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Sample records for ace inhibitors calcium

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. 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

  4. ACE inhibitor potentiation of bradykinin-induced venoconstriction

    PubMed Central

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

    1997-01-01

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

  5. Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

    PubMed Central

    2013-01-01

    Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

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

    PubMed

    Dalla Volta, S

    1994-12-01

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

  7. 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.

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

    PubMed Central

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

    2009-01-01

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

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

    SciTech Connect

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

    1988-07-01

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

  10. 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

  11. 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

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

    PubMed Central

    Wijesekara, Isuru; Kim, Se-Kwon

    2010-01-01

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

  13. 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

  14. 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

  15. 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

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

    PubMed

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

    1998-02-01

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

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

    PubMed

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

    2009-01-01

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

  18. 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.

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

    PubMed

    Shen, Shi; Yang, Xing; Shi, Yaqin

    2015-10-10

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

  20. 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.

  1. 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.

  2. 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: ...

  3. ACE inhibitors

    MedlinePlus

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

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

    PubMed

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

    2011-07-01

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

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

    PubMed

    Sr, Jiří Widimský

    2015-02-01

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

  6. 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

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

    PubMed

    Hansell, P; Palm, F

    2015-04-01

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

  8. 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

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

    PubMed

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

    1989-01-01

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

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

    PubMed Central

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

    2007-01-01

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

  11. 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

  12. 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

  13. 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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Valika, Ali A; Gheorghiade, Mihai

    2013-03-01

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

  17. Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry.

    PubMed

    Yu, Changhui; Tang, Wei; Wang, Yuhao; Shen, Qiang; Wang, Bin; Cai, Chunqing; Meng, Xiaojing; Zou, Fei

    2016-07-01

    The renin-angiotensin system (RAS) is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, angiogenesis, metabolism, migration and invasion. Meanwhile, the arm of angiotensin-converting enzyme (ACE)2/angiotensin-(1-7) [Ang-(1-7)]/Mas axis in connection with RAS is associated with anti-proliferative, vasodilatory and anti-metastatic properties. Previous studies have shown that Ang-(1-7) reduces the proliferation of orthotopic human breast tumor growth by inhibiting cancer-associated fibroblasts. However, the role of ACE/Ang-(1-7)/Mas axis in the metastasis of breast cancer cells is still unknown. In the present study, we found that ACE2 protein level is negatively correlated with the metastatic ability of breast cancer cells and breast tumor grade. Upregulation of ACE2/Ang-(1-7)/Mas axis inhibits breast cancer cell migration and invasion in vivo and in vitro. Mechanistically, ACE2/Ang-(1-7)/Mas axis activation inhibits store-operated calcium entry (SOCE) and PAK1/NF-κB/Snail1 pathways, and induces E-cadherin expression. In summary, our results demonstrate that downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of SOCE and PAK1/NF-κB/Snail1 pathways. These results provide new mechanisms by which breast cancer develop metastasis and shed light on developing novel anti-metastasis therapeutics for metastatic breast cancer by modulating ACE2/Ang-(1-7)/Mas axis. PMID:27063099

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

    PubMed

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

    2014-12-15

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

  19. 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

  20. The influence of scale inhibitors on calcium oxalate

    SciTech Connect

    Gill, J.S.

    1999-11-01

    Precipitation of calcium oxalate is a common occurrence in mammalian urinary tract deposits and in various industrial processes such as paper making, brewery fermentation, sugar evaporation, and tannin concentration. Between pH 3.5 to 4.5 the driving force for calcium oxalate precipitation increases almost by three fold. It is a complicated process to predict both the nature of a deposit and at which stage of a multi-effect evaporator a particular mineral will deposit, as this depends on temperature, pH, total solids, and kinetics of mineralization. It is quite a challenge to inhibit calcium oxalate precipitation in the pH range of 4--6. Al{sup 3+} ions provide excellent threshold inhibition in this pH range and can be used to augment traditional inhibitors such as polyphosphates and polycarboxylates.

  1. 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

  2. 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

  3. 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.

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

    PubMed Central

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

    1995-01-01

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

  5. Calcium carbonate scale control, effect of material and inhibitors.

    PubMed

    Macadam, J; Parsons, S A

    2004-01-01

    This paper focuses on developing a reproducible method for reducing calcium carbonate scale formation on heated surfaces where scaling can cause serious problems. It is known that calcium carbonate precipitation is sensitive to impurity ions, such as iron and zinc, even at trace concentration levels. In this paper two sets of experiments are reported. The first experiments were undertaken to investigate the effect of zinc, copper and iron dosing on CaCO3 nucleation and precipitation. Results from the experiments showed that the most effective inhibitor of CaCO3 precipitation was zinc and the effect was linked to dose levels and temperature. Copper and iron had little effect on precipitation in the dose range investigated. The second trial was undertaken to translate the precipitation data to scale formation. These tests were undertaken at 70 degrees C. 5 mg x L(-1) zinc dose reduced the scale formation by 35%. The effect of iron on calcium carbonate scaling rate was not significant. The physical nature of the material on which the scale is formed also influences the scaling. The scaling experiment was also used to investigate the effect of different surface material (stainless steel, copper and aluminium) on CaCO3 scale formation. Copper surface scaled the most. PMID:14982176

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. 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

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

    PubMed

    Onuigbo, Macaulay A C

    2011-01-01

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

  10. Fixed-Dose Combinations of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension: A Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors.

    PubMed

    Hsiao, Fu-Chih; Tung, Ying-Chang; Chou, Shing-Hsien; Wu, Lung-Sheng; Lin, Chia-Pin; Wang, Chun-Li; Lin, Yu-Sheng; Chang, Chee-Jen; Chu, Pao-Hsien

    2015-12-01

    Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking.Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered.There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98-1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082-1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071-1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050-1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses.ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status. PMID:26705234

  11. 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

  12. 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

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

    PubMed

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

    2000-03-01

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

  14. 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

  15. Inhibition of polar calcium movement and gravitropism in roots treated with auxin-transport inhibitors

    NASA Technical Reports Server (NTRS)

    Lee, J. S.; Mulkey, T. J.; Evans, M. L.

    1984-01-01

    Primary roots of maize (Zea mays L.) and pea (Pisum sativum L.) exhibit strong positive gravitropism. In both species, gravistimulation induces polar movement of calcium across the root tip from the upper side to the lower side. Roots of onion (Allium cepa L.) are not responsive to gravity and gravistimulation induces little or no polar movement of calcium across the root tip. Treatment of maize or pea roots with inhibitors of auxin transport (morphactin, naphthylphthalamic acid, 2,3,5-triiodobenzoic acid) prevents both gravitropism and gravity-induced polar movement of calcium across the root tip. The results indicate that calcium movement and auxin movement are closely linked in roots and that gravity-induced redistribution of calcium across the root cap may play an important role in the development of gravitropic curvature.

  16. Inhibition of polar calcium movement and gravitropism in roots treated with auxin-transport inhibitors.

    PubMed

    Lee, J S; Mulkey, T J; Evans, M L

    1984-01-01

    Primary roots of maize (Zea mays L.) and pea (Pisum sativum L.) exhibit strong positive gravitropism. In both species, gravistimulation induces polar movement of calcium across the root tip from the upper side to the lower side. Roots of onion (Allium cepa L.) are not responsive to gravity and gravistimulation induces little or no polar movement of calcium across the root tip. Treatment of maize or pea roots with inhibitors of auxin transport (morphactin, naphthylphthalamic acid, 2,3,5-triiodobenzoic acid) prevents both gravitropism and gravity-induced polar movement of calcium across the root tip. The results indicate that calcium movement and auxin movement are closely linked in roots and that gravity-induced redistribution of calcium across the root cap may play an important role in the development of gravitropic curvature. PMID:11540830

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

    PubMed Central

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

    2010-01-01

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

  18. EXAMINATION OF THE ANTICONVULSANT PROPERTIES OF VOLTAGE-SENSITIVE CALCIUM CHANNEL INHIBITORS IN AMYGDALA KINDLED SEIZURES

    EPA Science Inventory

    Representatives from three different classes of voltage-sensitive calcium (VSC) channel inhibitors were assessed for their protection against amygdala kindled seizures. dult male long Evans rats (n=12) were implanted with electrodes in the amygdala and were stimulated once daily ...

  19. Bax inhibitor 1, a modulator of calcium homeostasis, confers affective resilience.

    PubMed

    Hunsberger, Joshua G; Machado-Vieira, Rodrigo; Austin, Daniel R; Zarate, Carlos; Chuang, De-Maw; Chen, Guang; Reed, John C; Manji, Husseini K

    2011-07-27

    The endoplasmic reticulum (ER) is a critical site for intracellular calcium storage as well as protein synthesis, folding, and trafficking. Disruption of these processes is gaining support for contributing to heritable vulnerability of certain diseases. Here, we investigated Bax inhibitor 1 (BI-1), an anti-apoptotic protein that primarily resides in the ER and associates with B-cell lymphoma 2 (Bcl-2) and Bcl-XL, as an affective resiliency factor through its modulation of calcium homeostasis. We found that transgenic (TG) mice with BI-1 reinforced expression, via the neuronal specific enolase promoter, showed protection against the learned helplessness (LH) paradigm, an animal model to test stress coping. TG mice were also protected against anhedonia following both serotonin and catecholamine depletion as measured in two different models, the female urine sniffing test and the saccharine preference test. In addition, we used primary mouse cortical cultures to explore the ability of BI-1 to influence calcium homeostasis under basal conditions and also following challenge with thapsigargin (THPS), an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) that disrupts calcium homeostasis. TG neurons showed decreased basal cytosolic calcium levels and decreased Ca(2+) cytosolic accumulation following challenge with THPS as compared to WT neuronal cultures. Together, these data suggest that BI-1, through its actions on calcium homeostasis, may confer affective resiliency in multiple animal models of depression and anhedonia. PMID:21718971

  20. Rapid, high-temperature, field test method for evaluation of geothermal calcium carbonate scale inhibitors

    SciTech Connect

    Asperger, R.G.

    1986-09-01

    A new test method is described that allows the rapid field testing of calcium carbonate scale inhibitors at 500/sup 0/F (260/sup 0/C). The method evolved from use of a full-flow test loop on a well with a mass flow rate of about 1 x 10/sup 6/ lbm/hr (126 kg/s). It is a simple, effective way to evaluate the effectiveness of inhibitors under field conditions. Five commercial formulations were chosen for field evaluation on the basis of nonflowing, laboratory screening tests at 500/sup 0/F (260/sup 0/C). Four of these formulations from different suppliers controlled calcium carbonate scale deposition as measured by the test method. Two of these could dislodge recently deposited scale that had not age-hardened. Performance-profile diagrams, which were measured for these four effective inhibitors, show the concentration interrelationship between brine calcium and inhibitor concentrations at which the formulations will and will not stop scale formation in the test apparatus. With these diagrams, one formulation was chosen for testing on the full-flow brine line. The composition was tested for 6 weeks and showed a dramatic decrease in the scaling occurring at the flow-control valve. This scaling was about to force a shutdown of a major, long-term flow test being done for reservoir economic evaluations. The inhibitor stopped the scaling, and the test was performed without interruption.

  1. Ni++ as a competitive inhibitor of calcium transport in mitochondria.

    PubMed

    Bragadin, M; Viola, E R

    1997-06-01

    The kinetics of Ca++ uptake in rat liver mitochondria have been studied using the potassium diffusion potential. The advantage of this approach is that in this condition, the mitochondrial respiratory rate is not the limiting step, and therefore the effects of Ni++ on the Ca++ carrier can be studied. Our results suggest that Ni++ is a competitive inhibitor of the Ca++ carrier, but it is not transported into the mitochondria. PMID:9161009

  2. 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

  3. Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells

    PubMed Central

    Harper, Jacquie L.; Camerini-Otero, Carol S.; Li, An-Hu; Kim, Soon-Ai; Jacobson, Kenneth A.; Daly, John W.

    2016-01-01

    A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or m-trifluoromethyl (IC50 values: 3–6 μM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 μM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 μM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. PMID:12527326

  4. ACE blood test

    MedlinePlus

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  7. Protein arginine deiminase 2 binds calcium in an ordered fashion: Implications for inhibitor design

    SciTech Connect

    Slade, Daniel J.; Fang, Pengfei; Dreyton, Christina J.; Zhang, Ying; Fuhrmann, Jakob; Rempel, Don; Bax, Benjamin D.; Coonrod, Scott A.; Lewis, Huw D.; Guo, Min; Gross, Michael L.; Thompson, Paul R.

    2015-01-26

    Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ions that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.

  8. Protein arginine deiminase 2 binds calcium in an ordered fashion: Implications for inhibitor design

    DOE PAGESBeta

    Slade, Daniel J.; Fang, Pengfei; Dreyton, Christina J.; Zhang, Ying; Fuhrmann, Jakob; Rempel, Don; Bax, Benjamin D.; Coonrod, Scott A.; Lewis, Huw D.; Guo, Min; et al

    2015-01-26

    Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ionsmore » that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.« less

  9. Protein Arginine Deiminase 2 Binds Calcium in an Ordered Fashion: Implications for Inhibitor Design

    PubMed Central

    2015-01-01

    Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ions that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs. PMID:25621824

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  12. 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

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

    PubMed

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

    1996-01-01

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

  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. [Discovering L-type calcium channels inhibitors of antihypertensive drugs based on drug repositioning].

    PubMed

    Liang, Ying-xi; He, Yu-su; Jiang, Lu-di; Yue, Qiao-xin; Cui, Shuai; Bin, Li; Ye, Xiao-tong; Zhang, Xiao-hua; Zhang, Yang-ling

    2015-09-01

    This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible. PMID:26983215

  16. Investigation of function similarities between the sarcoplasmic reticulum and platelet calcium-dependent adenosinetriphosphatases with the inhibitors quercetin and calmidazolium

    SciTech Connect

    Fischer, T.H.; Campbell, K.P.; White, G.C. II

    1987-12-01

    The platelet and skeletal sarcoplasmic reticulum calcium-dependent adenosinetriphosphatases (Ca/sup 2 +/-ATPases) were functionally compared with respect to substrate activation by steady-state kinetic methods using the inhibitors quercetin and calmidazolium. Quercetin inhibited platelet and sarcoplasmic reticulum Ca/sup 2 +/-ATPase activities in a dose-dependent manner with IC/sub 50/ values of 25 and 10 ..mu..M, respectively. Calmidazolium also inhibited platelet and sarcoplasmic reticulum Ca/sup 2 +/-ATPase activities, with half-maximal inhibition measured at 5 and 4 ..mu..M, respectively. Both inhibitors also affected the (/sup 45/Ca) calcium transport activity of intact platelet microsomes at concentrations similar to those which reduced Ca/sup 2 +/-ATPase activity. These inhibitors were then used to examine substrate ligation by the platelet and sarcoplasmic reticulum calcium pump proteins. For both Ca/sup 2 +/-ATPase proteins, quercetin has an affinity for the E-Ca/sub 2/ (fully ligated with respect to calcium at the exterior high-affinity calcium binding sites, unligated with respect to ATP) conformational state of the protein that is approximately 10-fold grater than for other conformational states in the hydrolytic cycle. Quercetin can thus be considered a competitive inhibitor of the calcium pump proteins with respect to ATP. In contrast to the effect of quercetin, calmidazolium interacts with the platelet and sarcoplasmic reticulum Ca/sup 2 +/-ATPases in an uncompetitive manner. The dissociation constants for this inhibitor for the different conformational states of the calcium pump proteins were similar, indicating that calmidazolium has equal affinity for all of the reaction intermediates probed. These observations indicate that the substrate ligation processes are similar for the two pump proteins. This supports the concept that the hydrolytic cycles of the two proteins are comparable.

  17. Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus.

    PubMed

    Cui, Rui; Wang, Yizhuo; Wang, Liu; Li, Guiming; Lan, Ke; Altmeyer, Ralf; Zou, Gang

    2016-08-01

    Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants and young children worldwide, yet no vaccine or effective antiviral treatment is available. To search for new anti-RSV agents, we developed a cell-based assay that measures inhibition of RSV-induced cytopathic effect (CPE) and identified cyclopiazonic acid (CPA), an intracellular calcium ATPase inhibitor as a RSV inhibitor (EC50 values 4.13 μM) by screening of natural product library. CPA inhibited the replication of RSV strains belonging to both A and B subgroups and human parainfluenza virus type 3, but not Enterovirus 71. Mechanism of action study by time-of-addition assay and minigenome assay revealed that CPA acts at the step of virus genome replication and/or transcription. Moreover, two other calcium ATPase inhibitors (Thapsigargin and BHQ) and calcium ionophores (A23187 and ionomycin), but not calcium channel blockers (nifedipine, nimodipine, and tetrandrine), also had similar effect. These results indicate that an increase in intracellular calcium concentration is detrimental to RSV replication. Thus, our findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. PMID:27210812

  18. Calcium

    MedlinePlus

    ... of calcium dietary supplements are carbonate and citrate. Calcium carbonate is inexpensive, but is absorbed best when taken ... antacid products, such as Tums® and Rolaids®, contain calcium carbonate. Each pill or chew provides 200–400 mg ...

  19. Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA.

    PubMed

    Wang, Fei; Yan, Zhenzhen; Liu, Zhuguo; Wang, Sheng; Wu, Qiaoling; Yu, Shuo; Ding, Jiuping; Dai, Qiuyun

    2016-02-01

    MVIIA (ziconotide) is a specific inhibitor of N-type calcium channel, Cav2.2. It is derived from Cone snail and currently used for the treatment of severe chronic pains in patients unresponsive to opioid therapy. However, MVIIA produces severe side-effects, including dizziness, nystagmus, somnolence, abnormal gait, and ataxia, that limit its wider application. We previously identified a novel inhibitor of Cav2.2, ω-conopeptide SO-3, which possesses similar structure and analgesic activity to MVIIA's. To investigate the key residues for MVIIA toxicity, MVIIA/SO-3 hybrids and MVIIA variants carrying mutations in its loop 2 were synthesized. The substitution of MVIIA's loop 1 with the loop 1 of SO-3 resulted in significantly reduced Cav2.2 binding activity in vitro; the replacement of MVIIA loop 2 by the loop 2 of SO-3 not only enhanced the peptide/Cav2.2 binding but also decreased its toxicity on goldfish, attenuated mouse tremor symptom, spontaneous locomotor activity, and coordinated locomotion function. Further mutation analysis and molecular calculation revealed that the toxicity of MVIIA mainly arose from Met(12) in the loop 2, and this residue inserts into a hydrophobic hole (Ile(300), Phe(302) and Leu(305)) located between repeats II and III of Cav2.2. The combinative mutations of the loop 2 of MVIIA or other ω-conopeptides may be used for future development of more effective Cav2.2 inhibitors with lower side effects. PMID:26344359

  20. Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2.

    PubMed

    Kokotos, George; Hsu, Yuan-Hao; Burke, John E; Baskakis, Constantinos; Kokotos, Christoforos G; Magrioti, Victoria; Dennis, Edward A

    2010-05-13

    Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one (FKGK18) is the most potent inhibitor of GVIA iPLA(2) (X(I)(50) = 0.0002) ever reported. Being 195 and >455 times more potent for GVIA iPLA(2) than for GIVA cPLA(2) and GV sPLA(2), respectively, makes it a valuable tool to explore the role of GVIA iPLA(2) in cells and in vivo models. 1,1,1,2,2,3,3-Heptafluoro-8-(naphthalene-2-yl)octan-4-one inhibited GVIA iPLA(2) with a X(I)(50) value of 0.001 while inhibiting the other intracellular GIVA cPLA(2) and GV sPLA(2) at least 90 times less potently. Hexa- and octafluoro ketones were also found to be potent inhibitors of GVIA iPLA(2); however, they are not selective. PMID:20369880

  1. Potent and Selective Fluoroketone Inhibitors of Group VIA Calcium-Independent Phospholipase A2

    PubMed Central

    Kokotos, George; Hsu, Yuan-Hao; Burke, John E.; Baskakis, Constantinos; Kokotos, Christoforos G.; Magrioti, Victoria; Dennis, Edward A.

    2010-01-01

    Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA2 inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one (FKGK18) is the most potent inhibitor of GVIA iPLA2 (XI(50) 0.0002) ever reported. Being 195 and >455 times more potent for GVIA iPLA2 than for GIVA cPLA2 and GV sPLA2, respectively, makes it a valuable tool to explore the role of GVIA iPLA2 in cells and in vivo models. 1,1,1,2,2,3,3-Heptafluoro-8-(naphthalene-2-yl) octan-4-one inhibited GVIA iPLA2 with a XI(50) value of 0.001, while inhibiting the other intracellular GIVA cPLA2 and GV sPLA2 at least 90-times less potently. Hexa- and octa-fluoro ketones were also found to be potent inhibitors of GVIA iPLA2; however they are not selective. PMID:20369880

  2. Calcium

    MedlinePlus

    ... body stores more than 99 percent of its calcium in the bones and teeth to help make and keep them ... in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with soft bones that you eat, such as canned sardines and ...

  3. 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…

  4. Calcium

    MedlinePlus

    ... milligrams) of calcium each day. Get it from: Dairy products. Low-fat milk, yogurt, cheese, and cottage ... lactase that helps digest the sugar (lactose) in dairy products, and may have gas, bloating, cramps, or ...

  5. Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1

    PubMed Central

    Zhang, Zhongsheng; Ojo, Kayode K.; Johnson, Steven M.; Larson, Eric T.; He, Penqing; Geiger, Jennifer A.; Castellanos-Gonzalez, Alejandro; White, A. Clinton; Parsons, Marilyn; Merritt, Ethan A.; Maly, Dustin J.; Verlinde, Christophe L. M. J.; Van Voorhis, Wesley C.; Fan, Erkang

    2012-01-01

    Calcium-dependent protein kinase-1 (CDPK1) from Cryptosporidium parvum (CpCDPK1) and Toxoplasma gondii (TgCDPK1) have become attractive targets for discovering selective inhibitors to combat infections caused by these protozoa. We used structure-based design to improve a series of benzoylbenzimidazole-based compounds in terms of solubility, selectivity, and potency against CpCDPK1 and TgCDPK1. The best inhibitors show inhibitory potencies below 50 nM and selectivity well above 200-fold over two human kinases with small gatekeeper residues. PMID:22795629

  6. 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

  7. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties.

    PubMed

    Choudhary, M Iqbal; Nawaz, Sarfraz Ahmad; ul-Haq, Zaheer; Lodhi, M Arif; Ghayur, M Nabeel; Jalil, Saima; Riaz, Naheed; Yousuf, Sammer; Malik, Abdul; Gilani, Anwarul Hassan; ur-Rahman, Atta

    2005-08-19

    The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2 microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that compounds 1, 3, and 5 are the linear mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were found to be non-competitive inhibitors of BChE with K(i) values ranging between 27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5 extend up to the catalytic triad. A comparison of the docking results showed that all ligands generally adopt the same binding mode and lie parallel to the surface of the gorge. The superposition of the docked structures demonstrated that the non-flexible skeleton of the ligands always penetrates the aromatic gorge through the six-membered ring A, allowing their simultaneous interaction with more than one subsite of the active center. The affinity of ligands with AChE was found to be the cumulative effects of number of hydrophobic contacts and hydrogen bonding. Furthermore, all compounds also displayed dose-dependent (0.005-1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated rabbit jejunum preparations, compound 4 being the most active with an ED50 value of 0.09 +/- 0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+ -induced contractions, respectively. The cholinesterase inhibitory potential along with calcium antagonistic ability and safe profile in human neutrophil viability assay could make compounds 1-5 possible drug candidates for further study to treat Alzheimer's disease and

  8. Bioavailability of calcium and its absorption inhibitors in raw and cooked green leafy vegetables commonly consumed in India--an in vitro study.

    PubMed

    Amalraj, Augustine; Pius, Anitha

    2015-03-01

    The objectives of this research were to assess the bioavailability of calcium using equilibrium dialysis after simulated gastric digestion method in 20 commonly consumed green leafy vegetables (GLVs) from the typical Indian diet, provide data on the content of calcium absorption inhibitors, like oxalate, phytate, tannin and dietary fibres, and evaluate the inhibitory effect of these compounds on calcium bioavailability in raw and cooked GLVs. Cooking did not affect significantly calcium bioavailability in any GLVs. Sesbania grandiflora had a very high content of total oxalates, tannins and dietary fibers, which reduced calcium bioavailability. Calcium content was determined by atomic absorption spectroscopy, oxalate by titrimetry, phytate and tannin by colorimetric and dietary fibres by an enzymatic gravimetric method. Chenopodium album, Alternanthera philoxeroides and Centella asiatica, with lower total calcium content, had nearly twice as much bioavailable calcium than other GLVs, because of low fibres, oxalate, phytate and tannin content. PMID:25306367

  9. Effect of six kinds of scale inhibitors on calcium carbonate precipitation in high salinity wastewater at high temperatures.

    PubMed

    Li, Xiaochen; Gao, Baoyu; Yue, Qinyan; Ma, Defang; Rong, Hongyan; Zhao, Pin; Teng, Pengyou

    2015-03-01

    Precipitation of calcium carbonate (CaCO3) scale on heat transfer surfaces is a serious and expensive problem widely occurring in numerous industrial processes. In this study, we compared the scale inhibition effect of six kinds of commercial scale inhibitors and screened out the best one (scale inhibitor SQ-1211) to investigate its scale inhibition performance in highly saline conditions at high temperature through static scale inhibition tests. The influences of scale inhibitor dosage, temperature, heating time and pH on the inhibition efficiency of the optimal scale inhibitor were investigated. The morphologies and crystal structures of the precipitates were characterized by Scanning Electron Microscopy and X-ray Diffraction analysis. Results showed that the scale inhibition efficiency of the optimal scale inhibitor decreased with the increase of the reaction temperature. When the concentration of Ca2+ was 1600 mg/L, the scale inhibition rate could reach 90.7% at 80°C at pH8. The optimal scale inhibitor could effectively retard scaling at high temperature. In the presence of the optimal scale inhibitor, the main crystal structure of CaCO3 changed from calcite to aragonite. PMID:25766020

  10. 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.

  11. Effects of A Voltage Sensitive Calcium Channel Blocker and A Sodium-Calcium Exchanger Inhibitor on Apoptosis of Motor Neurons in Adult Spinal Cord Slices

    PubMed Central

    Momeni, Hamid Reza; Jarahzadeh, Mahsa

    2012-01-01

    Objective: The apoptosis of motor neurons is a critical phenomenon in spinal cord injuries. Adult spinal cord slices were used to investigate whether voltage sensitive calcium channels and Na+/Ca2+ exchangers play a role in the apoptosis of motor neurons. Materials and Methods: In this experimental research, the thoracic region of the adult mouse spinal cord was sliced using a tissue chopper and the slices were incubated in a culture medium in the presence or absence of N/L type voltage sensitive calcium channels blocker (loperamide, 100 µM) or Na+/Ca2+ exchangers inhibitor(bepridil, 20 µM) for 6 hours. 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium (MTT) staining was used to assess slice viability while morphological features of apoptosis in motor neurons were studied using fluorescent staining. Results: After 6 hours in culture, loperamideand bepridil not only increased slice viability, but also prevented motor neuron apoptosis and significantly increased the percentage of viable motor neurons in the ventral horns of the spinal cord. Conclusion: The results of this study suggest that voltage sensitive calcium channels and Na+/Ca2+ exchanger might be involved in the apoptosis of motor neurons in adult spinal cord slices. PMID:23508879

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

    PubMed

    Das, Undurti N

    2008-01-01

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

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

    PubMed Central

    Xiao, Liang; Haack, Karla K. V.

    2013-01-01

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

  14. ACES--Today and Tomorrow.

    ERIC Educational Resources Information Center

    Hackney, Harold

    1991-01-01

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

  15. High-throughput platform for design and screening of peptides as inhibitors of calcium oxalate monohydrate crystallization

    NASA Astrophysics Data System (ADS)

    Farmanesh, Sahar; Chung, Jihae; Chandra, Divya; Sosa, Ricardo D.; Karande, Pankaj; Rimer, Jeffrey D.

    2013-06-01

    Crystal growth modifiers present a versatile tool for controlling crystal shape and size. Our work described here focuses on the design and screening of short peptides as inhibitors of calcium oxalate monohydrate (COM) crystals using high-throughput approaches. We designed a small library of 13 peptides containing Ala and Asp amino acids arranged in varying sequences that mimic ubiquitous motifs in natural calcium-binding proteins. Peptides were screened using a quick assay to measure their efficacy for inhibiting COM crystallization. Our results show that subtle variations in the placement of Ala and Asp residues in the peptide sequence can have a profound effect on their inhibition potential. We were able to discover peptide sequences that inhibit COM crystallization more effectively than some of the well-known COM inhibitors, such as citrate. Our results also demonstrate that peptides can be engineered to bind to specific faces of COM crystals. Peptide sequences identified in this work are promising candidates for further development as therapies for biomineral-related diseases, such as kidney stone disease. Collectively, our work establishes new paradigms for the design, synthesis, and screening of peptides for controlling crystal habit with the potential to impact a variety of fields, including drug discovery, advanced materials, catalysis and separations.

  16. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    PubMed Central

    Rubio-Guerra, Alberto F; Castro-Serna, David; Barrera, Cesar I Elizalde; Ramos-Brizuela, Luz M

    2009-01-01

    Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS) are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension. PMID:21949615

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

    PubMed

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

    2004-02-01

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

  18. Mechanistic understanding of calcium-phosphonate solid dissolution and scale inhibitor return behavior in oilfield reservoir: formation of middle phase.

    PubMed

    Zhang, Ping; Shen, Dong; Ruan, Gedeng; Kan, Amy T; Tomson, Mason B

    2016-08-01

    Phosphonates are an important class of mineral scale inhibitors used for oilfield scale control. By injecting the phosphonate into an oilfield reservoir, calcium-phosphonate precipitate will form and subsequently release the phosphonate into produced water for scale control. In this study, a systematic procedure is developed to mechanistically characterize an acidic calcium-phosphonate amorphous material that is later developed into a middle phase and eventually a crystalline phase. The phosphonate used in this study is diethylenetriamine pentakis (methylene phosphonic acid) (DTPMP). An amorphous calcium-DTPMP solid is precipitated by mixing a calcium-containing solution with a DTPMP solution. The stoichiometry of this initially formed solid can be experimentally confirmed via a static dissolution test. Following another dynamic development test, two additional Ca-DTPMP solid phases, i.e., a middle phase and a crystalline phase have been observed. Electron microscopy and X-ray diffraction were employed to characterize the morphology and crystallinity of different Ca-DTPMP solids of interest. Evidently, the dynamic brine flushing of the Ca-DTPMP solid developed the initially amorphous material into a middle phase solid with an amorphous/microcrystalline structure and eventually into a crystalline material. Furthermore, a dissolution characterization study was carried out to determine the solubility product of the middle phase solid at different conditions. The obtained mechanistic understanding of the Ca-DTPMP solid related to precipitation chemistry, dissolution behavior and phase transition is critical to elucidate oilfield DTPMP return data and more importantly, can optimize the oilfield scale squeeze design to achieve an extended squeeze lifetime. PMID:27426410

  19. 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

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

    PubMed

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

    2010-04-01

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

  1. An ACE diagnosis.

    PubMed

    Nasher, Omar; Gupta, Anindya

    2013-01-01

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

  2. An ACE diagnosis

    PubMed Central

    Nasher, Omar; Gupta, Anindya

    2013-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Differential Effects of Phosphatase Inhibitors on the Calcium Homeostasis and Migration of HaCaT Keratinocytes

    PubMed Central

    Oláh, Tamás; Vincze, János; Gáll, Tamás; Balogh, Enikő; Nagy, Gábor; Bátori, Róbert; Lontay, Beáta; Erdődi, Ferenc; Csernoch, Laszlo

    2013-01-01

    Changes in intracellular calcium concentration ([Ca2+]i) as well as in the phosphorylation state of proteins have been implicated in keratinocyte wound healing revealed in scratch assays. Scratching confluent HaCaT monolayers decreased the number of cells displaying repetitive Ca2+ oscillations as well as the frequency of their Ca2+-transients in cells close to the wounded area and initiated migration of the cells into the wound bed. In contrast, calyculin-A (CLA) and okadaic acid (OA), known cell permeable inhibitors of protein phosphatase-1 and 2A, increased the level of resting [Ca2+]i and suppressed cell migration and wound healing of HaCaT cells. Furthermore, neither CLA nor OA influenced how scratching affected Ca2+ oscillations. It is assumed that changes in and alterations of the phosphorylation level of Ca2+-transport and contractile proteins upon phosphatase inhibition mediates cell migration and wound healing. PMID:23646108

  8. The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug-induced rhythmic contractions in the rat vas deferens.

    PubMed Central

    Hay, D. W.; Wadsworth, R. M.

    1983-01-01

    In the rat isolated vas deferens, methoxamine 8.1 microM produced an initial phasic response that declined towards baseline and was followed by rhythmic contractions that continued until wash-out. These responses were predominant in the epididymal half. BaCl2 1 mM produced a similar type of response which was not mediated by noradrenaline release or activation of alpha-adrenoceptors. The barium responses were similar in the epididymal and prostatic halves. Incubation in nominally Ca2+-free solution caused abolition or near abolition of rhythmic contractions produced by barium or methoxamine. The initial phasic response to methoxamine was abolished in Ca2+-free solution, whereas that produced by barium persisted. Rhythmic contractions produced by methoxamine or barium were inhibited by Mg2+ (2.4-20 mM) and by La3+ (1-5 mM). Mg2+ had selectivity for inhibition of the frequency of methoxamine- but not barium-induced rhythmic contractions. Despite their dependence on [Ca2+]o, barium- and methoxamine-induced rhythmic contractions were resistant to inhibition by calcium channel inhibitors. Verapamil, nifedipine and flunarazine inhibited the amplitude of rhythmic contractions more readily than the frequency (methoxamine IC50 for verapamil: amplitude = 29.8 +/- 5.40 microM, n = 6, frequency = 96.7 +/- 31.0 microM, n = 5, for nifedipine: amplitude = 2.42 +/- 0.34 microM, n = 7, frequency = 3.24 +/- 0.75 microM, n = 7, and for flunarizine: amplitude = 15.9 +/- 5.95 microM, n = 7, frequency = 153 +/- 28.6 microM, n = 7). There was no differentiation between inhibition of methoxamine and barium-induced responses. Like Mg2+, methoxyverapamil selectively inhibited the frequency of methoxamine-induced contractions (IC50: amplitude = 16.8 +/- 2.86 microM, n = 5, frequency = 2.07 +/- 0.81 microM, n = 5) but not barium-induced contractions (IC50: amplitude = 13.9 +/- 1.95 microM, n = 5, frequency = 48.5 +/- 8.98 microM, n = 5). Diazoxide (43.3-2167 microM) and nitroprusside (3

  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. High potency inhibition of hERG potassium channels by the sodium–calcium exchange inhibitor KB-R7943

    PubMed Central

    Cheng, Hongwei; Zhang, Yihong; Du, Chunyun; Dempsey, Christopher E; Hancox, Jules C

    2012-01-01

    BACKGROUND AND PURPOSE KB-R7943 is an isothiourea derivative that is used widely as a pharmacological inhibitor of sodium–calcium exchange (NCX) in experiments on cardiac and other tissue types. This study investigated KB-R7943 inhibition of hERG (human ether-à-go-go-related gene) K+ channels that underpin the cardiac rapid delayed rectifier potassium current, IKr. EXPERIMENTAL APPROACH Whole-cell patch-clamp measurements were made of hERG current (IhERG) carried by wild-type or mutant hERG channels and of native rabbit ventricular IKr. Docking simulations utilized a hERG homology model built on a MthK-based template. KEY RESULTS KB-R7943 inhibited both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ∼89 and ∼120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. Marked IhERG inhibition also occurred under ventricular action potential voltage clamp. IhERG inhibition by KB-R7943 exhibited both time- and voltage-dependence but showed no preference for inactivated over activated channels. Results of alanine mutagenesis and docking simulations indicate that KB-R7943 can bind to a pocket formed of the side chains of aromatic residues Y652 and F656, with the compound's nitrobenzyl group orientated towards the cytoplasmic side of the channel pore. The structurally related NCX inhibitor SN-6 also inhibited IhERG, but with a markedly reduced potency. CONCLUSIONS AND IMPLICATIONS KB-R7943 inhibits IhERG/IKr with a potency that exceeds that reported previously for acute cardiac NCX inhibition. Our results also support the feasibility of benzyloxyphenyl-containing NCX inhibitors with reduced potential, in comparison with KB-R7943, to inhibit hERG. PMID:21950687

  12. Interdomain communication in calcium pump as revealed in the crystal structures with transmembrane inhibitors

    PubMed Central

    Takahashi, Mihoko; Kondou, Youhei; Toyoshima, Chikashi

    2007-01-01

    Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum is an ATP-driven Ca2+ pump consisting of three cytoplasmic domains and 10 transmembrane helices. In the absence of Ca2+, the three cytoplasmic domains gather to form a compact headpiece, but the ATPase is unstable without an inhibitor. Here we describe the crystal structures of Ca2+-ATPase in the absence of Ca2+ stabilized with cyclopiazonic acid alone and in combination with other inhibitors. Cyclopiazonic acid is located in the transmembrane region of the protein near the cytoplasmic surface. The binding site partially overlaps with that of 2,5-di-tert-butyl-1,4-dihydroxybenzene but is separate from that of thapsigargin. The overall structure is significantly different from that stabilized with thapsigargin: The cytoplasmic headpiece is more upright, and the transmembrane helices M1–M4 are rearranged. Cyclopiazonic acid primarily alters the position of the M1′ helix and thereby M2 and M4 and then M5. Because M5 is integrated into the phosphorylation domain, the whole cytoplasmic headpiece moves. These structural changes show how an event in the transmembrane domain can be transmitted to the cytoplasmic domain despite flexible links between them. They also reveal that Ca2+-ATPase has considerable plasticity even when fixed by a transmembrane inhibitor, presumably to accommodate thermal fluctuations. PMID:17389383

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

    PubMed Central

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

    2014-01-01

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

  14. National Survey of ACE Programs.

    ERIC Educational Resources Information Center

    Constantino, Ernesto A.

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

  15. Epinephrine impairs insulin release by a mechanism distal to calcium mobilization. Similarity to lipoxygenase inhibitors

    SciTech Connect

    Metz, S.A.

    1988-01-01

    The mechanisms that enable epinephrine (EPI) and lipoxygenase inhibitors to impede insulin secretion are unknown. We examined the possibility that EPI inhibits Ca/sup 2 +/ fluxes as its major mechanism by studying /sup 45/Ca efflux from prelabeled, intact rat islets. EPI (2.5 x 10(-7) to 1 x 10(-5) M) inhibited insulin release induced by the influx of extracellular Ca/sup 2 +/ (46 mM K+) or the mobilization of intracellular Ca/sup 2 +/ stores (2 mM Ba/sup 2 +/), but it did not reduce the /sup 45/Ca efflux stimulated by either agonist. EPI also nullified insulin release induced by isobutylmethylxanthine or dibutyryl cAMP, with minimal or no effects on /sup 45/Ca efflux, and blocked the insulinotropic effects of 12-O-tetradecanoylphorbol-13-acetate (a direct activator of protein kinase C), which is believed primarily to sensitize the exocytotic apparatus to Ca/sup 2 +/ without mobilizing additional Ca/sup 2 +/. Previously we reported that similar effects were induced by inhibitors of pancreatic islet lipoxygenase. In this study, however, pretreatment with either the alpha 2-adrenergic antagonist yohimbine or pertussis toxin did not block the effects of lipoxygenase inhibitors, although either agent did block the effects of EPI. Thus, EPI, via an alpha 2-receptor mechanism, is able to reduce exocytosis largely distal to, or independent of, changes in Ca/sup 2 +/ flux, cAMP formation or its Ca/sup 2 +/-mobilizing action, or generation of protein kinase C activators. Therefore, EPI may reduce the sensitivity of the exocytotic apparatus to Ca/sup 2 +/. Inhibition of islet lipoxygenase may have a similar effect; however, in this case, the effect would have to be unrelated, or distal, to stimulation of alpha 2-receptors.

  16. The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels

    SciTech Connect

    King, Taj D.; Gandy, Johanna C.; Bijur, Gautam N. . E-mail: gautam@uab.edu

    2006-11-01

    The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is constitutively active, however its activity is markedly diminished following phosphorylation of Ser21 of GSK3{alpha} and Ser9 of GSK3{beta}. Although several kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively much less is known about the mechanisms that cause the dephosphorylation of GSK3 at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH-SY5Y cells, which increases intracellular calcium concentrations caused a transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3 at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and significantly blocked the KCl-induced dephosphorylation of GSK3{beta}, but not GSK3{alpha}. The phosphorylation of Akt was not affected by the overexpression of inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of cells with the GSK3 inhibitors lithium and SB216763 increased the levels of SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels.

  17. The effects of bepridil, compared with calcium-channel inhibitors and calmodulin antagonists on both spontaneous activity and contractions induced by potassium or phenylephrine in rat portal vein.

    PubMed

    Campbell, J K; Winslow, E; Marshall, R J

    1986-12-16

    Bepridil is known to block calcium channels in some vascular tissues. Recent work has shown that bepridil also antagonises calmodulin. The present study attempted to more fully characterize the vasodilator actions of bepridil by comparing it with the known calcium channel blocking drugs, nifedipine, diltiazem, verapamil and flunarizine, the calmodulin inhibitors, trifluoperazine and W7 and propylmethylenedioxyindene, which is thought to act intracellularly, on rat portal vein. The relative activities of the test drugs were compared on spontaneous activity and on all components of the contractile responses to potassium and phenylephrine. Bepridil inhibited all components of the potassium and phenylephrine responses equally, actions similar to those of the intracellular acting drugs. The exception to this was trifluoperazine which also exerted alpha-adrenoceptor blocking actions. In contrast the calcium channel blocking drugs, with the exception of verapamil, inhibited the tonic component of both spasmogen responses more than the phasic component. Bepridil like the intracellular acting drugs, but unlike the calcium channel blockers, markedly increased the frequency of spontaneous contractions whilst reducing amplitude. It is concluded that the profile of bepridil on rat portal vein more closely resembles that of intracellularly acting drugs than that of classical calcium channel inhibitors. PMID:3493163

  18. Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors.

    PubMed

    Pande, Jyoti; Grover, Ashok K

    2005-01-01

    Plasma membrane Ca2+ pumps (PMCA pumps) are Ca2+-Mg2+ ATPases that expel Ca2+ from the cytosol to extracellular space and are pivotal to cell survival and function. PMCA pumps are encoded by the genes PMCA1, -2, -3, and -4. Alternative splicing results in a large number of isoforms that differ in their kinetics and activation by calmodulin and protein kinases A and C. Expression by 4 genes and a multifactorial regulation provide redundancy to allow for animal survival despite genetic defects. Heterozygous mice with ablation of any of the PMCA genes survive and only the homozygous mice with PMCA1 ablation are embryolethal. Some PMCA isoforms may also be involved in other cell functions. Biochemical and biophysical studies of PMCA pumps have been limited by their low levels of expression. Delineation of the exact physiological roles of PMCA pumps has been difficult since most cells also express sarco/endoplasmic reticulum Ca2+ pumps and a Na+-Ca2+-exchanger, both of which can lower cytosolic Ca2+. A major limitation in the field has been the lack of specific inhibitors of PMCA pumps. More recently, a class of inhibitors named caloxins have emerged, and these may aid in delineating the roles of PMCA pumps. PMID:16333376

  19. 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

  20. Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients.

    PubMed

    López, Esther; Berna-Erro, Alejandro; Bermejo, Nuria; Brull, José María; Martinez, Rocío; Garcia Pino, Guadalupe; Alvarado, Raul; Salido, Ginés María; Rosado, Juan Antonio; Cubero, Juan José; Redondo, Pedro Cosme

    2013-05-01

    The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long-term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura-2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time-dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long-term administration of rapamycin to kidney transplant patients evokes alteration in platelet function. PMID:23577651

  1. Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by Toxoplasma gondii

    PubMed Central

    Lourido, Sebastian; Zhang, Chao; Lopez, Michael; Tang, Keliang; Barks, Jennifer; Wang, Qiuling; Wildman, Scott A.; Shokat, Kevan M.; Sibley, L. David

    2013-01-01

    Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogs in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vitro (low μM EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis, and perhaps related parasitic diseases. PMID:23470217

  2. Optimization of an Imidazopyridazine Series of Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 (PfCDPK1)

    PubMed Central

    2014-01-01

    A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less than 10 nM and in vitroP. falciparum antiparasite EC50 values down to 12 nM, although these compounds did not have suitable ADME properties to show in vivo efficacy in a mouse model. Structural modifications designed to address the ADME issues, in particular permeability, were initially accompanied by losses in antiparasite potency, but further optimization allowed a good balance in the compound profile to be achieved. Upon testing in vivo in a murine model of efficacy against malaria, high levels of compound exposure relative to their in vitro activities were achieved, and the modest efficacy that resulted raises questions about the level of effect that is achievable through the targeting of PfCDPK1. PMID:24689770

  3. Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain.

    PubMed

    Vink, S; Alewood, P F

    2012-11-01

    Chronic pain affects approximately 20% of people worldwide and places a large economic and social burden on society. Despite the availability of a range of analgesics, this condition is inadequately treated, with complete alleviation of symptoms rarely occurring. In the past 30 years, the voltage-gated calcium channels (VGCCs) have been recognized as potential targets for analgesic development. Although the majority of the research has been focused on Ca(v) 2.2 in particular, other VGCC subtypes such as Ca(v) 3.2 have recently come to the forefront of analgesic research. Venom peptides from marine cone snails have been proven to be a valuable tool in neuroscience, playing a major role in the identification and characterization of VGCC subtypes and producing the first conotoxin-based drug on the market, the ω-conotoxin, ziconotide. This peptide potently and selectively inhibits Ca(v) 2.2, resulting in analgesia in chronic pain states. However, this drug is only available via intrathecal administration, and adverse effects and a narrow therapeutic window have limited its use in the clinic. Other Ca(v) 2.2 inhibitors are currently in development and offer the promise of an improved route of administration and safety profile. This review assesses the potential of targeting VGCCs for analgesic development, with a main focus on conotoxins that block Ca(v) 2.2 and the developments made to transform them into therapeutics. PMID:22725651

  4. 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 ...

  5. 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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. 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

  9. TMEM16A Inhibitors Reveal TMEM16A as a Minor Component of Calcium-activated Chloride Channel Conductance in Airway and Intestinal Epithelial Cells*

    PubMed Central

    Namkung, Wan; Phuan, Puay-Wah; Verkman, A. S.

    2011-01-01

    TMEM16A (ANO1) functions as a calcium-activated chloride channel (CaCC). We developed pharmacological tools to investigate the contribution of TMEM16A to CaCC conductance in human airway and intestinal epithelial cells. A screen of ∼110,000 compounds revealed four novel chemical classes of small molecule TMEM16A inhibitors that fully blocked TMEM16A chloride current with an IC50 < 10 μm, without interfering with calcium signaling. Following structure-activity analysis, the most potent inhibitor, an aminophenylthiazole (T16Ainh-A01), had an IC50 of ∼1 μm. Two distinct types of inhibitors were identified. Some compounds, such as tannic acid and the arylaminothiophene CaCCinh-A01, fully inhibited CaCC current in human bronchial and intestinal cells. Other compounds, including T16Ainh-A01 and digallic acid, inhibited total CaCC current in these cells poorly, but blocked mainly an initial, agonist-stimulated transient chloride current. TMEM16A RNAi knockdown also inhibited mainly the transient chloride current. In contrast to the airway and intestinal cells, all TMEM16A inhibitors fully blocked CaCC current in salivary gland cells. We conclude that TMEM16A carries nearly all CaCC current in salivary gland epithelium, but is a minor contributor to total CaCC current in airway and intestinal epithelia. The small molecule inhibitors identified here permit pharmacological dissection of TMEM16A/CaCC function and are potential development candidates for drug therapy of hypertension, pain, diarrhea, and excessive mucus production. PMID:21084298

  10. Dendritic Glycopolymer as Drug Delivery System for Proteasome Inhibitor Bortezomib in a Calcium Phosphate Bone Cement: First Steps Toward a Local Therapy of Osteolytic Bone Lesions.

    PubMed

    Striegler, Christin; Schumacher, Matthias; Effenberg, Christiane; Müller, Martin; Seckinger, Anja; Schnettler, Reinhard; Voit, Brigitte; Hose, Dirk; Gelinsky, Michael; Appelhans, Dietmar

    2015-09-01

    Establishment of drug delivery system (DDS) in bone substitute materials for local treatment of bone defects still requires ambitious solutions for a retarded drug release. We present two novel DDS, a weakly cationic dendritic glycopolymer and a cationic polyelectrolyte complex, composed of dendritic glycopolymer and cellulose sulfate, for the proteasome inhibitor bortezomib. Both DDS are able to induce short-term retarded release of bortezomib from calcium phosphate bone cement in comparison to a burst-release of the drug from bone cement alone. Different release parameters have been evaluated to get a first insight into the release mechanism from bone cements. In addition, biocompatibility of the calcium phosphate cement, modified with the new DDS was investigated using human mesenchymal stromal cells. PMID:26018141

  11. 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

  12. Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels.

    PubMed

    Swensen, Andrew M; Herrington, James; Bugianesi, Randal M; Dai, Ge; Haedo, Rodolfo J; Ratliff, Kevin S; Smith, McHardy M; Warren, Vivien A; Arneric, Stephen P; Eduljee, Cyrus; Parker, David; Snutch, Terrance P; Hoyt, Scott B; London, Clare; Duffy, Joseph L; Kaczorowski, Gregory J; McManus, Owen B

    2012-03-01

    Biological, genetic, and clinical evidence provide validation for N-type calcium channels (Ca(V)2.2) as therapeutic targets for chronic pain. A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. Supporting this notion, we recently reported that in preclinical models, the state-dependent Ca(V)2 inhibitor (3R)-5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (TROX-1) has an improved therapeutic window compared with ziconotide. Here we characterize TROX-1 inhibition of Cav2.2 channels in more detail. When channels are biased toward open/inactivated states by depolarizing the membrane potential under voltage-clamp electrophysiology, TROX-1 inhibits Ca(V)2.2 channels with an IC(50) of 0.11 μM. The voltage dependence of Ca(V)2.2 inhibition was examined using automated electrophysiology. TROX-1 IC(50) values were 4.2, 0.90, and 0.36 μM at -110, -90, and -70 mV, respectively. TROX-1 displayed use-dependent inhibition of Ca(V)2.2 with a 10-fold IC(50) separation between first (27 μM) and last (2.7 μM) pulses in a train. In a fluorescence-based calcium influx assay, TROX-1 inhibited Ca(V)2.2 channels with an IC(50) of 9.5 μM under hyperpolarized conditions and 0.69 μM under depolarized conditions. Finally, TROX-1 potency was examined across the Ca(V)2 subfamily. Depolarized IC(50) values were 0.29, 0.19, and 0.28 μM by manual electrophysiology using matched conditions and 1.8, 0.69, and 1.1 μM by calcium influx for Ca(V)2.1, Ca(V)2.2, and Ca(V)2.3, respectively. Together, these in vitro data support the idea that a state-dependent, non-subtype-selective Ca(V)2 channel inhibitor can achieve an improved therapeutic window over the relatively state-independent Ca(V)2.2-selective inhibitor ziconotide in preclinical models of chronic pain. PMID:22188924

  13. The effects of intraganglionic injection of calcium/calmodulin-dependent protein kinase II inhibitors on pain-related behavior in diabetic neuropathy.

    PubMed

    Jelicic Kadic, A; Boric, M; Kostic, S; Sapunar, D; Puljak, L

    2014-01-01

    Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transmission of nociceptive input in diabetic neuropathy. The aim of this study was to test whether intraganglionic (i.g.) injection of CaMKII inhibitors may alleviate pain-related behavior in diabetic rats. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin intraperitoneally. Two weeks after diabetes induction, CaMKII inhibitors myristoil-AIP and KN93 were injected directly into the right L5 dorsal root ganglion (DRG). Behavioral testing with mechanical and thermal stimuli was performed before induction of diabetes, the day preceding the injection, as well as 2 and 24h after the i.g. injection. The expression of total CaMKII and its alpha isoform in DRG neurons was analyzed using immunohistochemistry. CaMKII inhibitors attenuated pain-related behavior in a modality-specific fashion. Attenuation of nociceptive behavior was accompanied with a corresponding decrease of CaMKII alpha expression in DRG neurons on the side of injection. A significant decrease of CaMKII alpha expression was seen in small- and medium-sized neurons. In conclusion, our study provides evidence that CaMKII inhibitors are potential pharmacological agents that should be further explored for treatment of diabetic neuropathy symptoms. PMID:24161721

  14. Enhancement of metallothionein gene expression in male Wistar (WF/NCr) rats by treatment with calmodulin inhibitors: potential role of calcium regulatory pathways in metallothionein induction.

    PubMed

    Shiraishi, N; Waalkes, M P

    1994-03-01

    Recent reports indicate that calmodulin inhibitors (CIs) can modify cadmium toxicity in rodents. For instance, pretreatment with CIs prevents cadmium-induced testicular damage in mice and substantially reduces such damage in rats, the latter effect coinciding with significant alterations in cadmium distribution. Although the basis of these effects is unclear, it is frequently observed that metal-binding proteins such as metallothionein (MT) are involved in acquired tolerance to cadmium and this could be true of tolerance induced by CIs. Thus, we examined the effects of various CIs on MT gene expression. Treatment of WF/NCr rats with known CIs, including trifluoperazine (TPZ), N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), calmidazolium (CMZ), chlorpromazine (CPZ), and the calcium ionophore, A23187, increased hepatic MT gene expression, as assessed by mRNA levels, in all cases. Furthermore, hepatic MT protein levels were 40 to 180 micrograms MT/g wet wt (g ww) in rats treated with CIs or A23187 compared to control levels of 10 micrograms MT/g ww. Treatment with CPZ and CMZ did not increase renal MT protein after exposure, although increases in renal MT mRNA were observed. However, the CIs TPZ and W7 and the calcium ionophore increased both renal MT protein and MT mRNA levels. In contrast, no increases in testicular MT mRNA or the testicular cadmium binding protein (TCBP) levels were seen with any of the treatments. Treatment with CIs or A23187 produced increases in zinc levels in the liver, but not in the kidneys or testes. These results indicate that CIs, such as TPZ, W7, CMZ, and CPZ, as well as the calcium ionophore A23187, have a marked stimulatory effect on hepatic and renal MT gene expression and that calcium regulatory pathways may play an important role in this induction of MT. PMID:8128501

  15. 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.

  16. The Dual Role of Fibrinogen as Inhibitor and Nucleator of Calcium Phosphate Phases: The Importance of Structure.

    PubMed

    Tsortos; Ohki; Zieba; Baier; Nancollas

    1996-01-15

    Constant composition and free drift methods have been used to investigate the abilities of human serum albumin (HSA) and fibrinogen to influence calcium phosphate precipitation. Both molecules inhibit hydroxyapatite (HAP) crystal growth when present in the solution phase. Fibrinogen, when immobilized at hydrophobicized germanium or silica surfaces, is able to nucleate calcium phosphate phases; at clean germanium or silica surfaces, it appears to be inactive. The apparent configuration of fibrinogen molecules at germanium or silica surfaces on which octadecyltrichlorosilane (OTS) was deposited probably exposes more negative sites for participation in nucleation. PMID:10479440

  17. Bromoenol Lactone, an Inhibitor of Calcium-Independent Phospholipase A2, Suppresses Carrageenan-Induced Prostaglandin Production and Hyperalgesia in Rat Hind Paw

    PubMed Central

    Tsuchida, Keiichiro; Ibuki, Takae; Matsumura, Kiyoshi

    2015-01-01

    Prostaglandin (PG) E2 and PGI2 are essential to hyperalgesia in inflammatory tissues. These prostaglandins are produced from arachidonic acid, which is cleaved from membrane phospholipids by the action of phospholipase A2 (PLA2). Which isozyme of PLA2 is responsible for the cleavage of arachidonic acid and the production of prostaglandins essential to inflammation-induced hyperalgesia is not clear. In this study, we examined the effects of two PLA2 isozyme-specific inhibitors on carrageenan-induced production of PGE2 and PGI2 in rat hind paw and behavioral nociceptive response to radiant heat. Local administration of bromoenol lactone (BEL), an inhibitor of calcium-independent PLA2 (iPLA2), significantly reduced carrageenan-induced elevation of prostaglandins in the inflamed foot pad 3 h after injection. It also ameliorated the hyperalgesic response between 1 h and 3 h after carrageenan injection. On the other hand, AACOCF3, an inhibitor of cytosolic PLA2, suppressed neither prostaglandin production nor the hyperalgesic response. BEL did not suppress the mRNA levels of iPLA2β, iPLA2γ, cyclooxygenase-2, microsomal prostaglandin E synthase, prostaglandin I synthase, or proinflammatory cytokines in the inflamed foot pad, indicating that BEL did not suppress inflammation itself. These results suggest that iPLA2 is involved in the production of prostaglandins and hyperalgesia at the inflammatory loci. PMID:26063975

  18. 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.

  19. Calcium antagonists.

    PubMed

    Grossman, Ehud; Messerli, Franz H

    2004-01-01

    Calcium antagonists were introduced for the treatment of hypertension in the 1980s. Their use was subsequently expanded to additional disorders, such as angina pectoris, paroxysmal supraventricular tachycardias, hypertrophic cardiomyopathy, Raynaud phenomenon, pulmonary hypertension, diffuse esophageal spasms, and migraine. Calcium antagonists as a group are heterogeneous and include 3 main classes--phenylalkylamines, benzothiazepines, and dihydropyridines--that differ in their molecular structure, sites and modes of action, and effects on various other cardiovascular functions. Calcium antagonists lower blood pressure mainly through vasodilation and reduction of peripheral resistance. They maintain blood flow to vital organs, and are safe in patients with renal impairment. Unlike diuretics and beta-blockers, calcium antagonists do not impair glucose metabolism or lipid profile and may even attenuate the development of arteriosclerotic lesions. In long-term follow-up, patients treated with calcium antagonists had development of less overt diabetes mellitus than those who were treated with diuretics and beta-blockers. Moreover, calcium antagonists are able to reduce left ventricular mass and are effective in improving anginal pain. Recent prospective randomized studies attested to the beneficial effects of calcium antagonists in hypertensive patients. In comparison with placebo, calcium antagonist-based therapy reduced major cardiovascular events and cardiovascular death significantly in elderly hypertensive patients and in diabetic patients. In several comparative studies in hypertensive patients, treatment with calcium antagonists was equally effective as treatment with diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors. From these studies, it seems that a calcium antagonist-based regimen is superior to other regimens in preventing stroke, equivalent in preventing ischemic heart disease, and inferior in preventing congestive heart failure

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

    ERIC Educational Resources Information Center

    Saunders, John

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

  1. 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

  2. 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

  3. Transdermal delivery of Angiotensin Converting Enzyme inhibitors.

    PubMed

    Helal, Fouad; Lane, Majella E

    2014-09-01

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

  4. ACE program/UNIX user manual

    SciTech Connect

    Feng-Berman, S.K.

    1993-01-12

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

  5. ACE program/UNIX user manual

    SciTech Connect

    Feng-Berman, S.K.

    1993-01-12

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

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

    PubMed

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

    2015-06-01

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

  7. 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.

  8. 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 ...

  9. Calcium supplements

    MedlinePlus

    ... TYPES OF CALCIUM SUPPLEMENTS Forms of calcium include: Calcium carbonate: Over-the-counter (OTC) antacid products, such as Tums and Rolaids, contain calcium carbonate. These sources of calcium do not cost much. ...

  10. Drugs Which Inhibit Osteoclast Function Suppress Tumor Growth through Calcium Reduction in Bone

    PubMed Central

    Li, Xin; Liao, Jinhui; Park, Serk In; Koh, Amy J; Sadler, William D; Pienta, Kenneth J; Rosol, Thomas J; McCauley, Laurie K

    2011-01-01

    Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear. Calcium is released during bone resorption and the calcium sensing receptor is an important regulator of cancer cell proliferation. The goal of this investigation was to elucidate the role of calcium released during bone resorption and to determine the impact of drugs which suppress bone resorption on tumor growth in bone. To compare tumor growth in a skeletal versus non-skeletal site, equal numbers of canine prostate cancer cells expressing luciferase (ACE-1luc) prostate cancer cells were inoculated into a simple collagen matrix, neonatal mouse vertebrae (vossicles), human de-proteinized bone, or a mineralized collagen matrix. Implants were placed subcutaneously into athymic mice. Luciferase activity was used to track tumor growth weekly and at one month tumors were dissected for histologic analysis. Luciferase activity and tumor size were greater in vossicles, de-proteinized bone and mineralized collagen matrix versus non-mineralized collagen implants. The human osteoblastic prostate carcinoma cell line C4-2b also grew better in a mineral rich environment with a greater proliferation of C4-2b cells reflected by Ki-67 staining. Zoledronic acid (ZA), a bisphosphonate, and recombinant OPG-Fc, a RANKL inhibitor, were administered to mice bearing vertebral implants (vossicles) containing ACE-1 osteoblastic prostate cancer cells. Vossicles or collagen matrices were seeded with ACE-1luc cells subcutaneously in athymic mice (2 vossicles, 2 collagen implants/mouse). Mice received ZA (5μg/mouse, twice/week), (OPG-Fc at 10mg/kg, 3 times/week) or vehicle, and luciferase activity was measured weekly. Histologic analysis of the tumors

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

    PubMed

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

    2013-07-01

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

  12. Intra-nucleus accumbens administration of the calcium/calmodulin-dependent protein kinase II inhibitor AIP induced antinociception in rats with mononeuropathy.

    PubMed

    Bian, Hui; Yu, Long-Chuan

    2015-07-10

    Calcium/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine- dependent protein kinase, which has been implicated in pain modulation at different levels of the central nervous system. The present study was performed in rats with mononeuropathy induced by left common sciatic nerve ligation. Unilateral sciatic nerve loose ligation produced decreases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation. Intra-nucleus accumbens (NAc) injection of 3 μg, 6 μg and 12 μg of myristoylated autocamtide-2-inhibitory peptide (AIP), the CaMKII inhibitor, dose-dependently increased the HWL to noxious thermal and mechanical stimulation in rats with mononeuropathy. Furthermore, intra-NAc administration of morphine, the HWL to noxious thermal and mechanical stimulation increased markedly, and there were no significant differences between morphine group and AIP group. Taken together, the results showed that intra-NAc injection of AIP induced significant antinociceptive effects in rats with mononeuropathy, indicating that CaMKII may play an important role in the transmission and/or modulation of nociceptive information in the NAc in rats with mononeuropathy. PMID:26022629

  13. Effects of inhibitors of eicosanoid synthesis in the uterus of ovariectomized rats and rats in natural oestrus: relation with calcium.

    PubMed

    Cantabrana, B; Baamonde, A; Andres-Trelles, F; Hidalgo, A

    1990-01-01

    1. The effects of 4 inhibitors of eicosanoid synthesis (ESIs)--mepacrine (MEP, 10(-5) - 3 x 10(-4) M), nordihydroguaiaretic acid (NDHGA, 10(-6) - 2 x 10(-5) M), indomethacin (IND, 2 x 10(-6) M and 2 x 10(-5) M) and imidazole (IMI, 10(-5) M and 10(-4) M)--on the motility induced by oxytocin (OT, 0.5 and 4 mU/ml) in uterus of rats in natural oestrus and of ovariectomized rats have been studied. 2. MEP, NDHGA and IND, but not IMI, inhibited the motility induced by both concentrations of OT in natural oestrus. Ovariectomy enhanced the effects of all ESIs, except the one of MEP. 3. MEP and NDHGA, but not IND or IMI, inhibited the contractions induced by methacholine (10(-5) M) and prostaglandin F2a (10(-6) M) and relaxed in a dose-dependent way the tonic component of the contractile response to KCl 60 mM (DI50: 6.14 +/- 0.38 and 1.38 +/- 0.29 x 10(-5) M, respectively). 4. CaCl2 (0.1-10 mM) reverted the relaxation of KCl contractions produced by MEP but not by NDHGA. PMID:2298392

  14. ω-Tbo-IT1–New Inhibitor of Insect Calcium Channels Isolated from Spider Venom

    PubMed Central

    Mikov, Alexander N.; Fedorova, Irina M.; Potapieva, Natalia N.; Maleeva, Ekaterina E.; Andreev, Yaroslav A.; Zaitsev, Alexey V.; Kim, Kira K.; Bocharov, Eduard V.; Bozin, Timur N.; Altukhov, Dmitry A.; Lipkin, Alexey V.; Kozlov, Sergey A.; Tikhonov, Denis B.; Grishin, Eugene V.

    2015-01-01

    Novel disulfide-containing polypeptide toxin was discovered in the venom of the Tibellus oblongus spider. We report on isolation, spatial structure determination and electrophysiological characterization of this 41-residue toxin, called ω-Tbo-IT1. It has an insect-toxic effect with LD50 19 μg/g in experiments on house fly Musca domestica larvae and with LD50 20 μg/g on juvenile Gromphadorhina portentosa cockroaches. Electrophysiological experiments revealed a reversible inhibition of evoked excitatory postsynaptic currents in blow fly Calliphora vicina neuromuscular junctions, while parameters of spontaneous ones were not affected. The inhibition was concentration dependent, with IC50 value 40 ± 10 nM and Hill coefficient 3.4 ± 0.3. The toxin did not affect frog neuromuscular junctions or glutamatergic and GABAergic transmission in rat brains. Ca2+ currents in Calliphora vicina muscle were not inhibited, whereas in Periplaneta americana cockroach neurons at least one type of voltage gated Ca2+ current was inhibited by ω-Tbo-IT1. Thus, the toxin apparently acts as an inhibitor of presynaptic insect Ca2+ channels. Spatial structure analysis of the recombinant ω-Tbo-IT1 by NMR spectroscopy in aqueous solution revealed that the toxin comprises the conventional ICK fold containing an extended β-hairpin loop and short β-hairpin loop which are capable of making “scissors-like mutual motions”. PMID:26611444

  15. General relativistic observables for the ACES experiment

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  16. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  18. Crystal structure and bonding analysis of the first dinuclear calcium(II)-proton-pump inhibitor (PPI) `butterfly molecule': a combined microcrystal synchrotron and DFT study.

    PubMed

    Cong, Hengjiang

    2016-04-01

    Proton-pump inhibitors (PPI) are prodrugs used widely to treat acid-related diseases since the late 1980s. After an extensive research effort it has become clear that the fundamental interactions between metal atoms and PPIs are of paramount importance for both drug release and long-term therapeutic safety. Unfortunately, until now, very little information has been available on this topic. In this paper, we report the crystal structure analysis of a novel calcium-PPI compound incorporating bridging and terminal deprotonated (R)-rabeprazole tricyclic ligands (L), namely bis[μ-(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]bis{dimethanol[(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]calcium(II)} methanol hexasolvate, [Ca2(C20H22N3O4S)4(CH3OH)4]·6CH3OH or [Ca2(L)4(CH3OH)4]·6CH3OH, which crystallizes from methanol in the polar C2 space group. Using low-temperature microcrystal synchrotron radiation, we demonstrate that this compound is in the form of a beautiful `butterfly molecule', consisting of a C2-symmetric dinuclear (CH3OH)2LCa(II)(μ2-L)2Ca(II)L(HOCH3)2 framework. A large amount of disorder is found within the bridging L ligand and the conformation of the fused tetrahydrofuran ring exhibits great variety. All the sulfinyl groups remain intact and the nonbonded Ca...Ca distance is significantly longer than in other calcium dimers, indicating steric hindrance in the bridging ligands. Considerable hydrogen bonding and aromatic C-H...π interactions co-operate to stabilize the whole complex, as well as to facilitate supramolecular assembly. Additional investigations into the bond nature were made using density functional theory (DFT) methods at the B3LYP/6-31G(d) level; geometry optimization, Mulliken atomic charges, MEP (molecular electrostatic potential), HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular

  19. Magnesium/Calcium Competition at Excitable Membranes.

    ERIC Educational Resources Information Center

    Belzer, Bill; Fry, Panni

    1998-01-01

    Considers some consequences of altering intracellular calcium supply by magnesium concentration changes. Focuses on using this procedure as an exercise with allied health students as they witness therapeutic uses of magnesium and other calcium entry inhibitors. (DDR)

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

    PubMed Central

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

    2016-01-01

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

  1. Protective effect of selected calcium channel blockers and prednisolone, a phospholipase-A2 inhibitor, against gentamicin and carbon tetrachloride-induced nephrotoxicity.

    PubMed

    Akindele, A J; Adeneye, A A; Olatoye, F; Benebo, A S

    2014-08-01

    The ameliorative effect of calcium channel blockers (CCBs) and a phospholipase-A2 inhibitor in drug-/chemical-induced nephrotoxicity was investigated. Rats were divided into 7 groups of 5 rats in each group. In the gentamicin model, group I rats were pretreated with normal saline (10 ml kg(-1)), while groups II-VII rats were pretreated with normal saline (10 ml kg(-1)), ascorbic acid (10 mg kg(-1)), nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)), respectively, perorally 1 h before intraperitoneal (i.p.) injection of gentamicin (40 mg kg(-1)) for 14 days. In the carbon tetrachloride (CCl4) model, rats were pretreated with CCBs and prednisolone for 7 days before inducing nephrotoxicity with 20% CCl4 (1.5 ml kg(-1)). Rats were thereafter killed and blood and tissue samples were collected for assessments. I.p. injections of gentamicin and CCl4 caused significant hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hyperchloremic alkalosis and reduced renal tissue levels of antioxidants. Also, significant reductions in the hemoglobin, packed cell volume, red blood cells, and platelet indices were observed. Pretreatments with nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)) significantly ameliorated the deleterious effects of gentamicin and CCl4 possibly via antioxidant and anti-lipoperoxidation mechanisms. The results obtained in this study suggest potential clinical usefulness of tested CCBs and prednisolone in drug-/chemical-induced nephrotoxicity. PMID:24220874

  2. Calcium - ionized

    MedlinePlus

    ... at both ionized calcium and calcium attached to proteins. You may need to have a separate ionized calcium test if you have factors that increase or decrease total calcium levels. These may include abnormal blood levels ...

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

    PubMed

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

    1993-01-01

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

  4. 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

  5. Remarks on KERMA Factors in ACE files

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  6. Calcium Oscillations

    PubMed Central

    Dupont, Geneviève; Combettes, Laurent; Bird, Gary S.; Putney, James W.

    2011-01-01

    Calcium signaling results from a complex interplay between activation and inactivation of intracellular and extracellular calcium permeable channels. This complexity is obvious from the pattern of calcium signals observed with modest, physiological concentrations of calcium-mobilizing agonists, which typically present as sequential regenerative discharges of stored calcium, a process referred to as calcium oscillations. In this review, we discuss recent advances in understanding the underlying mechanism of calcium oscillations through the power of mathematical modeling. We also summarize recent findings on the role of calcium entry through store-operated channels in sustaining calcium oscillations and in the mechanism by which calcium oscillations couple to downstream effectors. PMID:21421924

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

    PubMed

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

    1998-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. 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

  10. 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.

  11. 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.

  12. 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…

  13. 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…

  14. Treatment of Hypertension in Black Patients With Angiotensin-Converting Enzyme Inhibitors

    PubMed Central

    Shulman, Neil B.

    1988-01-01

    The prevalence of hypertension and the incidence of complications from uncontrolled elevated blood pressure in blacks is much greater than in the white population. In general, blacks have underlying differences in the factors relating to blood pressure level, including low plasma renin, and, in certain instances, a decreased ability to excrete sodium. The stepped-care approach in the management of the black hypertensive patient is similar to that taken with white patients, but racial differences in response to antihypertensive drugs exist that require careful consideration when choosing a treatment regimen. Thiazide diuretics are effective in blacks and are often used as initial therapy. Blacks tend to respond less well to β-blockers, but when combined with a diuretic, they are also effective. Encouraging data are available on the use of calcium channel blockers in blacks. When combined with a diuretic, the angiotensin-converting enzyme (ACE) inhibitors also provide an alternative to therapy for black patients. The use of low doses of ACE inhibitors has reduced the high incidence of adverse effects associated with this group of drugs in earlier studies. PMID:3280812

  15. 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

  16. [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

  17. 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.

  18. 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.

  19. The effect of clay minerals, pH, calcium and temperature on the adsorption of phosphonate scale inhibitor onto reservoir core and mineral separates

    SciTech Connect

    Jordan, M.M.; Sorbie, K.S.; Jiang, P.; Yuan, M.D.; Todd, A.C.; Thiery, L.

    1994-12-31

    During a scale inhibitor squeeze treatment, the dynamics of the inhibitor return is governed by the inhibitor/rock interaction. In the case of adsorption/desorption inhibitor treatments, this interaction is described through the inhibitor/rock adsorption isotherm. The rock mineralogy plays an important role in determining the nature of the adsorption isotherm and clays in particular are known to strongly affect the adsorption process. However, no previous work has (a) presented a systematic study of the effects of various clays on inhibitor adsorption and (b) clearly demonstrated the significance of this behavior for the squeeze process. It is the central objective of the work in this paper to carry out these tasks. In this paper, an extensive series of results from static bulk adsorption tests using pure mineral separates (quartz, kaolinite, chlorite and muscovite) as adsorbent and using phosphonate (DETPMP) as model inhibitor is presented. From these results, the order of importance of factors governing the phosphonate inhibitor level onto clays appears to be Temperature > pH > [Ca{sup 2+}]. To support the findings from the bulk adsorption tests, results from reservoir condition core floods are presented for reservoir rock from a North Sea field which contains significant quantities of clay (principally kaolinite). The field significance of these results for the inhibitor squeeze performance is demonstrated by using the field and outcrop isotherms in some model squeeze return calculations.

  20. Calcium Carbonate

    MedlinePlus

    Calcium carbonate is a dietary supplement used when the amount of calcium taken in the diet is not ... for healthy bones, muscles, nervous system, and heart. Calcium carbonate also is used as an antacid to relieve ...

  1. Calcium - urine

    MedlinePlus

    ... best treatment for the most common type of kidney stone , which is made of calcium. This type of ... the kidneys into the urine, which causes calcium kidney stones Sarcoidosis Taking too much calcium Too much production ...

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

    PubMed Central

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

    2014-01-01

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

  3. ACES-PHARAO : Microwave link data processing

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    PubMed

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

    2011-09-01

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

  5. Human Recombinant ACE2 Reduces the Progression of Diabetic Nephropathy

    PubMed Central

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

    2010-01-01

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

  6. Pharmacophore mapping based inhibitor selection and molecular interaction studies for identification of potential drugs on calcium activated potassium channel blockers, tamulotoxin

    PubMed Central

    Kumar, R. Barani; Suresh, M. Xavier

    2013-01-01

    Background: Tamulotoxin (TmTx) from Buthus tamulus was found to be a highly venomous toxin which accelerates the neurotransmitter release that directly affects the cardiovascular tissues and the respiratory system leading to death. TmTx from red Indian scorpion is a crucial inhibitor for Ca2+ activated K+ channel in humans. Objective: The study is aimed at the identification of potential inhibitors of TmTx through pharmacophore based inhibitor screening and understanding the molecular level interactions. Materials and Method: The potential inhibitors for TmTx were identified using pharmacophore model based descriptor information present in existing drugs with the analysis of pharmacokinetic properties. The compounds with good ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) descriptors were subjected to molecular interaction studies. The stability of bound toxin-inhibitor complex was studied using molecular dynamics simulation over a period of one nanosecond. Results: From a dataset of 3406 compounds, few compounds were selected as potential inhibitors based on the generated best pharmacophore models, pharmacokinetic analysis, molecular docking and molecular dynamics studies. Conclusion: In conclusion, two compounds containing better inhibition properties against TmTx are suggested to be better lead molecules for drug development in future and this study will help us to explore more inhibitors from natural origin against tamulotoxin. PMID:23772102

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

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

  8. 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%.

  9. 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

  10. 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

  11. Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na+/K+ ATPase on EDHF relaxations in the rat hepatic artery

    PubMed Central

    Andersson, David A; Zygmunt, Peter M; Movahed, Pouya; Andersson, Tomas L G; Högestätt, Edward D

    2000-01-01

    In the rat hepatic artery, the SKCa inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 μM) and d-tubocurarine (100 μM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM).The IKCa inhibitors clotrimazole (3 μM) and 2-chlorophenyl-bisphenyl-methanol (3 μM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 μM) had no effect in the presence of apamin.Ciclazindol (10 μM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated 86Rb+ influx via the Gardos channel (IKCa) in human erythrocytes.The Na+/K+ ATPase inhibitor ouabain (500 μM) and the KIR blocker Ba2+ (30 μM) neither alone nor in combination inhibited EDHF relaxations. Ba2+ was also without effect in the presence of either apamin or charybdotoxin.In contrast to EDHF, an increase in extracellular [K+] from 4.6 mM to 9.6, 14.6 and 19.6 mM inconsistently relaxed arteries. In K+-free physiological salt solution, re-admission of K+ always caused complete and sustained relaxations which were abolished by ouabain but unaffected by Ba2+.The present study provides pharmacological evidence for the involvement of SKCa and IKCa in the action of EDHF in the rat hepatic artery. Our results are not consistent with the idea that EDHF is K+ activating Na+/K+ ATPase and KIR in this blood vessel. PMID:10742306

  12. The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson’s Disease

    PubMed Central

    2011-01-01

    T-Type Ca2+ channel inhibitors hold tremendous therapeutic potential for the treatment of pain, epilepsy, sleep disorders, essential tremor, and other neurological disorders; however, a lack of truly selective tools has hindered basic research, and selective tools from the pharmaceutical industry are potentially burdened with intellectual property (IP) constraints. Thus, an MLPCN high-throughput screen (HTS) was conducted to identify novel T-type Ca2+ channel inhibitors free from IP constraints, and freely available through the MLPCN, for use by the biomedical community to study T-type Ca2+ channels. While the HTS provided numerous hits, these compounds could not be optimized to the required level of potency to be appropriate tool compounds. Therefore, a scaffold hopping approach, guided by SurflexSim, ultimately afforded ML218 (CID 45115620), a selective T-type Ca2+ (Cav3.1, Cav3.2, Cav3.3) inhibitor (Cav3.2, IC50 = 150 nM in Ca2+ flux; Cav3.2 IC50 = 310 nM; and Cav3.3 IC50 = 270 nM, respectively in patch clamp electrophysiology) with good DMPK properties, acceptable in vivo rat PK, and excellent brain levels. Electrophysiology studies in subthalamic nucleus (STN) neurons demonstrated robust effects of ML218 on the inhibition of T-type calcium current, inhibition of low threshold spike, and rebound burst activity. Based on the basal ganglia circuitry in Parkinson’s disease (PD), the effects of ML218 in STN neurons suggest a therapeutic role for T-type Ca2+ channel inhibitors, and ML218 was found to be orally efficacious in haloperidol-induced catalepsy, a preclinical PD model, with comparable efficacy to an A2A antagonist, a clinically validated PD target. ML218 proves to be a powerful new probe to study T-type Ca2+ function in vitro and in vivo, and freely available. PMID:22368764

  13. 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

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

    PubMed Central

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

    2009-01-01

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

  15. 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…

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

    ERIC Educational Resources Information Center

    Alt, Merilyn; Beatty, Dianne

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

  17. 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

  18. Calcium - urine

    MedlinePlus

    ... into the urine, which causes calcium kidney stones Sarcoidosis Taking too much calcium Too much production of ... Milk-alkali syndrome Proximal renal tubular acidosis Rickets Sarcoidosis Vitamin D Update Date 5/3/2015 Updated ...

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

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

  20. 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

  1. Calcium supplements

    MedlinePlus

    ... SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the human body. It helps build and protect your teeth ... absorb calcium. You can get vitamin D from sunlight exposure to your skin and from your diet. Ask your provider whether ...

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

    PubMed

    Pigman, E C; Scott, J L

    1993-07-01

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

  3. Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development

    PubMed Central

    Moon, Robert W.; Whalley, David; Bowyer, Paul W.; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K.; Howell, Steven A.; Grainger, Munira; Jones, Hayley M.; Ansell, Keith H.; Chapman, Timothy M.; Taylor, Debra L.; Osborne, Simon A.; Baker, David A.; Tatu, Utpal

    2015-01-01

    Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. PMID:26711771

  4. Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development.

    PubMed

    Green, Judith L; Moon, Robert W; Whalley, David; Bowyer, Paul W; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K; Howell, Steven A; Grainger, Munira; Jones, Hayley M; Ansell, Keith H; Chapman, Timothy M; Taylor, Debra L; Osborne, Simon A; Baker, David A; Tatu, Utpal; Holder, Anthony A

    2016-03-01

    Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. PMID:26711771

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

    PubMed

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

    2015-06-01

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

  6. 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.

  7. 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.

  8. Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder

    PubMed Central

    Umehara, Hidehiro; Numata, Shusuke; Tajima, Atsushi; Nishi, Akira; Nakataki, Masahito; Imoto, Issei; Sumitani, Satsuki; Ohmori, Tetsuro

    2016-01-01

    Background Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. Methods We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. Results While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. Conclusions Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients. PMID:27281126

  9. Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

    PubMed

    Namba, Masashi; Kim, Shokei; Zhan, Yumei; Nakao, Takafumi; Iwao, Hiroshi

    2002-05-01

    The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure. PMID:12135327

  10. Okadaic acid, a protein phosphatase inhibitor, blocks calcium changes, gene expression, and cell death induced by gibberellin in wheat aleurone cells.

    PubMed Central

    Kuo, A; Cappelluti, S; Cervantes-Cervantes, M; Rodriguez, M; Bush, D S

    1996-01-01

    The cereal aleurone functions during germination by secreting hydrolases, mainly alpha-amylase, into the starchy endosperm. Multiple signal transduction pathways exist in cereal aleurone cells that enable them to modulate hydrolase production in response to both hormonal and environmental stimuli. Gibberellic acid (GA) promotes hydrolase production, whereas abscisic acid (ABA), hypoxia, and osmotic stress reduce amylase production. In an effort to identify the components of transduction pathways in aleurone cells, we have investigated the effect of okadaic acid (OA), a protein phosphatase inhibitor, on stimulus-response coupling for GA, ABA, and hypoxia. We found that OA (100 nM) completely inhibited all the GA responses that we measured, from rapid changes in cytosolic Ca2+ through changes in gene expression and accelerated cell death. OA (100 nM) partially inhibited ABA responses, as measured by changes in the level of PHAV1, a cDNA for an ABA-induced mRNA in barley. In contrast, OA had no effect on the response to hypoxia, as measured by changes in cytosolic Ca2+ and by changes in enzyme activity and RNA levels of alcohol dehydrogenase. Our data indicate that OA-sensitive protein phosphatases act early in the transduction pathway of GA but are not involved in the response to hypoxia. These data provide a basis for a model of multiple transduction pathways in which the level of cytosolic Ca2+ is a key point of convergence controlling changes in stimulus-response coupling. PMID:8742711

  11. 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

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

    PubMed

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

    2015-11-01

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

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

    SciTech Connect

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

    1995-12-01

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

  14. Calcium in diet

    MedlinePlus

    ... of calcium dietary supplements include calcium citrate and calcium carbonate. Calcium citrate is the more expensive form of ... the body on a full or empty stomach. Calcium carbonate is less expensive. It is absorbed better by ...

  15. Calcium Test

    MedlinePlus

    ... as thyroid disease , parathyroid disorder , malabsorption , cancer, or malnutrition An ionized calcium test may be ordered when ... albumin , which can result from liver disease or malnutrition , both of which may result from alcoholism or ...

  16. Calcium Calculator

    MedlinePlus

    ... with Sarcopenia Skeletal Rare Disorders Data & Publications Facts and Statistics Vitamin D map Fracture Risk Map Hip Fracture ... Training Courses Working Groups Regional Audits Reports Facts and Statistics Popular content Calcium content of common foods What ...

  17. Calcium - ionized

    MedlinePlus

    ... levels. These may include abnormal blood levels of albumin or immunoglobulins. Normal Results Children: 4.8 to ... 2016:chap 245. Read More Acute kidney failure Albumin - blood (serum) test Bone tumor Calcium blood test ...

  18. PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor.

    PubMed

    Loupy, Alexandre; Ramakrishnan, Suresh Krishna; Wootla, Bharath; Chambrey, Régine; de la Faille, Renaud; Bourgeois, Soline; Bruneval, Patrick; Mandet, Chantal; Christensen, Erik Ilso; Faure, Hélène; Cheval, Lydie; Laghmani, Kamel; Collet, Corinne; Eladari, Dominique; Dodd, Robert H; Ruat, Martial; Houillier, Pascal

    2012-09-01

    Tight regulation of calcium levels is required for many critical biological functions. The Ca2+-sensing receptor (CaSR) expressed by parathyroid cells controls blood calcium concentration by regulating parathyroid hormone (PTH) secretion. However, CaSR is also expressed in other organs, such as the kidney, but the importance of extraparathyroid CaSR in calcium metabolism remains unknown. Here, we investigated the role of extraparathyroid CaSR using thyroparathyroidectomized, PTH-supplemented rats. Chronic inhibition of CaSR selectively increased renal tubular calcium absorption and blood calcium concentration independent of PTH secretion change and without altering intestinal calcium absorption. CaSR inhibition increased blood calcium concentration in animals pretreated with a bisphosphonate, indicating that the increase did not result from release of bone calcium. Kidney CaSR was expressed primarily in the thick ascending limb of the loop of Henle (TAL). As measured by in vitro microperfusion of cortical TAL, CaSR inhibitors increased calcium reabsorption and paracellular pathway permeability but did not change NaCl reabsorption. We conclude that CaSR is a direct determinant of blood calcium concentration, independent of PTH, and modulates renal tubular calcium transport in the TAL via the permeability of the paracellular pathway. These findings suggest that CaSR inhibitors may provide a new specific treatment for disorders related to impaired PTH secretion, such as primary hypoparathyroidism. PMID:22886306

  19. Calcium Carbonate.

    PubMed

    Al Omari, M M H; Rashid, I S; Qinna, N A; Jaber, A M; Badwan, A A

    2016-01-01

    Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables. PMID:26940168

  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. Calcium orthophosphates

    PubMed Central

    Dorozhkin, Sergey V.

    2011-01-01

    The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided. PMID:23507744

  2. Calcium Hydroxylapatite

    PubMed Central

    Yutskovskaya, Yana Alexandrovna; Philip Werschler, WM.

    2015-01-01

    Background: Calcium hydroxylapatite is one of the most well-studied dermal fillers worldwide and has been extensively used for the correction of moderate-to-severe facial lines and folds and to replenish lost volume. Objectives: To mark the milestone of 10 years of use in the aesthetic field, this review will consider the evolution of calcium hydroxylapatite in aesthetic medicine, provide a detailed injection protocol for a global facial approach, and examine how the unique properties of calcium hydroxylapatite provide it with an important place in today’s market. Methods: This article is an up-to-date review of calcium hydroxylapatite in aesthetic medicine along with procedures for its use, including a detailed injection protocol for a global facial approach by three expert injectors. Conclusion: Calcium hydroxylapatite is a very effective agent for many areas of facial soft tissue augmentation and is associated with a high and well-established safety profile. Calcium hydroxylapatite combines high elasticity and viscosity with an ability to induce long-term collagen formation making it an ideal agent for a global facial approach. PMID:25610523

  3. Regulation of protein degradation in muscle by calcium

    NASA Technical Reports Server (NTRS)

    Zeman, Richard J.; Kameyama, Tsuneo; Matsumoto, Kazue; Bernstein, Paul; Etlinger, Joseph D.

    1985-01-01

    Calcium-dependent regulation of intracellular protein degradation was studied in isolated rat skeletal muscles incubated in vitro in the presence of a large variety of agents known to affect calcium movement and distribution. The effect of different classes of protease inhibitors was tested to determine the responsible proteolytic systems involved in calcium-dependent degradation. The results suggest that nonlysosomal leupetin- and E-64-c-sensitive proteases are resposible for calcium-dependent proteolysis in muscle.

  4. 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.

  5. [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

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

    PubMed Central

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

    2015-01-01

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

  7. 1-[N, O-bis-(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), an inhibitor of calcium-dependent camodulin protein kinase II, inhibits both insulin- and hypoxia-stimulated glucose transport in skeletal muscle.

    PubMed Central

    Brozinick, J T; Reynolds, T H; Dean, D; Cartee, G; Cushman, S W

    1999-01-01

    Previous studies have indicated a role for calmodulin in hypoxia-and insulin-stimulated glucose transport. However, since calmodulin interacts with multiple protein targets, it is unknown which of these targets is involved in the regulation of glucose transport. In the present study, we have used the calcium-dependent calmodulin protein kinase II (CAMKII) inhibitor 1-[N, O-bis-(5-isoquinolinesulphonyl) -N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) to investigate the possible role of this enzyme in the regulation of glucose transport in isolated rat soleus and epitrochlearis muscles. KN-62 did not affect basal 2-deoxyglucose transport, but it did inhibit both insulin- and hypoxia-stimulated glucose transport activity by 46 and 40% respectively. 1-[N,O-Bis-(1, 5-isoquinolinesulphonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-04), a structural analogue of KN-62 that does not inhibit CAMKII, had no effect on hypoxia-or insulin-stimulated glucose transport. Accordingly, KN-62 decreased the stimulated cell-surface GLUT4 labelling by a similar extent as the inhibition of glucose transport (insulin, 49% and hypoxia, 54%). Additional experiments showed that KN-62 also inhibited insulin- and hypoxia-stimulated transport by 37 and 40% respectively in isolated rat epitrochlearis (a fast-twitch muscle), indicating that the effect of KN-62 was not limited to the slow-twitch fibres of the soleus. The inhibitory effect of KN-62 on hypoxia-stimulated glucose transport appears to be specific to CAMKII, since KN-62 did not inhibit hypoxia-stimulated 45Ca efflux from muscles pre-loaded with 45Ca, or hypoxia-stimulated glycogen breakdown. Additionally, KN-62 affected neither insulin-stimulated phosphoinositide 3-kinase nor Akt activity, suggesting that the effects of KN-62 are not due to non-specific effects of this inhibitor on these regions of the insulin-signalling cascade. The results of the present study suggest that CAMKII might have a distinct role in insulin- and hypoxia

  8. 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.

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

    PubMed

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

    2003-04-15

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

  10. 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.

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

    PubMed

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

    2012-09-15

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

  12. 77 FR 48527 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

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

  13. Role of calcium in gravity perception of plant roots

    NASA Astrophysics Data System (ADS)

    Evans, Michael L.

    Calcium ions may play a key role in linking graviperception by the root cap to the asymmetric growth which occurs in the elongation zone of gravistimulated roots. Application of calcium-chelating agents to the root cap inhibits gravitropic curvature without affecting growth. Asymmetric application of calcium to one side of the root cap induces curvature toward the calcium source, and gravistimulation induces polar movement of applied 45Ca2+ across the root cap toward the lower side. The action of calcium may be linked to auxin movement in roots since 1) auxin transport inhibitors interfere both with gravitropic curvature and gravi-induced polar calcium movement and 2) asymmetric application of calcium enhances auxin movement across the elongation zone of gravistimulated roots. Indirect evidence indicates that the calcium-modulated regulator protein, calmodulin, may be involved in either the transport or action of calcium in the gravitropic response mechanism of roots.

  14. The calcium-alkali syndrome.

    PubMed

    Arroyo, Mariangeli; Fenves, Andrew Z; Emmett, Michael

    2013-04-01

    The milk-alkali syndrome was a common cause of hypercalcemia, metabolic alkalosis, and renal failure in the early 20th century. It was caused by the ingestion of large quantities of milk and absorbable alkali to treat peptic ulcer disease. The syndrome virtually vanished after introduction of histamine-2 blockers and proton pump inhibitors. More recently, a similar condition called the calcium-alkali syndrome has emerged as a common cause of hypercalcemia and alkalosis. It is usually caused by the ingestion of large amounts of calcium carbonate salts to prevent or treat osteoporosis and dyspepsia. We describe a 78-year-old woman who presented with weakness, malaise, and confusion. She was found to have hypercalcemia, acute renal failure, and metabolic alkalosis. Upon further questioning, she reported use of large amounts of calcium carbonate tablets to treat recent heartburn symptoms. Calcium supplements were discontinued, and she was treated with intravenous normal saline. After 5 days, the calcium and bicarbonate levels normalized and renal function returned to baseline. In this article, we review the pathogenesis of the calcium-alkali syndrome as well as the differences between the traditional and modern syndromes. PMID:23543983

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

    PubMed

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    Dye, Allen

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    PubMed

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

    1997-05-01

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

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

    ERIC Educational Resources Information Center

    Whyte, Ann

    1991-01-01

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

  1. 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…

  2. Calcium and bones

    MedlinePlus

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  3. Get Enough Calcium

    MedlinePlus

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of calcium ...

  4. Calcium carbonate overdose

    MedlinePlus

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Some products that contain calcium carbonate are certain: ... and mineral supplements Other products may also contain calcium ...

  5. Calcium cyanide

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 28 , 2010 , the assessment summary for calcium cyanide is included in th

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. Multiple forms of calcium-dependent proteinase in crustacean muscle

    SciTech Connect

    Mykles, D.L.; Skinner, D.M.

    1986-01-01

    Four calcium-dependent proteinase (CDP) activities in lobster muscles have been resolved by high performance liquid chromatography. These activities differ in molecular weight and net charge. Though optimum activity occurred at high (5 and 10 mM) calcium at pH 6.8, the enzymes differ in activation at lower calcium concentrations. Only one of the CDPs is active at 100 ..mu..M calcium; none are active at 10 ..mu..M and below. Although all four CDPs are inhibited by the cysteine proteinase inhibitors leupeptin, E-64, and iodoacetamide, they show a differential response to the aspartic proteinase inhibitor pepstatin and the serine proteinase inhibitor PMSF. In contrast to CDPs from vertebrate tissues, crustacean muscles contain multiple forms that require calcium at millimolar levels. 17 refs., 6 figs.

  9. 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).

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

    NASA Astrophysics Data System (ADS)

    Hughes, Ryan; Bernath, Peter; Boone, Chris

    2014-11-01

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

  11. 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.

  12. 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.

  13. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calcium is required for the bone formation phase of bone remodeling. Typically about 5 nmol (200 mg) of calcium is removed from the adult skeleton and replaced each day. To supply this amount, one would need to consume about 600 mg of calcium, since calcium is not very efficiently absorbed. Calcium ...

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

    PubMed Central

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

    2014-01-01

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

  15. Calcium and bones (image)

    MedlinePlus

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human ... body, are continually being re-formed and incorporate calcium into their structure. Calcium is essential for the ...

  16. Calcium source (image)

    MedlinePlus

    Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

  17. Coronary Calcium Scan

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  18. Calcium hydroxide poisoning

    MedlinePlus

    Hydrate - calcium; Lime milk; Slaked lime ... Calcium hydroxide ... These products contain calcium hydroxide: Cement Limewater Many industrial solvents and cleaners (hundreds to thousands of construction products, flooring strippers, brick cleaners, cement ...

  19. Relationship between structure of phenothiazine analogues and their activity on platelet calcium fluxes.

    PubMed Central

    Enouf, J.; Lévy-Toledano, S.

    1984-01-01

    Phenothiazine analogues have been tested for their effect on calcium uptake into platelet membrane vesicles and on ionophore-induced platelet activation, both phenomena being Ca2+-dependent. Both calcium uptake into membrane vesicles and ionophore-induced platelet activation were inhibited by the drugs. Evidence for two inhibitors as potent as chlorpromazine and trifluoperazine was found. These drugs are apparently competitive inhibitors of calcium uptake. A structure-activity relationship has been established. The data suggest that the phenothiazines are able to inhibit calmodulin-insensitive calcium uptake of platelet membrane vesicles and that therefore they cannot be assumed to be selective inhibitors of calmodulin interactions under all circumstances. PMID:6697061

  20. Calcium, TRPC channels, and regulation of the actin cytoskeleton in podocytes: towards a future of targeted therapies.

    PubMed

    Wieder, Nicolas; Greka, Anna

    2016-07-01

    With more than 6,000 new pediatric patients with treatment-resistant nephrotic syndrome in the US each year alone, the unmet need for novel, podocyte-specific therapies is substantial. Recently, the established therapeutic benefit of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) was used as a starting point to gain insight into the pathomechanism of primary podocytopathies. A calcium (Ca(2+))-mediated pathway has been identified that connects the angiotensin type 1 receptor (AT1R) to podocyte cytoskeletal dynamics, essential for a functioning glomerular filtration barrier. This discovery provided an important missing piece in our understanding of the pathomechanism of filter barrier damage, revealing Ca(2+) signaling as critical for podocyte health and disease. The identification of the two Ca(2+) permeant channels TRPC5 and TRPC6 as mediators of this pathway not only bolstered the importance of podocyte cytoskeleton dynamics but also revealed promising drug targets for treatment-resistant nephrotic syndrome. This review will focus on this novel signaling pathway in primary podocytopathies and its implications for next-generation therapies for glomerular disease. PMID:26490951

  1. 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.

  2. Heavy Ion Temperatures As Observed By ACE/Swics

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

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

    PubMed

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

    2014-10-22

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

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

    PubMed Central

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

    2012-01-01

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

  6. 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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. 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 ...

  10. 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)

  11. 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.

  12. 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.

  13. ACE2 Global Digital Elevation Model : User Analysis

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed

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

    2015-12-01

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

  15. 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.

  16. 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.

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

    ERIC Educational Resources Information Center

    Golding, Barry; Davies, Merryn; Volkoff, Veronica

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

  18. 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…

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

    NASA Astrophysics Data System (ADS)

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

    2005-07-01

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

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

    SciTech Connect

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

    1991-03-15

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

  1. 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....

  2. 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…

  3. 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…

  4. 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.

  5. 77 FR 20835 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

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

  6. 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

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

    PubMed

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

    1993-01-01

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

  8. 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

  9. 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

  10. 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

  11. Studies on endogenous circulating calcium entry blocker and stimulator

    SciTech Connect

    Pang, P.K.T.; Yang, M.C.M.

    1986-03-01

    Several synthetic compounds have been studied extensively for their calcium entry blockade and stimulation in smooth muscles. It is hypothesized that there should be endogenous substances which control calcium entry into cells. We recently investigated the effect of some vasoactive hormones on calcium entry. Our studies on rat tail artery helical strip showed that the in vitro vasoconstriction produced by arginine vasopressin (AVP) decreased stepwise with decreasing concentration of both calcium. After exposure of the tail artery to calcium-free Ringer's solution for 1 minute or longer, the tissue lost its ability to respond to AVP. Subsequent addition of calcium to the medium produced immediate contraction. Measurements of low affinity lanthanum resistant pool of calcium with /sup 45/Ca showed that AVP increased calcium uptake by tail artery in a dose-dependent manner. In another study rat tail artery helical strip indicated that the vasorelaxing action of parathyroid hormone (PTH) was related to an inhibition of calcium uptake. AVP or 60 mM potassium chloride increased the low affinity lanthanum resistant pool of calcium in rate tail artery and PTH inhibited the increase. In conclusion, AVP and PTH may behave like endogenous calcium entry stimulator and inhibitor respectively in vascular tissues.

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

    ERIC Educational Resources Information Center

    McIntyre, John; Kimberley, Helen

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

  14. The putative P-gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P-glycoprotein expressing cell line MDCK II MDR1

    PubMed Central

    Saaby, Lasse; Tfelt-Hansen, Peer; Brodin, Birger

    2015-01-01

    Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P-glycoprotein (P-gp, ABCB1) substrate. We wished to evaluate in vitro whether co administration of a P-gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-to-apical transepithelial efflux across the MDCK II MDR1 monolayers with a permeability of 5.7 × 10−5 cm sec−1 compared to an apical to basolateral permeability of 1.3 × 10−5 cm sec-1. The efflux could be inhibited with the P-gp inhibitor zosuquidar. Zosuquidar (0.4 μmol/L) reduced the efflux ratio (PB-A/PA-B) for verapamil 4.6–1.6. The presence of telmisartan, however, only caused a slight reduction in P-gp-mediated verapamil transport to an efflux ratio of 3.4. Overall, the results of the present in vitro approach indicate, that clinical use of telmisartan as a P-gp inhibitor may not be an effective strategy for increasing brain uptake of verapamil by co-administration with telmisartan. PMID:26171231

  15. 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

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

    PubMed

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

    2011-03-01

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

  17. Calcium regulates caveolin-1 expression at the transcriptional level

    SciTech Connect

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming; Li, Yan; Liu, Dan; Zhang, Xue-Cheng; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. Black-Right-Pointing-Pointer An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. Black-Right-Pointing-Pointer Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. Black-Right-Pointing-Pointer Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca{sup 2+}/calcineurin/NFAT.

  18. Clouds in the Tropical Lowermost Stratosphere Observed by ACE

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  19. 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.

  20. [Do cows drink calcium?].

    PubMed

    Geishauser, T; Lechner, S; Plate, I; Heidemann, B

    2008-03-01

    The objective of this study was to investigate how well cows drink the Propeller calcium drink, and it's effect on blood calcium concentration. Drinking was tested in 120 cows right after calving, before cows drank anything else. 60 cows each were offered 20 liters of Propeller calcium drink or 20 liters of water. Cows drank the Propeller as good as water. 72% of all cows drank all 20 liters, 18% drank on average 8.2 liters and 10% drank less than 1 liter. Blood calcium concentration was studied in 16 cows right after calving. Eight cows each were offered 20 liters of Propeller calcium drink or no calcium drink. Blood calcium significantly increased ten minutes after Propeller intake and stayed significantly elevated for 24 hours. Without calcium drink blood calcium levels decreased significantly. Advantages of the new Propeller calcium drink over calcium gels or boli could be that cows now drink calcium themselves and that the Propeller increases blood calcium concentration rapidly and long lasting. PMID:18429501

  1. Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis.

    PubMed

    Vidadala, Rama Subba Rao; Rivas, Kasey L; Ojo, Kayode K; Hulverson, Matthew A; Zambriski, Jennifer A; Bruzual, Igor; Schultz, Tracey L; Huang, Wenlin; Zhang, Zhongsheng; Scheele, Suzanne; DeRocher, Amy E; Choi, Ryan; Barrett, Lynn K; Siddaramaiah, Latha Kallur; Hol, Wim G J; Fan, Erkang; Merritt, Ethan A; Parsons, Marilyn; Freiberg, Gail; Marsh, Kennan; Kempf, Dale J; Carruthers, Vern B; Isoherranen, Nina; Doggett, J Stone; Van Voorhis, Wesley C; Maly, Dustin J

    2016-07-14

    New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activity in vitro and in vivo. Unfortunately, 1 has potent human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q-T syndrome, and consequently presents a cardiotoxicity risk. Here, we describe the identification of an optimized TgCDPK1 inhibitor 32, which does not have a hERG liability and possesses a favorable pharmacokinetic profile in small and large animals. 32 is CNS-penetrant and highly effective in acute and latent mouse models of T. gondii infection, significantly reducing the amount of parasite in the brain, spleen, and peritoneal fluid and reducing brain cysts by >85%. These properties make 32 a promising lead for the development of a new antitoxoplasmosis therapy. PMID:27309760

  2. 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.

  3. Calcium and Vitamin D

    MedlinePlus

    ... to your weekly shopping list. Produce Serving Size Estimated Calcium* Collard greens, frozen 8 oz 360 mg ... Oranges 1 whole 55 mg Seafood Serving Size Estimated Calcium* Sardines, canned with bones 3 oz 325 ...

  4. Fenoprofen calcium overdose

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002649.htm Fenoprofen calcium overdose To use the sharing features on this page, please enable JavaScript. Fenoprofen calcium is a type of medicine called a nonsteroidal ...

  5. Calcium channel blocker overdose

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium channel blockers are a type of medicine used ...

  6. Fenoprofen calcium overdose

    MedlinePlus

    Fenoprofen calcium is a type of medicine called a nonsteroidal anti-inflammatory drug. It is a prescription pain medicine used to relieve symptoms of arthritis . Fenoprofen calcium overdose occurs when someone takes more than the ...

  7. Calcium and bones (image)

    MedlinePlus

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human body. Bones, like other tissues in the body, are continually being re-formed and incorporate calcium into their ...

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

    PubMed

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

    2006-09-01

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

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

    PubMed

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

    2006-07-01

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

  10. The importance of calcium in the regulation of megakaryocyte function.

    PubMed

    Di Buduo, Christian Andrea; Moccia, Francesco; Battiston, Monica; De Marco, Luigi; Mazzucato, Mario; Moratti, Remigio; Tanzi, Franco; Balduini, Alessandra

    2014-04-01

    Platelet release by megakaryocytes is regulated by a concert of environmental and autocrine factors. We previously showed that constitutively released adenosine diphosphate by human megakaryocytes leads to platelet production. Here we show that adenosine diphosphate elicits, in human megakaryocytes, an increase in cytosolic calcium concentration, followed by a plateau, which is lowered in the absence of extracellular calcium, suggesting the involvement of Store-Operated Calcium Entry. Indeed, we demonstrate that megakaryocytes express the major candidates to mediate Store-Operated Calcium Entry, stromal interaction molecule 1, Orai1 and canonical transient receptor potential 1, which are activated upon either pharmacological or physiological depletion of the intracellular calcium pool. This mechanism is inhibited by phospholipase C or inositol-3-phosphate receptor inhibitors and by a specific calcium entry blocker. Studies on megakaryocyte behavior, on extracellular matrix proteins that support proplatelet extension, show that calcium mobilization from intracellular stores activates signaling cascades that trigger megakaryocyte adhesion and proplatelet formation, and promotes extracellular calcium entry which is primarily involved in the regulation of the contractile force responsible for megakaryocyte motility. These findings provide the first evidence that both calcium mobilization from intracellular stores and extracellular calcium entry specifically regulate human megakaryocyte functions. PMID:24463213

  11. The importance of calcium in the regulation of megakaryocyte function

    PubMed Central

    Andrea Di Buduo, Christian; Moccia, Francesco; Battiston, Monica; De Marco, Luigi; Mazzucato, Mario; Moratti, Remigio; Tanzi, Franco; Balduini, Alessandra

    2014-01-01

    Platelet release by megakaryocytes is regulated by a concert of environmental and autocrine factors. We previously showed that constitutively released adenosine diphosphate by human megakaryocytes leads to platelet production. Here we show that adenosine diphosphate elicits, in human megakaryocytes, an increase in cytosolic calcium concentration, followed by a plateau, which is lowered in the absence of extracellular calcium, suggesting the involvement of Store-Operated Calcium Entry. Indeed, we demonstrate that megakaryocytes express the major candidates to mediate Store-Operated Calcium Entry, stromal interaction molecule 1, Orai1 and canonical transient receptor potential 1, which are activated upon either pharmacological or physiological depletion of the intracellular calcium pool. This mechanism is inhibited by phospholipase C or inositol-3-phosphate receptor inhibitors and by a specific calcium entry blocker. Studies on megakaryocyte behavior, on extracellular matrix proteins that support proplatelet extension, show that calcium mobilization from intracellular stores activates signaling cascades that trigger megakaryocyte adhesion and proplatelet formation, and promotes extracellular calcium entry which is primarily involved in the regulation of the contractile force responsible for megakaryocyte motility. These findings provide the first evidence that both calcium mobilization from intracellular stores and extracellular calcium entry specifically regulate human megakaryocyte functions. PMID:24463213

  12. Calcium and magnesium disorders.

    PubMed

    Goff, Jesse P

    2014-07-01

    Hypocalcemia is a clinical disorder that can be life threatening to the cow (milk fever) and predisposes the animal to various other metabolic and infectious disorders. Calcium homeostasis is mediated primarily by parathyroid hormone, which stimulates bone calcium resorption and renal calcium reabsorption. Parathyroid hormone stimulates the production of 1,25-dihydroxyvitamin D to enhance diet calcium absorption. High dietary cation-anion difference interferes with tissue sensitivity to parathyroid hormone. Hypomagnesemia reduces tissue response to parathyroid hormone. PMID:24980727

  13. Calcium and Mitosis

    NASA Technical Reports Server (NTRS)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  14. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter describes the roles of calcium and vitamin D in bone health. Calcium is required for the bone formation phase of bone remodeling and it also affects bone mass through its impact on the remodeling rate. Typically, about 5 nmol (200 mg) of calcium is removed from the adult skeleton and ...

  15. Calcium and bones

    MedlinePlus

    Bone strength and calcium ... or if your body does not absorb enough calcium, your bones can get weak or will not grow properly. ... injury. As you age, your body still needs calcium to keep your bones dense and strong. Most experts recommend at least ...

  16. 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.

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

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

  18. Management of calcium channel antagonist overdose.

    PubMed

    Salhanick, Steven D; Shannon, Michael W

    2003-01-01

    Calcium channel antagonists are used primarily for the treatment of hypertension and tachyarrhythmias. Overdose of calcium channel antagonists can be lethal. Calcium channel antagonists act at the L-type calcium channels primarily in cardiac and vascular smooth muscle preventing calcium influx into cells with resultant decreases in vascular tone and cardiac inotropy and chronotropy. The L-type calcium channel is a complex structure and is thus affected by a large number of structurally diverse antagonists. In the setting of overdose, patients may experience vasodilatation and bradycardia leading to a shock state. Patients may also be hyperglycaemic and acidotic due to the blockade of L-type calcium channels in the pancreatic islet cells that affect insulin secretion. Aggressive therapy is warranted in the setting of toxicity. Gut decontamination with charcoal, or whole bowel irrigation or multiple-dose charcoal in the setting of extended-release products is indicated. Specific antidotes include calcium salts, glucagon and insulin. Calcium salts may be given in bolus doses or may be employed as a continuous infusion. Care should be exercised to avoid the administration of calcium in the setting of concomitant digoxin toxicity. Insulin administration has been used effectively to increase cardiac inotropy and survival. The likely mechanism involves a shift to carbohydrate metabolism in the setting of decreased availability of carbohydrates due to decreased insulin secretion secondary to blockade of calcium channels in pancreatic islet cells. Glucose should be administered as well to maintain euglycaemia. Supportive care including the use of phosphodiesterase inhibitors, adrenergic agents, cardiac pacing, balloon pump or extracorporeal bypass is frequently indicated if antidotal therapy is not effective. Careful evaluation of asymptomatic patients, including and electrocardiogram and a period of observation, is indicated. Patients ingesting a nonsustained

  19. Air bubble contact with endothelial cells in vitro induces calcium influx and IP3-dependent release of calcium stores

    PubMed Central

    Sobolewski, Peter; Kandel, Judith; Klinger, Alexandra L.

    2011-01-01

    Gas embolism is a serious complication of decompression events and clinical procedures, but the mechanism of resulting injury remains unclear. Previous work has demonstrated that contact between air microbubbles and endothelial cells causes a rapid intracellular calcium transient and can lead to cell death. Here we examined the mechanism responsible for the calcium rise. Single air microbubbles (50–150 μm), trapped at the tip of a micropipette, were micromanipulated into contact with individual human umbilical vein endothelial cells (HUVECs) loaded with Fluo-4 (a fluorescent calcium indicator). Changes in intracellular calcium were then recorded via epifluorescence microscopy. First, we confirmed that HUVECs rapidly respond to air bubble contact with a calcium transient. Next, we examined the involvement of extracellular calcium influx by conducting experiments in low calcium buffer, which markedly attenuated the response, or by pretreating cells with stretch-activated channel blockers (gadolinium chloride or ruthenium red), which abolished the response. Finally, we tested the role of intracellular calcium release by pretreating cells with an inositol 1,4,5-trisphosphate (IP3) receptor blocker (xestospongin C) or phospholipase C inhibitor (neomycin sulfate), which eliminated the response in 64% and 67% of cases, respectively. Collectively, our results lead us to conclude that air bubble contact with endothelial cells causes an influx of calcium through a stretch-activated channel, such as a transient receptor potential vanilloid family member, triggering the release of calcium from intracellular stores via the IP3 pathway. PMID:21633077

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

    PubMed

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

    2003-09-01

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

  1. Calcium bioavailability from calcium fortified food products.

    PubMed

    Kohls, K

    1991-08-01

    The calcium balance of 12 presumed healthy human young adult subjects was assessed. Subjects consumed a constant laboratory-controlled diet supplemented with one of four calcium-fortified food products: orange juice (OJ), milk (M), experimental pasteurized processed cheese (T), soda (S), or a calcium carbonate plus vitamin D tablet (CC). Study length was 6 weeks with seven-day experimental periods (2-days allowed for adjustment with 5-days combined for purposes of analysis). All urine and fecal samples were collected by the subjects for the duration of the study. Blood samples were drawn at the end of each experimental period. Urine and fecal calcium contents were determined. Blood samples were analyzed for alkaline phosphatase. Results of this study indicate a higher fecal calcium content (mg/day) when subjects consumed CC and T, and when subjects consumed self-selected diets, than when given S, M, or OJ. Urinary calcium excretion was significantly lower when subjects consumed OJ than when they consumed M, T, or their self-selected diets. A significantly larger positive calcium balance was demonstrated when subjects consumed OJ as compared to T. Fecal transmit time did not vary significantly. Serum alkaline phosphatase was significantly lower when subjects consumed T than when they consumed self-selected diets. PMID:1765836

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

    PubMed

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

    2016-01-01

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

  3. 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

  4. 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.

  5. 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

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

    PubMed Central

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

    2014-01-01

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

  7. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum.

    PubMed

    Budu, Alexandre; Gomes, Mayrim M; Melo, Pollyana M; El Chamy Maluf, Sarah; Bagnaresi, Piero; Azevedo, Mauro F; Carmona, Adriana K; Gazarini, Marcos L

    2016-03-01

    Calcium and calmodulin (CaM) are important players in eukaryote cell signaling. In the present study, by using a knockin approach, we demonstrated the expression and localization of CaM in all erythrocytic stages of Plasmodium falciparum. Under extracellular Ca(2+)-free conditions, calmidazolium (CZ), a potent CaM inhibitor, promoted a transient cytosolic calcium ([Ca(2+)]cyt) increase in isolated trophozoites, indicating that CZ mobilizes intracellular sources of calcium. In the same extracellular Ca(2+)-free conditions, the [Ca(2+)]cyt rise elicited by CZ treatment was ~3.5 fold higher when the endoplasmic reticulum (ER) calcium store was previously depleted ruling out the mobilization of calcium from the ER by CZ. The effects of the Ca(2+)/H(+) ionophore ionomycin (ION) and the Na(+)/H(+) ionophore monensin (MON) suggest that the [Ca(2+)]cyt-increasing effect of CZ is driven by the removal of Ca(2+) from at least one Ca(2+)-CaM-related (CaMR) protein as well as by the mobilization of Ca(2+) from intracellular acidic calcium stores. Moreover, we showed that the mitochondrion participates in the sequestration of the cytosolic Ca(2+) elicited by CZ. Finally, the modulation of membrane Ca(2+) channels by CZ and thapsigargin (THG) was demonstrated. The opened channels were blocked by the unspecific calcium channel blocker Co(2+) but not by 2-APB (capacitative calcium entry inhibitor) or nifedipine (L-type Ca(2+) channel inhibitor). Taken together, the results suggested that one CaMR protein is an important modulator of calcium signaling and homeostasis during the Plasmodium intraerythrocytic cell cycle, working as a relevant intracellular Ca(2+) reservoir in the parasite. PMID:26689736

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

    PubMed

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

    2016-06-01

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

  9. CFTR Inhibitors

    PubMed Central

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

    2014-01-01

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

  10. 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

  11. 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

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

    PubMed

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

    1997-08-01

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

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

    PubMed

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

    2014-01-01

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

  14. 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

  15. Mineralization by Inhibitor Exclusion

    PubMed Central

    Price, Paul A.; Toroian, Damon; Lim, Joo Eun

    2009-01-01

    One of our goals is to understand the mechanisms that deposit mineral within collagen fibrils, and as a first step we recently determined the size exclusion characteristics of the fibril. This study revealed that apatite crystals up to 12 unit cells in size can access the water within the fibril, whereas molecules larger than a 40-kDa protein are excluded. Based on these observations, we proposed a novel mechanism for fibril mineralization: that macromolecular inhibitors of apatite growth favor fibril mineralization by selectively inhibiting crystal growth in the solution outside of the fibril. To test this mechanism, we developed a system in which crystal formation is driven by homogeneous nucleation at high calcium phosphate concentration and the only macromolecule in solution is fetuin, a 48-kDa inhibitor of apatite growth. Our experiments with this system demonstrated that fetuin determines the location of mineral growth; in the presence of fetuin mineral grows exclusively within the fibril, whereas in its absence mineral grows in solution outside the fibril. Additional experiments showed that fetuin is also able to localize calcification to the interior of synthetic matrices that have size exclusion characteristics similar to those of collagen and that it does so by selectively inhibiting mineral growth outside of these matrices. We termed this new calcification mechanism “mineralization by inhibitor exclusion,” the selective mineralization of a matrix using a macromolecular inhibitor of mineral growth that is excluded from that matrix. Future studies will be needed to evaluate the possible role of this mechanism in bone mineralization. PMID:19414589

  16. 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.

  17. 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.

  18. 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.

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

    Ha, Sung-Kyu

    2014-01-01

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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Calcium- and CaMKII-dependent chloride secretion induced by the microsomal Ca(2+)-ATPase inhibitor 2,5-di-(tert-butyl)-1,4-hydroquinone in cystic fibrosis pancreatic epithelial cells.

    PubMed Central

    Chao, A C; Kouyama, K; Heist, E K; Dong, Y J; Gardner, P

    1995-01-01

    Microsomal Ca(2+)-ATPase inhibitors such as thapsigargin (THG), cyclopiazonic acid (CPA) and 2,5-di-(tert-butyl)-1,4-hydroquinone (DBHQ) have been shown to inhibit Ca2+ reuptake by the intracellular stores and increase cytosolic free Ca2+ ([Ca2+]i). DBHQ is a commercially available non-toxic synthetic compound chemically unrelated to THG and CPA. In this study, we tested the feasibility of utilizing DBHQ to improve Cl- secretion via the Ca(2+)-dependent pathway, in the cystic fibrosis (CF)-derived pancreatic epithelial cell line CFPAC-1. DBHQ stimulated 125I efflux and mobilized intracellular free Ca2+ in a dose-dependent manner. The maximal effects were seen at concentrations of 25-50 microM. DBHQ (25 microM) caused a short-term rise in [Ca2+]i in the absence of ambient Ca2+, and a sustained elevation of [Ca2+]i in cell monolayers bathed in the efflux solution (1.2 mM Ca2+), which was largely attenuated by Ni2+ (5 mM). Bath-application of DBHQ induced an outwardly-rectifying whole-cell Cl- current, which was abolished by pipette addition of BAPTA (5 mM) or CaMK [273-302] (20 microM), an inhibitory peptide of multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII). Pretreatment of monolayers of CFPAC-1 cells with DBHQ for 4-5 min significantly increased the Ca(2+)-independent or autonomous activity of CaMKII assayed in the cell homogenates. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. Pretreatment of CFPAC-1 cells with up to 50 microM DBHQ for 6 h did not cause any detectable change in cell viability and did not significantly affect the cell proliferation rate. These results suggest that appropriate selective microsomal Ca(2+)-ATPase inhibitors may be therapeutically useful in improving Cl- secretion in CF epithelial cells. Images PMID:7560071

  12. Inhibition of crystallization of calcium oxalate by the extraction of Tamarix gallica L.

    PubMed

    Bensatal, Ahmed; Ouahrani, M R

    2008-12-01

    The main objective is to study the inhibitor effect of acid fraction of the extract of Tamarix gallica L on the crystallization of calcium oxalate. The extract of Tamarix gallica L is very rich by acid compounds that are used as an inhibitor of nephrolithiasis (calcium oxalate). Our study of the calcium oxalate crystallization is based on the model of turbidimetry by means of a spectrophotometer. The calcium oxalate formation is induced by the addition of oxalate solutions of sodium and of calcium chloride. The addition of inhibitor with various concentrations enabled us to give information on the percentage of inhibition. The comparison between the turbidimetric slopes with and without inhibitor gives the effectiveness of inhibitor for the acid fraction. By comparing the photographs of with and without inhibitor, we concluded that the extract of Tamarix gallica L acts at the stage of growth. The acid fraction of the extract of Tamarix gallica L gives an activity remarkable in the formation of urinary lithiasis (calcium oxalate); this effectiveness is due to the presence of functions of acid. PMID:19002446

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. (2R,3S,2”R,3”R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract

    PubMed Central

    Balemba, Onesmo B.; Lösch, Sofie; Patterson, Savannah; McMillan, John S.; Hofmann, Thomas; Mawe, Gary M.; Stark, Timo D.

    2016-01-01

    Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca2+) imaging was used to analyze the effect of GBB on Ca2+ flashes and Ca2+ waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1–5 and M7, and (2R,3S,2”R,3”R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2”R,3”R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2”R,3”R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca2+ flashes and Ca2+ waves. GBB, M3 and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials. L-type Ca2+ channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2”R,3”R)-manniflavanone. GBB and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3S,2”R,3”R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2”R,3”R)-manniflavanone relax smooth muscle by inhibiting L-type Ca2+ channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

  19. (2R,3S,2'' R,3''R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract.

    PubMed

    Balemba, Onesmo B; Stark, Timo D; Lösch, Sofie; Patterson, Savannah; McMillan, John S; Mawe, Gary M; Hofmann, Thomas

    2014-01-01

    Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca(2+)) imaging was used to analyze the effect of GBB on Ca(2+) flashes and Ca(2+) waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1-5 and M7, and (2R,3S,2'' R,3''R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2'' R,3''R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2''R,3'' R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca(2+) flashes and Ca(2+) waves. GBB, M3 and (2R,3 S,2''R,3''R)-manniflavanone inhibited action potentials. L-type Ca(2+) channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2''R,3'' R)-manniflavanone. GBB and (2R,3S,2'' R,3''R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3 S,2''R,3''R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2'' R,3''R)-manniflavanone relax smooth muscle by inhibiting L-type Ca(2+) channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

  20. Calcium modulation of doxorubicin cytotoxicity in yeast and human cells.

    PubMed

    Nguyen, Thi Thuy Trang; Lim, Ying Jun; Fan, Melanie Hui Min; Jackson, Rebecca A; Lim, Kim Kiat; Ang, Wee Han; Ban, Kenneth Hon Kim; Chen, Ee Sin

    2016-03-01

    Doxorubicin is a widely used chemotherapeutic agent, but its utility is limited by cellular resistance and off-target effects. To understand the molecular mechanisms regulating chemotherapeutic responses to doxorubicin, we previously carried out a genomewide search of doxorubicin-resistance genes in Schizosaccharomyces pombe fission yeast and showed that these genes are organized into networks that counteract doxorubicin cytotoxicity. Here, we describe the identification of a subgroup of doxorubicin-resistance genes that, when disrupted, leads to reduced tolerance to exogenous calcium. Unexpectedly, we observed a suppressive effect of calcium on doxorubicin cytotoxicity, where concurrent calcium and doxorubicin treatment resulted in significantly higher cell survival compared with cells treated with doxorubicin alone. Conversely, inhibitors of voltage-gated calcium channels enhanced doxorubicin cytotoxicity in the mutants. Consistent with these observations in fission yeast, calcium also suppressed doxorubicin cytotoxicity in human breast cancer cells. Further epistasis analyses in yeast showed that this suppression of doxorubicin toxicity by calcium was synergistically dependent on Rav1 and Vph2, two regulators of vacuolar-ATPase assembly; this suggests potential modulation of the calcium-doxorubicin interaction by fluctuating proton concentrations within the cellular environment. Thus, the modulatory effects of drugs or diet on calcium concentrations should be considered in doxorubicin treatment regimes. PMID:26891792

  1. Lead in calcium supplements.

    PubMed

    Scelfo, G M; Flegal, A R

    2000-04-01

    Intercalibrated measurements of lead in calcium supplements indicate the importance of rigorous analytical techniques to accurately quantify contaminant exposures in complex matrices. Without such techniques, measurements of lead concentrations in calcium supplements may be either erroneously low, by as much as 50%, or below the detection limit needed for new public health criteria. In this study, we determined the lead content of 136 brands of supplements that were purchased in 1996. The calcium in the products was derived from natural sources (bonemeal, dolomite, or oyster shell) or was synthesized and/or refined (chelated and nonchelated calcium). The dried products were acid digested and analyzed for lead by high resolution-inductively coupled plasma-mass spectrometry. The method's limit of quantitation averaged 0.06 microg/g, with a coefficient of variation of 1.7% and a 90-100% lead recovery of a bonemeal standard reference material. Two-thirds of those calcium supplements failed to meet the 1999 California criteria for acceptable lead levels (1.5 microg/daily dose of calcium) in consumer products. The nonchelated synthesized and/or refined calcium products, specifically antacids and infant formulas, had the lowest lead concentrations, ranging from nondetectable to 2.9 microg Pb/g calcium, and had the largest proportion of brands meeting the new criteria (85% of the antacids and 100% of the infant formulas). PMID:10753088

  2. Lead in calcium supplements.

    PubMed Central

    Scelfo, G M; Flegal, A R

    2000-01-01

    Intercalibrated measurements of lead in calcium supplements indicate the importance of rigorous analytical techniques to accurately quantify contaminant exposures in complex matrices. Without such techniques, measurements of lead concentrations in calcium supplements may be either erroneously low, by as much as 50%, or below the detection limit needed for new public health criteria. In this study, we determined the lead content of 136 brands of supplements that were purchased in 1996. The calcium in the products was derived from natural sources (bonemeal, dolomite, or oyster shell) or was synthesized and/or refined (chelated and nonchelated calcium). The dried products were acid digested and analyzed for lead by high resolution-inductively coupled plasma-mass spectrometry. The method's limit of quantitation averaged 0.06 microg/g, with a coefficient of variation of 1.7% and a 90-100% lead recovery of a bonemeal standard reference material. Two-thirds of those calcium supplements failed to meet the 1999 California criteria for acceptable lead levels (1.5 microg/daily dose of calcium) in consumer products. The nonchelated synthesized and/or refined calcium products, specifically antacids and infant formulas, had the lowest lead concentrations, ranging from nondetectable to 2.9 microg Pb/g calcium, and had the largest proportion of brands meeting the new criteria (85% of the antacids and 100% of the infant formulas). Images Figure 1 Figure 2 PMID:10753088

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

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

    SciTech Connect

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

    1986-05-01

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

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

    PubMed

    Imataki, Osamu; Tamai, Yotaro; Kawakami, Kimihiro

    2007-10-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2013-01-01

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

  9. ACE inhibitory activity of pangasius catfish (Pangasius sutchi) skin and bone gelatin hydrolysate.

    PubMed

    Mahmoodani, Fatemeh; Ghassem, Masomeh; Babji, Abdul Salam; Yusop, Salma Mohamad; Khosrokhavar, Roya

    2014-09-01

    Skin and bone gelatins of pangasius catfish (Pangasius sutchi) were hydrolyzed with alcalase to isolate Angiotensin Converting Enzyme (ACE) inhibitory peptides. Samples with the highest degree of hydrolysis (DH) were separated into different fractions with molecular weight cut-off (MWCO) sizes of 10, 3 and 1 kDa, respectively and assayed for ACE inhibitory activity. Skin and bone gelatins had highest DH of 64.87 and 68.48 % after 2 and 1 h incubation, respectively. Results from this study indicated that by decreasing the molecular weight of fractions, ACE inhibitory activity was increased. Therefore, F3 permeates (MWCO < 1 kDa) of skin (IC50 = 3.2 μg/ml) and bone (IC50 = 1.3 μg/ml) gelatins possessed higher ACE inhibitory activity compared to their untreated gelatins and corresponding hydrolyzed fractions. In this study, the major amino acids were Glycine followed by Proline with an increased amount of hydrophobic amino acid content in F3 permeates of skin (4.01 %) and bone (5.79 %) gelatin. Digestion stability against gastrointestinal proteases did not show any remarkable change on ACE inhibition potency of these permeates. It was concluded that alcalase hydrolysis of P. sutchi by-products could be utilized as a part of functional food or ingredients of a formulated drug in order to control high blood pressure. PMID:25190839

  10. Preparation of ACE Inhibitory Peptides from Mytilus coruscus Hydrolysate Using Uniform Design

    PubMed Central

    Wu, Jin-Chao; Cheng, Jie; Shi, Xiao-lai

    2013-01-01

    The angiotensin-I-converting enzyme (ACE) inhibitory peptides from mussel, Mytilus coruscus, were investigated and the variable factors, protease concentration, hydrolysis time, pH, and temperature, were optimized using Uniform Design, a new statistical experimental method. The results proved that the hydrolysate of alkali proteases had high ACE-inhibitory activity, especially the alkali protease E1. Optimization by Uniform Design showed that the best hydrolysis conditions for preparation of ACE-inhibitory peptides from Mytilus coruscus were protease concentration of 36.0 U/mL, hydrolysis time of 2.7 hours, pH 8.2, and Temperature at 59.5°C, respectively. The verification experiments under optimum conditions showed that the ACE-inhibitory activity (91.3%) were agreed closely with the predicted activity of 90.7%. The amino acid composition analysis of Mytilus coruscus ACE-inhibitory peptides proved that it had high percent of lysine, leucine, glycine, aspartic acid, and glutamic acid. PMID:23484103

  11. 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

  12. Focal adhesion kinases and calcium/calmodulin-dependent protein kinases regulate protein tyrosine phosphorylation in stallion sperm.

    PubMed

    González-Fernández, Lauro; Macías-García, Beatriz; Loux, Shavahn C; Varner, Dickson D; Hinrichs, Katrin

    2013-06-01

    Protein tyrosine phosphorylation (PY) is a hallmark of sperm capacitation. In stallion sperm, calcium inhibits PY at pH <7.8, mediated by calmodulin. To explore the mechanism of that inhibition, we incubated stallion sperm in media without added calcium, with calcium, or with calcium plus the calmodulin inhibitor W-7 (Ca/W-7 treatment). Treatment with inhibitors of calcium/calmodulin-dependent kinases, protein kinase A (PRKA), or Src family kinases suppressed the PY induced by the absence of added calcium, but not that induced by the Ca/W-7 treatment, indicating that PY in the absence of added calcium occurred via the canonical PRKA pathway, but that PY in the Ca/W-7 treatment did not. This suggested that when calmodulin was inhibited, calcium stimulated PY via a noncanonical pathway. Incubation with PF-431396, an inhibitor of focal adhesion kinases (FAKs), a family of calcium-induced protein tyrosine kinases, inhibited the PY induced both by the absence of added calcium and by the Ca/W-7 treatment. Western blotting demonstrated that both FAK family members, protein tyrosine kinases 2 and 2B, were phosphorylated in the absence of added calcium and in the Ca/W-7 treatment, but not in the presence of calcium without calmodulin inhibitors. Inhibition of FAK proteins inhibited PY in stallion sperm incubated under capacitating conditions (in the presence of calcium, bovine serum albumin, and bicarbonate at pH >7.8). These results show for the first time a role for calcium/calmodulin-dependent kinases in PRKA-dependent sperm PY; a non-PRKA-dependent pathway regulating sperm PY; and the apparent involvement of the FAK family of protein tyrosine kinases downstream in both pathways. PMID:23595906

  13. Overview of Aircraft Operations during ACE-Asia

    NASA Astrophysics Data System (ADS)

    Seinfeld, J. H.; Huebert, B.

    2001-12-01

    The NSF/NCAR C-130 flew 19 flights out of Iwakuni, Japan between March 31 and May 4, 2001, and data were collected on 7 ferry flights crossing the Pacific. Many of the instruments derived their air from low-turbulence inlets, which enabled studies of supermicron particles vs altitude. Several flights sampled two heavy dust outbreaks, where the aerosol mass concentration exceeded 1000 †g/m3. Size-dependent chemical measurements indicated that this dust did not dramatically change the sulfate size distribution (by causing SO2 to convert to sulfate on its alkaline surfaces), since the vast majority of the sulfate was still in a submicron accumulation mode. Similarly, while the scattering in dust was dominated by large particles, the particle absorption was almost exclusively submicron. We found extensive layering, with as many as 6 distinct dust layers (and clean layers between them) in one profile to 6 km. During ACE-Asia research missions were also conducted using a modified De Havilland DHC-6 Twin Otter aircraft operated by the California Institute of Technology and the Center for Interdisciplinary Remotely Piloted Aircraft studies (CIRPAS). A total of 19 research flights were conducted between March 31 and May 1, 2001 from the base of operations at the MCAS Iwakuni, Japan. The sampling area included portions of the Sea of Japan south and east of the Korean Peninsula, the East China Sea between China, Japan and Korea, and the Philippine Sea south of Japan. Collected aerosols were analyzed to determine their chemical composition and physical properties such as size distribution, hygroscopic growth, light scattering and absorption properties. Simultaneous radiative measurements were also made using the 14-channel Ames Airborne Tracking Sunphotometer (AATS-14), which measured solar beam transmission at 14 wavelengths (353-1558 nm), yielding aerosol optical depth (AOD) spectra and column water vapor (CWV). Vertical differentiation in profiles yielded aerosol

  14. Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

    NASA Technical Reports Server (NTRS)

    Betz, N. A.; Westhoff, B. A.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

  15. 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

  16. 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.

  17. [Proteasome inhibitor].

    PubMed

    Yagi, Hideo

    2014-06-01

    The ubiquitin-proteasome system plays an essential role in degradation of eukaryotic intracellular protein, including cell cycle regulation, cell growth and proliferation, and survival. Cancer cells generally have higher level of proteasome activity compared with normal cells, suggesting proteasome inhibition could be therapeutic target in oncology. Bortezomib, the first proteasome inhibitor introduced into the clinic, is approved for the treatment of patients with multiple myeloma (MM). Although it was approved as single agent in the relapsed setting, bortezomib is now predominantly used in combination with conventional and novel targeted agents because bortezomib has demonstrated additive and synergistic activity in preclinical studies. Recently, several second-generation proteasome inhibitors, such as carfilzomib and MLN9708, have been developed and entered into clinical trials. These agents were investigated in frontline MM in combination with lenalidomide and low-dose dexamethasone. These studies demonstrated positive efficacy and safety, and it is expected that they will be approved in near future. PMID:25016815

  18. [Calcium and health].

    PubMed

    Ortega Anta, Rosa M; Jiménez Ortega, Ana I; López-Sobaler, Ana M

    2015-01-01

    An adequate intake of calcium is only not limited to avoid the risk of osteoporosis and its benefits in longterm bone health, but also it has been linked to protection against various major diseases, such as hypertension, cancer, kidney stones, insulin resistance, diabetes... and several investigations suggest its importance in preventing and controlling obesity. Studies conducted in Spanish representative samples show that a high percentage of adults and children (> 75%) don't achieve the recommended intake of calcium. Moreover, are growing trends among the population suggesting that calcium intake and dairy consumption (main food source of the mineral) are high, and even excessive, in many individuals. This misconception results in that the calcium intake is increasingly far from the recommended one. The maximum tolerable intake of the mineral is fixed at 2.500 mg/day, but this intake is unusual, and it's more disturbing and frequent, to find intakes below the recommended calcium intakes (1.000 and 1.200 mg/day in adults, men and women, respectively). Data from different studies highlight the risk of an inadequate calcium intake and the damages that may affect the health in a long term. It is not about transmitting indiscriminate guidelines in order to increase the intake of calcium / dairy, but the recommended intakes must be met to achieve both the nutritional and health benefits. Also activities for demystification of misconceptions are need, increasingly frequent, that may impair health population. PMID:25862324

  19. Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease.

    PubMed

    Kehoe, Patrick G; Katzov, Hagit; Andreasen, Niels; Gatz, Maragaret; Wilcock, Gordon K; Cairns, Nigel J; Palmgren, Juni; de Faire, Ulf; Brookes, Anthony J; Pedersen, Nancy L; Blennow, Kaj; Prince, Jonathan A

    2004-04-01

    Studies on the role that genetic variation may play in a complex human disease can be empowered by an assessment of both disease risk in case-control or family models and of quantitative traits that reflect elements of disease etiology. An excellent example of this can be found for the epsilon4 allele of APOE in relation to Alzheimer's disease (AD) for which association with both risk and age-at-onset (AAO) is evident. Following a recent demonstration that variants of the gene encoding angiotensin I converting enzyme ( ACE) contribute to AD risk, we have explored the potential influence of ACE upon AAO in AD. A total of 2861 individuals from three European populations, including six independent AD samples, have been examined in this study. Three single nucleotide polymorphisms (SNPs) previously demonstrated to have maximum effects upon ACE plasma levels and that span the ACE locus were genotyped in these materials. A strong effect upon AAO was observed for marker rs4343 in exon 17 ( P<0.0001), but evidence was also obtained indicating a possible independent effect of marker rs4291 ( P=0.0095) located in the ACE promoter. Effects were consistent with data from previous studies suggesting association with AD in case-control models, whereby alleles demonstrated to confer risk to disease also appear to reduce AAO. Equivalent effects were evident regardless of APOE epsilon4 carrier status and in both males and females. These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology. PMID:14986105

  20. 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.

  1. Comparison of upper tropospheric carbon monoxide from MOPITT, ACE-FTS, and HIPPO-QCLS

    NASA Astrophysics Data System (ADS)

    Martínez-Alonso, Sara; Deeter, Merritt N.; Worden, Helen M.; Gille, John C.; Emmons, Louisa K.; Pan, Laura L.; Park, Mijeong; Manney, Gloria L.; Bernath, Peter F.; Boone, Chris D.; Walker, Kaley A.; Kolonjari, Felicia; Wofsy, Steven C.; Pittman, Jasna; Daube, Bruce C.

    2014-12-01

    Products from the Measurements Of Pollution In The Troposphere (MOPITT) instrument are regularly validated using in situ airborne measurements. However, few of these measurements reach into the upper troposphere, thus hindering MOPITT validation in that region. Here we evaluate upper tropospheric (~500 hPa to the tropopause) MOPITT CO profiles by comparing them to satellite Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) retrievals and to measurements from the High-performance Instrumented Airborne Platform for Environmental Research Pole to Pole Observations (HIPPO) Quantum Cascade Laser Spectrometer (QCLS). Direct comparison of colocated v5 MOPITT thermal infrared-only retrievals, v3.0 ACE-FTS retrievals, and HIPPO-QCLS measurements shows a slight positive MOPITT CO bias within its 10% accuracy requirement with respect to the other two data sets. Direct comparison of colocated ACE-FTS and HIPPO-QCLS measurements results in a small number of samples due to the large disparity in sampling pattern and density of these data sets. Thus, two additional indirect techniques for comparison of noncoincident data sets have been applied: tracer-tracer (CO-O3) correlation analysis and analysis of profiles in tropopause coordinates. These techniques suggest a negative bias of ACE-FTS with respect to HIPPO-QCLS; this could be caused by differences in resolution (horizontal, vertical) or by deficiencies in the ACE-FTS CO retrievals below ~20 km of altitude, among others. We also investigate the temporal stability of MOPITT and ACE-FTS data, which provide unique global CO records and are thus important in climate analysis. Our results indicate that the relative bias between the two data sets has remained generally stable during the 2004-2010 period.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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).

  7. Nh and CH in the Ace Satellite Solar Spectrumtitle of your Abstract

    NASA Astrophysics Data System (ADS)

    Bernath, P. F.; Ram, R. S.; Colin, R.

    2010-06-01

    The Canadian ACE (Atmospheric Chemistry Experiment) mission has a high resolution (0.02 cm-1) Fourier transform spectrometer (FTS) in low earth orbit. The primary ACE mission goal is the study ozone chemistry in the stratosphere although it is making a wide range of other measurements, for example, of organic molecules in the troposphere. In the normal operating mode, the ACE-FTS measures a sequence of atmospheric absorption spectra during sunrise and sunset (``solar occultation''). As part of the measurement sequence about 16 high sun exoatmospheric spectra are recorded for each occultation to serve as reference spectra. We have co-added 224782 pure solar spectra to produce the ACE solar atlas in the 750--4400 cm-1 spectral region [Hase et al., JQSRT 111, 521 (2010), see http://www.ace.uwaterloo.ca/solaratlas.html]. The ACE solar spectrum displays prominent vibration-rotation bands of CO, OH, NH and CH, and pure rotational lines of OH and NH. An improved spectroscopic analysis for OH has already been published [Bernath and Colin, JMS 257, 20 (2009)] and we now report on similar work for NH and CH. The vibration-rotation spectra of NH have been reinvestigated using laboratory spectra and infrared solar spectra recorded from orbit by the ACE and ATMOS instruments. In addition to identifying the previously unobserved 6-5 vibration-rotation band in the laboratory spectra, many additional high N rotational lines have been observed. By combining the new observations with the previously published data and recent far infrared data, an improved set of molecular constants and term values have been derived for the NH X^3Σ^- and A^3Π states. Vibration-rotation spectra of the CH X^2Π ground state have also been re-analyzed based on laboratory spectra, the ACE solar spectrum and published data. The previously unobserved 5-4 band has been measured and the other four bands (1-0 to 4-3) have been extended to higher J values. TEXT OF YOUR ABSTRACT

  8. 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

  9. 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.

  10. 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.

  11. 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…

  12. The Two-Component System GrvRS (EtaRS) Regulates ace Expression in Enterococcus faecalis OG1RF

    PubMed Central

    Singh, Kavindra V.; La Rosa, Sabina Leanti; Cohen, Ana Luisa V.; Murray, Barbara E.

    2014-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. PMID:25385790

  13. 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.

  14. T-lymphocyte induction of human monocyte angiotensin converting enzyme (ACE) is not dependent upon T-lymphocyte proliferation

    SciTech Connect

    Vuk-Pavlovic, Z.; Rohrbach, M.S.

    1986-03-05

    Human peripheral blood monocytes cultured in serum free media for seven days show a basal activity of the ectoenzyme ACE which is augmented 2-3 times by the presence of autologous peripheral blood T-lymphocytes. Since these two cell types are also involved in autologous mixed lymphocyte reaction if serum is present, the authors compared the ability of T-cells to stimulate ACE activity in the presence or absence of proliferation (measured by /sup 3/H-thymidine incorporation). By the seventh day, cultures with 5% AB/sup +/ serum showed significant increase in proliferation but no increase in ACE activity compared to the serum free cultures. Even higher proliferation rate achieved by co-culturing T-lymphocytes with allogeneic monocytes did not increase ACE production; on the contrary, ACE activity remained at the basal level. Monocyte-T-cell co-cultures stimulated with increasing concentrations of ConA or PHA showed dose dependent increases in proliferation but parallel decreases in ACE activity. Addition of soluble antigen (Candida albicans) also enhanced proliferation but not ACE synthesis. They conclude that T-lymphocyte induction of monocyte ACE is a result of cooperation between autologous cells which is not dependent upon T-cell proliferation.

  15. Mentoring Functions within the American Council on Education (ACE) Fellows Leadership Development Program: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Grotrian-Ryan, Sheri A.

    2012-01-01

    The purpose of this study was to examine and better comprehend the concept of mentoring within the American Council on Education (ACE) Fellows Program. This study addressed the functions of mentoring and how they applied to those participating in the ACE Fellows Program--from the Fellows' (or protégés') perspectives. A sequential…

  16. Indoleamines and calcium channels influence morphogenesis in in vitro cultures of Mimosa pudica L.

    PubMed Central

    Ramakrishna, Akula; Giridhar, Parvatam

    2009-01-01

    The present article reports the interplay of indoleamine neurohormones viz. serotonin, melatonin and calcium channels on shoot organogenesis in Mimosa pudica L. In vitro grown nodal segments were cultured on MS medium with B5 vitamins containing Serotonin (SER) and Melatonin (MEL) at 100 µM and indoleamine inhibitors viz. serotonin to melatonin conversion inhibitor p-chlorophenylalanine (p-CPA) at 40 µM, serotonin reuptake inhibitor (Prozac) 20 µM. In another set of experiment, calcium at 5 mM, calcium ionophore (A23187) 100 µM, and calcium channel blocker varapamil hydrochloride (1 mM) a calcium chelator EGTA (100 µM) were administered to the culture medium. The percentage of shoot multiplication, endogenous MEL and SER were monitored during shoot organogenesis. At 100 µM SER and MEL treatment 60% and 70% explants responded for shoot multiplication respectively. Medium supplemented with either SER or MEL along with calcium (5 mM) 75%–80% explants responded for organogenesis. SER or MEL along with calcium ionophore (A23187) at 100 µM 70% explants responded for shoot multiplication. p-CPA, prozac, verapamil and EGTA, shoot multiplication was reduced and endogenous pools of SER, MEL decreased by 40–70%. The results clearly demonstrated that indoleamines and calcium channels positively influenced shoot organogenesis in M. pudica L. PMID:20514228

  17. An assessment of the calcium content of rat liver mitochondria in vivo.

    PubMed Central

    Reinhart, P H; van de Pol, E; Taylor, W M; Bygrave, F L

    1984-01-01

    The effect of systematically altering the isolation conditions on the total calcium content of mitochondria isolated from perfused rat liver was examined. We showed that, under most isolation conditions, significant redistributions of mitochondrial calcium occurred resulting in up to 5-fold changes of the total calcium content. Mitochondrial Ca2+ flux inhibitors such as Ruthenium Red and nupercaine were only partially effective in inhibiting such redistributions. We present evidence indicating that the total calcium content of rat liver mitochondria in situ may approximate 2 nmol X (mg of protein)-1. PMID:6201164

  18. Purification and partial characterization of a calcium-stimulated protease from the cyanobacterium, Anabaena variabilis.

    PubMed

    Lockau, W; Massalsky, B; Dirmeier, A

    1988-03-01

    A calcium-stimulated protease was purified to apparent homogeneity from the heterocyst-forming cyanobacterium Anabaena variabilis ATCC 29413. As judged from experiments with inhibitors and chromogenic peptide substrates, the enzyme is a serine protease with a substrate specificity like trypsin. Its apparent relative molecular mass is 52,000. Calcium depletion inhibits the enzymic activity by 92%. Half-maximal activity requires about 0.5 microM free Ca2+. The enzyme binds to a hydrophobic column in a calcium-dependent manner, indicating calcium-induced exposure of a hydrophobic domain. The possible role of the protease in heterocyst differentiation is discussed. PMID:3127208

  19. Calcium in diet

    MedlinePlus

    ... level based on scientific research evidence. Adequate Intake (AI): This level is established when there is not ... enough calcium from the foods they eat. Infants (AI) 0 to 6 months: 200 milligrams per day ( ...

  20. Get Enough Calcium

    MedlinePlus

    ... Previous section Overview 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of ... Foods and Vitamins 3 of 4 sections Take Action: Vitamin D Get enough vitamin D. Vitamin D ...

  1. Stoichiometry of Calcium Medicines

    ERIC Educational Resources Information Center

    Pinto, Gabriel

    2005-01-01

    The topic of calcium supplement and its effects on human lives is presented in the way of questions to the students. It enables the students to realize the relevance of chemistry outside the classroom surrounding.

  2. Calcium pyrophosphate arthritis

    MedlinePlus

    ... that can cause attacks of arthritis. Like with gout, crystals form in the joints. But in calcium ... pyrophosphate arthritis can be misdiagnosed as: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis

  3. 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

  4. Treatment of calcium nephrolithiasis in the patient with hyperuricosuria.

    PubMed

    Arowojolu, Omotayo; Goldfarb, David S

    2014-12-01

    Nearly one-third of patients with calcium stones have hyperuricosuria. In vitro studies and clinical trials have investigated the relationship between uric acid and calcium stones, but the association between hyperuricosuria and calcium stone formation in patients is still being debated. Uric acid appears to cause salting out of calcium oxalate in human urine. However, the importance of this in vitro phenomenon to the proposed association is not supported in cross-sectional observational studies. A small placebo-controlled randomized clinical trial showed that allopurinol decreased the rate of recurrent calcium oxalate calculi in patients with hyperuricosuria and normocalciuria. An assessment of the effect of combination therapy of allopurinol with indapamide showed no additive effect. Allopurinol may have antioxidant effects that are responsible for its reducing calcium stone formation, which are independent of xanthine oxidase inhibition. In addition, a newer xanthine oxidoreductase inhibitor, febuxostat, may also be effective in the prevention of calcium stones, as it reduces urinary uric acid excretion. PMID:24687403

  5. Wind-induced plant motion immediately increases cytosolic calcium.

    PubMed Central

    Knight, M R; Smith, S M; Trewavas, A J

    1992-01-01

    Wind is one of the most unusual and more dramatic of the environmental signals to modify plant development. Wind-stimulated crops are also known to experience considerable reductions in growth and subsequent yield. There is at present no experimental data to suggest how wind signals are perceived and transduced by plant cells. We have genetically transformed Nicotiana plumbaginifolia to express aequorin and thus produced luminous plants that directly report cytosolic calcium by emitting blue light. With these plants we have found wind stimulation to cause immediate increases in cytosolic calcium and our evidence, based on the use of specific inhibitors, suggests that this calcium is mobilized from organelle sources. Our data further suggest that wind-induced movement of tissues, by mechanically stimulating and stressing constituent plant cells, is responsible for the immediate elevation of cytosolic calcium; increases occur only when the plant tissue is actually in motion. Repeated wind stimulation renders the cells refractory to further calcium signaling but responsiveness is rapidly recovered when stimulation is subsequently diminished. Our data suggest that mechanoperception in plant cells may possibly be transduced through intracellular calcium. Since mechanoperception and transduction are considered crucial to plant morphogenesis, our observations suggest that calcium could be central in the control and generation of plant form. Images PMID:11536497

  6. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice.

    PubMed

    Hung, Yi-Han; Hsieh, Wen-Yeh; Hsieh, Jih-Sheng; Liu, Fon-Chang; Tsai, Chin-Hung; Lu, Li-Che; Huang, Chen-Yi; Wu, Chien-Liang; Lin, Chih-Sheng

    2016-01-01

    Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2(-/-)) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2(-/-) mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2(-/-) mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2(-/-) mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2(-/-) mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury. PMID:27019629

  7. Angiotensin-converting enzyme 2 (ACE2) from raccoon dog can serve as an efficient receptor for the spike protein of severe acute respiratory syndrome coronavirus.

    PubMed

    Xu, Lili; Zhang, Yanfang; Liu, Yun; Chen, Zhiwei; Deng, Hongkui; Ma, Zhongbin; Wang, Hualin; Hu, Zhihong; Deng, Fei

    2009-11-01

    Raccoon dog is one of the suspected intermediate hosts of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, the angiotensin-converting enzyme 2 (ACE2) gene of raccoon dog (rdACE2) was cloned and sequenced. The amino acid sequence of rdACE2 has identities of 99.3, 89.2, 83.9 and 80.4 % to ACE2 proteins from dog, masked palm civet (pcACE2), human (huACE2) and bat, respectively. There are six amino acid changes in rdACE2 compared with huACE2, and four changes compared with pcACE2, within the 18 residues of ACE2 known to make direct contact with the SARS-CoV S protein. A HeLa cell line stably expressing rdACE2 was established; Western blot analyses and an enzyme-activity assay indicated that the cell line expressed ACE2 at a similar level to two previously established cell lines that express ACE2 from human and masked palm civet, respectively. Human immunodeficiency virus-backboned pseudoviruses expressing spike proteins derived from human SARS-CoV or SARS-CoV-like viruses of masked palm civets and raccoon dogs were tested for their entry efficiency into these cell lines. The results showed that rdACE2 is a more efficient receptor for human SARS-CoV, but not for SARS-CoV-like viruses of masked palm civets and raccoon dogs, than huACE2 or pcACE2. This study provides useful data to elucidate the role of raccoon dog in SARS outbreaks. PMID:19625462

  8. ACE2 deficiency reduces β-cell mass and impairs β-cell proliferation in obese C57BL/6 mice.

    PubMed

    Shoemaker, Robin; Yiannikouris, Frederique; Thatcher, Sean; Cassis, Lisa

    2015-10-01

    Drugs that inhibit the renin-angiotensin system (RAS) decrease the onset of type 2 diabetes (T2D). Pancreatic islets express RAS components, including angiotensin-converting enzyme 2 (ACE2), which cleaves angiotensin II (Ang II) to angiotensin-(1-7) [Ang-(1-7)]. Overexpression of ACE2 in pancreas of diabetic mice improved glucose homeostasis. The purpose of this study was to determine if deficiency of endogenous ACE2 contributes to islet dysfunction and T2D. We hypothesized that ACE2 deficiency potentiates the decline in β-cell function and augments the development of diet-induced T2D. Male Ace2(+/y) or Ace2(-/y) mice were fed a low-fat (LF) or high-fat (HF) diet for 1 or 4 mo. A subset of 1-mo HF-fed mice were infused with Sal (Sal), losartan (Los), or Ang-(1-7). At 4 mo, while both genotypes of HF-fed mice developed a similar level of insulin resistance, adaptive hyperinsulinemia was reduced in Ace2(-/y) vs. Ace2(+/y) mice. Similarly, in vivo glucose-stimulated insulin secretion (GSIS) was reduced in 1-mo HF-fed Ace2(-/y) compared with Ace2(+/y) mice, resulting in augmented hyperglycemia. The average islet area was significantly smaller in both LF- and HF-fed Ace2(-/y) vs. Ace2(+/y) mice. Additionally, β-cell mass and proliferation were reduced significantly in HF-fed Ace2(-/y) vs. Ace2(+/y) mice. Neither infusion of Los nor Ang-(1-7) was able to correct impaired in vivo GSIS of HF-fed ACE2-deficient mice. These results demonstrate a critical role for endogenous ACE2 in the adaptive β-cell hyperinsulinemic response to HF feeding through regulation of β-cell proliferation and growth. PMID:26389599

  9. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice

    PubMed Central

    Hung, Yi-Han; Hsieh, Wen-Yeh; Hsieh, Jih-Sheng; Liu, Fon-Chang; Tsai, Chin-Hung; Lu, Li-Che; Huang, Chen-Yi; Wu, Chien-Liang; Lin, Chih-Sheng

    2016-01-01

    Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2-/-) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2-/- mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2-/- mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2-/- mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2-/- mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury. PMID:27019629

  10. Calcium influx, but not intracellular calcium release, supports PACAP-mediated ERK activation in HEK PAC1 receptor cells.

    PubMed

    May, Victor; Clason, Todd A; Buttolph, Thomas R; Girard, Beatrice M; Parsons, Rodney L

    2014-11-01

    In HEK cells expressing GFP-tagged PAC1Hop1 receptors, PACAP augments ERK phosphorylation through two parallel pathways: one through PACAP/PAC1 receptor internalization/endosome MEK/ERK signaling and the other through PLC/DAG/PKC activation. We examined whether elevation of intracellular calcium ([Ca(2+)]i) was required for either of the PACAP/PAC1 receptor-mediated ERK activation mechanisms. The PACAP (25 nM)-induced elevation of [Ca(2+)]i was greater with cells maintained in Ca(2+)-containing than in Ca(2+)-deficient solution, suggesting that both calcium release from internal stores and calcium influx contributed to the rise in [Ca(2+)]i. A thapsigargin-induced increase in [Ca(2+)]i also was greater with calcium in the external solution. OAG, the cell permeable analogue of DAG, increased [Ca(2+)]i, but only in Ca(2+)-containing solution. Decreasing external calcium or depleting internal calcium stores did not block PACAP-induced PAC1 receptor internalization. Omission of calcium from the external solution, but not thapsigargin pretreatment, significantly blunted PACAP-stimulated ERK phosphorylation. The PKC inhibitor BimI decreased PACAP-mediated ERK activation in both Ca(2+)-containing or Ca(2+)-deficient solutions. In contrast, following Pitstop 2 pretreatment to block endocytic mechanisms, PACAP activated ERK only when calcium was present in the external solution. We conclude that the endosome signaling pathway is largely calcium-independent whereas calcium influx appears necessary for the PLC/DAG/PKC component of PACAP-induced ERK activation. PMID:24723666

  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. Diversity of ace, a gene encoding a microbial surface component recognizing adhesive matrix molecules, from different strains of Enterococcus faecalis and evidence for production of ace during human infections.

    PubMed

    Nallapareddy, S R; Singh, K V; Duh, R W; Weinstock, G M; Murray, B E

    2000-09-01

    Our previous work reported that most Enterococcus faecalis strains adhered to the extracellular matrix proteins collagen types I and IV and laminin after growth at 46 degrees C, but not 37 degrees C, and we subsequently identified an E. faecalis sequence, ace, that encodes a bacterial adhesin similar to the collagen binding protein Cna of Staphylococcus aureus. In this study, we examined the diversity of E. faecalis-specific ace gene sequences among different isolates obtained from various geographic regions as well as from various clinical sources. A comparison of nucleotide and deduced amino acid sequences of Ace from nine E. faecalis strains identified a highly conserved N-terminal A domain, followed by a variable B domain which contains two to five repeats of 47 amino acids in tandem array, preceded by a 20-amino-acid partial repeat. Using 17 other strains collected worldwide, the 5' region of ace that encodes the A domain was sequenced, and these sequences showed > or =97.5% identity. Among the previously reported five amino acids critical for collagen binding by Cna of S. aureus, four were found to be identical in Ace from all strains tested. Polyclonal immune rabbit serum prepared against recombinant Ace A derived from E. faecalis strain OG1RF detected Ace in mutanolysin extracts of seven of nine E. faecalis strains after growth at 46 degrees C; Ace was detected in four different molecular sizes that correspond to the variation in the B repeat region. To determine if there was any evidence to indicate that Ace might be produced under physiological conditions, we quantitatively assayed sera collected from patients with enterococcal infections for the presence of anti-Ace A antibodies. Ninety percent of sera (19 of 21) from patients with E. faecalis endocarditis showed reactivity with titers from 1:32 to >1:1,024; the only 2 sera which lacked antibodies to Ace A had considerably lower titers of antibodies to other E. faecalis antigens as well. Human

  13. 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

  14. Angiotensin-converting Enzyme Inhibitor and Statin Medication Use and Incident Mobility Limitation in Community Older Adults. The Health, Aging and Body Composition Study

    PubMed Central

    Gray, Shelly L.; Boudreau, Robert M.; Newman, Anne B.; Studenski, Stephanie A.; Shorr, Ronald I; Bauer, Douglas C.; Simonsick, Eleanor M.; Hanlon, Joseph T

    2012-01-01

    Objective Angiotensin-converting enzyme (ACE) inhibitors and statin medications have been proposed as potential agents to prevent or delay physical disability; yet limited research has evaluated whether such use in older community dwelling adults is associated with a lower risk of incident mobility limitation. Design Longitudinal cohort study Setting Health, Aging and Body Composition (Health ABC) Participants 3055 participants who were well functioning at baseline (e.g., no mobility limitations). Measurements Summated standardized daily doses (low, medium and high) and duration of ACE inhibitor and statin use was computed. Mobility limitation (two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health status, and health behaviors. Results At baseline, ACE inhibitors and statins were used by 15.2% and 12.9%, respectively and both increased to over 25% by year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.82–1.09) nor statin use (multivariate HR 1.02; 95% CI 0.87–1.17) was associated with a lower risk for mobility limitation. Similar findings were seen in analyses examining dose- and duration-response relationships and sensitivity analyses restricted to those with hypertension. Conclusions These findings indicate that ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively do not lower risk of mobility limitation, an important life quality indicator. PMID:22092102

  15. 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…

  16. 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

  17. 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.

  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. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  20. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  1. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  2. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  3. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  4. 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…

  5. Antihypertensive effects of silk fibroin hydrolysate by alcalase and purification of an ACE inhibitory dipeptide.

    PubMed

    Zhou, Fengjuan; Xue, Zhaohui; Wang, Jiehua

    2010-06-01

    Silk fibroin, which is normally discarded as an industrial byproduct in clothing plants, was hydrolyzed with alcalase. Angiotensin I converting enzyme (ACE) inhibitory activities of the silk fibroin hydrolysates (SFH) were investigated, and the hydrolysate with hydrolysis degree of 17% exhibited the highest ACE inhibitory activity. At the tested 600 mg/kg.d and 1200 mg/kg x d doses, SFH significantly lowered blood pressure of spontaneously hypertensive rats (SHR) after chronic oral administration. SFH was further purified using consecutive chromatographic methods on Sephadex G-15 column and reverse phase high-performance liquid chromatography (RP-HPLC) on an octadecylsilane column. After its purity was confirmed by analytical RP-HPLC and capillary electrophoresis, one ACE inhibitory dipeptide was isolated, and its molecular mass and amino acid sequence were determined as 238.2 Da and Gly-Tyr, respectively, by LC-ESI/MS. The results of this study suggest that silk fibroin byproducts have the possibility to become an effective source for ACE inhibitory peptides. PMID:20481470

  6. Acute stress and cardiovascular health: is there an ACE gene connection?

    PubMed

    Holman, E Alison

    2012-10-01

    Cardiovascular disorders (CVD) are associated with acute and posttraumatic stress responses, yet biological processes underlying this association are poorly understood. This study examined whether renin-angiotensin-aldosterone system activity, as indicated by a functional single nucleotide polymorphism (SNP) in the angiotensin converting enzyme (ACE) gene, is associated with both CVD and acute stress related to the September 11, 2001 (9/11) terrorist attacks. European-American respondents (N = 527) from a nationally representative longitudinal study of coping following 9/11 provided saliva for genotyping. Respondents had completed health surveys before 9/11 and annually for 3 years after, and acute stress assessments 9 to 23 days after 9/11. Respondents with rs4291 AA or TT genotypes reported high acute stress twice as often as those with the AT genotype. Individuals with the TT genotype were 43% more likely to report increased physician-diagnosed CVD over 3 years following 9/11, when the following variables were included in the model: (a) pre-9/11 CVD, mental health, and non-CVD ailments; (b) cardiac risk factors; (c) ongoing endocrine disorders; and (d) significant demographics. The ACE rs4291 TT genotype, which has been associated with HPA axis hyperactivity and higher levels of serum angiotensin converting enzyme (ACE), predicted acute stress response and reports of physician-diagnosed CVD in a national sample following collective stress. ACE gene function may be associated with both mental and physical health disorders following collective stress. PMID:23055331

  7. 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...

  8. 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.

  9. 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…

  10. 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

  11. 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…

  12. 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…

  13. 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

  14. 76 FR 69755 - National Customs Automation Program Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... was on trade compliance and the development of the Automated Commercial Environment (ACE), the planned..., 2008 (73 FR 50337) for more information. These new capabilities include functionality specific to the... published October 20, 2010 (75 FR 64737) for more information. In order to provide the link between...

  15. 75 FR 64737 - Automated Commercial Environment (ACE): Announcement of a National Customs Automation Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... Security Act of 2002 (see 68 FR 68140, December 5, 2003), and the advance data ocean carriers are required... rule, commonly known as 10 + 2 (see 73 FR 71730, November 25, 2008).\\1\\ Currently, this information is... ACE Systems of Record Notice (71 FR 3109), published in the Federal Register on January 19, 2006....

  16. 77 FR 4815 - Ace Info Solutions, Inc., and Information International Associates; Transfer of Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-31

    ...This notice announces that pesticide related information submitted to EPA's Office of Pesticide Programs (OPP) pursuant to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA), including information that may have been claimed as Confidential Business Information (CBI) by the submitter, will be transferred to Ace Info Solutions,......

  17. 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

  18. Expression and biochemical characterisation of recombinant AceA, a bacterial alpha-mannosyltransferase.

    PubMed

    Geremia, R A; Roux, M; Ferreiro, D U; Dauphin-Dubois, R; Lellouch, A C; Ielpi, L

    1999-07-01

    Biosynthesis of repeat-unit polysaccharides and N-linked glycans proceeds by sequential transfer of sugars from the appropriate sugar donor to an activated lipid carrier. The transfer of each sugar is catalysed by a specific glycosyltransferase. The molecular basis of the specificity of sugar addition is not yet well understood, mainly because of the difficulty of isolating these proteins. In this study, the aceA gene product expressed by Acetobacter xylinum, which is involved in the biosynthesis of the exopolysaccharide acetan, was overproduced in Escherichia coli and its function was characterised. The aceA ORF was subcloned into the expression vector pET29 in frame with the S.tag epitope. The recombinant protein was identified, and culture conditions were optimised for production of the soluble protein. The results of test reactions showed that AceA is able to transfer one alpha-mannose residue from GDP-mannose to cellobiose-P-P-lipid to produce alpha-mannose-cellobiose-P-P-lipid. AceA was not able to use free cellobiose as a substrate, indicating that the pyrophosphate-lipid moiety is needed for enzymatic activity. PMID:10485283

  19. Classification of Gaia16ace as type Ia supernova near maximum

    NASA Astrophysics Data System (ADS)

    Piascik, A. S.; Steele, I. A.

    2016-02-01

    We conducted a spectroscopic observation of transient Gaia16ace at 2016-02-11T02:56:31 UT. The transient was discovered by the Gaia Photometric Science survey on 2016-02-03T22:43:39 UT at position RA=13:48:32.33 DEC=-02:03:33.6.

  20. Educational Measurement. Fourth Edition. ACE/Praeger Series on Higher Education

    ERIC Educational Resources Information Center

    Brennan, Robert L., Ed.

    2006-01-01

    "Educational Measurement" has been the bible in its field since the first edition was published by ACE in 1951. The importance of this fourth edition of "Educational Measurement" is to extensively update and extend the topics treated in the previous three editions. As such, the fourth edition documents progress in the field and provides critical…

  1. Review of the ACE-FTS measurements and recent results for the troposphere and UTLS

    NASA Astrophysics Data System (ADS)

    Bernath, Peter

    The ACE satellite mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; and (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE is making a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) gives ACE coverage of tropical, mid-latitudes and polar regions. A high-resolution (0.02 cm-1 ) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4400 cm-1 ) is measuring the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. Aerosols and clouds are being monitored using the extinction of solar radiation at 0.525 and 1.02 microns as measured by two filtered imagers as well as by their infrared spectra. A dual spectrograph called MAESTRO was added to the mission to extend the wavelength coverage to the 280-1000 nm spectral region. The principal investigator for MAESTRO is T. McElroy of the Meteorological Service of Canada. The FTS and imagers have been built by ABB-Bomem in Quebec City, while the satellite bus has been made by Bristol Aerospace in Winnipeg. ACE was selected in the Canadian Space Agency's SCISAT-1 program, and was successfully launched by NASA on August 12, 2003 for a nominal 2-year mission. The first results of ACE have been presented in a special issue of Geophysics Research Letters in 2005 and recently a special issue on ACE validation has been prepared for Atmospheric Chemistry and Physics by K

  2. 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

  3. Controlled-release scale inhibitor for use in fracturing treatments

    SciTech Connect

    Powell, R.J.; Gdanski, R.D.; McCabe, M.A.; Buster, D.C.

    1995-11-01

    This paper describes results of laboratory and field testing of a solid, controlled-release scale inhibitor for use in fracturing treatments. Laboratory testing with a continuous flow apparatus has yielded inhibitor release rates under dynamic conditions. The inhibitor was tested to determine the minimum inhibitor concentration required to inhibit the formation of CaCO{sub 3}, CaSO{sub 4}, and BaSO{sub 4} scales in a brine. A model to predict the long-term release rate of the inhibitor was developed from data collected on the continuous flow apparatus. Data from treated wells will be compared with predictions of the model. Inhibitor release-rate testing in a continuous-flow apparatus shows that a solid, calcium-magnesium polyphosphate inhibitor has a sustained release profile. Release-rate testing shows that the inhibitor can be used up to 175 F. The inhibitor is compatible with both borate and zirconium crosslinked fracturing fluids and foamed fluids. The effective lifetime of the scale treatment can be predicted based on a model developed from laboratory data. The input variables required for the prediction include: temperature, water production, amount of inhibitor, minimum effective concentration of inhibitor for the specific brine. The model can be used to aid in the design of the scale inhibitor treatment.

  4. Coronal Sources and In Situ Properties of the Solar Winds Sampled by ACE During 1999 - 2008

    NASA Astrophysics Data System (ADS)

    Fu, Hui; Li, Bo; Li, Xing; Huang, Zhenghua; Mou, Chaozhou; Jiao, Fangran; Xia, Lidong

    2015-05-01

    We identify the coronal sources of the solar winds sampled by the ACE spacecraft during 1999 - 2008 and examine the in situ solar wind properties as a function of wind sources. The standard two-step mapping technique is adopted to establish the photospheric footpoints of the magnetic flux tubes along which the ACE winds flow. The footpoints are then placed in the context of EIT 284 Å images and photospheric magnetograms, allowing us to categorize the sources into four groups: coronal holes (CHs), active regions (ARs), the quiet Sun (QS), and "undefined". This practice also enables us to establish the response to solar activity of the fractions occupied by each type of solar wind, and of their speeds and O7+/O6+ ratios measured in situ. We find that during the maximum phase, the majority of ACE winds originate from ARs. During the declining phase, CHs and ARs are equally important contributors to the ACE solar winds. The QS contribution increases with decreasing solar activity and maximizes in the minimum phase when the QS appears to be the primary supplier of the ACE winds. With decreasing activity, the winds from all sources tend to become cooler, as represented by the increasingly low O7+/O6+ ratios. On the other hand, during each activity phase, the AR winds tend to be the slowest and are associated with the highest O7+/O6+ ratios, while the CH winds correspond to the other extreme, with the QS winds lying in between. Applying the same analysis method to the slow winds alone, here defined as the winds with speeds lower than 500 km s-1, we find basically the same overall behavior, as far as the contributions of individual groups of sources are concerned. This statistical study indicates that QS regions are an important source of the solar wind during the minimum phase.

  5. 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

  6. ACE-II genotype and I allele predicts ischemic stroke among males in south India

    PubMed Central

    Vijayan, Murali; Chinniah, Rathika; Ravi, Padma Malini; Mosses Joseph, Arun Kumar; Vellaiappan, Neethi Arasu; Krishnan, Jeyaram Illiayaraja; Karuppiah, Balakrishnan

    2014-01-01

    Two hundred ischemic stroke patients and 193 age and sex matched healthy controls were studied for the presence of Angiotensin Converting Enzyme Insertion/Deletion (ACE I/D) gene polymorphism. The PCR studies revealed that ACE ‘II’ (OR = 2.055; p = 0.004) genotype and ‘I’ (OR = 1.411; p = 0.018) alleles were significantly associated with IS patients. Gender specific analysis revealed a strong association of ‘II’ (OR = 2.044; p = 0.014) genotype and ‘I’ (OR = 1.531; p = 0.011) allele with male sex. Classification of patients based on TOAST criteria, revealed a significant association for ‘II’ genotype (OR = 1.713; p = 0.043) and ‘I’ (OR = 1.382; p = 0.039) allele in LVD patients only. When the data was stratified based on age and sex, a statistically significant association was observed for ACE ‘II’ genotype (OR = 2.288; p = 0.006) and ‘I’ allele (OR = 1.395; p = 0.054) in IS male patients of > 50 years of age. The ACE ‘D’ allele was found to be increased in controls (OR = 0.709; p = 0.018) than IS patients. Multivariate logistic regression analysis showed that smoking and diabetes were the most powerful independent risk factor in LVD type of stroke. Thus, we presented here an evidence for a strong association of ACE ‘II’ genotype and ‘I’ allele compounded by factors such as smoking and diabetes among south Indian IS patients. PMID:25606450

  7. 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

  8. Ozone Measurements from the Canadian Arctic Validation of ACE Campaign: 2004 and 2005

    NASA Astrophysics Data System (ADS)

    Walker, K. A.; Strong, K.; Berman, R.; Bernath, P. F.; Boone, C.; Drummond, J. R.; Fast, H.; Fraser, A.; Goutail, F.; Harwood, M.; Kerzenmacher, T. E.; Loewen, P.; Macquarrie, K.; McElroy, C. T.; Midwinter, C.; Mittermeier, R.; Skelton, R.; Strawbridge, K.; Sung, K.; Walker, J.; Wu, H.

    2005-12-01

    Two springtime validation campaigns have been conducted in the Canadian Arctic to provide correlative measurements for validating results from the Atmospheric Chemistry Experiment (ACE) satellite mission. The satellite has two instruments on-board: a high-resolution infrared Fourier Transform Spectrometer (ACE-FTS) and a dual UV-visible-NIR spectrophotometer called MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). The validation campaigns took place at Environment Canada's Arctic Stratospheric Ozone (AStrO) Observatory in Eureka, Nunavut (80 N, 86 W) between February and April in both 2004 and 2005. Seven ground-based instruments were operated during the 2004 campaign: a ground-based adaptation of the ACE-FTS (PARIS - Portable Atmospheric Research Interferometric Spectrometer), a ground-based version of the ACE-MAESTRO, a SunPhotoSpectrometer, a zenith-viewing UV-visible grating spectrometer, a Bomem DA8 Fourier transform spectrometer, a Differential Absorption Lidar and a Brewer spectrophotometer. For the 2005 campaign, a Systeme d'Analyse par Observations Zenithales (SAOZ) instrument and a second Brewer were added to the instrument complement. Also, balloon-borne ozonesonde and radiosonde sensors were flown frequently during both campaigns. This paper will focus on comparisons of ozone measurements made by the ground-based, balloon-borne and satellite-borne instruments during the two ACE Arctic Validation campaigns. Comparisons of both retrieved columns and profiles will be presented. Also, the results from the 2004 and 2005 campaigns will be intercompared to highlight the differences between the two years.

  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 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

  11. Modelling of calcium phosphates

    NASA Astrophysics Data System (ADS)

    Calderin Hidalgo, Lazaro Juan

    This work is a contribution to a large scale joint experimental and theoretical effort to understand the biological properties of silicon doped calcium phosphates undertaken by Queen's University and Millenium Biologix Corp. We have modeled calcium phosphates and silicon doped calcium phosphates in close relation to experiment in order to study possible location of silicon in the lattice. Density functional theory has been used to study the structural and dynamical properties of small systems of calcium phosphates to gain preliminary information on phosphates and the performance of the theoretical methods. The same methods were used to investigate structural and electronic properties of larger scale calcium phosphate systems, while a classical shell model was developed to investigate the dynamical properties of such large and complex systems. In the context of the shell model a method was devised to calculate the dynamical matrix corrected for the long range Coulomb interaction in the long wave length limit. It was necessary also to develop a theoretical expression for the dielectric function in the context of the shell model. Infrared spectra and thermal parameters were calculated based on these methods. We also propose some directions for future research.

  12. Autophagy inhibitors.

    PubMed

    Pasquier, Benoit

    2016-03-01

    Autophagy is a lysosome-dependent mechanism of intracellular degradation. The cellular and molecular mechanisms underlying this process are highly complex and involve multiple proteins, including the kinases ULK1 and Vps34. The main function of autophagy is the maintenance of cell survival when modifications occur in the cellular environment. During the past decade, extensive studies have greatly improved our knowledge and autophagy has exploded as a research field. This process is now widely implicated in pathophysiological processes such as cancer, metabolic, and neurodegenerative disorders, making it an attractive target for drug discovery. In this review, we will summarize the different types of inhibitors that affect the autophagy machinery and provide some potential therapeutic perspectives. PMID:26658914

  13. Calcium signaling mediates cold sensing in insect tissues

    PubMed Central

    Teets, Nicholas M.; Yi, Shu-Xia; Lee, Richard E.; Denlinger, David L.

    2013-01-01

    The ability to rapidly respond to changes in temperature is a critical adaptation for insects and other ectotherms living in thermally variable environments. In a process called rapid cold hardening (RCH), insects significantly enhance cold tolerance following brief (i.e., minutes to hours) exposure to nonlethal chilling. Although the ecological relevance of RCH is well-established, the underlying physiological mechanisms that trigger RCH are poorly understood. RCH can be elicited in isolated tissues ex vivo, suggesting cold-sensing and downstream hardening pathways are governed by brain-independent signaling mechanisms. We previously provided preliminary evidence that calcium is involved in RCH, and here we firmly establish that calcium signaling mediates cold sensing in insect tissues. In tracheal cells of the freeze-tolerant goldenrod gall fly, Eurosta solidaginis, chilling to 0 °C evoked a 40% increase in intracellular calcium concentration as determined by live-cell confocal imaging. Downstream of calcium entry, RCH conditions significantly increased the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) while reducing phosphorylation of the inhibitory Thr306 residue. Pharmacological inhibitors of calcium entry, calmodulin activation, and CaMKII activity all prevented ex vivo RCH in midgut and salivary gland tissues, indicating that calcium signaling is required for RCH to occur. Similar results were obtained for a freeze-intolerant species, adults of the flesh fly, Sarcophaga bullata, suggesting that calcium-mediated cold sensing is a general feature of insects. Our results imply that insect tissues use calcium signaling to instantly detect decreases in temperature and trigger downstream cold-hardening mechanisms. PMID:23671084

  14. Calcium-phospholipid enhanced protein phosphorylation in human placenta

    SciTech Connect

    Moore, J.J.; Moore, R.; Cardaman, R.C.

    1986-07-01

    Calcium-activated, phospholipid-dependent protein phosphorylation has not been studied in placenta. Human placental cytosol was subjected to an endogenous protein phosphorylation assay using (..gamma..-/sup 32/P)ATP in the presence of calcium and phosphatidylserine. Protein phosphorylation was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. When compared to basal levels, calcium (10/sup -6/ M) in combination with phosphatidylserine (50 ..mu..g/ml) significantly enhanced (P < 100) /sup 32/P incorporation into phosphoproteins having mol wt 47,000, 43,000, and 37,000. Half-maximal /sup 22/P incorporation was observed with 3.5 x 10/sup -7/ M Ca/sup 2 +/ in the presence of phosphatidylserine (50 ..mu..g/ml). The effect of phosphatidylserine was biphasic. In the presence of Ca 10/sup -6/ M, /sup 32/P incorporation increased to a maximum at 70 /sup +/g/ml of phosphatidylserine. The increase was suppressed at 150 ..mu..g/ml. Tetracaine caused a dose-dependent inhibition of calcium-activated, phospholipid-dependent enhancement of the three phosphoproteins. Calcium in the absence of phospholipid enhanced the phosphorylation of a protein of 98,000 mol wt. Phosphatidylserine suppressed this enhancement. Calmodulin (10/sup -6/ M) had no detectable effect upon phosphorylation beyond that of calcium alone, but the calmodulin inhibitor R-24571 specifically inhibited the calcium-stimulated 98,000 mol wt phosphoprotein. Calcium-activated, phospholipid-dependent phospholipid-dependent phosphoproteins are present in human placental cytosol; whether calcium-activated, calmodulin-dependent phosphoproteins also are present remains a question.

  15. 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

  16. 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

  17. Signal transduction inhibitors in treatment of myelodysplastic syndromes.

    PubMed

    Bachegowda, Lohith; Gligich, Oleg; Mantzaris, Ionnis; Schinke, Carolina; Wyville, Dale; Carrillo, Tatiana; Braunschweig, Ira; Steidl, Ulrich; Verma, Amit

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by ineffective hematopoiesis that results in reduced blood counts. Although MDS can transform into leukemia, most of the morbidity experienced by these patients is due to chronically low blood counts. Conventional cytotoxic agents used to treat MDS have yielded some encouraging results but are characterized by many adverse effects in the predominantly elderly patient population. Targeted interventions aimed at reversing the bone marrow failure and increasing the peripheral blood counts would be advantageous in this cohort of patients. Studies have demonstrated over-activated signaling of myelo-suppressive cytokines such as TGF-β, TNF-α and Interferons in MDS hematopoietic stem cells. Targeting these signaling cascades could be potentially therapeutic in MDS. The p38 MAP kinase pathway, which is constitutively activated in MDS, is an example of cytokine stimulated kinase that promotes aberrant apoptosis of stem and progenitor cells in MDS. ARRY-614 and SCIO-469 are p38 MAPK inhibitors that have been used in clinical trials and have shown activity in a subset of MDS patients. TGF-β signaling has been therapeutically targeted by small molecule inhibitor of the TGF-β receptor kinase, LY-2157299, with encouraging preclinical results. Apart from TGF-β receptor kinase inhibition, members of TGF-β super family and BMP ligands have also been targeted by ligand trap compounds like Sotatercept (ACE-011) and ACE-536. The multikinase inhibitor, ON-01910.Na (Rigosertib) has demonstrated early signs of efficacy in reducing the percentage of leukemic blasts and is in advanced stages of clinical testing. Temsirolimus, Deforolimus and other mTOR inhibitors are being tested in clinical trials and have shown preclinical efficacy in CMML. EGF receptor inhibitors, Erlotinib and Gefitinib have shown efficacy in small trials that may be related to off target effects. Cell cycle regulator inhibitors

  18. Signal transduction inhibitors in treatment of myelodysplastic syndromes

    PubMed Central

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by ineffective hematopoiesis that results in reduced blood counts. Although MDS can transform into leukemia, most of the morbidity experienced by these patients is due to chronically low blood counts. Conventional cytotoxic agents used to treat MDS have yielded some encouraging results but are characterized by many adverse effects in the predominantly elderly patient population. Targeted interventions aimed at reversing the bone marrow failure and increasing the peripheral blood counts would be advantageous in this cohort of patients. Studies have demonstrated over-activated signaling of myelo-suppressive cytokines such as TGF-β, TNF-α and Interferons in MDS hematopoietic stem cells. Targeting these signaling cascades could be potentially therapeutic in MDS. The p38 MAP kinase pathway, which is constitutively activated in MDS, is an example of cytokine stimulated kinase that promotes aberrant apoptosis of stem and progenitor cells in MDS. ARRY-614 and SCIO-469 are p38 MAPK inhibitors that have been used in clinical trials and have shown activity in a subset of MDS patients. TGF-β signaling has been therapeutically targeted by small molecule inhibitor of the TGF-β receptor kinase, LY-2157299, with encouraging preclinical results. Apart from TGF-β receptor kinase inhibition, members of TGF-β super family and BMP ligands have also been targeted by ligand trap compounds like Sotatercept (ACE-011) and ACE-536. The multikinase inhibitor, ON-01910.Na (Rigosertib) has demonstrated early signs of efficacy in reducing the percentage of leukemic blasts and is in advanced stages of clinical testing. Temsirolimus, Deforolimus and other mTOR inhibitors are being tested in clinical trials and have shown preclinical efficacy in CMML. EGF receptor inhibitors, Erlotinib and Gefitinib have shown efficacy in small trials that may be related to off target effects. Cell cycle regulator inhibitors

  19. 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

  20. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model.

    PubMed

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan

    2016-09-01

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2weeks. 48h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocyte count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. PMID:27343405

  1. Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling

    PubMed Central

    Bracken, Christina; Matthews, Douglas; O'Brien, Stephen; Schiavi, Susan; Wawersik, Stefan

    2011-01-01

    Alterations to the structure of the glomerular filtration barrier lead to effacement of podocyte foot processes, leakage of albumin, and the development of proteinuria. To better understand the signaling pathways involved in the response of the glomerular filtration barrier to injury, we studied freshly isolated rat glomeruli, which allows for the monitoring and pharmacologic manipulation of early signaling events. Administration of protamine sulfate rapidly damaged the isolated glomeruli, resulting in foot process effacement and albumin leakage. Inhibition of calcium channels and chelation of extracellular calcium reduced protamine sulfate-induced damage, suggesting that calcium signaling plays a critical role in the initial stages of glomerular injury. Calcineurin inhibitors (FK506 and cyclosporine A) and the cathepsin L inhibitor E64 all inhibited protamine sulfate-mediated barrier changes, which suggests that calcium signaling acts, in part, through calcineurin- and cathepsin L-dependent cleavage of synaptopodin, a regulator of actin dynamics. The mTOR inhibitor rapamycin also protected glomeruli, demonstrating that calcium signaling has additional calcineurin-independent components. Furthermore, activation of Akt through mTOR had a direct role on glomerular barrier integrity, and activation of calcium channels mediated this process, likely independent of phosphoinositide 3-kinase. Taken together, these results demonstrate the importance of calcium and related signaling pathways in the structure and function of the glomerular filtration barrier. PMID:21784900

  2. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    ERIC Educational Resources Information Center

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  3. Lipopolysaccharides upregulate calcium concentration in mouse uterine smooth muscle cells through the T-type calcium channels.

    PubMed

    Zhang, Lijuan; Wang, Lin; Jiang, Jingyi; Zheng, Dongming; Liu, Sishi; Liu, Caixia

    2015-03-01

    Infection is a significant cause of preterm birth. Abnormal changes in intracellular calcium signals are the ultimate triggers of early uterine contractions that result in preterm birth. T‑type calcium channels play an important role in the pathogenesis of cancer, as well as endocrine and cardiovascular diseases. However, there are limited studies on their role in uterine contractions and parturition. In the present study, mouse uterine smooth muscle cells were isolated and treated with lipopolysaccharides (LPS) to mimic the microenvironment of uterine infection in vitro to investigate the role of T‑type calcium channels in the process of infection‑induced preterm birth. The results from quantitative polymerase chain reaction and western blot analysis showed that LPS significantly induced the expression of the Cav3.1 and Cav3.2 subtypes of T‑type calcium channels. Measurements of intracellular calcium concentration showed a significant increase in response to LPS. However, these effects can be reversed by T‑type calcium channel blockers. Western blot analysis further indicated that LPS induced the activation of the nuclear factor (NF)‑κB signaling pathway, and endothelin‑1 (ET‑1) was significantly upregulated, whereas NF‑κB inhibitors significantly inhibited the LPS‑induced upregulation of Cav3.1, Cav3.2 and ET‑1 expression. In addition, ET‑1 directly induced Cav3.1 and Cav3.2 expression, whereas ET‑1 antagonists inhibited the LPS‑induced upregulation of Cav3.1 and Cav3.2 expression. In conclusion, the present study demonstrates that infection triggers the upregulation of T‑type calcium channels and promotes calcium influx. This process relies on the activation of the NF‑κB/ET‑1 signaling pathway. The T‑type calcium channel is expected to become an effective target for the prevention of infection‑induced preterm birth. PMID:25573237

  4. Native store-operated calcium channels are functionally expressed in mouse spinal cord dorsal horn neurons and regulate resting calcium homeostasis

    PubMed Central

    Xia, Jingsheng; Pan, Rong; Gao, Xinghua; Meucci, Olimpia; Hu, Huijuan

    2014-01-01

    Store-operated calcium channels (SOCs) are calcium-selective cation channels that mediate calcium entry in many different cell types. Store-operated calcium entry (SOCE) is involved in various cellular functions. Increasing evidence suggests that impairment of SOCE is responsible for numerous disorders. A previous study demonstrated that YM-58483, a potent SOC inhibitor, strongly attenuates chronic pain by systemic or intrathecal injection and completely blocks the second phase of formalin-induced spontaneous nocifensive behaviour, suggesting a potential role of SOCs in central sensitization. However, the expression of SOCs, their molecular identity and function in spinal cord dorsal horn neurons remain elusive. Here, we demonstrate that SOCs are expressed in dorsal horn neurons. Depletion of calcium stores from the endoplasmic reticulum (ER) induced large sustained calcium entry, which was blocked by SOC inhibitors, but not by voltage-gated calcium channel blockers. Depletion of ER calcium stores activated inward calcium-selective currents, which was reduced by replacing Ca2+ with Ba2+ and reversed by SOC inhibitors. Using the small inhibitory RNA knockdown approach, we identified both STIM1 and STIM2 as important mediators of SOCE and SOC current, and Orai1 as a key component of the Ca2+ release-activated Ca2+ channels in dorsal horn neurons. Knockdown of STIM1, STIM2 or Orai1 decreased resting Ca2+ levels. We also found that activation of neurokinin 1 receptors led to SOCE and activation of SOCs produced an excitatory action in dorsal horn neurons. Our findings reveal that a novel SOC signal is present in dorsal horn neurons and may play an important role in pain transmission. PMID:24860175

  5. A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development.

    PubMed

    Calderón-Noreña, Diana M; González-Novo, Alberto; Orellana-Muñoz, Sara; Gutiérrez-Escribano, Pilar; Arnáiz-Pita, Yolanda; Dueñas-Santero, Encarnación; Suárez, M Belén; Bougnoux, Marie-Elisabeth; Del Rey, Francisco; Sherlock, Gavin; d'Enfert, Christophe; Correa-Bordes, Jaime; de Aldana, Carlos R Vázquez

    2015-04-01

    Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages

  6. 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

  7. [Mitochondria, calcium homeostasis and calcium signaling].

    PubMed

    Zavodnik, I B

    2016-03-01

    Са2+ is a very important and versatile intracellular signal which controls numerous biochemical and physiological (pathophysiological) processes in the cell. Good evidence exists that mitochondria are sensors, decoders and regulators of calcium signaling. Precise regulation of calcium signaling in the cell involves numerous molecular targets, which induce and decode changes of Са2+ concentrations in the cell (pumps, channels, Са2+-binding proteins, Са2+-dependent enzymes, localized in the cytoplasm and organelles). Mitochondrial Са2+ uniporter accumulates excess of Са2+ in mitochondria, while Na+/Са2+- and H+/Са2+-antiporters extrude Са2+ in the cytoplasm. Mitochondrial Са2+ overloading results in formation of mitochondria permeability transition pores which play an important role in cell death under many pathological conditions. Mitochondria regulate Са2+ homeostasis and control important cellular functions such as metabolism, proliferation, survival. Identification of cellular and mitochondrial Ca2+ transporters and understanding their functional mechanisms open up new prospects for their using as therapeutic targets. PMID:27420625

  8. Mitochondrial calcium uptake capacity modulates neocortical excitability

    PubMed Central

    Sanganahalli, Basavaraju G; Herman, Peter; Hyder, Fahmeed; Kannurpatti, Sridhar S

    2013-01-01

    Local calcium (Ca2+) changes regulate central nervous system metabolism and communication integrated by subcellular processes including mitochondrial Ca2+ uptake. Mitochondria take up Ca2+ through the calcium uniporter (mCU) aided by cytoplasmic microdomains of high Ca2+. Known only in vitro, the in vivo impact of mCU activity may reveal Ca2+-mediated roles of mitochondria in brain signaling and metabolism. From in vitro studies of mitochondrial Ca2+ sequestration and cycling in various cell types of the central nervous system, we evaluated ranges of spontaneous and activity-induced Ca2+ distributions in multiple subcellular compartments in vivo. We hypothesized that inhibiting (or enhancing) mCU activity would attenuate (or augment) cortical neuronal activity as well as activity-induced hemodynamic responses in an overall cytoplasmic and mitochondrial Ca2+-dependent manner. Spontaneous and sensory-evoked cortical activities were measured by extracellular electrophysiology complemented with dynamic mapping of blood oxygen level dependence and cerebral blood flow. Calcium uniporter activity was inhibited and enhanced pharmacologically, and its impact on the multimodal measures were analyzed in an integrated manner. Ru360, an mCU inhibitor, reduced all stimulus-evoked responses, whereas Kaempferol, an mCU enhancer, augmented all evoked responses. Collectively, the results confirm aforementioned hypotheses and support the Ca2+ uptake-mediated integrative role of in vivo mitochondria on neocortical activity. PMID:23591650

  9. Calcium and olfactory transduction.

    PubMed

    Winegar, B D; Rosick, E R; Schafer, R

    1988-01-01

    1. Inorganic cations, organic calcium antagonists, and calmodulin antagonists were applied to olfactory epithelia of frogs (Rana pipiens) while recording electroolfactogram (EOG) responses. 2. Inorganic cations inhibited EOGs in a rank order, reflecting their calcium channel blocking potency: La3+ greater than Zn2+ greater than Cd2+ greater than Al3+ greater than Ca2+ greater than Sr2+ greater than Co2+ greater than Ba2+ greater than Mg2+. Barium ion significantly enhanced EOGs immediately following application. 3. Diltiazem and verapamil produced dose-dependent EOG inhibition. 4. Calmodulin antagonists inhibited EOGs without correlation to their anti-calmodulin potency. PMID:2904344

  10. Calcium metabolism in microgravity.

    PubMed

    Heer, M; Kamps, N; Biener, C; Korr, C; Boerger, A; Zittermann, A; Stehle, P; Drummer, C

    1999-09-01

    Unloading of weight bearing bones as induced by microgravity or immobilization has significant impacts on the calcium and bone metabolism and is the most likely cause for space osteoporosis. During a 4.5 to 6 month stay in space most of the astronauts develop a reduction in bone mineral density in spine, femoral neck, trochanter, and pelvis of 1%-1.6% measured by Dual Energy X-ray Absorption (DEXA). Dependent on the mission length and the individual turnover rates of the astronauts it can even reach individual losses of up to 14% in the femoral neck. Osteoporosis itself is defined as the deterioration of bone tissue leading to enhanced bone fragility and to a consequent increase in fracture risk. Thinking of long-term missions to Mars or interplanetary missions for years, space osteoporosis is one of the major concerns for manned spaceflight. However, decrease in bone density can be initiated differently. It either can be caused by increases in bone formation and bone resorption resulting in a net bone loss, as obtained in fast looser postmenopausal osteoporosis. On the other hand decrease in bone formation and increase in bone resorption also leads to bone losses as obtained in slow looser postmenopausal osteoporosis or in Anorexia Nervosa patients. Biomarkers of bone turnover measured during several missions indicated that the pattern of space osteoporosis is very similar to the pattern of Anorexia Nervosa patients or slow looser postmenopausal osteoporosis. However, beside unloading, other risk factors for space osteoporosis exist such as stress, nutrition, fluid shifts, dehydration and bone perfusion. Especially nutritional factors may contribute considerably to the development of osteoporosis. From earthbound studies it is known that calcium supplementation in women and men can prevent bone loss of 1% bone per year. Based on these results we studied the calcium intake during several European missions and performed an experiment during the German MIR 97 mission

  11. CALCIUM-INDUCED SUPRAMOLECULAR STRUCTURES IN THE CALCIUM CASEINATE SYSTEM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular details deciphering the spontaneous calcium-induced protein aggregation process in the calcium caseinate system remain obscure. Understanding this complex process could lead to potential new applications of this important food ingredient. In this work, we studied calcium-induced supra...

  12. Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism.

    PubMed

    Wang, Yu; Shoemaker, Robin; Thatcher, Sean E; Batifoulier-Yiannikouris, Frederique; English, Victoria L; Cassis, Lisa A

    2015-06-15

    We recently demonstrated that female mice are resistant to the development of obesity-induced hypertension through a sex hormone-dependent mechanism that involved adipose angiotensin-converting enzyme 2 (ACE2). In this study, we hypothesized that provision of 17β-estradiol (E2) to ovariectomized (OVX) high-fat (HF)-fed female hypertensive mice would reverse obesity-hypertension through an ACE2-dependent mechanism. Pilot studies defined dose-dependent effects of E2 in OVX female mice on serum E2 concentrations and uterine weights. An E2 dose of 36 μg/ml restored normal serum E2 concentrations and uterine weights. Therefore, HF-fed OVX female Ace2(+/+) and Ace2(-/-) mice were administered vehicle or E2 (36 μg/ml) for 16 wk. E2 administration significantly decreased body weights of HF-fed OVX female Ace2(+/+) and Ace2(-/-) mice of either genotype. At 15 wk, E2 administration decreased systolic blood pressure (SBP) of OVX HF-fed Ace2(+/+) but not Ace2(-/-) females during the light but not the dark cycle. E2-mediated reductions in SBP in Ace2(+/+) females were associated with significant elevations in adipose ACE2 mRNA abundance and activity and reduced plasma ANG II concentrations. In contrast to females, E2 administration had no effect on any parameter quantified in HF-fed male hypertensive mice. In 3T3-L1 adipocytes, E2 promoted ACE2 mRNA abundance through effects at estrogen receptor-α (ERα) and resulted in ERα-mediated binding at the ACE2 promoter. These results demonstrate that E2 administration to OVX females reduces obesity-induced elevations in SBP (light cycle) through an ACE2-dependent mechanism. Beneficial effects of E2 to decrease blood pressure in OVX obese females may result from stimulation of adipose ACE2. PMID:26078188

  13. Calcium carbonate with magnesium overdose

    MedlinePlus

    The combination of calcium carbonate and magnesium is commonly found in antacids. These medicines provide heartburn relief. Calcium carbonate with magnesium overdose occurs when someone takes more than the ...

  14. Calcium Content of Common Foods

    MedlinePlus

    ... 130 Waffle 80 g 47 Meat, fish and eggs Food Serving Size Calcium (mg) Egg 50 g 27 Red meat 120 g 7 ... foods Food Serving Size Calcium (mg) Quiche (cheese, eggs) 200 g 212 Omelette with cheese 120 g ...

  15. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  16. Children's Bone Health and Calcium

    MedlinePlus

    ... Trials Resources and Publications Children's Bone Health and Calcium: Condition Information Skip sharing on social media links ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  17. Alternative therapies for the management of inhibitors.

    PubMed

    Shima, M; Lillicrap, D; Kruse-Jarres, R

    2016-07-01

    The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains a major treatment complication encountered in the treatment of haemophilia. Not all patients with even the same severity and genotype develop inhibitors suggesting an underlying mechanism of tolerance against FVIII- or FIX-related immunity. One mechanism may be central tolerance observed in patients in whom the FVIII mutation enables some production of the protein. The other is a peripheral tolerance mechanism which may be evident in patients with null mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI-1, BAX801) has been developed for the haemostatic treatment of both congenital haemophilia with inhibitor (CHAWI) and acquired haemophilia A (AHA). In 28 subjects with AHA with life-/limb-threatening bleeding, rpFVIII reduced or stopped bleeding in all patients within 24 h. The cross-reactivity of anti-human FVIII antibodies to rpFVIII remains around 30-50%. Recently, new therapeutics based on the quite novel concepts have been developed and clinical studies are ongoing. These are humanized asymmetric antibody mimicking FVIIIa function by maintaining a suitable interaction between FIXa and FX (Emicizumab, ACE910), and small interfering RNAs (siRNA, ALN-AT3) suppress liver production of AT through post-transcriptional gene silencing and a humanized anti-TFPI monoclonal antibody (Concizumab). Their main advantages are longer half-life, subcutaneous applicability and efficacy irrespective of the presence of inhibitors which will make it easier to initiate more effective treatment especially early childhood. PMID:27405674

  18. Artemisinin Induces Calcium-Dependent Protein Secretion in the Protozoan Parasite Toxoplasma gondii▿ †

    PubMed Central

    Nagamune, Kisaburo; Beatty, Wandy L.; Sibley, L. David

    2007-01-01

    Intracellular calcium controls several crucial cellular events in apicomplexan parasites, including protein secretion, motility, and invasion into and egress from host cells. The plant compound thapsigargin inhibits the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA), resulting in elevated calcium and induction of protein secretion in Toxoplasma gondii. Artemisinins are natural products that show potent and selective activity against parasites, making them useful for the treatment of malaria. While the mechanism of action is uncertain, previous studies have suggested that artemisinin may inhibit SERCA, thus disrupting calcium homeostasis. We cloned the single-copy gene encoding SERCA in T. gondii (TgSERCA) and demonstrate that the protein localizes to the endoplasmic reticulum in the parasite. In extracellular parasites, TgSERCA partially relocalized to the apical pole, a highly active site for regulated secretion of micronemes. TgSERCA complemented a calcium ATPase-defective yeast mutant, and this activity was inhibited by either thapsigargin or artemisinin. Treatment of T. gondii with artemisinin triggered calcium-dependent secretion of microneme proteins, similar to the SERCA inhibitor thapsigargin. Artemisinin treatment also altered intracellular calcium in parasites by increasing the periodicity of calcium oscillations and inducing recurrent, strong calcium spikes, as imaged using Fluo-4 labeling. Collectively, these results demonstrate that artemisinin perturbs calcium homeostasis in T. gondii, supporting the idea that Ca2+-ATPases are potential drug targets in parasites. PMID:17766463

  19. Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate.

    PubMed

    Hou, S H; Zhao, J; Ellman, C F; Hu, J; Griffin, Z; Spiegel, D M; Bourdeau, J E

    1991-08-01

    We evaluated the acute effects of varying dialysate calcium concentration on plasma concentrations and dialyzer fluxes of calcium and phosphorus in adult hemodialysis patients. Seven individuals with stable end-stage renal failure were dialyzed 4 hours, three times weekly. The effects of dialysates containing 1.75, 1.25, or 0.75 mmol/L (70.1, 50.1, or 30.1 mg/L) of calcium were compared. Each patient was studied once at each bath calcium concentration. Compared with the predialysis mean value of 2.27 mmol/L (9.1 mg/dL), plasma total calcium concentration increased, remained constant, or decreased with the 1.75-, 1.25-, or 0.75-mmol/L calcium dialysates, respectively. The 0.75-mmol/L calcium dialysate did not cause signs or symptoms of hypocalcemia (and the plasma calcium concentration did not fall below 1.80 mmol/L [7.2 mg/dL]). Plasma phosphorus concentrations decreased equally from a predialysis mean value of 2.16 mmol/L (6.7 mg/dL), regardless of the dialysate calcium concentration. After 4 hours of treatment with the three different dialysates, the cumulative calcium fluxes were significantly different. With 1.75 mmol/L calcium, mean bodily calcium accumulation was 21.9 mmol (879 mg). With 1.25 mmol/L, there was no net calcium flux. With 0.75 mmol/L, mean patient calcium loss was 5.8 mmol (231 mg). Mean phosphorus removal after 4 hours was 32.5 mmol (1,006 mg) and was unaffected by dialysate calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1867178

  20. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    NASA Technical Reports Server (NTRS)

    Jorgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne; Civitelli, Roberto; Sorensen, Ole Helmer; Steinberg, Thomas H.

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium.

  1. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adequate intakes of vitamin D and calcium are essential preventative measures and essential components of any therapeutic regimen for osteoporosis. Vitamin D is also important for the prevention of falls. Current evidence suggests that a 25-hydroxyvitamin D level of 75 nmol/L (30 ng/ml) or higher ...

  2. High Blood Calcium (Hypercalcemia)

    MedlinePlus

    ... as sarcoidosis • Hormone disorders, such as overactive thyroid (hyperthyroidism) • A genetic condition called familial hypocalciuric hypercalcemia • Kidney ... topics: www.hormone.org (search for PHPT, calcium, hyperthyroidism, or osteoporosis) • MedlinePlus (National Institutes of Health-NIH): ...

  3. Calcium silicate insulation structure

    DOEpatents

    Kollie, Thomas G.; Lauf, Robert J.

    1995-01-01

    An insulative structure including a powder-filled evacuated casing utilizes a quantity of finely divided synthetic calcium silicate having a relatively high surface area. The resultant structure-provides superior thermal insulating characteristics over a broad temperature range and is particularly well-suited as a panel for a refrigerator or freezer or the insulative barrier for a cooler or a insulated bottle.

  4. Diet and calcium stones.

    PubMed Central

    Hughes, J; Norman, R W

    1992-01-01

    OBJECTIVE: To review the current literature on the dietary modification of urinary risk factors as a means of reducing the likelihood of recurrent stone formation and to develop practical dietary recommendations that might be useful to this end. DATA SOURCES: MEDLINE was searched for English-language articles published from 1983 to 1990. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA SYNTHESIS: Information on the dietary intake of calcium, oxalate, protein, sodium and fibre and on alcohol and fluid intake was used to develop practical guidelines on dietary modification. CONCLUSION: Dietary modification plays an important role in the reduction of urinary risk factors in patients with calcium stone disease of the urinary tract. As an initial form of prevention attention should be directed toward moderating the intake of calcium, oxalate, protein, sodium and alcohol and increasing the intake of fibre and water. Future research should include an assessment of the long-term reduction of dietary and urinary risk factors and the rates of recurrence of calcium stones. PMID:1310430

  5. Calcium biofortification of crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More than half of the world's population is deficient in calcium (Ca), iron (Fe), iodine (I), magnesium (Mg), selenium (Se), or zinc (Zn). The consumption of plants, directly or via livestock, containing inadequate concentrations of particular minerals causes these deficiencies. Agronomic and geneti...

  6. The Plasma Membrane Calcium Pump

    NASA Technical Reports Server (NTRS)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  7. Impregnating Coal With Calcium Carbonate

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

    1991-01-01

    Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

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

    PubMed

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

    2014-02-01

    ACE (angiotensin-1-converting enzyme) is a zinc metallopeptidase that plays a prominent role in blood pressure regulation and electrolyte homeostasis. ACE consists of two homologous domains that despite similarities of sequence and topology display differences in substrate processing and inhibitor binding. The design of inhibitors that selectively inhibit the N-domain (N-selective) could be useful in treating conditions of tissue injury and fibrosis due to build-up of N-domain-specific substrate Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro). Using a receptor-based SHOP (scaffold hopping) approach with N-selective inhibitor RXP407, a shortlist of scaffolds that consisted of modified RXP407 backbones with novel chemotypes was generated. These scaffolds were selected on the basis of enhanced predicted interaction energies with N-domain residues that differed from their C-domain counterparts. One scaffold was synthesized and inhibitory binding tested using a fluorogenic ACE assay. A molecule incorporating a tetrazole moiety in the P2 position (compound 33RE) displayed potent inhibition (K(i)=11.21±0.74 nM) and was 927-fold more selective for the N-domain than the C-domain. A crystal structure of compound 33RE in complex with the N-domain revealed its mode of binding through aromatic stacking with His388 and a direct hydrogen bond with the hydroxy group of the N-domain specific Tyr369. This work further elucidates the molecular basis for N-domain-selective inhibition and assists in the design of novel N-selective ACE inhibitors that could be employed in treatment of fibrosis disorders. PMID:24015848

  9. Association between ACE polymorphism, cognitive phenotype and APOE E4 allele in a Tunisian population with Alzheimer disease.

    PubMed

    Achouri-Rassas, Afef; Ali, Nadia Ben; Cherif, Aroua; Fray, Saloua; Siala, Hajer; Zakraoui, Nouria Oudiaa; Hadj-Fredj, Sondes; Kechaou, Mariem; Anane, Nadia; Echebi, Slim; Messaoud, Taieb; Belal, Samir

    2016-03-01

    Angiotensin-converting enzyme (ACE) has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the ACE gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), and is generally considered to be a disorder primarily affecting memory. We conducted a case-control study in a sample composed of 85 sporadic AD patients and 90 age- and sex-matched controls to investigate the possible effect of the polymorphism and cognitive profile. Our data revealed an association between the ACE polymorphism and AD risk. There was a significant difference in the ACE allele or genotype frequencies between cases and controls. The D/D genotype showed an increased risk for AD and in the amnestic group and the effect was independent on ApoE genotypes. PMID:26456241

  10. 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.

  11. 75 FR 82010 - AceInfo Solutions and Avaya Government Solutions, Koansys LLC, and Quality Associates Inc...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY AceInfo Solutions and Avaya Government Solutions, Koansys LLC, and Quality Associates Inc... completed their work. List of Subjects Environmental protection, Business and industry, Government...

  12. 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.

  13. ACE observations of magnetic waves arising from newborn interstellar pickup helium ions

    NASA Astrophysics Data System (ADS)

    Argall, Matthew R.; Fisher, Meghan K.; Joyce, Colin J.; Smith, Charles W.; Isenberg, Philip A.; Vasquez, Bernard J.; Schwadron, Nathan A.; Skoug, Ruth M.

    2015-11-01

    We report low-frequency magnetic waves that were observed by the Advanced Composition Explorer (ACE) spacecraft on day of year 180 of 1999 with characteristics consistent with the predictions of waves excited by newborn interstellar pickup He+ ions. This event was found by examining daily spectrograms of MAG data, a new data product that is now available to the community via the ACE Science Center. The event shown here is one of approximately 20 similar events that will be analyzed in future studies. This event is fairly typical of those we have found so far. The waves exist at spacecraft-frame frequencies between the He+ cyclotron frequency and approximately twice the H+ cyclotron frequency. Fluctuations are transverse to the mean magnetic field, are noncompressive, circularly polarized, have field-aligned minimum variance directions, and are left-hand polarized in the spacecraft frame as predicted by theory. The event lasts for just under 1 h.

  14. 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

  15. Systematic Variation in the Spectral Slope of the IMF at ACE

    NASA Astrophysics Data System (ADS)

    Thomson, David J.

    Inferences on turbulence in interplanetary plasmas commonly depend on the slope of the power spectrum. We have studied the slopes of spectra of the interplanetary magnetic field and charged particles from the HISCALE and EPAM detectors on Ulysses and ACE and find that it is systematically nonstationary. As an example, when the spectra are estimated on time blocks varying between three hours and one day, the average slope on the ACE GSE Y component of the IMF is close to -5/3, but fluctuations about this average are not random. Using 1-minute data, the slopes made from three hour data blocks offset by one hour gives a new time series. Solar rotation and its first harmonic are nearly absent in the spectrum of this series, but there are a series of strong peaks that may be convection or gravity modes.

  16. Solar Activity and GCR Particle Flux Variations: Assessment and Modeling with Ulysses and ACE/CRIS

    NASA Astrophysics Data System (ADS)

    Saganti, Premkumar

    Galactic Cosmic Ray (GCR) environment during the current and historically known lower solar minimum condition indicate some of the very high anticipated measurements of particle spectral data. Data from the Ulysses spacecraft in the polar orbit about the sun during the years 2004 and 2008 (about 5 AU) provided proton and alpha particle flux data and showed such anticipated high particle flux variations. Also, ACE/CRIS spacecraft data during the years 2007 and 2009 showed some of the high particle flux measurements of several heavy ions such as oxygen and iron. We present Ulysses and ACE/CRIS measured particle flux data and discuss their high density and variations in the context of the current low solar activity for depicting current space radiation environment.

  17. 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.

  18. 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

  19. CHARACTERIZATION OF CARBIDE LIME TO IDENTIFY SULFITE OXIDATION INHIBITORS

    EPA Science Inventory

    The report gives results of a study of carbide lime--a by-product of acetylene manufacture, primarily calcium hydroxide--used in a flue gas desulfurization (FGD) system at Louisville Gas and Electric (LGE). The study was undertaken to: identify sulfite ion oxidation inhibitors in...

  20. Interaction Between ACE I/D and ACTN3 R557X Polymorphisms in Polish Competitive Swimmers.

    PubMed

    Grenda, Agata; Leońska-Duniec, Agata; Kaczmarczyk, Mariusz; Ficek, Krzysztof; Król, Paweł; Cięszczyk, Paweł; Zmijewski, Piotr

    2014-09-29

    We hypothesized that the ACE ID / ACTN3 R577X genotype combination was associated with sprint and endurance performance. Therefore, the purpose of the present study was to determine the interaction between both ACE ID and ACTN3 R577X polymorphisms and sprint and endurance performance in swimmers. Genomic DNA was extracted from oral epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany). All samples were genotyped using a real-time poly- merase chain reaction. The ACE I/D and the ACTN3 R577X genotype frequencies met Hardy-Weinberg expectations in both swimmers and controls. When the two swimmer groups, long distance swimmers (LDS) and short distance swimmers (SDS), were compared with control subjects in a single test, a significant association was found only for the ACE polymorphism, but not for ACTN3. Additionally, four ACE/ACTN3 combined genotypes (ID/RX, ID/XX, II/RX and II/XX) were statistically significant for the LDS versus Control comparison, but none for the SDS versus Control comparison. The ACE I/D and the ACTN3 R577X polymorphisms did not show any association with sprint swimming, taken individually or in combination. In spite of numerous previous reports of associations with athletic status or sprint performance in other sports, the ACTN3 R577X polymorphism, in contrast to ACE I/D, was not significantly associated with elite swimming status when considered individually. However, the combined analysis of the two loci suggests that the co-occurrence of the ACE I and ACTN3 X alleles may be beneficial to swimmers who compete in long distance races. PMID:25414746