PARIS - Portable Atmospheric Research Interferometric Spectrometer), a terrestrial version of the ACE-MAESTRO, a SunPhotoSpectrometer, two CANDAC zenith-viewing UV-visible grating spectrometers, a Bomem DA8 Fourier transform spectrometer

  9. Interaction Between ACE I/D and ACTN3 R557X Polymorphisms in Polish Competitive Swimmers.

    PubMed

    Grenda, Agata; Leońska-Duniec, Agata; Kaczmarczyk, Mariusz; Ficek, Krzysztof; Król, Paweł; Cięszczyk, Paweł; Zmijewski, Piotr

    2014-09-29

    We hypothesized that the ACE ID / ACTN3 R577X genotype combination was associated with sprint and endurance performance. Therefore, the purpose of the present study was to determine the interaction between both ACE ID and ACTN3 R577X polymorphisms and sprint and endurance performance in swimmers. Genomic DNA was extracted from oral epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany). All samples were genotyped using a real-time poly- merase chain reaction. The ACE I/D and the ACTN3 R577X genotype frequencies met Hardy-Weinberg expectations in both swimmers and controls. When the two swimmer groups, long distance swimmers (LDS) and short distance swimmers (SDS), were compared with control subjects in a single test, a significant association was found only for the ACE polymorphism, but not for ACTN3. Additionally, four ACE/ACTN3 combined genotypes (ID/RX, ID/XX, II/RX and II/XX) were statistically significant for the LDS versus Control comparison, but none for the SDS versus Control comparison. The ACE I/D and the ACTN3 R577X polymorphisms did not show any association with sprint swimming, taken individually or in combination. In spite of numerous previous reports of associations with athletic status or sprint performance in other sports, the ACTN3 R577X polymorphism, in contrast to ACE I/D, was not significantly associated with elite swimming status when considered individually. However, the combined analysis of the two loci suggests that the co-occurrence of the ACE I and ACTN3 X alleles may be beneficial to swimmers who compete in long distance races. PMID:25414746

  10. Interaction Between ACE I/D and ACTN3 R557X Polymorphisms in Polish Competitive Swimmers

    PubMed Central

    Grenda, Agata; Leońska-Duniec, Agata; Kaczmarczyk, Mariusz; Ficek, Krzysztof; Król, Paweł; Cięszczyk, Paweł; Żmijewski, Piotr

    2014-01-01

    We hypothesized that the ACE ID / ACTN3 R577X genotype combination was associated with sprint and endurance performance. Therefore, the purpose of the present study was to determine the interaction between both ACE ID and ACTN3 R577X polymorphisms and sprint and endurance performance in swimmers. Genomic DNA was extracted from oral epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany). All samples were genotyped using a real-time poly- merase chain reaction. The ACE I/D and the ACTN3 R577X genotype frequencies met Hardy-Weinberg expectations in both swimmers and controls. When the two swimmer groups, long distance swimmers (LDS) and short distance swimmers (SDS), were compared with control subjects in a single test, a significant association was found only for the ACE polymorphism, but not for ACTN3. Additionally, four ACE/ACTN3 combined genotypes (ID/RX, ID/XX, II/RX and II/XX) were statistically significant for the LDS versus Control comparison, but none for the SDS versus Control comparison. The ACE I/D and the ACTN3 R577X polymorphisms did not show any association with sprint swimming, taken individually or in combination. In spite of numerous previous reports of associations with athletic status or sprint performance in other sports, the ACTN3 R577X polymorphism, in contrast to ACE I/D, was not significantly associated with elite swimming status when considered individually. However, the combined analysis of the two loci suggests that the co-occurrence of the ACE I and ACTN3 X alleles may be beneficial to swimmers who compete in long distance races. PMID:25414746

  11. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis

    PubMed Central

    Simões e Silva, AC; Silveira, KD; Ferreira, AJ; Teixeira, MM

    2013-01-01

    Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). Most available evidence supports a counter-regulatory role for Ang-(1-7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang-(1-7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang-(1-7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang-(1-7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang-(1-7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases. PMID:23488800

  12. Using ACE and Ulysses to investigate the heliographic transport of energetic particles

    NASA Astrophysics Data System (ADS)

    Robinson, Ian M.

    2002-03-01

    The Advanced Composition Explorer (ACE) and the Ulysses spacecraft follow radically different trajectories, allowing the Sun to be simultaneously studied from 2 different perspectives. Data from the low energy particle instruments carried by these spacecraft reveals energetic particles accelerated at the Sun can access large angular extents of the interplanetary medium. We look at a rare case when the heliographic transport of energetic electrons was apparently prevented and speculate upon the ability of the corona to inhibit the propagation of these particles.

  13. Carbon Dioxide (CO2) Retrievals from Atmospheric Chemistry Experiment (ACE) Solar Occultation Measurements

    NASA Technical Reports Server (NTRS)

    Rinsland, Curtis P.; Chiou, Linda; Boone, Chris; Bernath, Peter

    2010-01-01

    The Atmospheric Chemistry Experiment ACE satellite (SCISAT-1) was launched into an inclined orbit on 12 August 2003 and is now recording high signal-to-noise 0.02 per centimeter resolution solar absorption spectra covering 750-4400 per centimeter (2.3-13 micrometers). A procedure has been developed for retrieving average dry air CO2 mole fractions (X(sub CO2)) in the altitude range 7-10 kilometers from the SCISAT-1 spectra. Using the N2 continuum absorption in a window region near 2500 per centimeter, altitude shifts are applied to the tangent heights retrieved in version 2.2 SCISAT-1 processing, while cloudy or aerosol-impacted measurements are eliminated. Monthly-mean XCO2 covering 60 S to 60 N latitude for February 2004 to March 2008 has been analyzed with consistent trends inferred in both hemispheres. The ACE XCO2 time series have been compared with previously-reported surface network measurements, predictions based on upper tropospheric aircraft measurements, and space-based measurements. The retrieved X(sub CO2) from the ACE-FTS spectra are higher on average by a factor of 1.07 plus or minus 0.025 in the northern hemisphere and by a factor of 1.09 plus or minus 0.019 on average in the southern hemisphere compared to surface station measurements covering the same time span. The ACE derived trend is approximately 0.2% per year higher than measured at surface stations during the same observation period.

  14. Report on intercomparisons of condensation nucleus counter measurements during the ACE-1 intensive study

    SciTech Connect

    Weber, R.J.

    1997-06-01

    This report summarizes findings from intercomparisons of aerosol particle concentrations measured by condensation nucleus counters (CNC`s) on various platforms and ground-based stations during the Southern Hemisphere Marine Aerosol Characterization Experiment (ACE-1). Five CNC`s on the NCAR C-130 are intercompared. The C-130 CNC`s are then intercompared to ship ground-based measurements during periods of C-130 overflights.

  15. New and Improved Infrared Spectroscopy of Halogen-Containing Species for ACE-FTS Retrievals

    NASA Astrophysics Data System (ADS)

    Harrison, Jeremy J.

    2014-06-01

    The Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS), onboard the SCISAT-1 satellite, is a high-resolution (0.02 cm-1) instrument covering the 750-4400 cm-1 spectral region in solar occultation mode. Launched in August 2003, the ACE-FTS has been taking atmospheric measurements for over ten years. With long atmospheric pathlengths (˜300 km) and the sun as a radiation source, the ACE-FTS provides a low detection threshold for trace species in the atmosphere. In fact, it measures the vertical profiles of more molecules in the atmosphere than any other satellite instrument.

    Fluorine- and chlorine-containing molecules in the atmosphere are very strong greenhouse gases, meaning that even small amounts of these gases contribute significantly to the radiative forcing of climate. Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are regulated by the 1987 Montreal Protocol because they deplete the ozone layer. Hydrofluorocarbons (HFCs), which do not deplete the ozone layer and are not regulated by the Montreal Protocol, have been introduced as replacements for CFCs and HCFCs. HFCs have global-warming potentials many times greater than carbon dioxide, and are increasing in the atmosphere at a very fast rate. The quantification of the atmospheric abundances of such molecules from measurements taken by the ACE-FTS and other satellite instruments crucially requires accurate quantitative infrared spectroscopy. HITRAN contains absorption cross section datasets for a number of these species, but many of them have minor deficiencies that introduce systematic errors into satellite retrievals. This talk will focus on new and improved laboratory measurements for a number of important halogenated species.

  16. Economic evaluation of the annual cycle energy system (ACES). Final report. Volume III, appendices

    SciTech Connect

    Not Available

    1980-06-01

    This volume consists of seven appendices related to ACES, the first three of which are concerned with computer programs. The appendices are entitled: (A) ACESIM: Residential Program Listing; (B) Typical Inputs and Outputs of ACESIM; (C) CACESS: Commercial Building Program Listing; (D) Typical Weather-Year Selection Requirements; (E) Building Characteristics; (F) List of Major Variables Used in the Computer Programs; and (G) Bibliography. 79 references.

  17. Texas Hold'em: Secretary Spellings--the Ace in Bush's Hand

    ERIC Educational Resources Information Center

    Davis, Michelle R.

    2007-01-01

    President Bush has one ace in his hand when it comes to the No Child Left Behind Act (NCLB): Secretary of Education Margaret Spellings. Spellings, who has been working on education issues for Bush since the 1990s and his days as a Texas governor, is the person who from the very beginning has had to make NCLB work. She was a key architect of the…

  18. North Atlantic Aerosol Properties and Direct Radiative Effects: Key Results from TARFOX and ACE-2

    NASA Technical Reports Server (NTRS)

    Russell, P. B.; Livingston, J. M.; Schmid, B.; Bergstrom, R. A.; Hignett, P.; Hobbs, P. V.; Durkee, P. A.; Condon, Estelle (Technical Monitor)

    1998-01-01

    Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate in potentially significant ways. This aerosol radiative Forcing is a major source of uncertainty in understanding the observed climate change of the past century and in predicting, future climate. To help reduce this uncertainty, the International Global Atmospheric Chemistry Project (IGAC) has endorsed a series of multiplatform aerosol field campaigns. The Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the second Aerosol Characterization Experiment (ACE-2) were the first IGAC campaigns to address the impact of anthropogenic aerosols. Both TARFOX and ACE-2 gathered extensive data sets on aerosol properties and radiative effects. TARFOX focused on the urban-industrial haze plume flowing from the eastern United States over the western Atlantic Ocean, whereas ACE-2 studied aerosols carried over the eastern Atlantic from both European urban/industrial and African mineral sources. These aerosols often have a marked influence on the top-of-atmosphere radiances measured by satellites, as illustrated in Figure 1. Shown there are contours of aerosol optical depth derived from radiances measured by the AVHRR sensor on the NOAA-11 satellite. The contours readily show that aerosols originating in North America, Europe, and Africa impact the radiative properties of air over the North Atlantic. However, the accurate derivation of flux chances, or radiative forcing, from the satellite-measured radiances or 'etrieved optical depths remains a difficult challenge. In this paper we summarize key Initial results from TARFOX and, to a lesser extent ACE-2, with a focus on those results that allow an improved assessment of the flux changes caused by North Atlantic aerosols at middle and high latitudes.

  19. North Atlantic Aerosol Properties and Direct Radiative Effects: Key Results from TARFOX and ACE-2

    NASA Technical Reports Server (NTRS)

    Russell, P. B.; Livingston, J. M.; Schmid, B.; Bergstrom, Robert A.; Hignett, P.; Hobbs, P. V.; Durkee, P. A.

    2000-01-01

    Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate In potentially significant ways. This aerosol radiative forcing is a major source of uncertainty in understanding the observed climate change of the past century and in predicting future climate. To help reduce this uncertainty, the International Global Atmospheric Chemistry Project (IGAC) has endorsed a series of multiplatform aerosol field campaigns. The Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the second Aerosol Characterization Experiment (ACE-2) were the first IGAC campaigns to address the impact of anthropogenic aerosols, Both TARFOX and ACE-2 gathered extensive data sets on aerosol properties and radiative effects, TARFOX focused on the urban-industrial haze plume flowing from the eastern United States over the western Atlantic Ocean, whereas ACE-2 studied aerosols carried over the eastern Atlantic from both European urban/industrial and African mineral sources. These aerosols often have a marked influence on the top-of-atmosphere radiances measured by satellites. Shown there are contours of aerosol optical depth derived from radiances measured by the AVHRR sensor on the NOAA-11 satellite. The contours readily show that aerosols originating in North America, Europe, and Africa impact the radiative properties of air over the North Atlantic. However, the accurate derivation of flux changes, or radiative forcing, from the satellite measured radiances or retrieved optical depths remains a difficult challenge. In this paper we summarize key initial results from TARFOX and, to a lesser extent, ACE-2, with a focus on those results that allow an improved assessment of the flux changes caused by North Atlantic aerosols at middle latitudes.

  20. Histotripsy Focal Ablation of Implanted Prostate Tumor in an ACE-1 Canine Cancer Model

    PubMed Central

    Schade, George R.; Keller, Jill; Ives, Kim; Cheng, Xu; Rosol, Thomas J.; Keller, Evan; Roberts, William W.

    2015-01-01

    Purpose Histotripsy is a nonthermal ablative focused ultrasound technology with possible future applications for prostate cancer focal therapy. We used the ACE-1 prostate tumor model and evaluated the feasibility of treating prostate tumors with histotripsy. Materials and Methods A total of 10 immunosuppressed (cyclosporine treated) canine subjects received transrectal ultrasound guided percutaneous intraprostatic injection of ACE-1 canine prostate cancer cells. Prostates were serially imaged with transrectal ultrasound to monitor tumor growth. Subjects were sham treated (3) or underwent transabdominal histotripsy of the prostate, which targeted implanted tumor and adjacent parenchyma using a 750 kHz piezoelectric ultrasound therapy transducer. Prostates were examined histologically to confirm tumor and the histotripsy treatment effect. Results ACE-1 tumors were visualized on transrectal ultrasound in all 10 subjects within 2 weeks of tumor injection. Lesions demonstrated growth in the prostatic capsule, glandular lobules, fibrous septa and periurethral stroma with significant desmoplastic reaction and areas of central necrosis on histology. Lymph node and/or pulmonary metastases developed in 4 subjects. Ultrasound tumor localization and initiation of cavitation during histotripsy therapy were feasible in all treated subjects. Histologically there was evidence of homogenization of tumor and prostatic parenchyma in all 4 acute subjects with necrosis and hemorrhage in the 3 chronic subjects. Conclusions This study shows the feasibility of histotripsy destruction of prostate tumors in a canine ACE-1 model. It suggests a potential role for histotripsy based focal therapy for prostate cancer. Further studies are needed to better characterize the effects of histotripsy on malignant tissues. PMID:22999534

  1. Association of ACE Gene I/D polymorphism with migraine in Kashmiri population

    PubMed Central

    Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A.; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

    2016-01-01

    Introduction: Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. Materials and Methods: The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Results: Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. Conclusion: We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine. PMID:27011636

  2. Wild Mushrooms in Nepal: Some Potential Candidates as Antioxidant and ACE-Inhibition Sources

    PubMed Central

    Hai Bang, Tran; Suhara, Hiroto; Doi, Katsumi; Ishikawa, Hiroya; Fukami, Katsuya; Parajuli, Gopal Prasad; Katakura, Yoshinori; Yamashita, Shuntaro; Watanabe, Kazuo; Adhikari, Mahesh Kumar; Manandhar, Hira Kaji; Kondo, Ryuichiro; Shimizu, Kuniyoshi

    2014-01-01

    Twenty-nine mushrooms collected in the mountainous areas of Nepal were analyzed for antioxidant activity by different methods, including Folin-Ciocalteu, ORAC, ABTS, and DPPH assays. Intracellular H2O2-scavenging activity was also performed on HaCaT cells. The results showed that phenolic compounds are the main antioxidant of the mushrooms. Among studied samples, Inonotus andersonii, and Phellinus gilvus exhibited very high antioxidant activity with the phenolic contents up to 310.8 and 258.7 mg GAE/g extracts, respectively. The H2O2-scavenging assay on cells also revealed the potential of these mushrooms in the prevention of oxidative stress. In term of ACE-inhibition, results showed that Phlebia tremellosa would be a novel and promising candidate for antihypertensive studies. This mushroom exhibited even higher in vitro ACE-inhibition activity than Ganoderma lingzhi, with the IC50 values of the two mushrooms being 32 μg/mL and 2 μg/mL, respectively. This is the first time biological activities of mushrooms collected in Nepal were reported. Information from this study should be a valuable reference for future studies on antioxidant and ACE-inhibitory activities of mushrooms. PMID:24672576

  3. Probing the Dayside Magnetosphere: Measurements by ACE Soon After Launch, August 25, 1997

    NASA Astrophysics Data System (ADS)

    Briggs, H.; Glines, T.; Farrugia, C. J.; Jordanova, V. K.; Smith, C. W.

    2004-12-01

    Spacecraft ACE was launched on Aug. 25, 1997. In this poster we shall examine magnetic field data obtained by this spacecraft as it crossed through the dayside magnetosphere, entered a region around the magnetosphere called the magnetosheath (twice), and eventually crossed a weak bow shock. Then it entered the interplanetary medium characterized by a slow solar wind and a lower-than-usual magnetic field. Another craft called WIND was making measurements inside the solar wind. In this presentation we shall investigate the various regions of the Earth's dayside magnetosphere and magnetosheath encountered by ACE, highlighting their different magnetic properties. Finally we make comparisons between ACE magnetic field data and WIND solar wind data. The work represents the efforts of two New Hampshire high school students who participated in the UNH program Project SMART during the summer of 2004. Project SMART is an E/PO effort run by UNH to bring gifted high school students into the research environment and to motivate them to pursue a scientific career.

  4. A 90-day subchronic toxicity study and reproductive toxicity studies on ACE-inhibiting lactotripeptide.

    PubMed

    Dent, M P; O'Hagan, S; Braun, W H; Schaetti, P; Marburger, A; Vogel, O

    2007-08-01

    In recent years there has been an increasing body of literature describing the antihypertensive effects of peptides produced from milk protein. The tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), isolated from hydrolysed casein have been shown to lower blood pressure by inhibiting angiotensin I-converting enzyme (ACE). This has led to the use of these tripeptides, collectively referred to as lactotripeptide (LTP) as ingredients of functional foods intended to help control blood pressure. A programme of studies including a 90-day repeat-dose oral gavage toxicity study in the rat and an embryo-fetal (pre-natal) development study in the rabbit was conducted to ensure the safety of this ACE-inhibiting ingredient. In addition, a non-standard pre- and post-natal development study in the rat was performed. This study included direct dosing of the neonates, and was designed specifically to investigate renal development and to ensure that the bioactive peptides were not associated with the same type of fetopathy exhibited by ACE inhibiting drugs. These studies showed that there were no adverse effects of treatment at the highest doses tested. PMID:17383063

  5. Representation of global inland water heights within the forthcoming ACE2 GDEM

    NASA Astrophysics Data System (ADS)

    Benveniste, Jerome; Smith, Richard G.; Berry, Philippa A. M.

    The SRTM dataset provides the first near-global elevation model of the earth's continental land surface at 3" resolution. This unique dataset is currently used for a range of applications. However, there are a number of known quirks and omissions in these data, for example voids over large inland water extents and errors in height attributed to river locations, for example where surrounding tree canopy has been measured. Accordingly, an enhanced full global elevation dataset, ACE2, is currently being developed as an ESA initiative, a follow-on to the highly successful ACE GDEM. This development is utilising over 67 million height measurements (derived from multi-mission satellite radar altimetry using an expert system approach) to validate, error correct and augment the SRTM dataset to derive a full global GDEM at 3 arc second resolution. This paper presents results obtained from a global investigation into the representation of inland water heights within current GDEMs, and demonstrates the potential to include not only accurate mean heights for inland water targets, but also to characterise the temporal variation utilising decadal timeseries obtained from multimission satellite radar altimetry. The first full release of the ACE2 GDEM is scheduled for later this year.

  6. Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities

    PubMed Central

    Abdullah, Noorlidah; Ismail, Siti Marjiana; Aminudin, Norhaniza; Shuib, Adawiyah Suriza; Lau, Beng Fye

    2012-01-01

    Considering the importance of diet in prevention of oxidative stress-related diseases including hypertension, this study was undertaken to evaluate the in vitro antioxidant and ACE inhibitory activities of selected culinary-medicinal mushrooms extracted by boiling in water for 30 min. Antioxidant capacity was measured using the following assays: DPPH free radical scavenging activity, β-carotene bleaching, inhibition of lipid peroxidation, reducing power ability, and cupric ion reducing antioxidant capacity (CUPRAC). Antioxidant potential of each mushroom species was calculated based on the average percentages relative to quercetin and summarized as Antioxidant Index (AI). Ganoderma lucidum (30.1%), Schizophyllum commune (27.6%), and Hericium erinaceus (17.7%) showed relatively high AI. Total phenolics in these mushrooms varied between 6.19 to 63.51 mg GAE/g extract. In the ACE inhibitory assay, G. lucidum was shown to be the most potent species (IC50 = 50 μg/mL). Based on our findings, culinary-medicinal mushrooms can be considered as potential source of dietary antioxidant and ACE inhibitory agents. PMID:21716693

  7. In situ Observations of CIRs on STEREO, Wind, and ACE During 2007 - 2008

    NASA Astrophysics Data System (ADS)

    Mason, G. M.; Desai, M. I.; Mall, U.; Korth, A.; Bucik, R.; von Rosenvinge, T. T.; Simunac, K. D.

    2009-05-01

    During the 2007 and 2008 solar minimum period, STEREO, Wind, and ACE observed numerous Corotating Interaction Regions (CIRs) over spatial separations that began with all the spacecraft close to Earth, through STEREO separation angles of ˜ 80 degrees in the fall of 2008. Over 35 CIR events were of sufficient intensity to allow measurement of He and heavy ion spectra using the IMPACT/SIT, EPACT/STEP and ACE/ULEIS instruments on STEREO, Wind, and ACE, respectively. In addition to differences between the spacecraft expected on the basis of simple corotation, we observed several events where there were markedly different time-intensity profiles from one spacecraft to the next. By comparing the energetic particle intensities and spectral shapes along with solar wind speed we examine the extent to which these differences are due to temporal evolution of the CIR or due to variations in connection to a relatively stable interaction region. Comparing CIRs in the 1996 - 1997 solar minimum period vs. 2007 - 2008, we find that the 2007 - 2008 period had many more CIRs, reflecting the presence of more high-speed solar wind streams, whereas 1997 had almost no CIR activity.

  8. Production of ACE inhibitory peptides from sweet sorghum grain protein using alcalase: Hydrolysis kinetic, purification and molecular docking study.

    PubMed

    Wu, Qiongying; Du, Jinjuan; Jia, Junqiang; Kuang, Cong

    2016-05-15

    In this study, sweet sorghum grain protein (SSGP) was hydrolyzed using alcalase yielding ACE inhibitory peptides. A kinetic model was proposed to describe the enzymolysis process of SSGP. The kinetic parameters, a and b, were determined according to experimental data. It was found that the model was reliable to describe the kinetic behaviour for SSGP hydrolysis by alcalase. After hydrolysis, the SSGP hydrolysate with DH of 19% exhibited the strongest ACE inhibitory activity and the hydrolysate was then used to isolate ACE inhibitory peptides. A novel ACE inhibitory peptide was successfully purified from this hydrolysate by ultrafiltration, ion exchange chromatography, gel filtration chromatography, and reversed-phased high performance liquid chromatography (RP-HPLC). The amino acid sequence of the purified peptide was identified as Thr-Leu-Ser (IC50=102.1 μM). The molecular docking studies revealed that the ACE inhibition of the tripeptide was mainly attributed to its C-terminal Ser, which can effectively interact with the S1 and S2 pockets of ACE. Our studies suggest that the tripeptide from the SSGP hydrolysate can be utilized to develop functional food ingredients or pharmaceuticals for prevention of hypertension. PMID:26775955

  9. Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress

    PubMed Central

    Rabelo, Luiza A.; Todiras, Mihail; Nunes-Souza, Valéria; Qadri, Fatimunnisa; Szijártó, István András; Gollasch, Maik; Penninger, Josef M.; Bader, Michael; Santos, Robson A.; Alenina, Natalia

    2016-01-01

    Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20–22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance. PMID:27070147

  10. Comparative effectiveness of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers in patients with type 2 diabetes and retinopathy

    PubMed Central

    Shih, Chia-Jen; Chen, Hung-Ta; Kuo, Shu-Chen; Li, Szu-Yuan; Lai, Pi-Hsiang; Chen, Shu-Chen; Ou, Shuo-Ming; Chen, Yung-Tai

    2016-01-01

    Background: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. Methods: We conducted a propensity score–matched cohort study using Taiwan’s National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. Results: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87–1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87–1.04), including myocardial infarction (HR 1.03, 95% CI 0.88–1.20), ischemic stroke (HR 0.94, 95% CI 0.85–1.04) and cardiovascular death (HR 1.01, 95% CI 0.88–1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91–1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86–1.18). Results were similar in as-treated analyses. Interpretation: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy. PMID:27001739

  11. Results from the SolACES instrument onboard the International Space Station (ISS)

    NASA Astrophysics Data System (ADS)

    Schmidtke, Gerhard; Eparvier, Francis; Brunner, Raimund; Woods, Thomas; Jacobi, Christoph; Thuillier, Gerard; Nikutowski, Bernd; Erhardt, Christian

    2012-07-01

    The SolACES instrument has to be seen in the context of more than 50 years of intensive research in EUV spectroscopy in space with solar, terrestrial and planetary airglow and auroral emissions included. The results from four years of solar spectral irradiance (SSI) recordings performed by SolACES will be presented. The first part will cover the instrumental performance with respect to the primary capability of frequent in-orbit re-calibration in the ISS environment. Among the advantages of the measuring system there are multiple instrumental possibilities to cross-check the results providing a high degree of reliability to the spectral irradiance derived. The results from an inter-comparison of the global TEC variability with modelled global TEC using TIMED/SEE and SolACES EUV data and modelled global TEC using F10.7 data will be presented beyond the last solar minimum. The correlation of global TEC data with models using EUV data is higher than the correlation of global TEC with models using F10.7. Deviations of the modelled global TEC data from the modelled ones with SSI EUV data are pointing to geomagnetic disturbances e.g. as caused by solar wind and coronal mass ejections (CMEs). Similar to the short-term recordings exhibiting different temporal intensity changes in phase and amplitude with wavelength also the long-term SSI data show temporal shifts with wavelength during the extended solar minimum 2008-2009. Data from the ISS SOLAR instruments SOLSPEC and SolACES are suggesting that each solar emission reaches its own solar minimum. Finally a proposal will be explained to develop SSI indices from the data acquired so far. For the spectral region from 121-400 nm the reconstruction of SSI indices could be performed using the Mg II index and neutron-monitor measurements. The data available from the latest and still on-going space missions could provide the data sets to cover the wavelength range shorter than 121 nm. The path of the data analysis and the results

  12. Comparison of In Situ Aerosol Data from the ACE-Asia 2001 Experiment

    NASA Astrophysics Data System (ADS)

    Knobelspiesse, K. D.; Pietras, C.; Miller, M. A.; Reynolds, R. M.; Frouin, R.; Quinn, P. K.; Deschamps, P. Y.; Werdell, P. J.; Fargion, G. S.

    2002-05-01

    The Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia) is an international, multidisciplinary project to further knowledge about atmospheric aerosols. ACE-Asia included an intensive field measurement campaign during the spring of 2001 off the coasts of China, Japan and Korea. The Sensor Intercomparison and Merger for Biological and Interdisciplinary Oceanic Studies (SIMBIOS) Project participated in the ACE-Asia cruise of the R/V Ronald H. Brown, which departed from Hawaii on 2001/03/15, sailed west to the Sea of Japan, and finished in Yokosuka, Japan on 2001/04/19. The SIMBIOS Project compares and merges data projects from multiple ocean color missions. As In Situ data are essential for merger and comparison of satellite ocean color measurements, the Project is interested in instrumentation devopment and data base building. The SeaWiFS Bio-optical Archive and Storage System (SeaBASS) is the database used and maintained by the SIMBIOS project. The ACE-Asia cruise was an excellent opportunity to compare data from a variety of maritime sun photometers, as several aerosol conditions were experienced. These included low Aerosol Optical Thickness (AOT) maritime conditions near Hawaii and extremely high AOT dust conditions in the Sea of Japan. Concurrant measurements were made with the PREDE POM-01 Mark II radiometer, a Laboratoire d'Optique Atmosphérique (LOA) SIMBAD, a Laboratorie d'Optique Atmosphérique (LOA) SIMBAD-a, two Solar Light, Inc. Microtops II's, and Brookhaven National Laboratory's Fast Rotating Shadowband Radiometer (FRSR). In addition, a Micro Pulse Lidar (MPL) was deployed that provides vertical aerosol distributions. Data were processed utilizing new algorithms to screen errors due to improper pointing at the sun, a problem previously recognized for the Microtops II. Comparisons of AOT at 500nm and Angstrom Exponent were made for all the instruments. The hand held, direct solar sun photometers (Microtops II, SIMBAD and SIMBADa

  13. A Coupled Programme of Aerosol Research Within the OP3 and ACES Projects

    NASA Astrophysics Data System (ADS)

    McFiggans, G.; Aces Aerosol Teams, P A

    2008-12-01

    The oxidation of organic compounds in the troposphere plays a central role in the generation of ozone, and leads to the formation of secondary organic aerosol (SOA) and other secondary pollutants. Approximately 90% of organic material emitted globally is estimated to originate from biogenic sources, with almost half of all reactive biogenic volatile organic compounds (BVOC) being emitted from tropical and sub-tropical forests. It is becoming increasingly clear from observational studies that biogenic SOA (BSOA) is the dominant source of aerosol organic carbon concentrations in remote environments. This provides part of the motivation for the OP3 project. Ground-based aerosol measurements at the Global Atmosphere Watch (GAW) site in Danum Valley Conservation Area in OP3 were provided by a suite of instrumentation for full composition and physical property characterisation (size distribution, hygroscopicity and CCN activation). To further enhance our understanding of aerosol processes in the Borneo rainforest, additional capability was assembled within the UK NERC funded "Aerosol Coupling in the Earth System" (ACES) programme. Field component enhancements to the OP3 aerosol payload by ACES included a deployment of aerosol and precursor flux measurements within the forest canopy to characterise primary bioaerosol sources and in-canopy chemistry leading to formation of secondary aerosol components. In addition, measurements of VOCs and aerosol composition were made above an oil palm plantation to assess the impact of land-use change on aerosol processes. ACES is a coupled programme of field, chamber, mechanism development and modelling investigations aiming to reduce uncertainties in our fundamental understanding of BSOA formation and the subsequent impact on atmospheric composition. In addition to summarising aerosol field measurements within ACES / OP3, we will present an overview of the status of the ACES chamber and modelling results with the overall aim to: i

  14. SP_Ace: a new code to derive stellar parameters and elemental abundances

    NASA Astrophysics Data System (ADS)

    Boeche, C.; Grebel, E. K.

    2016-03-01

    Context. Ongoing and future massive spectroscopic surveys will collect large numbers (106-107) of stellar spectra that need to be analyzed. Highly automated software is needed to derive stellar parameters and chemical abundances from these spectra. Aims: We developed a new method of estimating the stellar parameters Teff, log g, [M/H], and elemental abundances. This method was implemented in a new code, SP_Ace (Stellar Parameters And Chemical abundances Estimator). This is a highly automated code suitable for analyzing the spectra of large spectroscopic surveys with low or medium spectral resolution (R = 2000-20 000). Methods: After the astrophysical calibration of the oscillator strengths of 4643 absorption lines covering the wavelength ranges 5212-6860 Å and 8400-8924 Å, we constructed a library that contains the equivalent widths (EW) of these lines for a grid of stellar parameters. The EWs of each line are fit by a polynomial function that describes the EW of the line as a function of the stellar parameters. The coefficients of these polynomial functions are stored in a library called the "GCOG library". SP_Ace, a code written in FORTRAN95, uses the GCOG library to compute the EWs of the lines, constructs models of spectra as a function of the stellar parameters and abundances, and searches for the model that minimizes the χ2 deviation when compared to the observed spectrum. The code has been tested on synthetic and real spectra for a wide range of signal-to-noise and spectral resolutions. Results: SP_Ace derives stellar parameters such as Teff, log g, [M/H], and chemical abundances of up to ten elements for low to medium resolution spectra of FGK-type stars with precision comparable to the one usually obtained with spectra of higher resolution. Systematic errors in stellar parameters and chemical abundances are presented and identified with tests on synthetic and real spectra. Stochastic errors are automatically estimated by the code for all the parameters

  15. Angiotensin I–Converting Enzyme Type 2 (ACE2) Gene Therapy Improves Glycemic Control in Diabetic Mice

    PubMed Central

    Bindom, Sharell M.; Hans, Chetan P.; Xia, Huijing; Boulares, A. Hamid; Lazartigues, Eric

    2010-01-01

    OBJECTIVE Several clinical studies have shown the benefits of renin-angiotensin system (RAS) blockade in the development of diabetes, and a local RAS has been identified in pancreatic islets. Angiotensin I–converting enzyme (ACE)2, a new component of the RAS, has been identified in the pancreas, but its role in β-cell function remains unknown. Using 8- and 16-week-old obese db/db mice, we examined the ability of ACE2 to alter pancreatic β-cell function and thereby modulate hyperglycemia. RESEARCH DESIGN AND METHODS Both db/db and nondiabetic lean control (db/m) mice were infected with an adenovirus expressing human ACE2 (Ad-hACE2-eGFP) or the control virus (Ad-eGFP) via injection into the pancreas. Glycemia and β-cell function were assessed 1 week later at the peak of viral expression. RESULTS In 8-week-old db/db mice, Ad-hACE2-eGFP significantly improved fasting glycemia, enhanced intraperitoneal glucose tolerance, increased islet insulin content and β-cell proliferation, and reduced β-cell apoptosis compared with Ad-eGFP. ACE2 overexpression had no effect on insulin sensitivity in comparison with Ad-eGFP treatment in diabetic mice. Angiotensin-(1–7) receptor blockade by d-Ala7–Ang-(1-7) prevented the ACE2-mediated improvements in intraperitoneal glucose tolerance, glycemia, and islet function and also impaired insulin sensitivity in both Ad-hACE2-eGFP– and Ad-eGFP–treated db/db mice. d-Ala7–Ang-(1-7) had no effect on db/m mice. In 16-week-old diabetic mice, Ad-hACE2-eGFP treatment improved fasting blood glucose but had no effect on any of the other parameters. CONCLUSIONS These findings identify ACE2 as a novel target for the prevention of β-cell dysfunction and apoptosis occurring in type 2 diabetes. PMID:20660625

  16. Bone Mineral Density Changes Among Women Initiating Blood Pressure Lowering Drugs: A SWAN Cohort Study

    PubMed Central

    Solomon, Daniel H.; Ruppert, Kristine; Zhao, Zhenping; Lian, YinJuan; Kuo, I-Hsin; Greendale, Gail A.; Finkelstein, Joel S.

    2016-01-01

    Purpose Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women’s Health Across the Nation. Methods We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14-years of observation were compared with non-users. Results Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of non-users. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (−0.28% vs −0.88%; p = 0.008) and the spine (−0.74% vs −1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in non-users. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (−0.35% vs −0.60%; p = 0.08) and a similar trend at the FN (−0.39% vs −0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (−0.48% vs −0.82%; p = 0.02), but not at the spine (−0.40% vs −0.56%; p = 0.23). Conclusions Neither ACEi nor BB were associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with non-users, as well as compared with ACEi and BB. PMID:26449354

  17. Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor.

    PubMed Central

    Telford, S E; Smith, A I; Lew, R A; Perich, R B; Madden, A C; Evans, R G

    1995-01-01

    1. We investigated the role of angiotensin converting enzyme (ACE) in the cardiovascular effects of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), a peptidase inhibitor selective for metalloendopeptidase (EP) E.C. 3.4.24.15. 2. In conscious rabbits, cFP (5 mg kg-1, i.v.) markedly slowed the degradation of [3H]-bradykinin, potentiated the depressor response to right atrial administration of bradykinin (10-1000 ng kg-1), and inhibited the pressor response to right atrial angiotensin I (10-100 ng kg-1). In each of these respects, the effects of cFP were indistinguishable from those of the ACE inhibitor, captopril (0.5 mg plus 10 mg kg-1h-1 i.v.). Furthermore, the effects of combined administration of cFP and captopril were indistinguishable from those of captopril alone. 3. In experimentally naive anaesthetized rats, cFP administration (9.3 mg kg-1, i.v.) was followed by a moderate but sustained fall in arterial pressure of 13 mmHg. However, in rats pretreated with bradykinin (50 micrograms kg-1) a more pronounced fall of 30 mmHg was observed. Captopril (5 mg kg-1) had similar hypotensive effects to those of cFP, and cFP had no effect when it was administered after captopril. 4. CFP displaced the binding of [125I]-351A (the p-hydroxybenzamidine derivative of lisinopril) from preparations of rat plasma ACE and solubilized lung membrane ACE (KD = 1.2 and 0.14 microM respectively), and inhibited rat plasma ACE activity (KI = 2.4 microM). Addition of phosphoramidon (10 microM), an inhibitor of a range of metalloendopeptidases, including neutral endopeptidase (E.C.3.4.24.11), markedly reduced the potency of cFP in these systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7620708

  18. The Evaluation of Dipeptidyl Peptidase (DPP)-IV, α-Glucosidase and Angiotensin Converting Enzyme (ACE) Inhibitory Activities of Whey Proteins Hydrolyzed with Serine Protease Isolated from Asian Pumpkin (Cucurbita ficifolia).

    PubMed

    Konrad, Babij; Anna, Dąbrowska; Marek, Szołtysik; Marta, Pokora; Aleksandra, Zambrowicz; Józefa, Chrzanowska

    2014-01-01

    In the present study, whey protein concentrate (WPC-80) and β-lactoglobulin were hydrolyzed with a noncommercial serine protease isolated from Asian pumpkin (Cucurbita ficifolia). Hydrolysates were further fractionated by ultrafiltration using membranes with cut-offs equal 3 and 10 kDa. Peptide fractions of molecular weight lower than 3 and 3-10 kDa were further subjected to the RP-HPLC. Separated preparations were investigated for their potential as the natural inhibitors of dipeptidyl peptidase (DPP-IV), α-glucosidase and angiotensin converting enzyme (ACE). WPC-80 hydrolysate showed higher inhibitory activities against the three tested enzymes than β-lactoglobulin hydrolysate. Especially high biological activities were exhibited by peptide fractions of molecular weight lower than 3 kDa, with ACE IC50 <0.64 mg/mL and DPP-IV IC50 <0.55 mg/mL. This study suggests that peptides generated from whey proteins may support postprandial glycemia regulation and blood pressure maintenance, and could be used as functional food ingredients in the diet of patients with type 2 diabetes. PMID:25364320

  19. Advancements in the safe identification of explosives using a Raman handheld instrument (ACE-ID)

    NASA Astrophysics Data System (ADS)

    Arnó, Josep; Frunzi, Michael; Kittredge, Marina; Sparano, Brian

    2014-05-01

    Raman spectroscopy is the technology of choice to identify bulk solid and liquid phase unknown samples without the need to contact the substance. Materials can be identified through transparent and semi-translucent containers such as plastic and glass. ConOps in emergency response and military field applications require the redesign of conventional laboratory units for: field portability; shock, thermal and chemical attack resistance; easy and intuitive use in restrictive gear; reduced size, weight, and power. This article introduces a new handheld instrument (ACE-IDTM) designed to take Raman technology to the next level in terms of size, safety, speed, and analytical performance. ACE-ID is ruggedized for use in severe climates and terrains. It is lightweight and can be operated with just one hand. An intuitive software interface guides users through the entire identification process, making it easy-to-use by personnel of different skill levels including military explosive ordinance disposal technicians, civilian bomb squads and hazmat teams. Through the use of embedded advanced algorithms, the instrument is capable of providing fluorescence correction and analysis of binary mixtures. Instrument calibration is performed automatically upon startup without requiring user intervention. ACE-ID incorporates an optical rastering system that diffuses the laser energy over the sample. This important innovation significantly reduces the heat induced in dark samples and the probability of ignition of susceptible explosive materials. In this article, the explosives identification performance of the instrument will be provided in addition to a quantitative evaluation of the safety improvements derived from the reduced ignition probabilities.

  20. Dust Aerosols at the Source Region During ACE-ASIA: A Surface/Satellite Perspective

    NASA Technical Reports Server (NTRS)

    Tsay, Si-Chee; Lau, William K. M. (Technical Monitor)

    2001-01-01

    ACE (Aerosol Characterization Experiment)-Asia is designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally occurring aerosols, which often exist in high concentrations over eastern Asia and along the rim of the western Pacific. The phase-I of ACE-Asia was conducted from March-May 2001 in the vicinity of the Gobi desert, East Coast of China, Yellow Sea, Korea, and Japan, along the pathway of Kosa (severe events that blanket East Asia with yellow desert dust, peaked in the Spring season). Asian dust typically originates in desert areas far from polluted urban regions. During transport, dust layers can interact with anthropogenic sulfate and soot aerosols from heavily polluted urban areas. Added to the complex effects of clouds and natural marine aerosols, dust particles reaching the marine environment can have drastically different properties than those from the source. Thus, understanding the unique temporal and spatial variations of Asian dust is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the mid-Pacific Ocean. During ACE-Asia we have measured continuously aerosol physical/optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from surface. The inclusion of flux measurements permits the determination of dust aerosol radiative flux in addition to measurements of loading and optical thickness. At the time of the Terra/MODIS, SeaWiFS, TOMS and other satellite overpasses, these ground-based observations can provide valuable data to compare with satellite retrievals over land. Preliminary results will be presented and discussed their implications in regional climatic effects.

  1. ACE gene insertion/deletion polymorphism modulates capillary permeability in hypertension.

    PubMed

    Dell'omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Fotino, Carmen; Del Prato, Stefano; Pedrinelli, Roberto

    2006-12-01

    A D/D (deletion/deletion) polymorphism within the ACE (angiotensin 1-converting enzyme) gene increases the risk of microalbuminuria, a predictor of atherosclerotic vascular disease, in essential hypertension. It is unknown, however, whether this genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of generalized endothelial dysfunction. In the present study, the ACE gene polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive men and 16 normotensive men as controls. Evaluation variables were TERalb (transcapillary escape rate of albumin; the 1-h decline rate of intravenous (125)I-albumin, a measure of integrity of systemic capillary endothelium), albuminuria and forearm vasodilation to intra-arterial acetylcholine, an index of NO (nitric oxide)-mediated vasomotion, in addition to a series of sensitive parameters of albumin permeation (blood pressure, metabolic status and smoking habits). Analyses were done by comparing D/D homozygotes with grouped I/D (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in D/D hypertensives, who had higher albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial acetylcholine. Fasting glucose and insulin, insulin sensitivity, 24-h blood pressure, smoking habits and metabolic parameters did not differ between the two groups. TERalb and urine albumin values were positively associated in the hypertensive subjects. In conclusion, ACE D/D homozygosis, independently of several confounding factors, associates with higher TERalb in men with essential hypertension. This may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for atherogenesis in the absence of grossly impaired NO-mediated arteriolar responsiveness. The parallel behaviour of TERalb and albuminuria suggests some shared genetically mediated determinant of renal

  2. Characterization of Dust Properties at the Source Region During ACE-Asia

    NASA Technical Reports Server (NTRS)

    Tsay, Si-Chee; Lau, William (Technical Monitor)

    2001-01-01

    ACE (Aerosol Characterization Experiment)-Asia is designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally-occurring aerosols, which often exist in high concentrations over eastern Asia and along the rim of the western Pacific. The phase-I of ACE-Asia was conducted from March-May 2001 in the vicinity of the Gobi desert, east coast of China, Yellow Sea, Korea, and Japan, along the pathway of Kosa (severe events that blanket East Asia with yellow desert dust, peaked in the Spring season). Asian dust typically originates in desert areas far from polluted urban regions. During transport, dust layers can interact with anthropogenic sulfate and soot aerosols from heavily polluted urban areas. Added to the complex effects of clouds and natural marine aerosols, dust particles reaching the marine environment can have drastically different properties than those from the source. Thus, understanding the unique temporal and spatial variations of Asian dust is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the mid-Pacific Ocean. During ACE-Asia we have measured continuously aerosol optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from surface. The inclusion of flux measurements permits the determination of dust aerosol radiative flux in addition to measurements of loading and optical thickness. At the time of the Terra/MODIS overpass, these ground-based observations can provide valuable data to compare with MODIS retrievals over land. Preliminary results will be presented and discussed their implications in regional climatic effects.

  3. A Global Aerosol Model Forecast for the ACE-Asia Field Experiment

    NASA Technical Reports Server (NTRS)

    Chin, Mian; Ginoux, Paul; Lucchesi, Robert; Huebert, Barry; Weber, Rodney; Anderson, Tad; Masonis, Sarah; Blomquist, Byron; Bandy, Alan; Thornton, Donald

    2003-01-01

    We present the results of aerosol forecast during the Aerosol Characterization Experiment (ACE-Asia) field experiment in spring 2001, using the Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport (GOCART) model and the meteorological forecast fields from the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The aerosol model forecast provides direct information on aerosol optical thickness and concentrations, enabling effective flight planning, while feedbacks from measurements constantly evaluate the model, making successful model improvements. We verify the model forecast skill by comparing model predicted total aerosol extinction, dust, sulfate, and SO2 concentrations with those quantities measured by the C-130 aircraft during the ACE-Asia intensive operation period. The GEOS DAS meteorological forecast system shows excellent skills in predicting winds, relative humidity, and temperature for the ACE-Asia experiment area as well as for each individual flight, with skill scores usually above 0.7. The model is also skillful in forecast of pollution aerosols, with most scores above 0.5. The model correctly predicted the dust outbreak events and their trans-Pacific transport, but it constantly missed the high dust concentrations observed in the boundary layer. We attribute this missing dust source to the desertification regions in the Inner Mongolia Province in China, which have developed in recent years but were not included in the model during forecasting. After incorporating the desertification sources, the model is able to reproduce the observed high dust concentrations at low altitudes over the Yellow Sea. Two key elements for a successful aerosol model forecast are correct source locations that determine where the emissions take place, and realistic forecast winds and convection that determine where the aerosols are transported. We demonstrate that our global model can not only account for the large

  4. No association of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension.

    PubMed

    Benjafield, Adam V; Wang, William Y S; Morris, Brian J

    2004-07-01

    Recent intriguing findings from genetic linkage, knockout, and physiologic studies in mice and rats led us to conduct the first investigation of the novel angiotensin-converting enzyme 2 gene (ACE2) in human hypertension (HT). We genotyped four single nucleotide polymorphisms (SNP) (A-->G at nucleotide 1075 in intron 1, G-->A at nucleotide 8790 in intron 3, C-->G at nucleotide 28330 in intron 11, and G-->C at nucleotide 36787 in intron 16) in HT (n = 152) and normotensive (NT, n = 193) groups having inherently high biological power (>80%) due to our inclusion only of subjects whose parents had the same BP status as themselves. The SNPs were in linkage disequilibrium (D' = 54% to 100%, P =.05 to 0.0001). Because ACE2 is on the X chromosome, data for each sex were analyzed separately. Minor allele frequencies in HT versus NT were as follows: for the intron 1 variant 0.21 versus 0.17 in female subjects (P =.31) and 0.25 versus 0.29 in male subjects (P =.60); intron 3 variant 0.22 versus 0.18 in female subjects (P =.35) and 0.15 versus 0.20 in male subjects (P =.47); intron 11 variant 0.39 versus 0.46 in male subjects (P = 0.17) and 0.31 versus 0.30 in male subjects (P =.96); intron 16 variant 0.20 versus 0.19 in female subjects (P =.72) and 0.17 versus 0.17 in male subjects (P =.95). Haplotype analysis was also negative. These data provide little support for ACE2 in genetic predisposition to HT. PMID:15233982

  5. The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training.

    PubMed

    Erskine, R M; Williams, A G; Jones, D A; Stewart, C E; Degens, H

    2014-08-01

    Alternative measures of muscle size, strength, and power to those used in previous studies could help resolve the controversy surrounding associations between polymorphisms of the angiotensin-I converting enzyme (ACE) and α-actinin-3 (ACTN3) genes and skeletal muscle phenotypes, and the responses to resistance training (RT). To this end, we measured quadriceps femoris muscle volume (Vm), physiological cross-sectional area (PCSA), maximum isometric force (Ft), specific force (Ft per unit PCSA), maximum isoinertial strength (1-RM), and maximum power (Wmax ; n = 40) before and after 9-week knee extension RT in 51 previously untrained young men, who were genotyped for the ACE I/D and ACTN3 R577X polymorphisms. ACTN3 R-allele carriers had greater Vm, 1-RM, and Wmax than XX homozygotes at baseline (all P < 0.05), but responses to RT were independent of ACTN3 genotype (all P > 0.05). Muscle phenotypes were independent of ACE genotype before (all P > 0.05) and after RT (all P > 0.01). However, people with the "optimal" ACE+ACTN3 genotype combination had greater baseline 1-RM and Wmax compared to those with the "suboptimal" profile (both P < 0.0125). We show for the first time that the ACTN3 R577X polymorphism is associated with human Vm and (independently and in combination with the ACE I/D polymorphism) influences 1-RM and Wmax. PMID:23384112

  6. ACE1, a copper-dependent transcription factor, activates expression of the yeast copper, zinc superoxide dismutase gene.

    PubMed Central

    Gralla, E B; Thiele, D J; Silar, P; Valentine, J S

    1991-01-01

    Copper, zinc superoxide dismutase (SOD1 gene product) (superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a copper-containing enzyme that functions to prevent oxygen toxicity. In the yeast Saccharomyces cerevisiae, copper levels exert some control over the level of SOD1 expression. We show that the ACE1 transcriptional activator protein, which is responsible for the induction of yeast metallothionein (CUP1) in response to copper, also controls the SOD1 response to copper. A single binding site for ACE1 is present in the SOD1 promoter region, as demonstrated by DNase I protection and methylation interference experiments, and is highly homologous to a high-affinity ACE1 binding site in the CUP1 promoter. The functional importance of this DNA-protein interaction is demonstrated by the facts that (i) copper induction of SOD1 mRNA does not occur in a strain lacking ACE1 and (ii) it does not occur in a strain containing a genetically engineered SOD1 promoter that lacks a functional ACE1 binding site. Images PMID:1924315

  7. Proton pump inhibitors

    MedlinePlus

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by glands in ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a ...

  8. Compounds from Epilobium angustifolium inhibit the specific metallopeptidases ACE, NEP and APN.

    PubMed

    Kiss, Anna; Kowalski, Józef; Melzig, Matthias F

    2004-10-01

    Willow herb (Epilobium angustifolium L.) extracts showed inhibitory activity against the metallopeptidases: neutral endopeptidase (NEP), angiotensin-converting enzyme (ACE), and aminopeptidase N (APN). A bioassay-guided fractionation led to the isolation of several flavonoids and phenolic acids and an ellagitannin. The dimeric macrocyclic ellagitannin oenothein B inhibited the neutral endopeptidases in a dose-dependent manner with IC50 = 20 microM. Other polyphenols showed weaker activity but their synergistic activity cannot be excluded. Taking into account the role of these peptidases in prostate diseases, the results may partly support and explain the use of Epilobium extracts in folk medicine. PMID:15490319

  9. SP.ACE: taking secondary school students' hearts and minds "up, up and away"

    NASA Astrophysics Data System (ADS)

    de Schrijver, Erik

    2005-08-01

    Secondary school students were given the opportunity to build and fly "pongsats" (small experiments weighing under 100 grams each, and packed inside a ping pong ball) on high-altitude balloons bound for 100000 feet, or 30 km: the edge of space. The need to acquire the knowledge and know-how to build successful experiments gave birth to the SP.ACE project. Over their last 3 years of secondary education, students are now learning about flight vehicles, the physical conditions in space, microcontrollers, sensors, programming, data logging, flight path analysis, and much more.

  10. Final Overview of ACES Simulation for Evaluation SARP Well-Clear Definitions

    NASA Technical Reports Server (NTRS)

    Santiago, Confesor; Johnson, Marcus A.; Isaacson, Doug; Hershey, David

    2014-01-01

    The UAS in the NAS project is studying the minimum operational performance standards for unmanned aerial systems (UAS's) detect-and-avoid (DAA) system in order to operate in the National Airspace System. The DoD's Science and research Panel (SARP) Well-Clear Workshop is investigating the time and spatial boundary at which an UAS violates well-clear. NASA is supporting this effort through use of its Airspace Concept Evaluation System (ACES) simulation platform. This briefing presents the final results to the SARP, which will be used to judge the three candidate well-clear definitions, and for the selection of the most operationally suitable option.

  11. Heavy Ion Flux Comparison of MARIE and ACE/CRIS Instruments

    NASA Technical Reports Server (NTRS)

    Lee, K. T.; Andersen, V.; Atwell, W.; Cleghorn, T.; Cucinotta, F.; Pinsky, L.; Saganti, P.; Turner, R.; Zeitlin, C.

    2003-01-01

    The charged particle spectrum for nuclei from protons to neon, (charge Z=10) has been observed during the cruise phase and in orbit around Mars by the MARIE charge particle spectrometer aboard the Odyssey spacecraft. The cruise data was taken between April 23, 2001 and August 11, 2001. The Mars orbit data was taken from March 5, 2002 through December 2002. Both the cruise data set and the orbital data set are compared with the simultaneous observations made by the CRIS instrument aboard the ACE space-craft, located at L1. Any detectable differences between the two spacecraft data sets could lead to the understanding of the radial dependence of solar modulation.

  12. SOHO/ACE observations of two consecutive CMEs from the same source region

    NASA Astrophysics Data System (ADS)

    Schettino, G.; Dasso, S.; Mandrini, C. H.; Poletto, G.; Romoli, M.

    2010-03-01

    On June 2, 2003, SOHO/LASCO coronagraph observed two CMEs at the West limb of the Sun, at 00.30 and 08:54 UT, respectively, which appeared to originate from the same source region. Both CMEs show the typical three-part structure. These events have been also observed by SOHO/UVCS, allowing us to infer their physical parameters. We also looked for interplanetary signatures of the CMEs in ACE `in situ' observations but we did not find evidence of the ejected flux rope; however, the solar wind appeared significantly distorted, probably as a consequence of the influence of both CMEs on their surrounding interplanetary plasma.

  13. Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function

    PubMed Central

    Becerra-Tomás, Nerea; Guasch-Ferré, Marta; Quilez, Joan; Merino, Jordi; Ferré, Raimon; Díaz-López, Andrés; Bulló, Mònica; Hernández-Alonso, Pablo; Palau-Galindo, Antoni; Salas-Salvadó, Jordi

    2015-01-01

    Abstract Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function. A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained. After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and −0.63 mm Hg in diastolic BP for CB; −0.71 mm Hg in systolic BP and −1.08 mm Hg in diastolic BP for LSB; and −0.75 mm Hg in systolic BP and −2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters. Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the

  14. Effects of angiotensin-converting enzyme inhibitors and beta blockers on clinical outcomes in patients with and without coronary artery obstructions at angiography (from a Register-Based Cohort Study on Acute Coronary Syndromes).

    PubMed

    Manfrini, Olivia; Morrell, Christine; Das, Rajiv; Barth, Julian H; Hall, Alistair S; Gale, Christopher P; Cenko, Edina; Bugiardini, Raffaele

    2014-05-15

    We sought to determine the effectiveness of angiotensin-converting enzyme (ACE) inhibition and β-blocker treatment as a function of the degree of coronary artery disease (CAD) obstruction at angiography. The Evaluation of Methods and Management of Acute Coronary Events registry enrolled patients who had been hospitalized for an acute coronary syndrome. There were 1,602 patients who had cardiac catheterization that were used for this analysis. The main outcome measures were evidence-based therapies prescribed at discharge and 6-month incidence of all-cause mortality. The cohort consisted of 1,252 patients with obstructive CAD (>50% luminal diameter obstructed) and 350 patients with nonobstructive CAD. Multivariate logistic regression analysis adjusted for further medications and other clinical factors was performed. Patients with nonobstructive CAD had significantly (p <0.001) higher rates of β-blocker (77.8% vs 63.3%) and lower rates of ACE-inhibitor (57.7% vs 66.4%) prescriptions. In patients with nonobstructive CAD, ACE-inhibitor therapy was clearly associated with a lower 6-month mortality (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.03 to 0.78, p = 0.004). No significant association between β-blocker use and death was found. In patients with obstructive CAD, both β blockers (OR 0.47, 95% CI 0.32 to 0.67, p <0.001) and ACE inhibitors (OR 0.47, 95% CI 0.26 to 0.87, p = 0.01) were significantly associated with a reduced risk of 6-month mortality. In conclusion, ACE-inhibitor therapy seems to be an effective first-line treatment for preventing the occurrence of mortality in patients with nonobstructive CAD. PMID:24698468

  15. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects.

    PubMed

    Uchida, Naoki; Sambe, Takehiko; Yoneyama, Koichiro; Fukazawa, Naoki; Kawanishi, Takehiko; Kobayashi, Shinichi; Shima, Midori

    2016-03-31

    ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to receive a single subcutaneous injection of ACE910 (Japanese: 0.001, 0.01, 0.1, 0.3, or 1 mg/kg; white: 0.1, 0.3, or 1 mg/kg; n = 6 per dose group) or placebo (n = 2 per dose group). ACE910 exhibited a linear PK profile and had a half-life of ∼4 to 5 weeks. In FVIII-neutralized plasma, ACE910 shortened activated partial thromboplastin time and increased peak height of thrombin generation in a dose-dependent manner. All adverse events were nonserious and did not lead to any subject's withdrawal. Neither clinical findings nor laboratory abnormalities indicating hypercoagulability were observed. Two of 48 subjects receiving ACE910 (1 Japanese and 1 white) were positive for anti-ACE910 antibodies (anti-drug antibodies [ADAs]). One subject tested positive for ADAs both before and after ACE910 administration, whereas the other became ADA positive after receiving ACE910. The PK and PD profiles of ACE910 were similar in healthy Japanese and white subjects and suggest that ACE910 will be an effective and convenient prophylactic treatment of hemophilia A. This trial was registered at www.clinicaltrials.jp as #JapicCTI-121934. PMID:26626991

  16. A first-in-human phase 1 study of ACE910, a novel factor VIII–mimetic bispecific antibody, in healthy subjects

    PubMed Central

    Uchida, Naoki; Sambe, Takehiko; Yoneyama, Koichiro; Fukazawa, Naoki; Kawanishi, Takehiko; Kobayashi, Shinichi

    2016-01-01

    ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to receive a single subcutaneous injection of ACE910 (Japanese: 0.001, 0.01, 0.1, 0.3, or 1 mg/kg; white: 0.1, 0.3, or 1 mg/kg; n = 6 per dose group) or placebo (n = 2 per dose group). ACE910 exhibited a linear PK profile and had a half-life of ∼4 to 5 weeks. In FVIII-neutralized plasma, ACE910 shortened activated partial thromboplastin time and increased peak height of thrombin generation in a dose-dependent manner. All adverse events were nonserious and did not lead to any subject’s withdrawal. Neither clinical findings nor laboratory abnormalities indicating hypercoagulability were observed. Two of 48 subjects receiving ACE910 (1 Japanese and 1 white) were positive for anti-ACE910 antibodies (anti-drug antibodies [ADAs]). One subject tested positive for ADAs both before and after ACE910 administration, whereas the other became ADA positive after receiving ACE910. The PK and PD profiles of ACE910 were similar in healthy Japanese and white subjects and suggest that ACE910 will be an effective and convenient prophylactic treatment of hemophilia A. This trial was registered at www.clinicaltrials.jp as #JapicCTI-121934. PMID:26626991

  17. ACE Act

    THOMAS, 112th Congress

    Rep. Polis, Jared [D-CO-2

    2011-12-01

    03/29/2012 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  18. ACE Troubleshooter.

    ERIC Educational Resources Information Center

    Collison, Michelle N-K

    2000-01-01

    Reports on the appointment of William B. Harvey as the new head of the American Council of Education's Office of Minorities in Higher Education. Notes the high expectations for Harvey, his goal of increasing partnerships between postsecondary and K-12 educational institutions, and his ideas for utilizing the Council's annual minority status…

  19. ACE Act

    THOMAS, 113th Congress

    Rep. Thompson, Glenn [R-PA-5

    2013-07-11

    09/13/2013 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  20. Use of β-Blockers, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Risk of Breast Cancer Recurrence: A Danish Nationwide Prospective Cohort Study

    PubMed Central

    Sørensen, Gitte Vrelits; Ganz, Patricia A.; Cole, Steven W.; Pedersen, Lars A.; Toft Sørensen, Henrik; Cronin-Fenton, Deirdre P.; Peter Garne, Jens; Christiansen, Peer M.; Lash, Timothy L.; Ahern, Thomas P.

    2013-01-01

    Purpose To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort. Patients and Methods We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year. Results Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3). Conclusion Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk. PMID:23650417

  1. Lack of Association Between ACE Indel Polymorphism and Cardiorespiratory Fitness in Physically Active and Sedentary Young Women

    PubMed Central

    Verlengia, Rozangela; Rebelo, Ana C.; Crisp, Alex H.; Kunz, Vandeni C.; dos Santos Carneiro Cordeiro, Marco A.; Hirata, Mario H.; Crespo Hirata, Rosario D.; Silva, Ester

    2014-01-01

    Background: Polymorphisms at the angiotensin-converting enzyme gene (ACE), such as the indel [rs1799752] variant in intron 16, have been shown to be associated with aerobic performance of athletes and non-athletes. However, the relationship between ACE indel polymorphism and cardiorespiratory fitness has not been always demonstrated. Objectives: The relationship between ACE indel polymorphism and cardiorespiratory fitness was investigated in a sample of young Caucasian Brazilian women. Patients and Methods: This study investigated 117 healthy women (aged 18 to 30 years) who were grouped as physically active (n = 59) or sedentary (n = 58). All subjects performed an incremental exercise test (ramp protocol) on a cycle-ergometer with 20-25 W/min increments. Blood samples were obtained for DNA extraction and to analyze metabolic and hormonal profiles. ACE indel polymorphism was determined by polymerase chain reaction (PCR) and fragment size analysis. Results: The physically active group had higher values of peak oxygen uptake (VO2 peak), carbon dioxide output (VCO2), ventilation (VE) and power output than the sedentary group (P < 0.05) at the peak of the exercise test. However, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not differ between groups. There was no relationship between ACE indel polymorphism and cardiorespiratory variables during the test in both the physically active and sedentary groups, even when the dominant (DD vs. D1 + 2) and recessive (2 vs. DI + DD) models of inheritance were tested. Conclusions: These results do not support the concept that the genetic variation at the ACE locus contributes to the cardiorespiratory responses at the peak of exercise test in physically active or sedentary healthy women. This indicates that other factors might mediate these responses, including the physical training level of the women. PMID:25520764

  2. Validation of ACE-FTS satellite data in the upper troposphere/lower stratosphere (UTLS) using non-coincident measurements

    NASA Astrophysics Data System (ADS)

    Hegglin, M. I.; Bernath, P. F.; Boone, C. D.; Daffer, W. H.; Hoor, P.; Manney, G. L.; Schiller, C.; Strong, K.; Walker, K. A.

    2007-09-01

    CO, O3, and H2O data in the upper troposphere/lower stratosphere (UTLS) measured by the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) on Canada's SCISAT-1 satellite are validated using aircraft measurements. In the UTLS, validation of chemical trace gas measurements is a challenging task due to small-scale variability in the tracer fields, strong gradients of the tracers across the tropopause, and scarcity of measurements suitable for validation purposes. Two alternative methods for the validation of the satellite data are introduced, which avoid the usual need for coincident measurements: tracer-tracer correlations, and vertical profiles relative to the tropopause height. Both largely reduce geophysical variability and thereby provide an "instantaneous climatology", allowing measurement comparison with non-coincident data which yields information about the precision, and a statistically meaningful error-assessment of the ACE-FTS satellite data. We found that the ACE-FTS CO and lower stratospheric O3 agree with the aircraft measurements within ±10% and ±5%, respectively. The ACE-FTS O3 in the UT exhibits a high bias of up to 40%. H2O indicates a low bias with relative differences of around 20% in the LS and 40% in the UT, respectively. When taking into account the smearing effect of the vertically limited spacing between measurements of the ACE-FTS instrument, the errors decrease by 5-15% around the tropopause. The ACE-FTS instrument hence offers unprecedented precision and vertical resolution in the UTLS, that will allow a new global perspective on UTLS tracer distributions.

  3. Association of plasminogen activator inhibitor-1 and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women

    PubMed Central

    Shakarami, Fatemeh; Akbari, Mohammad Taghi; Zare Karizi, Shohreh

    2015-01-01

    Background: Recurrent pregnancy loss (RPL) defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two) were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I) polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%), and 5 controls (5%) (p=0.006) so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84). In addition, 7 patients (7 %), and no one from the control group, were homozygote (I/I) for ACE polymorphism (p=0.034), suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL. PMID:26644791

  4. Auroral Current and Electrodynamics Structure (ACES) Observations of Ionospheric Feedback in the Alfven Resonator

    NASA Technical Reports Server (NTRS)

    Cohen, Ian J.; Lessard, Marc; Lund, Eric J.; Bounds, Scott R.; Kletzing, Craig; Kaeppler, Stephen R.; Sigsbee, Kristine M.; Streltsov, Anatoly V.; Labelle, James W.; Dombrowski, Micah P.; Pfaff, Robert F.; Rowland, Doug; Jones, Sarah; Anderson, Brian Jay; Heinselman, Craig J.; Gjerloev, Jesper W.; Dudok de Wit, Thierry

    2011-01-01

    In 2009, the Auroral Current and Electrodynamics Structure (ACES) High and Low sounding rockets were launched from the Poker Flat Rocket Range (PFRR) in Alaska, with the science objective of gathering in-situ data to quantify current closure in a discrete auroral arc. As ACES High crossed through the return current of an arc (that was monitored using an all sky camera from the ground at Fort Yukon), its instruments recorded clear Alfv nic signatures both poleward and equatorward of the return current region, but not within the main region of the return current itself. These data provide an excellent opportunity to study ionospheric feedback and how it interacts with the Alfv n resonator. We compare the observations with predictions and new results from a model of ionospheric feedback in the ionospheric Alfv n resonator (IAR) and report the significance and impact of these new data for the Magnetosphere-Ionosphere Coupling in the Alfv n Resonator (MICA) rocket mission to launch from PFRR this winter. MICA s primary science objectives specifically focus on better understanding the small-scale structure that the model predicts should exist within the return current region.

  5. Airborne Polarimeter Intercomparison for the NASA Aerosols-Clouds-Ecosystems (ACE) Mission

    NASA Technical Reports Server (NTRS)

    Knobelspiesse, Kirk; Redemann, Jens

    2014-01-01

    The Aerosols-Clouds-Ecosystems (ACE) mission, recommended by the National Research Council's Decadal Survey, calls for a multi-angle, multi-spectral polarimeter devoted to observations of atmospheric aerosols and clouds. In preparation for ACE, NASA funds the deployment of airborne polarimeters, including the Airborne Multi-angle SpectroPolarimeter Imager (AirMSPI), the Passive Aerosol and Cloud Suite (PACS) and the Research Scanning Polarimeter (RSP). These instruments have been operated together on NASA's ER-2 high altitude aircraft as part of field campaigns such as the POlarimeter DEfinition EXperiment (PODEX) (California, early 2013) and Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS, California and Texas, summer 2013). Our role in these efforts has been to serve as an assessment team performing level 1 (calibrated radiance, polarization) and level 2 (retrieved geophysical parameter) instrument intercomparisons, and to promote unified and generalized calibration, uncertainty assessment and retrieval techniques. We will present our progress in this endeavor thus far and describe upcoming research in 2015.

  6. Progress in Airborne Polarimeter Inter Comparison for the NASA Aerosols-Clouds-Ecosystems (ACE) Mission

    NASA Technical Reports Server (NTRS)

    Knobelspiesse, Kirk; Redemann, Jens

    2014-01-01

    The Aerosols-Clouds-Ecosystems (ACE) mission, recommended by the National Research Council's Decadal Survey, calls for a multi-angle, multi-spectral polarimeter devoted to observations of atmospheric aerosols and clouds. In preparation for ACE, NASA funds the deployment of airborne polarimeters, including the Airborne Multiangle SpectroPolarimeter Imager (AirMSPI), the Passive Aerosol and Cloud Suite (PACS) and the Research Scanning Polarimeter (RSP). These instruments have been operated together on NASA's ER-2 high altitude aircraft as part of field campaigns such as the POlarimeter DEfinition EXperiment (PODEX) (California, early 2013) and Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS, California and Texas, summer 2013). Our role in these efforts has been to serve as an assessment team performing level 1 (calibrated radiance, polarization) and level 2 (retrieved geophysical parameter) instrument intercomparisons, and to promote unified and generalized calibration, uncertainty assessment and retrieval techniques. We will present our progress in this endeavor thus far and describe upcoming research in 2015.

  7. ACE-inhibitory activity of enzymatic protein hydrolysates from lupin and other legumes.

    PubMed

    Boschin, Giovanna; Scigliuolo, Graziana Maria; Resta, Donatella; Arnoldi, Anna

    2014-02-15

    The objective of this investigation was to compare the angiotensin converting enzyme (ACE)-inhibitory activity of the hydrolysates obtained by pepsin digestion of proteins of some legumes, such as chickpea, common bean, lentil, lupin, pea, and soybean, by using the same experimental procedure. The ACE-inhibitory activity was measured by using the tripeptide hippuryl-histidyl-leucine (HHL), as model peptide, and HPLC-DAD, as analytical method. The peptide mixtures of all legumes were active, with soybean and lupin the most efficient, with IC50 values of 224 and 226 μg/ml, respectively. Considering the promising results obtained with lupin, and aiming to identify the protein(s) that release(s) the peptides responsible for the activity, the peptides obtained from the pepsin digestion of some industrial lupin protein isolates and purified protein fractions were tested. The most active mixture, showing an IC50 value of 138 μg/ml, was obtained hydrolysing a mixture of lupin α+β conglutin. PMID:24128446

  8. Airborne polarimeter intercomparison for the NASA Aerosol-Cloud-Ecosystem (ACE) mission

    NASA Astrophysics Data System (ADS)

    Knobelspiesse, K. D.; Redemann, J.

    2014-12-01

    The Aerosol-Cloud-Ecosystem (ACE) mission, recommended by the National Research Council's Decadal Survey, calls for a multi-angle, multi-spectral polarimeter devoted to observations of atmospheric aerosols and clouds. In preparation for ACE, NASA funds the deployment of airborne polarimeter prototypes, including the Airborne Multi-angle SpectroPolarimeter Imager (AirMSPI), the Passive Aerosol and Cloud Suite (PACS) and the Research Scanning Polarimeter (RSP). These instruments have been operated together on NASA's ER-2 high altitude aircraft as part of field campaigns such as the POlarimeter DEfinition EXperiment (PODEX) (California, early 2013) and Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS, California and Texas, summer 2013). Our role in these efforts has been to serve as an assessment team performing level 1 (calibrated radiance, polarization) and level 2 (retrieved geophysical parameter) instrument intercomparisons, and to promote unified and generalized calibration, uncertainty assessment and retrieval techniques. We will present our progress in this endeavor thus far and describe upcoming research in 2015.

  9. ACE EPAM and Van Allen Probes RBSPICE measurements of interplanetary oxygen injection to the inner magnetosphere

    NASA Astrophysics Data System (ADS)

    Patterson, J. D.; Manweiler, J. W.; Gerrard, A. J.; Lanzerotti, L. J.

    2015-12-01

    On March 17, 2015, a significant oxygen-rich interplanetary event was measure by the Advanced Composition Explorer (ACE) Electron Proton Alpha Monitor (EPAM) instrument. At the same time the Van Allen Probes Radiation Belt Storm Probes Ion Composition Experiment (RBSPICE) instrument recorded significant enhancements of oxygen in the inner magnetosphere. We present a detailed analysis of this event utilizing a new method of exploiting the EPAM Pulse Height Analyzer (PHA) data to precisely resolve helium and oxygen spectra within the 0.5 to 5 MeV/nuc range. We also present the flux, partial particle pressures, and pitch angle distributions of the ion measurements from RBSPICE. During this event, both EPAM and RBSPICE measured O:He ratios greater than 10:1. The pitch angle distributions from RBSPICE-B show a strong beam of oxygen at an L ~ 5.8 early on March 17th during orbit. The timing between the observations of the oxygen peak at ACE and the beam observed at RBSPICE-B is consistent with the travel-time required for energetic particle transport from L1 to Earth and access to the magnetosphere. We assert that the oxygen seen by RBSPICE during the initial phase of this event is the result of direct injection from the interplanetary medium of energetic ions. This poster contains the observations and detailed calculations to support this assertion.

  10. Analysis of WakeVAS Benefits Using ACES Build 3.2.1

    NASA Technical Reports Server (NTRS)

    Smith, Jeremy C.

    2005-01-01

    The FAA and NASA are currently engaged in a Wake Turbulence Research Program to revise wake turbulence separation standards, procedures, and criteria to increase airport capacity while maintaining or increasing safety. The research program is divided into three phases: Phase I near term procedural enhancements; Phase II wind dependent Wake Vortex Advisory System (WakeVAS) Concepts of Operations (ConOps); and Phase III farther term ConOps based on wake prediction and sensing. This report contains an analysis that evaluates the benefits of a closely spaced parallel runway (CSPR) Phase I ConOps, a single runway and CSPR Phase II ConOps and a single runway Phase III ConOps. A series of simulation runs were performed using the Airspace Concepts Evaluation System (ACES) Build 3.21 air traffic simulator to provide an initial assessment of the reduction in delay and cost savings obtained by the use of a WakeVAS at selected U.S. airports. The ACES simulator is being developed by NASA Ames Research Center as part of the Virtual Airspace Modelling and Simulation (VAMS) program.

  11. NASA-ACEE/Boeing 737 graphite-epoxy horizontal stabilizer service

    NASA Technical Reports Server (NTRS)

    Quinlivan, J. T.; Kent, J. A.; Wilson, D. R.

    1992-01-01

    The 737 graphite-epoxy horizontal stabilizer was developed by Boeing as part of the NASA-ACEE (Aircraft Energy Efficiency) Advanced Composite Structures Program. NASA-ACEE programs challenged large-transport manufacturers to use graphite material in redesigning existing aircraft components. The goal of the program was to develop the necessary data and technology to achieve production commitments to advanced composites. Boeing designed, fabricated, and certified five shipsets of horizontal stabilizers for the 737-200 airframe. The program was initiated in July 1977 and certification was achieved in August 1982. Schedule highlights are shown. The work performed on this program is reported in NASA technical summaries and final reports. Boeing introduced the stabilizer into commercial operation in 1984, and has maintained surveillance for seven years of in-service evaluation. Outstanding performance was demonstrated with no service incidents attributed to the graphite-epoxy structure. Boeing will continue to monitor and support these aircraft, adding to the database of commercial composite experience.

  12. The solar wind neon abundance observed with ACE/SWICS and ULYSSES/SWICS

    SciTech Connect

    Shearer, Paul; Raines, Jim M.; Lepri, Susan T.; Thomas, Jonathan W.; Gilbert, Jason A.; Landi, Enrico; Zurbuchen, Thomas H.; Von Steiger, Rudolf

    2014-07-01

    Using in situ ion spectrometry data from ACE/SWICS, we determine the solar wind Ne/O elemental abundance ratio and examine its dependence on wind speed and evolution with the solar cycle. We find that Ne/O is inversely correlated with wind speed, is nearly constant in the fast wind, and correlates strongly with solar activity in the slow wind. In fast wind streams with speeds above 600 km s{sup –1}, we find Ne/O = 0.10 ± 0.02, in good agreement with the extensive polar observations by Ulysses/SWICS. In slow wind streams with speeds below 400 km s{sup –1}, Ne/O ranges from a low of 0.12 ± 0.02 at solar maximum to a high of 0.17 ± 0.03 at solar minimum. These measurements place new and significant empirical constraints on the fractionation mechanisms governing solar wind composition and have implications for the coronal and photospheric abundances of neon and oxygen. The results are made possible by a new data analysis method that robustly identifies rare elements in the measured ion spectra. The method is also applied to Ulysses/SWICS data, which confirms the ACE observations and extends our view of solar wind neon into the three-dimensional heliosphere.

  13. Poisson's ratio prediction through dual stimulated fuzzy logic by ACE and GA-PS

    NASA Astrophysics Data System (ADS)

    Bagheripour, Parisa; Asoodeh, Mojtaba

    2014-08-01

    Poisson's ratio is one of the most important rock mechanical parameters having significance in both planning and post analysis of wellbore operations. Laboratory measurement of this parameter covers a broad range of costs, including sidewall sampling, preservation, and laboratory tests. This study proposes an improved strategy, called dual stimulated fuzzy logic by ACE and GA-PS for determining Poisson's ratio from conventional well log data in a rapid, precise, and cost-effective way. Firstly, conventional well log data are transformed to a higher correlated data space with Poisson's ratio through the use of alternative condition expectation (ACE) algorithm. This step simplifies the convoluted space of the problem and makes it easier to solve for fuzzy logic. Subsequently, transformed conventional well log data are fed to fuzzy logic model. To ensure that optimal fuzzy model is constructed, a hybrid genetic algorithm-pattern search (GA-PS) technique is employed for extracting fuzzy clusters (or rules). This step sets fuzzy logic to its optimal performance. The propounded strategy was successfully applied to data from carbonate reservoir rocks of an Iranian Oil Field. A comparison between present model and previous models showed superiority of current study.

  14. Smart tetroons for Lagrangian air-mass tracking during ACE 1

    NASA Astrophysics Data System (ADS)

    Businger, Steven; Johnson, Randy; Katzfey, Jack; Siems, Steven; Wang, Qing

    1999-05-01

    A series of "smart" tetroons was released from shipboard during the recent ACE 1 field experiment designed to monitor changes in the sulfur budget in a remote marine boundary layer (MBL) south of Tasmania, Australia. The smart tetroons were designed at NOAA Air Resources Laboratory Field Research Division to provide air parcel tracking information. The adjective smart here refers here to the fact that the buoyancy of the tetroons automatically adjusts through the action of a pump and valves when the tetroon travels vertically outside a range of pressures set prior to tetroon release. The smart tetroon design provides GPS location, barometric pressure, temperature, relative humidity, and tetroon status data via a transponder to the NCAR C-130 research aircraft flying in the vicinity of the tetroons. In this paper we will describe (1) the design and capability of the smart tetroons and their performance during the two Lagrangian experiments conducted during ACE 1, (2) the synoptic context of the Lagrangians, including the origin of the air parcels being tracked, and (3) the results of trajectory predictions derived from the National Center for Environmental Prediction (NCEP) Global Spectral Model (GSM) and Australia's Commonwealth Scientific and Industrial Research Organization (CSIRO) Division of Atmospheric Research (DAR) limited-area model.

  15. Validation of a Coupled Source Surface to MHD Model System at ACE and Ulysses

    NASA Astrophysics Data System (ADS)

    Detman, T.; Fry, C. D.; Smith, Z.; Dryer, M.; Intriligator, D.

    2005-05-01

    The Potential Field Source Surface model [Wang and Sheeley, 1988] combined with the Current Sheet modification [Schatten, 1971] is now in routine operation at the NWS Space Environment Center of NOAA. We use the sequence of source surface current sheet (SSCS) maps so produced. We developed a set of relatively simple empirical relationships to translate the SSCS map parameters into time-dependent MHD model lower boundary conditions at 0.1 AU. This system provides the 3D time-dependent slowly evolving background solar wind conditions in the inner heliosphere. To this system we add shock initiation perturbations to the lower boundary condition based on observed solar flares, CMEs and Type II solar radio bursts. The necessary shock descriptive parameters are generated in near real-time from these data. We compare simulated results with ACE solar wind observations. We have retrospectively adjusted the shock initiation parameters to maximize agreement with ACE observations, and extended the MHD model outer boundary to 10 AU. We will show results and comparisons of model results with Ulysses observations during the 2003 Halloween epoch. This work was partially funded by a NASA Living With a Star (LWS) TR&T grant through NOAA Work Order No.W-10,118 (ZS and TRD) and NASA Grant NAG-12527 (CDF and MD), by University Partnering for Operational Support program (UPOS) sponsored jointly by the U.S. Air Force and U.S. Army (CDF and MD), and by Carmel Research Center (DI).

  16. Binding constant determination of uranyl-citrate complex by ACE using a multi-injection method.

    PubMed

    Zhang, Yiding; Li, Linnan; Huang, Hexiang; Xu, Linnan; Li, Ze; Bai, Yu; Liu, Huwei

    2015-04-01

    The binding constant determination of uranyl with small-molecule ligands such as citric acid could provide fundamental knowledge for a better understanding of the study of uranyl complexation, which is of considerable importance for multiple purposes. In this work, the binding constant of uranyl-citrate complex was determined by ACE. Besides the common single-injection method, a multi-injection method to measure the electrophoretic mobility was also applied. The BGEs used contained HClO4 and NaClO4 , with a pH of 1.98 ± 0.02 and ionic strength of 0.050 mol/L, then citric acid was added to reach different concentrations. The electrophoretic mobilities of the uranyl-citrate complex measured by both of the two methods were consistent, and then the binding constant was calculated by nonlinear fitting assuming that the reaction had a 1:1 stoichiometry and the complex was [(UO2 )(Cit)](-) . The binding constant obtained by the multi-injection method was log K = 9.68 ± 0.07, and that obtained by the single-injection method was log K = 9.73 ± 0.02. The results provided additional knowledge of the uranyl-citrate system, and they demonstrated that compared with other methods, ACE using the multi-injection method could be an efficient, fast, and simple way to determine electrophoretic mobilities and to calculate binding constants. PMID:25598434

  17. Structural, functional, and ACE inhibitory properties of water-soluble polysaccharides from chickpea flours.

    PubMed

    Mokni Ghribi, Abir; Sila, Assaâd; Maklouf Gafsi, Ines; Blecker, Christophe; Danthine, Sabine; Attia, Hamadi; Bougatef, Ali; Besbes, Souhail

    2015-04-01

    The present study aimed to characterize and investigate the functional and angiotensin-I converting enzyme (ACE) inhibition activities of chickpea water-soluble polysaccharides (CPWSP). Physico-chemical characteristics were determined by nuclear magnetic resonance spectroscopy (NMR), Fourier transform-infrared spectroscopy (FT-IR) analysis, and X-ray diffractometry (XRD). Functional properties (water holding capacity: WHC, water solubility index: WSI, swelling capacity: SC, oil holding capacity: OHC, foaming, and emulsion properties) and ACE activities were also investigated using well-established procedures. The FT-IR spectra obtained for the CPWSP revealed two significant peaks, at about 3500 and 500 cm(-1), which corresponded to the carbohydrate region and were characteristic of polysaccharides. All spectra showed the presence of a broad absorption between 1500 and 670 cm(-1), which could be attributed to CH, CO, and OH bands in the polysaccharides. CPWSP had an XRD pattern that was typical for a semi-crystalline polymer with a major crystalline reflection at 19.6 °C. They also displayed important techno-functional properties (SWC, WSI, WHC, and OHC) that can be modulated according to temperature. The CPWSP were also noted to display good anti-hypertensive activities. Overall, the results indicate that CPWSP have attractive chemical, biological, and functional properties that make them potential promising candidates for application as alternative additives in various food, cosmetic, and pharmaceutical preparations. PMID:25643994

  18. [Diabetic nephropathy: current diagnostics and treatment].

    PubMed

    Werth, S; Lehnert, H; Steinhoff, J

    2015-05-01

    Diabetic kidney disease is a leading cause of renal failure in Germany. Albuminuria is an early diagnostic indicator of renal damage in diabetes and, aside from renal failure, a major risk factor of cardiovascular disease. An early diagnosis of diabetic kidney disease is of great importance to reduce associated cardiovascular mortality; glycemic control should aim for HbA1c levels of < 7 %. Guidelines on blood pressure differ, but it should generally be reduced to < 140/90 mmHg; stricter limits should be applied if albuminuria is present. ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARB) should be preferred for blood pressure control. A combination of ACE-Is and ARBs or a renin-inhibitor therapy does not improve cardiovascular outcome, instead it increases the rate of adverse events, e.g., hyperkalemia or renal failure. Lipid control, usually with statins, should be started at an early phase of renal failure. Vitamin D receptor activation and uric acid reduction might play a future role in the treatment of diabetic kidney disease. Pharmacological modification of inflammatory signaling appears to be promising but is not yet of clinical relevance. PMID:25762007

  19. Design and implementation of robust decentralized control laws for the ACES structure at Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Collins, Emmanuel G., Jr.; Phillips, Douglas J.; Hyland, David C.

    1990-01-01

    Many large space system concepts will require active vibration control to satisfy critical performance requirements such as line-of-sight accuracy. In order for these concepts to become operational it is imperative that the benefits of active vibration control be practically demonstrated in ground based experiments. The results of the experiment successfully demonstrate active vibration control for a flexible structure. The testbed is the Active Control Technique Evaluation for Spacecraft (ACES) structure at NASA Marshall Space Flight Center. The ACES structure is dynamically traceable to future space systems and especially allows the study of line-of-sight control issues.

  20. The ACEE program and basic composites research at Langley Research Center (1975 to 1986): Summary and bibliography

    NASA Technical Reports Server (NTRS)

    Dow, Marvin B.

    1987-01-01

    Composites research conducted at the Langley Research Center during the period from 1975 to 1986 is described, and an annotated bibliography of over 600 documents (with their abstracts) is presented. The research includes Langley basic technology and the composite primary structures element of the NASA Aircraft Energy Efficiency (ACEE) Program. The basic technology documents cited in the bibliography are grouped according to the research activity such as design and analysis, fatigue and fracture, and damage tolerance. The ACEE documents cover development of composite structures for transport aircraft.

  1. Overview of ACE-Asia Spring 2001 Investigations on Aerosol Radiative Effects and Related Aerosol Properties

    NASA Technical Reports Server (NTRS)

    Russell, Philip B.; Valero, F. P. J.; Flatau, P. J.; Bergin, M.; Holben, B.; Nakajima, T.; Pilewskie, P.; Bergstrom, R.; Hipskind, R. Stephen (Technical Monitor)

    2001-01-01

    A primary, ACE-Asia objective was to quantify the interactions between aerosols and radiation in the Asia-Pacific region. Toward this end, radiometric and related aerosol measurements were made from ocean, land, air and space platforms. Models that predict aerosol fields guided the measurements and are helping integrate and interpret results. Companion overview's survey these measurement and modeling components. Here we illustrate how these components were combined to determine aerosol radiative. impacts and their relation to aerosol properties. Because clouds can obscure or change aerosol direct radiative effects, aircraft and ship sorties to measure these effects depended on predicting and finding cloud-free areas and times with interesting aerosols present. Pre-experiment satellite cloud climatologies, pre-flight aerosol and cloud forecasts, and in-flight guidance from satellite imagery all helped achieve this. Assessments of aerosol regional radiative impacts benefit from the spatiotemporal coverage of satellites, provided satellite-retrieved aerosol properties are accurate. Therefore, ACE-Asia included satellite retrieval tests, as part of many comparisons to judge the consistency (closure) among, diverse measurements. Early results include: (1) Solar spectrally resolved and broadband irradiances and optical depth measurements from the C-130 aircraft and at Kosan, Korea yielded aerosol radiative forcing efficiencies, permitting comparisons between efficiencies of ACE-Asia and INDOEX aerosols, and between dust and "pollution" aerosols. Detailed results will be presented in separate papers. (2) Based on measurements of wavelength dependent aerosol optical depth (AOD) and single scattering albedo the estimated 24-h a average aerosol radiative forcing efficiency at the surface for photosynthetically active radiation (400 - 700 nm) in Yulin, China is approx. 30 W sq m per AOD(500 nm). (3) The R/V Brown cruise from Honolulu to Sea of Japan sampled an aerosol optical

  2. Scope of ACE in Australia. Volume 1: Implications for Improved Data Collection and Reporting [and] Volume 2: Analysis of Existing Information in National Education and Training Data Collection.

    ERIC Educational Resources Information Center

    Borthwick, J.; Knight, B.; Bender, A.; Loveder, P.

    These two volumes provide information on the scope of adult and community education (ACE) in Australia and implications for improved data collection and reporting. Volume 1 begins with a glossary. Chapter 1 addresses project objectives and processes and methodology. Chapter 2 analyzes the scope and diversity of ACE in terms of what is currently…

  3. In silico analysis and molecular docking studies of potential angiotensin-converting enzyme inhibitor using quercetin glycosides

    PubMed Central

    Muhammad, Syed Aun; Fatima, Nighat

    2015-01-01

    The purpose of this study was to analyze the inhibitory action of quercetin glycosides by computational docking studies. For this, natural metabolite quercetin glycosides isolated from buckwheat and onions were used as ligand for molecular interaction. The crystallographic structure of molecular target angiotensin-converting enzyme (ACE) (peptidyl-dipeptidase A) was obtained from PDB database (PDB ID: 1O86). Enalapril, a well-known brand of ACE inhibitor was taken as the standard for comparative analysis. Computational docking analysis was performed using PyRx, AutoDock Vina option based on scoring functions. The quercetin showed optimum binding affinity with a molecular target (angiotensin-converting-enzyme) with the binding energy of −8.5 kcal/mol as compared to the standard (−7.0 kcal/mol). These results indicated that quercetin glycosides could be one of the potential ligands to treat hypertension, myocardial infarction, and congestive heart failure. PMID:26109757

  4. Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism

    PubMed Central

    Wang, Yu; Shoemaker, Robin; Thatcher, Sean E.; Batifoulier-Yiannikouris, Frederique; English, Victoria L.

    2015-01-01

    We recently demonstrated that female mice are resistant to the development of obesity-induced hypertension through a sex hormone-dependent mechanism that involved adipose angiotensin-converting enzyme 2 (ACE2). In this study, we hypothesized that provision of 17β-estradiol (E2) to ovariectomized (OVX) high-fat (HF)-fed female hypertensive mice would reverse obesity-hypertension through an ACE2-dependent mechanism. Pilot studies defined dose-dependent effects of E2 in OVX female mice on serum E2 concentrations and uterine weights. An E2 dose of 36 μg/ml restored normal serum E2 concentrations and uterine weights. Therefore, HF-fed OVX female Ace2+/+ and Ace2−/− mice were administered vehicle or E2 (36 μg/ml) for 16 wk. E2 administration significantly decreased body weights of HF-fed OVX female Ace2+/+ and Ace2−/− mice of either genotype. At 15 wk, E2 administration decreased systolic blood pressure (SBP) of OVX HF-fed Ace2+/+ but not Ace2−/− females during the light but not the dark cycle. E2-mediated reductions in SBP in Ace2+/+ females were associated with significant elevations in adipose ACE2 mRNA abundance and activity and reduced plasma ANG II concentrations. In contrast to females, E2 administration had no effect on any parameter quantified in HF-fed male hypertensive mice. In 3T3-L1 adipocytes, E2 promoted ACE2 mRNA abundance through effects at estrogen receptor-α (ERα) and resulted in ERα-mediated binding at the ACE2 promoter. These results demonstrate that E2 administration to OVX females reduces obesity-induced elevations in SBP (light cycle) through an ACE2-dependent mechanism. Beneficial effects of E2 to decrease blood pressure in OVX obese females may result from stimulation of adipose ACE2. PMID:26078188

  5. Validation of ACE and OSIRIS ozone and NO2 measurements using ground-based instruments at 80° N

    NASA Astrophysics Data System (ADS)

    Adams, C.; Strong, K.; Batchelor, R. L.; Bernath, P. F.; Brohede, S.; Boone, C.; Degenstein, D.; Daffer, W. H.; Drummond, J. R.; Fogal, P. F.; Farahani, E.; Fayt, C.; Fraser, A.; Goutail, F.; Hendrick, F.; Kolonjari, F.; Lindenmaier, R.; Manney, G.; McElroy, C. T.; McLinden, C. A.; Mendonca, J.; Park, J.-H.; Pavlovic, B.; Pazmino, A.; Roth, C.; Savastiouk, V.; Walker, K. A.; Weaver, D.; Zhao, X.

    2012-05-01

    The Optical Spectrograph and Infra-Red Imager System (OSIRIS) and the Atmospheric Chemistry Experiment (ACE) have been taking measurements from space since 2001 and 2003, respectively. This paper presents intercomparisons between ozone and NO2 measured by the ACE and OSIRIS satellite instruments and by ground-based instruments at the Polar Environment Atmospheric Research Laboratory (PEARL), which is located at Eureka, Canada (80° N, 86° W) and is operated by the Canadian Network for the Detection of Atmospheric Change (CANDAC). The ground-based instruments included in this study are four zenith-sky differential optical absorption spectroscopy (DOAS) instruments, one Bruker Fourier transform infrared spectrometer (FTIR) and four Brewer spectrophotometers. Ozone total columns measured by the DOAS instruments were retrieved using new Network for the Detection of Atmospheric Composition Change (NDACC) guidelines and agree to within 3.2%. The DOAS ozone columns agree with the Brewer spectrophotometers with mean relative differences that are smaller than 1.5%. This suggests that for these instruments the new NDACC data guidelines were successful in producing a homogenous and accurate ozone dataset at 80° N. Satellite 14-52 km ozone and 17-40 km NO2 partial columns within 500 km of PEARL were calculated for ACE-FTS Version 2.2 (v2.2) plus updates, ACE-FTS v3.0, ACE-MAESTRO (Measurements of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation) v1.2 and OSIRIS SaskMART v5.0x ozone and Optimal Estimation v3.0 NO2 data products. The new ACE-FTS v3.0 and the validated ACE-FTS v2.2 partial columns are nearly identical, with mean relative differences of 0.0 ± 0.2% and -0.2 ± 0.1% for v2.2 minus v3.0 ozone and NO2, respectively. Ozone columns were constructed from 14-52 km satellite and 0-14 km ozonesonde partial columns and compared with the ground-based total column measurements. The satellite-plus-sonde measurements agree with the ground

  6. Validation of ACE and OSIRIS ozone and NO2 measurements using ground-based instruments at 80° N

    NASA Astrophysics Data System (ADS)

    Adams, C.; Strong, K.; Batchelor, R. L.; Bernath, P. F.; Brohede, S.; Boone, C.; Degenstein, D.; Daffer, W. H.; Drummond, J. R.; Fogal, P. F.; Farahani, E.; Fayt, C.; Fraser, A.; Goutail, F.; Hendrick, F.; Kolonjari, F.; Lindenmaier, R.; Manney, G.; McElroy, C. T.; McLinden, C. A.; Mendonca, J.; Park, J.-H.; Pavlovic, B.; Pazmino, A.; Roth, C.; Savastiouk, V.; Walker, K. A.; Weaver, D.; Zhao, X.

    2012-01-01

    The Optical Spectrograph and Infra-Red Imager System (OSIRIS) and the Atmospheric Chemistry Experiment (ACE) have been taking measurements from space since 2001 and 2003, respectively. This paper presents intercomparisons between ozone and NO2 measured by the ACE and OSIRIS satellite instruments and by ground-based instruments at the Polar Environment Atmospheric Research Laboratory (PEARL), which is located at Eureka, Canada (80° N, 86° W) and is operated by the Canadian Network for the Detection of Atmospheric Change (CANDAC). The ground-based instruments included in this study are four zenith-sky differential optical absorption spectroscopy (DOAS) instruments, one Bruker Fourier transform infrared spectrometer (FTIR) and four Brewer spectrophotometers. Ozone total columns measured by the DOAS instruments were retrieved using new Network for the Detection of Atmospheric Composition Change (NDACC) guidelines and agree to within 3.2%. The DOAS ozone columns agree with the Brewer spectrophotometers with mean relative differences that are smaller than 1.5%. This suggests that for these instruments the new NDACC data guidelines were successful in producing a homogenous and accurate ozone dataset at 80° N. Satellite 14-52 km ozone and 17-40 km NO2 partial columns within 500 km of PEARL were calculated for ACE-FTS Version 2.2 (v2.2) plus updates, ACE-FTS v3.0, ACE-MAESTRO (Measurements of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation) v1.2 and OSIRIS SaskMART v5.0x ozone and Optimal Estimation v3.0 NO2 data products. The new ACE-FTS v3.0 and the validated ACE-FTS v2.2 partial columns are nearly identical, with mean relative differences of 0.0 ± 0.2% for ozone and -0.2 ± 0.1% for v2.2 minus v3.3 NO2. Ozone columns were constructed from 14-52 km satellite and 0-14 km ozonesonde partial columns and compared with the ground-based total column measurements. The satellite-plus-sonde measurements agree with the ground-based ozone total

  7. Fixed-Dose Combinations of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension: A Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors.

    PubMed

    Hsiao, Fu-Chih; Tung, Ying-Chang; Chou, Shing-Hsien; Wu, Lung-Sheng; Lin, Chia-Pin; Wang, Chun-Li; Lin, Yu-Sheng; Chang, Chee-Jen; Chu, Pao-Hsien

    2015-12-01

    Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking.Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered.There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98-1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082-1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071-1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050-1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses.ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status. PMID:26705234

  8. Protective Effect of RA on Myocardial Infarction-Induced Cardiac Fibrosis via AT1R/p38 MAPK Pathway Signaling and Modulation of the ACE2/ACE Ratio.

    PubMed

    Liu, Qiaofeng; Tian, Jingwei; Xu, Yanan; Li, Chunmei; Meng, Xiangjing; Fu, Fenghua

    2016-09-01

    Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid, RA) is a major active constituent of Rosmarinus officinalis Linn. (rosemary) having significant anti-inflammatory, anti-apoptotic, and antioxidant effects. However, the cardioprotection of RA is still not understood. The present study was designed, for the first time, to investigate the cardioprotection of RA on myocardial infarction (MI)-induced cardiac fibrosis and to clarify the possible mechanisms. MI was induced in ad