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Sample records for ace inhibitor enalaprilat

  1. 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

  2. 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

  3. Upregulation of SERCA2a following short-term ACE inhibition (by enalaprilat) alters contractile performance and arrhythmogenicity of healthy myocardium in rat.

    PubMed

    Matus, Marek; Kucerova, Dana; Kruzliak, Peter; Adameova, Adriana; Doka, Gabriel; Turcekova, Katarina; Kmecova, Jana; Kyselovic, Jan; Krenek, Peter; Kirchhefer, Uwe; Mueller, Frank U; Boknik, Peter; Klimas, Jan

    2015-05-01

    Chronic angiotensin-converting enzyme inhibitor (ACEIs) treatment can suppress arrhythmogenesis. To examine whether the effect is more immediate and independent of suppression of pathological remodelling, we tested the antiarrhythmic effect of short-term ACE inhibition in healthy normotensive rats. Wistar rats were administered with enalaprilat (ENA, i.p., 5 mg/kg every 12 h) or vehicle (CON) for 2 weeks. Intraarterial blood pressure in situ was measured in A. carotis. Cellular shortening was measured in isolated, electrically paced cardiomyocytes. Standard 12-lead electrocardiography was performed, and hearts of anaesthetized open-chest rats were subjected to 6-min ischemia followed by 10-min reperfusion to examine susceptibility to ventricular arrhythmias. Expressions of calcium-regulating proteins (SERCA2a, cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase; CSQ, calsequestrin; TRD, triadin; PLB, phospholamban; Thr(17)-PLB-phosphorylated PLB at threonine-17, FKBP12.6, FK506-binding protein, Cav1.2-voltage-dependent L-type calcium channel alpha 1C subunit) were measured by Western blot; mRNA levels of L-type calcium channel (Cacna1c), ryanodine receptor (Ryr2) and potassium channels Kcnh2 and Kcnq1 were measured by qRT-PCR. ENA decreased intraarterial systolic as well as diastolic blood pressure (by 20%, and by 31%, respectively, for both P < 0.05) but enhanced shortening of cardiomyocytes at basal conditions (by 34%, P < 0.05) and under beta-adrenergic stimulation (by 73%, P < 0.05). Enalaprilat shortened QTc interval duration (CON 78 ± 1 ms vs. ENA 72 ± 2 ms; P < 0.05) and significantly decreased the total duration of ventricular fibrillations (VF) and the number of VF episodes (P < 0.05). Reduction in arrhythmogenesis was associated with a pronounced upregulation of SERCA2a (CON 100 ± 20 vs. ENA 304 ± 13; P < 0.05) and complete absence of basal Ca(2+)/calmodulin-dependent phosphorylation of PLB at Thr(17). Short-term ACEI treatment can provide protection

  4. 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.

  5. 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

  6. ACE Inhibitor in the treatment of cutaneous and lymphatic sarcoidosis.

    PubMed

    Kaura, Vinod; Kaura, Samantha H; Kaura, Claire S

    2007-01-01

    Angiotensin-converting enzyme is used as a marker for sarcoid activity. We describe a case of remission of cutaneous and lymphatic sarcoidosis in a patient treated with an ACE inhibitor for congestive heart failure and hypertension; the remission has continued over 4 years of follow-up. Because this is a report of only one case, there is a possibility of sampling error. Whether the patient's remission in this case was a serendipitous spontaneous remission that happened to occur during ACE inhibitor therapy or whether ACE inhibitor therapy can play a role in the treatment of sarcoidosis needs to be determined in a large clinical trial.

  7. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.

    PubMed

    Vuille-dit-Bille, Raphael N; Camargo, Simone M; Emmenegger, Luca; Sasse, Tom; Kummer, Eva; Jando, Julia; Hamie, Qeumars M; Meier, Chantal F; Hunziker, Schirin; Forras-Kaufmann, Zsofia; Kuyumcu, Sena; Fox, Mark; Schwizer, Werner; Fried, Michael; Lindenmeyer, Maja; Götze, Oliver; Verrey, François

    2015-04-01

    Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

  8. 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.

  9. Effect of angiotensin II receptor blockade on the interaction between enalaprilat and doxazosin in rat tail arteries.

    PubMed

    Marwood, J F

    1998-01-01

    1. Previous work has shown that enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), potentiated the actions of alpha 1-adrenoceptor antagonists; it was hypothesized that angiotensin II (AngII) modulated the activity of alpha 1-adrenoceptors. This hypothesis was tested in Sprague-Dawley rat isolated perfused tail arteries using the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD123319. 2. Losartan had no alpha 1-adrenoceptor antagonist effects at concentrations below 1 mumol/L. Similarly, losartan (0.1 mumol/L) had no effect on the alpha 1-adrenoceptor antagonist action of doxazosin (1, 10 nmol/L) nor on the potentiation of doxazosin by enalaprilat (1 mumol/L). 3. PD123319 (0.1 mumol/L) had no alpha 1-adrenoceptor antagonist effect but altered the mode of action of the alpha 1-adrenoceptor antagonist doxazosin: PD123319 changed doxazosin from a competitive to a non-competitive antagonist, as evidenced by the reduced slope of the dose-response curve for the alpha 1-adrenoceptor agonist phenylephrine. 4. These results suggest that AngII can modulate alpha 1-adrenoceptor function in rat tail arteries via an indirect action at AT2 receptors. However, the present results do not rule out the involvement of bradykinin, endothelin or prostaglandin in the modulation of alpha 1-adrenoceptor function by angiotensin II.

  10. Cutaneous allergy to insulin: could statins and ACE inhibitors play a role? A case report.

    PubMed

    Pitrola, D; MacIver, C; Mallipedhi, A; Udiawar, M; Price, D E; Stephens, J W

    2014-04-01

    Insulin allergy is rare. Both statins and angiotensin converting enzyme (ACE) inhibitors may cause local urticarial skin reactions and have been implicated to precipitate local reactions to insulin. We describe a case of a localised urticarial allergic reaction related to insulin use in a patient co-prescribed an ACE inhibitor and statin. PMID:24534533

  11. 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

  12. Statins, ACE inhibitors and ARBs in cardiovascular disease.

    PubMed

    Montecucco, Fabrizio; Mach, François

    2009-06-01

    Atherosclerotic cardiovascular disease (CVD) is the main cause of death in developed and developing countries. It is well accepted that several diseases - including hypertension, dyslipidemia and diabetes mellitus - increase CVD. More recently also chronic inflammatory diseases, such as rheumatoid arthritis, have been shown to accelerate CVD. This association further supports a responsible role for inflammatory processes in all stages of CVD pathophysiology. Clinically, CVD ranges through different acute and chronic syndromes with ischemic symptoms in distal tissues, including heart, cerebral region or peripheral arteries. Several treatments for reducing CVD are under investigation. In this review we focus on statins, angiotensin-converting-enzyme (ACE) inhibitors, and angiotensin-II receptor blockers (ARBs), updating therapeutic evidence from the last clinical trials with particular relevance to diabetic patients. PMID:19520311

  13. 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

  14. 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

  15. Angiotensin I-converting enzyme inhibitors potentiate bradykinin's inotropic effects independently of blocking its inactivation.

    PubMed

    Minshall, R D; Erdös, E G; Vogel, S M

    1997-08-01

    The positive inotropic effects of bradykinin (BK) and 2 analogs resistant to angiotensin I-converting enzyme (ACE) were potentiated on isolated guinea pig atrial preparations by enalaprilat. The stable BK analogs, dextran-BK and [Hyp3-Tyr(Me)8]-BK, were as active as BK. Pretreatment for 5 min with enalaprilat augmented the maximal positive inotropic effect of [Hyp3-Tyr(Me)8]-BK 2.8-fold, from 19% to 53% and that of BK from 28% to 42% over baseline; inotropic responses to dextran-BK (1 microM) were similarly increased. The activity of atrial ACE, a zinc-requiring enzyme, was completely inhibited by 8-hydroxyquinoline-5-sulfonic acid (QSA, 10 mM), which raised the maximal inotropic effect of BK to 39% above baseline. This value rose to 67% when in addition to QSA, 1 microM enalaprilat was added; enalaprilat thus, potentiated the effects of BK independently of enzyme inhibition. The positive inotropic effects to BK and its analogs decline with time in the presence of these agonists. After 10 min of exposure, the response to 1 microM [Hyp3-Tyr(Me)8]-BK decreased to about half, and after 20 min, to 0. Enalaprilat, when present in the tissue bath, prevented the decline in inotropy; even after tachyphylaxis occurred, it reversed this decrease in activity when added. The effects of 1 microM [Hyp3-Tyr(Me)8]-BK, in the absence or presence of enalaprilat, were abolished by the BK B2 receptor antagonist icatibant (0.75 microM). The results indicate that ACE inhibitors, by potentiating the BK effects and blocking BK B2-receptor desensitization, may contribute to the beneficial cardiac effects of BK independently of blocking its inactivation.

  16. Evaluation of renal function in elderly heart failure patients on ACE inhibitors

    PubMed Central

    Jolobe, O

    1999-01-01

    A total of 187 heart failure patients aged 65-92 years, with pretreatment serum creatinine levels below 200 µmol/l, were monitored for more than 12 months on angiotensin-converting enzyme (ACE) inhibitor therapy. Optimal ACE inhibitor dosage was found in 27% of patients, while a significant deterioration in renal function, characterised by >20% increase in serum creatinine to >200 µmol/l, occurred in 25 patients. This was most closely attributable to ACE inhibitor treatment per se (implying co-existence of bilateral renal artery stenosis) in only four cases, including one in whom renal deterioration was reproducible on inadvertent rechallenge. In the other 21, renal deterioration was attributable to diuretic-related blood volume depletion (two cases), nonsteroidal anti-inflammatory drugs (two cases), obstructive uropathy (two cases), preterminal renal shutdown (two cases), and the interaction between diuretic and ACE inhibitor dosage (including long-acting vs short-acting drugs) (13 cases). This study could serve as the basis for future comparisons of ACE-inhibitor-related renal deterioration when the entry requirement is optimal ACE inhibitor dosage.


Keywords: heart failure; elderly patients; angiotensin-converting enzyme inhibitors; renal deterioration PMID:10533630

  17. ACE inhibitors could be therapeutic for antisocial personality disorder.

    PubMed

    Hobgood, Donna K

    2013-11-01

    Antisocial personality traits are an important topic for research. The societal cost of these behaviors encourages efforts at a better understanding of central nervous system causes. Catecholamine genes are being studied to facilitate this understanding, and some tentative findings are being reached about several of these genes. It seems that many genes play a role to produce antisocial behaviors so complexity of elucidating each gene is obvious. One conclusion that could be drawn from the current research findings is that DA2 like receptors (DRD2, DRD3, DRD4) with alleles that decrease neurotransmission are facilitatory of antisocial behaviors. DA2 like receptors cause neuronal firing to inhibit many peripheral functions through adenylyl cyclase inhibition. When these receptors are less active by genetically decreased density, lower affinity, or by low dopamine levels as final common pathways then inhibition is released and a state of disinhibition can be said to describe this state. Peripheral metabolism is increased and behavioral activation is noted. Renin is disinhibited in this setting thus allowing sympathetic nervous system activation. The fight or flight behaviors thus produced, in the extreme, would be the setting of antisocial behavior. Research validates this hypothesis. Understanding this final common pathway toward antisocial behavior should lead to better treatment for individuals with this pattern of behavior before they have caused harm to themselves and others. ACE inhibitors are well tolerated drugs used in the treatment of hypertension and heart failure and would also treat antisocial behavior disorders.

  18. Tissue and plasma angiotensin converting enzyme and the response to ACE inhibitor drugs.

    PubMed Central

    MacFadyen, R J; Lees, K R; Reid, J L

    1991-01-01

    1. There is a body of circumstantial and direct evidence supporting the existence and functional importance of a tissue based RAS at a variety of sites. 2. The relation between circulatory and tissue based systems is complex. The relative importance of the two in determining haemodynamic effects is unknown. 3. Despite the wide range of ACE inhibitors already available, it remains unclear whether there are genuine differences related to tissue specificity. 4. Pathological states such as chronic cardiac failure need to be explored with regard to the contribution of tissue based ACE activities in generating acute and chronic haemodynamic responses to ACE inhibitors. 5. The role of tissue vs plasma ACE activity may be clarified by study of the relation between drug concentration and haemodynamic effect, provided that the temporal dissociation is examined and linked to circulating and tissue based changes in ACE activity, angiotensin peptides and sympathetic hormones. PMID:1849731

  19. A prospective study of frequency and characteristics of cough during ACE inhibitor treatment.

    PubMed

    Sato, Atsuhisa; Fukuda, Seiichi

    2015-01-01

    Angiotensin converting enzyme (ACE) inhibitors are reportedly effective, and positively indicated in patients with chronic heart failure with decreased contractility, after myocardial infarction, after cerebrovascular disorders, and in those with chronic kidney disease. However, the biggest challenge to continuous use of ACE inhibitors is the adverse reaction of cough. Accordingly, in the present study, we investigated the present state and characteristics of ACE inhibitor-induced cough in patients with essential hypertension currently being treated with an ACE inhibitor for an average of 18 months, who could be regularly checked for cough. Subjects in this study were 176 patients overall (mean age 67 ± 11 years old), 90 men and 86 women. The adverse reaction of cough was observed in 20% of patients, and more frequently in women than in men. However, in 26 of the patients with cough, the cough either resolved naturally or completely disappeared while the treatment continued, after which patients could continue taking the medication. Specifically, ACE inhibitor treatment was eventually discontinued due to cough in 5.1% of patients. Cough occurred less frequently with concomitant calcium antagonists or diuretics than with ACE inhibitor monotherapy. Cough as an adverse reaction occurred at a low frequency when medication was taken at bedtime. We considered a number of measures to counteract cough, then in addition to starting the ACE inhibitor treatment as early as possible, it is important to devise ways for the ACE inhibitor treatment to be continued for as long as possible, through the adept use of these measures.

  20. 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

  1. 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

  2. Antihypertensive treatment in renal transplant patients--is there a role for ACE inhibitors?

    PubMed

    Hausberg, M; Kosch, M; Hohage, H; Suwelack, B; Barenbrock, M; Kisters, K; Rahn, K H

    2001-01-01

    During the past two decades great progress was achieved with regards to short-term kidney graft survival. However, long-term graft survival did not improve similarly. Many factors contribute to chronic graft nephropathy eventually resulting in late graft loss, among these arterial hypertension is of major importance. In patients with chronic renal disease of diabetic and non-diabetic origin, angiotensin converting enzyme inhibitors have been convincingly shown to slow the progression of renal failure. The achieved nephroprotection correlates with the reduction of proteinuria by ACE inhibitor treatment. Also in renal transplant patients, ACE inhibitors have been shown unequivocally to reduce urinary protein excretion. The prevention of hyperfiltration, particular in the context of a reduced number of functional nephrons in patients with chronic graft nephropathy, could be important to prolong graft survival after renal transplantation. Moreover, ACE inhibitors may exert beneficial effects on immunologic processes contributing to chronic graft nephropathy. Many studies published in the last decade show convincingly that ACE inhibitors are safe and effective for the treatment of hypertension in renal allograft recipients. However, no data exist so far showing that ACE inhibitors are superior to other antihypertensive drugs in renal transplant patients and that they prolong graft survival. Studies investigating this issue are warranted. Apart from effects on the graft, ACE inhibitors may improve alterations of the cardiovascular system generally observed in renal transplant patients, such as structural alterations of large arteries, left ventricular hypertrophy, disturbed mechanical vessel wall properties and endothelial dysfunction. Therefore, angiotensin converting enzyme inhibitors could reduce cardiovascular morbidity and mortality in kidney transplant patients.

  3. Tailored therapy of ACE inhibitors in stable coronary artery disease: pharmacogenetic profiling of treatment benefit.

    PubMed

    Brugts, Jasper J; Boersma, Eric; Simoons, Maarten L

    2010-08-01

    Angiotensin-converting enzyme (ACE) inhibitors are among the most commonly used drugs in stable coronary artery disease as these agents have been proven to be effective for reducing the risk of cardiovascular morbidity and mortality. As with other drugs, individual variation in treatment benefit is likely. Such heterogeneity could be used to target ACE-inhibitor therapy to those patients most likely to benefit from treatment. However, prior attempts to target ACE-inhibitor therapy to those patients who are most likely to benefit of such prophylactic treatment in secondary prevention using clinical characteristics or the level of baseline risk appeared not to be useful. A new approach of 'tailored therapy' could be to integrate more patient-specific characteristics, such as the genetic information of patients. Pharmacogenetic research of ACE inhibitors in coronary artery disease patients is at a formative stage, and studies are limited. The Perindopril Genetic association (PERGENE) study is a large pharmacogenetic substudy of the randomized placebo-controlled European trial On Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery disease (EUROPA) trial, aimed to assess the feasibility of pharmacogenetic profiling of ACE-inhibitor therapy by perindopril. This article summarizes the recent findings of the PERGENE study and pharmacogenetic research of the treatment benefit of perindopril in stable coronary artery disease. PMID:20712529

  4. Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men?

    PubMed Central

    Leung, J.; Zhang, Y. F.; Bauer, D.; Ensrud, K. E.; Barrett-Connor, E.; Leung, P. C.

    2013-01-01

    Summary In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss. Introduction Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men. Methods Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study—The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4. Results Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm2) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss. Conclusion Use of ACE inhibitors but not ARB may marginally increase bone loss in older men. PMID:22080379

  5. SY 12-2 ACE INHIBITORS AND ARBS: SIMILARITIES AND DIFFERENCES IN CV RISK REDUCTION.

    PubMed

    Danser, Alexander

    2016-09-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) can be accomplished at the level of the angiotensin-generating enzymes renin and angiotensin-converting enzyme (ACE; using renin inhibitors or ACE inhibitors), the type 1 angiotensin II (AT1) receptor or mineralocorticoid receptor (MR; using angiotensin receptor blockers [ARBs] or MR blockers) and/or renin release (using beta-blockers). Several of these drugs are often combined-for example in heart failure-but such approaches may ultimately lead to RAAS annihilation with adverse consequences such as hypotension, renal dysfunction and hyperkalaemia. The biochemical consequences of each type of blockade are different. For instance, ACE inhibitors will lower angiotensin II, thus no longer allowing stimulation of both AT1 and type 2 angiotensin II (AT2) receptors, while ARBs raise angiotensin II, allowing selective stimulation of the unoccupied AT2 receptor. This might be of particular importance in women, in whom the protective AT2 receptor pathway is believed to be upregulated. Multiple clinical trials have compared the various types of RAAS blockers and/or their combination. This talk will summarize the current evidence with regard to similarities and differences between ACE inhibitors and ARBs, also considering their side-effect profile, dose and combination with other RAAS blockers. PMID:27643121

  6. Taking ACE inhibitors during pregnancy. Is it safe?

    PubMed Central

    Ratnapalan, Savithiri; Koren, Gideon

    2002-01-01

    QUESTION: A pregnant patient is taking enalapril for primary hypertension. How safe are angiotension-converting enzyme inhibitors (ACEI) during pregnancy? ANSWER: Evidence of whether ACEIs cause problems during the first trimester of pregnancy is reassuring. There is evidence that they cause severe renal and other problems during the second and third trimesters, however. These drugs should be avoided during pregnancy. PMID:12113190

  7. Potentially lethal ACE-inhibitor-induced angioedema in a child.

    PubMed

    Bukhari, Esraa; Safdar, Osama Y; Shalaby, Mohammed; AlSharif, Shafiqa Mj; Alsufiany, Khoulod; Kari, Jameela A

    2015-06-01

    We report a case of a 9-year-old female with known end-stage kidney disease who presented with sudden onset tongue swelling. A diagnosis of angiotensin-converting enzyme inhibitor-induced angioedema related to bradykinin accumulation was made. Her symptoms resolved shortly after discontinuation of captopril. Early diagnosis can save patients from severe upper airway obstruction.

  8. Potentially lethal ACE-inhibitor-induced angioedema in a child

    PubMed Central

    Bukhari, Esraa; Safdar, Osama Y; Shalaby, Mohammed; AlSharif, Shafiqa MJ; Alsufiany, Khoulod; Kari, Jameela A

    2015-01-01

    Key Clinical Message We report a case of a 9-year-old female with known end-stage kidney disease who presented with sudden onset tongue swelling. A diagnosis of angiotensin-converting enzyme inhibitor-induced angioedema related to bradykinin accumulation was made. Her symptoms resolved shortly after discontinuation of captopril. Early diagnosis can save patients from severe upper airway obstruction. PMID:26185642

  9. 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.

  10. 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.

  11. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs.

    PubMed

    Ruiz, F J; Salom, M G; Inglés, A C; Quesada, T; Vicente, E; Carbonell, L F

    1994-09-01

    Recently, in vivo and in vitro studies have implicated nitric oxide as a mediator of the vascular effects of angiotensin-converting enzyme inhibitors (ACEIs). In the present study we hypothesized that N-acetyl-L-cysteine (NAC), by increasing the availability of reduced sulfhydryl groups, would enhance the antihypertensive response to the ACEIs captopril and enalaprilat by a mechanism dependent on nitric oxide. The experiments were performed on instrumented, indomethacin-pretreated, awake spontaneously hypertensive rats (SHRs). Thirty minutes after a bolus of captopril (10 mg/kg iv) was administered, blood pressure decreased from 167 +/- 5 to 147 +/- 6 mmHg (n = 8). The pretreatment with the donor of thiol groups NAC (300 mg/kg iv) potentiated the depressor response to captopril because blood pressure decreased from 172 +/- 3 to 139 +/- 4 mmHg (n = 6). At the dose of 60 micrograms/kg iv, the ACEI enalaprilat did not acutely modify the blood pressure of SHRs (from 172 +/- 5 to 167 +/- 4 mmHg; n = 6). However, when the SHRs were pretreated with NAC, the same dose of enalaprilat significantly reduced blood pressure from 176 +/- 5 to 151 +/- 5 mmHg (n = 6). This potentiation of the depressor response to ACEIs, due to NAC, was not observed when SHRs were pretreated with the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 50 micrograms.kg-1.min-1 iv). The results of this study suggest that NAC, a donor of sulfhydryl groups, potentiates the antihypertensive response to captopril and enalaprilat in SHR by a nitric oxide-dependent mechanism.

  12. 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.

  13. 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.

  14. 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

  15. 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: ...

  16. Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to ACE Inhibitors in the Treatment of Hypertension.

    PubMed

    Prasad, Kailash

    2013-12-01

    Secoisolariciresionol diglucoside (SDG) is a plant lignan isolated from flaxseed and is phytoestrogen. SDG is a potent and long-acting hypotensive agent. Plant phytoestrogens have inhibitory effects on angiotensin-converting enzyme (ACE). The hypotensive effects of SDG, a phytoestrogen, may be mediated through inhibition of ACE. The objective of this study was to investigate if SDG-induced hypotension is mediated through inhibition of ACE. The Sprague Dawley male rats were anesthetized and trachea was cannulated. The right jugular vein was cannulated to administer the drug and the carotid artery was cannulated to record arterial pressures using PIOEZ-1 miniature model transducer (Becton, Dickinson and Company, Franklin Lakes, NJ) and Beckman dynograph (Beckman Instruments, Inc., Schiller Park, IL). The effects of angiotensin I (0.2 µg/kg, intravenously [IV]) in the absence and presence of SDG (10 mg/kg, IV), and SDG alone on systolic, diastolic, and mean arterial pressures were measured before and after 15, 30, and 60 minutes of drug administration. SDG decreased the systolic, diastolic, and mean arterial pressure by 37, 47, and 43%, respectively, at 15 minutes and 18.8, 21.2, and 20.3%, respectively, at 60 minutes. Angiotensin I increased the arterial pressure. SDG decreased angiotensin I-induced rise in the systolic, diastolic, and mean arterial pressures by 60, 58, and 51%, respectively, at 15 minutes and 48, 46, and 30%, respectively, at 60 minutes. The data suggest that SDG reduced the angiotensin I-induced rise in the arterial pressures and hence SDG is a potent ACE inhibitor.

  17. Effects of chronic treatment with losartan and enalaprilat on [3H]-norepinephrine release from isolated atria of Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Foucart, S; Patrick, S K; Oster, L; de Champlain, J

    1996-01-01

    The present study was designed to evaluate the effect of chronic treatment with losartan, an AT1 angiotensin II receptor antagonist, and enalaprilat, an angiotensin converting enzyme inhibitor, on the presynaptic modulation of [3H]-norepinephrine release from isolated atria of spontaneously hypertensive rats (SHR) and their respective control, the Wistar-Kyoto rats (WKY). The rats received either losartan (5 mg/kg/day) or enalaprilat (1 mg/kg/day) for 12 days by means of osmotic minipumps. The atria were isolated and incubated with [3H]-norepinephrine and the release of radioactivity was used as an index of norepinephrine release. The experimental protocol consisted of two electrical stimulations and the drugs were administered 20 min before the second stimulation. The modulatory action of angiotensin II (0.01 and 1 mumol/L), the alpha 2-adrenoceptor agonist, oxymetazoline (1 mumol/L), the alpha 2-adrenoceptor antagonist, idazoxan (1 mumol/L) and the beta 2-adrenoceptor agonist fenoterol (1 mumol/L) were tested. The results show that losartan or enalaprilat both similarly reduced the blood pressure in SHR. However, only the chronic losartan treatment, and not enalaprilat, abolished the facilitatory effect of exogenously administered angiotensin II on the release of radioactivity. The prejunctional alpha 2- and beta 2-adrenoceptor modulatory mechanisms were not altered by either chronic treatments. Similarly, the facilitatory effect of angiotensin II was blocked by acute administration of losartan but not by enalaprilat. Finally, the facilitatory action of bradykinin on the release of radioactivity was unchanged by chronic enalaprilat treatment. These results confirm the presence of facilitatory AT1 angiotensin II receptors on sympathetic nerve terminals of rat atria. These results also confirm that sympathetic nerve terminal blockade by losartan or the blockade of endogenous angiotensin II formation by enalaprilat are likely to participate in the antihypertensive

  18. What is the impact of the ACE gene insertion/deletion (I/D) polymorphism on the clinical effectiveness and adverse events of ACE inhibitors? – Protocol of a systematic review

    PubMed Central

    Scharplatz, M; Puhan, MA; Steurer, J; Bachmann, LM

    2004-01-01

    Background The Angiotensin Converting Enzyme (ACE) insertion/deletion (I/D) polymorphism has received much attention in pharmacogenetic research because observed variations in response to ACE inhibitors might be associated with this polymorphism. Pharmacogenetic testing raises the hope to individualise ACE inhibitor therapy in order to optimise its effectiveness and to reduce adverse effects for genetically different subgroups. However, the extent of its effect modification in patients treated with ACE inhibitors remains inconclusive. Therefore our objective is to quantify the effect modification of the insertion/deletion polymorphism of the angiotensin converting enzyme gene on any surrogate and clinically relevant parameters in patients with cardiovascular diseases, diabetes, renal transplantation and/or renal failure. Methods Systematic Review. We will perform literature searches in six electronic databases to identify randomised controlled trials comparing the effectiveness and occurrence of adverse events of ACE inhibitor therapy against placebo or any active treatment stratified by the I/D gene polymorphism. In addition, authors of trials, experts in pharmacogenetics and pharmaceutical companies will be contacted for further published or unpublished data. Hand searching will be accomplished by reviewing the reference lists of all included studies. The methodological quality of included papers will be assessed. Data analyses will be performed in clinically and methodologically cogent subgroups. The results of the quantitative assessment will be pooled statistically where appropriate to produce an estimate of the differences in the effect of ACE inhibitors observed between the three ACE genotypes. Discussion This protocol describes a strategy to quantify the effect modification of the ACE polymorphism on ACE inhibitors in relevant clinical domains using meta-epidemiological research methods. The results may provide evidence for the usefulness of pharmacogenetic

  19. Differential systemic and regional hemodynamic profiles of four angiotensin-I converting-enzyme inhibitors in the rat.

    PubMed

    Richer, C; Doussau, M P; Giudicelli, J F

    1989-12-01

    Angiotensin-converting enzyme (ACE) inhibitors decrease blood pressure by reducing systemic vascular resistance. That the peripheral vasodilating properties of ACE inhibitors might not be homogeneously distributed in all vascular beds and might differ from one drug to another has been investigated in the normotensive rat by the pulsed Doppler technique using the active components of four different ACE inhibitors: captopril, enalapril, perindopril, and ramipril. Systemic (cardiac output and blood pressure) and regional (kidney, mesentery, hindquarter) hemodynamic responses to saline or to cumulative bolus injections (0.01-1 mg/kg) of captopril, enalaprilat, perindoprilat, or ramiprilat were continuously monitored. The effects of successive bolus injections (0.3-300 ng/kg) of angiotensinII were also investigated. The four ACE inhibitors produced an almost complete blockade of plasma angiotensin-II converting-enzyme activity (83%, 100%, 100%, and 100%, respectively), induced dose-dependent decreases in mean blood pressure, did not significantly affect cardiac output, and reduced total peripheral and mesenteric vascular resistances to the same extent. Hindlimb vascular resistance was identically decreased, but to a lower extent than total peripheral resistance by enalaprilat, perindoprilat, and ramiprilat, whereas it was increased by captopril at low doses only. Renal resistance was markedly decreased by the four drugs, and especially by captopril. The decreasing rank order for ACE-inhibitor-induced vasodilation is exactly the same (renal greater than total peripheral = mesenteric greater than hindlimb vascular resistances) as that of angiotensin-H-induced regional vasoconstriction, indicating that the vasodilator properties of ACE inhibitors are mainly due to angiotensin-II vasomotor tone suppression. None of the investigated compounds significantly affected mesenteric and hindlimb blood flows, except captopril, which lowered the latter significantly

  20. Congenital renal tubular dysplasia and skull ossification defects similar to teratogenic effects of angiotensin converting enzyme (ACE) inhibitors.

    PubMed Central

    Kumar, D; Moss, G; Primhak, R; Coombs, R

    1997-01-01

    An apparently autosomal recessive syndrome of congenital renal tubular dysplasia and skull ossification defects is described in five infants from two separate, consanguineous, Pakistani Muslim kindreds. The clinical, pathological, and radiological features are similar to the phenotype associated with fetal exposure to angiotensin converting enzyme (ACE) inhibitors: intrauterine growth retardation, skull ossification defects, and fetal/ neonatal anuric renal failure associated with renal tubular dysplasia. There was no fetal exposure to ACE inhibitors in the affected infants. Phenotypic similarities between these familial cases and those associated with ACE inhibition suggest an abnormality of the "renin-angiotensin-aldosterone" system (RAS). It is postulated that the molecular pathology in this uncommon autosomal recessive proximal renal tubular dysgenesis could be related to mutations of the gene systems governing the RAS. Images PMID:9222960

  1. 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

  2. Therapeutic substitution post-patent expiry: the cases of ACE inhibitors and proton pump inhibitors.

    PubMed

    Vandoros, Sotiris

    2014-05-01

    This paper examines whether there is a switch in total (originator and generic) consumption after generic entry from molecules that face generic competition towards other molecules of the same class, which are still in-patent. Data from six European countries for the time period 1991 to 2006 are used to study the cases of angiotensin-converting enzyme inhibitors and proton pump inhibitors. Empirical evidence shows that patent expiry of captopril and enalapril led to a switch in total (off-patent originator and generic) consumption towards other in-patent angiotensin-converting enzyme inhibitors, whereas patent expiry of omeprazole led to a switch in consumption towards other proton pump inhibitors. This phenomenon makes generic policies ineffective and results in an increase in pharmaceutical expenditure due to the absence of generic alternatives in the market of in-patent molecules.

  3. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    SciTech Connect

    Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  4. 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

  5. Renal hemodynamics in hypertensive renal allograft recipients: effects of calcium antagonists and ACE inhibitors.

    PubMed

    Grekas, D; Dioudis, C; Kalevrosoglou, I; Alivanis, P; Derveniotis, V; Tourkantonis, A

    1996-06-01

    Hypertension present in more than 50% of successfully renal transplanted patients and its prevalence has slightly increased since the introduction of cyclosporine A. Twenty patients, 9 women and 11 men aged from 30 to 58 years, with stable cadaveric renal allograft function and moderate to severe hypertension, were included in the study. Renal artery graft stenosis causing hypertension were excluded. All patients were given triple drug immunosuppressive treatment with methylprednisolone, azathioprine and cyclosporine A (CsA) and their hypertension was treated with a nifedipine dose of 20 mg twice daily. To evaluate the effect of ACE inhibitors on renal hemodynamics and hypertension, a 4 mg/daily dose of perindopril was added to the above regimen for two months. Effective renal plasma flow (ERPF) decreased from 208 +/- 54 to 168 +/- 61 ml/min and renal vascular resistance (RVR) increased from 75 +/- 12 to 88 +/- 17 mm Hg/ml/min (P < 0.05 and P < 0.01, respectively). Mean blood pressure was significantly (P < 0.001) reduced by the combination of both agents in comparison to the blood pressure control by monotherapy with nifedipine. It is suggested that the combination of both antihypertensive agents was more effective than monotherapy with nifedipine in controlling blood pressure, but less favorable on the renal hemodynamic response in hypertensive renal transplant patients who were maintained on CsA.

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

    PubMed

    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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Model Development and Use of ACE Inhibitors for Preclinical Mitigation of Radiation-Induced Injury to Multiple Organs

    PubMed Central

    Medhora, Meetha; Gao, Feng; Wu, Qingping; Molthen, Robert C.; Jacobs, Elizabeth R.; Moulder, John E.; Fish, Brian L.

    2014-01-01

    The NIH/NIAID initiated a countermeasure program to develop mitigators for radiation-induced injuries from a radiological attack or nuclear accident. We have previously characterized and demonstrated mitigation of single organ injuries, such as radiation pneumonitis, pulmonary fibrosis or nephropathy by angiotensin converting enzyme (ACE) inhibitors. Our current work extends this research to examine the potential for mitigating multiple organ dysfunctions occurring in the same irradiated rats. Using total body irradiation (TBI) followed by bone marrow transplant, we tested four doses of X radiation (11, 11.25, 11.5 and 12 Gy) to develop lethal late effects. We identified three of these doses (11, 11.25 and 11.5 Gy TBI) that were lethal to all irradiated rats by 160 days to test mitigation by ACE inhibitors of injury to the lungs and kidneys. In this study we tested three ACE inhibitors at doses: captopril (88 and 176 mg/m2/day), enalapril (18, 24 and 36 mg/m2/day) and fosinopril (60 mg/m2/day) for mitigation. Our primary end point was survival or criteria for euthanization of morbid animals. Secondary end points included breathing intervals, other assays for lung structure and function and blood urea nitrogen (BUN) to assess renal damage. We found that captopril at 176 mg/m2/day increased survival after 11 or 11.5 Gy TBI. Enalapril at 18–36 mg/m2/day improved survival at all three doses (TBI). Fosinopril at 60 mg/m2/day enhanced survival at a dose of 11 Gy, although no improvement was observed for pneumonitis. These results demonstrate the use of a single countermeasure to mitigate the lethal late effects in the same animal after TBI. PMID:25361399

  12. ACE and platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host plant of Herba Cistanches) growing in Xinjiang

    PubMed Central

    Xing, Yachao; Liao, Jing; Tang, Yingzhan; Zhang, Peng; Tan, Chengyu; Ni, Hui; Wu, Xueqin; Li, Ning; Jia, Xiaoguang

    2014-01-01

    Background: Tamarix hohenackeri Bunge is a salt cedar that grows widespread in the desert mountains in Xinjiang. T. hohenackeri has not been investigated earlier, although there are many reports of phytochemical work on other Tamarix species. Materials and Methods: To find out natural angiotensin-converting enzyme (ACE) inhibitor and platelet aggregation inhibitors, the bioactive extract (ethyl acetate [EtOAc] fraction) from the dried aerial parts of T. hohenackeri were investigated. The active fraction was purified by repeated column chromatography, including silica gel, Sephadex LH-20 column, medium-pressure liquid chromatography (MPLC) (polyamide column) and high-performance liquid chromatography (HPLC). The isolated major constituents were tested for their anti-platelet aggregation activity. Results: Bioassay-directed separation of the EtOAc fraction of the 70% ethanol extract from the air-dried aerial parts of T. hohenackeri led to the isolation of a new triterpenoid lactone (1), together with 13 known compounds (2-14). It was the first time to focus on screening bioactive constituents for this plant. The chemical structures were established on the basis of spectral data (ESI-MS and NMR). The results showed that the flavonoid compounds (7 and 8) and phenolic compounds (9, 10, 11, and 14) were potential ACE inhibitors. And the flavonoid compounds (5 and 7) showed significant anti-platelet aggregation activities. Conclusion: On the basis of the chemical and biological data, the material basis of ACE inhibitory activity for the active part was the phenolic constituents. However, the flavonoid compounds were responsible for the anti-platelet aggregation. The primary structure and activity relationship were also discussed respectively. PMID:24914275

  13. Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia

    PubMed Central

    Gao, Yang; O'Caoimh, Rónán; Healy, Liam; Kerins, David M; Eustace, Joseph; Guyatt, Gordon; Sammon, David; Molloy, D William

    2013-01-01

    Objectives There is growing evidence that antihypertensive agents, particularly centrally acting ACE inhibitors (CACE-Is), which cross the blood–brain barrier, are associated with a reduced rate of cognitive decline. Given this, we compared the rates of cognitive decline in clinic patients with dementia receiving CACE-Is (CACE-I) with those not currently treated with CACE-Is (NoCACE-I), and with those who started CACE-Is, during their first 6 months of treatment (NewCACE-I). Design Observational case–control study. Setting 2 university hospital memory clinics. Participants 817 patients diagnosed with Alzheimer's disease, vascular or mixed dementia. Of these, 361 with valid cognitive scores were included for analysis, 85 CACE-I and 276 NoCACE-I. Measurements Patients were included if the baseline and end-point (standardised at 6 months apart) Standardised Mini-Mental State Examination (SMMSE) or Quick Mild Cognitive Impairment (Qmci) scores were available. Patients with comorbid depression or other dementia subtypes were excluded. The average 6-month rates of change in scores were compared between CACE-I, NoCACE-I and NewCACE-I patients. Results When the rate of decline was compared between groups, there was a significant difference in the median, 6-month rate of decline in Qmci scores between CACE-I (1.8 points) and NoCACE-I (2.1 points) patients (p=0.049), with similar, non-significant changes in SMMSE. Median SMMSE scores improved by 1.2 points in the first 6 months of CACE treatment (NewCACE-I), compared to a 0.8 point decline for the CACE-I (p=0.003) group and a 1 point decline for the NoCACE-I (p=0.001) group over the same period. Multivariate analysis, controlling for baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups, p=0.002. Conclusions Cognitive scores may improve in the first 6 months after CACE-I treatment and use of CACE-Is is associated with a reduced rate of cognitive

  14. [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

  15. Individualised therapy of angiotensin converting enzyme (ACE) inhibitors in stable coronary artery disease: overview of the primary results of the PERindopril GENEtic association (PERGENE) study.

    PubMed

    Brugts, J J; de Maat, M P M; Danser, A H J; Boersma, E; Simoons, M L

    2012-01-01

    In patients with stable coronary artery disease (CAD) without overt heart failure, ACE inhibitors are among the most commonly used drugs as these agents have been proven effective in reducing the risk of cardiovascular events. Considerable individual variations in the blood pressure response to ACE inhibitors are observed and as such heterogeneity in clinical treatment effect would be likely as well. Assessing the consistency of treatment benefit is essential for the rational and cost-effective prescription of ACE inhibitors. Information on heterogeneities in treatment effect between subgroups of patients could be used to develop an evidence-based guidance for the installation of ACE-inhibitor therapy. Obviously, therapy should only be applied in those patients who most likely will benefit. Attempts to develop such treatment guidance by using clinical characteristics have been unsuccessful. No heterogeneity in risk reduction by ACE inhibitors has been observed in relation to relevant clinical characteristics. A new approach to such 'guided-therapy' could be to integrate more patient-specific characteristics such as the patients' genetic information. If proven feasible, pharmacogenetic profiling could optimise patients' benefit of treatment and reduce unnecessary treatment of patients. Cardiovascular pharmacogenetic research of ACE inhibitors in coronary artery disease patients is in a formative stage and studies are limited. The PERGENE study is a large pharmacogenetic substudy of the EUROPA trial, aimed to assess the achievability of pharmacogenetic profiling. We provide an overview of the main results of the PERGENE study in terms of the genetic determinants of treatment benefit and blood pressure response. The main results of the PERGENE study show a pharmacogenetic profile related to the treatment benefit of perindopril identifying responders and non-responders to treatment. PMID:21688035

  16. The acute renal actions of angiotensin converting enzyme inhibitors in the sodium-depleted conscious primate are mediated by inhibition of the renin-angiotensin system.

    PubMed

    Humke, U; Levens, N; Wood, J; Hofbauer, K

    1992-01-01

    The purpose of this study was to determine if the changes in renal function acutely produced by an inhibitor of angiotensin converting enzyme (ACE) in the sodium-depleted conscious marmoset can be explained primarily by blockade of the renin-angiotensin system. Intravenous injection of a dose of the ACEI, enalaprilate (2 mg/kg), that produced a maximal lowering of blood pressure (BP), also decreased renal vascular resistance and increased renal blood flow. Glomerular filtration rate was unchanged by enalaprilat, leading to a fall in the filtration fraction. In comparison, a dose of the renin inhibitory monoclonal antibody, R-3-36-16 (0.1 mg/kg), that also produced a maximal fall in BP, produced similar changes in renal hemodynamics to those observed after administration of the ACEI. Combined administration of 2 mg/kg enalaprilat and 0.1 mg/kg R-3-36-16 produced changes in BP and renal hemodynamics similar to those produced by the same doses of either agent administered alone. Enalaprilat (2 mg/kg) significantly increased urine volume (UV) and urinary sodium excretion (UNaV). In contrast, these parameters were not significantly altered by 0.1 mg/kg R-3-36-16. However, when given at a 10-fold higher dose, the monoclonal antibody produced an increase in UNaV and UV identical to that produced by the ACEI alone. Enalaprilat did not increase UV and UNaV excretion to a greater extent than the high dose of the renin inhibitory antibody. These results demonstrate that acute administration of an ACEI affects BP and renal function in the sodium-depleted conscious primate primarily by inhibition of the renin-angiotensin system.

  17. Inhibitory effects of enalaprilat on rat cardiac fibroblast proliferation via ROS/P38MAPK/TGF-β1 signaling pathway.

    PubMed

    Yu, Min; Zheng, Yang; Sun, Hong-Xia; Yu, Du-Juan

    2012-01-01

    Enalaprilat (Ena.), an angiotensin II (Ang II) converting enzyme inhibitor (ACEI), can produce some therapeutic effects on hypertension, ventricular hypertrophy and myocardial remodeling in clinic, but its precise mechanism, especially its signaling pathways remain elusive. In this study, cardiac fibroblasts (CFb) was isolated by the trypsin digestion method; a BrdU proliferation assay was adopted to determine cell proliferation; an immunofluorescence assay was used to measure intracellular reactive oxygen species (ROS); immunocytochemistry staining and Western blotting assay were used to detect phosphorylated p38 mitogen activated protein kinase (p-p38MAPK) and transforming growth factor-β(1) (TGF-β(1)) protein expression, respectively. The results showed that Ang II (10(-7) M) stimulated the cardiac fibroblast proliferation which was inhibited by NAC (an antioxidant), SB203580 (a p38MAPK inhibitor) or enalaprilat; Ang II caused an burst of intracellular ROS level within thirty minutes, an increase in p-p38MAPK (3.6-fold of that in the control group), as well as an elevation of TGF-β(1) meantime; NAC, an antioxidant, and enalaprilat treatment attenuated cardiac fibroblast proliferation induced by Ang II and decreased ROS and p-p38MAPK protein levels in rat cardiac fibroblast; SB203580 lowered TGF-β(1) protein expression in rats' CFb in a dose-dependent manner. It could be concluded that enalaprilat can inhibit the cardiac fibroblast proliferation induced by Ang II via blocking ROS/P38MAPK/TGF-β(1) signaling pathways and the study provides a theoretical proof for the application of ACEIs in treating myocardial fibrosis and discovering the primary mechanism through which ACEIs inhibit CFb proliferation. PMID:22395404

  18. Interactions of angiotensin-converting enzyme, kinins and nitric oxide in circulation and the beneficial effects of ACE inhibitors in cardiovascular diseases.

    PubMed

    Magen, E; Viskoper, R J

    2000-12-01

    Renin-angiotensin-aldosterone systems play a critical role in the development and progression of cardiovascular diseases, and inhibitors of angiotensin-converting enzyme have proven effective for the treatment of these diseases. Since angiotensin II receptor antagonists can inhibit the effects of angiotensin II via ACE-independent pathways, e.g., chymase, they were considered to be more effective than ACEIs. On the other hand, ACE inhibitors can increase bradykinin, and thus, nitric oxide, which may cause potent cardioprotection, inhibition of smooth muscle proliferation and attenuation of inflammation mechanisms. It appears that angiotensin II receptor antagonists and ACEIs may mediate cardioprotection in different ways. This is the rationale to explore the possibility of a combined administration of both drugs for the treatment of chronic heart failure and other cardiovascular pathology. In this review we try to analyze the role of ACE, kinins and chymase inhibition in the pathophysiology and treatment of cardiovascular diseases.

  19. 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

  20. 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

  1. 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.

  2. 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

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

    PubMed

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

    2015-07-01

    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

  4. 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

  5. Efficacy and Safety of Complete RAAS Blockade with ALISKIREN in Patients with Refractory Proteinuria Who were already on Combined ACE Inhibitor, ARB, and Aldosterone Antagonist

    PubMed Central

    Sreelatha, M

    2016-01-01

    Introduction Proteinuria is always associated with intrinsic kidney disese and is a strong predictor of later development of End Stage Renal Disease (ESRD). As Renin Angiotensin Aldosterone System (RAAS) has a role in mediating proteinuria, inhibitors of this system are renoprotective and patients with refractory proteinuria are put on a combination of these agents. The routinely employed triple blockade of RAAS with Angiotensin Converting Enzyme (ACE) inhibitor, ARB and Aldosterone antagonist has many limitations. Addition of Aliskiren to this combination suppresses the RAAS at the earliest stage and can offset many of these limitations. Aim This study was conducted to assess the safety and efficacy of complete RAAS blockade by the addition of Aliskiren in those patients with refractory proteinuria who were already on triple blockade with ACE inhibitor, ARB and Aldosterone antagonist. Settings This study was conducted in Nephrology Department, Calicut Medical College. Materials and Methods A total of 36 patients with refractory proteinuria who were already on ACE inhibitor, ARB and Aldosterone antagonist were divided in to two groups A and B. Group A received Aliskiren in addition to the above combination whereas group B continued the same treatment for 12 weeks. Efficacy of the treatment was assessed by recording 24hr urine protein and safety by S.Creatinine, S.Potassium every 2 weeks of the treatment period. Statistical Analysis Statistical analysis of the lab values was done using SPSS software. Unpaired t-test, Paired t-test and Chi-square test were done for data analysis. Results Statistical analysis revealed that addition of Aliskiren to the combination therapy with ACE inhibitor+ ARB+ Aldosterone antagonist offers no advantage. But mean reduction in proteinuria was more with Group A than Group B. There is no statistically significant change in S.Creatinine and S.Potassium at the end of treatment. Conclusion As proteinuria is a strong risk factor for

  6. A review of the preclinical cardiovascular pharmacology of cilazapril, a new angiotensin converting enzyme inhibitor.

    PubMed

    Waterfall, J F

    1989-01-01

    1. Cilazapril is the monoethyl ester prodrug form of the di-acid cilazaprilat, a new angiotensin converting enzyme (ACE) inhibitor. Cilazaprilat has an IC50 of 1.9 nM as an inhibitor of rabbit lung ACE in vitro making it one of the most potent ACE inhibitors currently available. Studies on a wide range of other enzymes show that the inhibition is highly specific. 2. An oral dose of 0.1 mg kg-1 cilazapril evoked the same maximum degree of plasma ACE inhibition (approximately 76%) in the rat as 0.25 mg kg-1 enalapril. Cilazapril (0.25 mg kg-1 p.o.) inhibited plasma ACE by greater than 95%. The rate of recovery of ACE activity was slower with cilazapril (5-6% h-1) than with enalapril (10% h-1). 3. In anaesthetised rats cilazaprilat was equipotent with ramiprilat and slightly more potent (1.5x) than enalaprilat as an inhibitor of the angiotensin I pressor response. 4. Following oral administration to conscious rats and intravenous administration to anaesthetised dogs, cilazapril was 2-4.5x more potent than enalapril as an ACE inhibitor. 5. In cats cilazapril (0.1 and 0.3 mg kg-1 p.o.) dose dependently decreased plasma ACE activity and the angiotensin pressor response. Peak effects occurred at 2 h after dosing and plasma ACE inhibition was maintained at greater than or equal to 50% for up to 18 h. Mean arterial pressure was also decreased dose dependently with a peak effect at 3-4 h. 6. Daily oral dosing of cilazapril (30 mg kg-1 p.o.) to spontaneously hypertensive rats evoked a progressive and prolonged (24 h) antihypertensive response with a maximum decrease in systolic blood pressure of 110 mm Hg. 7. Cilazapril (10 mg kg-1 p.o. twice daily for 3.5 days) progressively decreased blood pressure in volume depleted renal hypertensive dogs. The maximum fall in systolic pressure was 39 +/- 6 mm Hg. 8. Haemodynamic studies in open chest anaesthetised dogs showed that the hypotensive response to intravenous cilazapril was accompanied by a reduction in total peripheral

  7. 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

  8. 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

  9. 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

  10. 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

  11. Membrane-associated zinc peptidase families: comparing ACE and ACE2.

    PubMed

    Guy, J L; Lambert, D W; Warner, F J; Hooper, N M; Turner, A J

    2005-08-01

    In contrast to the relatively ubiquitous angiotensin-converting enzyme (ACE), expression of the mammalian ACE homologue, ACE2, was initially described in the heart, kidney and testis. ACE2 is a type I integral membrane protein with its active site domain exposed to the extracellular surface of endothelial cells and the renal tubular epithelium. Here ACE2 is poised to metabolise circulating peptides which may include angiotensin II, a potent vasoconstrictor and the product of angiotensin I cleavage by ACE. To this end, ACE2 may counterbalance the effects of ACE within the renin-angiotensin system (RAS). Indeed, ACE2 has been implicated in the regulation of heart and renal function where it is proposed to control the levels of angiotensin II relative to its hypotensive metabolite, angiotensin-(1-7). The recent solution of the structure of ACE2, and ACE, has provided new insight into the substrate and inhibitor profiles of these two key regulators of the RAS. As the complexity of this crucial pathway is unravelled, there is a growing interest in the therapeutic potential of agents that modulate the activity of ACE2.

  12. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

    PubMed

    Sarro, Giovambattista De; Paola, Eugenio Donato Di; Gratteri, Santo; Gareri, Pietro; Rispoli, Vincenzo; Siniscalchi, Antonio; Tripepi, Giovanni; Gallelli, Luca; Citraro, Rita; Russo, Emilio

    2012-03-01

    The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

  13. 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

  14. 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

  15. Selective imidazoline agonist moxonidine plus the ACE inhibitor ramipril in hypertensive patients with impaired insulin sensitivity: partners in a successful MARRIAGE?

    PubMed

    Rayner, Brian

    2004-03-01

    Hypertension in combination with clinically overt diabetes mellitus is recognized as a particularly powerful combination of risk factors that greatly increases cardiovascular vulnerability. There is also evidence that presumed pre-diabetic conditions such as insulin resistance, hyperinsulinaemia and compensatory hyperglycaemia may amplify overall cardiovascular risk in patients with hypertension, especially when encountered as part of the condition known as metabolic syndrome X (Reaven's syndrome). The long-term benefits of antihypertensive therapy may be compromised if these drugs exert adverse effects on metabolic parameters such as insulin sensitivity, or if they promote a transition from pre-diabetes to overt diabetes. Class differences in the effects of antihypertensives on metabolic indices may therefore be an important consideration when choosing treatment for patients who exhibit these characteristics. Experience from clinical trials suggests that drugs that target the renin-angiotensin system may have metabolic advantages over drugs such as beta-blockers and diuretics, but this conclusion has not been proved definitively. Moxonidine, which selectively targets imidazoline type-1 receptors in the sympathetic vasomotor centres of the rostral-ventrolateral medulla, is an effective antihypertensive and has been reported to exert favourable metabolic effects in preclinical and clinical studies. The MARRIAGE study (Moxonidine And Ramipril Regarding Insulin And Glucose Evaluation) will extend these preliminary observations by comparing the effects of moxonidine and the ACE inhibitor ramipril--and the combination of both drugs--on metabolic and haemodynamic parameters in patients with hypertension and impaired fasting glycaemia. A description is provided of the design and conduct of MARRIAGE.

  16. Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

    PubMed Central

    Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

    2016-01-01

    Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

  17. 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…

  18. ACES: Final performance report

    NASA Astrophysics Data System (ADS)

    Baxter, V. D.

    1981-04-01

    The performance of the ACES in a single family residence near Knoxville, Tennessee was compared with that of two different air to air heat pumps in an identical house. Results show that energy was saved for the testing years. In addition to reducing consumption, the ACES significantly reduced integrated peak utility demands. Reinsulation of the ice storage bin reduced heat leakage rates by about 40 percent and resulted in increasing ground temperatures by an average of 5.60 C over first year levels. The demonstration project and the ACES concept are described. Data acquisition procedures, system modifications, steady state performance, annual cycle performance, and effects of modifications are discussed.

  19. 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.

  20. 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

  1. ACE inhibition can improve orthostatic proteinuria associated with nutcracker syndrome.

    PubMed

    Ha, Tae-Sun; Lee, Eun-Ju

    2006-11-01

    Left renal vein entrapment syndrome (nutcracker syndrome) was documented by magnetic resonance angiography (MRA) as a cause of orthostatic proteinuria in a 14-year-old girl female adolescent. Because of continuous proteinuria we performed a left renal biopsy which showed moderate mesangial hypercellularity. Her overt orthostatic proteinuria disappeared after a treatment of angiotensin-converting enzyme (ACE) inhibition. Nutcracker syndrome remains a rare but important cause of elevated protein excretion, which can induce mesangial changes and be improved by ACE inhibitor treatment.

  2. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism

    PubMed Central

    2004-01-01

    In the RAS (renin–angiotensin system), Ang I (angiotensin I) is cleaved by ACE (angiotensin-converting enzyme) to form Ang II (angiotensin II), which has effects on blood pressure, fluid and electrolyte homoeostasis. We have examined the kinetics of angiotensin peptide cleavage by full-length human ACE, the separate N- and C-domains of ACE, the homologue of ACE, ACE2, and NEP (neprilysin). The activity of the enzyme preparations was determined by active-site titrations using competitive tight-binding inhibitors and fluorogenic substrates. Ang I was effectively cleaved by NEP to Ang (1–7) (kcat/Km of 6.2×105 M−1·s−1), but was a poor substrate for ACE2 (kcat/Km of 3.3×104 M−1·s−1). Ang (1–9) was a better substrate for NEP than ACE (kcat/Km of 3.7×105 M−1·s−1 compared with kcat/Km of 6.8×104 M−1·s−1). Ang II was cleaved efficiently by ACE2 to Ang (1–7) (kcat/Km of 2.2×106 M−1·s−1) and was cleaved by NEP (kcat/Km of 2.2×105 M−1·s−1) to several degradation products. In contrast with a previous report, Ang (1–7), like Ang I and Ang (1–9), was cleaved with a similar efficiency by both the N- and C-domains of ACE (kcat/Km of 3.6×105 M−1·s−1 compared with kcat/Km of 3.3×105 M−1·s−1). The two active sites of ACE exhibited negative co-operativity when either Ang I or Ang (1–7) was the substrate. In addition, a range of ACE inhibitors failed to inhibit ACE2. These kinetic data highlight that the flux of peptides through the RAS is complex, with the levels of ACE, ACE2 and NEP dictating whether vasoconstriction or vasodilation will predominate. PMID:15283675

  3. 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

  4. 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

  5. Affinity purification of angiotensin converting enzyme inhibitory peptides using immobilized ACE.

    PubMed

    Megías, Cristina; Pedroche, Justo; Yust, María del Mar; Alaiz, Manuel; Girón-Calle, Julio; Millan, Francisco; Vioque, Javier

    2006-09-20

    A lung extract rich in angiotensin converting enzyme (ACE) and pure ACE were immobilized by reaction with the activated support 4 BCL glyoxyl-agarose. These immobilized ACE derivatives were used for purification of ACE inhibitory peptides by affinity chromatography. The immobilized lung extract was used to purify inhibitory peptides from sunflower and rapeseed protein hydrolysates that had been obtained by treatment of protein isolates with alcalase. The ACE binding peptides that were retained by the derivatives were specifically released by treatment with the ACE inhibitor captopril and further purified by reverse-phase C18 HPLC chromatography. Inhibitory peptides with IC50 50 and 150 times lower than those of the original sunflower and rapeseed hydrolysates, respectively, were obtained. The derivative prepared using pure ACE was used for purification of ACE inhibitory peptides from the same type of sunflower protein hydrolysate. ACE binding peptides were released from the ACE-agarose derivatives by treatment with 1 M NaCl and had an IC50 a little higher than those obtained using immobilized extract and elution with captopril. Affinity chromatography facilitated the purification of ACE inhibitory peptides and potentially other bioactive peptides present in food proteins.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

    PubMed Central

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Fülöp, Gábor Á.; Csató, Viktória; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Szentkirályi, István Elek; Maros, Tamás Miklós; Szerafin, Tamás; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo. PMID:24691203

  12. 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

  13. 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 ...

  14. 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

  15. 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

  16. ALTUS Cumulus Electrification Study (ACES)

    NASA Technical Reports Server (NTRS)

    Kim, Tony; Blakeslee, Richard; Russell, Larry W. (Technical Monitor)

    2002-01-01

    The ALTUS Cumulus Electrification Study (ACES) is an uninhabited aerial vehicle (UAV)-based project that will investigate thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES is being conducted to both investigate storm electrical activity and its relationship to storm morphology, and validate Tropical Rainfall Measurement Mission (TRMM) satellite measurements. In addition, as part of NASA's UAV-based science demonstration program, this project will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. Part of the demonstration involves getting approvals from the Federal Aviation Administration and the NASA airworthiness flight safety review board. ACES will employ 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 (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. ACES will contribute 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) offers a useful 'cloud-top' perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, 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. In addition, concurrent ground-based observations will enable the UAV measurements to be more completely interpreted and evaluated in the context of the thunderstorm structure, evolution, and

  17. Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow

    PubMed Central

    Sigurdsson, Sigurdur T; Paulson, Olaf B; Høj Nielsen, Arne; Strandgaard, Svend

    2014-01-01

    The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was the subject of this study. CBF was measured in Sprague–Dawley rats with laser Doppler technique. The blood pressure was lowered by controlled bleeding. Six groups of rats were studied: a control group and five groups given drugs intravenously: an ACE inhibitor (enalaprilat), an ARB (candesartan), a bradykinin-2 receptor antagonist (Hoe 140), a combination of enalaprilat and Hoe 140, and a combination of candesartan and Hoe 140. In the control group, the lower limit of CBF autoregulation was 54±9 mm Hg (mean±s.d.), with enalaprilat it was 46±6, with candesartan 39±8, with Hoe 140 53±6, with enalaprilat/Hoe 140 52±6, and with candesartan/Hoe 140 50±7. Both enalaprilat and candesartan lowered the lower limit of autoregulation of CBF significantly. The bradykinin antagonist abolished not only the effect of the ACE inhibitor but surprisingly also the effect of the ARB on the lower limit of CBF autoregulation, the latter suggesting an effect on intravascular bradykinin. PMID:24326391

  18. ACEE program rationale and implementation

    SciTech Connect

    Aiken, W.S. Jr.; Petersen, R.H.

    1982-08-01

    The impact of the Aircraft Energy Efficiency program (ACEE) on commercial aviation is examined. In addition to the emphasis on air transport fuel efficiency, topics such as airline operating costs, air transport effects on U.S. trade, and fuel price forecasts are addressed. An overview of the program and its contribution to aviation technology is included.

  19. 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

  20. 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.

  1. Shedding of the germinal angiotensin I-converting enzyme (gACE) involves a serine protease and is activated by epididymal fluid.

    PubMed

    Thimon, Véronique; Métayer, Sonia; Belghazi, Maya; Dacheux, Françoise; Dacheux, Jean-Louis; Gatti, Jean-Luc

    2005-11-01

    The present report describes how the soluble germinal angiotensin I-converting enzyme (gACE) appears in the epididymal fluid, where it has been identified in some laboratory rodents and domestic ungulates. We showed that this gACE results from an active proteolytic process that releases the enzyme's extracellular domain from sperm in a precise spatiotemporal location during epididymal transit and that this process involves serine protease activity. Using polyclonal antibodies against the C-terminal intracellular sequence of ACE, a fragment of approximately 10 kDa was detected on the sperm extract only in the epididymal region, where the gACE release occurs. The fluid enzyme was purified, and the cleavage site was determined by mass spectrometry to be between Arg622 and Leu623 of the mature sheep gACE sequence (equivalent to Arg627 and Arg1203 of the human mature gACE and somatic ACE sequences, respectively). Thereafter, the C-terminal Arg was removed, leaving Ala621 as a C-terminal. Using an in vitro assay, gACE cleavage from sperm was strongly increased by the presence of epididymal fluid from the release zone, and this increase was inhibited specifically by the serine protease-inhibitor AEBSF but not by para-aminobenzamidine. None of the other inhibitors tested, such as metallo- or cystein-protease inhibitors, had a similar effect on release. It was also found that this process did not involve changes in gACE phosphorylation. PMID:15987822

  2. 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.

  3. The Atmospheric Chemistry Experiment (ACE): MLT Results

    NASA Astrophysics Data System (ADS)

    Bernath, Peter

    2010-05-01

    ACE (also known as SCISAT) is making a comprehensive set of simultaneous measurements of numerous 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. The primary instrument is a high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4400 cm-1). ACE was launched by NASA on 12 August 2003 for a nominal 2-year mission; after 6 years on orbit the ACE-FTS performance is still excellent. The first results of ACE have been presented in a special issue of Geophysics Research Letters (http://www.agu.org/journals/ss/ACECHEM1/) in 2005 and recently a special issue on ACE validation has been prepared for Atmospheric Chemistry and Physics (http://www.atmos-chem-phys.net/special_issue114.html) by K. Walker and K. Strong; more information can be found at http://www.ace.uwaterloo.ca. The ACE mission goals were initially focussed mainly on polar ozone chemistry, and more recently have shifted more to the troposphere where organic pollutants such as methanol and formaldehyde have been detected. ACE makes limb observations from about 5 km (cloud free scenes) up to nearly 150 km in the lower thermosphere, where CO2 absorption is still weakly detectable. This talk will review ACE-FTS results in the mesosphere and lower thermosphere. Topics covered will include the mesospheric descent of NOx in the polar winter, spectra of polar mesospheric clouds, concentration profiles of CO2 (which do not match model predictions), and combined Odin-Osiris/ACE-FTS observations.

  4. Angiotensin converting enzyme inhibitors produced by Streptomyces chromofuscus. Discovery, taxonomy and fermentation.

    PubMed

    Nakatsukasa, W M; Wilgus, R M; Thomas, D N; Mertz, F P; Boeck, L D

    1985-08-01

    Culture A58365.1, NRRL 15098, identified as a new strain of Streptomyces chromofuscus, was found to produce two novel angiotensin converting enzyme (ACE) inhibitors, A58365A and A58365B. Fermentation medium studies afforded an increase in ACE inhibitor titers from less than 1 microgram/ml to greater than 20 micrograms/ml. Proline was the obligatory supplement for ACE inhibitor biosynthesis.

  5. 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

  6. Tissue ACE inhibition improves microcirculation in remote myocardium after coronary stenosis: MR imaging study in rats.

    PubMed

    Hiller, Karl-Heinz; Ruile, Philipp; Kraus, Günter; Bauer, Wolfgang R; Waller, Christiane

    2010-12-01

    ACE inhibition has been shown to improve left ventricular (LV) and myocardial blood flow. Previous data regarding changes in capillary density and angiogenesis during ACE inhibition are controversial. The aim of the following study was to determine myocardial microcirculation and heart function in the rat after coronary stenosis using non invasive MR imaging techniques. MR spin labeling and cine techniques have been performed in female Wistar rats 2weeks after coronary artery stenosis. In one group, animals were treated with quinapril in a dose of 6mg/kg/day. Perfusion, relative blood volume (RBV), LV mass and function were determined non-invasively 2weeks after treatment. Finally, fibrosis and capillary density were analyzed histologically. Additionally, hemodynamic measurements were realized in a further group in order to calculate systemic vascular resistance (SVR). Quinapril resulted in a significant increase in perfusion at rest in the remote and the poststenotic myocardium with improved systolic function and a decrease in SVR compared to the non treated control group. Additionally, maximum perfusion and RBV were slightly elevated whereas capillary density was unchanged among the groups. MRI allows for non-invasive quantification of functional microcirculation and heart function. In addition to the well known effect of ACE inhibition on systolic function, treatment with the tissue specific ACE inhibitor quinapril revealed an important microvascular improvement, especially at arteriolar level. These findings may support the use of tissue ACE inhibitors to improve cardiac microcirculation after ischemia.

  7. Expression of Magnaporthe grisea Avirulence Gene ACE1 Is Connected to the Initiation of Appressorium-Mediated Penetration▿

    PubMed Central

    Fudal, Isabelle; Collemare, Jérôme; Böhnert, Heidi U.; Melayah, Delphine; Lebrun, Marc-Henri

    2007-01-01

    Magnaporthe grisea is responsible for a devastating fungal disease of rice called blast. Current control of this disease relies on resistant rice cultivars that recognize M. grisea signals corresponding to specific secreted proteins encoded by avirulence genes. The M. grisea ACE1 avirulence gene differs from others, since it controls the biosynthesis of a secondary metabolite likely recognized by rice cultivars carrying the Pi33 resistance gene. Using a transcriptional fusion between ACE1 promoter and eGFP, we showed that ACE1 is only expressed in appressoria during fungal penetration into rice and barley leaves, onion skin, and cellophane membranes. ACE1 is almost not expressed in appressoria differentiated on Teflon and Mylar artificial membranes. ACE1 expression is not induced by cellophane and plant cell wall components, demonstrating that it does not require typical host plant compounds. Cyclic AMP (cAMP) signaling mutants ΔcpkA and Δmac1 sum1-99 and tetraspanin mutant Δpls1::hph differentiate melanized appressoria with normal turgor but are unable to penetrate host plant leaves. ACE1 is normally expressed in these mutants, suggesting that it does not require cAMP signaling or a successful penetration event. ACE1 is not expressed in appressoria of the buf1::hph mutant defective for melanin biosynthesis and appressorial turgor. The addition of hyperosmotic solutes to buf1::hph appressoria restores appressorial development and ACE1 expression. Treatments of young wild-type appressoria with actin and tubulin inhibitors reduce both fungal penetration and ACE1 expression. These experiments suggest that ACE1 appressorium-specific expression does not depend on host plant signals but is connected to the onset of appressorium-mediated penetration. PMID:17142568

  8. Angiotensin-converting enzyme inhibitors: measurement of relative inhibitory potency and serum drug levels by radioinhibitor binding displacement assay

    SciTech Connect

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

    1987-06-01

    Radioinhibitor binding displacement, a new method for the measurement of angiotensin-converting enzyme (ACE) competitive inhibitors, has been used to assess the relative potency of nine synthetic ACE inhibitors. MK351A, tyrosyl derivative of enalaprilic acid was iodinated with /sup 125/I and used as the radioligand. (/sup 125/I)MK351A bound to human serum ACE in a concentration-dependent manner. It was displaced in a concentration-dependent manner by all ACE inhibitors tested. Fifty percent displacement of bound (/sup 125/I)MK351A (DD50) for each ACE inhibitor correlated well with inhibitor potency ID50, estimated using an ACE enzymatic activity assay using Hip-His-Leu as substrate (r = 0.96, p less than 0.001; n = 9). The radioinhibitor binding displacement assay was used to measure serum concentration of enalaprilic acid (MK422) in human serum samples. Drug concentration estimated by radioinhibitor binding displacement assay correlated closely (r = 0.96, p less than 0.001; n = 22) with the drug concentration measured by a specific radioimmunoassay. The radioinhibitor binding displacement technique using (/sup 125/I)MK351A as the ligand for human serum ACE has general application to all competitive ACE inhibitors, allowing comparison of in vitro ACE inhibitor potencies and estimation of serum ACE inhibitor concentrations.

  9. 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.

  10. 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 ...

  11. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    PubMed Central

    Burckhardt, Bjoern B.; Laeer, Stephanie

    2015-01-01

    In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum). Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers. PMID:25873972

  12. ACE-FTS measurements of HCFC-22

    NASA Astrophysics Data System (ADS)

    Kolonjari, F.; Walker, K. A.; Boone, C. D.; Strahan, S.; McLinden, C. A.; Manney, G. L.; Daffer, W. H.; Bernath, P. F.

    2012-04-01

    In the 1980s scientists discovered an annual springtime minimum in stratospheric ozone over the Antarctic. It was determined that the decline in ozone concentration was primarily caused by catalytic reactions of ozone and chlorine. The emissions of anthropogenic chlorofluorocarbons (CFCs) were determined to be major sources of the chlorine. The Montreal Protocol on Substances that Deplete the Ozone Layer (with its subsequent amendments) restricts the emissions of ozone depleting substances. To fulfill the need for safe, stable replacements of CFCs, hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) were developed. The use of HCFC-22 as a replacement has led to an increase in its atmospheric abundance. This is of concern due to its ozone depletion potential and its global warming potential. The Atmospheric Chemistry Experiment (ACE) is a mission on-board the Canadian satellite SCISAT. The primary instrument on SCISAT is a high-resolution infrared Fourier Transform Spectrometer (ACE-FTS). With its wide spectral range, the ACE-FTS is capable of measuring an extensive range of gases including key CFC and HCFC species. The altitude distribution from the ACE-FTS profiles provides information that is complementary to the ground-based measurements that have been used to monitor these species. The global distribution of HCFC-22 has been computed from measurements by ACE-FTS. Both seasonal variations and an inter-hemispheric difference are observed. Additionally, a rapid increase in the global concentration of HCFC-22 has been observed since the start of the ACE mission in 2004. Comparisons to ground-based and air-borne measurements show good agreement with the ACE-FTS measurements. The global distributions of HCFC-22 have also been compared to a chemistry and transport model (CTM), the Global Modelling Initiative Combined Stratospheric-Tropospheric Model. There are distinct differences between the model results and ACE-FTS measurements. The causes and

  13. 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.

  14. Renin-angiotensin-aldosterone system inhibition: overview of the therapeutic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors.

    PubMed

    Mercier, Kelly; Smith, Holly; Biederman, Jason

    2014-12-01

    Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy in hypertensive diabetic patients with macroalbuminuria, microalbuminuria, or normoalbuminuria has been repeatedly shown to improve cardiovascular mortality and reduce the decline in glomerular filtration rate. Renin-angiotensin-aldosterone system (RAAS) blockade in normotensive diabetic patients with normoalbuminuria or microalbuminuria cannot be advocated at present. Dual RAAS inhibition with ACE inhibitors plus ARBs or ACE inhibitors plus direct renin inhibitors has failed to improve cardiovascular or renal outcomes but has predisposed patients to serious adverse events.

  15. Renin-angiotensin-aldosterone system inhibition: overview of the therapeutic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors.

    PubMed

    Mercier, Kelly; Smith, Holly; Biederman, Jason

    2014-12-01

    Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy in hypertensive diabetic patients with macroalbuminuria, microalbuminuria, or normoalbuminuria has been repeatedly shown to improve cardiovascular mortality and reduce the decline in glomerular filtration rate. Renin-angiotensin-aldosterone system (RAAS) blockade in normotensive diabetic patients with normoalbuminuria or microalbuminuria cannot be advocated at present. Dual RAAS inhibition with ACE inhibitors plus ARBs or ACE inhibitors plus direct renin inhibitors has failed to improve cardiovascular or renal outcomes but has predisposed patients to serious adverse events. PMID:25439533

  16. Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele.

    PubMed

    Qiu, Wei Qiao; Mwamburi, Mkaya; Besser, Lilah M; Zhu, Haihao; Li, Huajie; Wallack, Max; Phillips, Leslie; Qiao, Liyan; Budson, Andrew E; Stern, Robert; Kowall, Neil

    2013-01-01

    Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer's disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer's Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared with those who had not been taking an ACE inhibitor. In contrast, in the presence of ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype.

  17. The role of ACE2 in cardiovascular physiology.

    PubMed

    Oudit, Gavin Y; Crackower, Michael A; Backx, Peter H; Penninger, Josef M

    2003-04-01

    The renin-angiotensin system (RAS) is critically involved in cardiovascular and renal function and in disease conditions, and has been shown to be a far more complex system than initially thought. A recently discovered homologue of angiotensin-converting enzyme (ACE)--ACE2--appears to negatively regulate the RAS. ACE2 cleaves Ang I and Ang II into the inactive Ang 1-9 and Ang 1-7, respectively. ACE2 is highly expressed in kidney and heart and is especially confined to the endothelium. With quantitative trait locus (QTL) mapping, ACE2 was defined as a QTL on the X chromosome in rat models of hypertension. In these animal models, kidney ACE2 messenger RNA and protein expression were markedly reduced, making ACE2 a candidate gene for this QTL. Targeted disruption of ACE2 in mice failed to elicit hypertension, but resulted in severe impairment in myocardial contractility with increased angiotensin II levels. Genetic ablation of ACE in the ACE2 null mice rescued the cardiac phenotype. These genetic data show that ACE2 is an essential regulator of heart function in vivo. Basal renal morphology and function were not altered by the inactivation of ACE2. The novel role of ACE2 in hydrolyzing several other peptides-such as the apelin peptides, opioids, and kinin metabolites-raises the possibility that peptide systems other than angiotensin and its derivatives also may have an important role in regulating cardiovascular and renal function.

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

    PubMed

    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

  19. 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

  20. The Atmospheric Chemistry Experiment (ACE): Mission Overview

    NASA Astrophysics Data System (ADS)

    Bernath, P.

    2003-04-01

    The ACE 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; (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 will make 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) will give ACE coverage of tropical, mid-latitudes and polar regions. The solar occultation advantages are high sensitivity and self-calibration. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4100 cm-1) will measure the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. The ACE concept is derived from the now-retired ATMOS FTS instrument, which flew on the Space Shuttle in 1985, 1992, 1993, 1994. Climate-chemistry coupling may lead to the formation of an Arctic ozone hole. ACE will provide high quality data to confront these model predictions and will monitor polar chemistry as chlorine levels decline. The ACE-FTS can measure water vapor and HDO in the tropical tropopause region to study dehydration and strat-trop exchange. The molecular signatures of massive forest fires will evident in the ACE infrared spectra. The CO_2 in our spectra can be used to either retrieve atmospheric pressure or (if the instrument pointing knowledge proves to be satisfactory) for an independent retrieval of a CO_2 profile for carbon cycle science. Aerosols and clouds will be monitored using the extinction of solar

  1. Visual hallucinations related to angiotensin-converting enzyme inhibitor use: case reports and review.

    PubMed

    Doane, John; Stults, Barry

    2013-04-01

    Four patients experienced visual hallucinations that appear to have been precipitated by lisinopril. Other cases of visual hallucinations have been reported with other angiotensin-converting enzyme (ACE) inhibitors. Older patients, particularly those with a history of either dementia or mild cognitive impairment, may be at higher risk. Hallucinations resolved within 1 to 30 days after cessation of ACE inhibitors. Development of visual hallucinations after initiation of ACE inhibitors should prompt discontinuation of therapy. Visual hallucinations have been reported in one case involving an ARB. Visual hallucinations have not been associated with direct renin inhibitors. Consideration should be given to use of alternative, unrelated antihypertensive drug classes.

  2. 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…

  3. 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.

  4. 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.

  5. 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…

  6. 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

  7. 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

  8. Cardiac and renal distribution of ACE and ACE-2 in rats with heart failure.

    PubMed

    Cohen-Segev, Ravit; Francis, Bahaa; Abu-Saleh, Niroz; Awad, Hoda; Lazarovich, Aviva; Kabala, Aviva; Aronson, Doron; Abassi, Zaid

    2014-10-01

    Congestive heart failure is often associated with impaired kidney function. Over-activation of the renin-angiotensin-aldosterone system (RAAS) contributes to avid salt and water retention in heart failure. While the expression of angiotensin converting enzyme (ACE), a key enzyme in the synthesis of angiotensin II (Ang II), is well established, the expression of angiotensin converting enzyme-2 (ACE-2), an enzyme responsible for angiotensin 1-7 generation, is largely unknown. This issue is of a special interest since angiotensin 1-7 counteracts many of the proliferative and hypertensive effects of angiotensin II. Therefore, the present study was designed to investigate the expression of both enzymes in the kidney and heart of rats with heart failure. Heart failure (CHF) was induced in male Sprague Dawley rats (n=9) by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls (n=8). Two weeks after surgery, the animals were sacrificed and their hearts and kidneys were harvested for assessment of cardiac remodeling and ACE and ACE-2 immunoreactivity by immunohistochemical staining. ACE immunostaining was significantly increased in the kidneys (4.34 ± 0.39% vs. 2.96 ± 0.40%, P<0.05) and hearts (4.57 ± 0.54% vs. 2.19 ± 0.37%, P<0.01) of CHF rats as compared with their sham controls. In a similar manner, ACE-2 immunoreactivity was also elevated in the kidneys (4.65 ± 1.17% vs. 1.75 ± 0.29%, P<0.05) and hearts (5.48 ± 1.11% vs. 1.13 ± 0.26%, P<0.01) of CHF rats as compared with their healthy controls. This study showed that both ACE and ACE-2 are overexpressed in the cardiac and renal tissues of animals with heart failure as compared with their sham controls. The increased expression of the beneficial ACE-2 in heart failure may serve as a compensatory response to the over-activity of the deleterious isoform, namely, angiotensin converting enzyme 1(ACE-1).

  9. Validation of ozone measurements from the Atmospheric Chemistry Experiment (ACE)

    NASA Astrophysics Data System (ADS)

    Dupuy, E.; Walker, K. A.; Kar, J.; Boone, C. D.; McElroy, C. T.; Bernath, P. F.; Drummond, J. R.; Skelton, R.; McLeod, S. D.; Hughes, R. C.; Nowlan, C. R.; Dufour, D. G.; Zou, J.; Nichitiu, F.; Strong, K.; Baron, P.; Bevilacqua, R. M.; Blumenstock, T.; Bodeker, G. E.; Borsdorff, T.; Bourassa, A. E.; Bovensmann, H.; Boyd, I. S.; Bracher, A.; Brogniez, C.; Burrows, J. P.; Catoire, V.; Ceccherini, S.; Chabrillat, S.; Christensen, T.; Coffey, M. T.; Cortesi, U.; Davies, J.; de Clercq, C.; Degenstein, D. A.; de Mazière, M.; Demoulin, P.; Dodion, J.; Firanski, B.; Fischer, H.; Forbes, G.; Froidevaux, L.; Fussen, D.; Gerard, P.; Godin-Beekmann, S.; Goutail, F.; Granville, J.; Griffith, D.; Haley, C. S.; Hannigan, J. W.; Höpfner, M.; Jin, J. J.; Jones, A.; Jones, N. B.; Jucks, K.; Kagawa, A.; Kasai, Y.; Kerzenmacher, T. E.; Kleinböhl, A.; Klekociuk, A. R.; Kramer, I.; Küllmann, H.; Kuttippurath, J.; Kyrölä, E.; Lambert, J.-C.; Livesey, N. J.; Llewellyn, E. J.; Lloyd, N. D.; Mahieu, E.; Manney, G. L.; Marshall, B. T.; McConnell, J. C.; McCormick, M. P.; McDermid, I. S.; McHugh, M.; McLinden, C. A.; Mellqvist, J.; Mizutani, K.; Murayama, Y.; Murtagh, D. P.; Oelhaf, H.; Parrish, A.; Petelina, S. V.; Piccolo, C.; Pommereau, J.-P.; Randall, C. E.; Robert, C.; Roth, C.; Schneider, M.; Senten, C.; Steck, T.; Strandberg, A.; Strawbridge, K. B.; Sussmann, R.; Swart, D. P. J.; Tarasick, D. W.; Taylor, J. R.; Tétard, C.; Thomason, L. W.; Thompson, A. M.; Tully, M. B.; Urban, J.; Vanhellemont, F.; Vigouroux, C.; von Clarmann, T.; von der Gathen, P.; von Savigny, C.; Waters, J. W.; Witte, J. C.; Wolff, M.; Zawodny, J. M.

    2009-01-01

    This paper presents extensive {bias determination} analyses of ozone observations from the Atmospheric Chemistry Experiment (ACE) satellite instruments: the ACE Fourier Transform Spectrometer (ACE-FTS) and the Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (ACE-MAESTRO) instrument. Here we compare the latest ozone data products from ACE-FTS and ACE-MAESTRO with coincident observations from nearly 20 satellite-borne, airborne, balloon-borne and ground-based instruments, by analysing volume mixing ratio profiles and partial column densities. The ACE-FTS version 2.2 Ozone Update product reports more ozone than most correlative measurements from the upper troposphere to the lower mesosphere. At altitude levels from 16 to 44 km, the average values of the mean relative differences are nearly all within +1 to +8%. At higher altitudes (45-60 km), the ACE-FTS ozone amounts are significantly larger than those of the comparison instruments, with mean relative differences of up to +40% (about +20% on average). For the ACE-MAESTRO version 1.2 ozone data product, mean relative differences are within ±10% (average values within ±6%) between 18 and 40 km for both the sunrise and sunset measurements. At higher altitudes ( 35-55 km), systematic biases of opposite sign are found between the ACE-MAESTRO sunrise and sunset observations. While ozone amounts derived from the ACE-MAESTRO sunrise occultation data are often smaller than the coincident observations (with mean relative differences down to -10%), the sunset occultation profiles for ACE-MAESTRO show results that are qualitatively similar to ACE-FTS, indicating a large positive bias (mean relative differences within +10 to +30%) in the 45-55 km altitude range. In contrast, there is no significant systematic difference in bias found for the ACE-FTS sunrise and sunset measurements.

  10. Validation of ozone measurements from the Atmospheric Chemistry Experiment (ACE)

    NASA Astrophysics Data System (ADS)

    Dupuy, E.; Walker, K. A.; Kar, J.; Boone, C. D.; McElroy, C. T.; Bernath, P. F.; Drummond, J. R.; Skelton, R.; McLeod, S. D.; Hughes, R. C.; Nowlan, C. R.; Dufour, D. G.; Zou, J.; Nichitiu, F.; Strong, K.; Baron, P.; Bevilacqua, R. M.; Blumenstock, T.; Bodeker, G. E.; Borsdorff, T.; Bourassa, A. E.; Bovensmann, H.; Boyd, I. S.; Bracher, A.; Brogniez, C.; Burrows, J. P.; Catoire, V.; Ceccherini, S.; Chabrillat, S.; Christensen, T.; Coffey, M. T.; Cortesi, U.; Davies, J.; de Clercq, C.; Degenstein, D. A.; de Mazière, M.; Demoulin, P.; Dodion, J.; Firanski, B.; Fischer, H.; Forbes, G.; Froidevaux, L.; Fussen, D.; Gerard, P.; Godin-Beekman, S.; Goutail, F.; Granville, J.; Griffith, D.; Haley, C. S.; Hannigan, J. W.; Höpfner, M.; Jin, J. J.; Jones, A.; Jones, N. B.; Jucks, K.; Kagawa, A.; Kasai, Y.; Kerzenmacher, T. E.; Kleinböhl, A.; Klekociuk, A. R.; Kramer, I.; Küllmann, H.; Kuttippurath, J.; Kyrölä, E.; Lambert, J.-C.; Livesey, N. J.; Llewellyn, E. J.; Lloyd, N. D.; Mahieu, E.; Manney, G. L.; Marshall, B. T.; McConnell, J. C.; McCormick, M. P.; McDermid, I. S.; McHugh, M.; McLinden, C. A.; Mellqvist, J.; Mizutani, K.; Murayama, Y.; Murtagh, D. P.; Oelhaf, H.; Parrish, A.; Petelina, S. V.; Piccolo, C.; Pommereau, J.-P.; Randall, C. E.; Robert, C.; Roth, C.; Schneider, M.; Senten, C.; Steck, T.; Strandberg, A.; Strawbridge, K. B.; Sussmann, R.; Swart, D. P. J.; Tarasick, D. W.; Taylor, J. R.; Tétard, C.; Thomason, L. W.; Thompson, A. M.; Tully, M. B.; Urban, J.; Vanhellemont, F.; von Clarmann, T.; von der Gathen, P.; von Savigny, C.; Waters, J. W.; Witte, J. C.; Wolff, M.; Zawodny, J. M.

    2008-02-01

    This paper presents extensive validation analyses of ozone observations from the Atmospheric Chemistry Experiment (ACE) satellite instruments: the ACE Fourier Transform Spectrometer (ACE-FTS) and the Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (ACE-MAESTRO) instrument. The ACE satellite instruments operate in the mid-infrared and ultraviolet-visible-near-infrared spectral regions using the solar occultation technique. In order to continue the long-standing record of solar occultation measurements from space, a detailed quality assessment is required to evaluate the ACE data and validate their use for scientific purposes. Here we compare the latest ozone data products from ACE-FTS and ACE-MAESTRO with coincident observations from satellite-borne, airborne, balloon-borne and ground-based instruments, by analysing volume mixing ratio profiles and partial column densities. The ACE-FTS version 2.2 Ozone Update product reports more ozone than most correlative measurements from the upper troposphere to the lower mesosphere. At altitude levels from 16 to 44 km, the mean differences range generally between 0 and +10% with a slight but systematic positive bias (typically +5%). At higher altitudes (45-60 km), the ACE-FTS ozone amounts are significantly larger than those of the comparison instruments by up to ~40% (typically +20%). For the ACE-MAESTRO version 1.2 ozone data product, agreement within ±10% (generally better than ±5%) is found between 18 and 40 km for the sunrise and sunset measurements. At higher altitudes (45-55 km), systematic biases of opposite sign are found between the ACE-MAESTRO sunrise and sunset observations. While ozone amounts derived from the ACE-MAESTRO sunrise occultation data are often smaller than the coincident observations (by as much as -10%), the sunset occultation profiles for ACE-MAESTRO show results that are qualitatively similar to ACE-FTS and indicate a large positive bias (+10 to +30

  11. 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.

  12. [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

  13. 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.

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

    PubMed Central

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

    2011-01-01

    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

  15. 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%.

  16. 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.

  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. 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

  19. 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

  20. Identification of novel Saccharomyces cerevisiae proteins with nuclear export activity: cell cycle-regulated transcription factor ace2p shows cell cycle-independent nucleocytoplasmic shuttling.

    PubMed

    Jensen, T H; Neville, M; Rain, J C; McCarthy, T; Legrain, P; Rosbash, M

    2000-11-01

    Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5' RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G(1)-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G(1) but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner.

  1. Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats

    PubMed Central

    Dalpiaz, P. L. M.; Lamas, A. Z.; Caliman, I. F.; Ribeiro, R. F.; Abreu, G. R.; Moyses, M. R.; Andrade, T. U.; Gouvea, S. A.; Alves, M. F.; Carmona, A. K.; Bissoli, N. S.

    2015-01-01

    Background There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs). Methodology / Principal Findings Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats. Conclusion Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components. PMID:26010093

  2. 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…

  3. 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

  4. Genetic influences of angiotensin-converting enzyme inhibitor response: an opportunity for personalizing therapy?

    PubMed

    Brugts, Jasper J; Simoons, Maarten L

    2012-08-01

    The angiotensin-converting enzyme (ACE) inhibitors are a cornerstone drug therapy in the current treatment of patients with hypertension, stable coronary artery disease and heart failure. Individualizing therapy of ACE inhibitors with clinical risk factors in low-risk patients with stable coronary artery disease is not feasible. The concept of pharmacogenetics, by studying patient factors more individually, offers a first glimpse in the quest for the 'holy grail' of personalized medicine. As such, genetic targets in the direct pharmacodynamic pathway of ACE inhibitors, the renin-angiotensin-aldosterone system, is a plausible candidate for such an approach. In the past few decades, results of pharmacogenetic studies were scarce and inconsistent. However, recently the first reports of larger pharmacogenetic studies are now confirming that the 'pharmacogenetic approach' might be feasible in the future. The current review focuses on the recent developments in pharmacogenetic research in response to ACE inhibitors in patients with stable coronary artery disease. PMID:23030290

  5. 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

  6. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

    PubMed

    Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

    2016-09-20

    Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.

  7. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

    PubMed

    Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

    2016-09-20

    Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

  8. Angiotensin-converting enzyme inhibition studies by natural leech inhibitors by capillary electrophoresis and competition assay.

    PubMed

    Deloffre, Laurence; Sautiere, Pierre-Eric; Huybrechts, Roger; Hens, Korneel; Vieau, Didier; Salzet, Michel

    2004-06-01

    A protocol to follow the processing of angiotensin I into angiotensin II by rabbit angiotensin-converting enzyme (ACE) and its inhibition by a novel natural antagonist, the leech osmoregulator factor (LORF) using capillary zonal electrophoresis is described. The experiment was carried out using the Beckman PACE system and steps were taken to determine (a) the migration profiles of angiotensin and its yielded peptides, (b) the minimal amount of angiotensin II detected, (c) the use of different electrolytes and (d) the concentration of inhibitor. We demonstrated that LORF (IPEPYVWD), a neuropeptide previously found in leech brain, is able to inhibit rabbit ACE with an IC(50) of 19.8 micro m. Interestingly, its cleavage product, IPEP exhibits an IC(50) of 11.5 micro m. A competition assay using p-benzoylglycylglycylglycine and insect ACE established that LORF and IPEP fragments are natural inhibitors for invertebrate ACE. Fifty-four percent of insect ACE activity is inhibited with 50 micro m IPEP and 35% inhibition with LORF (25 mm). Extending the peptide at both N- and C-terminus (GWEIPEPYVWDES) and the cleavage of IPEP in IP abolished the inhibitory activity of both peptides. Immunocytochemical data obtained with antisera raised against LORF and leech ACE showed a colocalization between the enzyme and its inhibitor in the same neurons. These results showed that capillary zonal electrophoresis is a useful technique for following enzymatic processes with small amounts of products and constitutes the first evidence of a natural ACE inhibitor in invertebrates.

  9. AceCloud: Molecular Dynamics Simulations in the Cloud.

    PubMed

    Harvey, M J; De Fabritiis, G

    2015-05-26

    We present AceCloud, an on-demand service for molecular dynamics simulations. AceCloud is designed to facilitate the secure execution of large ensembles of simulations on an external cloud computing service (currently Amazon Web Services). The AceCloud client, integrated into the ACEMD molecular dynamics package, provides an easy-to-use interface that abstracts all aspects of interaction with the cloud services. This gives the user the experience that all simulations are running on their local machine, minimizing the learning curve typically associated with the transition to using high performance computing services.

  10. 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.

  11. The Canadian Arctic Atmospheric Chemistry Experiment (ACE) Validation Project: Overview and results from ten years of ACE operations

    NASA Astrophysics Data System (ADS)

    Walker, Kaley; Strong, Kimberly

    2014-05-01

    As of February 2014, the Canadian-led Atmospheric Chemistry Experiment (ACE) satellite mission has been making measurements of the Earth's atmosphere for ten years. As ACE operations have extended beyond the initial two-year mission, there is a continuing need to validate the trace gas data products from the ACE-Fourier Transform Spectrometer (ACE-FTS) and the Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (ACE-MAESTRO) instruments. Ground-based measurements provide critical data for the validation of satellite retrievals of trace gases and for the assessment of long-term stability of these measurements. In particular, validation comparisons are needed for ACE during Arctic springtime to understand better the measurements of species involved in stratospheric ozone chemistry. To this end, eleven Canadian Arctic Atmospheric Chemistry Experiment (ACE) Validation Campaigns have been conducted during the spring period (February - April in 2004 - 2014) at the Polar Environment Atmospheric Research Laboratory (PEARL) in Eureka, Nunavut (80°N, 86°W). This 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 zenith-viewing UV-visible grating spectrometers, a Bomem DA8 Fourier transform spectrometer, a Bruker 125HR Fourier transform spectrometer, a Systeme d'Analyse par Observations Zenithales (SAOZ) instrument, and several Brewer spectrophotometers. In the past several years, these results have been used to validate the measurements by the ACE-FTS and ACE-MAESTRO instruments on SCISAT as well

  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 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.

  13. 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.

  14. Investigating the selectivity of metalloenzyme inhibitors.

    PubMed

    Day, Joshua A; Cohen, Seth M

    2013-10-24

    The inhibitory activity of a broad group of known metalloenzyme inhibitors against a panel of metalloenzymes was evaluated. Clinically approved inhibitors were selected as well as several other reported metalloprotein inhibitors in order to represent a broad range of metal binding groups (MBGs), including hydroxamic acid, carboxylate, hydroxypyridinonate, thiol, and N-hydroxyurea functional groups. A panel of metalloenzymes, including carbonic anhydrase (hCAII), several matrix metalloproteinases (MMPs), angiotensin converting enzyme (ACE), histone deacetylase (HDAC-2), and tyrosinase (TY), was selected based on their clinical importance for a range of pathologies. In addition, each inhibitor was evaluated for its ability to remove Fe(3+) from holo-transferrin to gauge the ability of the inhibitors to access Fe(3+) from a primary transport protein. The results show that the metalloenzyme inhibitors are quite selective for their intended targets, suggesting that despite their ability to bind metal ions, metalloprotein inhibitors are not prone to widespread off-target enzyme inhibition activity.

  15. Investigating the Selectivity of Metalloenzyme Inhibitors

    PubMed Central

    Day, Joshua A.; Cohen, Seth M.

    2013-01-01

    The inhibitory activity of a broad group of known metalloenzyme inhibitors against a panel of metalloenzymes was evaluated. Clinically approved inhibitors were selected as well as several other reported metalloprotein inhibitors, in order to represent a broad range of metal binding groups (MBGs), including hydroxamic acid, carboxylate, hydroxypyridinonate, thiol, and N-hydroxyurea functional groups. A panel of metalloenzymes, including carbonic anhydrase (hCAII), several matrix metalloproteinases (MMPs), angiotensin converting enzyme (ACE), histone deacetylase (HDAC-2), and tyrosinase (TY) was selected based on their clinical importance for a range of pathologies. In addition, each inhibitor was evaluated for its ability to remove Fe3+ from holo-transferrin to gauge the ability of the inhibitors to access Fe3+ from a primary transport protein. The results show that the metalloenzyme inhibitors are quite selective for their intended targets, suggesting that despite their ability to bind metal ions, metalloprotein inhibitors are not prone to widespread off-target enzyme inhibition activity. PMID:24074025

  16. Molecular dynamics simulation and molecular docking studies of Angiotensin converting enzyme with inhibitor lisinopril and amyloid Beta Peptide.

    PubMed

    Jalkute, Chidambar Balbhim; Barage, Sagar Hindurao; Dhanavade, Maruti Jayram; Sonawane, Kailas Dasharath

    2013-06-01

    Angiotensin converting enzyme (ACE) cleaves amyloid beta peptide. So far this cleavage mechanism has not been studied in detail at atomic level. Keeping this view in mind, we performed molecular dynamics simulation of crystal structure complex of testis truncated version of ACE (tACE) and its inhibitor lisinopril along with Zn(2+) to understand the dynamic behavior of active site residues of tACE. Root mean square deviation results revealed the stability of tACE throughout simulation. The residues Ala 354, Glu 376, Asp 377, Glu 384, His 513, Tyr 520 and Tyr 523 of tACE stabilized lisinopril by hydrogen bonding interactions. Using this information in subsequent part of study, molecular docking of tACE crystal structure with Aβ-peptide has been made to investigate the interactions of Aβ-peptide with enzyme tACE. The residues Asp 7 and Ser 8 of Aβ-peptide were found in close contact with Glu 384 of tACE along with Zn(2+). This study has demonstrated that the residue Glu 384 of tACE might play key role in the degradation of Aβ-peptide by cleaving peptide bond between Asp 7 and Ser 8 residues. Molecular basis generated by this attempt could provide valuable information towards designing of new therapies to control Aβ concentration in Alzheimer's patient.

  17. Molecular and recombinational mapping of mutations in the Ace locus of Drosophila melanogaster

    SciTech Connect

    Nagoshi, R.N.; Gelbart, W.M.

    1987-11-01

    The Ace locus in Drosophila melanogaster is known to be the structural gene for acetylcholinesterase. Ace is located in a region of chromosome arm 3R which has been subjected to intensive genetic and molecular analysis. Previous deletion mapping studies have identified a 40-kb region with which the Ace gene resides. This report focuses on the further localization of Ace within this 40-kb interval. Within this region, selective fine structure recombinational analysis was employed to localize three recessive Ace lethals relative to unselected restriction site variations. These three mutations fall into a segment of 7 kb within the Ace interval. Fine structure recombinational analysis was also used to confirm that the Ace/sup -/ phenotype of one deletion, Df(3R)Ace/sup HD1/, co-segregated with the molecular deletion. This deletion does not fully remove Ace activity, but it behaves as a recessive Ace lethal. Df(3R)Ace/sup HD1/ is the most distal Ace lesion identified and indicates that the Ace locus must extend at least 16 kb. Several poly(A)transcripts are detectable in the region defined by the Ace lesions. The position and extent of the Ace locus, as well as the types of transcripts found, is consistent with the recent findings which identified Torpedo-AChE homologous cDNA sequences in this region.

  18. Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study

    PubMed Central

    Jiménez-Candil, J; Bermejo, J; Yotti, R; Cortina, C; Moreno, M; Cantalapiedra, J L; García-Fernández, M A

    2005-01-01

    Objective: To determine the effects of angiotensin converting enzyme (ACE) inhibitors in hypertensive patients with aortic valve stenosis (AS). Design: Observational, drug withdrawal, single blinded study, with randomisation of the order of tests. Setting: Hypertension and asymptomatic AS. Patients and interventions: 20 patients (aged 73 (9) years, valve area 0.7 (0.3) cm2, left ventricular ejection fraction ⩾ 45%) were enrolled. Each patient underwent two sets of tests (with and without taking the drug), each of which included clinical evaluation, Doppler echocardiogram, and symptom limited exercise echocardiography. Main outcome measures: Functional and haemodynamic variables while taking and not taking ACE inhibitors. Results: Drug intervention induced no change in patients’ subjective functional class. While taking ACE inhibitors, patients had a lower systolic blood pressure (140 (18) mm Hg with ACE inhibitors v 159 (12) mm Hg without ACE inhibitors, p  =  0.02), a higher mean pressure gradient (34 (15) mm Hg v 28 (18) mm Hg, p  =  0.037), and a higher left ventricular stroke work loss (19 (6)% v 14 (10)%, p  =  0.009). Other baseline functional and haemodynamic parameters were unmodified. Five patients had an abnormal blood pressure response during one of the exercise tests (two patients while taking the drug and three patients while not taking the drug). When taking ACE inhibitors, patients had a higher stroke volume at peak stress (59 (11) ml v 54 (25) ml, p  =  0.046). All other stress variables remained constant. Conclusions: In AS, the afterload relief caused by ACE inhibitors is blunted by a parallel increase in the pressure gradient. However, ACE inhibitors favourably affect stress haemodynamic function in most hypertensive patients with AS and should not be discontinued. PMID:16162624

  19. 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

  20. 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.

  1. 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.

  2. [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

  3. [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.

  4. Deletion of the aceE gene (encoding a component of pyruvate dehydrogenase) attenuates Salmonella enterica serovar Enteritidis.

    PubMed

    Pang, Ervinna; Tien-Lin, Chang; Selvaraj, Madhan; Chang, Jason; Kwang, Jimmy

    2011-10-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major food-borne pathogen. From a transposon insertion mutant library created previously using S. Enteritidis 10/02, one of the mutants was identified to have a 50% lethal dose (LD(50) ) at least 100 times that of the parental strain in young chicks, with an attenuation in a poorly studied gene encoding a component of pyruvate dehydrogenase, namely the aceE gene. Evaluation of the in vitro virulence characteristics of the ΔaceE∷kan mutant revealed that it was less able to invade epithelial cells, less resistant to reactive oxygen intermediate, less able to survive within a chicken macrophage cell line and had a retarded growth rate compared with the parental strain. Young chicks vaccinated with 2 × 10(9) CFU of the ΔaceE∷kan mutant were protected from the subsequent challenge of the parental strain, with the mutant colonized in the liver and spleen in a shorter time than the group infected with the parental strain. In addition, compared with the parental strain, the ΔaceE∷kan mutant did not cause persistent eggshell contamination of vaccinated hens.

  5. 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.

  6. 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.

  7. 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... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of...

  8. 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... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of...

  9. 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... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of...

  10. 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... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of...

  11. 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... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of...

  12. Young & ACE: Young Unemployed People and Adult and Community Education.

    ERIC Educational Resources Information Center

    Adult, Community, and Further Education Board, Melbourne (Australia).

    Pilot projects designed to increase the access of young unemployed Australians to adult and community education (ACE) were undertaken in one rural and one metropolitan adult, community and further education region with significant rates of unemployment among individuals aged 15-24 years. Two consortia were selected to conduct the pilot programs,…

  13. 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…

  14. The Economics of ACE Delivery. A Research Report.

    ERIC Educational Resources Information Center

    McIntyre, John; Brown, Tony; Ferrier, Fran

    The financial operations of providers of adult and community education (ACE) in New South Wales, Australia, were examined in a conceptual and empirical study. Enrollment data were analyzed and case studies of three community colleges and two community adult education centers in metropolitan, coastal, and rural communities were conducted. Four…

  15. 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.

  16. 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

  17. Influence of an oil soluble inhibitor on microbiologically influenced corrosion in a diesel transporting pipeline.

    PubMed

    Muthukumar, N; Maruthamuthu, S; Mohanan, S; Palaniswamy, N

    2007-01-01

    Microbial degradation of the oil soluble corrosion inhibitor (OSCI) Baker NC 351 contributed to a decrease in inhibitor efficiency. Corrosion inhibition efficiency was studied by the rotating cage and flow loop methods. The nature of the biodegradation of the corrosion inhibitor was also analysed using Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. The influence of bacterial activity on the degradation of the corrosion inhibitor and its influence on corrosion of API 5LX were evaluated using a weight loss technique and impedance studies. Serratia marcescens ACE2 and Bacillus cereus ACE4 can degrade aromatic and aliphatic hydrocarbons present in the corrosion inhibitor. The present study also discusses the demerits of the oil soluble corrosion inhibitors used in petroleum product pipeline.

  18. Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

    PubMed

    Penno, G; Chaturvedi, N; Talmud, P J; Cotroneo, P; Manto, A; Nannipieri, M; Luong, L A; Fuller, J H

    1998-09-01

    We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

  19. Regional aerosol properties: Comparisons of boundary layer measurements from ACE 1, ACE 2, Aerosols99, INDOEX, ACE Asia, TARFOX, and NEAQS

    NASA Astrophysics Data System (ADS)

    Quinn, Patricia K.; Bates, Timothy S.

    2005-07-01

    Means and variability of aerosol chemical composition and optical properties are compared for the first and second Aerosol Characterization Experiments (ACE 1 and ACE 2), a cruise across the Atlantic (Aerosols99), the Indian Ocean Experiment (INDOEX), the Asian Aerosol Characterization Experiment (ACE Asia), the Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX), and the New England Air Quality Study (NEAQS). These experiments were focused either on the remote marine atmosphere (ACE 1) or areas downwind of continental aerosol source regions including western Europe, North America, Africa, India, and Asia. Presented here are size-segregated concentrations of aerosol mass, sea salt, non-sea-salt (nss) SO4=, NH4+, NO3-, dust, organic carbon (OC), elemental carbon (EC), and nss K+, as well as mass ratios that are commonly used to identify aerosol sources and to assess aerosol processing (Cl- to Na+, OC to nss SO4=, EC to total carbon (TC), EC to nss SO4=, nss K+ to EC, Fe to Al, and Si to Al). Optical properties that are compared include size-segregated scattering, backscattering, and absorption coefficients, and single-scattering albedo at 550 nm. Size-segregated mass scattering and mass absorption efficiencies for the total aerosol and mass extinction efficiencies for the dominant chemical components also are compared. In addition, we present the contribution to light extinction by the dominant chemical components for each region. All data are based on shipboard measurements performed at a relative humidity of 55 ± 5%. Scattering coefficients and single-scattering albedos also are reported at ambient relative humidity (RH) using published values of f(RH). Finally, aerosol optical depths from each region are compared. Identical sampling protocols were used in all experiments in order to eliminate sampling biases and to make the data directly comparable. Major findings include (1) nss SO4= makes up only 16 to 46% of the submicron aerosol mass

  20. 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).

  1. Curriculum innovation in an accelerated BSN program: the ACE Model.

    PubMed

    Suplee, Patricia D; Glasgow, Mary Ellen

    2008-01-01

    As the demand for registered nurses continues to rise, so too has the creation of accelerated baccalaureate nursing programs for second-degree students. This article describes an 11-month Accelerated Career Entry (ACE) Nursing Program's innovative curriculum design, which has a heavy emphasis on technology, professional socialization, and the use of a standardized patient experience as a form of summative evaluation. In addition, challenges of this program are presented. Since 2002, the ACE Program has graduated over 500 students with an average first-time NCLEX pass rate of 95-100%. Although the number of graduates from accelerated programs does not solve the severe nursing shortage, the contributions of these intelligent, assertive, pioneering graduates are important for health care.

  2. Possible Improvements of the ACE Diversity Interchange Methodology

    SciTech Connect

    Etingov, Pavel V.; Zhou, Ning; Makarov, Yuri V.; Ma, Jian; Guttromson, Ross T.; McManus, Bart; Loutan, Clyde

    2010-07-26

    North American Electric Reliability Corporation (NERC) grid is operated by about 131 balancing authorities (BA). Within each BA, operators are responsible for managing the unbalance (caused by both load and wind). As wind penetration levels increase, the challenges of managing power variation increases. Working independently, balancing area with limited regulating/load following generation and high wind power penetration faces significant challenges. The benefits of BA cooperation and consolidation increase when there is a significant wind energy penetration. To explore the benefits of BA cooperation, this paper investigates ACE sharing approach. A technology called ACE diversity interchange (ADI) is already in use in the western interconnection. A new methodology extending ADI is proposed in the paper. The proposed advanced ADI overcoming some limitations existing in conventional ADI. Simulations using real statistical data of CAISO and BPA have shown high performance of the proposed advanced ADI methodology.

  3. 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.

  4. 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.

  5. ACE inhibition prevents diastolic Ca2+ overload and loss of myofilament Ca2+ sensitivity after myocardial infarction

    PubMed Central

    Zalvidea, Santiago; Andre, Lucas; Loyer, Xavier; Cassan, Cécile; Sainte-Marie, Yannis; Thireau, Jérôme; Sjaastad, Ivar; Heymes, Christophe; Pasquié, Jean-Luc; Cazorla, Olivier; Aimond, Franck; Richard, Sylvain

    2012-01-01

    Prevention of adverse cardiac remodeling after myocardial infarction (MI) remains a therapeutic challenge. Angiotensin-converting enzyme inhibitors (ACE-I) are a well-established first-line treatment. ACE-I delay fibrosis, but little is known about their molecular effects on cardiomyocytes. We investigated the effects of the ACE-I delapril on cardiomyocytes in a mouse model of heart failure (HF) after MI. Mice were randomly assigned to three groups: Sham, MI, and MI-D (6 weeks of treatment with a non-hypotensive dose of delapril started 24h after MI). Echocardiography and pressure-volume loops revealed that MI induced hypertrophy and dilatation, and altered both contraction and relaxation of the left ventricle. At the cellular level, MI cardiomyocytes exhibited reduced contraction, slowed relaxation, increased diastolic Ca2+ levels, decreased Ca2+-transient amplitude, and diminished Ca2+ sensitivity of myofilaments. In MI-D mice, however, both mortality and cardiac remodeling were decreased when compared to non-treated MI mice. Delapril maintained cardiomyocyte contraction and relaxation, prevented diastolic Ca2+ overload and retained the normal Ca2+ sensitivity of contractile proteins. Delapril maintained SERCA2a activity through normalization of P-PLB/PLB (for both Ser16-PLB and Thr17-PLB) and PLB/SERCA2a ratios in cardiomyocytes, favoring normal reuptake of Ca2+ in the sarcoplasmic reticulum. In addition, delapril prevented defective cTnI function by normalizing the expression of PKC, enhanced in MI mice. In conclusion, early therapy with delapril after MI preserved the normal contraction/relaxation cycle of surviving cardiomyocytes with multiple direct effects on key intracellular mechanisms contributing to preserve cardiac function. PMID:22280358

  6. User`s guide 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 User`s Guide describes the use of the ACE-IT training software.

  7. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.

    PubMed

    Nagai, Ryoji; Murray, David B; Metz, Thomas O; Baynes, John W

    2012-03-01

    This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.

  8. 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.

  9. Rediscovering ACE: Novel insights into the many roles of the angiotensin-converting enzyme

    PubMed Central

    Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Bernstein, Ellen A.; Janjulia, Tea; Taylor, Brian; Giani, Jorge F.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Shi, Peng D.; Fuchs, Sebastien; Bernstein, Kenneth E.

    2013-01-01

    Angiotensin converting enzyme (ACE) is best known for the catalytic conversion of angiotensin I to angiotensin II. However, the use of gene-targeting techniques has led to mouse models highlighting many other biochemical properties and actions of this enzyme. This review discusses recent studies examining the functional significance of ACE tissue-specific expression and the presence in ACE of two independent catalytic sites with distinct substrates and biological effects. It is these features which explain why ACE makes important contributions to many different physiological processes including renal development, blood pressure control, inflammation and immunity. PMID:23686164

  10. Validation of NO2 and NO from the Atmospheric Chemistry Experiment (ACE)

    NASA Astrophysics Data System (ADS)

    Kerzenmacher, T.; Wolff, M. A.; Strong, K.; Dupuy, E.; Walker, K. A.; Amekudzi, L. K.; Batchelor, R. L.; Bernath, P. F.; Berthet, G.; Blumenstock, T.; Boone, C. D.; Bramstedt, K.; Brogniez, C.; Brohede, S.; Burrows, J. P.; Catoire, V.; Dodion, J.; Drummond, J. R.; Dufour, D. G.; Funke, B.; Fussen, D.; Goutail, F.; Griffith, D. W. T.; Haley, C. S.; Hendrick, F.; Höpfner, M.; Huret, N.; Jones, N.; Kar, J.; Kramer, I.; Llewellyn, E. J.; López-Puertas, M.; Manney, G.; McElroy, C. T.; McLinden, C. A.; Melo, S.; Mikuteit, S.; Murtagh, D.; Nichitiu, F.; Notholt, J.; Nowlan, C.; Piccolo, C.; Pommereau, J.-P.; Randall, C.; Raspollini, P.; Ridolfi, M.; Richter, A.; Schneider, M.; Schrems, O.; Silicani, M.; Stiller, G. P.; Taylor, J.; Tétard, C.; Toohey, M.; Vanhellemont, F.; Warneke, T.; Zawodny, J. M.; Zou, J.

    2008-10-01

    Vertical profiles of NO2 and NO have been obtained from solar occultation measurements by the Atmospheric Chemistry Experiment (ACE), using an infrared Fourier Transform Spectrometer (ACE-FTS) and (for NO2) an ultraviolet-visible-near-infrared spectrometer, MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). In this paper, the quality of the ACE-FTS version 2.2 NO2 and NO and the MAESTRO version 1.2 NO2 data are assessed using other solar occultation measurements (HALOE, SAGE II, SAGE III, POAM III, SCIAMACHY), stellar occultation measurements (GOMOS), limb measurements (MIPAS, OSIRIS), nadir measurements (SCIAMACHY), balloon-borne measurements (SPIRALE, SAOZ) and ground-based measurements (UV-VIS, FTIR). Time differences between the comparison measurements were reduced using either a tight coincidence criterion, or where possible, chemical box models. ACE-FTS NO2 and NO and the MAESTRO NO2 are generally consistent with the correlative data. The ACE-FTS and MAESTRO NO2 volume mixing ratio (VMR) profiles agree with the profiles from other satellite data sets to within about 20% between 25 and 40 km, with the exception of MIPAS ESA (for ACE-FTS) and SAGE II (for ACE-FTS (sunrise) and MAESTRO) and suggest a negative bias between 23 and 40 km of about 10%. MAESTRO reports larger VMR values than the ACE-FTS. In comparisons with HALOE, ACE-FTS NO VMRs typically (on average) agree to ±8% from 22 to 64 km and to +10% from 93 to 105 km, with maxima of 21% and 36%, respectively. Partial column comparisons for NO2 show that there is quite good agreement between the ACE instruments and the FTIRs, with a mean difference of +7.3% for ACE-FTS and +12.8% for MAESTRO.

  11. 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

  12. 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 ...

  13. Screening of Zulu medicinal plants for angiotensin converting enzyme (ACE) inhibitors.

    PubMed

    Duncan, A C; Jäger, A K; van Staden, J

    1999-12-15

    Twenty plants used by traditional healers in South Africa for the treatment of high blood pressure were investigated for their anti-hypertensive properties, utilizing the angiotensin converting enzyme assay. A hit rate of 65% was achieved, with the highest inhibition (97%) obtained by Adenopodia spicata leaves. A further seven plants exhibited an inhibition greater than 70% and five more over 50%. The leaves of the plants showed the greatest levels of inhibition. There was little difference in the overall hit rate between ethanolic and aqueous extracts, although in most cases there was a marked difference in activity between aqueous and ethanolic extracts from the same species. Plants exhibiting inhibition levels greater than 50% were further tested for the presence of tannins in order to eliminate possible false positives. Active plants that did not contain tannins were Agapanthus africanus, Agave americana, Clausena anisata, Dietes iridioides, Mesembruanthemum spp., Stangeria eriopus and Tulbaghia violacea.

  14. 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.

  15. 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.

  16. 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)

  17. 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…

  18. 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.

  19. Validation of NO2 and NO from the Atmospheric Chemistry Experiment (ACE)

    NASA Astrophysics Data System (ADS)

    Kerzenmacher, T.; Wolff, M. A.; Stong, K.; Dupuy, E.; Walker, K. A.; Amekudzi, L. K.; Batchelor, R. L.; Bernath, P. F.; Berthet, G.; Blumenstock, T.; Boone, C. D.; Bramstedt, K.; Brogniez, C.; Brohede, S.; Burrows, J. P.; Catoire, V.; Dodion, J.; Drummond, J. R.; Dufour, D. G.; Funke, B.; Fussen, D.; Goutail, F.; Griffith, D. W. T.; Haley, C. S.; Hendrick, F.; Höpfner, M.; Huret, N.; Jones, N.; Kar, J.; Kramer, I.; Llewellyn, E. J.; López-Puertas, M.; Manney, G.; McElroy, C. T.; McLinden, C. A.; Melo, S.; Mikuteit, S.; Murthag, D.; Nichitiu, F.; Notholt, J.; Nowlan, C.; Piccolo, C.; Pommereau, J.-P.; Randall, C.; Raspollini, P.; Ridolfi, M.; Richter, A.; Schneider, M.; Schrems, O.; Silicani, M.; Stiller, G. P.; Taylor, J.; Tétard, C.; Toohey, M.; Vanhellemont, F.; Warneke, T.; Zawodny, J. M.; Zou, J.

    2008-02-01

    Vertical profiles of NO2 and NO have been obtained from solar occultation measurements by the Atmospheric Chemistry Experiment (ACE), using an infrared Fourier Transform Spectrometer, ACE-FTS, and an ultraviolet-visible-near-infrared spectrometer, MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). In this paper, the quality of the ACE-FTS version 2.2 NO2 and NO and the MAESTRO version 1.2 NO2 data are assessed using other solar occultation measurements (HALOE, SAGE II, SAGE III, POAM III, SCIAMACHY), stellar occultation measurements (GOMOS), limb measurements (MIPAS, OSIRIS), nadir measurements (SCIAMACHY), balloon measurements (SPIRALE, SAOZ) and ground-based measurements (UV-VIS, FTIR). Time differences between the comparison measurements were reduced using either a tight coincidence criterion, or where possible, chemical box models. ACE-FTS NO2 and NO and the MAESTRO NO2 are generally consistent with the correlative data. The ACE-FTS NO2 VMRs agree with the satellite data sets to within about 20% between 25 and 40 km, and suggest a negative bias between 23 and 40 km of about textminus10%. In comparisons with HALOE, ACE-FTS NO VMRs typically agree to ±8% from 22 to 64 km and to +10% from 93 to 105 km. Partial column comparisons for NO2 show that there is fair agreement between the ACE instruments and the FTIRs, with a mean difference of +7.3% for ACE-FTS and +12.8% for MAESTRO.

  20. 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.

  1. 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 U.S. Customs and Border Protection Automated Commercial Environment (ACE): Announcement of a... required advance ocean and rail data through the Automated Commercial Environment (ACE). This notice... application period for participation, outlines the development and evaluation methodology to be used,...

  2. 77 FR 20835 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... 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 Records Notice: 71 FR 3109 (January 19, 2006). Terms/Conditions for Access to the ACE Portal and...

  3. 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....

  4. Absence of cell surface expression of human ACE leads to perinatal death.

    PubMed

    Michaud, Annie; Acharya, K Ravi; Masuyer, Geoffrey; Quenech'du, Nicole; Gribouval, Olivier; Morinière, Vincent; Gubler, Marie-Claire; Corvol, Pierre

    2014-03-15

    Renal tubular dysgenesis (RTD) is a recessive autosomal disease characterized most often by perinatal death. It is due to the inactivation of any of the major genes of the renin-angiotensin system (RAS), one of which is the angiotensin I-converting enzyme (ACE). ACE is present as a tissue-bound enzyme and circulates in plasma after its solubilization. In this report, we present the effect of different ACE mutations associated with RTD on ACE intracellular trafficking, secretion and enzymatic activity. One truncated mutant, R762X, responsible for neonatal death was found to be an enzymatically active, secreted form, not inserted in the plasma membrane. In contrast, another mutant, R1180P, was compatible with life after transient neonatal renal insufficiency. This mutant was located at the plasma membrane and rapidly secreted. These results highlight the importance of tissue-bound ACE versus circulating ACE and show that the total absence of cell surface expression of ACE is incompatible with life. In addition, two missense mutants (W594R and R828H) and two truncated mutants (Q1136X and G1145AX) were also studied. These mutants were neither inserted in the plasma membrane nor secreted. Finally, the structural implications of these ACE mutations were examined by molecular modelling, which suggested some important structural alterations such as disruption of intra-molecular non-covalent interactions (e.g. salt bridges).

  5. 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…

  6. 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…

  7. 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.

  8. 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

  9. 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

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

    2014-08-13

    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.

  10. 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

  11. 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

  12. 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

  13. Polar Vortex Structure with ACE and OSIRIS Ozone Data

    NASA Astrophysics Data System (ADS)

    Evans, W. F.

    2005-12-01

    The polar vortex is the dominant feature of stratospheric wind field. The ACE instrument on SCISAT-1 can map ozone fields from 8 to 50 km in 16 days. The OSIRIS instrument on ODIN can map the ozone fields at 2 km intervals from 10 km to over 65 km on a daily basis. They can also provide aerosol maps at the lower levels. These can be used for dynamical studies such as vortex breakdown. Four years of ozone data from the OSIRIS instrument on ODIN have been processed using the Kerr three wavelength algorithm. The OSIRIS ozone data is on the web as orbital slices. TOMS like maps have been formed at 2 km intervals from 10 km to 42 km by mapping the OSIRIS ozone product onto polar map projections. This mapset allows investigations of the vertical structure and evolution of the vortex. The downward motion in the vortex is clearly demonstrated by aerosol maps which show a clean vortex due to the descent within the vortex. The Antarctic vortex and the Arctic vortex were investigated using the ACE profiles and the OSIRIS ozone product. OSIRIS data is available from Oct 1, 2001 to April 30, 2005 as maps at 2km intervals from 10 km to 42 km. An example is demonstrated using the split vortex event of September 25, 2002; the split extends from 14 km up to 42 km. However, the 10 km and 12 km levels showed no vortex during the split. There is a close relationship of vortex ozone with PV and hence to the vortex wind. These maps are used to study the vortex in the Arctic and the Antarctic. In particular, the vortex breakdown in the two hemispheres is compared. The ozone vortex extends up to 55 km at the wind null region. There are significant differences in the hemispheres in the vortex below 24 km. A comparison of the features of the Arctic and Antarctic vorticies was conducted. The Antarctic vortex usually extends from 10 km up to over 42 km whereas in the Arctic, the vortex is only obvious from 16 km to 42km. The main hemispheric differences seem to be in the lower stratosphere

  14. Platelet Inhibitors.

    PubMed

    Shifrin, Megan M; Widmar, S Brian

    2016-03-01

    Antithrombotic medications have become standard of care for management of acute coronary syndrome. Platelet adhesion, activation, and aggregation are essential components of platelet function; platelet-inhibiting medications interfere with these components and reduce incidence of thrombosis. Active bleeding is a contraindication for administration of platelet inhibitors. There is currently no reversal agent for platelet inhibitors, although platelet transfusion may be used to correct active bleeding after administration of platelet inhibitors. PMID:26897422

  15. Pharmacological evidence of bradykinin regeneration from extended sequences that behave as peptidase-activated B2 receptor agonists.

    PubMed

    Charest-Morin, Xavier; Roy, Caroline; Fortin, Emile-Jacques; Bouthillier, Johanne; Marceau, François

    2014-01-01

    While bradykinin (BK) is known to be degraded by angiotensin converting enzyme (ACE), we have recently discovered that Met-Lys-BK-Ser-Ser is paradoxically activated by ACE. We designed and evaluated additional "prodrug" peptides extended around the BK sequence as potential ligands that could be locally activated by vascular or blood plasma peptidases. BK regeneration was estimated using the contractility of the human umbilical vein as model of vascular functions mediated by endogenous B2 receptors (B2Rs) and the endocytosis of the fusion protein B2R-green fluorescent protein (B2R-GFP) expressed in Human Embryonic Kidney 293 cells. Of three BK sequences extended by a C-terminal dipeptide, BK-His-Leu had the most desirable profile, exhibiting little direct affinity for the receptor but a significant one for ACE (as shown by competition of [(3)H]BK binding to B2R-GFP or of [(3)H]enalaprilat to recombinant ACE, respectively). The potency of the contractile effect of this analog on the vein was reduced 18-fold by the ACE inhibitor enalaprilat, pharmacologically evidencing BK regeneration in situ. BK-Arg, a potential substrate of arginine carboxypeptidases, had a low affinity for B2Rs and its potency as a contractile agent was reduced 15-fold by tissue treatment with an inhibitor of these enzymes, Plummer's inhibitor. B2R-GFP internalization in response to 100 nM of the extended peptides recapitulated these findings, as enalaprilat selectively inhibited the effect of BK-His-Leu and Plummer's inhibitor, that of BK-Arg. The two peptidase inhibitors did not affect BK-induced effects in either assay. The novel C-terminally extended BKs had no or very little affinity for the kinin B1 receptor (competition of [(3)H]Lys-des-Arg(9)-BK binding). The feasibility of peptidase-activated B2R agonists is illustrated by C-terminal extensions of the BK sequence.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Corrosion inhibitor

    SciTech Connect

    Wisotsky, M.J.; Metro, S.J.

    1989-10-31

    A corrosion inhibitor for use in synthetic ester lubricating oils is disclosed. It comprises an effective amount of: at least one aromatic amide; and at least one hydroxy substituted aromatic compound. The corrosion inhibitor thus formed is particularly useful in synthetic ester turbo lubricating oils.

  1. The Ace locus of Drosophila melanogaster: structural gene for acetylcholinesterase with an unusual 5' leader.

    PubMed Central

    Hall, L M; Spierer, P

    1986-01-01

    The Ace locus of Drosophila melanogaster has been mapped at the molecular level. cDNA clones from the locus have been isolated and their sequence determined, confirming that Ace forms the structural gene for acetylcholinesterase (AChE). The cDNAs have a 1950 nucleotide open reading frame from which the complete amino acid sequence of AChE has been deduced. The Drosophila enzyme is found to have extensive homology to the known sequence of Torpedo AChE. Ace cDNAs have an unusual structure with a long 5' leader and several short upstream open reading frames. Images Fig. 2. PMID:3024971

  2. 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.

  3. Differential regulation of the cellulase transcription factors XYR1, ACE2, and ACE1 in Trichoderma reesei strains producing high and low levels of cellulase.

    PubMed

    Portnoy, Thomas; Margeot, Antoine; Seidl-Seiboth, Verena; Le Crom, Stéphane; Ben Chaabane, Fadhel; Linke, Rita; Seiboth, Bernhard; Kubicek, Christian P

    2011-02-01

    Due to its capacity to produce large amounts of cellulases, Trichoderma reesei is increasingly being investigated for second-generation biofuel production from lignocellulosic biomass. The induction mechanisms of T. reesei cellulases have been described recently, but the regulation of the genes involved in their transcription has not been studied thoroughly. Here we report the regulation of expression of the two activator genes xyr1 and ace2, and the corepressor gene ace1, during the induction of cellulase biosynthesis by the inducer lactose in T. reesei QM 9414, a strain producing low levels of cellulase (low producer). We show that all three genes are induced by lactose. xyr1 was also induced by d-galactose, but this induction was independent of d-galactose metabolism. Moreover, ace1 was carbon catabolite repressed, whereas full induction of xyr1 and ace2 in fact required CRE1. Significant differences in these regulatory patterns were observed in the high-producer strain RUT C30 and the hyperproducer strain T. reesei CL847. These observations suggest that a strongly elevated basal transcription level of xyr1 and reduced upregulation of ace1 by lactose may have been important for generating the hyperproducer strain and that thus, these genes are major control elements of cellulase production.

  4. Altered cardiac bradykinin metabolism in experimental diabetes caused by the variations of angiotensin-converting enzyme and other peptidases.

    PubMed

    Adam, Albert; Leclair, Patrick; Montpas, Nicolas; Koumbadinga, Gérémy Abdull; Bachelard, Hélène; Marceau, François

    2010-04-01

    The peptidases angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) mediate most of the kinin catabolism in normal cardiac tissue and are the molecular targets of inhibitory drugs that favorably influence diabetic complications. We studied the variations of those kininases in the myocardium of rats in experimental diabetes. ACE and NEP activities were significantly decreased in heart membranes 4-8weeks post-streptozotocin (STZ) injection. However, insulin-dependent diabetes did not modify significantly bradykinin (BK) half-life (t(1/2)) while the effect of both ACE (enalaprilat) and ACE and NEP (omapatrilat) inhibitors on BK degradation progressively decreased, which may be explained by the upregulation of other unidentified metallopeptidase(s). In vivo insulin treatment restored the activities of both ACE and NEP. ACE and NEP activities were significantly higher in hearts of young Zucker rats than in those of Sprague-Dawley rats. BK t(1/2) and the effects of peptidase inhibitors on t(1/2) varied accordingly. It is concluded that kininase activities are subjected to large and opposite variations in rat cardiac tissue in type I and II diabetes models. A number of tissue or molecular factors may determine these variations, such as remodeling of cardiac tissue, ectoenzyme shedding to the extracellular fluid and the pathologic regulation of peptidase gene expression.

  5. 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

  6. 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

  7. 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

  8. Angiotensin I-converting enzyme inhibitor peptides derived from the endostatin-containing NC1 fragment of human collagen XVIII.

    PubMed

    Farias, Shirley L; Sabatini, Regiane A; Sampaio, Tatiana C; Hirata, Izaura Y; Cezari, Maria Helena S; Juliano, Maria A; Sturrock, Edward D; Carmona, Adriana K; Juliano, Luiz

    2006-05-01

    Extracellular matrix and soluble plasma proteins generate peptides that regulate biological activities such as cell growth, differentiation and migration. Bradykinin, a peptide released from kininogen by kallikreins, stimulates vasodilatation and endothelial cell proliferation. Various classes of substances can potentiate these biological actions of bradykinin. Among them, the best studied are bradykinin potentiating peptides (BPPs) derived from snake venom, which can also strongly inhibit angiotensin I-converting enzyme (ACE) activity. We identified and synthesized sequences resembling BPPs in the vicinity of potential proteolytic cleavage sites in the collagen XVIII molecule, close to endostatin. These peptides were screened as inhibitors of human recombinant wild-type ACE containing two intact functional domains; two full-length ACE mutants containing only a functional C- or N-domain catalytic site; and human testicular ACE, a natural form of the enzyme that only contains the C-domain. The BPP-like peptides inhibited ACE in the micromolar range and interacted preferentially with the C-domain. The proteolytic activity involved in the release of BPP-like peptides was studied in human serum and human umbilical-vein endothelial cells. The presence of enzymes able to release these peptides in blood led us to speculate on a physiological mechanism for the control of ACE activities.

  9. 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.

  10. 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

  11. 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

  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. 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

  14. 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.

  15. 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.

  16. First science observations with the ACES echelle spectrograph

    NASA Astrophysics Data System (ADS)

    Reynolds, Robert O.; Lloyd-Hart, Michael

    2004-09-01

    The use of spectrographs with telescopes having high order adaptive optics (AO) systems offers the possibility of achieving near diffraction-limited spectral resolution with ground-based telescopes, as well as important advantages for instrument design. The use of an optical fiber to couple the instrument to the telescope affords additional advantages such as flexibility in the placement of the instrument and improved homogeneity of the input illumination function. In the case of Steward Observatory's Adaptively Coupled Echelle Spectrograph (ACES), the instrument is normally coupled to the telescope with an 8 micron diameter near single-mode optical fiber, although the instrument can be used at fixed focus locations without the fiber for telescopes so equipped. The use of a fiber coupler results in the phenomenon known as 'modal noise', where the transmission of multiple modes in the fiber leads to a wavelength-dependent variation in illumination that limits flat fielding precision. We have largely eliminated this effect through the use of an automated fiber stretcher device. We report here on improvements to the fiber feed optics and on interim observations made with the instrument at a conventional telescope not equipped with adaptive optics.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. The Atmospheric Chemistry Experiment (ace): CO, CH_4 and N_2O Isotopologues

    NASA Astrophysics Data System (ADS)

    Bernath, Peter F.; Buzan, Eric M.; Beale, Christopher A.; Yousefi, Mahdi; Boone, Chris

    2016-06-01

    ACE (also known as SCISAT) is making a comprehensive set of simultaneous measurements of numerous trace gases, thin clouds, aerosols and temperature by solar occultation from a satellite in low earth orbit. A high inclination orbit gives ACE coverage of tropical, mid-latitudes and polar regions. The primary instrument is a high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating in the 750--4400 cm-1 region, which provides the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. Aerosols and clouds are being monitored through the extinction of solar radiation using two filtered imagers as well as by their infrared spectra. Although now in its thirteenth year, the ACE-FTS is still operating nominally. A short introduction and overview of the ACE mission will be presented (see http://www.ace.uwaterloo.ca for more information). This talk will focus on ACE observations of the CO, CH_4 and N_2O isotopologues, and comparisons with chemical transport models.

  3. Targeting the ACE2 and Apelin Pathways Are Novel Therapies for Heart Failure: Opportunities and Challenges

    PubMed Central

    Kazemi-Bajestani, Seyyed M. R.; Patel, Vaibhav B.; Wang, Wang; Oudit, Gavin Y.

    2012-01-01

    Angiotensin-converting enzyme 2 (ACE2)/Ang II/Ang 1–7 and the apelin/APJ are two important peptide systems which exert diverse effects on the cardiovascular system. ACE2 is a key negative regulator of the renin-angiotensin system (RAS) where it metabolizes angiotensin (Ang) II into Ang 1–7, an endogenous antagonist of Ang II. Both the prolonged activation of RAS and the loss of ACE2 can be detrimental as they lead to functional deterioration of the heart and progression of cardiac, renal, and vascular diseases. Recombinant human ACE2 in an animal model of ACE2 knockout mice lowers Ang II. These interactions neutralize the pressor and subpressor pathologic effects of Ang II by producing Ang 1–7 levels in vivo, that might be cardiovascular protective. ACE2 hydrolyzes apelin to Ang II and, therefore, is responsible for the degradation of both peptides. Apelin has emerged as a promising peptide biomarker of heart failure. The serum level of apelin in cardiovascular diseases tends to be decreased. Apelin is recognized as an imperative controller of systemic blood pressure and myocardium contractility. Dysregulation of the apelin/APJ system may be involved in the predisposition to cardiovascular diseases, and enhancing apelin action may have important therapeutic effects. PMID:22655211

  4. Drug repositioning and pharmacophore identification in the discovery of hookworm MIF inhibitors.

    PubMed

    Cho, Yoonsang; Vermeire, Jon J; Merkel, Jane S; Leng, Lin; Du, Xin; Bucala, Richard; Cappello, Michael; Lolis, Elias

    2011-09-23

    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.

  5. 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.

  6. Binding of the angiotensin-converting enzyme inhibitor, RACX-65, to trout gills

    SciTech Connect

    Olson, K.R.; Evan, A.P.; Ryan, J.W.

    1986-03-01

    Galardy et al. have shown that in rainbow trout, Salmo gairdneri, nearly all of the angiotensin converting enzyme (ACE) activity is found in the gills. In the present study, binding and localization of the angiotensin-converting enzyme inhibitor N-(1(S)-carboxanili-dopropyl)-L-Ala-L-Pro (RAC-X-65) to trout gill was examined in homogenized gill tissues, an isolated perfused gill and by autoradiography. RAC-X-65 inhibited gill ACE as effectively as it inhibits human ACE; the apparent Ki for gill homogenates fell over 15 min from 3 x 10/sup -9/M to 5.5 x 10/sup -10/M. In the arterioarterial pathway (supplying the systematic circulation) of the perfused gill, /sup 3/H-RAC-X-65 extraction (compared to the inert volume maker, /sup 14/C-sucrose) decreased from 72.2 +/- 4.5% after 6 min perfusion to 54.7 +/- 6.8% (14 min) and 38.4 +/- 9.0% after 20 min (N = 6). By 40 min, extraction was less then 10% indicating saturation of ACE binding sites. Relatively little extraction was observed in the gill arteriovenous pathway. Autoradiography of gills perfused with /sup 3/H-RAC-X-65 demonstrated that the pillar cells are the major site of /sup 3/H accumulation and, therefore, probably contain most of the ACE activity.

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

    PubMed Central

    Cho, Yoonsang; Vermeire, Jon J.; Merkel, Jane S.; Leng, Lin; Du, Xin; Bucala, Richard; Cappello, Michael; Lolis, Elias

    2011-01-01

    SUMMARY 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. PMID:21944748

  8. Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

    SciTech Connect

    Villard, E.; Soubrier, F.; Tiret, L.; Rakotovao, R. Cambien, F.; Visvikis, S.

    1996-06-01

    Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms could be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.

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

    PubMed

    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.

  10. Rapid screening and identification of active ingredients in licorice extract interacting with V3 loop region of HIV-1 gp120 using ACE and CE-MS.

    PubMed

    Li, Zhongjie; Zhao, Yiran; Lin, Weiwei; Ye, Min; Ling, Xiaomei

    2015-01-01

    The binding of envelope protein gp120 to glycosphingolipids is very important during the human immunodeficiency virus entering into the host cell. This step occurs in the V3 loop region in particularly. The conserved core sequence of V3 loop in gp120 was named R15K. Anti-HIV drug targeting to R15K would avoid the drug-resistance caused by HIV-1 genetic diversity. Here, for the first time, affinity capillary electrophoresis (ACE) and capillary electrophoresis-mass spectrometry (CE-MS) were used for establishing a simple, rapid and effective method of screening the licorice extract for biological activity (anti-HIV), which avoided the complicated isolation and purification process. R15K, 3'-sialyllactose (the positive control), and d-galactose (the negative control) were used for the development and validation of ACE method. After the interaction between licorice extract and R15K was confirmed by ACE, the relative active ingredients were isolated by SPE and their structures were determined by CE-ESI-MS online. In this research, two mixtures from licorice extract were found to be active. Furthermore, glycyrrhizin and licorice saponin G2 were verified as the main ingredients that significantly interacted with R15K via CE-MS and LC-MS. The results of quantitative assays showed that the active mixture contained glycyrrhizin of 74.23% and licorice saponin G2 of 9.52%. Calculated by Scatchard analysis method, glycyrrhizin/R15K complex had the highest binding constant (1.69 ± 0.08) × 10(7)L/mol among 27 compounds isolated from licorice extract. The anti-HIV activity of glycyrrhizin was further confirmed by bioactive experiment of cellular level. This strategy might provide a high throughput screening and identifying platform for seeking HIV-1 inhibitors in natural products.

  11. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax.

    PubMed

    Kma, Lakhan; Gao, Feng; Fish, Brian L; Moulder, John E; Jacobs, Elizabeth R; Medhora, Meetha

    2012-01-01

    Our long-term goal is to use angiotensin converting enzyme (ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradiation. Rats that survived acute pneumonitis (at 6-12 weeks) were evaluated monthly for synthesis of lung collagen. Other endpoints included breathing rate, wet to dry lung weight ratio, and analysis of lung structure. Treatment with captopril (145-207 mg/m(2)/day) or enalapril (19-28 mg/m(2)/day), but not fosinopril (19-28 mg/m(2)/day), decreased morbidity from acute pneumonitis. Lung collagen in the surviving irradiated rats was increased over that of controls by 7 months after irradiation. This increase in collagen synthesis was not observed in rats treated with any of the three ACE inhibitors. Analysis of the lung morphology at 7 months supports the efficacy of ACE inhibitors against radiation-induced fibrosis. The effectiveness of fosinopril against fibrosis, but not against acute pneumonitis, suggests that pulmonary fibrosis may not be a simple consequence of injury during acute pneumonitis. In summary, three structurally-different ACE inhibitors mitigate the increase in collagen synthesis 7 months following irradiation of the whole thorax and do so, even when therapy is started one week after irradiation. PMID:22302041

  12. Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817

    SciTech Connect

    Ward, W.F.; Molteni, A.; Ts'ao, C.H.

    1989-02-01

    The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of 60Co gamma rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose-response curves in the CL242817-treated rats was essentially zero, precluding calculation of DRF values for PGI2 and TXA2 production. Lung HP content also increased with increasing radiation dose, and CL242817 significantly attenuated this response (DRF = 1.5). These data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril, rather it is a therapeutic action shared by other members of this class of compounds. These data also provide the first evidence that ACE inhibitors exhibit antifibrotic activity in irradiated rat lung.

  13. The onboard imagers for the Canadian ACE SCISAT-1 mission

    NASA Astrophysics Data System (ADS)

    Gilbert, K. L.; Turnbull, D. N.; Walker, K. A.; Boone, C. D.; McLeod, S. D.; Butler, M.; Skelton, R.; Bernath, P. F.; Chateauneuf, F.; Soucy, M.-A.

    2007-06-01

    The Atmospheric Chemistry Experiment (ACE) onboard the Canadian Space Agency's SCISAT-1 satellite has been in orbit since August of 2003. Its broad objective is to study the problem of stratospheric ozone depletion, particularly in the Arctic. The main instruments are two spectrometers, one an infrared Fourier Transform Spectrometer and the other a dual optical spectrophotometer sensitive in the UV and visible. Also included are two filtered imagers used to measure altitude profiles of atmospheric extinction and detect thin clouds. The nominal center wavelengths of the filters are 525 nm for the visible (VIS) imager and 1020 nm for the near-infrared (NIR) imager. With the decommissioning of other satellite instruments used to monitor global aerosols [i.e., Stratospheric Aerosol and Gas Experiment II (SAGE II), SAGE III, Polar Ozone and Aerosol Measurement (POAM) III, Halogen Occultation Experiment (HALOE)], the imagers provide much needed continuity in this data record. The data product from the imagers is still, however, in a preliminary state. Funding restrictions in the prelaunch period were responsible for an incomplete characterization of the imagers' optics and electronics and prevented corrections being made for the problems found during testing. Postlaunch data analysis to correct for image artifacts is ongoing. A comparison with coincidental measurements from SAGE II shows that systematic errors from the preliminary analysis are within 5 and 20% for the VIS and NIR imagers, respectively, for uninverted profiles of optical depth. Despite the preliminary nature of the imager results, a paper describing the imagers and the initial operational data processing code is timely because the data are already being used.

  14. 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.

  15. Hypertension and ace gene insertion/deletion polymorphism in pediatric renal transplant patients.

    PubMed

    Serdaroglu, Erkin; Mir, Sevgi; Berdeli, Afig

    2005-10-01

    The objective of the present study was to define the risk factors for hypertension and to analyze the influence of insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) on hypertension in pediatric renal transplant recipients. Twenty-six pediatric renal transplant recipients with stable renal function and treated with the same immunosuppression protocol were included in the study. Their mean age was 12.5 +/- 3.3 yr and mean time after transplantation was 38.5 +/- 39.8 month. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed by SpaceLabs (90207) device. The I/D polymorphism of the ACE was determined by PCR and ACE serum level was analyzed by colorimetric method. Hypertension was present in 15 patients (57.7%) by causal blood pressure measurements and 19 patients (73.1%) by ABPM. Twenty-two patients (84.6%) were found to be non-dipper and eight of them had reverse dipping. Only time after transplantation (38 +/- 31 vs. 79 +/-49 month, p = 0.016) and cyclosporin A trough plasma levels (206 +/-78 vs. 119 +/- 83 ng/mL, p = 0.020) influenced the presence of hypertension by multiple logistic regression analysis. The distribution of genotypes were II = 2 (7.7%), ID = 8 (30.8%), DD = 16 (61.5%). There was no effect of ACE gene I/D polymorphism or serum ACE levels on hypertension prevalence and circadian variability of blood pressures. Hypertension was related to the time after transplantation and cyclosporin A levels. The ACE gene I/D polymorphism and serum ACE levels did not influence the blood pressure values or circadian variability of blood pressure among pediatric renal transplant patients. PMID:16176418

  16. 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.

  17. Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients.

    PubMed

    Seripa, Davide; Paroni, Giulia; Matera, Maria G; Gravina, Carolina; Scarcelli, Carlo; Corritore, Michele; D'Ambrosio, Luigi P; Urbano, Maria; D'Onofrio, Grazia; Copetti, Massimiliano; Kehoe, Patrick G; Panza, Francesco; Pilotto, Alberto

    2011-09-01

    The association between angiotensin-converting enzyme (ACE) genotypes and functional decline in older adults remains controversial. To assess if ACE gene variations influences functional abilities at older age, the present study explored the association between the common ACE insertion/deletion (I/D) polymorphism and disability measured with activities of daily living (ADL) in hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I, I/D, and D/D) in a population of 2,128 hospitalized older patients divided according to presence or absence of ADL disability. Logistic regression analysis adjusted for possible confounding factors, identified an association between the I/I genotype with ADL disability (OR=1.54, 95% CI 1.04-2.29). This association was significant in men (OR=2.01, 95% CI 1.07-3.78), but not in women (OR=1.36, 95% CI 0.82-2.25). These results suggested a possible role of the ACE polymorphism as a genetic marker for ADL disability in hospitalized older patients.

  18. 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

  19. 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.

  20. The association between ace gene variation and aerobic capacity in winter endurance disciplines.

    PubMed

    Orysiak, J; Zmijewski, P; Klusiewicz, A; Kaliszewski, P; Malczewska-Lenczowska, J; Gajewski, J; Pokrywka, A

    2013-12-01

    The aim of the study was to examine the possible relationship between I/D polymorphism of ACE gene and selected indices of aerobic capacity among male and female athletes practising winter endurance sports. Sixty-six well-trained athletes (female n = 26, male n = 40), aged 18.4 ± 2.8 years, representing winter endurance sports (cross-country skiing, n = 48; biathlon, n = 8; Nordic combined, n = 10) participated in the study. Genotyping for ACE I/D polymorphism was performed using polymerase chain reaction. Maximal oxygen consumption (VO2max), maximal running velocity (Vmax) and running velocity at anaerobic threshold (VAT4) were determined in an incremental test to volitional exhaustion on a motorized treadmill. The ACE genotype had no significant effect on absolute VO2max, relative VO2max (divided by body mass or fat free body mass), VAT4 or Vmax. No interaction effect of gender x ACE genotype was found for each of the examined aerobic capacity indices. ACE gene variation was not found to be a determinant of aerobic capacity in either female or male Polish, well-trained endurance athletes participating in winter sports.

  1. Mixed inhibitors of angiotensin-converting enzyme (EC 3.4.15.1) and enkephalinase (EC 3.4.24.11): rational design, properties, and potential cardiovascular applications of glycopril and alatriopril.

    PubMed Central

    Gros, C; Noël, N; Souque, A; Schwartz, J C; Danvy, D; Plaquevent, J C; Duhamel, L; Duhamel, P; Lecomte, J M; Bralet, J

    1991-01-01

    Angiotensin-converting enzyme (ACE) and enkephalinase, two cell surface metallopeptidases, are responsible for angiotensin II formation and atrial natriuretic factor (ANF) degradation, respectively, and thereby play a critical role in the metabolism of hormonal peptides exerting essentially opposite actions in cardiovascular regulations. To affect simultaneously both hormonal systems by a single molecular structure, we have designed glycoprilat and alatrioprilat [(S)-N-[3-(3,4-methylene-dioxyphenyl)-2-(mercaptomethyl)-1-oxoprop yl] glycine and -alanine, respectively]. In vitro the two compounds inhibit both ACE and enkephalinase activities with similar, nanomolar potencies, and in vivo, glycopril and alatriopril, the corresponding diester prodrugs, occupy the two enzyme molecules in lung at similar low dosages (0.2-0.5 mg/kg of body weight, per os). The high potency of these compounds is attributable to interaction of the methylenedioxy group with the S1 subsite of ACE and of the aromatic ring with the S1' subsite of enkephalinase. In rodents, low doses of these mixed inhibitors exert typical actions of ACE inhibitors--i.e., prevention of angiotensin I-induced hypertension--as well as of enkephalinase inhibitors--i.e., protection from 125I-ANF degradation or enhancement of diuresis and natriuresis following acute extracellular volume expansion. In view of the known counterbalanced physiological actions of the two hormonal peptides, whose metabolism is controlled by ACE and enkephalinase, mixed inhibitors of the two peptidases show promise for the treatment of various cardiovascular and salt-retention disorders. PMID:1851998

  2. Arctic weather during the FIRE/ACE flights in 1998

    NASA Astrophysics Data System (ADS)

    Wylie, Donald P.

    2001-07-01

    The weather systems, cyclones and anticyclones, along with air trajectories and cloud forms, are compared to past studies of the Arctic to assess compatibility of the 4-month study of FIRE/ACE with past climatologies. The frequency and movement of cyclones (lows) and anticyclones (highs) followed the general eastward and northeastward directions indicated by past studies. Most cyclones (lows) came from eastern Siberia and the Bering Sea to the south and moved north across the Bering Straight or Alaska into the Arctic Ocean. They generally weakened in central pressure as they moved poleward. Anticyclones (highs) were most common in the eastern Beaufort Sea near Canada in June and July, as predicted from previous studies. However, many cyclones and anticyclones moved in westward directions, which is rare in other latitudes. Erratic changes in shape and intensity on a daily basis also were observed. The NOAA National Center for Environmental Prediction (NCEP) analysis generally reflected the SHEBA Ship WMO observations which it used. However, NCEP temperatures were biased warm by 1.0° to 1.5°C in April and early May. In July, when the surface temperatures were at the freezing/thawing point, the NCEP analysis changed to a cold bias of -1.0°C. Dew points had smaller biases except for July where they were biased cold by -1.4°C. Wind speeds had a -2 m/s low bias for the six windiest days. Surface barometric pressures had consistently low biases from -1.2 to -2.8 hPa in all four months. Air parcel historical trajectories were mainly from the south or from local anticyclonic gyres in the Beaufort Sea. Most air came to the SHEBA ship from the North Pacific Ocean or from Alaska and Canada and occasionally from eastern Siberia. Very few trajectories traced back across the pole to Europe and central Asia. Cloud cover was high, as expected, from 69 to 86% of the time. Satellite data also indicate frequent stratus, altostratus, and cirrus clouds (occurring 61% of the time

  3. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure.

    PubMed

    Patel, Vaibhav B; Zhong, Jiu-Chang; Grant, Maria B; Oudit, Gavin Y

    2016-04-15

    Heart failure (HF) remains the most common cause of death and disability, and a major economic burden, in industrialized nations. Physiological, pharmacological, and clinical studies have demonstrated that activation of the renin-angiotensin system is a key mediator of HF progression. Angiotensin-converting enzyme 2 (ACE2), a homolog of ACE, is a monocarboxypeptidase that converts angiotensin II into angiotensin 1-7 (Ang 1-7) which, by virtue of its actions on the Mas receptor, opposes the molecular and cellular effects of angiotensin II. ACE2 is widely expressed in cardiomyocytes, cardiofibroblasts, and coronary endothelial cells. Recent preclinical translational studies confirmed a critical counter-regulatory role of ACE2/Ang 1-7 axis on the activated renin-angiotensin system that results in HF with preserved ejection fraction. Although loss of ACE2 enhances susceptibility to HF, increasing ACE2 level prevents and reverses the HF phenotype. ACE2 and Ang 1-7 have emerged as a key protective pathway against HF with reduced and preserved ejection fraction. Recombinant human ACE2 has been tested in phase I and II clinical trials without adverse effects while lowering and increasing plasma angiotensin II and Ang 1-7 levels, respectively. This review discusses the transcriptional and post-transcriptional regulation of ACE2 and the role of the ACE2/Ang 1-7 axis in cardiac physiology and in the pathophysiology of HF. The pharmacological and therapeutic potential of enhancing ACE2/Ang 1-7 action as a novel therapy for HF is highlighted.

  4. 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

  5. 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.

  6. Role of Serratia marcescens ACE2 on diesel degradation and its influence on corrosion.

    PubMed

    Rajasekar, Aruliah; Babu, Thambidurai Ganesh; Pandian, Shunmugiah Thevar Karutha; Maruthamuthu, Sundaram; Palaniswamy, Narayanan; Rajendran, Annamalai

    2007-09-01

    A facultative anaerobic species Serratia marcescens ACE2 isolated from the corrosion products of diesel transporting pipeline in North West, India was identified by 16S rDNA sequence analysis. The role of Serratia marcesens ACE2 on biodegradation of diesel and its influence on the corrosion of API 5LX steel has been elucidated. The degrading strain ACE2 is involved in the process of corrosion of steel API 5LX and also utilizes the diesel as an organic source. The quantitative biodegradation efficiency (BE) of diesel was 58%, calculated by gas-chromatography-mass spectrum analysis. On the basis of gas-chromatography-mass spectrum (GC-MS), Fourier Transform infrared spectroscopy (FTIR) and X-ray diffractometer (XRD), the involvement of Serratia marcescens on degradation and corrosion has been investigated. This basic study will be useful for the development of new approaches for detection, monitoring and control of microbial corrosion.

  7. Serum ACE Level in Sarcoidosis Patients with Typical and Atypical HRCT Manifestation

    PubMed Central

    Kahkouee, Shahram; Samadi, Katayoon; Alai, Ali; Abedini, Atefeh; Rezaiian, Lida

    2016-01-01

    Summary Background Sarcoidosis is an inflammatory disease that affects multiple organs. Before widespread use of computed tomography (CT), the severity of sarcoidosis was assessed based on chest X-ray abnormalities. HRCT can distinguish between active inflammatory changes and irreversible fibrosis. In this study, we analyzed different ACE levels in 148 patients diagnosed with sarcoidosis. Material/Methods We categorized these patients based on their HRCT results into four groups: 1) patients diagnosed with chronic disease; 2) patients diagnosed with non-chronic disease; 3) patients who exhibited typical HRCT changes; and 4) patients who exhibited atypical HRCT changes. Afterward the mean ACE level of each group was calculated and compared. Result The HRCT scans of chronic sarcoidosis patients tended to show more atypical sarcoidosis patterns. Moreover, there was a reverse correlation between chronicity and ACE level (P-value <0.05). Conclusions HRCT is another modality which would be useful when the diagnosis of sarcoidosis is not definite. PMID:27733890

  8. In Vivo Effects of Bradykinin B2 Receptor Agonists with Varying Susceptibility to Peptidases.

    PubMed

    Jean, Mélissa; Gera, Lajos; Charest-Morin, Xavier; Marceau, François; Bachelard, Hélène

    2015-01-01

    We reported evidence of bradykinin (BK) regeneration from C-terminal extended BK sequences that behave as peptidase-activated B2 receptor (B2R) agonists. Further to these in vitro studies, we carried out in vivo experiments to verify hemodynamic effects of BK analogs exhibiting variable susceptibility toward vascular and blood plasma peptidases. Rats were anesthetized and instrumented to record blood pressure and heart rate responses to bolus intravenous (i.v.) injection of increasing doses of BK, B-9972 (D-Arg-[Hyp(3),Igl(5),Oic(7),Igl(8)]-BK), BK-Arg, BK-His-Leu or BK-Ala-Pro, in the absence or presence of specific inhibitors. In some experiments, pulsed Doppler flow probes measured hindquarter Doppler shift in response to i.v. injections of kinins. BK caused rapid, transient and dose-related hypotensive effects. These effects were potentiated ∼15-fold by the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, but extensively inhibited by icatibant (a B2R antagonist) and not influenced by the Arg-carboxypeptidase (CP) inhibitor (Plummer's inhibitor). The hypotensive responses elicited by the peptidase-resistant B2R agonist, B-9972, were not affected by enalaprilat, but were inhibited by icatibant. The hypotensive responses to BK-Arg were abolished by pre-treatment with either the Arg-CP inhibitor or icatibant, pharmacologically evidencing BK regeneration. The hypotensive effects of BK-His-Leu and BK-Ala-Pro, previously reported as ACE-activated substrates, were abolished by icatibant, but not by enalaprilat. In vivo regeneration of BK from these two C-terminally extended analogs with no affinity for the B2R must follow alternative cleavage rules involving unidentified carboxypeptidase(s) when ACE is blocked. The transient hypotensive responses to BK and three tested analogs coincided with concomitant vasodilation (increased Doppler shift signal). Together, these results provide in vivo evidence that interesting hypotensive and vasodilator effects can be

  9. In Vivo Effects of Bradykinin B2 Receptor Agonists with Varying Susceptibility to Peptidases

    PubMed Central

    Jean, Mélissa; Gera, Lajos; Charest-Morin, Xavier; Marceau, François; Bachelard, Hélène

    2016-01-01

    We reported evidence of bradykinin (BK) regeneration from C-terminal extended BK sequences that behave as peptidase-activated B2 receptor (B2R) agonists. Further to these in vitro studies, we carried out in vivo experiments to verify hemodynamic effects of BK analogs exhibiting variable susceptibility toward vascular and blood plasma peptidases. Rats were anesthetized and instrumented to record blood pressure and heart rate responses to bolus intravenous (i.v.) injection of increasing doses of BK, B-9972 (D-Arg-[Hyp3,Igl5,Oic7,Igl8]-BK), BK-Arg, BK-His-Leu or BK-Ala-Pro, in the absence or presence of specific inhibitors. In some experiments, pulsed Doppler flow probes measured hindquarter Doppler shift in response to i.v. injections of kinins. BK caused rapid, transient and dose-related hypotensive effects. These effects were potentiated ∼15-fold by the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, but extensively inhibited by icatibant (a B2R antagonist) and not influenced by the Arg-carboxypeptidase (CP) inhibitor (Plummer’s inhibitor). The hypotensive responses elicited by the peptidase-resistant B2R agonist, B-9972, were not affected by enalaprilat, but were inhibited by icatibant. The hypotensive responses to BK-Arg were abolished by pre-treatment with either the Arg-CP inhibitor or icatibant, pharmacologically evidencing BK regeneration. The hypotensive effects of BK-His-Leu and BK-Ala-Pro, previously reported as ACE-activated substrates, were abolished by icatibant, but not by enalaprilat. In vivo regeneration of BK from these two C-terminally extended analogs with no affinity for the B2R must follow alternative cleavage rules involving unidentified carboxypeptidase(s) when ACE is blocked. The transient hypotensive responses to BK and three tested analogs coincided with concomitant vasodilation (increased Doppler shift signal). Together, these results provide in vivo evidence that interesting hypotensive and vasodilator effects can be

  10. In Vivo Effects of Bradykinin B2 Receptor Agonists with Varying Susceptibility to Peptidases.

    PubMed

    Jean, Mélissa; Gera, Lajos; Charest-Morin, Xavier; Marceau, François; Bachelard, Hélène

    2015-01-01

    We reported evidence of bradykinin (BK) regeneration from C-terminal extended BK sequences that behave as peptidase-activated B2 receptor (B2R) agonists. Further to these in vitro studies, we carried out in vivo experiments to verify hemodynamic effects of BK analogs exhibiting variable susceptibility toward vascular and blood plasma peptidases. Rats were anesthetized and instrumented to record blood pressure and heart rate responses to bolus intravenous (i.v.) injection of increasing doses of BK, B-9972 (D-Arg-[Hyp(3),Igl(5),Oic(7),Igl(8)]-BK), BK-Arg, BK-His-Leu or BK-Ala-Pro, in the absence or presence of specific inhibitors. In some experiments, pulsed Doppler flow probes measured hindquarter Doppler shift in response to i.v. injections of kinins. BK caused rapid, transient and dose-related hypotensive effects. These effects were potentiated ∼15-fold by the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, but extensively inhibited by icatibant (a B2R antagonist) and not influenced by the Arg-carboxypeptidase (CP) inhibitor (Plummer's inhibitor). The hypotensive responses elicited by the peptidase-resistant B2R agonist, B-9972, were not affected by enalaprilat, but were inhibited by icatibant. The hypotensive responses to BK-Arg were abolished by pre-treatment with either the Arg-CP inhibitor or icatibant, pharmacologically evidencing BK regeneration. The hypotensive effects of BK-His-Leu and BK-Ala-Pro, previously reported as ACE-activated substrates, were abolished by icatibant, but not by enalaprilat. In vivo regeneration of BK from these two C-terminally extended analogs with no affinity for the B2R must follow alternative cleavage rules involving unidentified carboxypeptidase(s) when ACE is blocked. The transient hypotensive responses to BK and three tested analogs coincided with concomitant vasodilation (increased Doppler shift signal). Together, these results provide in vivo evidence that interesting hypotensive and vasodilator effects can be

  11. SIGACE Code for Generating High-Temperature ACE Files; Validation and Benchmarking

    NASA Astrophysics Data System (ADS)

    Sharma, Amit R.; Ganesan, S.; Trkov, A.

    2005-05-01

    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.

  12. 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

  13. Modelling of the production of ACE inhibitory hydrolysates of horse mackerel using proteases mixtures.

    PubMed

    Pérez-Gálvez, R; Morales-Medina, R; Espejo-Carpio, F; Guadix, A; Guadix, E M

    2016-09-14

    Fish protein hydrolysates from Mediterranean horse mackerel were produced by using a mixture of two commercial endoproteases (i.e. subtilisin and trypsin) at different levels of substrate concentration (2.5 g L(-1), 5 g L(-1), and 7.5 g L(-1) of protein), temperature (40 °C, 47.5 °C, and 55 °C) and percentage of subtilisin in the enzyme mixture (0%, 25%, 50%, 75% and 100%). A crossed mixture process model was employed to predict the degree of hydrolysis (DH) and the ACE inhibitory activity of the final hydrolysates as a function of the experimental factors. Both models were optimized for a maximum DH and ACE inhibition. A maximum DH (17.1%) was predicted at 2.54 g L(-1) of substrate concentration, 40 °C and an enzyme mixture comprising 38.3% of subtilisin and 61.7% of trypsin. Although its proteolytic activity is limited, the presence of trypsin in the enzyme mixture allowed obtaining higher degrees of hydrolysis at low temperatures, which is desirable to minimize thermal deactivation of the proteins. Similarly, a percentage of ACE inhibition above 48% was attained at 2.5 g L(-1) of protein, 40 °C and a 1 : 1 mixture of both proteases. Higher values of ACE inhibition could be attained by increasing both the temperature and the amount of trypsin in the enzyme mixture (e.g. 50% ACE inhibition at 55 °C and 81.5% of trypsin). Finally, those hydrolysates exhibiting the highest levels of ACE inhibition were subjected to simulated gastrointestinal digestion. These assays confirmed the resistance of active fractions against their degradation by digestive enzymes. PMID:27526864

  14. 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

  15. A cladistic model of ACE sequence variation with implications for myocardial infarction, Alzheimer disease and obesity.

    PubMed

    Katzov, Hagit; Bennet, Anna M; Kehoe, Patrick; Wiman, Björn; Gatz, Margaret; Blennow, Kaj; Lenhard, Boris; Pedersen, Nancy L; de Faire, Ulf; Prince, Jonathan A

    2004-11-01

    Sequence variation in ACE, which encodes angiotensin I converting enzyme, contributes to a large proportion of variability in plasma ACE levels, but the extent to which this impacts upon human disease is unresolved. Most efforts to associate ACE with other heritable traits have involved a single Alu insertion/deletion polymorphism, despite the probable existence of other functional sequence variants with effects that may not be consistently detectable by solely typing the Alu indel. Here, utilizing single nucleotide polymorphisms (SNPs) that differentiate major ACE clades in European populations, we demonstrate a number of significant phenotype associations across more than 4000 Swedish individuals. In a systematic analysis of metabolic phenotypes, effects were detected upon several traits, including fasting plasma glucose levels, insulin levels and measures of obesity (P-values ranging from 0.046 to 8.4 x 10(-6)). Extending cladistic models to the study of myocardial infarction and Alzheimer disease, significant associations were observed with greater effect sizes than those typically obtained in large-scale meta-analyses based on the Alu indel. Population frequencies of ACE genotypes were also found to change with age, congruent with previous data suggesting effects upon longevity. Clade models consistently outperformed those based upon single markers, reinforcing the importance of taking into consideration the possible confounding effects of allelic heterogeneity in this genomic region. Utilizing computational tools, potential functional variants are highlighted that may underlie phenotypic variability, which is discussed along with the broader implications these results may have for studies attempting to link variation in ACE to human disease.

  16. 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.

  17. 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.

  18. 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.

  19. 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).

  20. 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.

  1. 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.

  2. 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

  3. Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or β-blockers for treating hypertension

    PubMed Central

    Bisognano, John D; McLaughlin, Trent; Roberts, Craig S; Tang, Simon SK

    2007-01-01

    This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP) ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus) and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort) were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were −17.5/−8.8, −15.7/−6.3, and −13.0/−8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs. PMID:18078009

  4. Dipeptidase-inactivated tACE action in vivo: selective inhibition of sperm-zona pellucida binding in the mouse.

    PubMed

    Deguchi, Eishi; Tani, Taeko; Watanabe, Hitomi; Yamada, Shuichi; Kondoh, Gen

    2007-11-01

    The angiotensin-converting enzyme (ACE) plays a crucial role in male fertilization and is a key regulator of blood pressure. Testicular ACE (tACE), the germinal specific isozyme expressed on different promoters, exclusively carries out the role of ACE in fertility, although the site and mode of action are not well known. To investigate the contribution of tACE in fertilization, we produced transgenic mouse lines carrying a dipeptidase-inactivated mutant. Although the transgenic mice showed normal blood pressure, kidney morphology, and fertility, reduced fertilization was observed after in vitro fertilization (IVF). The sperm-zona pellucida (ZP) binding was exclusively impaired in these lines in a manner similar to that observed in an Ace knockout mouse. The dipeptidase activity was reduced in epididymal ingredients but not in the testis. Furthermore, direct application of mutant protein did not suppress sperm-ZP binding of intact sperm during IVF, implying that the dipeptidase-inactivated mutant affects sperm modification in the epididymis for ZP binding. Our results indicate that the dipeptidase-inactivated tACE acts in vivo, suggesting that tACE contributes to fertilization as a dipeptidase at least in the epididymis.

  5. 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.

  6. 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…

  7. Egg ovotransferrin‐derived ACE inhibitory peptide IRW increases ACE2 but decreases proinflammatory genes expression in mesenteric artery of spontaneously hypertensive rats

    PubMed Central

    Majumder, Kaustav; Liang, Guanxiang; Chen, Yanhong; Guan, LeLuo; Davidge, Sandra T.

    2015-01-01

    Scope Egg ovotransferrin‐derived angiotensin converting enzyme (ACE) inhibitory peptide IRW was previously shown to reduce blood pressure in spontaneously hypertensive rats through reduced vascular inflammation and increased nitric oxide‐mediated vasorelaxation. The main objective of the present study was to investigate the molecular mechanism of this peptide through transcriptome analysis by RNAseq technique. Methods and results Total RNA was extracted from kidney and mesenteric arteries; the RNAseq libraries (from untreated and IRW‐treated groups) were constructed and subjected to sequence using HiSeq 2000 system (Illumina) system. A total of 12 764 and 13 352 genes were detected in kidney and mesenteric arteries, respectively. The differentially expressed (DE) genes between untreated and IRW‐treated groups were identified and the functional analysis through ingenuity pathway analysis revealed a greater role of DE genes identified from mesenteric arteries than that of kidney in modulating various cardiovascular functions. Subsequent qPCR analysis further confirmed that IRW significantly increased the expression of ACE‐2, ABCB‐1, IRF‐8, and CDH‐1 while significantly decreased the expression ICAM‐1 and VCAM‐1 in mesenteric arteries. Conclusion Our research showed for the first time that ACE inhibitory peptide IRW could contribute to its antihypertensive activity through increased ACE2 and decreased proinflammatory genes expression. PMID:26016560

  8. 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

  9. Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System

    PubMed Central

    Poglitsch, Marko; Domenig, Oliver; Schwager, Cornelia; Stranner, Stefan; Peball, Bernhard; Janzek, Evelyne; Wagner, Bettina; Jungwirth, Helmut; Loibner, Hans; Schuster, Manfred

    2012-01-01

    Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase of the renin-angiotensin-system (RAS) which is known to cleave several substrates among vasoactive peptides. Its preferred substrate is Angiotensin II, which is tightly involved in the regulation of important physiological functions including fluid homeostasis and blood pressure. Ang 1–7, the main enzymatic product of ACE2, became increasingly important in the literature in recent years, as it was reported to counteract hypertensive and fibrotic actions of Angiotensin II via the MAS receptor. The functional connection of ACE2, Ang 1–7, and the MAS receptor is also referred to as the alternative axis of the RAS. In the present paper, we describe the recombinant expression and purification of human and murine ACE2 (rhACE2 and rmACE2). Furthermore, we determined the conversion rates of rhACE2 and rmACE2 for different natural peptide substrates in plasma samples and discovered species-specific differences in substrate specificities, probably leading to functional differences in the alternative axis of the RAS. In particular, conversion rates of Ang 1–10 to Ang 1–9 were found to be substantially different when applying rhACE2 or rmACE2 in vitro. In contrast to rhACE2, rm ACE2 is substantially less potent in transformation of Ang 1–10 to Ang 1–9. PMID:22518284

  10. 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…

  11. 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

  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. 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…

  14. 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…

  15. 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.

  16. Economic evaluation of the Annual Cycle Energy System (ACES), volume 3, appendices

    NASA Astrophysics Data System (ADS)

    1980-06-01

    Seven appendices related to ACES, the first three of which are concerned with computer programs are presented. The appendices are entitled: ACESIM: Residential Program Listing; Typical inputs and outputs OF ACESIM; CACESS: Commercial Building Program Listing; Typical Weather Year Selection Requirements; Building Characteristics; List of AJOR Variables Used in the Computer Programs; and Bibliography.

  17. 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…

  18. 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…

  19. 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

  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. 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.

  2. 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...

  3. 77 FR 4815 - Ace Info Solutions, Inc., and Information International Associates; Transfer of Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-31

    ... coding, Web 2.0 project support for wikis and blogs and web site design. OPP has determined that access... accordance with 40 CFR 2.307(h)(3) and 2.308(i)(2). Ace Info Solutions, Inc., and its subcontractor... public access reference and referral: 1. EPA Desktop Library support; 2. Electronic resources...

  4. 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

  5. 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

  6. Angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphism in Mexican populations.

    PubMed

    Vargas-Alarcón, Gilberto; Hernández-Pacheco, Guadalupe; Rodríguez-Pérez, José Manuel; Pérez-Hernández, Nonanzit; Pavón, Zinnia; Fragoso, José Manuel; Juarez-Cedillo, Teresa; Villarreal-Garza, Cynthia; Granados, Julio

    2003-12-01

    The angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphism was determined in 211 Mexican healthy individuals belonging to different Mexican ethnic groups (98 Mestizos, 64 Teenek, and 49 Nahuas). ACE polymorphism differed among Mexicans with a high frequency of the D allele and the D/D genotype in Mexican Mestizos. The D/D genotype was absent in Teenek and present in only one Nahua individual (2.0%). When comparisons were made, we observed that Caucasian, African, and Asian populations presented the highest frequencies of the D allele, whereas Amerindian (Teenek and Pima) and Australian Aboriginals showed the highest frequencies of the I allele. The distribution of I/D genotype was heterogeneous in all populations: Australian Aboriginals presented the lowest frequency (4.9%), whereas Nahuas presented the highest (73.4%). The present study shows the frequencies of a polymorphism not analyzed previously in Mexican populations and establishes that this polymorphism distinguishes the Amerindian populations of other groups. On the other hand, since ACE alleles have been associated with genetic susceptibility to developing cardiovascular diseases and hypertension, knowledge of the distribution of these alleles could help to define the true significance of ACE polymorphism as a genetic susceptibility marker in the Amerindian populations.

  7. 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

  8. The angiotensin-converting enzyme inhibitor captopril inhibits poly(ADP-ribose)polymerase activation and exerts beneficial effects in an ovine model of burn and smoke injury

    PubMed Central

    Asmussen, Sven; Bartha, Eva; Olah, Gabor; Sbrana, Elena; Rehberg, Sebastian W.; Yamamoto, Yusuke; Enkhbaatar, Perenlei; Hawkins, Hal K.; Ito, Hiroshi; Cox, Robert A.; Traber, Lillian D.; Traber, Daniel L.; Szabo, Csaba

    2011-01-01

    We investigated the effect of the angiotensin converting enzyme (ACE) inhibitor captopril in a clinically relevant ovine model of smoke and burn injury, with special reference to oxidative stress, activation of poly(ADP-ribose) polymerase in the lung and in circulating leukocytes. Female, adult sheep (28–40 kg) were divided into 3 groups. After tracheostomy and under deep anesthesia both vehicle-control (n=5) and captopril (20 mg/kg/d, iv., starting 0.5 hour before the injury) treated (n=5) groups were subjected to 2×20%, third degree burn injury and were insufflated with 48 breaths of cotton smoke. A sham group not receiving burn/smoke was also studied (n=5). Animals were mechanically ventilated and fluid resuscitated for 24 h in the awake state. Burn and smoke injury resulted in an upregulation of ACE in the lung, evidenced by immunohistochemical determination and Western blotting. Burn and smoke injury resulted in pulmonary dysfunction, as well as systemic hemodynamic alterations. Captopril treatment of burn and smoke animals improved PaO2/FiO2 ratio and pulmonary shunt fraction and reduced the degree of lung edema. There was a marked increase in PAR levels in circulating leukocytes after burn/smoke injury, which was significantly decreased by captopril. The pulmonary level of ACE and the elevated pulmonary levels of TGF-β in response to burn and smoke injury were significantly decreased by captopril treatment. Our results suggest that the ACE inhibitor captopril exerts beneficial effects on the pulmonary function in burn/smoke injury. The effects of the ACE inhibitor may be related to the prevention of ROS-induced PARP over-activation. ACE inhibition may also exert additional beneficial effects by inhibiting the expression of the pro-fibrotic mediator TGF-β. PMID:21701415

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. SY 12-1 RENIN ANGIOTENSIN PATHWAY BEYOND ACE AND ANGIOTENSIN II RECEPTORS: HOW IT RELATES TO THE PATHOPHYSIOLOGY OF HYPERTENSION.

    PubMed

    Burrell, Louise

    2016-09-01

    The renin-angiotensin system (RAS) plays a major role in the pathogenesis of hypertension, a major risk factor for stroke, coronary events, heart failure and kidney disease. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II, which mediates its effects via the angiotensin type 1 receptor (AT1R). An "alternate" arm of the RAS is now known to exist in which the monocarboxypeptidase ACE2 counterbalances the effects of the classic RAS through degradation of the vasoconstrictor peptide, Ang II, and generation of the vasodilatory peptide, Ang 1-7. ACE2 is highly expressed in tissues of cardiovascular relevance including the heart, blood vessels and kidney. The catalytically active ectodomain of ACE2 undergoes shedding resulting in ACE2 in the circulation. The finding that the ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats suggests that the ACE2 gene may be a candidate gene for hypertension. It is hypothesised 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. Studies in experimental models of hypertension have measured ACE2 gene, protein and/or activity, in either the heart or kidney and/or plasma, usually at one time point, and most commonly in animals with established hypertension. As experimental studies report that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, increasing or activating 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. The available data indicates that plasma ACE2 activity is low in healthy subjects, but elevated in patients with

  16. 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

  17. 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

  18. 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.

  19. Calcium-channel blockade (nitrendipine) in combination with ACE inhibition (captopril) in the treatment of mild to moderate hypertension.

    PubMed

    Gennari, C; Nami, R; Pavese, G; Gragnani, S; Bianchini, C; Buracchi, P

    1989-06-01

    The antihypertensive efficacy of a combination of calcium-channel blockers and angiotensin-converting-enzyme (ACE) inhibitors in severe primary hypertension is well known, but a synergistic action of this drug combination in mild to moderate primary hypertension is still not established. Therefore, the aim of the present study was to evaluate the efficacy and tolerability of monotherapy with nitrendipine (20 mg) or captopril (100 mg), and of their combination (nitrendipine 10 mg plus captopril 50 mg), in patients suffering from mild to moderate primary hypertension, according to a single-blind, randomized, placebo-controlled design. After the first 4-week monotherapy period, both nitrendipine and captopril induced a significant decrease in systolic and diastolic blood pressure (BP) (p less than 0.001). Furthermore, nitrendipine caused a significant increase in heart rate (HR), while no change in HR was observed in patients treated with captopril. Several side effects were observed, both in the nitrendipine-treated patients (facial flushing, headache, malleolar edema) and in the captopril-treated patients (initial hypotension, dizziness, gastrointestinal disorders). However, these side effects were mild and were well tolerated. In the second combined 4-week therapy period, systolic and diastolic BP of patients treated with 10 mg nitrendipine combined with 50 mg captopril continued to decrease to a degree significantly lower (p less than 0.001) than that observed at the end of the monotherapy period. Simultaneously, no change in HR values occurred when compared to basal values. Furthermore, the incidence and intensity of some side effects observed during the combined therapy period were lower than those of the monotherapy period.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Anti-hypertensive effect of oral controlled-release microspheres containing an ACE inhibitor (delapril hydrochloride) in rats.

    PubMed

    Akiyama, Y; Yoshioka, M; Horibe, H; Inada, Y; Hirai, S; Kitamori, N; Toguchi, H

    1994-08-01

    An oral controlled-release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti-hypertensive, delapril hydrochloride. The in-vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic-lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in-vivo release profile was in good agreement with the in-vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I-induced pressor response was also sustained showing consistency with the plasma concentration-time curve.

  1. Extreme hyperkalaemia caused by concomitant use of a NSAID and an ace inhibitor in an elderly patient.

    PubMed

    Rogulj, Dinko; Hauptfeld, Marko; Iskra, Mojca Savnik; Zorko, Vanda Kostevc; Strasek, Milena

    2010-06-01

    Extreme hyperkalaemia is a life-threatening electrolyte disorder. It is relatively common in patients with severe renal insufficiency. This report describes a case of extreme hyperkalaemia caused by drugs in an 82-year-old female patient without severe renal insufficiency, who was successfully treated without haemodialysis. The patient had been treated for arterial hypertension and type 2 diabetes mellitus for 30 years. Over the last years she had been receiving enalapril and metformin. Three weeks before the admission to the hospital, she was receiving a non-steroidal anti-inflammatory drug (NSAID) because of the back pain. She was admitted to hospital due to a collapse and weakness in the limbs. Laboratory tests showed extreme hyperkalaemia, high blood sugar, metabolic acidosis, elevated serum creatinine and blood urea nitrogen (BUN), and a slightly elevated serum sodium. On ECG, we noticed typical signs of hyperkalaemia.The patient was treated with a slow intravenous bolus of calcium gluconate and intravenous infusion of sodium chloride with insulin, glucose with insulin and sodium bicarbonte. After the treatment, all laboratory findings normalised together and the patient felt better. This case shows that physicians should be very careful when prescribing NSAIDs to elderly patients treated with drugs that affect renal function.

  2. 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.

  3. 76 FR 37136 - Post-Summary Corrections to Entry Summaries Filed in ACE Pursuant to the ESAR IV Test

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... to conduct a National Customs Automation Program test concerning new Automated Commercial Environment... requirements, and test development and evaluation methods. DATES: The ESAR IV test will commence July 25, 2011... INFORMATION: Background I. Automated Commercial Environment (ACE) Test Programs Automated...

  4. 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.

  5. ACE 1992 summary data report: Aircraft measurements of meteorological parameters and SF6. Technical memo

    SciTech Connect

    Watkins, B.A.; Boatman, J.F.; Wellman, D.L.; Wilkison, S.W.

    1993-02-01

    Meteorological parameters and sulfur hexafluoride (SF6) were measured with the NOAA King Air C-90 aircraft during October 1992 in central Florida as part of the Air Force Technical Applications Command (AFTAC) Airborne Collection Equipment (ACE 1992) experiment. Airborne sampling was used to locate a plume containing SF6 as a tracer. Before take off, a trajectory model was used to provide the expected plume path. An onboard tracking program gave current predictions of the location of the plume, based on the location of tetroons expected to travel with the plume. Once the plume was located, samples were collected of triethyl phosphate oxide and methyl salicylate, which had been released with the SF6. This report discusses the objectives of ACE 1992, the instrumentation used and the data obtained by the NOAA King Air ground and airborne operation.

  6. 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

  7. 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.

  8. ACE inhibition by astilbin isolated from Erythroxylum gonocladum (Mart.) O.E. Schulz.

    PubMed

    Lucas-Filho, M D; Silva, G C; Cortes, S F; Mares-Guia, T R; Perpétua Ferraz, V; Serra, C P; Braga, F C

    2010-04-01

    Erythroxylum species have several traditional uses in different countries, including the treatment of hypertension. The ethanol extract from E. gonocladum aerial parts, a species endemic to the Brazilian cerrado, elicited a concentration-dependent inhibition of angiotensin converting enzyme (ACE) (pIC(50)=4.53+/-0.05). Extract fractionation led to the isolation of two compounds, whose structures were assigned by spectrometric data as astilbin and beta-sitosterol, along with a mixture of palmitic, stearic and linolenic acids. This is the first report on the occurrence of these compounds on E. gonocladum. Astilbin promoted significant ACE inhibition in vitro (pIC(50)=5.86+/-0.33) and its activity did not differ from captopril, when both compounds were assayed at 10 microM concentration.

  9. HDAC Inhibitors.

    PubMed

    Olzscha, Heidi; Bekheet, Mina E; Sheikh, Semira; La Thangue, Nicholas B

    2016-01-01

    Lysine acetylation in proteins is one of the most abundant posttranslational modifications in eukaryotic cells. The dynamic homeostasis of lysine acetylation and deacetylation is dictated by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). Important substrates for HATs and HDACs are histones, where lysine acetylation generally leads to an open and transcriptionally active chromatin conformation. Histone deacetylation forces the compaction of the chromatin with subsequent inhibition of transcription and reduced gene expression. Unbalanced HAT and HDAC activity, and therefore aberrant histone acetylation, has been shown to be involved in tumorigenesis and progression of malignancy in different types of cancer. Therefore, the development of HDAC inhibitors (HDIs) as therapeutic agents against cancer is of great interest. However, treatment with HDIs can also affect the acetylation status of many other non-histone proteins which play a role in different pathways including angiogenesis, cell cycle progression, autophagy and apoptosis. These effects have led HDIs to become anticancer agents, which can initiate apoptosis in tumor cells. Hematological malignancies in particular are responsive to HDIs, and four HDIs have already been approved as anticancer agents. There is a strong interest in finding adequate biomarkers to predict the response to HDI treatment. This chapter provides information on how to assess HDAC activity in vitro and determine the potency of HDIs on different HDACs. It also gives information on how to analyze cellular markers following HDI treatment and to analyze tissue biopsies from HDI-treated patients. Finally, a protocol is provided on how to detect HDI sensitivity determinants in human cells, based on a pRetroSuper shRNA screen upon HDI treatment. PMID:27246222

  10. 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

  11. 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.

  12. Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors

    PubMed Central

    Douglas, Ross G.; Sharma, Rajni K.; Masuyer, Geoffrey; Lubbe, Lizelle; Zamora, Ismael; Acharya, K. Ravi; Chibale, Kelly; Sturrock, Edward D.

    2013-01-01

    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 (Ki=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-domainselective inhibition and assists in the design of novel N-selective ACE inhibitors that could be employed in treatment of fibrosis disorders. PMID:24015848

  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. 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.

  15. 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…

  16. 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.

  17. 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.

  18. 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

  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, 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.

  20. 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.

  1. Functional study on the mutations in the silkworm (Bombyx mori) acetylcholinesterase type 1 gene (ace1) and its recombinant proteins.

    PubMed

    Wang, Ju-mei; Wang, Bin-bin; Xie, Yi; Sun, Shan-shan; Gu, Zhi-ya; Ma, Lie; Li, Fan-chi; Zhao, Yi-fan; Yang, Bin; Shen, Wei-de; Li, Bing

    2014-01-01

    The acetylcholinesterase of Lepidoptera insects is encoded by two genes, ace1 and ace2. The expression of the ace1 gene is significantly higher than that of the ace2 gene, and mutations in ace1 are one of the major reasons for pesticide resistance in insects. In order to investigate the effects of the mutations in ace1's characteristic sites on pesticide resistance, we generated mutations for three amino acids using site-directed mutagenesis, which were Ala(GCG)303Ser(TCG), Gly(GGA)329Ala(GCA) and Leu (TCT)554Ser(TTC). The Baculovirus expression system was used for the eukaryotic expression of the wild type ace1 (wace1) and the mutant ace1 (mace1). SDS-PAGE and Western blotting were used to detect the targeting proteins with expected sizeof about 76 kDa. The expression products were purified for the determination of AChE activity and the inhibitory effects of physostigmine and phoxim. We observed no significant differences in the overall activity of the wild type and mutant AChEs. However, with 10 min of physostigmine (10 μM) inhibition, the remaining activity of the wild type AChE was significantly lower than that of the mutant AChE. Ten min inhibition with 33.4 μM phoxim also resulted in significantly lower remaining activity of the wild type AChE than that of the mutant AChE. These results indicated that mutations for the three amino acids reduced the sensitivity of AChE to physostigmine and phoxim, which laid the foundation for future in vivo studies on AChE's roles in pesticide resistance.

  2. Isolation, hyperexpression, and sequencing of the aceA gene encoding isocitrate lyase in Escherichia coli.

    PubMed Central

    Matsuoka, M; McFadden, B A

    1988-01-01

    A structural gene for isocitrate lyase was isolated from a cosmid containing an ace locus of the Escherichia coli chromosome. Cloning and expression under control of the tac promoter in a multicopy plasmid showed that a 1.7-kilobase-pair DNA segment was sufficient for complementation of an aceA deletion mutation and overproduction of isocitrate lyase. DNA sequence analysis of the cloned gene and N-terminal protein sequencing of the cloned and wild-type enzymes revealed an entire aceA gene which encodes a 429-amino-acid residue polypeptide whose C-terminus is histidine. The deduced amino acid sequence for the 47.2-kilodalton subunit of E. coli isocitrate lyase could be aligned with that for the 64.8-kilodalton subunit of the castor bean enzyme with 39% identity except for limited N- and C-terminal regions and a 103-residue stretch that was unique for the plant enzyme and started approximately in the middle of that peptide. Images PMID:3049537

  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. 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.

  5. 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

  6. Aerosol Forcing During INDOEX and ACE-Asia as Determined From Aircraft and Grou nd Measurements

    NASA Astrophysics Data System (ADS)

    Marsden, D. C.; Valero, F. P.; Bush, B. C.; Pope, S. K.; Leitner, A. S.

    2002-12-01

    A suite of radiometers was flown on the NCAR C-130 aircraft throughout the INDOEX and ACE-Asia experiments to measure broadband and spectral irradiances. Identical instruments were placed in the zenith and nadir positions, allowing net flux and optical depth to be determined. The radiative forcing efficiency (aerosol forcing per unit optical depth) was determined below the aerosol layer, i.e. at an altitude of about 40 meters. This was measured in the spectral range s 220 to 3910 nm (total solar forcing) and 680 to 3300 nm (near infrared) and in seven spectral channels covering contiguously the visible range from 400 to 700 nm. Surface measurements of solar insolation as well as aerosol column optical depth were made at Kaashidoo, Maldives (INDOEX) and at Cheju Island, South Korea (ACE-Asia). These measurements, in conjunction with aerosol-free model simulations, are used to determine the radiative forcing at the surface for the visible, near-infrared, and total solar spectral bandpasses. During INDOEX the diurnally averaged broadband surface aerosol radiative forcing was -72.2+/- 5.5 W m-2 per unit optical depth at 500 nm with roughly half being contributed from the visible (-38.5+/- 4.0 W m-2). The corresponding results during ACE-Asia were: broadband -73.1+/- 9.7 W m-2, visible -41.7+/- 4.7 W m-2, and near infrared -36.3+/- -5.6 W m-2.

  7. 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

  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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Optical Aerosol Properties Over the Asian Pacific Ocean during ACE-Asia

    NASA Astrophysics Data System (ADS)

    Rood, M. J.; Carrico, C. M.; Kus, P.

    2001-12-01

    The effect of aerosol particles on the atmospheric radiative-energy balance at critical locations around the globe is an area or research that to be better characterized. This research has allowed shipboard measurements of climatically relevant ambient-aerosol optical properties between Hawaii and the coast of China to characterize "clean marine conditions" and then along the coast of China to characterize "polluted conditions" and "mineral dust conditions." Aerosol light scattering properties and in particular the increase in light scattering coefficient with increasing controlled relative humidity (f(RH)) during ACE-Asia showed a wider diversity of profiles than during ACE-1, ACE-2 or at a U.S. continental site. During the Pacific crossing, the signature was clearly marine-seasalt dominated (very hygroscopic with large magnitude growth with a clear deliquescent/crystallization hysteresis loop) and quite similar to the background marine conditions of Cape Grim during ACE-1. Other times when flow was off the Asian continent, the dependence of scattering on controlled RH was quite similar to results obtained in Sagres Portugal during outflow of European air masses (ACE-2, hygroscopic with smoother changes in scattering with increasing RH conditions though some deliquescent/crystallization features). When the aerosol consisted of a large part mineral dust species, the hygroscopic growth in light scattering was quite suppressed. Mineral dust dominated aerosols showed very little growth in light scattering as a function of RH and at times was nearly hygrophobic. However, along with the suppressed hygroscopic growth, deliquescent (step-change) features were often more pronounced than the cases of the more hygroscopic urban-industrial influenced aerosols. These results will also be integrated with laboratory light scattering measurements and field absorption measurements for comparison of light scattering and albedo measurements made by other independent techniques

  15. 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

  16. Results of ACE 1, ACE 2, AEROSOLS99, INDOEX, TARFOX, and NEAQS: What Have We Learned? Where Do We Go From Here?

    NASA Astrophysics Data System (ADS)

    Quinn, P. K.; Bates, T. S.

    2003-12-01

    Since 1995, a series of international field experiments has focused on the measurement of aerosol properties in marine regions downwind of continental emissions. A goal of these experiments has been the characterization of regional aerosol properties and their controlling processes in order to improve estimates of aerosol direct and indirect radiative forcing. The first Aerosol Characterization Experiment (ACE 1) purposefully steered clear of any continental plumes in order to characterize the "background" aerosol upon which anthropogenic perturbations could be imposed. ACE 2 focused on the European plume, INDOEX (Indian Ocean Experiment) on the plume emanating from the Indian subcontinent, ACE Asia on the Asian plume, and TARFOX (Tropospheric Aerosol Radiative Forcing Observational Experiment) and NEAQS (New England Air Quality Study) on the eastern U.S. plume. In addition, measurements of dust and biomass burning aerosols from Africa were made the Atlantic Aerosols99 cruise. With the exception of TARFOX, all experiments included the shipboard sampling of aerosol chemical, physical, and optical properties. The shipboard sampling was done with standardized protocols to minimize sampling biases and to make the data from the different regions directly comparable. Regional aerosol properties from the North American, European, African, Asian, and Indian plumes will be compared and the major findings from these experiments will be presented. Properties that will be compared include the relative contribution of the dominant chemical components to aerosol mass and light extinction, the absolute concentrations of the chemical components, light scattering and absorption by the aerosol, single scattering albedo, and aerosol optical depth. Since TARFOX was an aircraft study we include only data collected at altitudes less than 300 m. In addition to using standardized sampling protocols on the ship, over-determined data sets were collected so that a measured aerosol property

  17. 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

  18. No contribution of angiotensin-converting enzyme (ACE) gene variants to severe obesity: a model for comprehensive case/control and quantitative cladistic analysis of ACE in human diseases.

    PubMed

    Bell, Christopher G; Meyre, David; Petretto, Enrico; Levy-Marchal, Claire; Hercberg, Serge; Charles, Marie Aline; Boyle, Cliona; Weill, Jacques; Tauber, Maïte; Mein, Charles A; Aitman, Timothy J; Froguel, Philippe; Walley, Andrew J

    2007-03-01

    Candidate gene analyses are often inconclusive owing to genetic or phenotypic heterogeneity, low statistical power, selection of nonfunctional SNPs, and inadequate statistical analysis of the genetic architecture. Angiotensin-converting enzyme (ACE) is involved in adipocyte growth and function and the ACE-processed angiotensin II inhibits adipocyte differentiation. Associations between body mass index (BMI) and ACE polymorphisms have been reported in general populations, but the contribution to severe obesity of this gene, which is located under an obesity genome-scan linkage peak on 17q23, is unknown. ACE is one of the most studied genes and markers responsible for variation in circulating ACE enzyme levels have been extensively characterised. Eight of these variants were genotyped in 1054 severely obese cases and 918 nonobese controls, as well as 116 nuclear families from the genome scan (n=447), enabling the known clades to be inferred. Qualitative analysis of individual single-nucleotide polymorphisms (SNPs), haplotypes, clades, and diploclades demonstrated no significant associations (P<0.05) after minimal correction for multiple testing. Quantitative analysis of clades and diploclades for BMI, waist-to-hip ratio, or ZBMI in children were also not significant. This rigorous, large-scale study of common, well-defined, severe polygenic obesity provides strong evidence that functionally relevant sequence variation in ACE, whether it is defined at the level of SNPs, haplotypes, or clades, is not associated with severe obesity in French Caucasians. Such a study design exemplifies the strategy needed to clearly define the contribution of the ACE gene to the plethora of complex genetic diseases where weak associations have been previously reported.

  19. Correlation between ultra-high performance liquid chromatography-tandem mass spectrometry and reversed-phase thin-layer chromatography hydrophobicity data for evaluation of angiotensin-converting enzyme inhibitors absorption.

    PubMed

    Odovic, Jadranka V; Markovic, Bojan D; Injac, Rade D; Vladimirov, Sote M; Karljikovic-Rajic, Katarina D

    2012-10-01

    In this research seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, benazepril) were studied to evaluate the correlation between their absorption and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) and reversed-phase thin-layer chromatography (RP-TLC) hydrophobicity data (φ(0) or C(0) parameters, respectively). Their absorption values were in the range of 25-60%, while calculated KOWWIN logP values were from -0.94 to 6.61. Additionally, perindopril (absorption 70%, KOWWIN logP 2.59) and moexipril (absorption 22%, KOWWIN logP 3.36) were introduced for the theoretical considerations due to their high/low absorption values which were on the opposite sites in comparison with the majority of ACE inhibitors (25-60%). In the theoretical considerations it was shown that the solubility data (logS) must be considered, as independent variable, simultaneously with KOWWIN logP to obtain reliable correlation (r(2)=0.7208) between absorption and ACE inhibitors lipophilicity. As the main topic of this study, the relationships between literature available and absorption data predicted by multiple linear regression (MLR) using logS values besides chromatographically obtained hydrophobicity parameters C(0) (r(2)=0.6424) or φ(0) (r(2)=0.6762) were studied proving that these parameters could be used in ACE inhibitors absorption evaluation. The UHPLC-MS method provides the direct application of experimentally obtained φ(0) values that is the advantage of this method. For better MLR correlation of ACE inhibitors absorption with C(0) parameters (RP-TLC) and logS, mathematical conversion of C(0) parameters to logC(0) values was necessary based on requisite for probability value of regression analysis (P<0.05). The accordance and differences between hydrophobicity parameters obtained by UHPLC-MS and RP-TLC were defined.

  20. The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial Mediterranean fever.

    PubMed

    Yigit, Serbülent; Tural, Sengul; Tekcan, Akın; Tasliyurt, Turker; Inanir, Ahmet; Uzunkaya, Süheyla; Kismali, Gorkem

    2014-05-01

    Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.

  1. Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.

    PubMed

    İnal, Esra Erkol; Görükmez, Orhan; Eroğlu, Selma; Görükmez, Özlem; Solak, Özlem; Topak, Ali; Yakut, Tahsin

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.

  2. The appropriate dose of angiotensin‐converting‐enzyme inhibitors or angiotensin receptor blockers in patients with dilated cardiomyopathy. The higher, the better?

    PubMed Central

    Konishi, Masaaki; von Haehling, Stephan

    2015-01-01

    Abstract Heart failure is a major public issue, and dilated cardiomyopathy (DCM) is one of the common etiologies of heart failure. DCM is generally progressive, and some patients with DCM need heart transplant despite optimal medical and mechanical therapy. Current guidelines recommend inhibitors of renin–angiotensin–aldosterone system, namely angiotensin‐converting‐enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), and mineralocorticoid receptor antagonist as well as beta‐blockers for the medical treatment of heart failure with reduced ejection fraction, including DCM. Furthermore, because they have beneficial effects on the outcome of heart failure in a dose‐related fashion, they should be titrated to the target dose. In clinical practice, the underuse and under‐dose of these agents matter; however, the efficacy and safety of supramaximal dose of ACE inhibitor or ARB have never been investigated in the patients with DCM. In this issue of ESC Heart Failure, it is demonstrated that benazepril or valsartan at supramaximal dose improved left ventricular function and reduced cardiovascular events compared with each drug at low dose, respectively. In this editorial, the current evidence concerning the use of ACE inhibitor or ARB in patients with HF and future prospective will be discussed.

  3. 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

  4. Combined suppression of the intrarenal and circulating vasoconstrictor renin-ACE-ANG II axis and augmentation of the vasodilator ACE2-ANG 1-7-Mas axis attenuates the systemic hypertension in Ren-2 transgenic rats exposed to chronic hypoxia.

    PubMed

    Červenka, L; Bíbová, J; Husková, Z; Vaňourková, Z; Kramer, H J; Herget, J; Jíchová, Š; Sadowski, J; Hampl, V

    2015-01-01

    The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks´ hypoxia. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks´ exposure to chronic hypoxia did not alter SBP and MAP. Surprisingly, in TGR it decreased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposure to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR. PMID:25194129

  5. Enterococcus faecalis strains from food, environmental, and clinical origin produce ACE-inhibitory peptides and other bioactive peptides during growth in bovine skim milk.

    PubMed

    Gútiez, Loreto; Gómez-Sala, Beatriz; Recio, Isidra; del Campo, Rosa; Cintas, Luis M; Herranz, Carmen; Hernández, Pablo E

    2013-08-16

    Enterococcus faecalis isolates from food and environmental origin were evaluated for their angiotensin-converting enzyme (ACE)-inhibitory activity (ACE-IA) after growth in bovine skim milk (BSM). Most (90% active) but not all (10% inactive) E. faecalis strains produced BSM-derived hydrolysates with high ACE-IA. Known ACE-inhibitory peptides (ACE-IP) and an antioxidant peptide were identified in the E. faecalis hydrolysates by reversed-phase high-performance liquid chromatography-tandem mass spectrometry (RP-HPLC-MS/MS). Antimicrobial activity against Pediococcus damnosus CECT4797 and Listeria ivanovii CECT913 was also observed in the E. faecalis hydrolysates. The incidence of virulence factors in the E. faecalis strains with ACE-IA and producers of ACE-IP was variable but less virulence factors were observed in the food and environmental strains than in the clinical reference strains. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) based analysis demonstrated that food and environmental E. faecalis strains were genetically different from those of clinical origin. When evaluated, most E. faecalis strains of clinical origin also originated BSM-derived hydrolysates with high ACE-IA due to the production of ACE-IP. Accordingly, the results of this work suggest that most E. faecalis strains of food, environmental and clinical origin produce BSM-derived bioactive peptides with human health connotations and potential biotechnological applications.

  6. Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine.

    PubMed

    Ball, Stephen G; White, William B

    2003-05-22

    In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan

  7. Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine.

    PubMed

    Ball, Stephen G; White, William B

    2003-05-22

    In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan

  8. 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.

  9. Evaluating MOPITT and ACE Upper-Tropospheric Carbon Monoxide Retrievals with HIPPO In-Situ Measurements

    NASA Astrophysics Data System (ADS)

    Martinez-Alonso, S.; Deeter, M. N.; Emmons, L. K.; Gille, J. C.; Pan, L.; Park, M.; Worden, H. M.; Bernath, P. F.; Boone, C.; Kolonjari, F.; Walker, K. A.; Daube, B. C.; Pittman, J. V.; Wofsy, S. C.

    2013-12-01

    The MOPITT (Measurements Of Pollution In The Troposphere) instrument on board NASA's Terra satellite has been measuring tropospheric carbon monoxide (CO) since 2000, providing the longest global CO record to date. The MOPITT dataset has been validated against in situ measurements in the past. Unfortunately, few of the in situ profiles reach into the upper troposphere (UT). Thus, our understanding of MOPITT performance in the UT is limited. ACE-FTS (the Fourier Transform Spectrometer on board the Atmospheric Chemistry Experiment, from the Canadian Space Agency) has been monitoring, among others, CO in the lower mesosphere, stratosphere, and upper troposphere since 2004. Here we present a comparison of MOPITT and ACE-FTS retrievals in the UT and evaluate the performance and temporal stability of the two instruments, of importance in climate analyses. MOPITT and ACE-FTS measurements are also contrasted with airborne HIPPO-QCLS (Quantum Cascade Laser Spectrometer on the HIAPER Pole to Pole Observations experiment) profiles, which we consider our 'truth' due to their high resolution, precision, and accuracy. Comparing these three datasets requires bridging large differences in their sampling resolution and observation types. MOPITT is a nadir-looking, cross-track scanning gas correlation radiometer which acquires ~200,000 measurements per day in the near and thermal infrared with a ground instantaneous field of view (GIFOV) of 22x22 km2 and a swath width around 640 km; global coverage is attained in approximately 3 days. MOPITT provides total CO column and vertical CO profiles with 10 pressure layers between the surface and 100 hPa. We analyze vertical CO profiles derived from the thermal infrared channels only, using day-and-night, cloud-free, otherwise unfiltered level 2 data. ACE-FTS is a limb sounder, high resolution (0.02 cm-1) infrared spectrometer with a GIFOV of ~500x500 km2 and 3-4 km vertical resolution which acquires up to 30 measurements per day. We analyze

  10. Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with placental hypoxia and reduced umbilical blood flow velocity

    PubMed Central

    Pulgar, Victor M.; Lindsey, Sarah H.; Yamane, Larissa; Varagic, Jasmina; McGee, Carolynne; daSilva, Mauro; Lopes Bonfa, Paula; Gurley, Susan B.; Brosnihan, K. Bridget

    2015-01-01

    Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal weight at late gestation; however, whether uteroplacental vascular and/or hemodynamic disturbances underlie this growth-restricted phenotype is unknown. Uterine artery reactivity and flow velocities, umbilical flow velocities, trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO) and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood pressure was higher in pregnant ACE2 KO vs. WT mice (102.3 ± 5.1 vs. 85.1 ± 1.9 mmHg, n = 5–6), the magnitude of difference was similar to that observed in nonpregnant ACE2 KO vs. WT mice. Maternal urinary protein excretion, serum creatinine, and kidney or heart weights were not different in ACE2 KO vs. WT. Fetal weight and pup-to-placental weight ratio were lower in ACE2 KO vs. WT mice. A higher sensitivity to Ang II [pD2 8.64 ± 0.04 vs. 8.5 ± 0.03 (−log EC50)] and greater maximal contraction to phenylephrine (169.0 ± 9.0 vs. 139.0 ± 7.0% KMAX), were associated with lower immunostaining for Ang II receptor 2 and fibrinoid content of the uterine artery in ACE2 KO mice. Uterine artery flow velocities and trophoblast invasion were similar between study groups. In contrast, umbilical artery peak systolic velocities (60.2 ± 4.5 vs. 75.1 ± 4.5 mm/s) and the resistance index measured using VEVO 2100 ultrasound were lower in the ACE2 KO vs. WT mice. Immunostaining for pimonidazole, a marker of hypoxia, and hypoxia-inducible factor-2α were higher in the trophospongium and placental labyrinth of the ACE2 KO vs. WT. In summary, placental hypoxia and uterine artery dysfunction develop before major growth of the fetus occurs and may explain the fetal growth restricted phenotype. PMID:25968580

  11. 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.

  12. 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.

  13. Airborne Sunphotometry of Aerosol Optical Depth and Columnar Water Vapor During ACE-Asia

    NASA Technical Reports Server (NTRS)

    Redemann, Jens; Schmid, B.; Russell, P. B.; Livingston, J. M.; Eilers, J. A.; Ramirez, S. A.; Kahn, R.; Hipskind, R. Stephen (Technical Monitor)

    2001-01-01

    During the Intensive Field Campaign (IFC) of the Aerosol Characterization Experiment - Asia (ACE-Asia), March-May 2001, the 6-channel NASA Ames Airborne Tracking Sunphotometer (AATS-6) operated during 15 of the 19 research flights aboard the NCAR C- 130, while its 14-channel counterpart (AATS- 14) was flown successfully on all 18 research flights of a Twin Otter aircraft operated by the Center for Interdisciplinary Remotely Piloted Aircraft Studies (CIRPAS), Monterey, CA. ACE-Asia was the fourth in a series of aerosol characterization experiments and focused on aerosol outflow from the Asian continent to the Pacific basin. Each ACE was designed to integrate suborbital and satellite measurements and models so as to reduce the uncertainty in calculations of the climate forcing due to aerosols. The Ames Airborne Tracking Sunphotometers measured solar beam transmission at 6 (380-1021 nm, AATS-6) and 14 wavelengths (353-1558 nm, AATS-14) respectively, yielding aerosol optical depth (AOD) spectra and column water vapor (CWV). Vertical differentiation in profiles yielded aerosol extinction and water vapor concentration. The wavelength dependence of AOD and extinction indicates that supermicron dust was often a major component of the aerosol. Frequently this dust-containing aerosol extended to high altitudes. For example, in data flights analyzed to date 34 +/- 13% of full-column AOD(525 nm) was above 3 km. In contrast, only 10 +/- 4% of CWV was above 3 km. In this paper, we will show first sunphotometer-derived results regarding the spatial variation of AOD and CWV, as well as the vertical distribution of aerosol extinction and water vapor concentration. Preliminary comparison studies between our AOD/aerosol extinction data and results from: (1) extinction products derived using in situ measurements and (2) AOD retrievals using the Multi-angle Imaging Spectro-Radiometer (MISR) aboard the TERRA satellite will also be presented.

  14. 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

  15. Cooperative Activation of a Eukaryotic Transcription Factor: Interaction between Cu(I) and Yeast ACE1 Protein

    NASA Astrophysics Data System (ADS)

    Furst, Peter; Hamer, Dean

    1989-07-01

    Cu ions activate yeast metallothionein gene transcription by altering the conformation and DNA-binding activity of the ACE1 transcription factor. We show that this conformational switch occurs in an all-or-none highly cooperative fashion (Hill coefficient = 4). Analysis of the subunit composition of ACE1 bound to DNA indicates that cooperativity results from the binding of multiple Cu(I) ions to the cysteine-rich DNA-binding domain. Surprisingly, DNA has little effect on the interaction between Cu(I) and ACE1 as assayed by partial proteolysis; this suggests that the effect of the metal on DNA binding is primarily kinetic rather than thermodynamic. Although Ag(I) also activates ACE1, it acts less cooperatively than the smaller Cu(I) ion and the resulting metalloprotein has a reduced affinity for DNA. The cooperative interaction between Cu and ACE1 allows the cell to respond to a small change in metal concentration by a large change in gene expression.

  16. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity.

    PubMed

    Sharifi, Ali M; Darabi, Radbod; Akbarloo, Nasrin

    2003-10-24

    Tribulus terrestris is a natural herb used for treating many diseases including hypertension. According to previous reports, aqueous extract of tribulus fruits may have some antihypertensive effect with an unknown mechanism. The present study investigated the antihypertensive mechanism of tribulus in 2K1C hypertensive rats by measurement of circulatory and local ACE activity in aorta, heart, kidney and lung. Four groups of rats were selected; control, sham, operated or hypertensive and tribulus treated hypertensive group. Hypertension was induced using silver clip on renal artery by surgery. Four weeks after surgery, a single daily dose of 10 mg/kg of lyophilized aqueous extract of tribulus fruit were given orally to 2K1C rats for four weeks. ACE activity was determined by high performance liquid chromatography (HPLC). Blood pressure was measured by the tail-cuff method. The systolic blood pressure (SBP) was significantly increased in 2K1C rats compared to control rats. The SBP of tribulus fed hypertensive rats was significantly decreased compared to hypertensive rats. The ACE activity in all tissues of 2K1C rats including: aorta, heart, kidney, lung as well as serum were significantly increased compared to normal rats. The ACE activity in all tissues of tribulus fed hypertensive rats was significantly lower than that of hypertensive rats, which was more pronounced in kidney. These results indicated that there is a negative correlation between consumption of tribulus and ACE activity in serum and different tissues in 2K1C rats.

  17. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury.

    PubMed

    Yang, Penghui; Gu, Hongjing; Zhao, Zhongpeng; Wang, Wei; Cao, Bin; Lai, Chengcai; Yang, Xiaolan; Zhang, LiangYan; Duan, Yueqiang; Zhang, Shaogeng; Chen, Weiwen; Zhen, Wenbo; Cai, Maosheng; Penninger, Josef M; Jiang, Chengyu; Wang, Xiliang

    2014-11-13

    Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.

  18. Proton pump inhibitors

    MedlinePlus

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This ...

  19. 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.

  20. 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.

  1. 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:

  2. 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:

  3. 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…

  4. 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

  5. Expression of the lipid transfer protein Ace-AMP1 in transgenic wheat enhances antifungal activity and defense responses.

    PubMed

    Roy-Barman, Subhankar; Sautter, Christof; Chattoo, Bharat B

    2006-08-01

    To enhance fungal disease resistance, wheat plants (cv. Bobwhite) were engineered to constitutively express the potent antimicrobial protein Ace-AMP1 from Allium cepa, driven by a maize ubiquitin promoter along with its first intron. The bar gene was used for selection of putative transformants on medium containing phosphinothricin (PPT). Transgene inheritance, integration and stability of expression were confirmed over two generations by PCR, Southern, northern and western blot analyses, respectively. The levels of Ace-AMP1 in different transgenic lines correlated with the transcript levels of the transgene. Up to 50% increase in resistance to Blumeria graminis f. sp. tritici was detected in detached leaf assays. In ears of transgenic wheat inoculated with Neovossia indica, Ace-AMP1 intensified expression of defense-related genes. Elevated levels of salicylic acid and of transcripts of phenylalanine ammonia lyase (PAL), glucanase (PR2) and chitinase (PR3) in the transgenic plants indicated manifestation of systemic acquired resistance (SAR). PMID:16906444

  6. Antioxidant, antibacterial and ACE-inhibitory activity of four monofloral honeys in relation to their chemical composition.

    PubMed

    León-Ruiz, Virginia; González-Porto, Amelia V; Al-Habsi, Nasser; Vera, Soledad; San Andrés, María Paz; Jauregi, Paula

    2013-11-01

    Different monofloral honeys from Castilla-La Mancha (Spain) have been studied in order to determine their main functional and biological properties. Thyme honey and chestnut honey possess the highest antioxidant capacity, which is due to their high vitamin C (in thyme honey) and total polyphenolic content (in chestnut honey). On the other hand, chestnut honey showed high antimicrobial activity against Staphylococcus aureus and Escherichia coli, whilst others had no activity against S. aureus and showed very small activity against E. coli. Moreover it was found that the antimicrobial activity measured in chestnut honey was partly due to its lysozyme content. In addition the angiotensin I-converting enzyme (ACE) inhibitory activity was measured, and the ACE inhibition is one mechanism by which antihypertensive activity is exerted in vivo. All the types of honey showed some activity but chestnut honey had the highest ACE inhibitory activity. PMID:24056722

  7. ACE-Asia: Size/Time/Compositionally Resolved Aerosols During ACE-Asia Using Continuously Sampling DRUM Technology and Synchrotron-XRF Analysis

    NASA Astrophysics Data System (ADS)

    Cahill, T. A.; Cliff, S. S.; Jimenez-Cruz, M.; Perry, K. D.

    2001-12-01

    The adaptation of focused beam technology to continuously sampling drum impactors (DRUMs) has allowed for an unprecedented number of size/time/compositional analyses of aerosols during the Spring, 2001 ACE-Asia study and a summer follow-on. While continuously sampling and sizing inertial drum impactors have been available for aerosol monitoring and research for the past 30 years, cost and sensitivity considerations have generally limited their use, even in research studies. These constraints have been greatly relaxed by our application of synchrotron X-ray fluorescence (S-XRF) analysis for elemental analysis of aerosols, both increasing sensitivity and decreasing cost. The intense polarized x-ray beams of the Lawrence Berkeley National Laboratory's Advanced Light Source (ALS) allows us to eliminate 99% of all the background normally present in x-ray analysis while matching the x-ray beam spot to the 0.2 mm "footprint" of our DRUM impactors. This combination allows non-destructive analyses of elements from sodium to uranium (with some minor elements masked by interferences) with a time resolution set during analysis, not during sampling. The DELTA Group and its many collaborators executed a 21 site network of continuously sampling 3 and 8 stage DRUM impactors for the 6 weeks of ACE-Asia. Fewer than 5% of the potential 80,000 samples were lost due to sampling problems. During S-XRF analysis, a nominal time resolution of 6 hrs was chosen, with 2 hrs available as needed during aerosol episodes. The 168 mm drum strips were mounted in frames and exposed to the "white" polarized x-ray beam of ALS Beam Line 10.3.1 for 30 seconds, yielding quantitative elemental determinations from sodium through molybdenum plus heavy elements, certified by 80 analytical standards and NIST SRMs. Minimum detectable limits ranged from 0.1 ng/m3 for sulfur to 0.005 ng/m3 for transition metals such as zinc, allowing scores of positive elemental determinations in each spectrum. During ACE

  8. ACE inhibition with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension.

    PubMed

    Petersen, J R; Drabaek, H; Gleerup, G; Mehlsen, J; Petersen, L J; Winther, K

    1996-03-01

    The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied. Thirteen patients with mild to moderate essential hypertension completed this randomized, double-blinded, placebo-controlled, crossover study. After a three-week run-in period the patients entered three periods lasting four weeks each, wherein they were treated with placebo, spirapril, or hydrochlorothiazide. Blood pressure, hemodynamic variables (stroke volume, heart rate, cardiac output, index of contractility, and systemic vascular resistance), echocardiography (left ventricular mass), and Doppler-derived atrial to early (A/E)-ratio velocity time integrals (VTI) were measured at the end of each of the four periods. Spirapril lowered the A/E-ratio VTIs (0.57, 0.12-1.00) (P < 0.02) as compared with both placebo (0.80, 0.50-2.67) and hydrochlorothiazide (0.83, 0.44-1.25), and the drug normalized the A/E-ratio VTI in those patients with elevated values. The hemodynamic variables, left ventricular mass, and end-systolic wall stress were unchanged during all three treatments. There were no significant changes in mean blood pressure during the treatment periods. These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension. It thereby seems able to improve left ventricular diastolic function. The effect is not dependent upon changes in hemodynamic variables, blood pressure, left ventricular mass, or end-systolic wall stress.

  9. Comparison of the Cobas 4800 HPV Test and the Seeplex HPV4A ACE with the Hybrid Capture 2 Test

    PubMed Central

    Ki, Eun Young; Kim, Hee Eun; Choi, Yeong-Jin; Park, Jong-Sup; Kang, Chang Seok; Lee, Ahwon

    2013-01-01

    Background: It is well-known that persistent cervical infections with high-risk human papillomavirus (HPV) are related to the development of high-grade cervical intraepithelial neoplasia and invasive cervical cancer and that infection with HPV 16 and HPV 18 accounts for approximately 70% of all cases of invasive cervical cancer. Methods: We performed 3 HPV molecular tests―the Cobas 4800 HPV test, the Seeplex HPV4A ACE, and the hybrid capture 2 (HC2) test―in 146 cervical swab samples to compare between these three tests. Results: There was a concordance rate of 82.8% between the results of the Cobas 4800 HPV and the HC2 test and a concordance rate of 84.9% between the results of the Seeplex HPV4A ACE and the HC2 test. Between the Cobas 4800 HPV test and the Seeplex HPV4A ACE, there was a concordance rate of 89.6% in the detection of high-risk HPV between the results and a concordance rate of 98.7% in the detection of HPV 16 or 18. When an abnormal Pap test was defined as ≥low grade squamous intraepithelial lesion (LSIL), the sensitivity of the Cobas 4800 HPV test, the Seeplex HPV4A ACE and the HC2 test were 71.1%, 80.0%, and 88.9%, respectively, while their specificities were 76.4%, 74.5%, and 67.9%, respectively. Conclusions: The results of this study suggest that the Cobas 4800 HPV test and the Seeplex HPV4A ACE may be as effective as the HC2 test in detecting HR HPV and that the concordance between the results of the Cobas 4800 HPV test and the Seeplex HDV4A ACE may be higher in the detection of HPV 16 and HPV18 than concerning high-risk HPV. PMID:23329882

  10. Temperature and pressure retrievals from the Atmospheric Chemistry Experiment (ACE): a new technique and comparison with COSMIC

    NASA Astrophysics Data System (ADS)

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

    We present results of a new technique to retrieve temperature and pressure profiles from satellite 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). This technique benefits from high signal strength, high resolution, and self calibration. The CSA and NASA's Jet Propulsion Laboratory (JPL) developed a proposal to send a similar instrument to Mars: the Mars Atmospheric Trace Molecule Occultation Spectrometer (MATMOS, later canceled). To support this we have developed a new set of retrieval algorithms based on GGG used by the Total Carbon Column Observing Network (TCCON) and have applied these algorithms to ACE-FTS data. When performing temperature retrievals, the current approach of the ACE team is to fix the volume mixing ratio of CO_2 and carry out spectral fitting, varying temperature. While this method works very well and has been well validated, it relies on several assumptions, emph{a priori} knowledge, and data from models. Operating at another planet, these emph{a priori} are unknown and the models have not been developed to a suitable level. We demonstrate that by analyzing vibration-rotation bands of CO_2, we can retrieve vertical profiles of both temperature and pressure. Our retrieved temperature profiles are compared to those from ACE and the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC), and are used to retrieve volume mixing ratio vertical profiles for several gases, such as methane. The effects that variability in temperature and pressure have on retrieved VMR profiles is shown and retrieved VMR profiles are compared with those from ACE.

  11. Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats.

    PubMed

    Klimas, Jan; Olvedy, Michael; Ochodnicka-Mackovicova, Katarina; Kruzliak, Peter; Cacanyiova, Sona; Kristek, Frantisek; Krenek, Peter; Ochodnicky, Peter

    2015-08-01

    Since the identification of the alternative angiotensin converting enzyme (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new complex target for a pharmacological intervention. We investigated the expression of RAS components in the heart and kidney during the development of hypertension and its perinatal treatment with losartan in young spontaneously hypertensive rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR treated with losartan only until week 4 of age and discontinued until week 9. In the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged. Continuous losartan administration reduced LV weight (0.43 ± 0.02; P < 0.05 versus SHR) but did not influence altered cardiac RAS expression. Increased blood pressure in SHR (149 ± 2 in SHR versus 109 ± 2 mmHg in Wistar; P < 0.05) was associated with a lower renal expressions of renin, Agtr1a and Mas and with an increase in ACE2. Continuous losartan administration lowered blood pressure to control levels (105 ± 3 mmHg; P < 0.05 versus SHR), however, only renal renin and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR). Conclusively, prevention of hypertension and LV hypertrophy development by losartan was unrelated to cardiac or renal expression of Mas. Increased renal Ace2, and its further increase by losartan suggests the influence of locally generated Ang-(1-7) in organ response to the developing hypertension in SHRs.

  12. 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.

  13. 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.

  14. GrACE-PPM: A distributed dynamic adaptive mesh CFD Environment for accelerated inhomogeneous compressible flows

    NASA Astrophysics Data System (ADS)

    Zhang, Shuang; Parashar, Manish; Zabusky, Norman

    2001-11-01

    We merge the PPM compressible algorithm (VH-1 (M. Parashar, Grid Adaptive Computational Engine. 2001. http://www.caip.rutgers.edu/ parashar/TASSL/Projects/GrACE/Gmain.html)) with the new Grid Adaptive Computation Engine (GrACE ( J. M. Blondin and J. Hawley, Virginia Hydrodynamics Code. http://wonka.physics.ncsu.edu/pub/VH-1/index.html)). The latter environment uses the Berger-Oliger AMR algorithm and has many high-performance computation features such as data parallelism, data and computation locality, etc. We discuss the performance (scaling) resulting from examining the space of four parameters: top coarse level resolution; number of refinement levels; number of processors; duration of calculation. We validate the new code by applying it to the 2D shock-curtain interaction problem (N. J. Zabusky and S. Zhang. "Shock - planar curtain interactions in 2D: Emergence of vortex double layers, vortex projectiles and decaying stratified turbulence." Revised submitted Physics of Fluids, July, 2001.). We discuss the visualization and quantification of AMR data sets.

  15. 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.

  16. 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).

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. SolACES: Level 1 Data Evaluation and Intercomparison with other EUV Data

    NASA Astrophysics Data System (ADS)

    Erhardt, Christian; Brunner, Raimund; Schmidtke, Gerhard; Nikutowski, Bernd

    2012-07-01

    In the field of terrestrial climatology the continuous measuring the solar irradiance with highest possible accuracy is an important issue. In this context the analysis of the accuracy of the SolACES Level 1 data and the presentation of the results will be dealt with first. Special subject of interest is the investigation of the different variability of solar emissions as generated primarily in the lower and upper chromosphere, in the transition region and in the corona during the period of the SolACES mission of 4 years up to now. A detailed inter-comparison of these data with relevant data available in the science community for the same period from 2008-2012 will cover the main part of the talk. It is the aim to present a first approach matching these data by the international efforts going on with the TIGER/COSPAR symposia and workshops such as the Solar EUV-IR Irradiance Workshop in Freiburg (2009) and the Solar EUV Inter- Calibration and Validation Workshop in Boulder (2011).

  3. 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

  4. Mobilizing resilience and recovery in response to adverse childhood experiences (ACE): a Restorative Integral Support (RIS) case study.

    PubMed

    Larkin, Heather; Beckos, Brooke A; Shields, Joseph J

    2012-01-01

    The Restorative Integral Support (RIS) model is a comprehensive, whole person approach to addressing adversity and trauma. The Adverse Childhood Experiences (ACE) Study conducted by the Centers for Disease Control (CDC) and Kaiser Permanente reveals a relationship between childhood trauma and adult health and social problems. The current empirical case study presents the Committee on the Shelterless (COTS), in Petaluma, CA, as an example of one social service agency employing RIS to break cycles of homelessness. By applying RIS, research-based programming is offered within a culture of recovery that mobilizes resilience through social affiliations. The authors recommend RIS model implementation and research in programs serving populations with ACE backgrounds.

  5. 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.

  6. 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.

  7. The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene 'knockout' mice: sex differences and implications for the treatment of attention deficit hyperactivity disorder.

    PubMed

    Porter, Ashley J; Pillidge, Katharine; Grabowska, Ewelina M; Stanford, S Clare

    2015-04-01

    Mice lacking functional neurokinin-1 receptors (NK1R-/-) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R-/- and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R-/- mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R-/- and wildtype mice. Both antagonists increased the locomotor activity of NK1R-/- mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R-/- and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R-/- mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder.

  8. 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

  9. 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

  10. 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

  11. 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 adult rats by left anterior descending coronary artery ligation, and animals were then administered RA (50, 100, or 200 mg/kg) by gavage. Compared with the model group, RA treatment ameliorated changes in the left ventricular systolic pressure (LVSP), +dp/dtmax, and -dp/dtmax after 4 weeks. This was associated with attenuation of infarct size, collagen volume fraction (CVF), expression of collagen I, collagen III, alpha smooth muscle actin (α-SMA), and hydroxyproline (Hyp) concentrations. RA treatment was also associated with decreased angiotensin-converting enzyme (ACE) expression and increased ACE2 expression, as well as decreased expression of angiotensin type 1 receptor (AT1R) and phospho-p38 mitogen-activated protein kinase (p38 MAPK). Thus, RA can protect against cardiac dysfunction and fibrosis following MI, likely due to decreasing ACE expression and increasing ACE2 expression via the AT1R/p38 MAPK pathway. PMID:27538767

  12. CO2 Washout Testing of the REI and EM-ACES Space Suits

    NASA Technical Reports Server (NTRS)

    Mitchell, Kate; Norcross, Jason

    2011-01-01

    Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy and eventually unconsciousness or even death. Symptoms depend on several factors including partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject and physiological differences between subjects. The objective of this test was to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) across a range of workloads and flow rates for which ground testing is nominally performed. Three subjects were tested in each suit. In all but one case, each subject performed the test twice to allow for comparison between tests. Suit pressure was maintained at 4.3 psid. Subjects wore the suit while resting, performing arm ergometry, and walking on a treadmill to generate metabolic workloads of approximately 500 to 3000 BTU/hr. Supply airflow was varied at 6, 5 and 4 actual cubic feet per minute (ACFM) at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored real-time via gas analyzers with sampling tubes connected to the oronasal mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the air outlet from the suit. Real-time metabolic rate was used to adjust the arm ergometer or treadmill workload to meet target metabolic rates. In both suits, inspired CO2 was primarily affected by the metabolic rate of the subject, with increased metabolic rate resulting in increased inspired ppCO2. Suit flow rate also affected inspired ppCO2, with decreased flow causing small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates greater than or equal to 2000 BTU/hr. Results were consistent between suits, with

  13. Enrichment of ACE inhibitory peptides in navy bean (Phaseolus vulgaris) using lactic acid bacteria.

    PubMed

    Rui, Xin; Wen, Delan; Li, Wei; Chen, Xiaohong; Jiang, Mei; Dong, Mingsheng

    2015-02-01

    The present study was conducted to explore a novel strategy to enhance angiotensin I-converting enzyme (ACE) inhibitory activities of navy bean by preparation of navy bean milk (NBM) which was then subjected to fermentation of four lactic acid bacteria (LAB) strains, namely, Lactobacillus bulgaricus, Lactobacillus helveticus MB2-1, Lactobacillus plantarum B1-6, and Lactobacillus plantarum 70810. With the exception of L. helveticus MB2-1, the other three selected strains had good growth performances in NBM with viable counts increased to log 8.30-8.39 cfu ml(-1) during 6 h of fermentation, and thus were selected for the following investigations. Protein contents of NBM significantly reduced when treated with L. bulgaricus and L. plantarum B1-6, and the electrophoresis patterns showed the preferable proteins for LAB strains to hydrolyze were α- and β-type phaseolins, whereas γ-type phaseolin was resistant to hydrolysis. RP-HPLC analysis demonstrated all fermented NBM had higher intensities of peaks with retention times between 2.5 and 3.5 min indicative of formation of small peptides. All fermented NBM showed higher ACE inhibitory activity compared to the unfermented ones, for which 2 h, 3 h, and 5 h were found to be the optimum fermentation periods for respectively L. plantarum 70810, L. plantarum B1-6 and L. bulgaricus, with IC50 values of 109 ± 5.1, 108 ± 1.1, and 101 ± 2.2 μg protein ml(-1). The subsequent in vitro gastrointestinal simulation afforded all fermented extracts reduced IC50 values and the extracts fermented by L. plantarum B1-6 exerted the lowest IC50 value of 21 ± 2.1 μg protein ml(-1). The research has broadened our knowledge bases on the effect of LAB fermentation on the degradation of navy bean proteins and the capacity to release ACE inhibitory peptides. The approach was promising to obtain probiotic products with potential to serve as functional ingredients targeting hypertension.

  14. Aerodynamically controlled expansion (ACE) nozzle for short takeoff and vertical landing aircraft

    NASA Astrophysics Data System (ADS)

    Terrier, Douglas Anthony

    2000-10-01

    An Aerodynamically Controlled Expansion (ACE) propulsion nozzle that improves hover thrust performance by 2.5 percent in a short take off and vertical landing (STOVL) aircraft has been developed. The ACE concept employs a carefully defined step in the nozzle internal contour that interacts with the boundary layer to induce flow separation in the divergent section, thereby relieving over-expansion losses during hover. This study specifies design parameters for a passive boundary layer control step for application on the Joint Strike Fighter (JSF). In addition, parametric performance predictions presented herein provide a basic understanding of how the step concept can be applied to overcome undesirable over-expansion in generalized supersonic nozzle flows. The aerodynamic phenomena governing the interaction of the step with the nozzle flow were investigated in an extensive, parametric CFD analysis. The CFD analysis matrix consists of thirty-three axi-symmetric nozzle cases including expansion area ratios (A9/A 8) of 1.1, 1.3 and 1.5, slot area ratios (A s/A8) of 1.0 (baseline), 1.1 and 1.2, and covering the nozzle pressure ratio (NPR) range of 2.0 to 8.0. The CFD results define the NPR at which flow separation occurs as a function of A9/A8, and A s/A8, and the effect of the step on nozzle performance. Results indicate that the onset of separation occurs at higher NPR with increasing A9/A 8 and increasing As/A 8. For the case of the JSF nozzle with A9/ A8 = 1.3, the CFD analysis predicted that a nozzle having an As/A8 = 1.1 produces an improvement of approximately 2.5 percent in hover thrust relative to the baseline with a minimal adverse impact at other design conditions. Twelve percent scale models representing the baseline, and step sizes of 1.1 and 1.2 were tested in the Lockheed Martin Thrust Measurement Facility (TMF). Test results showed excellent agreement with CFD predictions and validated the step performance. Preliminary design integration studies support

  15. CO2 Washout Testing of the REI and EM-ACES Space Suits

    NASA Technical Reports Server (NTRS)

    Mitchell, Kathryn C.; Norcross, Jason

    2012-01-01

    When a space suit is used during ground testing, adequate carbon dioxide (CO2) washout must be provided for the suited subject. Symptoms of acute CO2 exposure depend on partial pressure of CO2 (ppCO2), metabolic rate of the subject, and other factors. This test was done to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) for a range of workloads and flow rates for which ground testing is nominally performed. Three subjects were tested in each suit. In all but one case, each subject performed the test twice. Suit pressure was maintained at 4.3 psid. Subjects wore the suit while resting, performing arm ergometry, and walking on a treadmill to generate metabolic workloads of about 500 to 3000 BTU/hr. Supply airflow was varied between 6, 5, and 4 actual cubic feet per minute (ACFM) at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored in real time by gas analyzers with sampling tubes connected to the mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the suit air outlet. Real-time metabolic rate was used to adjust the arm ergometer or treadmill workload to meet target metabolic rates. In both suits, inspired CO2 was affected mainly by the metabolic rate of the subject: increased metabolic rate significantly (P < 0.05) increased inspired ppCO2. Decreased air flow caused small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates . 2000 BTU/hr. CO2 washout values of the EM-ACES were slightly but not significantly better than those of the REI suit. Regression equations were developed for each suit to predict the mean inspired ppCO2 as a function of metabolic rate and suit flow rate. This paper provides detailed descriptions of the test hardware, methodology, and results as well as implications for future

  16. Technology advancement for the ASCENDS mission using the ASCENDS CarbonHawk Experiment Simulator (ACES)

    NASA Astrophysics Data System (ADS)

    Obland, M. D.; Antill, C.; Browell, E. V.; Campbell, J. F.; CHEN, S.; Cleckner, C.; Dijoseph, M. S.; Harrison, F. W.; Ismail, S.; Lin, B.; Meadows, B. L.; Mills, C.; Nehrir, A. R.; Notari, A.; Prasad, N. S.; Kooi, S. A.; Vitullo, N.; Dobler, J. T.; Bender, J.; Blume, N.; Braun, M.; Horney, S.; McGregor, D.; Neal, M.; Shure, M.; Zaccheo, T.; Moore, B.; Crowell, S.; Rayner, P. J.; Welch, W.

    2013-12-01

    The ASCENDS CarbonHawk Experiment Simulator (ACES) is a NASA Langley Research Center project funded by NASA's Earth Science Technology Office 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) multiple transmitter and telescope-aperture operations, (2) high-efficiency CO2 laser transmitters, (3) a high bandwidth detector and transimpedance amplifier (TIA), and (4) advanced algorithms for cloud and aerosol discrimination. The instrument architecture is being developed for ACES to operate on a high-altitude aircraft, and it will be directly scalable to meet the ASCENDS mission requirements. The above technologies are critical for developing an airborne simulator and spaceborne instrument with lower platform consumption of size, mass, and power, and with improved performance. This design employs several laser transmitters and telescope-apertures to demonstrate column CO2 retrievals with alignment of multiple laser beams in the far-field. ACES will transmit five laser beams: three from commercial lasers operating near 1.57-microns, and two from the Exelis atmospheric oxygen (O2) fiber laser amplifier system operating near 1.26-microns. The Master Oscillator Power Amplifier at 1.57-microns measures CO2 column concentrations using an Integrated-Path Differential Absorption (IPDA) lidar approach. O2 column amounts needed for calculating the CO2 mixing ratio will be retrieved using the Exelis laser system with a similar IPDA approach. The three aperture telescope design was built to meet the constraints of the Global Hawk high-altitude unmanned aerial vehicle (UAV). This assembly integrates fiber-coupled transmit collimators for all of the laser transmitters and fiber-coupled optical signals from the three telescopes to the aft optics and detector package. The detector

  17. A Detailed Physiologically Based Model to Simulate the Pharmacokinetics and Hormonal Pharmacodynamics of Enalapril on the Circulating Endocrine Renin-Angiotensin-Aldosterone System

    PubMed Central

    Claassen, Karina; Willmann, Stefan; Eissing, Thomas; Preusser, Tobias; Block, Michael

    2013-01-01

    The renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathogenesis of cardiovascular disorders including hypertension and is one of the most important targets for drugs. A whole body physiologically based pharmacokinetic (wb PBPK) model integrating this hormone circulation system and its inhibition can be used to explore the influence of drugs that interfere with this system, and thus to improve the understanding of interactions between drugs and the target system. In this study, we describe the development of a mechanistic RAAS model and exemplify drug action by a simulation of enalapril administration. Enalapril and its metabolite enalaprilat are potent inhibitors of the angiotensin-converting-enzyme (ACE). To this end, a coupled dynamic parent-metabolite PBPK model was developed and linked with the RAAS model that consists of seven coupled PBPK models for aldosterone, ACE, angiotensin 1, angiotensin 2, angiotensin 2 receptor type 1, renin, and prorenin. The results indicate that the model represents the interactions in the RAAS in response to the pharmacokinetics (PK) and pharmacodynamics (PD) of enalapril and enalaprilat in an accurate manner. The full set of RAAS-hormone profiles and interactions are consistently described at pre- and post-administration steady state as well as during their dynamic transition and show a good agreement with literature data. The model allows a simultaneous representation of the parent-metabolite conversion to the active form as well as the effect of the drug on the hormone levels, offering a detailed mechanistic insight into the hormone cascade and its inhibition. This model constitutes a first major step to establish a PBPK-PD-model including the PK and the mode of action (MoA) of a drug acting on a dynamic RAAS that can be further used to link to clinical endpoints such as blood pressure. PMID:23404365

  18. Fixed-Dose Combinations of Renin–Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension

    PubMed Central

    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

    2015-01-01

    Abstract 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

  19. Adult Competency Education Kit. Basic Skills in Speaking, Math, and Reading for Employment. Part Q. ACE Competency Based Job Descriptions: #91--Meat Cutter; #92--Shipping Clerk; #93--Long Haul Truck Driver; #94--Truck Driver--Light.

    ERIC Educational Resources Information Center

    San Mateo County Office of Education, Redwood City, CA. Career Preparation Centers.

    This fourteenth of fifteen sets of Adult Competency Education (ACE) Based Job Descriptions in the ACE kit contains job descriptions for Meat Cutter, Shipping Clerk, Long Haul Truck Driver, and Truck Driver--Light. Each begins with a fact sheet that includes this information: occupational title, D.O.T. code, ACE number, career ladder, D.O.T.…

  20. Adult Competency Education Kit. Basic Skills in Speaking, Math, and Reading for Employment. Part R. ACE Competency Based Job Descriptions: #95--Bus Driver; #98--General Loader; #99--Forklift Operator; #100--Material Handler.

    ERIC Educational Resources Information Center

    San Mateo County Office of Education, Redwood City, CA. Career Preparation Centers.

    This fifteenth of fifteen sets of Adult Competency Education (ACE) Competency Based Job Descriptions in the ACE kit contains job descriptions for Bus Driver, General Loader, Forklift Operator, and Material Handler. Each begins with a fact sheet that includes this information: occupational title, D.O.T. code, ACE number, career ladder, D.O.T.…

  1. Adult Competency Education Kit. Basic Skills in Speaking, Math, and Reading for Employment. Part F. ACE Competency Based Job Descriptions: #20--Body Fender Mechanic; #21--New Car Get-Ready Person.

    ERIC Educational Resources Information Center

    San Mateo County Office of Education, Redwood City, CA. Career Preparation Centers.

    This third of sixteen sets of Adult Competency Education (ACE) Based Job Descriptions in the ACE kit contains job descriptions for Body Fender Mechanic and New Car Get-Ready Person. 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 developmental…

  2. Using the Admitted Class Evaluation Service (ACES) to Conduct Institution-Specific Admission or Placement Validity Studies

    ERIC Educational Resources Information Center

    Shaw, Emily J.

    2011-01-01

    Presented at the 23rd Annual Historically Black Colleges & Universities (HBCU) Conference in Atlanta, GA, in September 2011. Admitted Class Evaluation Service (ACES) is the College Board's free online service that predicts how admitted students will perform at a college or university generally, and how successful students will be in specific…

  3. Pretreatment of garlic powder using sweep frequency ultrasound and single frequency countercurrent ultrasound: optimization and comparison for ACE inhibitory activities.

    PubMed

    Ma, Haile; Huang, Liurong; Peng, Lei; Wang, Zhenbin; Yang, Qiaorong

    2015-03-01

    The sweep frequency ultrasound (SFU) and single frequency countercurrent ultrasound (SFCU) pretreatments were modeled and compared based on production of angiotensin I-converting enzyme (ACE) inhibitory peptides from garlic hydrolysates. Two mathematical models were developed to show the effect of each variable and their combinatorial interactions on ACE inhibitory activity. The optimum levels of the parameters in SFU were determined using uniform design, which revealed these as follows: total ultrasonic time 1.5 h, on-time of pulse 18 s and off-time of pulse 3 s. Under optimized conditions, the experimental values of SFU and SFCU were 65.88% and 67.78%, which agreed closely with the predicted values of 63.44% and 67.33%. The SFU and SFCU pretreatments both resulted in higher ACE inhibitory activity compared with untreated garlic (p<0.05). However, there were no significant differences in the ACE inhibitory activities and IC₅₀ values obtained from SFCU and SFU pretreatments under optimum conditions (p>0.05).

  4. ACE2/Ang 1-7 axis: A critical regulator of epicardial adipose tissue inflammation and cardiac dysfunction in obesity.

    PubMed

    Patel, Vaibhav B; Basu, Ratnadeep; Oudit, Gavin Y

    2016-01-01

    Obesity is characterized by an excessive fat accumulation in adipose tissues leading to weight gain and 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; activated RAS and angiotensin (Ang) II production results in worsening of cardiovascular diseases and angiotensin converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. ACE2 is expressed in the adipocytes and its expression is upregulated in response to high fat diet induced obesity in mice. Loss of ACE2 results in heart failure with preserved ejection fraction which is mediated in part by epicardial adipose tissue inflammation. Angiotensin 1-7 reduces the obesity associated cardiac dysfunction predominantly via its role in adiponectin expression and attenuation of epicardial adipose tissue inflammation. Human heart disease is also linked with inflammed epicardial adipose tissue. Here, we discuss the important interpretation of the novel of ACE2/Ang 1-7 pathway in obesity associated cardiac dysfunction. PMID:27617176

  5. An Assessment for Learning System Called ACED: Designing for Learning Effectiveness and Accessibility. Research Report. ETS RR-07-26

    ERIC Educational Resources Information Center

    Shute, Valerie J.; Hansen, Eric G.; Almond, Russell G.

    2007-01-01

    This paper reports on a 3-year, NSF-funded research and development project called ACED: Adaptive Content with Evidence-based Diagnosis. The purpose of the project was to design, develop, and evaluate an assessment for learning (AfL) system for diverse students, using Algebra I content related to geometric sequences (i.e., successive numbers…

  6. Yeasts from Colombian Kumis as source of peptides with Angiotensin I converting enzyme (ACE) inhibitory activity in milk.

    PubMed

    Chaves-López, Clemencia; Tofalo, Rosanna; Serio, Annalisa; Paparella, Antonello; Sacchetti, Giampiero; Suzzi, Giovanna

    2012-09-17

    This study investigated the possibility of using yeast strains in fermented milks to obtain products with high Angiotensin I-converting enzyme (ACE) inhibitory activity and low bitter taste. Ninety-three yeast strains isolated from Colombian Kumis in different geographic regions were molecularly identified, and their milk fermentation performances were determined. Molecular identification evidenced that Galactomyces geotrichum, Pichia kudriavzevii, Clavispora lusitaniae and Candida tropicalis, were the dominant species. Eighteen out of 93 strains produced fermented milk with ACE-inhibitory (ACEI) activity values ranging from 8.69 to 88.19%. Digestion of fermented milk samples by pepsin and pancreatin demonstrated an increase in ACEI activity, with C. lusitaniae KL4A as the best producer of ACEI peptides. Moreover, sensory analysis of the products containing the major ACE-inhibitory activity pointed out that P. kudriavzevii KL84A and Kluyveromyces marxianus KL26A could be selected as potential adjunct starter cultures in Kumis, since they made a considerable contribution to the ACE inhibitory activity and produced fermented milk without bitter taste. In this study we observed that Colombian Kumis can be an excellent vehicle for the isolation of yeasts with a potential to enhance bioactive peptides produced during milk fermentation. PMID:22938834

  7. Evaluation of a Web-Based Professional Development Program (Project ACE) for Teachers of Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rakap, Salih; Jones, Hazel A.; Emery, Alice Kaye

    2015-01-01

    This article describes the development, implementation, and second-year evaluation of Project Autism Competencies for Endorsement (ACE), a web-based professional development (PD) program that is designed to train teachers currently working in the field to meet the unique and diverse needs of children with autism spectrum disorders (ASDs). A…

  8. ACUTE-TO-CHRONIC ESTIMATION (ACE V 2.0) WITH TIME-CONCENTRATION-EFFECT MODELS: USER MANUAL AND SOFTWARE

    EPA Science Inventory

    Ellersieck, Mark R., Amha Asfaw, Foster L. Mayer, Gary F. Krause, Kai Sun and Gunhee Lee. 2003. Acute-to-Chronic Estimation (ACE v2.0) with Time-Concentration-Effect Models: User Manual and Software. EPA/600/R-03/107. U.S. Environmental Protection Agency, National Health and Envi...

  9. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates.

    PubMed

    Ghanbari, Raheleh; Zarei, Mohammad; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2015-01-01

    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions. PMID:26690117

  10. Angiotensin I converting enzyme (ACE) inhibitory activity of hetero-chitooligosaccharides prepared from partially different deacetylated chitosans.

    PubMed

    Park, Pyo-Jam; Je, Jae-Young; Kim, Se-Kwon

    2003-08-13

    Angiotensin I converting enzyme (ACE) inhibitory activity of hetero-chitooligosaccharides (hetero-COSs) prepared from partially different deacetylated chitosans was investigated. Partially deacetylated chitosans, 90, 75, and 50% deacetylated chitosan, were prepared from crab chitin by N-deacetylation with 40% sodium hydroxide solution for durations. In addition, nine kinds of hetero-COSs with relatively high molecular masses (5000-10 000 Da; 90-HMWCOSs, 75-HMWCOSs, and 50-HMWCOSs), medium molecular masses (1000-5000 Da; 90-MMWCOSs, 75-MMWCOSs, and 50-MMWCOSs), and low molecular masses (below 1000 Da; 90-LMWCOSs, 75-LMWCOSs, and 50-LMWCOSs) were prepared using an ultrafiltration membrane bioreactor system. ACE inhibitory activity of hetero-COSs was dependent on the degree of deacetylation of chitosans. 50-MMWCOSs that are COSs hydrolyzed from 50% deacetylated chitosan, the relatively lowest degree of deacetylation, exhibited the highest ACE inhibitory activity, and the IC(50) value was 1.22 +/- 0.13 mg/mL. In addition, the ACE inhibition pattern of the 50-MMWCOSs was investigated by Lineweaver-Burk plots, and the inhibition pattern was found to be competitive.

  11. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates

    PubMed Central

    Ghanbari, Raheleh; Zarei, Mohammad; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2015-01-01

    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions. PMID:26690117

  12. 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

    ... AGENCY AceInfo Solutions and Avaya Government Solutions, Koansys LLC, and Quality Associates Inc.; Transfer of Data AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: This notice... Solutions, Koansys LLC, and Quality Associates Inc. have been awarded a contract to perform work for...

  13. Transgenic rose lines harboring an antimicrobial protein gene, Ace-AMP1, demonstrate enhanced resistance to powdery mildew ( Sphaerotheca pannosa).

    PubMed

    Li, Xiangqian; Gasic, Ksenjia; Cammue, Bruno; Broekaert, Willem; Korban, Schuyler S

    2003-12-01

    An antimicrobial protein gene, Ace-AMP1, was introduced into Rosa hybrida cv. Carefree Beauty via Agrobacterium-mediated transformation. A total of 500 putative transgenic plants were obtained from 100 primary embryogenic calli co-cultivated with A. tumefaciens following selection on a regeneration medium containing 100 mg/l kanamycin. Polymerase chain reaction analysis of these putative transgenic lines, using primers for both Ace-AMP1 and neomycin phosphotransferase ( npt II) genes, showed that 62% of these plants were positive for both transgenes. These lines were further confirmed for stable integration of Ace-AMP1 and npt II genes by Southern blotting. Transcription of the Ace-AMP1 transgene in various transgenic rose lines was determined using Northern blotting. Transgenic rose lines inoculated with conidial spores of Sphaerotheca pannosa (Wallr.: Fr.) Lev. var. rosae showed enhanced resistance to powdery mildew using both a detached-leaf assay and an in vivo greenhouse whole-plant assay. PMID:14508687

  14. Aerosols released during large-scale integral MCCI tests in the ACE Program

    SciTech Connect

    Fink, J.K.; Thompson, D.H.; Spencer, B.W.; Sehgal, B.R.

    1992-04-01

    As part of the internationally sponsored Advanced Containment Experiments (ACE) program, seven large-scale experiments on molten core concrete interactions (MCCIs) have been performed at Argonne National Laboratory. One of the objectives of these experiments is to collect and characterize all the aerosols released from the MCCIs. Aerosols released from experiments using four types of concrete (siliceous, limestone/common sand, serpentine, and limestone/limestone) and a range of metal oxidation for both BWR and PWR reactor core material have been collected and characterized. Release fractions were determined for UO{sup 2}, Zr, the fission-products: BaO, SrO, La{sub 2}O{sub 3}, CeO{sub 2}, MoO{sub 2}, Te, Ru, and control materials: Ag, In, and B{sub 4}C. Release fractions of UO{sub 2} and the fission products other than Te were small in all tests. However, release of control materials was significant.

  15. Aerosols released during large-scale integral MCCI tests in the ACE Program

    SciTech Connect

    Fink, J.K.; Thompson, D.H.; Spencer, B.W. ); Sehgal, B.R. )

    1992-01-01

    As part of the internationally sponsored Advanced Containment Experiments (ACE) program, seven large-scale experiments on molten core concrete interactions (MCCIs) have been performed at Argonne National Laboratory. One of the objectives of these experiments is to collect and characterize all the aerosols released from the MCCIs. Aerosols released from experiments using four types of concrete (siliceous, limestone/common sand, serpentine, and limestone/limestone) and a range of metal oxidation for both BWR and PWR reactor core material have been collected and characterized. Release fractions were determined for UO{sup 2}, Zr, the fission-products: BaO, SrO, La{sub 2}O{sub 3}, CeO{sub 2}, MoO{sub 2}, Te, Ru, and control materials: Ag, In, and B{sub 4}C. Release fractions of UO{sub 2} and the fission products other than Te were small in all tests. However, release of control materials was significant.

  16. Aerosol and melt chemistry in the ACE molten core-concrete interaction experiments

    SciTech Connect

    Fink, J.K.; Thompson, D.H.; Spencer, B.W.; Sehgal, B.R.

    1995-01-01

    Experimental results are discussed from the internationally sponsored Advanced Containment Experiments (ACE) Program on the melt behavior and aerosols released during the interaction of molten reactor core material with concrete. A broad range of parameters were addressed in the experimental program: Seven large-scale tests were performed using four types of concrete (siliceous, limestone/sand, serpentine, and limestone) and a range of metal oxidations for both boiling water and pressurized waster reactor core debris. The release aerosols contained mainly constitutents of the concrete. In the tests with metal and limestone/sand siliceous concrete, silicon compounds comprised 50% or more of the aerosol mass. Releases of uranium and low-volatility fission-product elements were small in all tests. Releases of tellurium and neutron absorber materials (silver, indium, and boron from boron carbide) were high.

  17. Analysis of Wake VAS Benefits Using ACES Build 3.2.1: VAMS Type 1 Assessment

    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. The Phase III Wake VAS ConOps is one element of the Virtual Airspace Modelling and Simulation (VAMS) program blended concepts for enhancing the total system wide capacity of the National Airspace System (NAS). This report contains a VAMS Program Type 1 (stand-alone) assessment of the expected capacity benefits of Wake VAS at the 35 FAA Benchmark Airports and determines the consequent reduction in delay using the Airspace Concepts Evaluation System (ACES) Build 3.2.1 simulator.

  18. Characterization of Dust Properties during ACE-Asia and PRIDE: A Column Satellite-Surface Perspective

    NASA Technical Reports Server (NTRS)

    Lau, William K. M. (Technical Monitor); Tsay, Si-Chee; Hsu, N. Christina; Herman, Jay R.; Ji, Q. Jack

    2002-01-01

    Many recent field experiments are designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally occurring aerosols, which often exist in high concentration over particular pathways around the globe. For example, the ACE-Asia (Aerosol Characterization Experiment-Asia) was conducted from March-May 2001 in the vicinity of the Taklimakan and Gobi deserts, 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). The PRIDE (Puerto RIco Dust Experiment, July 2000) was designed to measure the properties of Saharan dust transported across the Atlantic Ocean to the Caribbean. Dust particles typically originate 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 dust aerosols is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the ocean. During ACE-Asia and PRIDE we had measured aerosol physical/optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from ground-based remote sensing. The inclusion of flux measurements permits the determination of aerosol radiative flux in addition to measurements of loading and optical depth. 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. We will present the results and discuss their implications in regional climatic effects.

  19. Zernike moments as a useful tool for ACE imager aerological data retrieval (stratospheric temperature and cloud product)

    NASA Astrophysics Data System (ADS)

    Dodion, Jan; Fussen, Didier; Filip, Vanhellemont; Mateshvili, Nina; Christine, Bingen; Maxime, Stapelle; Dekemper, Emmanuel; Gilbert, Kathy; Walker, Kaley; Bernath, Peter

    The Atmospheric Chemistry Experiment (ACE) was launched in August 2003 aboard the Canadian satellite SCISAT-I, and is at present fully operational. ACE circles the Earth at an altitude of 650 km with an orbital inclination of 74° . Solar occultation is the primary observation technique used by the on board instruments, which consist of a high resolution Fourier Transform spectrometer (ACE-FTS), a dual optical spectrophotometer (MAESTRO) and two filtered imagers, subject of this presentation. While the Sun is setting below or rising from behind the Earth's horizon, at every timestamp, the imagers capture a snapshot of the Sun as seen through the atmosphere. On these pictures, the apparent Sun width is about 25 km at the tangent point and the apparent Sun height varies from almost 0.7 km in the optically thick, lower troposphere where the Sun image is highly flattened by the refraction to its maximum (about 25 km at the tangent point) where refractive effects are negligible. Used in image processing, image moments are certain particular weighted averages (moments) of the image pixel's intensities, or functions of those moments, usually chosen to have some attractive property on interpretation. Zernike moments were first introduced by Teague (1980) based on the complex, orthogonal functions called Zernike polynomials. Though computationally very complex compared to geometric and Legendre moments, Zernike moments have proved to be superior in terms of their feature representation capability and low noise sensitivity. Also, the construction of different moment invariants makes them well suited for our research. A detailed image analysis of ACE imager data using Zernike moments provides us the necessary information for the retrieval of temperature profiles from a series of distorted images of an object of known shape such as the Sun. These temperature profiles are validated with ACE-FTS data. Besides, a preliminary cloud product could be derived and, in addition, a

  20. Library Screen Identifies Enterococcus faecalis CcpA, the Catabolite Control Protein A, as an Effector of Ace, a Collagen Adhesion Protein Linked to Virulence

    PubMed Central

    Gao, Peng; Pinkston, Kenneth L.; Bourgogne, Agathe; Cruz, Melissa R.; Garsin, Danielle A.; Murray, Barbara E.

    2013-01-01

    The Enterococcus faecalis cell wall-anchored protein Ace is an important virulence factor involved in cell adhesion and infection. Expression of Ace on the cell surface is affected by many factors, including stage of growth, culture temperature, and environmental components, such as serum, urine, and collagen. However, the mechanisms that regulate or modulate Ace display are not well understood. With interest in identifying genes associated with Ace expression, we utilized a whole-cell enzyme-linked immunosorbent assay (ELISA)-based screening method to identify mutants from a transposon insertion mutant library which exhibited distinct Ace surface expression profiles. We identified a ccpA insertion mutant which showed significantly decreased levels of Ace surface expression at early growth phase versus those of wild-type OG1RF. Confirmation of the observation was achieved through flow cytometry and complementation analysis. Compared to the wild type, the E. faecalis ccpA mutant had an impaired ability to adhere to collagen when grown to early exponential phase, consistent with the lack of Ace expression in the early growth phase. As a key component of carbon catabolite regulation, CcpA has been previously reported to play a critical role in regulating expression of proteins involved in E. faecalis carbohydrate uptake and utilization. Our discovery is the first to associate CcpA with the production of a major E. faecalis virulence factor, providing new insights into the regulation of E. faecalis pathogenesis. PMID:23974022

  1. Library screen identifies Enterococcus faecalis CcpA, the catabolite control protein A, as an effector of Ace, a collagen adhesion protein linked to virulence.

    PubMed

    Gao, Peng; Pinkston, Kenneth L; Bourgogne, Agathe; Cruz, Melissa R; Garsin, Danielle A; Murray, Barbara E; Harvey, Barrett R

    2013-10-01

    The Enterococcus faecalis cell wall-anchored protein Ace is an important virulence factor involved in cell adhesion and infection. Expression of Ace on the cell surface is affected by many factors, including stage of growth, culture temperature, and environmental components, such as serum, urine, and collagen. However, the mechanisms that regulate or modulate Ace display are not well understood. With interest in identifying genes associated with Ace expression, we utilized a whole-cell enzyme-linked immunosorbent assay (ELISA)-based screening method to identify mutants from a transposon insertion mutant library which exhibited distinct Ace surface expression profiles. We identified a ccpA insertion mutant which showed significantly decreased levels of Ace surface expression at early growth phase versus those of wild-type OG1RF. Confirmation of the observation was achieved through flow cytometry and complementation analysis. Compared to the wild type, the E. faecalis ccpA mutant had an impaired ability to adhere to collagen when grown to early exponential phase, consistent with the lack of Ace expression in the early growth phase. As a key component of carbon catabolite regulation, CcpA has been previously reported to play a critical role in regulating expression of proteins involved in E. faecalis carbohydrate uptake and utilization. Our discovery is the first to associate CcpA with the production of a major E. faecalis virulence factor, providing new insights into the regulation of E. faecalis pathogenesis.

  2. Leucine-684: A conserved residue of an AMP-acetyl CoA synthetase (AceCS) from Leishmania donovani is involved in substrate recognition, catalysis and acetylation.

    PubMed

    Soumya, Neelagiri; Tandan, Hitendra; Damre, Mangesh V; Gangwal, Rahul P; Sangamwar, Abhay T; Singh, Sushma

    2016-04-15

    AMP-acetyl CoA synthetase (AMP-AceCS) is a key enzyme which catalyzes the activation of acetate to acetyl CoA, an important intermediate at the cross roads of various anabolic and catabolic pathways. Multiple sequence alignment of Leishmania donovani AceCS with other organisms revealed the presence of a highly conserved leucine residue at 684 position which is known to be crucial for acetylation by protein acetyl transferases in other organisms. In an attempt to understand the role of leucine residue at 684 position in L. donovani acetyl CoA synthetase (LdAceCS), it was mutated to proline (P) by site directed mutagenesis. Kinetic analysis of the L684P-LdAceCS mutant revealed approximately two fold increased binding affinity with acetate, whereas fivefold decreased affinity was observed with ATP. There was insignificant change in secondary structure as revealed by CD however, two fold decreased fluorescence intensity was observed at an emission maxima of 340 nm. Interestingly, L684P mutation abolished the acetylation of the mutant enzyme indicating the importance of L684 in acetylation of the enzyme. Changes in biochemical parameters of the mutant protein were validated by homology modeling of the wild type and mutant LdAceCS enzyme using Salmonella enterica AceCS crystal structure as template. Our data provides evidence for the role of leucine 684 residue in substrate recognition, catalysis and acetylation of the AceCS enzyme.

  3. Characterization of ACE Inhibitory Peptides from Mactra veneriformis Hydrolysate by Nano-Liquid Chromatography Electrospray Ionization Mass Spectrometry (Nano-LC-ESI-MS) and Molecular Docking

    PubMed Central

    Liu, Rui; Zhu, Yunhan; Chen, Jiao; Wu, Hao; Shi, Lei; Wang, Xinzhi; Wang, Lingchong

    2014-01-01

    Food-derived bioactive compounds are gaining increasing significance in life sciences. In the present study, we identified angiotensin I-converting enzyme (ACE)-inhibitory peptides from Mactra veneriformis hydrolysate using a nano-LC-MS/MS method. Mactra veneriformis hydrolysate was first separated into four fractions (F1–F4) based on molecular weight by ultrafiltration. The fraction with molecular weight lower than 1 kDa (F1) showed the highest ACE inhibitory activity. F1 was then analyzed by a high throughput nano-LC-MS/MS method and sequences of peptides in F1 were calculated accordingly. The 27 peptides identified as above were chemically synthesized and tested for ACE-inhibitory activity. The hexapeptide VVCVPW showed the highest potency with an IC50 value of 4.07 μM. We then investigated the interaction mechanism between the six most potent peptides and ACE by molecular docking. Our docking results suggested that the ACE inhibitory peptides bind to ACE via interactions with His383, His387, and Glu411 residues. Particularly, similar to the thiol group of captopril, the cysteine thiol group of the most potent peptide VVCVPW may play a key role in the binding of this peptide to the ACE active site. PMID:24983637

  4. Novel corrosion inhibitor technology

    SciTech Connect

    Van de Ven, P.; Fritz, P.; Pellet, R.

    1999-11-01

    A novel, patented corrosion inhibitor technology has been identified for use in heat transfer applications such as automotive and heavy-duty coolant. The new technology is based on a low-toxic, virtually depletion-free carboxylic acid corrosion inhibitor package that performs equally well in mono ethylene glycol and in less toxic propylene glycol coolants. An aqueous inhibitor concentrate is available to provide corrosion protection where freezing protection is not an issue. In the present paper, this inhibitor package is evaluated in the different base fluids: mono ethylene glycol, mono propylene glycol and water. Results are obtained in both standardized and specific corrosion tests as well as in selected field trials. These results indicate that the inhibitor package remains effective and retains the benefits previously identified in automotive engine coolant applications: excellent corrosion protection under localized conditions, general corrosion conditions as well as at high temperature.

  5. Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

    PubMed

    Fan, Jinqi; Zou, Lili; Cui, Kun; Woo, Kamsang; Du, Huaan; Chen, Shaojie; Ling, Zhiyu; Zhang, Quanjun; Zhang, Bo; Lan, Xianbin; Su, Li; Zrenner, Bernhard; Yin, Yuehui

    2015-01-01

    The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

  6. The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa.

    PubMed

    Baek, Rena C; Palmer, Rachel; Pomponio, Robert J; Lu, Yuefeng; Ma, Xiwen; McVie-Wylie, Alison J

    2016-09-01

    Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D, D/D), disease severity at baseline and response to enzyme replacement therapy (ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation. PMID:27489778

  7. Specific MAPK inhibitors prevent hyperglycemia-induced renal diseases in type 1 diabetic mouse model.

    PubMed

    Hong, Zhe; Hong, Zongyuan; Wu, Denglong; Nie, Hezhongrong

    2016-08-01

    Mitogen-activated protein kinase (MAPK) and renin-angiotensin system (RAS) play critical roles in the process of renal diseases, but their interaction has not been comprehensively discussed. In the present studies, we investigated the renoprotective effects of MPAK inhibitors on renal diseases in type 1 diabetic mouse model, and clarify the crosstalk among MAPK signaling. Type 1 diabetic mouse model was established in male C57BL/6 J mice, and treated with or without 10 mg/kg MAPK blockers, including ERK inhibitor PD98059, p38 inhibitor SB203850, and JNK inhibitor SP600125 for four weeks. Hyperglycemia induced renal injuries, but treating them with MAPK inhibitors significantly decreased glomerular volume and glycogen in renal tissues. Although slightly changed body weight and fasting blood glucose levels, MAPK inhibitors attenuated blood urea nitrogen, urea protein, and microalbuminuria. Administration also reduced the diabetes-induced RAS activation, including angiotensin II converting enzyme (c) and Ang II, which contributed to its renal protective effects in the diabetic mice. In addition, the anti-RAS of MAPK inhibitor treatment markedly reduced gene expression of tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase, fibrotic accumulation, and transforming growth factor-β1 levels in renal tissues. Furthermore, chemical inhibitors and genetic siRNA results identified the crosstalk among the three MAPK signaling, and proved JNK signaling played a critical role in MAPK-mediated ACE pathway in hyperglycemia state. Collectively, these results support the therapeutic effects of MAPK-specific inhibitors, especially JNK inactivation, on hyperglycemia-induced renal damages. PMID:27389030

  8. Synthetic inhibitors of endopeptidase EC 3.4.24.15: potency and stability in vitro and in vivo.

    PubMed Central

    Lew, R. A.; Tomoda, F.; Evans, R. G.; Lakat, L.; Boublik, J. H.; Pipolo, L. A.; Smith, A. I.

    1996-01-01

    1. The role of the metalloendopeptidase EC 3.4.24.15 (EP 24.15) in peptide metabolism in vivo is unknown, in part reflecting the lack of a stable enzyme inhibitor. The most commonly used inhibitor, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP-AAY-pAB, Ki = 16 nM), although selective in vitro, is rapidly degraded in the circulation to cFP-Ala-Ala, an angiotensin converting enzyme (ACE) inhibitor. This metabolite is thought to be generated by neutral endopeptidase (NEP; EC 3.4.24.11), as the Ala-Tyr bond of cFP-AAY-pAB is cleaved by NEP in vitro. In the present study, we have examined the role of NEP in the metabolism of cFP-AAY-pAB in vivo, and have tested a series of inhibitor analogues, substituted at the second alanine, for both potency and stability relative to the parent compound. 2. Analogues were screened for inhibition of fluorescent substrate cleavage by recombinant rat testes EP 24.15. D-Ala or Asp substitution abolished inhibitory activity, while Val-, Ser- and Leu-substituted analogues retained activity, albeit at a reduced potency. A relative potency order of Ala (1) > Val (0.3) > Ser (0.16) > Leu (0.06) was observed. Resistance to cleavage by NEP was assessed by incubation of the analogues with rabbit kidney membranes. The parent compound was readily degraded, but the analogues were twice (Ser) and greater than 10 fold (Leu and Val) more resistant to cleavage. 3. Metabolism of cFP-AAY-pAB and the Val-substituted analogue was also examined in conscious rabbits. A bolus injection of cFP-AAY-pAB (5 mg kg-1, i.v.) significantly reduced the blood pressure response to angiotensin I, indicating ACE inhibition. Pretreatment with NEP inhibitors, SCH 39370 or phosphoramidon, slowed the loss of cFP-AAY-pAB from the plasma, but did not prevent inhibition of ACE. Injection of 1 mg kg-1 inhibitor resulted in plasma concentrations at 10 s of 23.5 microM (cFP-AAY-pAB) and 18.0 microM (cFP-AVY-pAB), which fell 100 fold over 5 min. Co-injection of

  9. [Effect of Astragali Radix in improving early renal damage in metabolic syndrome rats through ACE2/Mas pathway].

    PubMed

    Wang, Qiong-ying; Liang, Wei; Jiang, Cheng; Li, Ning-yin; Xu, Han; Yang, Mi-na; Lin, Xin; Yu, Heng; Chang, Peng; Yu, Jing

    2015-11-01

    To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues. PMID:27071265

  10. Assessment of water vapor isotopologue measurements by ACE-FTS and Odin-SMR

    NASA Astrophysics Data System (ADS)

    Bauer, Ralf; Sheese, Patrick; Walker, Kaley; Urban, Joachim; Murtagh, Donal; Boone, Chris; Bernath, Peter; Manney, Gloria

    2015-04-01

    Knowing the isotopic composition of trace gases can improve our understanding of processes in the Earth's atmosphere causing isotopic fractionation. In many studies, isotopologue (molecules of identical chemical but different isotopic composition) amounts are primarily discussed as δ values, which are defined relative to a standard, e.g.: ( ) 18 (VM RH182 O /VM RH162 O ) δ O (o) = (V-M-R-18-/V-M-R-16-)VSMOW-- 1 * 1000 H2 O H2 O with VSMOW as Vienna Standard Mean Ocean Water. This study targets the water vapor isotopologues H218O and H217O in the stratosphere and lower mesosphere using δ18O and δ17O for the comparison. Over the past decades, H218O and H217O profiles have been measured with balloon-borne (e.g. FIRS-2, Mk IV) and space-borne (e.g. ATMOS/SL3) instruments. The satellite instruments ACE-FTS (Atmospheric Chemistry Experiment - Fourier Transform Spectrometer) on the Canadian satellite SCISAT and SMR (Sub-Millimetre Radiometer) on the Swedish satellite Odin provide a significantly larger number of individual profiles with global coverage. Both instruments are still operational and provide data products for more than 10 years. Assessing their data quality is of key importance before conclusions can be drawn from these results. ACE-FTS on SCISAT is an infrared Fourier Transform Spectrometer with a high spectral resolution of 0.02 cm-1 and a spectral range from 750 to 4400 cm-1. It measures using solar occultation viewing geometry. SCISAT is in a high inclination orbit at an altitude of 650 km. It was launched in August 2003 and has been performing routine measurements since February 2004. SMR on Odin measures millimetre wave emissions from the atmosphere with a 1.1 m telescope in the 486 to 581 GHz range with four tunable radiometers. Odin was launched in February 2001 into a quasi-polar sun-synchronous orbit at about 600 km altitude. Spectral regions for the target trace gases are selected for SMR using different measurement modes and thus not all

  11. A systematic review on randomized control trials on rennin angiotensin aldosterone system inhibitors role in managing hypertension among hemodialysis patients.

    PubMed

    Aftab, Raja Ahsan; Khan, Amer Hayat; Adnan, Azreen Syazril; Jannah, Nurul

    2016-01-01

    Randomized control trials (RCTs) are considered as most rigors way of determining the cause-effect relationship of a treatment and outcome. Activation of rennin angiotensin aldosterone system (RAAS) is an important contributor to hypertension in hemodialysis patients. The prevalence of hypertension in hemodialysis patients varies from 60% to 80% and hypertension management alone with conventional hemodialysis is insufficient. Hence, the current review was aimed to investigate the effect of RAAS inhibitors in managing hypertension among hemodialysis patients in a randomized control trial. Using PUBMED and EMBASE databases, randomized control trial with primary or secondary outcomes related to the effect of RAAS inhibitors on blood pressure among hemodialysis patients were included for analysis. The current review also assessed the quality of reporting of RCT. A total of eight RCT met inclusion criteria for current review. According to modified jaded scale, one (12.5%) study scored four points for quality reporting, whereas two (25%) studies scored one point that was the least score. The mean score for all included studies was 2.25. Six (75%) of the eight RCT included, involved ARB in hypertension management among hemodialysis patients, whereas two (25%) studies involved angiotensin-converting enzyme (ACE) inhibitors. Of the siz RCT involving ARB, two (33.3%) RCT also included ACE inhibitors comparison group. Altogether six (75%) studies report a reduction in blood pressure with the use of RAAS inhibitors compared to control group; however, of the six studies, two (33.3%) reported that the reduction in blood pressure was not significant. Whereas, two (25%) studies reported no reduction in blood pressure compared to the control group. The findings from current review do not indicate a clear pattern for a role of RAAS inhibitors for hypertension control among hemodialysis patients. PMID:26853680

  12. Potential of protease inhibitor in 3-nitropropionic acid induced Huntington's disease like symptoms: mitochondrial dysfunction and neurodegeneration.

    PubMed

    Hariharan, Ashwini; Shetty, Shruthi; Shirole, Trupti; Jagtap, Aarti G

    2014-12-01

    Huntington's disease (HD) is a genetic, neurodegenerative disorder mainly characterized by motor dysfunction, cognitive decline and psychiatric disturbances. 3-Nitropropionic acid (3-NP) is an inhibitor of succinate dehydrogenase (Complex II) of the mitochondrial respiratory chain, which thereby reduces production of ATP. It induces neurotoxicity by causing striatal degeneration, energy deficit and oxidative stress. Angiotensin converting enzyme (ACE) is an important protease in the renin angiotensin system (RAS) responsible for the conversion of Angiotensin I to Angiotensin II. Angiotensin-II stimulates mitochondrial oxidant release leading to depression of energy metabolism. ACE inhibitors have shown promise in disorders like stress, anxiety, and depression in addition to showing beneficial effects in cognitive disorders like Alzheimer's. Angiotensin-II inhibition enhances energy production by lowering mitochondrial oxidant production, and hence protects mitochondrial structure. Trandolapril is a centrally active ACE inhibitor. 3-NP administered systematically (20mg/kg, i.p) for 4 days consecutively induced HD like symptoms - loss of body weight, neurobehavioral alterations like memory dysfunction (elevated plus maze, Morris water maze performance), Hind-limb impairment (Narrow beam test), motor incoordination (locomotor activity). Biochemical studies on brain tissue showed increased lipid peroxidation, nitrite levels and acetylcholinesterase activity along with decreased levels of reduced glutathione, catalase activity. Mitochondrial enzyme complex activities (I, II, IV and MTT assay) were found to be significantly lowered in brain mitochondria. Administration of Trandolapril (4 and 6 mg/kg, p.o) daily for 12 days showed significant improvement in body weight, neurobehavioral parameters, oxidative stress and mitochondrial enzyme activities in rat brain. These findings were further confirmed by histopathological studies which showed improvement in 3-NP induced

  13. Potential of protease inhibitor in 3-nitropropionic acid induced Huntington's disease like symptoms: mitochondrial dysfunction and neurodegeneration.

    PubMed

    Hariharan, Ashwini; Shetty, Shruthi; Shirole, Trupti; Jagtap, Aarti G

    2014-12-01

    Huntington's disease (HD) is a genetic, neurodegenerative disorder mainly characterized by motor dysfunction, cognitive decline and psychiatric disturbances. 3-Nitropropionic acid (3-NP) is an inhibitor of succinate dehydrogenase (Complex II) of the mitochondrial respiratory chain, which thereby reduces production of ATP. It induces neurotoxicity by causing striatal degeneration, energy deficit and oxidative stress. Angiotensin converting enzyme (ACE) is an important protease in the renin angiotensin system (RAS) responsible for the conversion of Angiotensin I to Angiotensin II. Angiotensin-II stimulates mitochondrial oxidant release leading to depression of energy metabolism. ACE inhibitors have shown promise in disorders like stress, anxiety, and depression in addition to showing beneficial effects in cognitive disorders like Alzheimer's. Angiotensin-II inhibition enhances energy production by lowering mitochondrial oxidant production, and hence protects mitochondrial structure. Trandolapril is a centrally active ACE inhibitor. 3-NP administered systematically (20mg/kg, i.p) for 4 days consecutively induced HD like symptoms - loss of body weight, neurobehavioral alterations like memory dysfunction (elevated plus maze, Morris water maze performance), Hind-limb impairment (Narrow beam test), motor incoordination (locomotor activity). Biochemical studies on brain tissue showed increased lipid peroxidation, nitrite levels and acetylcholinesterase activity along with decreased levels of reduced glutathione, catalase activity. Mitochondrial enzyme complex activities (I, II, IV and MTT assay) were found to be significantly lowered in brain mitochondria. Administration of Trandolapril (4 and 6 mg/kg, p.o) daily for 12 days showed significant improvement in body weight, neurobehavioral parameters, oxidative stress and mitochondrial enzyme activities in rat brain. These findings were further confirmed by histopathological studies which showed improvement in 3-NP induced

  14. 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

  15. Aerosol Optical Properties and Chemical Composition Measured on the Ronald H. Brown During ACE-Asia

    NASA Astrophysics Data System (ADS)

    Quinn, P. K.; Bates, T. S.; Miller, T. L.; Coffman, D.

    2001-12-01

    Measurements of aerosol chemical, physical, and optical properties were made onboard the NOAA R/V Ronald H. Brown during the ACE-Asia Intensive Field Program to characterize Asian aerosol as it was transported across the Pacific Ocean. The ship traveled across the Pacific from Hawaii to Japan and into the East China Sea and the Sea of Japan. Trajectories indicate that remote marine air masses were sampled on the transit to Japan. In the ACE-Asia study region air masses from Japan, China, Mongolia, and the Korea Peninsula were sampled. A variety of aerosol types were encountered including those of marine, volcanic, crustal, and industrial origin. Presented here, for the different air masses encountered, are aerosol optical properties (scattering and absorption coefficients, single scattering albedo, Angstrom Exponent, and aerosol optical depth) and chemical composition (major ions, total organic and black carbon, and trace elements). Scattering by submicron aerosol (55 % RH and 550 nm) was less than 20 1/Mm during the transit from Hawaii to Japan. In continental air masses, values ranged from 60 to 320 1/Mm with the highest submicron scattering coefficients occurring during prefrontal conditions with a low marine boundary layer height and trajectories from Japan. For the continental air masses, the ratio of scattering by submicron to sub-10 micron aerosol during polluted conditions averaged 0.8 and during a dust event 0.41. Aerosol optical depth (500 nm) ranged from 0.08 during the Pacific transit to 1.3 in the prefrontal conditions described above. Optical depths during dust events ranged from 0.2 to 0.6. Submicron non-sea salt (nss) sulfate concentrations ranged from 0.5 ug/m-3 during the Pacific transit to near 30 ug/m-3 during the prefrontal conditions described above. Black carbon to total carbon mass ratios in air masses from Asia averaged 0.18 with highest values (0.32) corresponding to trajectories crossing the Yangtze River valley.

  16. Evaluation of Aerosol Properties over Ocean from Moderate Resolution Imaging Spectroradiometer (MODIS) during ACE-Asia

    NASA Technical Reports Server (NTRS)

    Chu, D. A.; Remer, L. A.; Kaufman, Y. J.; Schmid, B.; Redemann, J.; Knobelspiesse, K.; Chern, J.-D.; Livingston, J.; Russell, P. B.; Xiong, X.; Ridgway, W.

    2005-01-01

    The Aerosol Characterization Experiment-Asia (ACE-Asia) was conducted in March-May 2001 in the western North Pacific in order to characterize the complex mix of dust, smoke, urban/industrial pollution, and background marine aerosol that is observed in that region in springtime. The Moderate Resolution Imaging Spectroradiometer (MODIS) provides a large-scale regional view of the aerosol during the ACE-Asia time period. Focusing only on aerosol retrievals over ocean, MODIS data show latitudinal and longitudinal variation in the aerosol characteristics. Typically, aerosol optical depth (tau(sub a)) values at 0.55 micrometers are highest in the 30 deg. - 50 deg. latitude band associated with dust outbreaks. Monthly mean tau(sub a) in this band ranges approx. 0.40-70, although large differences between monthly mean and median values indicate the periodic nature of these dust outbreaks. The size parameters, fine mode fraction (eta), and effective radius (r(sub eff)) vary between monthly mean values of eta = 0.47 and r(sub eff)= 0.75 micrometers in the cleanest regions far offshore to approximately eta = 0.85 and r(sub eff) =.30 micrometers in near-shore regions dominated by biomass burning smoke. The collocated MODIS retrievals with airborne, ship-based, and ground-based radiometers measurements suggest that MODIS retrievals of spectral optical depth fall well within expected error (DELTA tau(sub a) = plus or minus 0.03 plus or minus 0.05 tau(sub a)) except in situations dominated by dust, in which cases MODIS overestimate both the aerosol loading and the aerosol spectral dependence. Such behavior is consistent with issues related to particle nonsphericity. Comparisons of MODIS-derived r(sub eff) with AERONET retrievals at the few occurrences of collocations show MODIS systematically underestimates particle size by 0.2 micrometers. Multiple-year analysis of MODIS aerosol size parameters suggests systematic differences between the year 2001 and the years 2000 and 2002

  17. Spectral Absorption of Solar Radiation by Aerosols during ACE-Asia

    NASA Technical Reports Server (NTRS)

    Bergstrom, R. W.; Pilewskie, P.; Pommier, J.; Rabbette, M.; Russell, P. B.; Schmid, B.; Redermann, J.; Higurashi, A.; Nakajima, T.; Quinn, P. K.

    2004-01-01

    As part of the Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia), the upward and downward spectral solar radiant fluxes were measured with the Spectral Solar Flux Radiometer (SSFR), and the aerosol optical depth was measured with the Ames Airborne Tracking Sunphotometer (AATS-14) aboard the Center for INterdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) Twin Otter aircraft. IN this paper, we examine the data obtained for two cases: a moderately thick aerosol layer, 12 April, and a relatively thin aerosol case, 16 April 2001. ON both days, the Twin Otter flew vertical profiles in the Korean Strait southeast of Gosan Island. For both days we determine the aerosol spectral absorption of the layer and estimate the spectral aerosol absorption optical depth and single-scattering albedo. The results for 12 April show that the single-scattering albedo increases with wavelength from 0.8 at 400 nm to 0.95 at 900 nm and remains essentially constant from 950 to 1700 nm. On 16 April the amount of aerosol absorption was very low; however, the aerosol single-scattering albedo appears to decrease slightly with wavelength in the visible region. We interpret these results in light of the two absorbing aerosol species observed during the ACE-asia study: mineral dust and black carbon. The results for 12 April are indicative of a mineral dust-black carbon mixture. The 16 April results are possibly caused by black carbon mixed with nonabsorbing pollution aerosols. For the 12 April case we attempt to estimate the relative contributions of the black carbon particles and the mineral dust particles. We compare our results with other estimates of the aerosol properties from a Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) satellite analysis and aerosol measurements made aboard the Twin Otter, aboard the National Oceanic and Atmospheric Administration Ronald H Brown ship, and at ground sites in Gosan and Japan. The results indicate a relatively complicated aerosol

  18. Clear Sky Column Closure Studies of Urban-Marine and Mineral-Dust Aerosols Using Aircraft, Ship, Satellite and Ground-Based Measurements in ACE-2

    NASA Technical Reports Server (NTRS)

    Schmid, Beat; Russell, Philip B.; Livingston, John M.; Gasso, Santiago; Hegg, Dean A.; Collins, Donald R.; Flagan, Richard C.; Seinfeld, John H.; Oestroem, Elisabeth; Noone, Kevin J.; Durkee, Philip A.; Jonsson, Haflidi H.; Welton, Ellsworth J.; Voss, Kenneth J.; Gordon, Howard R.; Formenti, Paola; Andreae, Meinrat O.; Kapustin, Vladimir N.; Bates, Timothy S.; Quinn, Patricia K.

    2000-01-01

    As part of the second Aerosol Characterization Experiment (ACE-2), European urban-marine and African mineral-dust aerosols were measured aboard the Pelican aircraft, the Research Vessel Vodyanitskiy from the ground and from satellites.

  19. Developing an Evaluation Tool for Assessing Clinical Ethics Consultation Skills in Simulation Based Education: The ACES Project.

    PubMed

    Wasson, Katherine; Parsi, Kayhan; McCarthy, Michael; Siddall, Viva Jo; Kuczewski, Mark

    2016-06-01

    The American Society for Bioethics and Humanities has created a quality attestation (QA) process for clinical ethics consultants; the pilot phase of reviewing portfolios has begun. One aspect of the QA process which is particularly challenging is assessing the interpersonal skills of individual clinical ethics consultants. We propose that using case simulation to evaluate clinical ethics consultants is an approach that can meet this need provided clear standards for assessment are identified. To this end, we developed the Assessing Clinical Ethics Skills (ACES) tool, which identifies and specifies specific behaviors that a clinical ethics consultant should demonstrate in an ethics case simulation. The aim is for the clinical ethics consultant or student to use a videotaped case simulation, along with the ACES tool scored by a trained rater, to demonstrate their competence as part of their QA portfolio. The development and piloting of the tool is described. PMID:25794891

  20. Developing an Evaluation Tool for Assessing Clinical Ethics Consultation Skills in Simulation Based Education: The ACES Project.

    PubMed

    Wasson, Katherine; Parsi, Kayhan; McCarthy, Michael; Siddall, Viva Jo; Kuczewski, Mark

    2016-06-01

    The American Society for Bioethics and Humanities has created a quality attestation (QA) process for clinical ethics consultants; the pilot phase of reviewing portfolios has begun. One aspect of the QA process which is particularly challenging is assessing the interpersonal skills of individual clinical ethics consultants. We propose that using case simulation to evaluate clinical ethics consultants is an approach that can meet this need provided clear standards for assessment are identified. To this end, we developed the Assessing Clinical Ethics Skills (ACES) tool, which identifies and specifies specific behaviors that a clinical ethics consultant should demonstrate in an ethics case simulation. The aim is for the clinical ethics consultant or student to use a videotaped case simulation, along with the ACES tool scored by a trained rater, to demonstrate their competence as part of their QA portfolio. The development and piloting of the tool is described.

  1. A Survey of Magnetic Waves Excited by Newborn Interstellar He+ Observed by the ACE Spacecraft at 1 au

    NASA Astrophysics Data System (ADS)

    Fisher, Meghan K.; Argall, Matthew R.; Joyce, Colin J.; Smith, Charles W.; Isenberg, Philip A.; Vasquez, Bernard J.; Schwadron, Nathan A.; Skoug, Ruth M.; Sokół, Justyna M.; Bzowski, Maciej; Zurbuchen, Thomas H.; Gilbert, Jason A.

    2016-10-01

    We report observations of low-frequency waves at 1 au by the magnetic field instrument on the Advanced Composition Explorer (ACE/MAG) and show evidence that they arise due to newborn interstellar pickup He+. Twenty-five events are studied. They possess the generally predicted attributes: spacecraft-frame frequencies slightly greater than the He+ cyclotron frequency, left-hand polarization in the spacecraft frame, and transverse fluctuations with minimum variance directions that are quasi-parallel to the mean magnetic field. Their occurrence spans the first 18 years of ACE operations, with no more than 3 such observations in any given year. Thus, the events are relatively rare. As with past observations by the Ulysses and Voyager spacecraft, we argue that the waves are seen only when the background turbulence is sufficiently weak as to allow for the slow accumulation of wave energy over many hours.

  2. Malathion Resistance Status and Mutations in Acetylcholinesterase Gene (Ace) in Japanese Encephalitis and Filariasis Vectors from Endemic Area in India.

    PubMed

    Misra, Brij Ranjan; Gore, Milind

    2015-05-01

    Japanese encephalitis (JE) and lymphatic filariasis (LF) are endemic in estern part of Uttar Pradesh in India and transmitted by Culex mosquitoes (Diptera: Culicidae). JE vaccination and mass drug administration for JE and LF management is being undertaken respectively. In addition to this, indoor residual spraying and fogging are used for the control of mosquito vectors. Organophosphate resistance in mosquito is dependent on alteration in acetylcholinesterase (Ace) gene. Hence, it is important to evaluate organophosphate resistance in Culex tritaeniorhynchus Giles (JE vector) and Culex quinquefasciatus Say (LF vector). The current study showed the presence of resistant populations and F331W mutation in Cx. tritaeniorhynchus and G119S mutation in Cx. quinquefasciatus insensitive Ace genes. Resistant populations of these two vectors increase the chances of spreading of resistance in the natural population and may cause failure of intervention programs that include organophosphates against these two vectors in future.

  3. Pathway modulators and inhibitors.

    PubMed

    Smith, John A

    2009-07-01

    Inhibitors of specific cellular pathways are useful for investigating the roles of proteins of unknown function, and for selectively inhibiting a protein in complex pathways to uncover its relationships to other proteins in this and other interacting pathways. This appendix provides links to Web sites that describe cellular processes and pathways along with the various classes of inhibitors, numerous references, downloadable diagrams, and technical tips.

  4. Update on TNF Inhibitors.

    PubMed

    Kerdel, Francisco A

    2016-06-01

    The introduction of tumor necrosis factor (TNF)-α inhibitors dramatically improved the management of psoriasis. Some newer or investigational biologics with different mechanisms of action have demonstrated noninferiority or superiority to etanercept, the first self-injectable anti-TNF-α agent to become available in the United States. Nonetheless, TNF-α inhibitors are likely to remain a mainstay of therapy for many years.

  5. Synthetic inhibitors of elastase.

    PubMed

    Edwards, P D; Bernstein, P R

    1994-03-01

    For more than two decades investigators around the world, in both academic and industrial institutions, have been developing inhibitors of human neutrophil elastase. A number of very elegant and insightful strategies have been reported. In the case of reversible peptidic inhibitors, this has resulted in the identification of some extremely potent compounds with dissociation constants in the 10(-11) M range. This is quite an accomplishment considering that these low molecular-weight inhibitors are only tri- and tetrapeptides. In the case of the heterocyclic-based inhibitors, the challenge of balancing the heterocycle's inherent reactivity and aqueous stability with the stability of the enzyme-inhibitor adduct has been meet by either using a latent, reactive functionality which is only activated within the enzyme, or by incorporating features which selectively obstruct deacylation but have little effect on the enzyme acylation step. The underlying goal of this research has been the identification of agents to treat diseases associated with HNE. Several animal models have been developed for evaluating the in vivo activity of elastase inhibitors, and compounds have been shown to be effective in all of these models by the intravenous, intratrachael or oral routes of administration. However, only a very small percentage of compounds have possessed all the necessary properties, including lack of toxicity, for progression into the clinic. The peptidyl TFMK ICI 200,880 (25-12) has many of the desired characteristics of a drug to treat the diseases associated with HNE: chemical stability, in vitro and in vivo activity, a long duration of action, and adequate metabolic stability. Currently ICI 200,880 is the only low molecular-weight HNE inhibitor known to be undergoing clinical trials, and may be the compound which finally demonstrates the clinical utility of a synthetic HNE inhibitor. PMID:8189835

  6. 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

  7. Antenatal betamethasone exposure is associated with lower ANG-(1-7) and increased ACE in the CSF of adult sheep.

    PubMed

    Marshall, Allyson C; Shaltout, Hossam A; Pirro, Nancy T; Rose, James C; Diz, Debra I; Chappell, Mark C

    2013-10-01

    Antenatal betamethasone (BM) therapy accelerates lung development in preterm infants but may induce early programming events with long-term cardiovascular consequences. To elucidate these events, we developed a model of programming whereby pregnant ewes are administered BM (2 doses of 0.17 mg/kg) or vehicle at the 80th day of gestation and offspring are delivered at term. BM-exposed (BMX) offspring develop elevated blood pressure; decreased baroreflex sensitivity; and alterations in the circulating, renal, and brain renin-angiotensin systems (RAS) by 6 mo of age. We compared components of the choroid plexus fourth ventricle (ChP4) and cerebral spinal fluid (CSF) RAS between control and BMX male offspring at 6 mo of age. In the choroid plexus, high-molecular-weight renin protein and ANG I-intact angiotensinogen were unchanged between BMX and control animals. Angiotensin-converting enzyme 2 (ACE2) activity was threefold higher than either neprilysin (NEP) or angiotensin 1-converting enzyme (ACE) in control and BMX animals. Moreover, all three enzymes were equally enriched by approximately 2.5-fold in ChP4 brush-border membrane preparations. CSF ANG-(1-7) levels were significantly lower in BMX animals (351.8 ± 76.8 vs. 77.5 ± 29.7 fmol/mg; P < 0.05) and ACE activity was significantly higher (6.6 ± 0.5 vs. 8.9 ± 0.5 fmol·min(-1)·ml(-1); P < 0.05), whereas ACE2 and NEP activities were below measurable limits. A thiol-sensitive peptidase contributed to the majority of ANG-(1-7) metabolism in the CSF, with higher activity in BMX animals. We conclude that in utero BM exposure alters CSF but not ChP RAS components, resulting in lower ANG-(1-7) levels in exposed animals. PMID:23948771

  8. Hypotensive, Angiotensin Converting Enzyme (ACE) Inhibitory and Diuretic Activities of the Aqueous-methanol Extract of Ipomoea reniformis

    PubMed Central

    Jabeen, Qaiser; Aslam, Naveed

    2013-01-01

    Ipomoea reniformis Roxb. (Convolvulaceae) is a small, weedy herb used for the management of cardiac problems in traditional systems of medicine in India and Pakistan. Objective of the present study was to investigate the hypotensive, diuretic and angiotensin converting enzyme (ACE) inhibitory activities of the aqueous-methanol (30:70) crude extract of the dried aerial parts of I. reniformis (Ir.Cr.) in rats. To record blood pressure lowering effects of the Ir.Cr, different doses of the extract were administered through jugular vein to the ketamine-diazepam anesthetized normotensive rats and blood pressure was recorded via carotid artery. ACE inhibitory activity of the extract was studied in-vitro; using hippuryl-l-histidyl-l-leucine as substrate, the product hippurate was quantified spectrophotometrically after reacting with cyanuric chloride/dioxane reagent. Effects of intraperitoneal administration of the extract on urine and urinary electrolyte excretion were also investigated in rats. The extract (Ir.Cr.) produced 21.51 ± 3.41, 28.99 ± 2.30, 53.34 ± 0.88 and 61.71 ± 3.37% fall in mean arterial blood pressure of the anesthetized rats at the doses of 0.1, 0.3, 1.0 and 3.0 mg/Kg, respectively. Ir.Cr. was found to have serum ACE inhibitory activity, with IC50 value of 422 ± 21.16 μg/mL. The extract also increased urine volume and urinary Na+ excretion significantly at the doses of 30 and 50 mg/Kg in rats. The study concludes that the crude extract of Ipomoea reniformis (Ir.Cr.) has hypotensive, ACE inhibitory and diuretic activities, which provide the scientific justification for the traditional uses of the plant as cardioprotective, antihypertensive and diuretic remedy. PMID:24523757

  9. Validation of ACE-FTS measurements of CFC-11, CFC-12, and HCFC-22 using ground-based FTIR spectrometers

    NASA Astrophysics Data System (ADS)

    Kolonjari, F.; Walker, K. A.; Mahieu, E.; Batchelor, R. L.; Bernath, P. F.; Boone, C.; Conway, S. A.; Dan, L.; Griffin, D.; Harrett, A.; Kasai, Y.; Kagawa, A.; Lindenmaier, R.; Strong, K.; Whaley, C.

    2013-12-01

    Satellite datasets can be an effective global monitoring tool for long-lived compounds in the atmosphere. The Atmospheric Chemistry Experiment (ACE) is a mission on-board the Canadian satellite SCISAT-1. The primary instrument on SCISAT-1 is a high-resolution infrared Fourier transform spectrometer (ACE-FTS) which is capable of measuring a range of gases including key chlorofluorocarbon (CFC) and hydrochlorofluorocarbon (HCFC) species. These families of species are of interest because of their significant contribution to anthropogenic ozone depletion and to global warming. To assess the quality of data derived from satellite measurements, validation using other data sources is essential. Ground-based Fourier transform infrared (FTIR) spectrometers are particularly useful for this purpose. In this study, five FTIR spectrometers located at four sites around the world are used to validate the CFC-11 (CCl3F), CFC-12 (CCl2F2), and HCFC-22 (CHClF2) retrieved profiles from ACE-FTS measurements. These species are related because HCFC-22 was the primary replacement for CFC-11 and CFC-12 in refrigerant and propellant applications. The FTIR spectrometers used in this study record solar absorption spectra at Eureka (Canada), Jungfraujoch (Switzerland), Poker Flat (USA), and Toronto (Canada). The retrieval of CFC-11, CFC-12, and HCFC-22 are not standard products for many of these instruments, and as such, a harmonization of retrieval parameters between the sites has been conducted. The retrievals of these species from the FTIR spectra are sensitive from the surface to approximately 20 km, while the ACE-FTS profiles extend from approximately 6 to 30 km. For each site, partial column comparisons between coincident measurements of the three species and a validation of the observed trends will be discussed.

  10. A newly developed tool for intra-tracheal temperature and humidity assessment in laryngectomized individuals: the Airway Climate Explorer (ACE).

    PubMed

    Zuur, J K; Muller, S H; de Jongh, F H C; van der Horst, M J; Shehata, M; van Leeuwen, J; Sinaasappel, M; Hilgers, F J M

    2007-08-01

    The aim of this study is to develop a postlaryngectomy airway climate explorer (ACE) for assessment of intratracheal temperature and humidity and of influence of heat and moisture exchangers (HMEs). Engineering goals were within-device condensation prevention and fast response time characteristics. The ACE consists of a small diameter, heated air-sampling catheter connected to a heated sensor house, containing a humidity sensor. Air is sucked through the catheter by a controlled-flow pump. Validation was performed in a climate chamber using a calibrated reference sensor and in a two-flow system. Additionally, the analyser was tested in vivo. Over the clinically relevant range of humidity values (5-42 mg H2O/l air) the sensor output highly correlates with the reference sensor readings (R2 > 0.99). The 1-1/e response times are all <0.5 s. A first in vivo pilot measurement was successful. The newly developed, verified, fast-responding ACE is suitable for postlaryngectomy airway climate assessment.

  11. Accelerated Cartesian expansion (ACE) based framework for the rapid evaluation of diffusion, lossy wave, and Klein-Gordon potentials

    SciTech Connect

    Baczewski, Andrew David; Vikram, Melapudi; Shanker, Balasubramaniam; Kempel, Leo

    2010-08-27

    Diffusion, lossy wave, and Klein–Gordon equations find numerous applications in practical problems across a range of diverse disciplines. The temporal dependence of all three Green’s functions are characterized by an infinite tail. This implies that the cost complexity of the spatio-temporal convolutions, associated with evaluating the potentials, scales as O(Ns2Nt2), where Ns and Nt are the number of spatial and temporal degrees of freedom, respectively. In this paper, we discuss two new methods to rapidly evaluate these spatio-temporal convolutions by exploiting their block-Toeplitz nature within the framework of accelerated Cartesian expansions (ACE). The first scheme identifies a convolution relation in time amongst ACE harmonics and the fast Fourier transform (FFT) is used for efficient evaluation of these convolutions. The second method exploits the rank deficiency of the ACE translation operators with respect to time and develops a recursive numerical compression scheme for the efficient representation and evaluation of temporal convolutions. It is shown that the cost of both methods scales as O(NsNtlog2Nt). Furthermore, several numerical results are presented for the diffusion equation to validate the accuracy and efficacy of the fast algorithms developed here.

  12. Aerosols, Chemistry, and Radiative Forcing: A 3-D Model Analysis of Satellite and ACE-Asia data (ACMAP)

    NASA Technical Reports Server (NTRS)

    Chin, Mian; Ginoux, Paul; Torres, Omar; Zhao, Xue-Peng

    2005-01-01

    We propose a research project to incorporate a global 3-D model and satellite data into the multi-national Aerosol Characterization Experiment-Asia (ACE-Asia) mission. Our objectives are (1) to understand the physical, chemical, and optical properties of aerosols and the processes that control those properties over the Asian-Pacific region, (2) to investigate the interaction between aerosols and tropospheric chemistry, and (3) to determine the aerosol radiative forcing over the Asia-Pacific region. We will use the Georgia TecWGoddard Global Ozone Chemistry Aerosol Radiation and Transport (GOCART) model to link satellite observations and the ACE-Asia measurements. First, we will use the GOCART model to simulate aerosols and related species, and evaluate the model with satellite and in-situ observations. Second, the model generated aerosol vertical profiles and compositions will be used to validate the satellite products; and the satellite data will be used for during- and post- mission analysis. Third, we will use the model to analyze and interpret both satellite and ACE- Asia field campaign data and investigate the aerosol-chemistry interactions. Finally, we will calculate aerosol radiative forcing over the Asian-Pacific region, and assess the influence of Asian pollution in the global atmosphere. We propose a research project to incorporate a global 3-D model and satellite data into

  13. User`s guide for the Augmented Computer Exercise for Inspection Training (ACE-IT), Version 2.0 software

    SciTech Connect

    Dobranich, P.R.; Horak, K.E.; Evanko, D.A.

    1998-04-01

    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 (hosts). Traditional training techniques include lectures, 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 is used for training both inspectors and hosts to conduct a hypothetical challenge inspection under the Chemical Weapons Convention (CWC). The training covers the entire sequence of events in the challenge inspection regime, from initial notification of an inspection through post-inspection activities. The primary emphasis of the training tool is on conducting the inspection itself, and in particular, implementing the concept of managed access. (Managed access is a technique used to assure the inspectors that the facility is in compliance with the CWC, while at the same time protecting sensitive information unrelated to the CWC.) Information for all of the activities is located in the electronic {open_quotes}Exercise Manual.{close_quotes} In addition, interactive menus are used to negotiate access to each room and to alternate information during the simulated inspection. ACE-IT also demonstrates how various inspection provisions impact compliance determination and the protection of sensitive information.

  14. Accelerated Cartesian expansion (ACE) based framework for the rapid evaluation of diffusion, lossy wave, and Klein-Gordon potentials

    DOE PAGES

    Baczewski, Andrew David; Vikram, Melapudi; Shanker, Balasubramaniam; Kempel, Leo

    2010-08-27

    Diffusion, lossy wave, and Klein–Gordon equations find numerous applications in practical problems across a range of diverse disciplines. The temporal dependence of all three Green’s functions are characterized by an infinite tail. This implies that the cost complexity of the spatio-temporal convolutions, associated with evaluating the potentials, scales as O(Ns2Nt2), where Ns and Nt are the number of spatial and temporal degrees of freedom, respectively. In this paper, we discuss two new methods to rapidly evaluate these spatio-temporal convolutions by exploiting their block-Toeplitz nature within the framework of accelerated Cartesian expansions (ACE). The first scheme identifies a convolution relation inmore » time amongst ACE harmonics and the fast Fourier transform (FFT) is used for efficient evaluation of these convolutions. The second method exploits the rank deficiency of the ACE translation operators with respect to time and develops a recursive numerical compression scheme for the efficient representation and evaluation of temporal convolutions. It is shown that the cost of both methods scales as O(NsNtlog2Nt). Furthermore, several numerical results are presented for the diffusion equation to validate the accuracy and efficacy of the fast algorithms developed here.« less

  15. Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample.

    PubMed

    Wollinger, L M; Dal Bosco, S M; Rempe, C; Almeida, S E M; Berlese, D B; Castoldi, R P; Arndt, M E; Contini, V; Genro, J P

    2015-12-29

    The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

  16. An intercomparison study of isotopic ozone profiles from the ACE-FTS, JEM-SMILES, and Odin-SMR instruments

    NASA Astrophysics Data System (ADS)

    Jones, A.; Walker, K. A.; Suzuki, M.; Kasai, Y.; Shiotani, M.; Urban, J.; Bernath, P. F.; Manney, G. L.

    2012-12-01

    Observations of various atmospheric isotopologue species are a valuable source of information, as they can improve our current understanding of the atmosphere. For example, isotopic signatures in atmospheric profiles can be used to investigate atmospheric dynamical processes, while differences in the isotopic composition of atmospheric trace gases can be traced to effects due to their sources and sinks. This study focuses on the intercomparison of three satellite missions that provide measurements of isotopic species. The Atmospheric Chemistry Experiment-Fourier Transform Spectrometer (ACE-FTS) aboard the Canadian satellite SCISAT (launched in August 2003) was designed to investigate the composition of the upper troposphere, stratosphere, and mesosphere. ACE-FTS utilizes solar occultation to measure temperature, pressure, and vertical profiles of over thirty chemical species, including isotopologue profiles for; O3, H2O, CH4, N2O, CO, CO2 and NO. Global coverage for each species is obtained approximately over one year and with a vertical resolution of typically 3-4 km. ACE-FTS O3 isotopologue volume mixing ratio profiles are firstly compared to data measured by the Superconducting Sub-Millimeter-wave Limb Emission Sounder (SMILES), onboard the Japanese Experiment Module (JEM) of the International Space Station (ISS), and the Sub-Millimetre Radiometer (SMR) aboard the Swedish Odin satellite. Secondly, we intercompare the isotopic fractionation profiles for each ozone isotopologue product measured by the three instruments to further ascertain a level of confidence in the measurements.

  17. Investigation of ion energy and angular distributions at the wafer edge in rf capacitively coupled reactors using CFD-ACE+

    NASA Astrophysics Data System (ADS)

    Bhoj, Ananth; Roy, Abhra; Jain, Kunal; Xiong, Zhongmin

    2015-09-01

    Dual frequency capacitively coupled reactors are now commonly used in microelectronics fabrication. The extent of possible independent control of ion fluxes and ion energy and angular distribution (IEADs) by varying HF and LF signals is currently a topic of great interest. In this study, we report on investigations of IEADs in single and dual frequency CCPs, including the wafer edge refinement using CFD-ACE+. The current algorithms in CFD-ACE+ allow the determination of total power at the electrode or in the discharge. To account for the presence of two or more rf sources connected to a powered electrode, the existing numerical algorithms for power targeting were enhanced to track current at the electrode as a function of time, vary voltage and determine power as a function of frequency. The Monte Carlo transport module for heavy species in CFD-ACE+ was recently enhanced to compute IEADs in rf discharges. Results for the effect of varying power and pressure on IEADs were compared to semi-analytical models and data reported in Gahan et al.. The validated model was applied to investigate the effect of details of HF and LF signals on IEADs in Argon discharges.

  18. Deactivating Cochlear Implant Electrodes Based on Pitch Information for Users of the ACE Strategy.

    PubMed

    Vickers, Deborah; Degun, Aneeka; Canas, Angela; Stainsby, Thomas; Vanpoucke, Filiep

    2016-01-01

    There is a wide range in performance for cochlear implant (CI) users and there is some evidence to suggest that implant fitting can be modified to improve performance if electrodes that do not provide distinct pitch information are de-activated. However, improvements in performance may not be the same for users of all CI devices; in particular for those with Cochlear devices using n-of-m strategies (ACE or SPEAK).The goal of this research was to determine for users of Cochlear devices (CP810 or CP900 series processors) if speech perception could be improved when indiscriminable electrodes were de-activated and this was also compared to when the same number of discriminable electrodes were de-activated.A cross-over study was conducted with 13 adult CI users who received experimental maps with de-activated channels for a minimum of 2 months and these were compared to optimised clinical maps.The findings showed that there were no significant benefits of electrode de-activation on speech perception and that there was a significant deterioration in spectro-temporal ripple perception when electrodes were switched off. There were no significant differences between de-activation of discriminable or indiscriminable electrodes.These findings suggest that electrode de-activation with n-of-m strategies may not be beneficial. PMID:27080652

  19. ACE/SWICS Observations of Heavy Ion Dropouts within the Solar Wind

    NASA Astrophysics Data System (ADS)

    Weberg, Micah J.; Zurbuchen, Thomas H.; Lepri, Susan T.

    2012-11-01

    We present the first in situ observations of heavy ion dropouts within the slow solar wind, observed for select elements ranging from helium to iron. For iron, these dropouts manifest themselves as depletions of the Fe/H ratio by factors up to ~25. The events often exhibit mass-dependent fractionation and are contained in slow, unsteady wind found within a few days from known stream interfaces. We propose that such dropouts are