ACE-inhibitorer er fortsat førstevalg ved behandling af hjertesvigt--en gennemgang af et Cochranereview

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Gadsbøll, Niels; Torp-Pedersen, Christian Tobias

2013-01-01

A new Cochrane metaanalysis has reviewed the literature on the use of angiotensin receptor blockers (ARB) in patients with heart failure and left ventricular systolic dysfunction. The conclusion supports the present recommendation from the European Society of Cardiology that angiotensin converting...... enzyme inhibitors (ACE-I) are first choice and that ARBs should be reserved to patients who are intolerant to ACE-Is. Neither ACE-Is nor ARBs are effective in the treatment of heart failure patients with normal left ventricular function....

Rapid screening and identification of ACE inhibitors in snake venoms using at-line nanofractionation LC-MS.

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Mladic, Marija; de Waal, Tessa; Burggraaff, Lindsey; Slagboom, Julien; Somsen, Govert W; Niessen, Wilfried M A; Manjunatha Kini, R; Kool, Jeroen

2017-10-01

This study presents an analytical method for the screening of snake venoms for inhibitors of the angiotensin-converting enzyme (ACE) and a strategy for their rapid identification. The method is based on an at-line nanofractionation approach, which combines liquid chromatography (LC), mass spectrometry (MS), and pharmacology in one platform. After initial LC separation of a crude venom, a post-column flow split is introduced enabling parallel MS identification and high-resolution fractionation onto 384-well plates. The plates are subsequently freeze-dried and used in a fluorescence-based ACE activity assay to determine the ability of the nanofractions to inhibit ACE activity. Once the bioactive wells are identified, the parallel MS data reveals the masses corresponding to the activities found. Narrowing down of possible bioactive candidates is provided by comparison of bioactivity profiles after reversed-phase liquid chromatography (RPLC) and after hydrophilic interaction chromatography (HILIC) of a crude venom. Additional nanoLC-MS/MS analysis is performed on the content of the bioactive nanofractions to determine peptide sequences. The method described was optimized, evaluated, and successfully applied for screening of 30 snake venoms for the presence of ACE inhibitors. As a result, two new bioactive peptides were identified: pELWPRPHVPP in Crotalus viridis viridis venom with IC 50  = 1.1 μM and pEWPPWPPRPPIPP in Cerastes cerastes cerastes venom with IC 50  = 3.5 μM. The identified peptides possess a high sequence similarity to other bradykinin-potentiating peptides (BPPs), which are known ACE inhibitors found in snake venoms.

Evaluation of ACE inhibitors lipophilicity using in silico and chromatographically obtained hydrophobicity parameters

Directory of Open Access Journals (Sweden)

Odović Jadranka V.

2013-01-01

Full Text Available The aim of this study was to compare different calculation methods to determine lipophilicity, expressed as logP value, of seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, and benazapril with significantly different structure. Experimentally determined n-octanol/water partition coefficients, logPO/W values, were obtained from relevant literature. The correlations between all collected logP values were studied and the best agreements between calculated logP and experimentally determined logPO/W values, were observed for KOWWINlogP or MilogP values (r = 0.999 or r = 0.974, respectively. The correlations between all collected logP values and chromatographically (reversed-phase thin-layer chromatography obtained hydrophobicity parameters, RM0 and C0, were established. The good correlations (r > 0.90 were obtained in the majority of relationships. The KOWWINlogP was established as the most suitable hydrophobicity parameter of investigated group of ACE inhibitors with r = 0.981 for correlation with RM0 and r = 0.977 for correlation with C0 parameters (water-methanol mobile phase. Using multiple linear regressions, it was established that application of two selected logP, calculated by different mathematical approaches, led to very good correlation due to the benefits of both calculation methods. The good relationships indicate that the computed logP, with careful selection of method calculation, can be useful in ACE inhibitors lipophilicity evaluation, as high-throughput screening technique.

The association between ACE inhibitors and the complex regional pain syndrome: Suggestions for a neuro-inflammatory pathogenesis of CRPS.

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de Mos, M; Huygen, F J P M; Stricker, B H Ch; Dieleman, J P; Sturkenboom, M C J M

2009-04-01

Antihypertensive drugs interact with mediators that are also involved in complex regional pain syndrome (CRPS), such a neuropeptides, adrenergic receptors, and vascular tone modulators. Therefore, we aimed to study the association between the use of antihypertensive drugs and CRPS onset. We conducted a population-based case-control study in the Integrated Primary Care Information (IPCI) database in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during an expert visit (using IASP criteria), or if they had been diagnosed by a medical specialist. Up to four controls per cases were selected, matched on gender, age, calendar time, and injury. Exposure to angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, beta-blockers, calcium channel blockers, and diuretics was assessed from the automated prescription records. Data were analyzed using multivariate conditional logistic regression. A total of 186 cases were matched to 697 controls (102 confirmed during an expert visit plus 84 with a specialist diagnosis). Current use of ACE inhibitors was associated with an increased risk of CRPS (OR(adjusted): 2.7, 95% CI: 1.1-6.8). The association was stronger if ACE inhibitors were used for a longer time period (OR(adjusted): 3.0, 95% CI: 1.1-8.1) and in higher dosages (OR(adjusted): 4.3, 95% CI: 1.4-13.7). None of the other antihypertensive drug classes was significantly associated with CRPS. We conclude that ACE inhibitor use is associated with CRPS onset and hypothesize that ACE inhibitors influence the neuro-inflammatory mechanisms that underlie CRPS by their interaction with the catabolism of substance P and bradykinin.

Associations between ACE-Inhibitors, Angiotensin Receptor Blockers, and Lean Body Mass in Community Dwelling Older Women.

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Bea, Jennifer W; Wassertheil-Smoller, Sylvia; Wertheim, Betsy C; Klimentidis, Yann; Chen, Zhao; Zaslavsky, Oleg; Manini, Todd M; Womack, Catherine R; Kroenke, Candyce H; LaCroix, Andrea Z; Thomson, Cynthia A

2018-01-01

Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women's Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition ( n =10,635) at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (%) was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p =0.001). There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term.

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive subjects in response to ACE inhibitors.

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Heidari, Farzad; Vasudevan, Ramachandran; Mohd Ali, Siti Zubaidah; Ismail, Patimah; Etemad, Ali; Pishva, Seyyed Reza; Othman, Fauziah; Abu Bakar, Suhaili

2015-12-01

Several studies show that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with hypertension in various populations. The present study sought to determine the association of the I/D gene polymorphism among Malay male essential hypertensive subjects in response to ACE inhibitors (enalapril and lisinopril). A total of 72 patients with newly diagnosed hypertension and 72 healthy subjects were recruited in this study. Blood pressure was recorded from 0 to 24 weeks of treatment with enalapril or lisinopril. Genotyping of the I/D polymorphism was carried out using a standard PCR method. Statistically significant association of the D allele of the ACE gene was observed between the case and control subjects (p ACE gene. Patients carrying the DD genotype had higher blood pressure-lowering response when treated with ACE inhibitors enalapril or lisinopril than those carrying ID and II genotypes, suggesting that the D allele may be a possible genetic marker for essential hypertension among Malay male subjects. © The Author(s) 2014.

Perindopril and residual chronic subdural hematoma volumes six weeks after burr hole surgery

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Poulsen, Frantz Rom; Munthe, Sune; Søe, Morten

2014-01-01

OBJECTIVE: Recurrence rates of between 5% and 25% have been reported following surgery for chronic subdural hematoma (CSH). A previous study showed that the treatment with angiotensin converting enzyme (ACE) inhibitors decreases the risk of recurrence. To test the effects of ACE inhibitors...

The angiotensin converting enzyme (ACE) inhibitor, captopril disrupts the motility activation of sperm from the silkworm, Bombyx mori.

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Nagaoka, Sumiharu; Kawasaki, Saori; Kawasaki, Hideki; Kamei, Kaeko

2017-11-01

Angiotensin I-converting enzyme (also known as peptidyl dicarboxypeptidase A, ACE, and EC 3.4.15.1), which is found in a wide range of organisms, cleaves C-terminal dipeptides from relatively short oligopeptides. Mammalian ACE plays an important role in the regulation of blood pressure. However, the precise physiological functions of insect ACE homologs have not been understood. As part of our effort to elucidate new physiological roles of insect ACE, we herein report a soluble ACE protein in male reproductive secretions from the silkmoth, Bombyx mori. Seminal vesicle sperm are quiescent in vitro, but vigorous motility is activated by treatment with either a glandula (g.) prostatica homogenate or trypsin in vitro. When seminal vesicle sperm were pre-incubated with captopril, a strong and specific inhibitor of mammalian ACE, and then stimulated to initiate motility by the addition of the g. prostatica homogenate or trypsin, the overall level of acquired motility was reduced in an inhibitor-concentration-dependent manner. In the course of this project, we detected ACE-related carboxypeptidase activity that was inhibited by captopril in both the vesicular (v.) seminalis of the noncopulative male reproductive tract and in the spermatophore that forms in the female bursa copulatrix at the time of mating, just as in an earlier report on the tomato moth, Lacanobia oleracea, which belongs to a different lepidopteran species (Ekbote et al., 2003a). Two distinct genes encoding ACE-like proteins were identified by analysis of B. mori cDNA, and were named BmAcer and BmAcer2, respectively [the former was previously reported by Quan et al. (2001) and the latter was first isolated in this paper]. RT-qPCR and Western blot analyses indicated that the BmAcer2 was predominantly produced in v. seminalis and transferred to the spermatophore during copulation, while the BmAcer was not detected in the adult male reproductive organs. A recombinant protein of BmAcer2 (devoid of a signal

Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

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Adeghate, E; Hasan, M Y; Ponery, A S; Nurulain, S M; Petroianu, G A

2005-12-01

The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p catalase positive cells in the clofibrate group is higher than in the moexipril group (p inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

Addition of vitamin D reverses the decline in GFR following treatment with ACE inhibitors/angiotensin receptor blockers in patients with chronic kidney disease.

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Soares, Abel Esteves; Maes, Michael; Godeny, Paula; Matsumoto, Andressa Keiko; Barbosa, Décio Sabbatini; da Silva, Taysa Antonia F; Souza, Flávio Henrique M O; Delfino, Vinicius Daher Alvares

2017-12-15

Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m 2 ) patients with and without vitamin D deficiency. The patients ingested six-month cholecalciferol 50,000IU oral supplementation to chronic kidney disease patients with vitamin D deficiency. We hypothesize changes in estimated glomerular filtration rate over study period. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials. Copyright © 2017. Published by Elsevier Inc.

ACE inhibitors and calcium antagonists in the treatment of congestive heart failure

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Hansen, J F

1995-01-01

heart failure in the SOLVD trials. In post-myocardial infarction patients, the calcium antagonist nifedipine did not affect mortality or morbidity; diltiazem improved prognosis in patients without congestive heart failure and in patients with non-Q-wave infarction; and verapamil improved prognosis...... by prevention of reinfarction and sudden death. Combination treatment with both verapamil, which has pronounced antiischemic properties and prevents sudden death and reinfarction, and an ACE inhibitor, which prevents the progression of heart failure, is a possibility for future cardiovascular therapy...

Evaluation of coronary blood flow reserve by 13N-NH3 positron emission computed tomography (PET) with dipyridamole in the treatment of hypertension with the ACE inhibitor (Cilazapril)

International Nuclear Information System (INIS)

Masuda, Daisuke; Nohara, Ryuji; Tamaki, Nagara

2000-01-01

The purpose of this study was to evaluate the effect of treatment with an angiotensin-converting enzyme (ACE) inhibitor (Cilazapril) for early hypertensive patients in terms of coronary blood flow reserve evaluated by 13 NH 3 -positron emission tomography (PET). Before and after 12 weeks of ACE inhibitor treatment, 13 NH 3 -PET with dipyridamole provocation test was performed, and definite myocardial perfusion and coronary flow reserve (CFR) were calculated. Compared to our normal subjects previously reported (2.61±0.74), average coronary flow reserve was decreased (1.70±0.64 in hypertensive patients), and improved after treatment (1.77±0.52), but not significantly. Of 12 patients, five (42%) showed improved coronary flow reserve from 1.34 to 1.99 without a significant change in the resting flow. Only one patient (8%) showed deterioration after the ACE inhibitor treatment. The coronary vascular resistance (CVR) after ACE inhibitor treatment of the patients with CFR <2.0 decreased significantly compared with those with CFR ≥2.0 (p<0.03). These results indicate that hypertensive patients at the early stage show decreased coronary flow reserve despite having normal resting flow. Treatment with an ACE inhibitor (Cilazapril) for 12 weeks improved coronary flow reserve in 42% of our patients. The CVR of the patients with CFR <2.0 showed improvement compared to those with CFR ≥2.0. This result indicates that an ACE inhibitor (e.g., Cilazapril) should be one of the choices for improving CFR if hypertensive patients in early stage show signs of ischemia or diastolic dysfunction, which may be one of the sequels of reserve restriction. (author)

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

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

2014-01-01

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

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

DEFF Research Database (Denmark)

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...

Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

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Zhang, Yanling; Ma, Lulu; Wu, Junyan; Chen, Tingting

2015-06-01

Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations.

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Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2017-01-01

To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

ACE phenotyping in Gaucher disease.

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Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

2018-04-01

Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Angiotensin-Converting Enzyme Inhibitor/Calcium Antagonist Combination Therapy on Renal Function in Hypertensive Patients With Chronic Kidney Disease: Chikushi Anti-Hypertension Trial - Benidipine and Perindopril.

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Okuda, Tetsu; Okamura, Keisuke; Shirai, Kazuyuki; Urata, Hidenori

2018-02-01

Appropriate blood pressure control suppresses progression of chronic kidney disease (CKD). If an angiotensin-converting enzyme (ACE) inhibitor is ineffective, adding a calcium antagonist is recommended. We compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD. Patients who failed to achieve the target blood pressure (systolic/diastolic: < 130/80 mm Hg) with perindopril monotherapy were randomized to either combined therapy with perindopril and the L-type calcium antagonist amlodipine (group A) or perindopril and the T/L type calcium antagonist benidipine (group B). The primary endpoint was the change of the estimated glomerular filtration rate (eGFR) after 2 years. Eligible patients had a systolic pressure ≥ 130 mm Hg and/or diastolic pressure ≥ 80 mm Hg and CKD (urine protein (+) or higher, eGFR < 60 min/mL/1.73 m 2 ). After excluding 38 patients achieving the target blood pressure with perindopril monotherapy, 121 patients were analyzed (62 in group A and 59 in group B). Blood pressure decreased significantly in both groups, but there was no significant change of the eGFR. However, among patients with diabetes, eGFR unchanged in group B (n = 37, 59.1 ± 15.1 vs. 61.2 ± 27.9, P = 0.273), whereas decreased significantly in group A (n = 31, 57.3 ± 16.0 vs. 53.7 ± 16.7, P = 0.005). In hypertensive patients with diabetic nephropathy, combined therapy with an ACE inhibitor and T/L type calcium antagonist may prevent deterioration of renal function more effectively than an ACE inhibitor/L type calcium antagonist combination.

A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension

DEFF Research Database (Denmark)

Petersen, L J; Petersen, J R; Talleruphuus, U

2001-01-01

Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment with ...

Effect of pre-stroke use of ACE inhibitors on ischemic stroke severity

Directory of Open Access Journals (Sweden)

Caplan Louis

2005-06-01

Full Text Available Abstract Background Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEI are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity. Methods We retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI. We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7, moderate (NIHSS 8–13 or severe (NIHSS [greater than or equal to] 14. We analyzed demographic data, risk-factor profile, blood pressure (BP and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not. Results Thirty- three patients (26% were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2–21 among ACEI-treated patients vs. 9 (range 1–36 in non-ACEI patients (p = 0.036. Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03. Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups. Conclusion Our results

Different angiotensin-converting enzyme inhibitors have similar clinical efficacy after myocardial infarction

DEFF Research Database (Denmark)

Hansen, Morten L; Gislason, Gunnar H; Køber, Lars

2008-01-01

What is already known about this subject: Treatment with an angiotensin-converting enzyme (ACE) inhibitor benefits many patients with cardiovascular disease. ACE inhibitors are generally assumed to be equally effective, but this has never been fully verified in clinical trials. What this study adds...... important and not which ACE inhibitor is used. AIM: Therapy with angiotensin-converting enzyme (ACE) inhibitors is common after myocardial infarction (MI). Given the lack of randomized trials comparing different ACE inhibitors, the association among ACE inhibitors after MI in risk for mortality...

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.

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Rahimi, Zohreh

2012-10-01

Angiotensin converting enzyme (ACE) gene encodes ACE, a key component of renin angiotensin system (RAS), plays an important role in blood pressure homeostasis by generating the vasoconstrictor peptide angiotensin II. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.

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

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Prasad, Kailash

2013-12-01

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

Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients?

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Sarkar, Taposh; Singh, Narinder Pal; Kar, Premashish; Husain, Syed Akhtar; Kapoor, Seema; Pollipalli, Sunil Kumar; Kumar, Anish; Garg, Neena

2016-06-01

Hypertension is one of the important contributing factors linked with both causation and development of kidney disease. It is a multifactorial, polygenic, and complex disorder due to interaction of several risk genes with environmental factors. The present study was aimed to explore genetic polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients. Three hundred patients were enrolled in the study. Ninety were hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients without CKD were taken as controls. Demographic data including age, sex, Body mass index (BMI), and other risk factors were also recorded. DNA was extracted from blood by salting out method. Genotyping of ACE gene was done by PCR technique. All the statistical analysis was done by using Epi Info and SPSS version 16 software (SPSS Inc., Chicago, IL). Mean age was higher in the control group (p ACE gene (OR = 1.42, 95% CI = 0.72-2.81). Similarly, the risk for CKD among hypertensive patients was also associated with D allele of ACE gene (OR = 1.25, 95% CI = 0.86-1.79). It is concluded that ACE-DD genotype may be a risk factor for the causation and development of chronic kidney failure among hypertensive patients.

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

Science.gov (United States)

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

Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group

DEFF Research Database (Denmark)

Flather, M D; Yusuf, S; Køber, L

2000-01-01

enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. FINDINGS: Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality...... was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite...... of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p...

EFFECT OF CHRONIC ACE-INHIBITION ON THE DIAGNOSTIC-VALUE OF RENOGRAPHY FOR RENOVASCULAR HYPERTENSION - A PRELIMINARY-REPORT

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VISSCHER, CA; DEZEEUW, D; HUISMAN, RM

1995-01-01

We compared the effects of acute and chronic ACE inhibition (ACEi) on the I-123-hippurate in the stenotic kidney of two 2-kidney, 1-clip hypertensive dogs. In the period after clip implantation poststenotic renograms without ACEi of both dogs were normal. Acute ACEi always resulted in delayed

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

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

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

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

2016-01-01

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

Prevalence of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism in South Indian population with hypertension and chronic kidney disease.

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Shanmuganathan, R; Kumaresan, R; Giri, P

2015-01-01

Chronic Kidney Disease (CKD) is associated with a high risk of developing further severe complications such as, cardiovascular disease and eventually End Stage Renal Disease (ESRD) leading to death. Hypertension plays a key role in the progression of renal failure and is also a chief risk factor for the occurrence of End Stage Renal Disease (ESRD). This study investigates the possible association of insertion (I) and deletion (D) polymorphism of ACE gene in patients of Chronic Kidney Disease (CKD) with and without hypertension (HT). Total 120 participants with 30 members in each group (Control, HT, CKD and CKD-HT) were chosen followed by informed consent. Blood samples were collected and subjected to biochemical analyses and nested PCR amplification was performed to genotype the DNA, for ACE I/D using specific primers. Statistical analyses were performed using SPSS version 13. Allele and genotypic frequency was calculated by direct gene counting method. Comparison of the different genotypes was done by using Chi square test. Odd's ratios were calculated with a 95% confidence interval limit. The ACE genotype were distributed as II, 27 (90%); DD, 2 (6.67%) and ID, 1 (3.33%) in control, II, 1 (3.33%); DD, 5 (16.67%) and ID, 24 (80%) in HT, II, 4 (13.33%); DD, 24 (80%) and ID, 2 (6.67%) in CKD and II, 0 (0%); DD, 2 (6.67%) and ID, 28 (93.33%) in CKD-HT group. D allele of ACE gene confers a greater role in genetic variations underlying CKD and hypertension. This result suggest that CKD patients should be offered analysis for defects in ACE I/D polymorphisms, especially if they are hypertensive.

Chronic Treatment with Ang-(1-7 Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes

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Mariam H. M. Yousif

2014-01-01

Full Text Available Angiotensin-(1-7 [Ang-(1-7] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED but its molecular actions in the diabetic corpus cavernosum (CC are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7 on vascular reactivity in the rat corpus cavernosum (CC and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS such as angiotensin-converting enzyme (ACE, ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2, and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7 with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7 reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7 treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7 in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism.

ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

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Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-08-01

The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg -1 d -1 ), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg -1 min -1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca 2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R

Prevalence of angiotensin converting enzyme (ACE gene insertion/deletion polymorphism in South Indian population with hypertension and chronic kidney disease

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R Shanmuganathan

2015-01-01

Full Text Available Context: Chronic Kidney Disease (CKD is associated with a high risk of developing further severe complications such as, cardiovascular disease and eventually End Stage Renal Disease (ESRD leading to death. Hypertension plays a key role in the progression of renal failure and is also a chief risk factor for the occurrence of End Stage Renal Disease (ESRD. Aim: This study investigates the possible association of insertion (I and deletion (D polymorphism of ACE gene in patients of Chronic Kidney Disease (CKD with and without hypertension (HT. Settings and Design: Total 120 participants with 30 members in each group (Control, HT, CKD and CKD-HT were chosen followed by informed consent. Materials and Methods: Blood samples were collected and subjected to biochemical analyses and nested PCR amplification was performed to genotype the DNA, for ACE I/D using specific primers. Statistical Analysis: Statistical analyses were performed using SPSS version 13. Allele and genotypic frequency was calculated by direct gene counting method. Comparison of the different genotypes was done by using Chi square test. Odd′s ratios were calculated with a 95% confidence interval limit. Results: The ACE genotype were distributed as II, 27 (90%; DD, 2 (6.67% and ID, 1 (3.33% in control, II, 1 (3.33%; DD, 5 (16.67% and ID, 24 (80% in HT, II, 4 (13.33%; DD, 24 (80% and ID, 2 (6.67% in CKD and II, 0 (0%; DD, 2 (6.67% and ID, 28 (93.33% in CKD-HT group. Conclusions: D allele of ACE gene confers a greater role in genetic variations underlying CKD and hypertension. This result suggest that CKD patients should be offered analysis for defects in ACE I/D polymorphisms, especially if they are hypertensive.

The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease

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Jafar, Tazeen H; Stark, Paul C; Schmid, Christopher H

2005-01-01

BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors...... of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine......%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study

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Parikh, Megha A.; Aaron, Carrie P.; Hoffman, Eric A.; Schwartz, Joseph E.; Madrigano, Jaime; Austin, John H. M.; Lovasi, Gina; Watson, Karol; Stukovsky, Karen Hinckley

2017-01-01

Rationale: Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. Objectives: To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. Methods: The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45–84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than −950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. Results: Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. Conclusions: In a large population-based study, ACE

Elevated ACE activity is not associated with asthma, COPD, and COPD co-morbidity

DEFF Research Database (Denmark)

Lee, Julie; Nordestgaard, Børge G; Dahl, Morten

2009-01-01

The angiotensin-converting enzyme (ACE) gene is a potential candidate gene for risk of asthma, COPD, and COPD co-morbidity. In 9034 Danish adults, we determined whether individuals homozygous or heterozygous for the ACE D allele are at greater risk of asthma, COPD, or COPD co-morbidity compared...... with ACE II homozygous individuals. In the general population, serum ACE activity increased with the number of D alleles (Kruskal-Wallis ANOVA: II vs. ID, p....4-1.2). The results were similar upon adjustment for sex, age, smoking status, body mass index, total cholesterol, and ACE inhibitor/angiotensin II type 1 receptor blocker use. These data suggest that lifelong genetically elevated ACE activity is not a major risk factor for asthma or COPD, or for ischemic heart...

Angiotensin converting enzyme (ACE and ACE2 bind integrins and ACE2 regulates integrin signalling.

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Nicola E Clarke

Full Text Available The angiotensin converting enzymes (ACEs are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2 is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.

Alu insertion/deletion of ACE gene polymorphism might not affect ...

African Journals Online (AJOL)

Widodo

2016-09-03

Sep 3, 2016 ... a Biology Department, Faculty of Mathematics and Natural Sciences, Brawijaya ... Subjects and methods: The serum bradykinin and I/D polymorphism have been ..... Japanese hypertensive patients receiving an ACE inhibitor.

Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease.

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Mlak, Radosław; Homa-Mlak, Iwona; Powrózek, Tomasz; Mackiewicz, Barbara; Michnar, Marek; Krawczyk, Paweł; Dziedzic, Marcin; Rubinsztajn, Renata; Chazan, Ryszarda; Milanowski, Janusz; Małecka-Massalska, Teresa

2016-04-01

Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought.

Initial effect of enalapril on kidney function in patients with moderate to severe chronic nephropathy

DEFF Research Database (Denmark)

Kamper, A L; Thomsen, H S; Nielsen, S L

1990-01-01

in their renal function. Thirty-one patients were studied, 26 on chronic antihypertensive treatment with drugs other than ACE inhibitors and 5 untreated normotensive. 51Cr-EDTA plasma clearance and renal technetium-99m dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were made before and 24 h after start...

Animal and Plant Proteins as Precursors of Peptides with ACE Inhibitory Activity – An in silico Strategy of Protein Evaluation

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Anna Iwaniak

2009-01-01

Full Text Available This paper presents a modern in silico approach useful in the evaluation of proteins as a source of ACE inhibitors. All protein sequences analyzed were derived from the BIOPEP database. To determine the protein value, the following criteria of evaluation were applied: the profile of potential biological (ACE inhibitory activity of a protein, the frequency of the occurrence of fragments with ACE inhibitory activity (A and the potential biological activity of a protein (B. The results, based on a statistical analysis, indicate that milk proteins can be a better source of ACE inhibitors than wheat gliadins. Moreover, all analyzed gliadins possessed more potent ACE inhibitors than chicken meat proteins. No significant differences were observed when comparing A values between soy globulins and β-lactoglobulins. Although criteria such as the profile of potential biological activity of protein, as well as parameters A and B, can be suitable tools in protein evaluation, the proteolytic digestion of protein needs to be considered. Moreover, computerised methods of classifying proteins according to different algorithms are often subjective due to discretion in interpretation of the results.

ACE inhibitors could be therapeutic for antisocial personality disorder.

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Hobgood, Donna K

2013-11-01

Antisocial personality traits are an important topic for research. The societal cost of these behaviors encourages efforts at a better understanding of central nervous system causes. Catecholamine genes are being studied to facilitate this understanding, and some tentative findings are being reached about several of these genes. It seems that many genes play a role to produce antisocial behaviors so complexity of elucidating each gene is obvious. One conclusion that could be drawn from the current research findings is that DA2 like receptors (DRD2, DRD3, DRD4) with alleles that decrease neurotransmission are facilitatory of antisocial behaviors. DA2 like receptors cause neuronal firing to inhibit many peripheral functions through adenylyl cyclase inhibition. When these receptors are less active by genetically decreased density, lower affinity, or by low dopamine levels as final common pathways then inhibition is released and a state of disinhibition can be said to describe this state. Peripheral metabolism is increased and behavioral activation is noted. Renin is disinhibited in this setting thus allowing sympathetic nervous system activation. The fight or flight behaviors thus produced, in the extreme, would be the setting of antisocial behavior. Research validates this hypothesis. Understanding this final common pathway toward antisocial behavior should lead to better treatment for individuals with this pattern of behavior before they have caused harm to themselves and others. ACE inhibitors are well tolerated drugs used in the treatment of hypertension and heart failure and would also treat antisocial behavior disorders. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

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Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

2018-05-24

Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

Potential savings of harmonising hospital and community formularies for chronic disease medications initiated in hospital.

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Lauren Lapointe-Shaw

Full Text Available Hospitals in Canada manage their formularies independently, yet many inpatients are discharged on medications which will be purchased through publicly-funded programs. We sought to determine how much public money could be saved on chronic medications if hospitals promoted the initiation of agents with the lowest outpatient formulary prices.We used administrative databases for the province of Ontario to identify patients initiated on a proton pump inhibitor (PPI, angiotensin-converting enzyme (ACE inhibitor or angiotensin receptor blocker (ARB following hospital admission from April 1(st 2008-March 31(st 2009. We assessed the cost to the Ontario Drug Benefit Program (ODB over the year following initiation and determined the cost savings if prescriptions were substituted with the least expensive agent in each class.The cost for filling all PPI, ACE inhibitor and ARB prescriptions was $ 2.48 million, $968 thousand and $325 thousand respectively. Substituting the least expensive agent could have saved $1.16 million (47% for PPIs, $162 thousand (17% for ACE inhibitors and $14 thousand (4% for ARBs over the year following discharge.In a setting where outpatient prescriptions are publicly funded, harmonising outpatient formularies with inpatient therapeutic substitution resulted in modest cost savings and may be one way to control rising pharmaceutical costs.

Evaluation of whether the ACE gene I/D polymorphism constitutes a risk factor for chronic obstructive pulmonary disease in the Turkish population.

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Ayada, C; Toru, U; Genç, O; Yerlikaya, A; Sahin, S; Turgut, S; Turgut, G

2014-12-12

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction that occurs as a result of the normal inflammatory process to protect against harmful irritants and chemicals. Another physiological regulatory process, the renin angiotensin system (RAS), plays an important role in the pathology of many diseases. Angiotensin converting enzyme (ACE) is a key enzyme of RAS. We investigated the frequency of the ACE gene I/D polymorphism in patients with COPD in Turkey. This study was performed on 47 unrelated patients with COPD and 64 healthy subjects. DNA samples were isolated from peripheral blood, and ACE DNA was amplified by polymerase chain reaction. The frequencies of ACE genotypes were 27.7, 55.3, and 17% for DD, ID, and II in the COPD group, respectively, and 43.8, 43.8, and 12.4% in the control group. There was no statistically significant difference between groups (X(2) = 3.078; df = 2; P = 0.220). The distributions of ACE gene D alleles were 38.2% (N = 52) in the COPD group and 61.8% (N = 84) in the control group; and those of I alleles were 48.8% (N = 42) in the COPD group and 51.2% (N = 44) in the control group. There was no statistically significant difference between groups for allele frequency (X(2) = 2.419; df = 2; P = 0.120). We believe these results can be useful for large-scale population genetic research considering the frequency of the ACE gene variation in COPD patients in the Turkish population.

Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele.

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Qiu, Wendy Wei Qiao; Lai, Angela; Mon, Timothy; Mwamburi, Mkaya; Taylor, Warren; Rosenzweig, James; Kowall, Neil; Stern, Robert; Zhu, Haihao; Steffens, David C

2014-02-01

The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD. This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers. Copyright © 2014. Published by Elsevier Inc.

Natural products inhibitors of the angiotensin converting enzyme (ACE: a review between 1980 - 2000

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José M. Barbosa-Filho

Full Text Available Inhibition of Angiotensin Converting Enzyme (ACE is a modern therapeutic target in the treatment of hypertension. Within the enzyme cascade of the renin-angiotensin system, ACE removes histidyl-leucine from angiotensin I to form the physiologically active octapeptide angiotensin II, one of the most potent known vasoconstrictors. Therefore, a rationale for treating hypertension would be to administer drugs or natural compounds which selectively inhibit ACE. The present work constitutes a review of the literature of plants and chemically defined molecules from natural sources with in vitro anti-hypertensive potential based on the inhibition of ACE. The review refers to 321 plants, the parts utilized, type of extract and whether they are active or not. It includes also the names of 158 compounds isolated from higher plants, marine sponges and algae, fungi and snake venom. Some aspects of recent research with natural products directed to produce anti-hypertensive drugs are discussed. In this review, 148 references were cited.

High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.

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Akif, Mohd; Georgiadis, Dimitris; Mahajan, Aman; Dive, Vincent; Sturrock, Edward D; Isaac, R Elwyn; Acharya, K Ravi

2010-07-16

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE. 2010 Elsevier Ltd. All rights reserved.

ACE and SGLT2 inhibitors: the future for non-diabetic and diabetic proteinuric renal disease.

Science.gov (United States)

Perico, Norberto; Ruggenenti, Piero; Remuzzi, Giuseppe

2017-04-01

Most chronic nephropathies progress relentlessly to end-stage kidney disease. Research in animals and humans has helped our understanding of the mechanisms of chronic kidney disease progression. Current therapeutic strategies to prevent or revert renal disease progression focus on reduction of urinary protein excretion and blood pressure control. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors and/or angiotensin II type 1 receptor blockers is the most effective treatment to achieve these purposes in non-diabetic and diabetic proteinuric renal diseases. For those individuals in which nephroprotection by RAS blockade is only partial, sodium-glucose linked cotransporter-2 (SGLT2) inhibitors could be a promising new class of drugs to provide further renoprotective benefit when added on to RAS blockers. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Research progress of dipeptidyl peptidase 4 inhibitors on healing of chronic diabetic foot ulcers].

Science.gov (United States)

Gao, Yunyi; Liang, Yujie; Ran, Xingwu

2018-05-01

To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. DPP-4 inhibitors can accelerated the ulcer healing. The mechanisms probably include inhibiting the expression of the matrix metalloproteinase (MMP) and restoring the balance of the wound MMP and the tissue inhibitors of MMP; promoting recruitment of endothelial progenitor cells and augmenting angiogenesis; optimizing extracellular matrix construction and the immune response to persistent hypoxia in chronic diabetes wounds, and so on. At present, clinical researches show that DPP-4 inhibitors may be considered as an adjuvant treatment for chronic diabetic foot ulcers. DPP-4 inhibitors show promise in the local wound healing of chronic diabetic foot ulcers. However, more strictly designed, adequately powered, long-term follow-up, and high-quality randomized control trials are needed to further verify their efficacy and safety for chronic diabetic foot ulcers.

Angiotensin-Converting Enzyme (ACE) I/D and Alpha-Adducin (ADD1) G460W Gene Polymorphisms in Turkish Patients with Severe Chronic Tinnitus.

Science.gov (United States)

Yuce, Salim; Sancakdar, Enver; Bağcı, Gokhan; Koc, Sema; Kurtulgan, Hande Kucuk; Bağcı, Binnur; Doğan, Mansur; Uysal, İsmail Onder

2016-04-01

Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI). The Tinnitus Handicap Inventory (THI) was used to evaluate the tinnitus severity. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used for genotyping. With regard to the ACE I/D polymorphism, there was no significant difference in genotype and allele frequencies between the patient group and control group. However, a statistically significant difference was found in genotype (pgene polymorphism. Combined genotype analysis showed that the ACE II /ADD1 GW genotype was statistically significantly higher in the patient group than in the control group (X2: 7.15, p=0.007). The odds ratio value of the GW genotype was 2.5 (95% CI=1.4-4.7) (pgene polymorphism and susceptibility to severe chronic tinnitus. It was found that the GW genotype increased the disease risk by 2.5-fold compared with other genotypes. This indicates that ADD1 G460W polymorphism could be an important factor in the pathophysiology of tinnitus.

Fatal angioedema induced by angiotensin conversion enzyme (ACE ...

African Journals Online (AJOL)

ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at primary to tertiary health care levels in South Africa. Angioedema is considered a rare, but potentially fatal side-effect of this agent, with a reported ...

Chronic School Absenteeism and the Role of Adverse Childhood Experiences.

Science.gov (United States)

Stempel, Hilary; Cox-Martin, Matthew; Bronsert, Michael; Dickinson, L Miriam; Allison, Mandy A

To examine the association between chronic school absenteeism and adverse childhood experiences (ACEs) among school-age children. We conducted a secondary analysis of data from the 2011-2012 National Survey of Children's Health including children 6 to 17 years old. The primary outcome variable was chronic school absenteeism (≥15 days absent in the past year). We examined the association between chronic school absenteeism and ACEs by logistic regression with weighting for individual ACEs, summed ACE score, and latent class analysis of ACEs. Among the 58,765 school-age children in the study sample, 2416 (4.1%) experienced chronic school absenteeism. Witnessing or experiencing neighborhood violence was the only individual ACE significantly associated with chronic absenteeism (adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.20-2.01). Having 1 or more ACE was significantly associated with chronic absenteeism: 1 ACE (aOR 1.35, 95% CI 1.02-1.79), 2 to 3 ACEs (aOR 1.81, 95% CI 1.39-2.36), and ≥4 ACEs (aOR 1.79, 95% CI 1.32-2.43). Three of the latent classes were also associated with chronic absenteeism, and children in these classes had a high probability of endorsing neighborhood violence, family substance use, or having multiple ACEs. ACE exposure was associated with chronic school absenteeism in school-age children. To improve school attendance, along with future graduation rates and long-term health, these findings highlight the need for an interdisciplinary approach to address child adversity that involves pediatricians, mental health providers, schools, and public health partners. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Sacubitril/Valsartan: A Review in Chronic Heart Failure with Reduced Ejection Fraction.

Science.gov (United States)

McCormack, Paul L

2016-03-01

Sacubitril/valsartan (Entresto™; LCZ696) is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was recently approved in the US and the EU for the treatment of chronic heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF). In the large, randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure (composite primary endpoint) significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan was also superior to enalapril in reducing death from any cause and in limiting the progression of heart failure. Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events. Symptomatic hypotension was significantly more common with sacubitril/valsartan than with enalapril; the incidence of angio-oedema was low. Therefore, sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF, and is likely to influence the basic approach to treatment.

Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease.

Science.gov (United States)

Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Kei; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J; Uchida, Shunya

2014-12-15

An inhibition in the renin-angiotensin system (RAS) is one of the most widely used therapies to treat chronic kidney disease. However, its effect is occasionally not sufficient and additional treatments may be required. Recently, we reported that nicorandil exhibited renoprotective effects in a mouse model of diabetic nephropathy. Here we examined if nicorandil can provide an additive protection on enalapril in chronic kidney disease. Single treatment with either enalapril or nicorandil significantly ameliorated glomerular and tubulointerstitial injury in the rat remnant kidney while the combination of these two compounds provided additive effects. In addition, an increase in oxidative stress in remnant kidney was also blocked by either enalapril or nicorandil while the combination of the drugs was more potent. A mechanism was likely due for nicorandil to preventing manganase superoxide dismutase (MnSOD) and sirtuin (Sirt)3 from being reduced in injured kidneys. A study with cultured podocytes indicated that the antioxidative effect could be mediated through sulfonylurea receptor (SUR) in the mitochondrial KATP channel since blocking SUR with glibenclamide reduced MnSOD and Sirt3 expression in podocytes. In conclusion, nicorandil may synergize with enalapril to provide superior protection in chronic kidney disease. Copyright © 2014 the American Physiological Society.

Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

Science.gov (United States)

He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

2013-01-01

Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension. Results The results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls. Conclusion ACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH. PMID:24098401

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

DEFF Research Database (Denmark)

Meurs, Kathryn M.; Olsen, Lisbeth H.; Reimann, Maria J.

2018-01-01

a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated......Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified...... with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism...

The renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure is not dependent on enhanced kinin activity.

Science.gov (United States)

Nabokov, A; Amann, K; Gassmann, P; Schwarz, U; Orth, S R; Ritz, E

1998-01-01

Angiotensin-converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of glomerulosclerosis both in experimental models of uraemia and in patients with renal failure. It has not been documented, however, whether this is due to a decrease in angiotensin II generation or is a consequence of elevated local level of bradykinin. Morphometric investigation of renal tissue was performed in 5/6 nephrectomized (SNx) rats, i.e. untreated or treated with the ACE inhibitor ramipril (SNx-RAM), the B2 kinin receptor antagonist HOE 140 (SNx-HOE), or a combination of both (SNx-RAM + HOE) over 8 weeks. A further group of SNx received delayed treatment with ramipril from week 5 onward (SNx-RAMD). In addition, a sham-operated (SHAM) control group was studied. Systolic blood pressure was significantly lower in both SNx-RAM and SNx-RAM + HOE groups compared to (untreated) SNx. The glomerulosclerosis index (GSI) was substantially higher in the (untreated) SNx group (0.24 +/- 0.04) vs SHAM (0.02 +/- 0.01). A significantly higher GSI was found in the SNx-HOE group (0.45 +/- 0.08) as compared to (untreated) SNx. However, in the SNx-RAM, SNx-RAM + HOE, and SNx-RAMD groups, the GSI was lowered to a similar extent (0.1 +/- 0.02, 0.09 +/- 0.02, and 0.07 +/- 0.01 respectively). In addition, a concomitant attenuation of tubulointerstitial damage was noted in all the above groups. Increased kinin activity does not appear to play a major role in the renoprotective effect of ACE inhibitors in the remnant kidney model.

Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [(111)In-DOTA]MG11-first estimates for clinical translation.

Science.gov (United States)

Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Valkema, Roelf; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

2016-12-01

We have recently shown that treatment of mice with the neutral endopeptidase (NEP) inhibitor phosphoramidon (PA) improves the bioavailability and tumor uptake of biodegradable radiopeptides. For the truncated gastrin radiotracer [(111)In-DOTA]MG11 ([(DOTA)DGlu(10)]gastrin(10-17)), this method led to impressively high tumor-to-kidney ratios. Translation of this concept in the clinic requires the use of certified NEP inhibitors, such as thiorphan (TO) and its orally administered prodrug racecadotril (Race). Besides NEP, angiotensin-converting enzyme (ACE) has also been implicated in the catabolism of gastrin analogs. In the present study, we first compared the effects induced by NEP inhibition (using PA, TO, or Race) and/or by ACE inhibition (using lisinopril, Lis) on the biodistribution profile of [(111)In-DOTA]MG11 in mice. In addition, we compared the efficacy of PA and TO at different administered doses to enhance tumor uptake. [(111)In-DOTA]MG11 was coinjected with (a) vehicle, (b) PA (300 μg), (c) TO (150 μg), (d) Lis (100 μg), (e) PA (300 μg) plus Lis (100 μg), or (f) 30-40 min after intraperitoneal (ip) injection of Race (3 mg) in SCID mice bearing AR42J xenografts. In addition, [(111)In-DOTA]MG11 was coinjected with vehicle, or with progressively increasing amounts of PA (3, 30, or 300 μg) or TO (1.5, 15, and 150 μg) in SCID mice bearing twin A431-CCK2R(+/-) tumors. In all above cases, biodistribution was conducted at 4 h postinjection (pi). During NEP inhibition, the uptake of [(111)In-DOTA]MG11 in the AR42J tumors impressively increased from 1.8 ± 1.0 % ID/g (controls) to 15.3 ± 4.7 % ID/g (PA) and 12.3 ± 3.6 % ID/g (TO), while with Race tumor values reached 6.8 ± 2.8 % ID/g. Conversely, Lis had no effect on tumor uptake and no additive effect when coinjected with PA. During the dose dependence study in mice, PA turned out to be more efficacious in enhancing tumor uptake of [(111)In-DOTA]MG11 in the CCK2R

Association of angiotensin-converting enzyme inhibitor therapy and comorbidity in diabetes: results from the Vermont diabetes information system

Directory of Open Access Journals (Sweden)

MacLean Charles D

2008-12-01

Full Text Available Abstract Background Angiotensin converting enzyme inhibitors (ACE inhibitors reduce peripheral vascular resistance via blockage of angiotensin converting enzyme (ACE. ACE inhibitors are commonly used to treat congestive heart failure and high blood pressure, but other effects have been reported. In this study, we explored the association between ACE inhibitor therapy and the prevalence of comorbid conditions in adults with diabetes Methods We surveyed 1003 adults with diabetes randomly selected from community practices. Patients were interviewed at home and self-reported their personal and clinical characteristics including comorbidity. Current medications were obtained by direct observation of medication containers. We built logistic regression models with the history of comorbidities as the outcome variable and the current use of ACE inhibitors as the primary predictor variable. We adjusted for possible confounding by social (age, sex, alcohol drinking, cigarette smoking and clinical factors (systolic blood pressure, body mass index (BMI, glycosolated hemoglobin (A1C, number of comorbid conditions, and number of prescription medications. Results ACE users reported a history of any cancer (except the non-life-threatening skin cancers less frequently than non-users (10% vs. 15%; odd ratio = 0.59; 95% confidence interval [0.39, 0.89]; P = 0.01; and a history of stomach ulcers or peptic ulcer disease less frequently than non-users (12% vs. 16%, odd ratio = 0.70, [0.49, 1.01], P = 0.06. After correcting for potential confounders, ACE inhibitors remained significantly inversely associated with a personal history of cancer (odds ratio = 0.59, [0.39, 0.89]; P = 0.01 and peptic ulcer disease (odd ratio = 0.68, [0.46, 1.00], P = 0.05. Conclusion ACE inhibitor use is associated with a lower likelihood of a history of cancer and peptic ulcers in patients with diabetes. These findings are limited by the cross sectional study design, self-report of comorbid

BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

Science.gov (United States)

Cuellar, Sandra; Vozniak, Michael; Rhodes, Jill; Forcello, Nicholas; Olszta, Daniel

2017-01-01

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors

NARCIS (Netherlands)

Mahmoudpour, Seyed H.; Veluchamy, Abirami; Siddiqui, Moneeza K.; Asselbergs, Folkert W.; Souverein, Patrick C.; De Keyser, Catherine E.; Hofman, Albert; Lang, Chim C.; Doney, Alexander S.F.; Stricker, Bruno H.; De Boer, Anthonius; Maitland-Van Der Zee, Anke H.; Palmer, Colin N.A.

2017-01-01

Objectives To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker. Methods Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and

Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.

Directory of Open Access Journals (Sweden)

Cristina Zanchi

Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.

ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis.

Directory of Open Access Journals (Sweden)

Cecilia Riquelme

Full Text Available Duchenne muscular dystrophy (DMD is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7 (Ang-(1-7, a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in mdx mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7 production, in wild type (wt and mdx skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA muscle. Furthermore, we evaluated the effect of ACE2 overexpression in mdx TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the mdx muscle. Finally, mdx gastrocnemius muscles from mice infused with Ang-(1-7, which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype.

Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and {beta}-adrenergic desensitization in heart failure after myocardial infarction in rats

Energy Technology Data Exchange (ETDEWEB)

Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro [Toyama Medical and Pharmaceutical Univ. (Japan)] [and others

2002-11-01

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of {beta}-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by {sup 131}I-metaiodobenzylguanidine (MIBG), {beta}-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to {beta}-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of {beta}-adrenergic pathway in this model of heart failure. (author)

Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and β-adrenergic desensitization in heart failure after myocardial infarction in rats

International Nuclear Information System (INIS)

Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro

2002-01-01

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of β-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131 I-metaiodobenzylguanidine (MIBG), β-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to β-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of β-adrenergic pathway in this model of heart failure. (author)

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

International Nuclear Information System (INIS)

Lin, Xinchun; Bernloehr, Christian; Hildebrandt, Tobias; Stadler, Florian J.; Doods, Henri; Wu, Dongmei

2016-01-01

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

Energy Technology Data Exchange (ETDEWEB)

Lin, Xinchun [Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140 (United States); Bernloehr, Christian; Hildebrandt, Tobias [Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach (Germany); Stadler, Florian J., E-mail: fjstadler@szu.edu.cn [Shenzhen Engineering Laboratory for Advanced Technology of Ceramics, Shenzhen 518060 (China); Doods, Henri [Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach (Germany); Wu, Dongmei, E-mail: dongmeiwu@bellsouth.net [Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140 (United States); Department of BIN Convergence Technology, Chonbuk National University (Korea, Republic of)

2016-08-15

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence.

Science.gov (United States)

Masuyer, Geoffrey; Yates, Christopher J; Sturrock, Edward D; Acharya, K Ravi

2014-10-01

Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.

BTK inhibitors in chronic lymphocytic leukemia: a glimpse to the future

NARCIS (Netherlands)

Spaargaren, M.; de Rooij, M. F. M.; Kater, A. P.; Eldering, E.

2015-01-01

The treatment of chronic lymphocytic leukemia (CLL) with inhibitors targeting B cell receptor signaling and other survival mechanisms holds great promise. Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK), has received widespread

Novel angiotensin-converting enzyme (ACE) inhibitory peptides derived from boneless chicken leg meat.

Science.gov (United States)

Terashima, Masaaki; Baba, Takako; Ikemoto, Narumi; Katayama, Midori; Morimoto, Tomoko; Matsumura, Saki

2010-06-23

Four peptides that inhibit angiotensin-converting enzyme (ACE) were separated from the hydorlysate of boneless chicken leg meat digested with artificial gastric juice (pepsin). Two peptides were identified as the peptides encrypted in myosin heavy chain. The peptide P1 (MNVKHWPWMK) corresponds to the amino acid sequence from amino acids 825 to 834 of myosin heavy chain, and the peptide P4 (VTVNPYKWLP) corresponds to the amino acid sequence from amino acids 125 to 135 of myosin heavy chain. They are novel ACE inhibitory peptides derived from chicken, and IC(50) values of P1 and P4 were determined as 228 and 5.5 microM, respectively. Although these values were much larger than 0.022 microM for captopril, a typical synthetic ACE inhibitor, they are comparable to IC(50) values reported for various ACE inhibitory peptides derived from foods. Because the peptide P4 has a relatively low IC(50) value, it is a good starting substance for designing food supplements for hypertensive patients.

TO THE 110-TH ANNIVERSARY OF RENIN FINDING. FIGHT OF TITANS: ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND SARTANS

Directory of Open Access Journals (Sweden)

L. N. Malay

2009-01-01

Full Text Available Angiotensin converting enzyme (ACE inhibitors and angiotensin II receptor blockers (ARB slow down progression of cardiovascular diseases and reduce risk of mortality and life threatening complications. What it is better to prescribe for patient in a concrete clinical case – ACE inhibitors or ARB? Authors compare these drug classes (mechanism of action, indications, evidense base of clinical trails, treatment costs and safety. The place of ACE inhibitors and ARB in modern therapy of cardiovascular diseases is defined. Results of the recent trails (ONTARGET, TRANCEND, PRoFESS, I-PRESERVE are discussed.

Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

OpenAIRE

He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

2013-01-01

Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written i...

Use of ACE-inhibitors and falls in patients with Parkinson's disease.

Science.gov (United States)

Laudisio, Alice; Lo Monaco, Maria Rita; Silveri, Maria Caterina; Bentivoglio, Anna Rita; Vetrano, Davide L; Pisciotta, Maria Stella; Brandi, Vincenzo; Bernabei, Roberto; Zuccalà, Giuseppe

2017-05-01

Falls represent a major concern in patients with Parkinson's disease (PD); however, currently acknowledged treatments for PD are not effective in reducing the risk of falling. The aim was to assess the association of use of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with falls among patients with PD. We analysed data of 194 elderly with PD attending a geriatric Day Hospital. Self-reported history of falls that occurred over the last year, as well as use of drugs, including ACEIs and angiotensin II receptor blockers (ARBs) were recorded. The association of the occurrence of any falls with use of ACEIs, and ARBs was assessed by logistic regression analysis. The association between the number of falls and use of ACEIs, and ARBs was assessed according to Poisson regression. In logistic regression, after adjusting for potential confounders, use of ACEIs was associated with a reduced probability of falling over the last year (OR=0.15, 95% CI=0.03-0.81; P=0.028). This association did not vary with blood pressure levels (P for the interaction term=0.528). Also, using Poisson regression, use of ACEIs predicted a reduced number of falls among participants who fell (PR=0.31; 95% CI=0.10-0.94; P=0.039). No association was found between use of ARBs and falls. Our results indicate that use of ACEIs might be independently associated with reduced probability, and a reduced number of falls among patients with PD. Dedicated studies are needed to define the single agents and dosages that might most effectively reduce the risk of falling in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

[Competition between branded and generic drugs in Austria: evidence from the market for ACE inhibitors].

Science.gov (United States)

Mahlich, J C; Stadler, I

2012-01-01

The market for pharmaceuticals in Austria is highly regulated and manufacturers cannot set prices freely after patent expiration of the pioneer drug. We wanted to examine the effect of price regulation on price competition between branded and generic drugs in Austria. We examined the Austrian market for ACE inhibitors and describe competitive dynamics by means of 6 indices. We compared our results with those of Grabowski and Vernon who studied the US market. According to our analysis the competition amongst the producers of generic drugs is not great and consequently, compared to the USA, over time the prices for generic products decrease less and their market share increases less. This is due to a market-oriented system in the USA which waives most regulatory provisions. Our conclusions are in line with the findings by Danzon und Chao (2000) who argue that in a price-regulated market competitive dynamics are less strongly developed. From a politico-economic view, the necessity of price regulations in the pharmaceutical market seems questionable, as price regulations generally also cause other negative effects, such as distorted economic incentives for research and development investments. © Georg Thieme Verlag KG Stuttgart · New York.

ACE up the sleeve - are vascular patients medically optimized?

LENUS (Irish Health Repository)

Coveney, A P

2011-03-01

To examine the current medical management of arteriopathic patients attending a vascular surgical service at a university teaching hospital over a 6-month period. The prescribing of antiplatelets, statins, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers and beta-blockers was specifically examined. Vascular patients are often under the care of multiple specialties, and therefore the influence of different medical specialties on the patients\\' medical management was also examined.

Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita.

Science.gov (United States)

Cui, Ruqiang; Zhang, Lei; Chen, Yuyan; Huang, Wenkun; Fan, Chengming; Wu, Qingsong; Peng, Deliang; da Silva, Washington; Sun, Xiaotang

2017-05-01

The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant. Copyright © 2017. Published by Elsevier Inc.

Comparative study on the ACE inhibitors Quinapril and Captopril for the (Angiotensin converting enzyme) treatment of the decompensated cardiac insufficiency in dog

International Nuclear Information System (INIS)

Morisse, B.; Kersten, U.

1994-01-01

In a randomized study of 52 dogs the efficacy and safety of captopril and quinapril in the treatment of canine heart failure is studied. The drugs were found to be comparably effective. The recommended dosage schedule for the short acting captopril is three times daily 0.5 mg/kg body weight. Quinapril belongs to a newer generation of ACE inhibitors with a longer half life than captopril and the treatment was started with a single dose of 0.5 mg/kg body weight. This dosage schedule was sufficient for the successful therapy of most of the dogs with heart failure phase II (12 of 13), but in 4 of 7 dogs with heart failure phase III and in all of the patients with phase IV the single dose had to be increased and/or the dosing interval of quinapril had to be shortened, because they still showed complaints due to heart failure. We recommend to adjust the dosage schedule of quinapril individually to the severity of heart failure. Therapy should be started once daily with an application of 0,5 mg/kg body weight and the dog should be controlled about one week later. If there are still symptoms of decompensated heart failure, the dosage may be increased gradually until a maximum dosage of 0.5 mg/kg three times daily. Especially for patients with severe heart failure we recommend at least when treatment is started a concomitant diuretic therapy. Echocardiographic evaluation of cardiac function shows if there is an indication for positive inotropic support witha digitalis glycoside. Quinapril, a novel inhibitor of the angiotensin-converting enzyme can ease the management of canine heart failure, because at least in dogs with mild to moderate heart failure dosing interval is longer compared with captopril. Moreover, quinapril is available as 5 mg tablets whereas the smallest captopril tablets contain 12.5 mg agent. It has to be mentioned that expenses for a treatment with ACE inhibitors are significantly higher than for a therapy with digitalis, so frequently above all the

ACE polymorphism does not determine short-term renal response to ACE-inhibition in proteinuric patients

NARCIS (Netherlands)

vanderKleij, FGH; Navis, GJ; Gansevoort, RT; Scheffer, H; deZeeuw, D; deJong, PE

1997-01-01

Background. The renal response to ACE inhibition is known to vary between individuals. The ACE genotype is a determinant of the ACE concentrations in plasma and tissue, and therefore might affect the renal response to ACE inhibition in renal patients. Methods. To test this hypothesis we studied the

Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE

OpenAIRE

Rella, Monika; Elliot, Joann L; Revett, Timothy J; Lanfear, Jerry; Phelan, Anne; Jackson, Richard M; Turner, Anthony J; Hooper, Nigel M

2007-01-01

Abstract Background Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple ...

New ACE-Inhibitory Peptides from Hemp Seed (Cannabis sativa L.) Proteins.

Science.gov (United States)

Orio, Lara P; Boschin, Giovanna; Recca, Teresa; Morelli, Carlo F; Ragona, Laura; Francescato, Pierangelo; Arnoldi, Anna; Speranza, Giovanna

2017-12-06

A hemp seed protein isolate, prepared from defatted hemp seed meals by alkaline solubilization/acid precipitation, was subjected to extensive chemical hydrolysis under acid conditions (6 M HCl). The resulting hydrolysate was fractionated by semipreparative RP-HPLC, and the purified fractions were tested as inhibitors of angiotensin converting enzyme (ACE). Mono- and bidimensional NMR experiments and LC-MS analyses led to the identification of four potentially bioactive peptides, i.e. GVLY, IEE, LGV, and RVR. They were prepared by solid-phase synthesis, and tested for ACE-inhibitory activity. The IC 50 values were GVLY 16 ± 1.5 μM, LGV 145 ± 13 μM, and RVR 526 ± 33 μM, confirming that hemp seed may be a valuable source of hypotensive peptides.

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

International Nuclear Information System (INIS)

Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

2010-01-01

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

The role of enzyme and substrate concentration in the evaluation of serum angiotensin converting enzyme (ACE) inhibition by enalaprilat in vitro.

Science.gov (United States)

Weisser, K; Schloos, J

1991-10-09

The relationship between serum angiotensin converting enzyme (ACE) activity and concentration of the ACE inhibitor enalaprilat was determined in vitro in the presence of different concentrations (S = 4-200 mM) of the substrate Hip-Gly-Gly. From Henderson plots, a competitive tight-binding relationship between enalaprilat and serum ACE was found yielding a value of approximately 5 nM for serum ACE concentration (Et) and an inhibition constant (Ki) for enalaprilat of approximately 0.1 nM. A plot of reaction velocity (Vi) versus total inhibitor concentration (It) exhibited a non-parallel shift of the inhibition curve to the right with increasing S. This was reflected by apparent Hill coefficients greater than 1 when the commonly used inhibitory sigmoid concentration-effect model (Emax model) was applied to the data. Slopes greater than 1 were obviously due to discrepancies between the free inhibitor concentration (If) present in the assay and It plotted on the abscissa and could, therefore, be indicators of tight-binding conditions. Thus, the sigmoid Emax model leads to an overestimation of Ki. Therefore, a modification of the inhibitory sigmoid Emax model (called "Emax tight model") was applied, which accounts for the depletion of If by binding, refers to It and allows estimation of the parameters Et and IC50f (free concentration of inhibitor when 50% inhibition occurs) using non-linear regression analysis. This model could describe the non-symmetrical shape of the inhibition curves and the results for Ki and Et correlated very well with those derived from the Henderson plots. The latter findings confirm that the degree of ACE inhibition measured in vitro is, in fact, dependent on the concentration of substrate and enzyme present in the assay. This is of importance not only for the correct evaluation of Ki but also for the interpretation of the time course of serum ACE inhibition measured ex vivo. The non-linear model has some advantages over the linear Henderson

An angiotensin-converting enzyme inhibitor in the combination treatment of rheumatoid arthritis

Directory of Open Access Journals (Sweden)

E. B. Komarova

2017-01-01

Full Text Available Angiotensin-converting enzyme (ACE inhibitors have anti-inflammatory and antiproliferative properties and can affect the processes of angiogenesis, by reducing the effects of angiotensin II (ATII. The use of ACE inhibitors in the combination therapy of rheumatoid arthritis (RA can be also effective for monitoring disease activity and for reducing a cardiovascular risk.Objective: to evaluate the efficacy of an ACE inhibitor in the combination therapy of RA.Patients and methods. Eighty-four patients with RA and endothelial dysfunction were examined; the mean age was 40.12±10.2 years; the mean disease duration was 4.22±3.43 years. All the patients had a blood level of ATII of >9 pg/ml. Enzyme immunoassay was used to measure the levels of tumor necrosis factor-α (TNF-α (Vector-Best, Russia, intercellular adhesion molecules 1 (ICAM-1 (Diaclone, France, vascular endothelial growth factor (VEGF and ATII (Diagnostic, Canada. Wrist ultrasonography using the Doppler ultrasound apparatus ESAOTE MyLAB40 was carried out to assess synovial vascularization. The patients were divided into two groups. Group 1 included 43 patients who were assigned to receive standard therapy for RA according to the rheumatic disease treatment protocols; Group 2 comprised 41 patients who received the standard therapy plus ACE inhibitors 2.5–5 mg/day.Results. The use of ACE inhibitors in the 12-month combination therapy of RA patients led to an improvement in the endothelial regulation of vascular tone, to a decrease in the blood concentration of ICAM-1, to a reduction in the intensity of synovial angiogenesis and in the blood level of VEGF by 39%, and a more significant drop in the levels of CRP and TNF-? and in DAS28 by 1.2 scores as compared to those in the standard therapy.

Adverse childhood experiences, chronic diseases, and risky health behaviors in Saudi Arabian adults: a pilot study.

Science.gov (United States)

Almuneef, Maha; Qayad, Mohammed; Aleissa, Majid; Albuhairan, Fadia

2014-11-01

Adverse childhood experiences (ACEs) have been linked with risky health behaviors and the development of chronic diseases in adulthood. This study examined associations between ACEs, chronic diseases, and risky behaviors in adults living in Riyadh, Saudi Arabia in 2012 using the ACE International Questionnaire (ACE-IQ). A cross-sectional design was used, and adults who were at least 18 years of age were eligible to participate. ACEs event scores were measured for neglect, household dysfunction, abuse (physical, sexual, and emotional), and peer and community violence. The ACE-IQ was supplemented with questions on risky health behaviors, chronic diseases, and mood. A total of 931 subjects completed the questionnaire (a completion rate of 88%); 57% of the sample was female, 90% was younger than 45 years, 86% had at least a college education, 80% were Saudi nationals, and 58% were married. One-third of the participants (32%) had been exposed to 4 or more ACEs, and 10%, 17%, and 23% had been exposed to 3, 2, or 1 ACEs respectively. Only 18% did not have an ACE. The prevalence of risky health behaviors ranged between 4% and 22%. The prevalence of self-reported chronic diseases ranged between 6% and 17%. Being exposed to 4 or more ACEs increased the risk of having chronic diseases by 2-11 fold, and increased risky health behaviors by 8-21 fold. The findings of this study will contribute to the planning and development of programs to prevent child maltreatment and to alleviate the burden of chronic diseases in adults. Copyright © 2014 Elsevier Ltd. All rights reserved.

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

Science.gov (United States)

Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

2018-02-01

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

DEFF Research Database (Denmark)

Kamper, A L; Thomsen, H S; Nielsen, S L

1990-01-01

function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51Cr-EDTA plasma clearance fell by 14% (P less than 0.01), but renal uptake of 99mTc-DMSA increased by 10% (P less than 0.01). It is concluded that DMSA in chronic renal failure is mainly taken......Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney...

Identification and characterisation of the angiotensin converting enzyme-3 (ACE3 gene: a novel mammalian homologue of ACE

Directory of Open Access Journals (Sweden)

Phelan Anne

2007-06-01

Full Text Available Abstract Background Mammalian angiotensin converting enzyme (ACE plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. Conclusion In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.

Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.

Directory of Open Access Journals (Sweden)

Louise M Burrell

Full Text Available We previously reported that exogenous angiotensin (Ang 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE activity. This study investigated if the addition of an ACE inhibitor (ACEi to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day, Ang 1-7 (subcutaneous 24 μg/kg/h or dual therapy (all groups, n = 12. A control group (n = 10 of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.

The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

DEFF Research Database (Denmark)

Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

1996-01-01

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril...... on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated...... in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P

Preface ACE 2013

NARCIS (Netherlands)

Katayose, Haruhiro; Reidsma, Dennis; Katayose, Haruhiro; Nijholt, Antinus

2013-01-01

These are the proceedings of the 10th International Conference on Advances in Computer Entertainment (ACE 2013), hosted by the Human Media Interaction research group of the Centre for Telematics and Information Technology at the University of Twente, The Netherlands. The ACE series of conferences,

An Angiotensin I-Converting Enzyme Mutation (Y465D) Causes a Dramatic Increase in Blood ACE via Accelerated ACE Shedding

Science.gov (United States)

Gordon, Kerry; Nesterovitch, Andrew B.; Lünsdorf, Heinrich; Chen, Zhenlong; Castellon, Maricela; Popova, Isolda A.; Kalinin, Sergey; Mendonca, Emma; Petukhov, Pavel A.; Schwartz, David E.

2011-01-01

Background Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE. Methodology/Principal Findings HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE - between Arg1203 and Ser1204 - was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another. Conclusions/Significance The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase). PMID:21998728

An angiotensin I-converting enzyme mutation (Y465D causes a dramatic increase in blood ACE via accelerated ACE shedding.

Directory of Open Access Journals (Sweden)

Sergei M Danilov

Full Text Available Angiotensin I-converting enzyme (ACE metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D substitution, distal to the stalk region, in the N domain of ACE.HEK and CHO cells expressing mutant (Tyr465Asp ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE--between Arg1203 and Ser1204--was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another.The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase.

Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

Science.gov (United States)

Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

2008-12-01

Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

Sodium-Glucose Linked Transporter-2 Inhibitors in Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

L. Zanoli

2015-01-01

Full Text Available SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.

Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial

DEFF Research Database (Denmark)

NN, NN; Yusuf, S; Teo, K

2008-01-01

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular...

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

International Nuclear Information System (INIS)

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

2016-01-01

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 2 weeks. 48 h 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. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and

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

Energy Technology Data Exchange (ETDEWEB)

Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

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 2 weeks. 48 h 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. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and

The ACE gene and human performance: 12 years on.

Science.gov (United States)

Puthucheary, Zudin; Skipworth, James R A; Rawal, Jai; Loosemore, Mike; Van Someren, Ken; Montgomery, Hugh E

2011-06-01

associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele exists in greater frequency in those who migrated from the lowlands. Unfortunately, if the ACE genotype does influence metabolic efficiency, associations with peak maximal oxygen consumption have yet to be rigorously demonstrated. The ACE genotype is an important but single factor in the determinant of sporting phenotype. Much of the mechanisms underlying this remain unexplored despite 12 years of research.

Gender difference of serum angiotensin-converting enzyme (ACE) activity in DD genotype of ACE insertion/deletion polymorphism in elderly Chinese.

Science.gov (United States)

Zhang, Ya-Feng; Cheng, Qiong; Tang, Nelson L S; Chu, Tanya T W; Tomlinson, Brian; Liu, Fan; Kwok, Timothy C Y

2014-12-01

In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. © The Author(s) 2013.

Angiotensin-converting enzyme (ACE) inhibitory potential of standardized Mucuna pruriens seed extract.

Science.gov (United States)

Chaudhary, Sushil Kumar; De, Apurba; Bhadra, Santanu; Mukherjee, Pulok K

2015-01-01

Mucuna pruriens Linn. (Fabaceae) is a tropical legume, traditionally used for controlling blood pressure. Inhibition of angiotensin-converting enzyme (ACE) is one of the successful strategies for controlling hypertension. The present study evaluated the ACE inhibition potential of the standardized extract of M. pruriens seeds. Standardization of the extract and its fractions were carried out by RP-HPLC method [methanol and 1% v/v acetic acid in water (5:95 v/v)] using levodopa as a marker. The ACE inhibition activity of the extract and fractions was evaluated at different concentrations (20, 40, 60, 80, and 100 µg/mL) using the HPLC-DAD and the UV spectrophotometric method. The liberation of hippuric acid (HA) from hippuryl-L-histidyl-L-leucine (HHL) was estimated in the spectrophotometric method and RP-HPLC assay at 228 nm. Methanol extract and aqueous fraction showed a maximum activity with IC50 values of 38.44 ± 0.90 and 57.07 ± 2.90 µg/mL (RP-HPLC), and 52.68 ± 2.02 and 67.65 ± 2.40 µg/mL (spectrophotometry), respectively. The study revealed that the aqueous extract contains the highest amount of levodopa. Eventually the methanol extract showed highest ACE inhibition activity except levodopa alone. It was further observed that the inhibition was altered with respect to the change in the content of levodopa in the extract. Thus, it can be assumed that levodopa may be responsible for the ACE inhibition activity of M. pruriens seeds. It can be concluded that M. pruriens seed is a potential ACE inhibitor can be explored further as an effective antihypertensive agent.

Combining aspirin with angiotensin converting enzyme inhibitors in heart failure: how safe is it?

Science.gov (United States)

Mehta, H; Mahajan, A; Bansal, N; Vaidya, S; Pathak, L

1998-11-01

The above discussion on the interaction of aspirin and ACE inhibitors seems to suggest that aspirin in high doses may have adverse interaction with ACE inhibitors in patients with heart failure but the data obtained is not sufficient or conclusive to recommended omission of aspirin in patients with heart failure. This raises a query in the mind of the physician whether to use a combination or not? The role of aspirin in the early period after myocardial infarction is well established so is the role of ACE inhibitors. Hence in patients with myocardial infarction and preserved left ventricular function it would not be wrong to administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In patients with large myocardial infarction or heart failure, warfarin may be an option but still needs to be documented in large trials. As suggested long term use of aspirin after infarction is still ambiguous and may be harmful in patients with heart failure with its anticedent side effects. But long term benefits of ACE inhibitors in heart failure are well documented. Hence if a choice has to be made whether to discontinue either of the two drugs it would be preferable to stop the aspirin. To answer the issue of use of aspirin in patients with heart failure it would be essential to conduct a double blind randomized trial comparing known anti-thrombotic treatment, aspirin and anti-coagulants on mortality in patients with heart failure, especially caused by coronary artery disease. Such a trial is underway at the present and till the results are available it should be left to clinical judgement of the physician whether to administer aspirin in patients with heart failure after weighing the benefits versus risk.

Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa.

Science.gov (United States)

Ojeda, Deyanira; Jiménez-Ferrer, Enrique; Zamilpa, Alejandro; Herrera-Arellano, Armando; Tortoriello, Jaime; Alvarez, Laura

2010-01-08

The beverages of Hibiscus sabdariffa calyces are widely used in Mexico as diuretic, for treating gastrointestinal disorders, liver diseases, fever, hypercholesterolemia and hypertension. Different works have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans, and recently, we demonstrated that this effect is due to angiotensin converting enzyme (ACE) inhibitor activity. The aim of the current study was to isolate and characterizer the constituents responsible of the ACE activity of the aqueous extract of Hibiscus sabdariffa. Bioassay-guided fractionation of the aqueous extract of dried calyces of Hibiscus sabdariffa using preparative reversed-phase HPLC, and the in vitro ACE Inhibition assay, as biological monitor model, were used for the isolation. The isolated compounds were characterized by spectroscopic methods. The anthocyanins delphinidin-3-O-sambubioside (1) and cyanidin-3-O-sambubioside (2) were isolated by bioassay-guided purification. These compounds showed IC(50) values (84.5 and 68.4 microg/mL, respectively), which are similar to those obtained by related flavonoid glycosides. Kinetic determinations suggested that these compounds inhibit the enzyme activity by competing with the substrate for the active site. The competitive ACE inhibitor activity of the anthocyanins 1 and 2 is reported for the first time. This activity is in good agreement with the folk medicinal use of Hibiscus sabdariffa calyces as antihypertensive. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Blood pressure response to conventional and low-dose enalapril in chronic renal failure

DEFF Research Database (Denmark)

Elung-Jensen, Thomas; Heisterberg, Jens; Kamper, Anne-Lise

2003-01-01

AIMS: In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present...... study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. METHODS: As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data...

A ROLE OF ANGIOTENSIN-CONVERTING ENZYME IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE SUMMARY

Directory of Open Access Journals (Sweden)

N. D. Elshin

2017-01-01

Full Text Available Activation of angiotensin-converting enzyme (ACE is observed in lung tissues, induced sputum (IS, and, to a lesser extent in blood serum. Vascular hypertension is noted in 40 % of patients with chronic obstructive pulmonary disease (COPD. Therefore, many COPD patients receive ACE inhibitor therapy. Studies of ACE production by specific protein levels or ACE1 gene expression may represent sufficient clinical interest in COPD and upon its treatment using hypotensive drugs.The objective of the work was to study the normal ACE1 expression in control persons and COPD patients, and to assess correlations between the АСЕ1 genotypes and clinical parameters in patients with COPD.Materials and methods. The study included 124 patients with grade II-III COPD. ACE1 activity in blood leukocytes was determined by means of qPCR using fluorescent probes. As a reference gene for data normalization, the GAPDH gene was selected. The data on gene expression were evaluated according to the ∆∆Cq method. The insertion/deletion (I/D polymorphism of the АСЕ1 gene was determined with standard PCR technique according to the amplicon length after their detecting in agarose gel.Results. We have found a significantly increased AСЕ1 gene expression among patients with COPD upon exacerbation and after treatment, compared to control group. Frequencies of I/D genotypes and АСЕ1 gene alleles did not differ significantly between total group of patients and comparison groups, thus showing no association between this polymorphism and COPD risk. In combined sample group (95 tests, the D/D genotype has shown a moderate, but significant correlation with ACE1 mRNA expression in peripheral blood leukocytes.

Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

International Nuclear Information System (INIS)

Kamper, A.L.; Thomsen, H.S.; Nielsen, S.L.; Strandgaard, S.; Herlev Hospital

1990-01-01

Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51 Cr-EDTA plasma clearance fell by 14% (P 99m Tc-DMSA increased by 10% (P<0.01). It is concluded that DMSA in chronic renal failure is mainly taken up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR. (orig.)

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

Directory of Open Access Journals (Sweden)

Saurabh Chattopadhyay

Full Text Available Angiotensin-converting enzyme (ACE regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS. Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

Science.gov (United States)

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

Energy Technology Data Exchange (ETDEWEB)

Li, Hong-Bao [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Ma, Le [Department of Public Health, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Miao, Yu-Wang [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Lu, Yan [Department of Clinical Laboratory, Sanaitang Hospital, Lanzhou 730030 (China); Song, Xin-Ai [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

2014-09-01

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91{sup phox}) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension.

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

International Nuclear Information System (INIS)

Li, Hong-Bao; Qin, Da-Nian; Ma, Le; Miao, Yu-Wang; Zhang, Dong-Mei; Lu, Yan; Song, Xin-Ai; Zhu, Guo-Qing; Kang, Yu-Ming

2014-01-01

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91 phox ) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension

Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

DEFF Research Database (Denmark)

Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

2011-01-01

OBJECTIVE: High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than...... to increased risk of hypoglycemia generated from a negative binominal model were long diabetes duration (p high S-ACE level (p = 0.0497) when adjusted for ACE genotype. In the stratified analysis, S-ACE and insulin dosage were associated with hypoglycemia in girls (p = 0.026 and 0...

Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

DEFF Research Database (Denmark)

Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Z

2006-01-01

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

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

International Nuclear Information System (INIS)

Kma, L.; Gao, F.; Fish, B.L.; Moulder, J.E.; Jacobs, E.R.; Medhora, M.

2012-01-01

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

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

Science.gov (United States)

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.

Chronic heart failure

African Journals Online (AJOL)

enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone ... It has a predictive power of 90% in this situation (c-statistic. 0.90). It is a useful rule-out ... Psychosocial support and the treatment of depression are becoming ...

Identification of ace inhibitory cryptides in Tilapia protein hydrolysate by UPLC-MS/MS coupled to database analysis.

Science.gov (United States)

Yesmine, Ben Henda; Antoine, Bonnet; da Silva Ortência Leocádia, Nunes Gonzalez; Rogério, Boscolo Wilson; Ingrid, Arnaudin; Nicolas, Bridiau; Thierry, Maugard; Jean-Marie, Piot; Frédéric, Sannier; Stéphanie, Bordenave-Juchereau

2017-05-01

An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry method was developed and applied to identify short angiotensin-I-converting enzyme (ACE) inhibitory cryptides in Tilapia (Oreochromis Niloticus) protein hydrolyzate. A database was created with previously identified ACE-inhibitory di- and tripeptides and the lowest molecular weight fraction of Tilapia hydrolysate was analysed for coincidences. Only VW and VY were identified. Further analysis of collected fractions conducted to the identification of 51 different peptides in major fractions. 19 peptides selected were synthesised and tested for their ACE inhibitory potential. TL, TI, IK, LR, LD, IQ, DI, AILE, ALLE, ALIE and AIIE were identified as new ACE inhibitors. The findings from this study point UPLC-MS/MS combined with the creation of a database as an efficient technique to identify specific short peptides within a complex hydrolysate, in addition with de novo sequencing. This efficient characterisation of bioactive factors like cryptides in protein hydrolysates will extend their use as functional foods. Copyright © 2017 Elsevier B.V. All rights reserved.

The angiotensin-converting enzyme (ACE) gene insertion/ deletion dimorphism tracks with higher serum ace activities in both younger and older subjects

International Nuclear Information System (INIS)

Frossard, Philippe M.; Hill, Susan H.; Obineche, Enyioma N.; Lestringant, Gilles G.

1998-01-01

The absence of a 287 base pair alu sequence in the ACE gene (D allele) is associated with higher ACE levels than its presence (I allele) in adults. We carried out a case control study of thr ACE*I/D dimorphism in relation to circulating ACE activities to evaluate associations between the two variables in adults, compared to younger (18 years or less) individuals. Genotypes of the ACE*I/D dimorphism were determined on DNA samples from a population of 164 random (unrelated) Emirtaes nationals, composed of groups: 112 subjects above 18 years of age (range=20-77), and 52 subjects of 18 years or less (range=1-18) and analyzed for putative associations with serum ACE activities. ACE*I/D genotypes of the 164 individualds were determined by assays based on polymerase chain reaction. ACE activities were determined on serum samples of these subjects bu colorimetric assays. The D allele was associared with increasd ACE values in both adult and younger individuals. Mean ACE activity levels associated with II, ID and DD genotypes, however, were 42%-61% higher in the 18 years and under group of subjects. The ACE*I/D marker accounted for 28% of the variance of the phenomenon determining ACE levels in adults, and for 30% among youngsters. The ACE*I/D dimorphism is correlated strongly with circulating ACE activities in both and young Emirati, subjects and the corresponding mean ACE activities were significantly higher among the youngsters. (author)

Characterization of the relationship between APOBEC3B deletion and ACE Alu insertion.

Directory of Open Access Journals (Sweden)

Kang Wang

Full Text Available The insertion/deletion (I/D polymorphism of the angiotensin converting enzyme (ACE, commonly associated with many diseases, is believed to have affected human adaptation to environmental changes during the out-of-Africa expansion. APOBEC3B (A3B, a member of the cytidine deaminase family APOBEC3s, also exhibits a variable gene insertion/deletion polymorphism across world populations. Using data available from published reports, we examined the global geographic distribution of ACE and A3B genotypes. In tracking the modern human dispersal routes of these two genes, we found that the variation trends of the two I/D polymorphisms were directly correlated. We observed that the frequencies of ACE insertion and A3B deletion rose in parallel along the expansion route. To investigate the presence of a correlation between the two polymorphisms and the effect of their interaction on human health, we analyzed 1199 unrelated Chinese adults to determine their genotypes and other important clinical characteristics. We discovered a significant difference between the ACE genotype/allele distribution in the A3B DD and A3B II/ID groups (P = 0.045 and 0.015, respectively, indicating that the ACE Alu I allele frequency in the former group was higher than in the latter group. No specific clinical phenotype could be associated with the interaction between the ACE and A3B I/D polymorphisms. A3B has been identified as a powerful inhibitor of Alu retrotransposition, and primate A3 genes have undergone strong positive selection (and expansion for restricting the mobility of endogenous retrotransposons during evolution. Based on these findings, we suggest that the ACE Alu insertion was enabled (facilitated by the A3B deletion and that functional loss of A3B provided an opportunity for enhanced human adaptability and survival in response to the environmental and climate challenges arising during the migration from Africa.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

Science.gov (United States)

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: The Rotterdam study

NARCIS (Netherlands)

R. van der Knaap (Ronald); C. Siemes (Claire); J.W.W. Coebergh (Jan Willem); P. Tikka-Kleemola (Päivi); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

2008-01-01

textabstractBACKGROUND. Angiotensin I-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and the ACE insertion/deletion (I/D) gene polymorphism all influence serum angiotensin II action. Because angiotensin II levels have been associated with cancer, the objective of the current

Association of Angiotensin-Converting Enzyme ACE Gene Polymorphism with ACE Activity and Susceptibility to Vitiligo in Egyptian Population.

Science.gov (United States)

Badran, Dahlia I; Nada, Hesham; Hassan, Ranya

2015-05-01

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in the Indians and Koreans, but not in those of English or Turkish background. We investigated the ACE (I/D) polymorphism in vitiligo patients for the first time in Egypt and compared serum ACE levels between vitiligo patients and controls. The present study was carried out in 100 vitiligo patients (40 males and 60 females) and in 100 healthy controls of an Egyptian population using the polymerase chain reaction genotyping method. The ACE genotype and allele frequency was significantly different between vitiligo patients and controls. Our results revealed a significant increase in the frequency of the ACE I allele (p=0.002; odds ratio: 1.99; 95% confidence intervals: 1.207-3.284) with an overrepresentation of I/D genotype in the vitiligo patient group. Furthermore, there was a significant difference between the segmental, nonsegmental, and focal vitiligo in ACE gene genotype distribution. Serum ACE levels were significantly increased in vitiligo patients compared to controls (p=0.034). This study suggests that, for the first time, ACE gene polymorphism confers susceptibility to vitiligo in the Egyptian population.

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.

Science.gov (United States)

AlBacha, Jeanne d'Arc; Khoury, Mira; 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, PACE 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 (Del/4G) are at high risk for the onset of CVDs.

Adverse Childhood Experiences among a Community of Resilient Centenarians and Seniors: Implications for a Chronic Disease Prevention Framework.

Science.gov (United States)

Spencer-Hwang, Rhonda; Torres, Xochitl; Valladares, Johanny; Pasco-Rubio, Marco; Dougherty, Molly; Kim, Wonha

2018-03-11

Research has linked adverse childhood experiences (ACEs) with chronic disease in adults and diminished life span. Adverse biological embedding of ACEs potentially occurs through inflammatory mechanisms; inflammatory marker alterations are identified as candidate biomarkers for mediating health consequences. Lifestyle practices of residents of California's Loma Linda Blue Zone, one of five worldwide longevity hotspots, may provide insight into inflammation remediation and chronic disease prevention. Little research has been done on centenarians' early-life experiences or on ACEs in a longevity community. To interview centenarians and seniors in this region regarding their childhood experiences to inform chronic disease prevention frameworks. Qualitative study of Loma Linda Blue Zone community members. Childhood exposures and practices were assessed using focus groups and semistructured key informant interviews, with open-ended questions on general hardships and ACEs and supplemented with lifestyle and resiliency factor questions. Data were audiorecorded and transcribed. Integrative grounded theory methods guided coding and theming. Exposure to ACEs and practice of resiliency factors. Participants (7 centenarians and 29 seniors) reported exposure to multiple ACEs (domains: Economic deprivation, family dysfunction, and community violence). Community members reported practicing resiliency factors, each with anti-inflammatory properties suggesting mitigation of ACE-related toxic stress. This is one of the first studies of its kind to identify a community of resilient members despite their tremendous burden of ACEs. Embedding the identified resiliency factors into chronic disease prevention frameworks has potential for mitigating systemic inflammation, alleviating chronic disease burden, and promoting a culture of health.

Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design.

Science.gov (United States)

Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi

2006-03-31

Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of "domain-specific" second-generation ACE inhibitors.

On the influence of alkali metal- and alkaline earth metal chlorides on the rate on inhibition of cholinesterases by organic phosphorus inhibitors

International Nuclear Information System (INIS)

Brestkin, A.P.; Shataeva, G.A.

1975-01-01

Influence of LiCl, NaCl, KCl, RbCl, CsCl, MgCl 2 , CaCl 2 , CrCl 2 , BaCl 2 on bimolecular constant (K 2 ) of the interaction rate of acetylcholinesterazo (ACE) and butylcholinesterazo (BuCE) with phosphororganic inhibitors was studied. K 2 value with increasing of the electrolite concentration for the interaction of ACE and BuCE with charged inhibitor is significantly decreased and significantly increased in case of interaction with neutral inhibitor

Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging

International Nuclear Information System (INIS)

Soeki, Takeshi; Tamura, Yoshiyuki; Bandou, Kanji; Tanaka, Hideji; Takeichi, Naoki; Shinohara, Hisanori; Yui, Yasuko; Fukuda, Nobuo; Sui, Osamu

1998-01-01

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62±11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n=7), hypertension (n=2), and atrial fibrillation (n=1). Radioiodinated metaiodobenzyl guanidine ( 123 I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, left ventricular ejection fraction (LVEF) increased significantly from 38.3±6.9% to 47.5±14.7%; sub-maximal exercise time increased significantly from 205±112 to 272±120 seconds; the heart to mediastinum (H/M) ratio of 123 I-MIBG increased significantly (early image: 1.99±0.38 versus 2.20±0.50; delayed image: 1.86±0.44 versus 2.09±0.51); and the washout rate of 123 I-MIBG decreased slightly from 29.1±9.1% to 25.4±7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123 I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. (author)

Short-term treatment with diminazene aceturate ameliorates the reduction in kidney ACE2 activity in rats with subtotal nephrectomy.

Directory of Open Access Journals (Sweden)

Elena Velkoska

Full Text Available Angiotensin converting enzyme (ACE 2 is an important modulator of the renin angiotensin system (RAS through its role to degrade angiotensin (Ang II. Depletion of kidney ACE2 occurs following kidney injury due to renal mass reduction and may contribute to progressive kidney disease. This study assessed the effect of diminazine aceturate (DIZE, which has been described as an ACE2 activator, on kidney ACE2 mRNA and activity in rats with kidney injury due to subtotal nephrectomy (STNx. Sprague Dawley rats were divided into Control groups or underwent STNx; rats then received vehicle or the DIZE (s.c. 15 mg/kg/day for 2 weeks. STNx led to hypertension (P<0.01, kidney hypertrophy (P<0.001 and impaired kidney function (P<0.001 compared to Control rats. STNx was associated with increased kidney cortical ACE activity, and reduced ACE2 mRNA in the cortex (P<0.01, with reduced cortical and medullary ACE2 activity (P<0.05, and increased urinary ACE2 excretion (P<0.05 compared to Control rats. Urinary ACE2 activity correlated positively with urinary protein excretion (P<0.001, and negatively with creatinine clearance (P=0.04. In STNx rats, DIZE had no effect on blood pressure or kidney function, but was associated with reduced cortical ACE activity (P<0.01, increased cortical ACE2 mRNA (P<0.05 and increased cortical and medullary ACE2 activity (P<0.05. The precise in vivo mechanism of action of DIZE is not clear, and its effects to increase ACE2 activity may be secondary to an increase in ACE2 mRNA abundance. In ex vivo studies, DIZE did not increase ACE2 activity in either Control or STNx kidney cortical membranes. It is not yet known if chronic administration of DIZE has long-term benefits to slow the progression of kidney disease.

ACES CONTINUOUS DATA V1

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National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was Based at the Naval Air Facility Key West in Florida. ACES researchers in August 2002 conducted overflights of...

ACES CONTINUOUS DATA V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was based at the Naval Air Facility Key West in Florida. During August, 2002, ACES researchers conducted overflights of...

ACES TRIGGERED DATA V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was based at the Naval Air Facility Key West in Florida. During August 2002, ACES researchers conducted overflights of...

ACES TIMING DATA V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was based at the Naval Air Facility Key West in Florida. During August or 2002, ACES researchers overflights of...

ACES TRIGGERED DATA V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was Based at the Naval Air Facility Key West in Florida. ACES researchers in August 2002 conducted overflights of...

ACES LOG DATA V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was Based at the Naval Air Facility Key West in Florida. ACES researchers in August 2002 conducted overflights of...

ACES TIMING DATA V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was Based at the Naval Air Facility Key West in Florida. ACES researchers in August 2002 conducted overflights of...

The ACE experiment

CERN Multimedia

Maximilien Brice

2006-01-01

The Antiproton Cell Experiment (ACE) as shown by Michael Holzscheiter (spokesperson), Niels Bassler (co-spokesperson) and Helge Knudsen. ACE is located on the Antiproton Decelerator (AD) at CERN. An antiproton annihilates a proton in the nucleus of a cancer cell, producing a pair of gamma rays, destroying the entire cell and some surrounding cells. Many fewer antiprotons are required in this treatment than in the equivalent proton hadron therapy, so there is less risk of healthy tissue damage.

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

Science.gov (United States)

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

2016-01-01

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

The Evaluation of Angiotensin-Converting Enzyme Inhibitors in Renal Elimination with Selected Molecular Descriptors

Directory of Open Access Journals (Sweden)

Trbojevic Jovana

2017-06-01

Full Text Available Angiotensin-converting enzyme (ACE inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril and their renal elimination data, from relevant literature, were investigated. The ’molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS; an electronic descriptor, polar surface area (PSA;, a constitutional parameter, molecular mass (Mr; and a geometric descriptor, volume value (Vol, as well as lipophilicity descriptors (logP values, were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742. In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors’ renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425 or the geometric descriptor (volume value (R2 = 0.7224 as an independent variable. The application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.

Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia.

Science.gov (United States)

Radich, Jerald P; Mauro, Michael J

2017-08-01

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors has led to a reduction in mortalities. Thus, the estimated prevalence of CML is increasing. The National Comprehensive Cancer Network and the European Leukemia Net guidelines incorporate frequent molecular monitoring of the fusion BCR-ABL transcript to ensure that patients reach and keep treatment milestones. Most patients with CML are diagnosed in the chronic phase, and approximately 10% to 30% of these patients will at some time in their course meet definition criteria of resistance to imatinib. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

DEFF Research Database (Denmark)

Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

2011-01-01

High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than 1000 chil...... children and adolescents with type 1 diabetes being part of the Danish Registry of Childhood diabetes over a 10-yr period....

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

Science.gov (United States)

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

Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by {sup 123}I-MIBG imaging

Energy Technology Data Exchange (ETDEWEB)

Soeki, Takeshi; Tamura, Yoshiyuki; Bandou, Kanji; Tanaka, Hideji; Takeichi, Naoki; Shinohara, Hisanori; Yui, Yasuko; Fukuda, Nobuo; Sui, Osamu [Zentsuji National Hospital, Kagawa (Japan)

1998-11-01

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62{+-}11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n=7), hypertension (n=2), and atrial fibrillation (n=1). Radioiodinated metaiodobenzyl guanidine ({sup 123}I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, left ventricular ejection fraction (LVEF) increased significantly from 38.3{+-}6.9% to 47.5{+-}14.7%; sub-maximal exercise time increased significantly from 205{+-}112 to 272{+-}120 seconds; the heart to mediastinum (H/M) ratio of {sup 123}I-MIBG increased significantly (early image: 1.99{+-}0.38 versus 2.20{+-}0.50; delayed image: 1.86{+-}0.44 versus 2.09{+-}0.51); and the washout rate of {sup 123}I-MIBG decreased slightly from 29.1{+-}9.1% to 25.4{+-}7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and {sup 123}I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. (author)

Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

Science.gov (United States)

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

2015-07-01

Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc

Histone Deacetylase Inhibitors Are Protective in Acute but Not in Chronic Models of Ototoxicity

Directory of Open Access Journals (Sweden)

Chao-Hui Yang

2017-10-01

Full Text Available Previous studies have reported that modification of histones alters aminoglycoside-induced hair cell death and hearing loss. In this study, we investigated three FDA-approved histone deacetylase (HDAC inhibitors (vorinostat/SAHA, belinostat, and panobinostat as protectants against aminoglycoside-induced ototoxicity in murine cochlear explants and in vivo in both guinea pigs and CBA/J mice. Individually, all three HDAC inhibitors reduced gentamicin (GM-induced hair cell loss in a dose-dependent fashion in explants. In vivo, however, treatment with SAHA attenuated neither GM-induced hearing loss and hair cell loss in guinea pigs nor kanamycin (KM-induced hearing loss and hair cell loss in mice under chronic models of ototoxicity. These findings suggest that treatment with the HDAC inhibitor SAHA attenuates aminoglycoside-induced ototoxicity in an acute model, but not in chronic models, cautioning that one cannot rely solely on in vitro experiments to test the efficacy of otoprotectant compounds.

Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.

Science.gov (United States)

Rangel, Marina; dos Santos, Jéssica Cassilla; Ortiz, Paula Helena Lima; Hirata, Mario; Jasiulionis, Miriam Galvonas; Araujo, Ronaldo C; Ierardi, Daniela Filippini; Franco, Maria do Carmo

2014-01-01

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (PACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (PACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Saba Saleem

Full Text Available 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.

A meta-analysis of the accuracy of the Addenbrooke's Cognitive Examination (ACE) and the Addenbrooke's Cognitive Examination-Revised (ACE-R) in the detection of dementia.

Science.gov (United States)

Larner, Andrew J; Mitchell, Alex J

2014-04-01

The Addenbrooke's Cognitive Examination (ACE) and its Revised version (ACE-R) are relatively new screening tools for cognitive impairment that may improve upon the well-known Mini-Mental State Examination (MMSE) and other brief batteries. We systematically reviewed diagnostic accuracy studies of ACE and ACE-R. Published studies comparing ACE, ACE-R and MMSE were comprehensively sought and critically appraised. A meta-analysis of suitable studies was conducted. Of 61 possible publications identified, meta-analysis of qualifying studies encompassed 5 for ACE (1,090 participants) and 5 for ACE-R (1156 participants); of these, 9 made direct comparisons with the MMSE. Sensitivity and specificity of the ACE were 96.9% (95% CI = 92.7% to 99.4%) and 77.4% (95% CI = 58.3% to 91.8%); and for the ACE-R were 95.7% (95% CI = 92.2% to 98.2%) and 87.5% (95% CI = 63.8% to 99.4%). In a modest prevalence setting, such as primary care or general hospital settings where the prevalence of dementia may be approximately 25%, overall accuracy of the ACE (0.823) was inferior to ACE-R (0.895) and MMSE (0.882). In high prevalence settings such as memory clinics where the prevalence of dementia may be 50% or higher, overall accuracy again favored ACE-R (0.916) over ACE (0.872) and MMSE (0.895). The ACE-R has somewhat superior diagnostic accuracy to the MMSE while the ACE appears to have inferior accuracy. The ACE-R is recommended in both modest and high prevalence settings. Accuracy of newer versions of the ACE remain to be determined.

Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

DEFF Research Database (Denmark)

Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe Nørgaard

2005-01-01

OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from...... pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13). Women, elderly patients and patients taking loop......-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged or = 80 years and patients not taking loop...

Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

DEFF Research Database (Denmark)

Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe N

2005-01-01

pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13). Women, elderly patients and patients taking loop-diuretics...... and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged or = 80 years and patients not taking loop-diuretics...... received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people...

Role of ACE and IL-1β Gene Polymorphisms in Erythropoeitin Hyporesponsive Patients with Chronic Kidney Disease with Anemia.

Science.gov (United States)

Nand, N; Deshmukh, A R; Joshi, S; Sachdeva, M P; Sakthivel

2017-02-01

Hyporesponse to erythropoietin is a common problem seen in around 5-10% of patients. Recently the focus from these remediable factors has been shifted to the non-modifiable innate factors i.e polymorphism of ACE and IL-1B gene and studies have shown that DD genotype and IL-1B CC genotype have lower erythropoietin requirement. The aim of our study was to evaluate the role of ACE and IL-1B gene polymorphisms in erythropoietin hyporesponse in CKD patients with anemia. A total of 50 patients were selected. After taking pre-informed written consent, they were segregated into two groups, group A and B with 25 patients in each group. Group A included CKD stage III-IV patients and Group B included CKD stage V patients who were on regular maintenance. All patients were given erythroepoietin and response was monitored using erythropoietin resistance index (ERI). Genotyping of ACE and IL-1B genes were done and serum levels of ACE and IL-1B were measured. Mean values of ERI were compared between different genotype subgroups and analysed using binary regression analysis. The study group included 6 patients with diabetic nephropathy and out of these 4(66.6%) had DD genotype. On comparing the effect of ACE polymorphism on ERI levels it was seen that the mean ERI values in DD subgroup were significantly lower (16.97±5.35, 21.88±6.25, 22.69±8.35 at 1,3 and 5th month) as compared to ID (18.16±3.39, 24.17±3.66, 32.74±9.95 and II (20.73±5.17, 27.74±7.30, 41.08±13.83 U/Kg/g/dL). In the case of IL-1B the mean ERI values were lowest in the TT subgroup (16.46±4.45, 21.96±5.77,23.98±8.48) as compared to CC (19.49 ±5.62,25.46±7.07, 33.59±12.61) and CT (18.12±4.27,24.14±5.70, 31.89±13.83 U/Kg/g/dL). The mean serum values of ACE were in a decreasing trend i.e DD> ID> II (238.05 ± 52.46, 194.73±50.28 and 162.99±39.71 ng/ml, (p 0.05). D allele positively affected the serum ACE level but there was no association between IL-1B genotype and its levels. ACE gene polymorphism

Comparison of the diabetes guidelines from the ADA/EASD and the AACE/ACE.

Science.gov (United States)

Cornell, Susan

To compare recent diabetes guideline updates from the American Diabetes Association-European Association for the Study of Diabetes (ADA/EASD) and the American Association of Clinical Endocrinologists-American College of Endocrinology (AACE/ACE). The ADA/EASD guideline continues to advocate a stepwise approach to glycemic control that initiates with metformin and intensifies treatment incrementally to dual and triple therapy at 3-month intervals until the patient is at their individualized goal. The AACE/ACE guideline provides a broader choice of first-line medications, with a suggested hierarchy of use, and it encourages initial dual and triple therapy if the glycated hemoglobin (A1C) level is high enough at diagnosis (7.5%-9.0% and >9.0%, respectively). Target A1C levels are higher in the ADA/EASD guideline (≤7.0%) compared with the AACE/ACE guideline (≤6.5%), although both statements indicate that targets should be adjusted to specific clinical scenarios based on safety. Both guidelines now include the new sodium-glucose cotransporter-2 inhibitors among their choices of acceptable glucose-lowering medications and endorse the overall cardiovascular and pancreatic safety of incretin therapies, and the safety of pioglitazone vis-a-vis bladder cancer. In practice, the ADA/EASD guidelines tend to be more user-friendly for general practitioners because of the simple stepwise intensification regimen, whereas the AACE/ACE guidelines are more commonly followed by specialists (endocrinologists) because of the more aggressive A1C targets. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

ACES ELECTRIC FIELD MILL V1

Data.gov (United States)

National Aeronautics and Space Administration — The ALTUS Cloud Electrification Study (ACES) was based at the Naval Air Facility Key West in Florida. ACES researchers in August 2002 conducted overflights of...

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

Energy Technology Data Exchange (ETDEWEB)

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.

Mutations in serine protease inhibitor Kazal type 1 are strongly associated with chronic pancreatitis

OpenAIRE

Drenth, J P H; te Morsche, R; Jansen, J B M J

2002-01-01

Background: Although chronic pancreatitis is associated with risk factors such as alcoholism, hyperparathyroidism, and hypertriglyceridaemia, little is known of the actual aetiology of the disease. It is thought that inappropriate activation of trypsinogen causes pancreatitis, and indeed in cases of hereditary pancreatitis mutations of cationic trypsinogen (PRSS1) have been described. As serine protease inhibitor Kazal type 1 (SPINK1) is a potent natural inhibitor of pancreatic trypsin activi...

Blood pressure response to conventional and low-dose enalapril in chronic renal failure

DEFF Research Database (Denmark)

Elung-Jensen, Thomas; Heisterberg, Jens; Kamper, Anne-Lise

2003-01-01

AIMS: In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present...... study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. METHODS: As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data...... potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR. CONCLUSIONS: In moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective...

A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction

DEFF Research Database (Denmark)

Abdulla, Jawdat; Abildstrøm, Steen Zabell; Køber, Lars Valeur

2004-01-01

AIM: To determine by meta-analysis whether angiotensin-converting enzyme (ACE) inhibitors improve exercise tolerance in patients with symptomatic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: After literature search 13 multi-centre double blind parallel group trials that eval......% compared with placebo. CONCLUSION: In addition to the pronounced effect on mortality and morbidity in patients with symptomatic LVSD, ACE inhibitors have improving effect on functional capacity measured as exercise tolerance time....

Beginning RPG Maker VX Ace

CERN Document Server

Perez, Darrin

2014-01-01

Beginning RPG Maker VX Ace takes you through the process of using the RPG Maker VX Ace game development engine to create your very own role playing game. The book has been designed with the complete beginner in mind who has little to no experience with the engine. Tutorials and exercises will take you from installing the software to putting the final touches upon your first project. Game design can be quite a daunting challenge, as it generally involves a large amount of programming know-how on top of having to plan everything out that makes a good game what it is. RPG Maker VX Ace

User's manual ACE/ONED (Version 1.0)

International Nuclear Information System (INIS)

Lee, Ki Bok; Lee, Jeong Chan; Song, Jae Seung; Lee, Chang Kyu; Ji, Sung Kyun; Song, Jae Woong; Kim, Yong Rae; Chang, Jong Hwa

1996-03-01

This report explains installation of ACE/ONED code, structure of input and output, how to prepare input and introduces some sample inputs. ACE/ONED developed by KAERI is a two-group one-dimensional diffusion theory code for nuclear design and reactor simulations. The usage of ACE/ONED encompasses core follow calculation, load-following calculation, plant power control simulation, xenon oscillation simulation, control rod maneuvering, and so on. ACE/ONED programmed of FORTRAN 77 in most part can be run on almost all kinds of computer including personal computer. 4 tabs., 4 figs., 8 refs. (Author) .new

How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

DEFF Research Database (Denmark)

Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

2010-01-01

An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...... of heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

Understanding Antegrade Colonic Enema (ACE) Surgery

Science.gov (United States)

... Enema (ACE) Surgery Menu Overview Procedure Details Risks / Benefits What is antegrade colonic enema (ACE) surgery? Antegrade ... Accepted Insurance Make a Donation Refer a Patient Phone Directory Blog, News & Mobile Apps Consult QD Health Essentials Newsroom Mobile Apps ...

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.

Science.gov (United States)

Chong, Jimmy; Leung, Bonnie; Poole, Phillippa

2017-09-19

Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE 4 ) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013. To evaluate the efficacy and safety of oral PDE 4 inhibitors in the management of stable COPD. We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search October 2016). We found other trials from web-based clinical trials registers. We included RCTs if they compared oral PDE 4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. One review author extracted data and a second review author checked the data. We reported pooled data in Review Manager as mean differences (MD), standardised mean differences (SMD) or odds ratios (OR). We converted the odds ratios into absolute treatment effects in a 'Summary of findings' table. Thirty-four separate RCTs studying roflumilast (20 trials with 17,627 participants) or cilomilast (14 trials with 6457 participants) met the inclusion criteria, with a duration of between six weeks and one year. These included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II-IV), with a mean age of 64 years.We considered that the methodological quality of the 34 published and unpublished trials was acceptable overall. Treatment with a PDE 4 inhibitor was associated with a significant improvement in forced expiratory volume in one second (FEV 1 ) over the trial period compared with placebo (MD 51.53 mL, 95% confidence interval (CI) 43.17 to 59.90, 27

Prostatic-Like Syndrome in a Woman with Chronic Lymphocytic Leukemia: Sequential Kinase Inhibitor Therapy

Directory of Open Access Journals (Sweden)

Diego Velasco-Rodríguez

2017-01-01

Full Text Available Chronic lymphocytic leukemia (CLL is an incurable lymphoproliferative disorder with a heterogeneous genetic and clinical course. Two kinase inhibitors, ibrutinib and idelalisib, have demonstrated achievement of complete and durable remissions in relapse/refractory genetically unselected CLL patients. We present a case of relapsed CLL with extensive disease and hourglass deformity of urinary bladder as a result of the compression of two extraperitoneal paravesical soft tissue bulky masses, with excellent response to sequential kinase inhibitor therapy.

Conoco serves an ACE

Energy Technology Data Exchange (ETDEWEB)

Cottrill, A.; Jackson, G. [Arup Energy (United Kingdom)

2001-06-01

The Hang Tuah gas platform recently installed in Conoco's West Natuna field off Indonesia is the first example in the world of a low-cost, relocatable platform based on the ACE concept developed by Arup Energy in the UK. It is expected to operate at two other locations in the West Natuna block during its 25-year lifetime. The ACE platform, which can operate at depths up to 100 m, has four main components: the deck in the form of a barge, strand jacks to lower the four lattice legs on a rectangular steel gravity base, and a jacking system. The background to the decision to opt for the ACE concept, its advantages, the delivery contract, the platform's flexibility, and its fabrication and installation are described. The weights of the various components and the levels to which loads can be raised are summarised in a table. The areas where cost savings are made with this design are explained in a side box.

Validation of ozone measurements from the Atmospheric Chemistry Experiment (ACE

Directory of Open Access Journals (Sweden)

E. Dupuy

2009-01-01

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

CHANGES IN RENAL-FUNCTION INDUCED BY ACE-INHIBITION IN THE CONSCIOUS 2-KIDNEY, ONE-CLIP GOLDBLATT HYPERTENSIVE DOG

NARCIS (Netherlands)

JONKER, GJ; VISSCHER, CA; DEZEEUW, D; HUISMAN, RM; PIERS, DA; BEEKHUIS, H; VANDERHEM, GK

In order to study why the diagnostic sensitivity of I-123-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV),

Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

Directory of Open Access Journals (Sweden)

Avital F. Barak

2011-12-01

Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Directory of Open Access Journals (Sweden)

L. L. Vysotskaya

2015-01-01

Full Text Available Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib and second line (nilotinib, overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of chronic pain.

Science.gov (United States)

Delgado, Pedro L

2006-01-01

Depression and painful symptoms occur frequently together. Over 75% of depressed patients report painful symptoms such as headache, stomach pain, neck and back pain as well as non-specific generalized pain. In addition, World Health Organization data have shown that primary care patients with chronic pain have a four fold greater risk of becoming depressed than pain-free patients. Increasingly, pain is considered as an integral symptom of depression and there evidence to suggest that pain and depression may arise from a common neurobiological dysfunction. Serotonergic cell bodies, in the raphe nucleus, and noradrenergic cell bodies in the locus coeruleus send projections to various parts of the brain, where they are involved in the control of mood, movement, cognitive functioning and emotions. In addition both serotonergic and noradrenergic neurons project to the spinal cord. These descending pathways serve to inhibit input from the intestines, skeletal muscles and other sensory inputs. Usually, these inhibitory effects are modest, but in times of stress, in the interest of the survival of the individual, they can completely inhibit the input from painful stimuli. A dysfunction of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological symptoms of depression and somatic pain symptoms such as chronic pain, fibromyalgia, non-cardiac chest pain, or irritable bowel syndrome. In view of this, it is not surprising that tricyclic antidepressants have been a standard treatment of chronic pain for many years. In contrast and in spite of their improved tolerance, selective serotonin reuptake inhibitors do not appear to be particularly effective in the treatment of pain. Recently, a number of open and controlled trials with selective serotonin and noradrenaline reuptake inhibitors such as venlafaxine, milnacipran and duloxetine, suggest that these compounds may be more effective in relieving pain

Circulating ACE2 activity correlates with cardiovascular disease development

Directory of Open Access Journals (Sweden)

Katalin Úri

2016-12-01

Full Text Available It was shown recently that angiotensin-converting enzyme activity is limited by endogenous inhibition in vivo, highlighting the importance of angiotensin II (ACE2 elimination. The potential contribution of the ACE2 to cardiovascular disease progression was addressed. Serum ACE2 activities were measured in different clinical states (healthy, n=45; hypertensive, n=239; heart failure (HF with reduced ejection fraction (HFrEF n=141 and HF with preserved ejection fraction (HFpEF n=47. ACE2 activity was significantly higher in hypertensive patients (24.8±0.8 U/ml than that in healthy volunteers (16.2±0.8 U/ml, p=0.01. ACE2 activity further increased in HFrEF patients (43.9±2.1 U/ml, p=0.001 but not in HFpEF patients (24.6±1.9 U/ml when compared with hypertensive patients. Serum ACE2 activity negatively correlated with left ventricular systolic function in HFrEF, but not in hypertensive, HFpEF or healthy populations. Serum ACE2 activity had a fair diagnostic value to differentiate HFpEF from HFrEF patients in this study. Serum ACE2 activity correlates with cardiovascular disease development: it increases when hypertension develops and further increases when the cardiovascular disease further progresses to systolic dysfunction, suggesting that ACE2 metabolism plays a role in these processes. In contrast, serum ACE2 activity does not change when hypertension progresses to HFpEF, suggesting a different pathomechanism for HFpEF, and proposing a biomarker-based identification of these HF forms.

Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade.

Science.gov (United States)

Sawada, Yoko; Sakamoto, Yuri; Toh, Mariko; Ohara, Nozomi; Hatanaka, Yuiko; Naka, Ayano; Kishimoto, Yoshimi; Kondo, Kazuo; Iida, Kaoruko

2015-12-01

This study aimed to examine the effects of Val-Pro-Pro (VPP), a food-derived peptide with an angiotensin-converting enzyme (ACE) inhibitory property, on obesity-linked insulin resistance, and adipose inflammation in vivo and in vitro. C57BL/6J mice were fed high-fat high-sucrose diet and VPP (0.1% in water) for 4 months. For in vitro analysis, coculture of 3T3-L1 adipocytes overexpressing either ACE (3T3-ACE) or green fluorescent protein (3T3-GFP) and RAW264 macrophages was conducted with VPP. In diet-induced obese mice, VPP improved insulin sensitivity, concomitant with a significant decrease in tumor necrosis factor α (TNF-α) and IL-1β expression in adipose tissue, with a tendency (p = 0.06) toward decreased CC chemokine ligand 5 expression. Additionally, VPP administration inhibited macrophage accumulation and activation in fat tissues. In vitro, VPP attenuated TNF-α mRNA induced by ACE overexpression in 3T3-L1 adipocytes. TNF-α and IL-1β expression decreased following VPP treatment of RAW264 macrophage and 3T3-ACE adipocyte cocultures, but not in RAW264-3T3-GFP adipocyte cocultures. Our data suggest that VPP inhibits adipose inflammation in the interaction between adipocytes and macrophages, acting as an ACE inhibitor, thereby improving obesity-related insulin resistance. Thus, ingestion of VPP may be a viable protective and therapeutic strategy for insulin resistance and obesity-associated adipose inflammation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiple ace genes encoding acetylcholinesterases of Caenorhabditis elegans have distinct tissue expression.

Science.gov (United States)

Combes, Didier; Fedon, Yann; Toutant, Jean-Pierre; Arpagaus, Martine

2003-08-01

ace-1 and ace-2 genes encoding acetylcholinesterase in the nematode Caenorhabditis elegans present 35% identity in coding sequences but no homology in noncoding regions (introns, 5'- and 3'-untranslated regions). A 5'-region of ace-2 was defined by rescue of ace-1;ace-2 mutants. When green fluorescent protein (GFP) expression was driven by this regulatory region, the resulting pattern was distinct from that of ace-1. This latter gene is expressed in all body-wall and vulval muscle cells (Culetto et al., 1999), whereas ace-2 is expressed almost exclusively in neurons. ace-3 and ace-4 genes are located in close proximity on chromosome II (Combes et al., 2000). These two genes were first transcribed in vivo as a bicistronic messenger and thus constitute an ace-3;ace-4 operon. However, there was a very low level of monocistronic mRNA of ace-4 (the upstream gene) in vivo, and no ACE-4 enzymatic activity was ever detected. GFP expression driven by a 5' upstream region of the ace-3;ace-4 operon was detected in several muscle cells of the pharynx (pm3, pm4, pm5 and pm7) and in the two canal associated neurons (CAN cells). A dorsal row of body-wall muscle cells was intensively labelled in larval stages but no longer detected in adults. The distinct tissue-specific expression of ace-1, ace-2 and ace-3 (coexpressed only in pm5 cells) indicates that ace genes are not redundant.

Efficacy of lycopene on modulation of renal antioxidant enzymes, ACE and ACE gene expression in hyperlipidaemic rats.

Science.gov (United States)

Khan, Nazish Iqbal; Noori, Shafaq; Mahboob, Tabassum

2016-07-01

We aimed to evaluate the efficacy of lycopene on renal tissue antioxidant enzymes and angiotensin converting enzyme (ACE) gene expression and serum activity in diet-induced hyperlipidaemia. Thirty-two female Wistar albino rats (200-250 g weight), 5-6 months of age, were randomly selected and divided into four groups. Group I received normal diet; group II received 24 g high fat diet/100 g of daily diet; group III received 24 g high fat diet/100 g daily diet and 200 ml of lycopene extract (twice a week) for 8 weeks; and group IV received 200 ml oral lycopene extract twice a week for 8 weeks. A marked increase was observed in plasma urea and creatinine levels, serum C-reactive protein, kidney weight, tissue renal malonyldialdehyde level, ACE gene expression and serum level, while a decrease catalase level among hyperlipidaemic rats was observed. Histologically, interstitial inflammation and proliferation was seen. Lycopene supplementation significantly decreased plasma urea and creatinine, serum ACE, renal tissue malonyldialdehyde level and C-reactive protein level, while it increased tissue antioxidant enzymes level and total protein. Tissue inflammation and proliferation was improved. This finding suggests that supplementation of lycopene is effective for renal antioxidant enzymes, ACE gene expression and ACE serum level in hyperlipidaemic rats. © The Author(s) 2016.

Effects of gamma irradiation on microbiological, phytochemical content, antioxidant activity and inhibition of angiotensin converting enzyme (ACE) Activity of Peperomia pellucida (L.) Kunth

NARCIS (Netherlands)

Mun'im, Abdul; Ramadhani, Fitria; Chaerani, Kartika; Amelia, Lili; Arrahman, Arif

2017-01-01

Objective: Gamma irradiation is an effective technique can be used to reduce contaminants in herbal products. Peperomia pellucida (L.) Kunth belongs to Piperaceae family has some biological activity, such as antioxidant and ACE inhibitor. The aimed of this research was to determine the effects of

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states

Directory of Open Access Journals (Sweden)

Cunningham TJ

2014-09-01

Full Text Available Timothy J Cunningham,1 Earl S Ford,1 Janet B Croft,1 Melissa T Merrick,2 Italia V Rolle,3 Wayne H Giles1 1Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA; 2Division of Violence Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA; 3Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA Purpose: Adverse childhood experiences (ACEs before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD in the general population. Materials and methods: Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs and their corresponding 95% confidence intervals (CIs for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Results: Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61, sexual abuse (PR =1.69, 95% CI: 1.36, 2.10, living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81, witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72, and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80 during childhood compared to those with no individual ACEs

99mTc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice

International Nuclear Information System (INIS)

Kaloudi, Aikaterini; Nock, Berthold A.; Lymperis, Emmanouil; Krenning, Eric P.; Jong, Marion de; Maina, Theodosia

2016-01-01

Introduction: In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE-inhibition on the pharmacokinetic profile of three 99m Tc-labeled gastrins of varying peptide chain length: [ 99m Tc]SG6 ([ 99m Tc-N 4 -Gln 1 ]gastrin(1–17)), [ 99m Tc]DG2 ([ 99m Tc-N 4 -Gly 4 ,DGlu 5 ]gastrin(4–17)) and [ 99m Tc]DG4 ([ 99m Tc-N 4 -DGlu 10 ]gastrin(10–17)). Methods: Mouse blood samples were collected 5 min after injection of each of [ 99m Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431-CCK2R(+/−) xenografts at 4 h postinjection (pi). [ 99m Tc]SG6 or [ 99m Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [ 99m Tc]DG2 control and PA animal groups were only included. Results: Treatment of mice with PA induced significant stabilization of 99m Tc-radiotracers in peripheral blood, while treatment with Lis or Lis + PA affected the stability of des(Glu) 5 [ 99m Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (P < 0.01). Only [ 99m Tc]DG4 profited by single Lis (2.06 ± 0.39%ID/g vs 0.99 ± 0.13%ID/g in controls) or combined Lis + PA coinjection (8.91 ± 1.61%ID/g vs 4.89 ± 1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [ 99m Tc]DG4 (< 1.9%ID/g) resulting in the most optimal tumor-to-kidney ratios. Conclusions: In situ NEP/ACE

ACE Gene in Egyptian Ischemic Stroke Patients.

Science.gov (United States)

Mostafa, Magdy A; El-Nabiel, Lobna M; Fahmy, Nagia Aly; Aref, Hany; Shreef, Edrees; Abd El-Tawab, Fathy; Abdulghany, Osama M

2016-09-01

Angiotensin-1-converting enzyme (ACE) is a crucial player in vascular homeostasis and in the pathogenesis of atherosclerosis and hypertension. The present study was conducted to determine whether there is an association between the ACE insertion/deletion (I/D) polymorphism and ischemic stroke in Egyptian population. Also, we analyzed the ACE gene I/D polymorphism as a risk factor for small-vessel (SV) versus large-vessel (LV) disease. Sixty patients with ischemic stroke were included: 30 with SV disease and 30 with LV disease. In addition, a control group of 30 apparent healthy subjects were studied. Clinical assessment, computed tomography, magnetic resonance imaging brain, and genetic study using the polymerase chain reaction of ACE gene were done for all subjects. We found that the distribution of ACE gene polymorphism frequency was significantly different between the 3 groups. The DD genotype was far more common in stroke patients compared to controls. It was also significantly more common in each of the patient groups compared to controls but rather similar in the 2 patient groups with SV and LV diseases. We found that the ACE gene deletion/deletion genotype is common in Egyptian patients with non-cardioembolic ischemic stroke but does not appear to be specific neither to SV nor to LV disease. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

Directory of Open Access Journals (Sweden)

T. D. Kaplanov

2015-12-01

Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

Directory of Open Access Journals (Sweden)

T. D. Kaplanov

2005-01-01

Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

Regulation of the aceI multidrug efflux pump gene in Acinetobacter baumannii.

Science.gov (United States)

Liu, Qi; Hassan, Karl A; Ashwood, Heather E; Gamage, Hasinika K A H; Li, Liping; Mabbutt, Bridget C; Paulsen, Ian T

2018-06-01

To investigate the function of AceR, a putative transcriptional regulator of the chlorhexidine efflux pump gene aceI in Acinetobacter baumannii. Chlorhexidine susceptibility and chlorhexidine induction of aceI gene expression were determined by MIC and quantitative real-time PCR, respectively, in A. baumannii WT and ΔaceR mutant strains. Recombinant AceR was prepared as both a full-length protein and as a truncated protein, AceR (86-299), i.e. AceRt, which has the DNA-binding domain deleted. The binding interaction of the purified AceR protein and its putative operator region was investigated by electrophoretic mobility shift assays and DNase I footprinting assays. The binding of AceRt with its putative ligand chlorhexidine was examined using surface plasmon resonance and tryptophan fluorescence quenching assays. MIC determination assays indicated that the ΔaceI and ΔaceR mutant strains both showed lower resistance to chlorhexidine than the parental strain. Chlorhexidine-induced expression of aceI was abolished in a ΔaceR background. Electrophoretic mobility shift assays and DNase I footprinting assays demonstrated chlorhexidine-stimulated binding of AceR with two sites upstream of the putative aceI promoter. Surface plasmon resonance and tryptophan fluorescence quenching assays suggested that the purified ligand-binding domain of the AceR protein was able to bind with chlorhexidine with high affinity. This study provides strong evidence that AceR is an activator of aceI gene expression when challenged with chlorhexidine. This study is the first characterization, to our knowledge, of a regulator controlling expression of a PACE family multidrug efflux pump.

High prevalence of risk factors in coronary artery disease in EUROPA gives HOPE for ACE inhibitors after PEACE

DEFF Research Database (Denmark)

Pedersen, S.A.; Galatius, S.; Olsen, M.H.

2008-01-01

ventricular systolic dysfunction, diabetes, myocardial infarction and hypertension in an unselected and consecutive population of patients with documented CAD and evaluate the potential need for ACE-I treatment in a real-life scenario. Methods: We searched a database containing all invasive cardiac...

(99m)Tc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice.

Science.gov (United States)

Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

2016-06-01

In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE-inhibition on the pharmacokinetic profile of three (99m)Tc-labeled gastrins of varying peptide chain length: [(99m)Tc]SG6 ([(99m)Tc-N4-Gln(1)]gastrin(1-17)), [(99m)Tc]DG2 ([(99m)Tc-N4-Gly(4),DGlu(5)]gastrin(4-17)) and [(99m)Tc]DG4 ([(99m)Tc-N4-DGlu(10)]gastrin(10-17)). Mouse blood samples were collected 5min after injection of each of [(99m)Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431-CCK2R(+/-) xenografts at 4h postinjection (pi). [(99m)Tc]SG6 or [(99m)Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [(99m)Tc]DG2 control and PA animal groups were only included. Treatment of mice with PA induced significant stabilization of (99m)Tc-radiotracers in peripheral blood, while treatment with Lis or Lis+PA affected the stability of des(Glu)5 [(99m)Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (PTc]DG4 profited by single Lis (2.06±0.39%ID/g vs 0.99±0.13%ID/g in controls) or combined Lis+PA coinjection (8.91±1.61%ID/g vs 4.89±1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [(99m)Tc]DG4 (Tc-radioligands based on different-length gastrins. Truncated [(99m)Tc]DG4 exhibited overall the most attractive profile during combined NEP/ACE-inhibition in mouse models, providing new

Association between spironolactone added to beta-blockers and ACE inhibition and survival in heart failure patients with reduced ejection fraction: a propensity score-matched cohort study.

Science.gov (United States)

Frankenstein, L; Katus, H A; Grundtvig, M; Hole, T; de Blois, J; Schellberg, D; Atar, D; Zugck, C; Agewall, S

2013-10-01

Heart failure (CHF) guidelines recommend mineralocorticoid receptor antagonists for all symptomatic patients treated with a combination of ACE inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers. As opposed to both eplerenone trials, patients in RALES (spironolactone) received almost no beta-blockers. Since pharmacological properties differ between eplerenone and spironolactone, the prognostic benefit of spironolactone added to this baseline combination therapy needs clarification. We included 4,832 CHF patients with chronic systolic dysfunction from the Norwegian Heart Failure Registry and the heart failure outpatients' clinic of the University of Heidelberg. Propensity scores for spironolactone receipt were calculated for each patient and used for matching to patients without spironolactone. During a total follow-up of 17,869 patient-years, 881 patients (27.0 %) died in the non-spironolactone group and 445 (28.4 %) in the spironolactone group. Spironolactone was not associated with improved survival, neither in the complete sample (HR 0.82; 95 % CI 0.64-1.07; HR 1.03; 95 % CI 0.88-1.20; multivariate and propensity score adjusted respectively), nor in the propensity-matched cohort (HR 0.98; 95 % CI 0.82-1.18). In CHF outpatients we were unable to observe an association between the use of spironolactone and improved survival when administered in addition to a combination of ACE/ARB and beta-blockers.

ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

International Nuclear Information System (INIS)

Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt

2002-01-01

Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much

ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

Energy Technology Data Exchange (ETDEWEB)

Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt [Department of Nuclear Medicine, University of Vienna (Austria)

2002-03-01

Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much

The Atmospheric Chemistry Experiment (ACE): Mission Overview

Science.gov (United States)

Bernath, P. F.; Boone, C.; Walker, K.; McLeod, S.; Nassar, R.

2003-12-01

The ACE mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE will make a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) gives ACE coverage of tropical, mid-latitudes and polar regions. The solar occultation advantages are high sensitivity and self-calibration. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4100 cm-1) will measure the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. The ACE concept is derived from the now-retired ATMOS FTS instrument, which flew on the Space Shuttle in 1985, 1992, 1993, 1994. Climate-chemistry coupling may lead to the formation of an Arctic ozone hole. ACE will provide high quality data to confront these model predictions and will monitor polar chemistry as chlorine levels decline. The ACE-FTS can measure water vapor and HDO in the tropical tropopause region to study dehydration and strat-trop exchange. The molecular signatures of massive forest fires will evident in the ACE infrared spectra. The CO2 in our spectra can be used to either retrieve atmospheric pressure or (if the instrument pointing knowledge proves to be satisfactory) for an independent retrieval of a CO2 profile for carbon cycle science. Aerosols and clouds will be monitored using the extinction of solar radiation at

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction.

Science.gov (United States)

Baroletti, Steven A; Gabardi, Steven; Magee, Colm C; Milford, Edgar L

2003-06-01

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.

ACE blood test

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003567.htm ACE blood test To use the sharing features on this page, ... Alternative Names Serum angiotensin-converting enzyme; SACE Images Blood test References Carty RP, Pincus MR, Sarafraz-Yazdi E. ...

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Listing of Available ACE Data Tables

Energy Technology Data Exchange (ETDEWEB)

Conlin, Jeremy Lloyd [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-01-31

This document is divided into multiple sections. Section 2 lists some of the more frequently used ENDF/B reaction types that can be used with the FM input card. The remaining sections (described below) contain tables showing the available ACE data tables for various types of data. These ACE data libraries are distributed by the Radiation Safety Information Computational Center (RSICC) with MCNP6.

The presence of PAI-1 4G/5G and ACE DD genotypes increases the risk of early-stage AVF thrombosis in hemodialysis patients.

Science.gov (United States)

Güngör, Yahya; Kayataş, Mansur; Yıldız, Gürsel; Özdemir, Öztürk; Candan, Ferhan

2011-01-01

In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, β-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x(2) = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

ACE I/D genotype, adiposity, and blood pressure in children

Directory of Open Access Journals (Sweden)

Rothschild Max

2009-03-01

Full Text Available Abstract Background Angiotensin converting enzyme (ACE is a possible candidate gene that may influence both body fatness and blood pressure. Although several genetic studies have been conducted in adults, relatively few studies have examined the contribution of potential candidate genes, and specifically ACE I/D, on adiposity and BP phenotypes in childhood. Such studies may prove insightful for the development of the obesity-hypertension phenotype early in life. The purpose of this study was to examine differences in body fatness and resting blood pressure (BP by ACE I/D genotype, and determine if the association between adiposity and BP varies by ACE I/D genotype in children. Methods 152 children (75 girls, 77 boys were assessed for body composition (% body fat using dual energy x-ray absorbtiometry and resting BP according to American Heart Association recommendations. Buccal cell samples were genotyped using newly developed PCR-RFLP tests for two SNPs (rs4341 and rs4343 in complete linkage disequilibrium with the ACE I/D polymorphism. Partial correlations were computed to assess the ociations between % body fat and BP in the total sample and by genotype. ANCOVA was used to examine differences in resting BP by ACE I/D genotype and fatness groups. Results Approximately 39% of youth were overfat based on % body fat (>30% fat in girls, 25% fat in boys. Body mass, body mass index, and fat-free mass were significantly higher in the ACE D-carriers compared to the II group (p Conclusion ACE D-carriers are heavier than ACE II children; however, BP did not differ by ACE I/D genotype but was adversely influenced in the overfat D-carriers. Further studies are warranted to investigate the genetics of fatness and BP phenotypes in children.

Sanus-Ace: Negotiating a Memorandum of Understanding in external corporate venturing.

OpenAIRE

VANHAVERBEKE, Wim

2014-01-01

This negotiation case describes a situation in which an investment manager of a large chemical company (ACE) has to decide about a corporate venturing investment in a small high-tech start-up (Sanus). To win board approval for this investment, an ACE business unit (in this case, ACE Food Specialties) must write a letter of commitment. The investment manager of ACE Venturing cannot invest in the start-up without a MoU between the start-up and the business unit of ACE. This case provides the re...

How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

DEFF Research Database (Denmark)

Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

2010-01-01

An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

Science.gov (United States)

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O 2 consumption (VO 2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO 2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD

The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

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Ilana Zalcberg Renault

2011-12-01

Full Text Available Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging.

The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

Science.gov (United States)

Renault, Ilana Zalcberg; Scholl, Vanesa; Hassan, Rocio; Capelleti, Paola; de Lima, Marcos; Cortes, Jorge

2011-01-01

Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging. PMID:23049363

Prevalence and prognostic significance of adrenergic escape during chronic β-blocker therapy in chronic heart failure

Science.gov (United States)

Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

2009-01-01

Aims Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to β-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different β-blocker agents and doses. Methods and results This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable β-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual β-blocker agents used and the dose equivalent taken, the prevalence of AE was 31–39%. Norepinephrine levels neither correlated with heart rate (r = 0.02; 95% CI: −0.08–0.11; P = 0.74) nor were they related to underlying rhythm (P = 0.09) or the individual β-blocker agent used (P = 0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387–2.645; χ2: 15.60). Conclusion We verified the presence of AE in CHF patients on chronic stable β-blocker therapy, irrespective of the individual β-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape. PMID:19168516

Prevalence and prognostic significance of adrenergic escape during chronic beta-blocker therapy in chronic heart failure.

Science.gov (United States)

Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

2009-02-01

Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60). We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

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Susan R. Mendley

2015-01-01

Full Text Available We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty.

Agile Coalition Environment (ACE)

National Research Council Canada - National Science Library

McGuire, Michele; Daniel, Dale

2004-01-01

.... Interoperability is achieved across all applications, platforms, and security domains. ACE is presented as a network capability that can be applied to the Coalition Enterprise Information Exchange System (CENTRIXS...

AceCloud: Molecular Dynamics Simulations in the Cloud.

Science.gov (United States)

Harvey, M J; De Fabritiis, G

2015-05-26

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

Guideline adherence for pharmacotherapy of chronic systolic heart failure in general practice: a closer look on evidence-based therapy.

Science.gov (United States)

Peters-Klimm, F; Müller-Tasch, T; Schellberg, D; Remppis, A; Barth, A; Holzapfel, N; Jünger, J; Herzog, W; Szecsenyi, J

2008-04-01

There is robust evidence for effective pharmacotherapy of chronic (systolic) heart failure (CHF) which has led to the creation of guidelines, but many surveys evaluating CHF treatment show an under-utilisation of relevant drugs, while setting and patient population appear to be crucial for adequate appraisal of treatment patterns. To evaluate the guideline adherence (GA) of general practitioners (GPs) in a well-defined patient population with CHF in primary care (PC). A cross-sectional analysis was performed with the data of 167 patients enrolled in 37 GP practices (Germany) with documented left ventricular systolic dysfunction (LVEF: 33.3 +/- 6.9%). GA was assessed as usual (prescribing "yes" or "no"), through evaluation of target dosing, while adjusting for potential clinical contraindications, and through a modified Guideline Adherence Indicator-3 (mGAI-3), which assesses three relevant groups of substances according to New York Heart Association (NYHA) functional class: ACE-Inhibitors (ACE-I) or angiotensin receptor blockers (ARB), beta-blockers (BB) and aldosterone-antagonists (AA). Prescription rates for ACE-I/ARB, BB or both were 80%, 75% and 62%, respectively. The proportion of target doses reached for ACE-I was 16%, for BB only 8%. When adjusted for potential (mainly relative) contraindications (COPD, heart rate <60/min, hypotension, hyperkalaemia and renal dysfunction), the percentage of target doses reached increased to 49% for ACE-I/ARBs and 46% for BB. Application of the mGAI-3 showed moderate to perfect GA for usual assessment, proportion of target dose reached and adjusted in 83%, 16% and 55% of the patients, respectively. In the context of this patient and doctor setting, life-saving treatment was provided above average when assessed by usual criteria. The application of additional criteria showed further room for improvement. Future interventions aiming at optimisation should be tailored to the needs of doctors and patients likewise.

Optical coherence tomography findings after chronic total occlusion interventions: Insights from the “AngiographiC evaluation of the everolimus-eluting stent in chronic Total occlusions” (ACE-CTO) study (NCT01012869)

Energy Technology Data Exchange (ETDEWEB)

Sherbet, Daniel P.; Christopoulos, Georgios; Karatasakis, Aris; Danek, Barbara Anna; Kotsia, Anna; Navara, Rachita; Michael, Tesfaldet T.; Roesle, Michele; Rangan, Bavana V.; Haagen, Donald [VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, TX (United States); Garcia, Santiago [Minneapolis VA Healthcare System and University of Minnesota, Minneapolis, MN (United States); Maniu, Calin [Bon Secours Health System, Suffolk, VA (United States); Pershad, Ashish [Banner Good Samaritan Medical Center, Phoenix, AZ (United States); Abdullah, Shuaib M.; Hastings, Jeffrey L.; Kumbhani, Dharam J.; Luna, Michael; Addo, Tayo; Banerjee, Subhash [VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, TX (United States); Brilakis, Emmanouil S., E-mail: esbrilakis@gmail.com [VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, TX (United States)

2016-10-15

Background: There is limited information on optical coherence tomography (OCT) findings after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). OCT allows high resolution imaging that can enhance understanding of the vascular response after stenting of chronically occluded vessels. Methods: The Angiographic Evaluation of the Everolimus-Eluting Stent in Chronic Total Occlusions (ACE-CTO) study collected angiographic and clinical outcomes from 100 patients undergoing CTO PCI with the everolimus-eluting stent (EES). OCT was performed 8-months post stenting in 62 patients. Every third frame was analyzed throughout the course of the stented arterial segment. Lumen contours were semi-automatically traced and stent struts were manually delineated, with automatic measurement of the strut to lumen distance. Struts on the luminal side of the lumen contour were classified as malapposed if the distance to the lumen contour exceeded 0.108 mm. Results: A total of 44,450 struts in 6047 frames were analyzed, of which 4113 9.3%, 95% confidence intervals [CI] 9.0% to 9.5%) were malapposed and 1230 (2.8%, 95% CI 2.6% to 2.9%) were uncovered. Fifty-five of 62 patients (88.7%, 95% CI 78.5% to 98.4%) had at least one malapposed stent strut and 50 patients (80.7%, 95% CI 69.2% to 88.6%) had at least one uncovered stent strut. Mean strut-intimal thickness of the apposed and malapposed struts was 0.126 ± 0.140 mm and − 0.491 ± 0.440 mm, respectively. Conclusion: High rates of stent strut malapposition and incomplete stent strut coverage were observed after CTO PCI using EES, highlighting unique challenges associated with stent implantation in CTOs. - Highlights: • Percutaneous coronary intervention with drug-eluting stents for chronic total occlusion is associated with a 40% rate of binary in-stent restenosis at 8 months • Of patients who receive a drug eluting stent for a chronic total occlusion 88.7% will have stent strut malapposition and 80.7% will

Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

Science.gov (United States)

Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

2014-01-01

Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

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Lindsey J. Reese

2012-01-01

Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

The PAI-1 4G/5G and ACE I/D polymorphisms and risk of recurrent pregnancy loss: a case-control study.

Science.gov (United States)

Kim, Jin Ju; Choi, Young Min; Lee, Sung Ki; Yang, Kwang Moon; Paik, Eun Chan; Jeong, Hyeon Jeong; Jun, Jong Kwan; Han, Ae Ra; Hong, Min A

2014-12-01

Thrombophilia has been postulated to be a contributor to the pathophysiology of recurrent pregnancy loss (RPL). We investigated the role of the plasminogen activator inhibitor type 1 (PAI-1) 4G/5G and angiotensin converting enzyme (ACE) I/D polymorphisms in Korean patients with RPL. Genotyping was performed using the TaqMan assay in 227 RPL patients and 304 controls. The genotype distributions of both polymorphisms in the RPL group did not differ from those of controls. Because the frequency of being homozygous for ACE D/D and the PAI-I 4G/4G combination has been reported to be significantly higher in RPL patients, this was also analyzed. However, no significant difference was noted; 3.1% of RPL patients had both ACE D/D and PAI-I 4G/4G, as did 4.9% of controls (P = 0.791). The current study suggests that both polymorphisms, either alone or in combination, are not major determinants of the development of RPL in Korean women. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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Małgorzata Darewicz

2014-08-01

Full Text Available 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.

Influence of Enalapril on the progression of chronic renal failure in diabetic nephropathy and nephropathies of and other aethiology: A two-year study

Directory of Open Access Journals (Sweden)

Trbojević Jasna

2002-01-01

Full Text Available Chronic renal failure (CRF is almost always associated with high arterial blood pressure. Adequate control of hypertension slows down the progression of the disease, Inhibitors of angiotenzin-converting enzyme (ACE inhibitors have proved to be very efficacious in decreasing high blood pressure. The aim of this study was to assess the influence of ACE inhibitor enalapril on the progression of CRF in patients with diabetic nephropathy and nephropathies of other origin. During 1998 and 1999 thirty patients (20 males and 10 females, aged 525+1.3 have been followed-up at the Department of Nephrology, Clinical Centre of Serbia. On regular monthly controls serum creatinine, urea, calcium and protein levels, creatinine clearance, and blood pressure, were measured. All patients were suggested a low protein diet. Progression of the disease was expressed by the slope of the regression line showing reciprocal serum creatinine values. Proteinaemia was significantly higher in diabetic patients after 12 months (p<0.35 but in the next 12 months the difference between groups disappeared. The same patients had significantly lower serum urea (p<0.05 after 24 months and creatinine values (p<0.05 dur ing the whole study. Other variables changed in the same manner and with similar progression in both groups. The direction of slope lines suggested recovery of kidney function in both examined groups. However, a smaller slope in patients with diabetic nephropathy together with other results showed that enalapril had better influence on slowing down the progression of CRF in this group of patients.

Chronic kidney disease in HIV infec tion: early detec tion and ...

African Journals Online (AJOL)

2007-08-16

Aug 16, 2007 ... Side-effects related to treatment of HIV, including those due to: • antiretroviral therapy .... angiotensin-converting enzyme inhibitors. (ACE-I), dyslipidaemias (if .... 1996; 28: 202-208. 16. Burns GC, Subir PK, Toth IR, Sivak SL.

Renal outcomes with aliskiren in patients with type 2 diabetes

DEFF Research Database (Denmark)

Heerspink, Hiddo J Lambers; Persson, Frederik; Brenner, Barry M

2016-01-01

ALTITUDE trial, 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease were randomly assigned (1:1) to receive aliskiren 300 mg per day or placebo as an adjunct to ACE inhibitors or ARBs. Randomisation was stratified on the basis of baseline urinary albumin......Background: The primary results of the ALTITUDE trial showed no benefit of aliskiren on renal outcomes (doubling of serum creatinine and end-stage renal disease) when used as an adjunct to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients with type 2...... diabetes and chronic kidney disease or cardiovascular disease. We did a prespecified analysis of the ALTITUDE trial to analyse the effects of aliskiren on surrogate renal outcomes in all patients and on primary renal outcomes in subgroups of patients. Methods: In the double-blind, randomised, controlled...

Angiotensin-converting enzyme inhibitor use and protection against pneumonia in patients with diabetes

NARCIS (Netherlands)

van de Garde, Ewoudt M W; Souverein, Patrick C; Hak, Eelko; Deneer, Vera H M; van den Bosch, Jules M M; Leufkens, Hubert G M

OBJECTIVES: Because of the high risk of pneumonia in patients with diabetes, we aimed to assess the effect of angiotensin-converting enzyme (ACE) inhibitor use on the occurrence of pneumonia in a general population of patients with diabetes. METHODS: The study population comprised all patients in

The ACE2 gene: its potential as a functional candidate for cardiovascular disease.

Science.gov (United States)

Burrell, Louise M; Harrap, Stephen B; Velkoska, Elena; Patel, Sheila K

2013-01-01

The RAS (renin-angiotensin system) plays an important role in the pathophysiology of CVD (cardiovascular disease), and RAS blockade is an important therapeutic strategy in the management of CVD. A new counterbalancing arm of the RAS is now known to exist in which ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Altered ACE2 expression is associated with cardiac and vascular disease in experimental models of CVD, and ACE2 is increased in failing human hearts and atherosclerotic vessels. In man, circulating ACE2 activity increases with coronary heart disease, as well as heart failure, and a large proportion of the variation in plasma ACE2 levels has been attributed to hereditary factors. The ACE2 gene maps to chromosome Xp22 and this paper reviews the evidence associating ACE2 gene variation with CVD and considers clues to potential functional ACE2 variants that may alter gene expression or transcriptional activity. Studies to date have investigated ACE2 gene associations in hypertension, left ventricular hypertrophy and coronary artery disease, but the results have been inconsistent. The discrepancies may reflect the sample size of the studies, the gender or ethnicity of subjects, the cardiovascular phenotype or the ACE2 SNP investigated. The frequent observation of apparent sex-dependence might be of special importance, if confirmed. As yet, there are no studies to concurrently assess ACE2 gene polymorphisms and circulating ACE2 activity. Large-scale carefully conducted clinical studies are urgently needed to clarify more precisely the potential role of ACE2 in the CVD continuum.

Differential ACE expression among tissues in allele-specific Wistar rat lines

NARCIS (Netherlands)

Kamilic, Jelena; Lely, A. Titia; van Goor, Harry; Buikema, Hendrik; Tent, Hilde; Navis, Gerjan J.; Korstanje, Ron

In humans, the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene accounts for half of the variance in plasma ACE activity. The deletion allele is associated with high plasma ACE activity, cardiovascular disease, and renal disease. In rat, a similar association is found

Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

Science.gov (United States)

Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

2014-08-01

Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to

Sodium intake modifies the negative prognostic value of renal damage prior to treatment with ACE inhibitors on proteinuria induced by adriamycin

NARCIS (Netherlands)

Kramer, Andrea B.; Bos, Hendrik; van Goor, Harry; Navis, Gerjan J.

2006-01-01

Background: Antiproteinuric treatment by ACE inhibition (ACEi) provides renoprotection. However, resistance to antiproteinuric intervention occurs frequently, resulting in progressive renal damage. The extent of renal damage prior to treatment with ACEi reversely correlates with the antiproteinuric

Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort.

Science.gov (United States)

Durán-Barragán, S; McGwin, G; Vilá, L M; Reveille, J D; Alarcón, G S

2008-07-01

To examine if angiotensin-converting enzyme (ACE) inhibitor use delays the occurrence of renal involvement and decreases the risk of disease activity in SLE patients. SLE patients (Hispanics, African Americans and Caucasians) from the lupus in minorities: nature vs nurture (LUMINA) cohort were studied. Renal involvement was defined as ACR criterion and/or biopsy-proven lupus nephritis. Time-to-renal involvement was examined by univariable and multivariable Cox proportional hazards regression analyses. Disease activity was examined with a case-crossover design and a conditional logistic regression model; in the case intervals, a decrease in the SLAM-R score >or=4 points occurred but not in the control intervals. Eighty of 378 patients (21%) were ACE inhibitor users; 298 (79%) were not. The probability of renal involvement free-survival at 10 yrs was 88.1% for users and 75.4% for non-users (P = 0.0099, log rank test). Users developed persistent proteinuria and/or biopsy-proven lupus nephritis (7.1%) less frequently than non-users (22.9%), P = 0.016. By multivariable Cox proportional hazards regression analyses, ACE inhibitors use [hazard ratio (HR) 0.27; 95% CI 0.09, 0.78] was associated with a longer time-to-renal involvement occurrence whereas African American ethnicity (HR 3.31; 95% CI 1.44, 7.61) was with a shorter time. ACE inhibitor use (54/288 case and 254/1148 control intervals) was also associated with a decreased risk of disease activity (HR 0.56; 95% CI 0.34, 0.94). ACE inhibitor use delays the development of renal involvement and associates with a decreased risk of disease activity in SLE; corroboration of these findings in other lupus cohorts is desirable before practice recommendations are formulated.

CORRELATION BETWEEN ANGIOTENSIN-CONVERTING ENZYME INHIBITORS LIPOPHILICITY AND PROTEIN BINDING DATA

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Jasna Trbojević-Stanković

2012-01-01

Full Text Available Angiotensin-converting enzyme (ACE inhibitors represent a significant group of drugs primarily used in the treatment of hypertension and congestive heart failure. In this research, seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, benazepril were studied to evaluate the relationship between their protein binding and calculated (logP values or ultra-high performance liquid chromatographytandem mass spectrometry (UHPLC-MS and reversed-phase thin-layer chromatography (RP-TLC lipophilicity data (ϕ0, CHI or C0 parameters, respectively. Their protein binding data varied from negligible (lisinopril to 99% (fosinopril, while calculated logPKOWWINvalues ranged from -0.94 (lisinopril to 6.61 (fosinopril. The good correlations were established between protein binding values and logPKOWWIN data (R2=0.7520 as well as between protein binding and chromatographic hydrophobicity data, ϕ0, CHI or C0parameters (R2 were 0.6160, 0.6242 and 0.6547, respectively. The possible application of hydrophobicity data in drugs protein binding evaluation can be of great importance in drug bioavailability.

Validation of ACE-FTS N2O measurements

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G. P. Stiller

2008-08-01

Full Text Available The Atmospheric Chemistry Experiment (ACE, also known as SCISAT, was launched on 12 August 2003, carrying two instruments that measure vertical profiles of atmospheric constituents using the solar occultation technique. One of these instruments, the ACE Fourier Transform Spectrometer (ACE-FTS, is measuring volume mixing ratio (VMR profiles of nitrous oxide (N2O from the upper troposphere to the lower mesosphere at a vertical resolution of about 3–4 km. In this study, the quality of the ACE-FTS version 2.2 N2O data is assessed through comparisons with coincident measurements made by other satellite, balloon-borne, aircraft, and ground-based instruments. These consist of vertical profile comparisons with the SMR, MLS, and MIPAS satellite instruments, multiple aircraft flights of ASUR, and single balloon flights of SPIRALE and FIRS-2, and partial column comparisons with a network of ground-based Fourier Transform InfraRed spectrometers (FTIRs. Between 6 and 30 km, the mean absolute differences for the satellite comparisons lie between −42 ppbv and +17 ppbv, with most within ±20 ppbv. This corresponds to relative deviations from the mean that are within ±15%, except for comparisons with MIPAS near 30 km, for which they are as large as 22.5%. Between 18 and 30 km, the mean absolute differences for the satellite comparisons are generally within ±10 ppbv. From 30 to 60 km, the mean absolute differences are within ±4 ppbv, and are mostly between −2 and +1 ppbv. Given the small N2O VMR in this region, the relative deviations from the mean are therefore large at these altitudes, with most suggesting a negative bias in the ACE-FTS data between 30 and 50 km. In the comparisons with the FTIRs, the mean relative differences between the ACE-FTS and FTIR partial columns (which cover a mean altitude range of 14 to 27 km are within ±5.6% for eleven of the twelve contributing stations. This mean relative difference is negative at ten stations

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

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M. Schneider

2008-10-01

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

[Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

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Afanasiev, S A; Muslimova, E F; Rebrov, T Y; Sergienko, T N; Repin, A N

2016-09-01

to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

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

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John D Bisognano

2007-11-01

Full Text Available John D Bisognano1, Trent McLaughlin2, Craig S Roberts3, Simon SK Tang31Internal Medicine Department, Cardiology Division, the University of Rochester Medical Center, Rochester, NY, USA; 2NDC Health, Phoenix, Arizona, USA; 3Pfizer Inc, New York, NY, USAAbstract: This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs, angiotensin-converting enzyme (ACE inhibitors, and angiotensin receptor blockers (ARBs added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were –17.5/–8.8, –15.7/–6.3, and –13.0/–8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.Keywords: hypertension, amlodipine besylate, lisinopril, valsartan, Joint National Committee (JNC 6 and 7

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

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Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

2014-01-01

Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

Reducing cardiovascular risk : protecting the kidney

NARCIS (Netherlands)

Dobre, Daniela; Lambers Heerspink, Hiddo J.; de Zeeuw, Dick

2009-01-01

Progressive decline of renal function in chronic kidney disease (CKD), measured by a reduced glomerular filtration rate or albuminuria, is linked to an increased risk of cardiovascular (CV) disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), most

Serum concentrations of nitrite and malondialdehyde as markers of oxidative stress in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

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Maria Juracy Petrola

2012-01-01

Full Text Available BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22(q34,11 translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. OBJETIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

Viral kinetics in patients with chronic hepatitis C treated with the serine protease inhibitor BILN 2061

NARCIS (Netherlands)

Herrmann, Eva; Zeuzem, Stefan; Sarrazin, Christoph; Hinrichsen, Holger; Benhamou, Yves; Manns, Michael P.; Reiser, Markus; Reesink, Henk; Calleja, José L.; Forns, Xavier; Steinmann, Gerhard G.; Nehmiz, Gerhard

2006-01-01

We analysed viral kinetics from a 2-day treatment with BILN 2061, a serine protease inhibitor of hepatitis C virus, in patients chronically infected with genotype 1 hepatitis C virus. The efficiency (E), describing inhibition of viral production, was above 99.45% in all patients with minor or

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

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Das Undurti N

2008-10-01

Full Text Available Abstract 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 β 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 ~80%. Essential fatty acids (EFAs and their long-chain metabolites: γ-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-γ 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 ω-3 and ω-6 fatty acids and the co

Hyperprolactinemia contributes to reproductive deficit in male rats chronically administered PDE5 inhibitors (sildenafil and tadalafil and opioid (tramadol

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V.U. Nna

2016-09-01

Conclusion: Serum prolactin concentration correlated negatively with male reproductive hormones and may play a major role in reproductive deficits associated with chronic use of PDE5 inhibitors and opioids.

Single nucleotide polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with essential hypertension and increased ACE enzyme levels in Mexican individuals.

Science.gov (United States)

Martínez-Rodríguez, Nancy; Posadas-Romero, Carlos; Villarreal-Molina, Teresa; Vallejo, Maite; Del-Valle-Mondragón, Leonardo; Ramírez-Bello, Julian; Valladares, Adan; Cruz-López, Miguel; Vargas-Alarcón, Gilberto

2013-01-01

To explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels. Nine ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR) in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes. Under a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363) were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA), H2 (GGATG), H3 (AGATG), and H4 (AGACA). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively). According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively). Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1) as compared to H1/H1 individuals (P = 0.0048). The results suggest that single nucleotide polymorphisms and the "GGATG" haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels.

DNA methylation analysis of the angiotensin converting enzyme (ACE gene in major depression.

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Peter Zill

Full Text Available 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.

Advanced Center for Engineering (ACE)

Data.gov (United States)

Federal Laboratory Consortium — Cave Automatic Virtual Environment (CAVE™)The ACE Team provides the ability to conduct fullscale interactive virtual CAD reviews using the CAVE.CapabilitiesTARDEC's...

Consumption of an aqueous cyanophyta extract derived from Arthrospira platensis is associated with reduction of chronic pain: results from two human clinical pilot studies

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Jensen GS

2016-05-01

Full Text Available Gitte S Jensen,1 Victoria L Attridge,1 Steve G Carter,1 Jesse Guthrie,2 Axel Ehmann,2 Kathleen F Benson1 1NIS Labs, 2Cerule LLC, Klamath Falls, OR, USA Objectives: The aim of this study was to evaluate the effects of consumption of an aqueous cyanophyta extract (ACE from Arthrospira platensis on chronic pain in humans, in two clinical pilot studies. Design and interventions: The two pilot studies each involved 12 subjects experiencing chronic pain. The initial study followed an open-label 4-week study design involving consumption of 1 g ACE per day. A subsequent placebo-controlled, single-blind, crossover study involved consumption of 500 mg ACE, 250 mg ACE, or 0 mg ACE (placebo per day for 1-week duration, separated by 1-week washout period. Subjects: Adult subjects of both sexes, with chronic joint-related pain for at least 6 months prior to enrollment, were recruited after obtaining written informed consent. Outcome measures: Visual analog scales were used to score pain at rest and during physical activity for each person's primary and secondary areas of chronic pain. An activities of daily living questionnaire was used to collect data on physical functioning. Results: The data showed rapid reduction of chronic pain in people consuming ACE, where the reduction in pain scores for each person's primary pain area reached a high level of statistical significance after 2 weeks of consumption (P<0.01, both when at rest and when being physically active. Secondary pain areas when physically active showed highly significant improvements within 1 week of consumption of 1 g/d (P<0.001 and borderline significant improvements within 1 week of consuming 500 mg/d (P<0.065 and 250 mg/d (P<0.05. This was accompanied by an increased ability to perform daily activities (P<0.05. A small but significant weight loss was observed during the 4-week study, as the average body mass index dropped from 31.4 to 29.4 (P<0.01. Conclusion: Consumption of ACE was associated

The validity of the Addenbrooke's Cognitive Examination-Revised (ACE-R) in acute stroke.

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Morris, Katie; Hacker, Vicki; Lincoln, Nadina Berrice

2012-01-01

The purpose was to examine the validity of the Addenbrooke's Cognitive Examination Revised (ACE-R) as a screening measure to detect cognitive impairment after stroke. Stroke patients in hospital were recruited and the ACE-R, which includes the Mini-Mental Status Examination (MMSE), was administered, followed by a battery of neuropsychological tests, which served as the 'gold standard' for classification of cognitive impairment. The diagnostic validity of the ACE-R was determined by ROC analysis. Of the 101 patients who completed the ACE-R, 61 also completed the neuropsychological assessment. Both the MMSE and the ACE-R were found to have inadequate diagnostic validity for the detection of overall cognitive impairment (MMSE AUC = 0.53, p > 0.05; ACE-R AUC = 0.53, p > 0.05). The ACE-R subscales predicted impairment in specific cognitive domains significantly better than chance; Visuospatial (AUC = 0.71, p cognitive functioning. The ACE-R was not a suitable measure to screen for overall cognitive impairment in acute stroke patients, but was able to detect impairment in visuospatial, attention and executive domains.

ACE - Manufacturer Identification Code (MID)

Data.gov (United States)

Department of Homeland Security — The ACE Manufacturer Identification Code (MID) application is used to track and control identifications codes for manufacturers. A manufacturer is identified on an...

Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population.

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Firouzabadi, Negar; Shafiei, Massoumeh; Bahramali, Ehsan; Ebrahimi, Soltan Ahmed; Bakhshandeh, Hooman; Tajik, Nader

2012-12-30

Genetic factors contribute substantially to the likelihood of developing major depressive disorder (MDD). The importance of renin-angiotensin system (RAS) elements in cognition and behaviour and their involvement in aetiology and treatment of depression imply that RAS gene polymorphism(s) associated with RAS overactivity might also be associated with depression. In the present study, genotype and allele frequencies of six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 191 depressed and 104 healthy individuals using polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum angiotensin-converting enzyme (ACE) activity was assayed using a high-performance liquid chromatography (HPLC) method. The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3). Significant higher serum ACE activity (P=0.0001) as well as higher diastolic blood pressure (P=0.036) were observed in depressed patients compared to the healthy control group. Depressed patients carrying GG genotype of the A2350G polymorphism had a significantly higher serum ACE activity (P=0.02) than individuals with either AA or AG genotype. In conclusion, this study supports the hypothesis of RAS overactivity in depression in that the genotype associated with higher serum ACE activity in an Iranian population was also associated with MDD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Blood type gene locus has no influence on ACE association with Alzheimer's disease.

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Braae, Anne; Medway, Christopher; Carrasquillo, Minerva; Younkin, Steven; Kehoe, Patrick G; Morgan, Kevin

2015-04-01

The ABO blood group locus was recently found to contribute independently and via interactions with angiotensin-converting enzyme (ACE) gene variation to plasma levels of ACE. Variation in ACE has previously been not only implicated as individually conferring susceptibility for Alzheimer's disease (AD) but also proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, whereas the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variations in the genetic susceptibility of 2067 AD cases compared with 1376 nondemented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice.

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Tyrankiewicz, Urszula; Olkowicz, Mariola; Skórka, Tomasz; Jablonska, Magdalena; Orzylowska, Anna; Bar, Anna; Gonet, Michal; Berkowicz, Piotr; Jasinski, Krzysztof; Zoladz, Jerzy A; Smolenski, Ryszard T; Chlopicki, Stefan

2018-01-01

Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1-7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1-10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1-7) pathway, whereas the end

The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis

DEFF Research Database (Denmark)

Nicolini, Franck E; Ibrahim, Amr R; Soverini, Simona

2013-01-01

The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64...... patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according...... to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315...

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

Science.gov (United States)

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

Nephroprotective effects of b-carotene on ACE gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity in rats.

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Fazal, Yumna; Fatima, Syeda Nuzhat; Shahid, Syed Muhammad; Mahboob, Tabassum

2016-07-01

β -carotene is one of carotenoid natural pigments, which are produced by plants and are accountable for the bright colors of various fruits and vegetables. These pigments have been widely studied for their ability to prevent chronic diseases and toxicities. This study was designed to evaluate the effects of β-carotene on angiotensin converting enzyme (ACE) gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity. Total 24 albino wistar rats of male sex (200-250gm) were divided into 6 groups as Group-1: The control remained untreated; Group-2: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks; Group-3: Received β-carotene orally (200mg/kg b.w), for 24 weeks; and Group-4: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks + received β-carotene orally (200mg/kg b.w), for further 12 weeks. The expression of ACE gene in thioacetamide induced renal toxicity in rats as well as supplemented with β-carotene was investigated and compared their level with control groups by using the quantitative RT-PCR method. The ACE gene expression was significantly increase in TAA rats as compare to control rats specifies that TAA induced changes in ACE gene of kidney, elevated renal ACE has been correlated with increase hypertensive end organ renal damage. The quantity of ACE gene were diminish in our rats who received β-Carotene after TAA is administered, for this reason they seemed to be defended against increased ACE levels in kidney bought by TAA. In pre- and post-treatment groups, we studied the role of β-Carotene against thioacetamide in the kidney of Wistar rats. Experimental confirmation from our study illustrates that β-Carotene can certainly work as a successful radical-trapping antioxidant our results proved that TAA injury increased lipid peroxidation and diminish antioxidant GSH, SOD and CAT in renal tissue. Since β-Carotene administration recover renal lipid peroxidation and antioxidants, it give the impression that

An investigation of the concomitant use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and diuretics.

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Bucsa, C; Moga, D C; Farcas, A; Mogosan, C; Dumitrascu, D L

2015-08-01

To determine in retrospective data the prevalence at hospital discharge of co-prescribing angiotensin-converting enzyme inhibitors (ACE-I) and non-steroidal anti-inflammatory drugs (NSAIDs) and ACE-I/NSAIDs and diuretics and to identify factors associated with the co-prescription. Secondary, we evaluated the extent of serum creatinine and potassium monitoring in patients treated with ACE-I and these associations and determined the prevalence of values above the upper normal limit (UNL) in monitored patients. Hospitalized patients with ACE-I in their therapy at discharge were included in 3 groups as follows: ACE-I, DT (double therapy with ACE-I and NSAIDs) and TT (triple therapy with ACE-I, NSAIDs and diuretics) groups. We evaluated differences on demographic characteristics, co-morbidities, medications, laboratory monitoring and quantified the patients with serum creatinine and potassium levels above the UNL using descriptive statistics. Logistic regression analysis with backward elimination was performed to identify significant predictors of combination therapy. Of 9960 admitted patients, 1214 were prescribed ACE-I, 40 were prescribed ACE-I/NSAIDs and 22 were prescribed ACE-I/NSAIDs/diuretics (3.13% and 1.72%, respectively, of the patients prescribed with ACE-I). Serum creatinine and potassium were monitored for the great majority of patients from all groups. The highest percentage of hyperkalemia was found in the DT group (10% of the patients) and of serum creatinine above UNL in the TT group (45.45%). The logistic regression final model showed that younger patients and monitoring for potassium were significantly associated with combination therapy. The prevalence of patients receiving DT/TT was relatively low and their monitoring during hospitalization was high. Factors associated with the combinations were younger patients and patients not tested for serum potassium.

Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.

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Centeno, José M; Burguete, María C; Castelló-Ruiz, María; Enrique, María; Vallés, Salvador; Salom, Juan B; Torregrosa, Germán; Marcos, José F; Alborch, Enrique; Manzanares, Paloma

2006-07-26

A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH2) and PACEI34 (Ac-RKWLFW-NH2), and also a LfcinB-derived peptide, LfcinB17-31 (Ac-FKCRRWQWRMKKLGA-NH2). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.

Addenbrooke's Cognitive Examination (ACE) for the diagnosis and differential diagnosis of dementia.

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Larner, A J

2007-07-01

The Addenbrooke's Cognitive Examination (ACE) is reported to be a highly sensitive and specific "bedside" test for the diagnosis of dementia, but large pragmatic studies of its use in day-to-day clinical practice are lacking. This study measured diagnostic accuracy of ACE in a large cohort of consecutive patients referred to a dedicated Cognitive Function Clinic. Consecutive new referrals over a 3.5-year period were administered the ACE (n=285). ACE scores and subscores (VLOM ratio) were compared to clinical diagnoses of dementia and dementia subtype, established on the basis of widely accepted diagnostic criteria and at least 12-month follow-up. ACE had good sensitivity, specificity, and positive predictive value for the diagnosis of dementia, with excellent diagnostic accuracy as measured by area under the receiver operating characteristic curve. However, a lower cutoff than that used in the index paper was required for optimum test sensitivity and specificity. ACE VLOM ratio subscore for the differential diagnosis of Alzheimer's disease and frontotemporal dementia proved less accurate. This study suggests that ACE is useful for the diagnosis of dementia in routine clinical practice but that other instruments may be required for the differential diagnosis of the dementia syndrome.

Coexistence of ACE (I/D) and PAI-1 (4G/5G) gene variants in recurrent miscarriage in Polish population.

Science.gov (United States)

Kurzawińska, Grażyna; Barlik, Magdalena; Drews, Krzysztof; Różycka, Agata; Seremak-Mrozikiewicz, Agnieszka; Ożarowski, Marcin; Klejewski, Andrzej; Czerny, Bogusław; Wolski, Hubert

2016-01-01

Recurrent miscarriage (RM) is one of the most common obstetric complications. Numerous studies have suggested that genetic variants leading to an impaired balance between coagulation and fibrinolysis may contribute to elevated risk of pregnancy loss. The aim of the study was to investigate a possible association between angiotensin-converting enzyme (ACE, rs1799752) I/D and plasminogen activator inhibitor type 1 (PAI-1, rs1799768) 4G/5G polymorphisms with RM among Polish women. DNA was extracted from peripheral blood samples of 152 women with a history of ≥ 2 consecutive pregnancy losses before 22 weeks of gestation, and 180 healthy controls with at least 1 live birth at term and no history of pregnancy loss. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to identify the polymorphisms. No statistically significant differences were found in genotype and allele frequencies of the studied polymorphisms. The most relevant difference between the study group and controls was found for the ID genotype distribution of the ACE gene (52.6 vs. 46.7%, OR = 1.27, p = 0.28). The analysis of genotype coexistence revealed a higher incidence of the combination of the ACE II and the PAI-1 4G/4G genotypes in the control group (10.0 vs.5.9% in control group; p = 0.17). The obtained results suggest no apparent association between the ACE I/D, PAI-1 4G/5G polymorphisms and increased RM susceptibility in the analyzed Polish population.

Adverse childhood experiences (ACE) and adult attachment interview (AAI) in a non-clinical population.

Science.gov (United States)

Thomson, Paula; Jaque, S Victoria

2017-08-01

Adverse childhood experiences (ACE) tend to be interrelated rather than independently occurring. There is a graded effect associated with ACE exposure and pathology, with an increase when ACE exposure is four or more. This study examined a sample of active individuals (n=129) to determine distribution patterns and relationships between ACEs, attachment classification, unresolved mourning (U), and disclosure difficulty. The results of this study demonstrated a strong relationship between increased ACEs and greater unresolved mourning. Specifically, the group differences for individuals who experienced no ACE (n=42, 33%), those with 1-3 ACEs (n=48, 37.8%), and those with ≥4 ACEs (n=37, 29.1%) revealed a pattern in which increased group ACE exposure was associated with greater lack of resolution for past trauma/loss experiences, more adult traumatic events, and more difficulty disclosing past trauma. Despite ≥4 ACEs, 51.4% of highly exposed individuals were classified as secure in the Adult Attachment Interview. Resilience in this group may be related to a combination of attachment security, college education, and engagement in meaningful activities. Likewise, adversity may actually encourage the cultivation of more social support, goal efficacy, and planning behaviors; factors that augment resilience to adversity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

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Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki [Sapporo Medical University School of Medicine, Second Department of Internal Medicine (Cardiology), Sapporo (Japan)

2005-02-01

Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac{sup 123}I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

International Nuclear Information System (INIS)

Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki

2005-01-01

Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac 123 I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

Determinants of Executive Directors’ Remuneration in Malaysia’s ACE Market

OpenAIRE

Hong, Chee Yoong

2016-01-01

This purpose of this study is to analyse and evaluate the determinants of executive directors' remuneration of public listed companies in Malaysia's ACE Market. This study is using panel data analysis on 76 public listed companies in ACE Market from 2009 to 2013 (5 years) with the total of 380 observations. Similar to AIM Market in UK, ACE Market is set up to facilitate emerging companies, which are important to Malaysia economic growth, to raise capital easily. Unfortunately, these companies...

POMB/ACE chemotherapy for mediastinal germ cell tumours.

Science.gov (United States)

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.

Angiotensin converting enzyme (ACE D/I) polymorphism and its ...

African Journals Online (AJOL)

Hepatitis C virus (HCV) infection is a global health problem in Egypt and causes different liver disease spectrum. Evidence indicates that angiotensin I converting enzyme (ACE) gene polymorphism may play a role in determining disease progression. We aimed to determine the association of ACE gene I/D polymorphism ...

Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

Science.gov (United States)

Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

2004-11-01

The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

Angiotensin Converting Enzyme Inhibitor Has a Protective Effect on Decompression Sickness in Rats

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Aleksandra Mazur

2018-03-01

Full Text Available Introduction: Commercial divers, high altitude pilots, and astronauts are exposed to some inherent risk of decompression sickness (DCS, though the mechanisms that trigger are still unclear. It has been previously showed that diving may induce increased levels of serum angiotensin converting enzyme. The renin angiotensin aldosterone system (RAAS is one of the most important regulators of blood pressure and fluid volume. The purpose of the present study was to control the influence of angiotensin II on the appearance of DCS.Methods: Sprague Dawley rats have been pre-treated with inhibitor of angiotensin II receptor type 1 (losartan; 10 mg/kg, angiotensin-converting enzyme (ACE inhibitor (enalapril; 10 mg/kg, and calcium-entry blocker (nifedipine; 20 mg/kg. The experimental groups were treated for 4 weeks before exposure to hyperbaric pressure while controls were not treated. Seventy-five rats were subjected to a simulated dive at 1000 kPa absolute pressure for 45 min before starting decompression. Clinical assessment took place over a period of 60 min after surfacing. Blood samples were collected for measurements of TBARS, interleukin 6 (IL-6, angiotensin II (ANG II and ACE.Results: The diving protocol induced 60% DCS in non-treated animals. This ratio was significantly decreased after treatment with enalapril, but not other vasoactive drugs. Enalapril did not change ANG II or ACE concentration, while losartant decreased post dive level of ACE but not ANG II. None of the treatment modified the effect of diving on TBARS and IL-6 values.Conclusion: Results suggests that the rennin angiotensin system is involved in a process of triggering DCS but this has to be further investigated. However, a vasorelaxation mediated process, which potentially could increase the load of inert gas during hyperbaric exposure, and antioxidant properties were excluded by our results.

Single nucleotide polymorphisms of the angiotensin-converting enzyme (ACE gene are associated with essential hypertension and increased ACE enzyme levels in Mexican individuals.

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Nancy Martínez-Rodríguez

Full Text Available AIM: To explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels. METHODS: Nine ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes. RESULTS: Under a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363 were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA, H2 (GGATG, H3 (AGATG, and H4 (AGACA. Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively. According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively. Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1 as compared to H1/H1 individuals (P = 0.0048. CONCLUSION: The results suggest that single nucleotide polymorphisms and the "GGATG" haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels.

Betydningen af deletionspolymorfi i ACE-genet for progression af ACE-haemmerbehandlet diabetisk nyresygdom

DEFF Research Database (Denmark)

Tarnow, L; Parving, H H; Jacobsen, P

1998-01-01

The aim of the study was to evaluate the effect of an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene on progression of diabetic nephropathy. We performed an observational follow-up study of 35 patients with insulin-dependent diabetes and diabetic nephropathy. Pati...

Imminent angiotensin-converting enzyme inhibitor from microbial source for cancer therapy

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Lida Ebrahimi

2017-01-01

Full Text Available Background: Drugs targeting Angiotensin I-converting enzyme (ACE have been used broadly in cancer chemotherapy. The recent past coupled with our results demonstrates the effective use of ACE inhibitors (ACEi as anticancer agents, and they are potentially relevant in deriving new inhibitors. Methods: Bacterial strains were isolated from cow milk collected in Coimbatore, Tamil Nadu, India and plated on nutrient agar medium. The identity of the strain was ascertained by 16s rRNA gene sequencing method and was submitted to the NCBI GenBank nucleotide database. Various substrates were screened for ACEi production by the fermentation with the isolated strain. ACEi was purified by sequential steps of ethanol precipitation, ion exchange column chromatography and gel filtration column chromatography. The apparent molecular mass was determined by SDS-PAGE. The anticancer property was analyzed by studying the cytotoxicity effects of ACEi using Breast cancer MCF-7 cell lines Results: The isolate coded as BUCTL09 was selected and identified as Micrococcus luteus. Among the seven substrates, only beef extract fermented broth showed an inhibition of 79% and was reported as the best substrate. The peptide was purified and molecular mass was determined. The IC50 value of peptide was found to be 59.5 μg/ ml. The purified peptide has demonstrated to induce apoptosis of cancer cell.Conclusions: The results of this study revealed that Peptide has been determined as an active compound that inhibited the activity of ACE. These properties indicate the possibilities of the use of purified protein as a potent anticancer agent.

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

OpenAIRE

Mendley, Susan R.; Spyropoulos, Fotios; Counts, Debra R.

2015-01-01

We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correc...

Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors.

Science.gov (United States)

Sasaki, Koji; Kantarjian, Hagop M; Jain, Preetesh; Jabbour, Elias J; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Takahashi, Koichi; Pemmaraju, Naveen; Daver, Naval; Pierce, Sherry A; O'Brien, Susan M; Cortes, Jorge E

2016-01-15

Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment. Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction. A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period. In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. © 2015 American Cancer Society.

Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease.

Science.gov (United States)

Wysocki, Jan; Goodling, Anne; Burgaya, Mar; Whitlock, Kathryn; Ruzinski, John; Batlle, Daniel; Afkarian, Maryam

2017-08-01

The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin ( n = 9) or vehicle ( n = 15) and people with long-standing type 1 diabetes, with ( n = 37) or without ( n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively ( P animals ( P animals ( P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 10 9 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy. Copyright © 2017 the American Physiological Society.

HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

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A. A. Aleksandrov

2008-01-01

Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

Clinical usefulness of a dual L/N-type Ca2+ channel blocker, cilnidipine, in patients with chronic heart failure. Assessment with 123I-MIBG myocardial scintigraphy

International Nuclear Information System (INIS)

Ito, Kazuki; Nishikawa, Susumu; Adachi, Yoshihiko; Kato, Shuuji; Azuma, Akihiro; Matsubara, Hiroaki

2003-01-01

Sympathetic nerve system is activated as a compensatory mechanism in heart failure. However excessive activation of sympathetic nerve system deteriorates disease state. Sympathetic nerve system can be suppressed with N-type Ca 2+ channel blocker. An antihypertensive drug, cilnidipine, is a dual L/N-type Ca 2+ channel blocker. We studies usefulness of cilnidipine in treating with chronic heart failure with 123 I-MIBG myocardial scintigraphy. We enrolled 24 patients with stable chronic heart failure. Twelve patients were treated with angiotensin converting enzyme (ACE)-inhibitors, diuretics and cardiotonics (control group), and the other 12 patients were treated with ACE-inhibitors, diuretics, cardiotonics and cilnidipine (cilnidipine group). We examined blood pressure, heart rate, norepinephrine level, brain natriuretic peptide (BNP) level, cardiothoracic ratio on chest X-ray, ejection fraction of left ventricle on two-dimensional echocardiography, count rate of heart to mediastinum (H/M) and washout rate (WOR) on 123 I-MIBG myocardial scintigraphy before and six months after medication. Symptom was improved in 8 patients in the control group and 10 patients in the cilnidipine group after medication. And another parameters were also improved in the both groups after medication. However the degree of change in blood pressure (mmHg) was 21.2±8.0 in the cilnidipine group and 10.8±9.1 in the control group, that in heart rate (/min) was 24.1±6.8 and 16.2±11.0, that in BNP level (pg/ml) was 65.2±12.0 and 42.8±11.1, that in H/M was 0.30±0.08 and 0.19±0.09, that in WOR was 19.4±5.6 and 12.2±7.0, respectively. And the degree of these changes were larger in the cilnidipine group (p 2+ channel blocker, might be useful in treating with chronic heart failure. (author)

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure　- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

Science.gov (United States)

Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

2016-05-25

It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (Pdiuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both Pdiuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

Science.gov (United States)

Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

1996-05-01

Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

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

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Angiotensin converting enzyme (A.C.E.) test system... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of angiotensin...

REDUCTION OF CUMULATIVE CARDIOVASCULAR RISK IN PATIENTS WITH ARTERIAL HYPERTENSION: THE ROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ACCORDING TO THE NEW EUROPEAN RECOMMENDATIONS

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M. N. Mamedov

2015-12-01

Full Text Available Conception of total cardio-vascular risk plays important role in defining tactics of arterial hypertension therapy according to the new European recommendations. Choice of antihypertensive therapy is based on meta-analysis of large clinical studies with hard end points. It is recommended to use five classes of antihypertensive drugs in mono- and combined therapy. Angiotensin converting enzyme (ACE inhibitors keep important place in the therapy of arterial hypertension accompanying with risk factors and associated diseases. Enalapril is one of the widely used ACE inhibitors, its efficiency was proved in prospective clinical studies. In high risk patients monotherapy with Enam (enalapril, Dr. Reddy’s decreases blood pressure and leads to positive metabolic changes. This results in significant risk reduction of cardio-vascular complications.

REDUCTION OF CUMULATIVE CARDIOVASCULAR RISK IN PATIENTS WITH ARTERIAL HYPERTENSION: THE ROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ACCORDING TO THE NEW EUROPEAN RECOMMENDATIONS

Directory of Open Access Journals (Sweden)

M. N. Mamedov

2007-01-01

Full Text Available Conception of total cardio-vascular risk plays important role in defining tactics of arterial hypertension therapy according to the new European recommendations. Choice of antihypertensive therapy is based on meta-analysis of large clinical studies with hard end points. It is recommended to use five classes of antihypertensive drugs in mono- and combined therapy. Angiotensin converting enzyme (ACE inhibitors keep important place in the therapy of arterial hypertension accompanying with risk factors and associated diseases. Enalapril is one of the widely used ACE inhibitors, its efficiency was proved in prospective clinical studies. In high risk patients monotherapy with Enam (enalapril, Dr. Reddy’s decreases blood pressure and leads to positive metabolic changes. This results in significant risk reduction of cardio-vascular complications.

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

Science.gov (United States)

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 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

Molecular and Recombinational Mapping of Mutations in the Ace Locus of Drosophila melanogaster

OpenAIRE

Nagoshi, Rodney N.; Gelbart, William M.

1987-01-01

The Ace locus in Drosophila melanogaster is known to be the structural gene for acetylcholinesterase. Ace is located in a region of chromosome arm 3R which has been subjected to intensive genetic and molecular analysis. Previous deletion mapping studies have identified a 40-kb region within which the Ace gene resides. This report focuses on the further localization of Ace within this 40-kb interval. Within this region, selective fine structure recombinational analysis was employed to localize...

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink

NARCIS (Netherlands)

Mahmoudpour, Seyed Hamidreza; Baranova, Ekaterina Vitalievna; Souverein, Patrick C.; Asselbergs, Folkert W.; de Boer, Anthonius; Maitland-van der Zee, Anke Hilse

2016-01-01

AimThe aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population. MethodsTwo nested case-control studies were

Renal graft failure after addition of an angiotensin II receptor antagonist to an angiotensin-converting enzyme inhibitor

DEFF Research Database (Denmark)

Kamper, Anne-Lise; Nielsen, Arne Høj; Baekgaard, Niels

2002-01-01

Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report descri...

Effect of Zhen-wu decoction on chronic heart failure in rats

African Journals Online (AJOL)

... has been an increased hospitalization burden, and makes HF a global public health problem. The most effective and commonly used drugs for treatment of HF are angiotensin-converting enzyme (ACE) inhibitors, β-adrenoceptor blockers, and digitalis [5-7]. The American Heart. Association (AHA) and European Society of ...

Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats.

Science.gov (United States)

Shahid, Syed Muhammad; Fatima, Syeda Nuzhat; Mahboob, Tabassum

2013-09-01

Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System (RAS), involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high (pACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased (pACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease.

ACE: A Collaborative School Consultation Program for Secondary School Teachers

Science.gov (United States)

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…

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

Science.gov (United States)

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.

Brazilian adaptation of the Addenbrooke's Cognitive Examination-Revised (ACE-R

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Viviane Amaral Carvalho

Full Text Available Abstract The Addenbrooke's Cognitive Examination-Revised (ACE-R is a highly sensitive and specific tool for the detection of mild dementia. It is particularly useful in differentiating Alzheimer's disease from frontotemporal dementia. While the first version of the test battery has been adapted in many countries, its revised version has not, probably because it was published very recently. Objective: To translate and adapt the ACE-R for use in the Brazilian population. Methods: Two independent translations were made from English into Portuguese, followed by two independent back-translations. Few adaptations in accordance to the Brazilian culture and language were made and a first version of the instrument produced. This former version of the ACE-R was administered to 21 cognitively healthy subjects aged 60 years or more, with different educational levels. Results: The mean age of the studied sample of healthy elderly was 75.4 years (ranging from 60 to 89 years. Small additional modifications were necessary after the evaluation of the first ten subjects in order to improve comprehension of the test. The final Portuguese version of the ACE-R was produced and was found to be well understood by the remaining 11 subjects, taking an average of 15 minutes to be administered. Conclusions: The Brazilian version of the ACE-R proved to be a promising cognitive instrument for testing both in research and clinical settings. With this regard, additional studies are currently being carried out in our unit in order to investigate the diagnostic properties of the ACE-R in our milieu.

Brazilian adaptation of the Addenbrooke's Cognitive Examination-Revised (ACE-R).

Science.gov (United States)

Carvalho, Viviane Amaral; Caramelli, Paulo

2007-01-01

The Addenbrooke's Cognitive Examination-Revised (ACE-R) is a highly sensitive and specific tool for the detection of mild dementia. It is particularly useful in differentiating Alzheimer's disease from frontotemporal dementia. While the first version of the test battery has been adapted in many countries, its revised version has not, probably because it was published very recently. To translate and adapt the ACE-R for use in the Brazilian population. Two independent translations were made from English into Portuguese, followed by two independent back-translations. Few adaptations in accordance to the Brazilian culture and language were made and a first version of the instrument produced. This former version of the ACE-R was administered to 21 cognitively healthy subjects aged 60 years or more, with different educational levels. The mean age of the studied sample of healthy elderly was 75.4 years (ranging from 60 to 89 years). Small additional modifications were necessary after the evaluation of the first ten subjects in order to improve comprehension of the test. The final Portuguese version of the ACE-R was produced and was found to be well understood by the remaining 11 subjects, taking an average of 15 minutes to be administered. The Brazilian version of the ACE-R proved to be a promising cognitive instrument for testing both in research and clinical settings. With this regard, additional studies are currently being carried out in our unit in order to investigate the diagnostic properties of the ACE-R in our milieu.

Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

Science.gov (United States)

Salvetti, Guido; Di Salvo, Claudio; Ceccarini, Giovanni; Abramo, Antonio; Fierabracci, Paola; Magno, Silvia; Piaggi, Paolo; Vitti, Paolo; Santini, Ferruccio

2016-06-01

The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes.

Advanced Collaborative Emissions Study (ACES)

Energy Technology Data Exchange (ETDEWEB)

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.

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

Science.gov (United States)

Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

2010-08-01

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

Advances in Computer Entertainment. 10th International Conference, ACE 2013

NARCIS (Netherlands)

Reidsma, Dennis; Katayose, H.; Nijholt, Antinus; Unknown, [Unknown

2013-01-01

These are the proceedings of the 10th International Conference on Advances in Computer Entertainment (ACE 2013), hosted by the Human Media Interaction research group of the Centre for Telematics and Information Technology at the University of Twente, The Netherlands. The ACE series of conferences,

Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer's disease.

Science.gov (United States)

Fazal, Karim; Perera, Gayan; Khondoker, Mizanur; Howard, Robert; Stewart, Robert

2017-07-01

Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). To compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis. In the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. In people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Selective cyclooxygenase-2 inhibitor use and progression of renal function in patients with chronic kidney disease: a single-center retrospective cohort study

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Kaewput W

2016-11-01

Full Text Available Wisit Kaewput,1,2 Preedee Disorn,2 Bancha Satirapoj2 1Department of Military and Community Medicine, Phramongkutklao College of Medicine, 2Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Background: The use of selective COX-2 (sCOX-2 inhibitors with acute kidney injury, salt water retention, and cardiovascular events have been correlated in subjects with normal kidney function, but sCOX-2 inhibitor use concerning the progression of chronic kidney disease (CKD remains uncertain. Objectives: To determine the progression of renal function and electrolyte abnormalities among CKD patients after using sCOX-2 inhibitors during short- and long-term periods. Methods: The study employed a retrospective cohort design comprising all types of CKD patients with and without sCOX-2 inhibitors (celecoxib and etoricoxib. Data collected included medical data, estimated glomerular filtration rate (eGFR, and serum electrolytes at 3 and 6 months between January 2009 and January 2014. Subjects attended the outpatient clinic and were then followed up until discontinuation of the drugs at years 1 and 2 until May 2016. Results: Ninety-two CKD patients on sCOX-2 inhibitors and 92 CKD patients without sCOX-2 inhibitors were included. The sCOX-2 inhibitor group showed more decline in eGFR than the control group at 3 and 6 months of follow-up (–8.27±9.75 vs –1.64±6.05 mL/min/1.73 m2, P<0.001 and –12.36±6.48 vs –4.31±5.11 mL/min/1.73 m2, P=0.001, respectively and at 1 and 2 years of follow-up after subjects discontinued sCOX-2 (–6.84±10.34 vs –1.61±8.93 mL/min/1.73 m2, P=0.004 and –10.26±10.19 vs –5.12±8.61 mL/min/1.73 m2, P=0.005, respectively. In addition, the sCOX-2 inhibitor group had significantly more increased serum potassium during the study follow-up than the control group. Conclusion: The sCOX-2 inhibitors are associated with an increased risk for rapid eGFR decline and hyperkalemia in both the

Adverse Childhood Experiences (ACEs) questionnaire and Adult Attachment Interview (AAI): implications for parent child relationships.

Science.gov (United States)

Murphy, Anne; Steele, Miriam; Dube, Shanta Rishi; Bate, Jordan; Bonuck, Karen; Meissner, Paul; Goldman, Hannah; Steele, Howard

2014-02-01

Although Adverse Childhood Experiences (ACEs) are linked to increased health problems and risk behaviors in adulthood, there are no studies on the association between ACEs and adults' states of mind regarding their early childhood attachments, loss, and trauma experiences. To validate the ACEs questions, we analyzed the association between ACEs and emotional support indicators and Adult Attachment Interview (AAI) classifications in terms of unresolved mourning regarding past loss or trauma and discordant states of mind in cannot classify (U/CC) interviews. Seventy-five urban women (41 clinical and 34 community) completed a questionnaire on ACEs, which included 10 categories of abuse, neglect, and household dysfunction, in addition to emotional support. Internal psychological processes or states of mind concerning attachment were assessed using the AAI. ACE responses were internally consistent (Cronbach's α=.88). In the clinical sample, 84% reported≥4 ACEs compared to 27% among the community sample. AAIs judged U/CC occurred in 76% of the clinical sample compared to 9% in the community sample. When ACEs were≥4, 65% of AAIs were classified U/CC. Absence of emotional support in the ACEs questionnaire was associated with 72% of AAIs being classified U/CC. As the number of ACEs and the lack of emotional support increases so too does the probability of AAIs being classified as U/CC. Findings provide rationale for including ACEs questions in pediatric screening protocols to identify and offer treatment reducing the intergenerational transmission of risk associated with problematic parenting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of the optimized conditions for genotyping of ACE ID ...

African Journals Online (AJOL)

ACE ID polymorphism is inevitable for genetic epidemiology of several cardiovascular and non cardiovascular diseases due to its direct influence on ACE activity level. In the present work, conditions were optimized for its analysis using conventional and direct blood PCR (DB PCR). Blood samples from nine normotensive ...

Differentiation of semantic dementia and Alzheimer's disease using the Addenbrooke's Cognitive Examination (ACE).

Science.gov (United States)

Davies, R Rhys; Dawson, Kate; Mioshi, Eneida; Erzinçlioğlu, Sharon; Hodges, John R

2008-04-01

The Addenbrooke's Cognitive Examination (ACE) is a simple diagnostic tool bridging the gap between the very brief Mini Mental State Exam (MMSE) and much longer test batteries used by neuropsychologists which has proven extremely popular internationally. We aimed to assess the ability of the ACE to differentiate semantic dementia (SD) from Alzheimer's disease (AD). The ACE was administered to three groups: SD patients (n = 40) and two separate groups of AD patients (n = 40 in each), matched for overall ACE or MMSE score. Significant differences were found between SD and both AD groups for the ACE sub-scores of naming, reading and orientation in time. Discriminant analysis (SD versus AD) led to the formulation of a 'semantic index' (naming plus reading minus scores for serial-7s, orientation in time and drawing). Application of the semantic index to the patient data found values of less than zero to be predictive of SD rather than AD with 88% sensitivity and 90% specificity. Validation analysis in an independent sample of 24 SD and AD patients proved even more favourable. The overall ACE score is known to be a sensitive, and specific, indicator of early neurodegenerative dementia; this study shows that the ACE can also be used to detect SD through application of the semantic index.

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

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Jin-Chao Wu

2013-01-01

Full Text Available 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.

AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

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Lagarde Michel

2016-01-01

Full Text Available AceDoPC® is a structured phospholipid or acetyl-LysoPC-DHA made to prevent docosahexaenoic acyl migrating from the sn-2 to sn-1 position of the phospholipid, however keeping the main physical-chemical properties of LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC® allows DHA crossing a re-constituted blood-brain barrier with higher efficiency than non-esterified DHA or PC-DHA. When injected to blood of rats, AceDoPC® is processed within the brain to deliver DHA to phosphatidyl-choline and -ethanolamine. When injected to rats following the induction of an ischemic stroke, AceDoPC® prevents the extension of brain lesions more efficiently than DHA. Overall, these properties make AceDoPC® a promising phospholipid carrier of DHA to the brain.

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

Energy Technology Data Exchange (ETDEWEB)

Dobranich, P.R.; Widney, T.W.; Goolsby, P.T. [Sandia National Labs., Albuquerque, NM (United States). Cooperative Monitoring Center and Regional Security; Nelson, J.D.; Evanko, D.A. [Ogden Environmental and Energy Services, Inc., Albuquerque, NM (United States)

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.

Renoprotective effects of benazepril: current perspective.

Science.gov (United States)

Stompór, Tomasz; Napora, Maria; Olszewski, Artur

2011-06-01

Cardiovascular (CV) disease, its associated risk factors and continued progression run in parallel with renal deterioration (cardio-renal syndrome). Most guidelines promote early treatment, including the use of ACE inhibitors to control CV risk in patients with chronic renal failure. The renoprotective effects of the ACE inhibitor, benazepril, independent of blood pressure control, have been demonstrated, as monotherapy or in combination with amlodipine or hydrochlorothiazide, in large clinical trials: Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) and Gauging Albuminuria Reduction with Lotrel in Diabetic Patients with Hypertension (GUARD) in patients with mild-to-severe chronic kidney disease. In the ACCOMPLISH trial, CV outcomes and renoprotective effects were greater in patients receiving benazepril in combination with amlodipine; the GUARD trial demonstrated that combined benazepril/hydrochlorothiazide was more effective than amlodipine combined with benazepril in reducing baseline urinary albumin:creatinine ratio and normalizing urinary albumin:creatinine ratio in patients with baseline microalbuminuria, although this effect was accompanied with a greater decrease in glomerular filtration rate than with benazepril/amlodipine. While this is not a study in patients with overt renal disease (patients had severe CV diseases), the ACCOMPLISH trial is the first large study to date to show the added benefit of combining ACE inhibitors and calcium-channel blockers in renal protection. Future large, well-controlled trials, designed to evaluate hard renal outcomes, are required to identify which patients will benefit most from particular combination treatment strategies in renoprotection.

ACE Insertion/Deletion Polymorphism and Diabetic Nephropathy: Clinical Implications of Genetic Information

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Sung-Kyu Ha

2014-01-01

Full Text Available 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.

ACE-FTS version 3.0 data set: validation and data processing update

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Claire Waymark

2014-01-01

Full Text Available On 12 August 2003, the Canadian-led Atmospheric Chemistry Experiment (ACE was launched into a 74° inclination orbit at 650 km with the mission objective to measure atmospheric composition using infrared and UV-visible spectroscopy (Bernath et al. 2005. The ACE mission consists of two main instruments, ACE-FTS and MAESTRO (McElroy et al. 2007, which are being used to investigate the chemistry and dynamics of the Earth’s atmosphere.  Here, we focus on the high resolution (0.02 cm-1 infrared Fourier Transform Spectrometer, ACE-FTS, that measures in the 750-4400 cm-1 (2.2 to 13.3 µm spectral region.  This instrument has been making regular solar occultation observations for more than nine years.  The current ACE-FTS data version (version 3.0 provides profiles of temperature and volume mixing ratios (VMRs of more than 30 atmospheric trace gas species, as well as 20 subsidiary isotopologues of the most abundant trace atmospheric constituents over a latitude range of ~85°N to ~85°S.  This letter describes the current data version and recent validation comparisons and provides a description of our planned updates for the ACE-FTS data set. [...

The ACES mission: scientific objectives and present status

Science.gov (United States)

Cacciapuoti, L.; Dimarcq, N.; Salomon, C.

2017-11-01

"Atomic Clock Ensemble in Space" (ACES) is a mission in fundamental physics that will operate a new generation of atomic clocks in the microgravity environment of the International Space Station (ISS). The ACES clock signal will combine the medium term frequency stability of a space hydrogen maser (SHM) and the long term stability and accuracy of a frequency standard based on cold cesium atoms (PHARAO). Fractional frequency stability and accuracy of few parts in 1016 will be achieved. The on-board time base distributed on Earth via a microwave link (MWL) will be used to test fundamental laws of physics (Einstein's theories of Special and General Relativity, Standard Model Extension, string theories…) and to develop applications in time and frequency metrology, universal time scales, global positioning and navigation, geodesy and gravimetry. After a general overview on the mission concept and its scientific objectives, the present status of ACES instruments and sub-systems will be discussed.

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

Science.gov (United States)

Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

2013-01-01

Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

Validity of the T-ACE in pregnancy in predicting child outcome and risk drinking.

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Chiodo, Lisa M; Sokol, Robert J; Delaney-Black, Virginia; Janisse, James; Hannigan, John H

2010-01-01

Preventing fetal alcohol spectrum disorders (FASDs) requires detection of in-pregnancy maternal risk drinking. The widely used T-ACE screen has been applied in various ways, although the impact of those different uses on effectiveness is uncertain. We examined relations among different T-ACE scoring criteria, maternal drinking, and child outcome. Self-reported across-pregnancy maternal drinking was assessed in 75 African-American women. The different T-ACE criteria used varied the level of drinking that defined tolerance (two or three drinks) and the total T-ACE score cut-points (two or three). Receiver operator curves and regression analysis assessed the significance of relations. Increasing the total T-ACE score cut-point to 3 almost doubled specificity in detecting risk drinking whereas maintaining adequate sensitivity, equivalent to that in the original report, and identified substantially more neurobehavioral deficits in children. Redefining tolerance at three drinks did not improve T-ACE effectiveness in predicting outcomes. This study is among the first to show the ability of an in-pregnancy T-ACE assessment to predict child neurodevelopmental outcome. In addition, increasing the total T-ACE score criterion (from 2 to 3) improved identification of non-drinking mothers and unaffected children with little loss in detection of drinkers and affected children. Efficient in-pregnancy screens for risk drinking afford greater opportunities for intervention that could prevent/limit FASDs. Published by Elsevier Inc.

Assessing Cost-Effectiveness in Obesity (ACE-Obesity: an overview of the ACE approach, economic methods and cost results

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Swinburn Boyd

2009-11-01

Full Text Available Abstract Background The aim of the ACE-Obesity study was to determine the economic credentials of interventions which aim to prevent unhealthy weight gain in children and adolescents. We have reported elsewhere on the modelled effectiveness of 13 obesity prevention interventions in children. In this paper, we report on the cost results and associated methods together with the innovative approach to priority setting that underpins the ACE-Obesity study. Methods The Assessing Cost Effectiveness (ACE approach combines technical rigour with 'due process' to facilitate evidence-based policy analysis. Technical rigour was achieved through use of standardised evaluation methods, a research team that assembles best available evidence and extensive uncertainty analysis. Cost estimates were based on pathway analysis, with resource usage estimated for the interventions and their 'current practice' comparator, as well as associated cost offsets. Due process was achieved through involvement of stakeholders, consensus decisions informed by briefing papers and 2nd stage filter analysis that captures broader factors that influence policy judgements in addition to cost-effectiveness results. The 2nd stage filters agreed by stakeholders were 'equity', 'strength of the evidence', 'feasibility of implementation', 'acceptability to stakeholders', 'sustainability' and 'potential for side-effects'. Results The intervention costs varied considerably, both in absolute terms (from cost saving [6 interventions] to in excess of AUD50m per annum and when expressed as a 'cost per child' estimate (from Conclusion The use of consistent methods enables valid comparison of potential intervention costs and cost-offsets for each of the interventions. ACE-Obesity informs policy-makers about cost-effectiveness, health impact, affordability and 2nd stage filters for important options for preventing unhealthy weight gain in children. In related articles cost-effectiveness results and

ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes

DEFF Research Database (Denmark)

Færch, Louise H; Sejling, Anne-Sophie; Lajer, Maria

2015-01-01

AIMS: Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause ...

Application of plug-plug technique to ACE experiments for discovery of peptides binding to a larger target protein: a model study of calmodulin-binding fragments selected from a digested mixture of reduced BSA.

Science.gov (United States)

Saito, Kazuki; Nakato, Mamiko; Mizuguchi, Takaaki; Wada, Shinji; Uchimura, Hiromasa; Kataoka, Hiroshi; Yokoyama, Shigeyuki; Hirota, Hiroshi; Kiso, Yoshiaki

2014-03-01

To discover peptide ligands that bind to a target protein with a higher molecular mass, a concise screening methodology has been established, by applying a "plug-plug" technique to ACE experiments. Exploratory experiments using three mixed peptides, mastoparan-X, β-endorphin, and oxytocin, as candidates for calmodulin-binding ligands, revealed that the technique not only reduces the consumption of the protein sample, but also increases the flexibility of the experimental conditions, by allowing the use of MS detection in the ACE experiments. With the plug-plug technique, the ACE-MS screening methodology successfully selected calmodulin-binding peptides from a random library with diverse constituents, such as protease digests of BSA. Three peptides with Kd values between 8-147 μM for calmodulin were obtained from a Glu-C endoprotease digest of reduced BSA, although the digest showed more than 70 peaks in its ACE-MS electropherogram. The method established here will be quite useful for the screening of peptide ligands, which have only low affinities due to their flexible chain structures but could potentially provide primary information for designing inhibitors against the target protein. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brazilian adaptation of the Addenbrooke’s Cognitive Examination-Revised (ACE-R)

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Carvalho, Viviane Amaral; Caramelli, Paulo

2007-01-01

The Addenbrooke’s Cognitive Examination-Revised (ACE-R) is a highly sensitive and specific tool for the detection of mild dementia. It is particularly useful in differentiating Alzheimer’s disease from frontotemporal dementia. While the first version of the test battery has been adapted in many countries, its revised version has not, probably because it was published very recently. Objective To translate and adapt the ACE-R for use in the Brazilian population. Methods Two independent translations were made from English into Portuguese, followed by two independent back-translations. Few adaptations in accordance to the Brazilian culture and language were made and a first version of the instrument produced. This former version of the ACE-R was administered to 21 cognitively healthy subjects aged 60 years or more, with different educational levels. Results The mean age of the studied sample of healthy elderly was 75.4 years (ranging from 60 to 89 years). Small additional modifications were necessary after the evaluation of the first ten subjects in order to improve comprehension of the test. The final Portuguese version of the ACE-R was produced and was found to be well understood by the remaining 11 subjects, taking an average of 15 minutes to be administered. Conclusions The Brazilian version of the ACE-R proved to be a promising cognitive instrument for testing both in research and clinical settings. With this regard, additional studies are currently being carried out in our unit in order to investigate the diagnostic properties of the ACE-R in our milieu. PMID:29213390

Improved guideline adherence to pharmacotherapy of chronic systolic heart failure in general practice--results from a cluster-randomized controlled trial of implementation of a clinical practice guideline.

Science.gov (United States)

Peters-Klimm, Frank; Müller-Tasch, Thomas; Remppis, Andrew; Szecsenyi, Joachim; Schellberg, Dieter

2008-10-01

Clinical practice guidelines (CPG) reflect the evidence of effective pharmacotherapy of chronic (systolic) heart failure (CHF) which needs to be implemented. This study aimed to evaluate the effect of a new, multifaceted intervention (educational train-the-trainer course plus pharmacotherapy feedback = TTT) compared with standard education on guideline adherence (GA) in general practice. Thirty-seven participating general practitioners (GPs) were randomized (18 vs. 19) and included 168 patients with ascertained symptomatic CHF [New York Heart Association (NYHA) II-IV]. Groups received CPG, the TTT intervention consisted of four interactive educational meetings and a pharmacotherapy feedback, while the control group received a usual lecture (Standard). Outcome measure was GA assessed by prescription rates and target dosing of angiotensin converting enzyme (ACE) inhibitors (ACE-I) or angiotensin receptor blockers (ARB), beta-blockers (BB) and aldosterone antagonists (AA) at baseline and 7-month follow-up. Group comparisons at follow-up were adjusted to GA, sex, age and NYHA stage at baseline. Prescription rates at baseline (n = 168) were high (ACE-I/ARB 90, BB 79 and AA 29%) in both groups. At follow up (n = 146), TTT improved compared with Standard regarding AA (43% vs. 23%, P = 0.04) and the rates of reached target doses of ACE-I/ARB (28% vs. 15%, P = 0.04). TTT group achieved significantly higher mean percentages of daily target dose (52% vs. 42%, mean difference 10.3%, 95% CI 0.84-19.8, P = 0.03). Despite of pre-existing high GA in both groups and an active control group, the multifaceted intervention was effective in quality of care measured by GA. Further research is needed on the choice of interventions in different provider populations.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

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Ramanathan, Gnanasambandan; Ghosh, Santu; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar V K S

2016-06-01

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia.

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Pleyer, Christopher; Wiestner, Adrian; Sun, Clare

2018-05-15

Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib. While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents. This review discusses the impact of ibrutinib and idelalisib on the immune system, including infectious and auto-immune complications as well as their specific effects on the B-cell, T-cell, and myeloid compartment.

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

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

2015-09-01

Egg ovotransferrin-derived angiotensin converting enzyme (ACE) inhibitory peptide IRW was previously shown to reduce blood pressure in spontaneously hypertensive rats through reduced vascular inflammation and increased nitric oxide-mediated vasorelaxation. The main objective of the present study was to investigate the molecular mechanism of this peptide through transcriptome analysis by RNAseq technique. Total RNA was extracted from kidney and mesenteric arteries; the RNAseq libraries (from untreated and IRW-treated groups) were constructed and subjected to sequence using HiSeq 2000 system (Illumina) system. A total of 12 764 and 13 352 genes were detected in kidney and mesenteric arteries, respectively. The differentially expressed (DE) genes between untreated and IRW-treated groups were identified and the functional analysis through ingenuity pathway analysis revealed a greater role of DE genes identified from mesenteric arteries than that of kidney in modulating various cardiovascular functions. Subsequent qPCR analysis further confirmed that IRW significantly increased the expression of ACE-2, ABCB-1, IRF-8, and CDH-1 while significantly decreased the expression ICAM-1 and VCAM-1 in mesenteric arteries. Our research showed for the first time that ACE inhibitory peptide IRW could contribute to its antihypertensive activity through increased ACE2 and decreased proinflammatory genes expression. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aggressive Periodontitis and Chronic Arthritis: Blood Mononuclear Cell Gene Expression and Plasma Protein Levels of Cytokines and Cytokine Inhibitors

DEFF Research Database (Denmark)

Sørensen, Lars Korsbæk Connor; Poulsen, Anne Havemose; Bendtzen, Klaus

2009-01-01

-inflammatory cytokines and cytokine receptors in patients with periodontitis and patients with arthritis representing two examples of chronic inflammatory diseases, such as periodontitis and arthritis. To identify possible disease-specific characteristics of subjects with periodontitis relative to subjects with chronic......TNF-RI plasma levels in patients with LAgP and RA. CONCLUSIONS: The study demonstrated only a few changes in the PBMC expression of various cytokine and cytokine inhibitor genes in aggressive periodontitis and chronic arthritis compared to controls. There were a few similarities among disease groups...... inflammation in general, patients with arthritis (juvenile idiopathic arthritis [JIA] and rheumatoid arthritis [RA]) were included. METHODS: The study population consisted of white adults periodontitis (LAgP; n = 18), generalized aggressive periodontitis...

MSCs with ACE II gene affect apoptosis pathway of acute lung injury induced by bleomycin.

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Zhang, Xiaomiao; Gao, Fengying; Li, Qian; Dong, Zhixia; Sun, Bo; Hou, Lili; Li, Zhuozhe; Liu, Zhenwei

2015-02-01

The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively. The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p ACE II performed a better effect than single stem in most indexes, including AI (p ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI.

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Directory of Open Access Journals (Sweden)

Sema Inanir

2016-04-01

Full Text Available Abstract Background Major depressive disorder (MDD is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE has an important role in renin-angiotensin system (RAS and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D polymorphism of ACE gene. Objective The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

The effect of an angiotensin-converting enzyme inhibitor on water and electrolyte balance in water-restricted sheep

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R.A. Meintjies

1999-07-01

Full Text Available The importance of angiotensin II in the regulation of water and electrolyte balance in sheep is questionable. In this trial the effects of an angiotensin-converting enzyme (ACE inhibitor were quantified in sheep on restricted water intake. Comparing the phase of water restriction only with that of water restriction plus ACE inhibition, significant increases were observed during the latter phase in urine volume, sodium and potassium excretion via the urine, sodium concentration in the plasma and osmolar clearance. Urine osmolarity decreased with inhibition of angiotensin II formation while variables such as water, sodium and potassium loss via the faeces were unaffected. Most of the renal effects of ACE inhibition, except the increase in urinary potassium excretion, were explicable in terms of the established functions of angiotensin II. Furthermore, results of this trial indicate that angiotensin II has no significant effect on the intestine in regulating water and electrolyte excretion via the faeces.

Alabama Cooperative Extension System - ACES.edu

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Marshall Mobile Monroe Montgomery Morgan Perry Pickens Pike Randolph Russell Shelby St. Clair Sumter Marengo Tuscaloosa Greene Pickens Sumter Conecuh Escambia Monroe Clarke Choctaw Washington Baldwin Mobile Office Communications & Marketing Information Technology ACES Publications & Store 4-H &

The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease.

Science.gov (United States)

Zatelli, A; Roura, X; D'Ippolito, P; Berlanda, M; Zini, E

2016-01-01

Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

deletion polymorphism of ACE gene and Alzheimerв€™s disease

African Journals Online (AJOL)

Omayma M. Hassanin

2014-06-27

Jun 27, 2014 ... ease, 45 males and 39 females aged 65 ± 7 years from the Geriatric Department at Ain-Shams Uni- ..... alternative therapy provided by the ACE protein. .... enzyme (ACE) gene polymorphism in relation to physical perfor-.

ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

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Seong-Jong Lee

2015-01-01

Full Text Available 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.

Association of Angiotensin-Converting Enzyme (ACE) Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

Science.gov (United States)

Rashed, Laila; Abdel Hay, Rania; Mahmoud, Rania; Hasan, Nermeen; Zahra, Amr; Fayez, Salwa

2015-01-01

Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE) plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D) polymorphism of the ACE gene was reported be associated with the development of vitiligo. Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL)-6) and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide) in vitiligo patients. This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively. The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026). However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115). There were statistically significant higher VIDA score (P = 0.007), and serum IL-6 (P ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls. As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

Angiotensin I - Converting Enzyme (ACE) gene polymorphism in relation to physical performance, cognition and survival

DEFF Research Database (Denmark)

Frederiksen, Henrik; Gaist, David; Bathum, Lise

2003-01-01

Studies of younger individuals have suggested an association between ACE genotype and physical and cognitive performance. Using a longitudinal study of elderly twins we studied the association between ACE genotype and physical and cognitive functioning and survival in old age.......Studies of younger individuals have suggested an association between ACE genotype and physical and cognitive performance. Using a longitudinal study of elderly twins we studied the association between ACE genotype and physical and cognitive functioning and survival in old age....

Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease?

NARCIS (Netherlands)

Grootendorst, D. C.; Gauw, S. A.; Baan, R.; Kelly, J.; Murdoch, R. D.; Sterk, P. J.; Rabe, K. F.

2003-01-01

Maintenance treatment with PDE(4) inhibitor cilomilast improves FEV(1) in chronic obstructive pulmonary disease (COPD) patients. We investigated the acute bronchodilating effects of a single dose of cilomilast with or without concomitant administration of inhaled salbutamol and/or ipratropium

Proton pump inhibitor-responsive chronic cough without acid reflux: a case report

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Nobata Kouichi

2007-08-01

Full Text Available Abstract Background Because 24-h esophageal pH monitoring is quite invasive, the diagnosis of gastroesophageal reflux disease (GERD-associated cough has usually been made based merely on the clinical efficacy of treatment with proton pump inhibitor (PPI. Case presentation We recently encountered two patients with PPI-responsive chronic non-productive cough for whom switching from bronchodilators and glucocorticosteroids to PPI resulted in improvement of cough. The cough returned nearly to pre-administration level a few weeks after discontinuation of PPI. Though GERD-associated cough was suspected, 24-h esophageal pH monitoring revealed that the cough rarely involved gastric acid reflux. Following re-initiation of PPI, the cough disappeared again. Conclusion PPI may improve cough unrelated to gastric acid reflux.

Verification and validation of ACE-format library created from ENDF/B-VII.0

International Nuclear Information System (INIS)

Chen Chaobin; Hu Zehua; Zhang Benai; Chen Yixue; Wu Jun

2009-01-01

ENDF/B-VII.0, released by the USA Cross Section Evaluation Working Group(CSEWG) in December 2006, was developed in five years since the previous release of ENDF/B-VI.8 and was demonstrated to contain much better physical representations of the data and to perform much better than previus ENDF evaluations over a broad range of applications. We generated ACE-format pointwise cross section library from the ENDF/B-VII.0 neutron reaction sublibrary with the processing code NJOY. The paper provides an overview of ENDF/B-VII.0, a summary of the ACE-format files producing process and a detail description of the validation of the ACE-format library. The conclusion is that the ACE-format library produced is correct. (authors)

PAPR reduction in FBMC using an ACE-based linear programming optimization

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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

Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

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Yang, Chun-Hua; Lu, Yi; Chen, Xue-Xia; Xian, Wen-Feng; Tu, Wei-Feng; Li, Hong-Yan

2015-12-01

The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association. © The Author(s) 2015.

Validation of the Spanish Version of the Addenbrooke's Cognitive Examination-Revised (ACE-R).

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Torralva, T; Roca, M; Gleichgerrcht, E; Bonifacio, A; Raimondi, C; Manes, F

2011-01-01

The Addenbrooke's Cognitive Examination Revised (ACE-R) is an improved version of the earlier brief screening test which has been validated in English with high sensitivity and specificity to detect cognitive dysfunction. The aim of this study was to validate the Spanish version of the ACE-R in an Argentine population. A group of patients with Alzheimer Disease (AD) and patients with behavioural variant Frontotemporal Dementia (bvFTD) paired by age, sex, and years of education with healthy controls were assessed using the ACE-R. Stage of dementia was measured with the Clinical Dementia Rating Scale (CDR). The English version of the ACE-R was first translated into Spanish and then back-translated into English by two blind independent experts. Internal reliability was very good (Cronbach's alpha=0.89). Concurrent validity, determined by the correlation between total ACE-R and CDR was significant (Pcognitive impairment and has shown to discriminate between bvFTD and AD. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA.

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Packer, Milton

2016-10-01

Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long-term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data

NARCIS (Netherlands)

van Wieringen, W.N.; Belien, J.A.M.; Vosse, S.; Achame, E.M.; Ylstra, B.

2006-01-01

Summary: We describe a tool, called ACE-it (Array CGH Expression integration tool). ACE-it links the chromosomal position of the gene dosage measured by array CGH to the genes measured by the expression array. ACE-it uses this link to statistically test whether gene dosage affects RNA expression. ©

ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus.

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Pan, Yan-Hong; Wang, Min; Huang, Yan-Mei; Wang, Ying-Hui; Chen, Yin-Ling; Geng, Li-Jun; Zhang, Xiao-Xi; Zhao, Hai-Lu

2016-01-01

Association between ACE gene I/D polymorphism and the risk of overweight/obesity remains controversial. We investigated the possible relationship between ACE gene I/D polymorphism and obesity in Chinese type 2 diabetes mellitus (T2DM) patients. In this study, obesity was defined as a body mass index (BMI) value ≥ 25 kg/m 2 and subjects were classified into 4 groups (lean, normal, overweight, and obese). PCR (polymerase chain reaction) was used to detect the ACE gene I/D polymorphism in T2DM patients. Metabolic measurements including blood glucose, lipid profile, and blood pressure were obtained. Frequencies of the ACE genotypes (DD, ID, and II) were not significant among the 4 groups of BMI-defined patients ( P = 0.679) while ACE II carriers showed higher systolic blood pressure (SBP) and pulse pressure (PP) (all P ACE gene I/D polymorphism with obesity is insignificant in Chinese patients with T2DM. SBP and PP might be higher in the ACE II carriers than in the DD and ID carriers.

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

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

2015-04-01

Mice lacking functional neurokinin-1 receptors (NK1R-/-) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R-/- and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R-/- mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R-/- and wildtype mice. Both antagonists increased the locomotor activity of NK1R-/- mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R-/- and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R-/- mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

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

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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.

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

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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.

Association of Angiotensin-Converting Enzyme (ACE Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

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Laila Rashed

Full Text Available Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D polymorphism of the ACE gene was reported be associated with the development of vitiligo.Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL-6 and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide in vitiligo patients.This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively.The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026. However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115. There were statistically significant higher VIDA score (P = 0.007, and serum IL-6 (P < 0.001 in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007 when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls.As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

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

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

2014-01-01

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

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

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Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People' s Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

2014-02-01

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

Space Weather Drivers in the ACE Era

Science.gov (United States)

Vogt, M.; Puhl-Quinn, P.; Jordanova, V. K.; Smith, C. W.; Cohen, C. M.

2004-12-01

The Advanced Composition Explorer (ACE) spacecraft was launched Aug.~25, 1997 [Stone et al., 1998]. Beginning shortly after launch and continuing to the present day ACE has provided real-time data telemetry of solar wind conditions upstream of the Earth. The real-time data includes solar wind speed and density, magnetic field direction and magnitude, and a range of energetic particle intensities [Zwickl et al., 1999]. The real-time data product is provided within 5 minutes of observation and many partners from both industry and science use these data for a variety of purposes. The most common purpose of practical industrial application involves mitigation of lost services arising from magnetospheric storm activity. Many space weather efforts are directed at providing improved predictions of magnetospheric response that can be applied to real-time data in the hope of better predicting the vulnerability and required action of industry to approaching disturbances. It therefore seems prudent that following 6 years of activity including one solar maximum period we should evaluate the nature and strength of the largest disturbances observed with the hope of better assessing the industrial response. Simply put: ``Did ACE observe disturbances that were as large as those seen previously during the space age?'' If not, it may be the case that industry must evaluate its response to the real-time warnings and not become complacent by the simple act of survival. We compare the most intense space weather events of the ACE era with those recorded on the Omnitape data set spanning 40+ years of spacecraft measurements in the near-Earth environment. We compare both magnetospheric response parameters and solar wind drivers. In addition, we compare the large energetic particle events over the same time frame. Stone, E.~C., et al., Space Science Rev., 86(1-4), 357-408, 1998. Zwickl, R.~D., et al., Space Science Rev., 86(1-4), 633-648, 1998.

Production of antioxidant and ACE-inhibitory peptides from Kluyveromyces marxianus protein hydrolysates: Purification and molecular docking

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Mahta Mirzaei

2018-04-01

Full Text Available Kluyveromyces marxianus protein hydrolysates were prepared by two different sonicated-enzymatic (trypsin and chymotrypsin hydrolysis treatments to obtain antioxidant and ACE-inhibitory peptides. Trypsin and chymotrypsin hydrolysates obtained by 5 h, exhibited the highest antioxidant and ACE-inhibitory activities. After fractionation using ultrafiltration and reverse phase high performance liquid chromatography (RP-HPLC techniques, two new peptides were identified. One fragment (LL-9, MW = 1180 Da with the amino acid sequence of Leu-Pro-Glu-Ser-Val-His-Leu-Asp-Lys showed significant ACE inhibitory activity (IC50 = 22.88 μM while another peptide fragment (VL-9, MW = 1118 Da with the amino acid sequence of Val-Leu-Ser-Thr-Ser-Phe-Pro-Pro-Lys showed the highest antioxidant and ACE inhibitory properties (IC50 = 15.20 μM, 5568 μM TE/mg protein. The molecular docking studies revealed that the ACE inhibitory activities of VL-9 is due to interaction with the S2 (His513, His353, Glu281 and S′1 (Glu162 pockets of ACE and LL-9 can fit perfectly into the S1 (Thr345 and S2 (Tyr520, Lys511, Gln281 pockets of ACE. Keywords: K. marxianus, Bioactive peptides, Antioxidant, ACE inhibitory, Protein hydrolysate

Screening for Adverse Childhood Experiences (ACEs) in an Integrated Pediatric Care Model

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Purewal, Sukhdip K.; Bucci, Monica; Wang, Lisa Gutiérrez; Koita, Kadiatou; Marques, Sara Silvério; Oh, Debora; Harris, Nadine Burke

2016-01-01

Adverse childhood experiences (ACEs) are stressful or traumatic events that place children at risk of negative health, mental health, and behavioral outcomes. The Center for Youth Wellness (CYW), working in partnership with the Bayview Child Health Center (BCHC), pioneered ACE screening for children and adolescents. This article describes the…

Molecular and Thermodynamic Mechanisms of the Chloride-dependent Human Angiotensin-I-converting Enzyme (ACE)*

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Yates, Christopher J.; Masuyer, Geoffrey; Schwager, Sylva L. U.; Akif, Mohd; Sturrock, Edward D.; Acharya, K. Ravi

2014-01-01

Somatic angiotensin-converting enzyme (sACE), a key regulator of blood pressure and electrolyte fluid homeostasis, cleaves the vasoactive angiotensin-I, bradykinin, and a number of other physiologically relevant peptides. sACE consists of two homologous and catalytically active N- and C-domains, which display marked differences in substrate specificities and chloride activation. A series of single substitution mutants were generated and evaluated under varying chloride concentrations using isothermal titration calorimetry. The x-ray crystal structures of the mutants provided details on the chloride-dependent interactions with ACE. Chloride binding in the chloride 1 pocket of C-domain ACE was found to affect positioning of residues from the active site. Analysis of the chloride 2 pocket R522Q and R522K mutations revealed the key interactions with the catalytic site that are stabilized via chloride coordination of Arg522. Substrate interactions in the S2 subsite were shown to affect chloride affinity in the chloride 2 pocket. The Glu403-Lys118 salt bridge in C-domain ACE was shown to stabilize the hinge-bending region and reduce chloride affinity by constraining the chloride 2 pocket. This work demonstrated that substrate composition to the C-terminal side of the scissile bond as well as interactions of larger substrates in the S2 subsite moderate chloride affinity in the chloride 2 pocket of the ACE C-domain, providing a rationale for the substrate-selective nature of chloride dependence in ACE and how this varies between the N- and C-domains. PMID:24297181

The Evaluation of Dipeptidyl Peptidase (DPP)-IV, α-Glucosidase and Angiotensin Converting Enzyme (ACE) Inhibitory Activities of Whey Proteins Hydrolyzed with Serine Protease Isolated from Asian Pumpkin (Cucurbita ficifolia).

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Konrad, Babij; Anna, Dąbrowska; Marek, Szołtysik; Marta, Pokora; Aleksandra, Zambrowicz; Józefa, Chrzanowska

2014-01-01

In the present study, whey protein concentrate (WPC-80) and β-lactoglobulin were hydrolyzed with a noncommercial serine protease isolated from Asian pumpkin ( Cucurbita ficifolia ). Hydrolysates were further fractionated by ultrafiltration using membranes with cut-offs equal 3 and 10 kDa. Peptide fractions of molecular weight lower than 3 and 3-10 kDa were further subjected to the RP-HPLC. Separated preparations were investigated for their potential as the natural inhibitors of dipeptidyl peptidase (DPP-IV), α-glucosidase and angiotensin converting enzyme (ACE). WPC-80 hydrolysate showed higher inhibitory activities against the three tested enzymes than β-lactoglobulin hydrolysate. Especially high biological activities were exhibited by peptide fractions of molecular weight lower than 3 kDa, with ACE IC50 food ingredients in the diet of patients with type 2 diabetes.

The angiotensin-converting enzyme (ACE) gene family of Bombyx mori.

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Yan, Hai-Yan; Mita, Kazuei; Zhao, Xia; Tanaka, Yoshikazu; Moriyama, Minoru; Wang, Huabin; Iwanaga, Masashi; Kawasaki, Hideki

2017-04-15

We previously reported regarding an ecdysone-inducible angiotensin-converting enzyme (ACE) gene. We found another four ACE genes in the Bombyx genome. The present study was undertaken to clarify the evolutionally changed function of the ACE of Bombyx mori. Core regions of deduced amino acid sequences of ACE genes were compared with those of other insect ACE genes. Five Bombyx genes have the conserved Zn 2+ -binding-site motif (HEXXH); however, BmAcer4 has only one and BmAcer3 has no catalytic ligand. BmAcer1 and BmAcer2 were expressed in several organs. BmAcer3 was expressed in testes, and BmAcer4 and BmAcer5 were expressed in compound eyes; however, the transcription levels of these three genes were very low. Quantitative RT-PCR and Western analysis were conducted to determine the tissue distribution and developmental expression of BmAcer1and BmAcer2. Transcripts of BmAcer1 and BmAcer2 were found in the reproductive organs during the larval and pupal stages. BmAcer1 was dominant in fat bodies during the feeding stage and showed high expression in the epidermis, wing discs, and pupal wing tissues after the wandering stage. Its expression patterns in epidermis, wing discs, and wing tissues resembled the hemolymph ecdysteroid titer in the larval and pupal stages. Acer1 was observed in the hemolymph at all stages, appearing to be the source of it are fat bodies, wings, and epidermis, and functioning after being secreted into the hemolymph. BmAcer2 was abundant in the midgut during the feeding stage and after the wandering stage and in silk glands after the pupal stage. We conclude that the evolution of BmAcer occurred through duplication, and, thereafter, functional diversification developed. Copyright © 2017 Elsevier B.V. All rights reserved.

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: Recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group.

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Rea, Delphine; Ame, Shanti; Berger, Marc; Cayuela, Jean-Michel; Charbonnier, Aude; Coiteux, Valérie; Cony-Makhoul, Pascale; Dubruille, Viviane; Dulucq, Stéphanie; Etienne, Gabriel; Legros, Laurence; Nicolini, Franck; Roche-Lestienne, Catherine; Escoffre-Barbe, Martine; Gardembas, Martine; Guerci-Bresler, Agnès; Johnson-Ansah, Hyacinthe; Rigal-Huguet, Françoise; Rousselot, Philippe; Mahon, François-Xavier

2018-05-03

The ultimate goal of chronic myeloid leukemia management in the tyrosine kinase inhibitor (TKI) era for patients who obtain deep molecular responses is maintaining a durable off-treatment response after treatment discontinuation; this situation is called treatment-free remission (TFR). Knowledge accumulated during the last 10 years justifies moving TFR strategies from research to clinical practice. Twenty experts from the French Chronic Myeloid Leukemia Study Group (France Intergroupe des Leucémies Myéloïdes Chroniques), including 17 hematologists, 2 molecular biologists, and 1 cytogeneticist, critically reviewed published data with the goal of developing evidence-based recommendations for TKI discontinuation in clinical practice. Clinically relevant questions were addressed, including the selection of candidate patients (with known prognostic factors for outcomes taken into account), detailed monitoring procedures during the treatment-free phase, a definition of relapse requiring therapy resumption, and monitoring after treatment reintroduction. This work presents consensus statements with the aim of guiding physicians and biologists by means of pragmatic recommendations for safe TKI discontinuation in daily practice. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Telomere length is associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy

DEFF Research Database (Denmark)

Fyhrquist, Frej; Eriksson, Anders; Saijonmaa, Outi

2013-01-01

INTRODUCTION: Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length...... and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype. METHODS: We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I...

Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease.

Science.gov (United States)

Tekatas, Demet D; Bahcecioglu, Ibrahim H; Ispiroglu, Murat; Sahin, Abdurrahman; Ilhan, Necip; Yalniz, Mehmet; Demirel, Ulvi

2016-01-01

In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins

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Marwa Yousr

2015-12-01

Full Text Available 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.

Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins.

Science.gov (United States)

Yousr, Marwa; Howell, Nazlin

2015-12-07

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.

PENGARUH DEGRADASI ENZIM PROTEOLITIK TERHADAP AKTIVITAS ANGIOTENSIN CONVERTING ENZYME INHIBITOR BEKASAM DENGAN Lactobacillus plantarum B1765 (The Effect of Degradation of Proteolitic Enzyme on Angiotensin Converting Enzyme Inhibitor Activity of Bekasam with Lactobacillus plantarum B1765

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Prima Retno Wikandari

2016-10-01

Full Text Available This research studied the effect of digestive enzyme degradation on the Angiotensin Converting Enzyme Inhibitor (ACEI activity and the stability of bekasam peptide and ACEI activity. Water extract of bekasam was subjected to pepsin and trypsin. The stability of peptide was measured from the changes of peptide concentration before and after treatment by those enzymes. The stability of ACEI activity was measured by hypuric acid liberated from Hip-His-Leu as ACE substrate and determined by spectrophotometer. The results showed that proteolytic enzyme degradation did not affect the concentration of peptide (p>0,05 and the mean concentration 36.72. It was closely related with the ACEI activity that did not change significantly before and after digestion by pepsin and trypsin (p>0,05 and the mean ACEI activity was 70.73. It showed that ACEI activity of bekasam did not change by the degradation of digestive enzyme. Keywords: bekasam, fermented fish, peptides, ACEI activity ABSTRAK Penelitian ini bertujuan untuk mengkaji pengaruh degradasi enzim pencernaan proteolitik terhadap stabilitas peptida dan aktivitas Angiotensin Converting Enzyme Inhibitor (ACEI bekasam yang difermentasi dengan kultur starter Lactobacillus plantarum B1765. Terhadap ekstrak bekasam diberi perlakuan enzim proteolitik pepsin dan tripsin. Pengujian stabilitas peptida diukur dengan ada tidaknya perubahan jumlah peptida setelah perlakuan enzim menggunakan metode formol, sedangkan aktivitas ACEI dilakukan dengan mengetahui jumlah asam hipurat dari substrat Hip-His-Leu yang dibebaskan oleh ACE diukur dengan spektrofotometer. Hasil pengujian menunjukkan perlakuan enzim proteolitik tidak berpengaruh pada konsentrasi peptida dengan p>0,05 dengan nilai rata-rata konsentrasi peptida sebesar 36,72. Hal ini berkorelasi dengan aktivitas ACEI yang juga menunjukkan tidak ada pengaruh antara perlakuan sebelum dan setelah degradasi enzim (p>0,05 dengan rata-rata aktivitas ACEI sebesar 70,73. Hasil

The role of JAK1/2 inhibitors in the treatment of chronic myeloproliferative neoplasms.

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Keohane, Clodagh; Mesa, Ruben; Harrison, Claire

2013-01-01

In 2005, the description of the JAK2V617F mutation for the first time provided a molecular key to enable more rapid diagnosis and target for novel therapeutics in the myeloproliferative neoplasms. In 2007, the first-in-class agent INC18424, ruxolitinib, JAKafi, or JAKAVI was first tested in patients with intermediate-risk 2 or high-risk myelofibrosis regardless of whether they possessed the JAK2V617F mutation. Patients treated with this agent had major reduction in splenomegaly as well as impressive reduction, and in some cases resolution, of symptoms. This study was followed by the two Controlled Myelofibrosis Study with Oral JAK Inhibitor Therapy (COMFORT) trials (the first-ever phase III trials in myelofibrosis), which confirmed results in these aspects were superior to either placebo or standard care, and updated results show a survival advantage with this therapy. This paper discusses these results and data from other JAK inhibitors while speculating on the future of these therapies. It also reflects on the fact that the true targets and agents' mode of action are uncertain. Unlike targeted therapy for chronic myeloid leukemia (CML), these agents do not deliver molecular remission, and it is not clear whether their predominant benefit is mediated via JAK2, JAK1, or both. Nonetheless, the advent of the JAK inhibitor is a welcome advance and has made a dramatic improvement to the therapeutic landscape of these conditions.

ACE variants interact with the RAS pathway to confer risk and protection against type 2 diabetic nephropathy

DEFF Research Database (Denmark)

Ahluwalia, Tarun Veer Singh; Ahuja, Monica; Rai, Taranjit Singh

2009-01-01

Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Among candidate genes examined for susceptibility to diabetic nephropathy, angiotensin-converting enzyme (ACE) gene has been found to be associated with pathogenesis......, in the present study, we evaluated the association of ACE haplotypes and the interactions of ACE, angiotensinogen (AGT), and angiotensin II receptor type I (AGTR1) gene polymorphisms with DNP in Asian Indians. We genotyped seven variants of the RAS pathway genes (ACE, AGT, and AGTR1) in type 2 diabetic cohorts...... and progression of diabetic nephropathy. However, the role of other renin-angiotensin system (RAS) polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Recent studies also show that ACE haplotypes may be better predictors to disease susceptibility. Thus...

Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

Science.gov (United States)

Valdez-Haro, A; Valle, Y; Valdes-Alvarado, E; Casillas-Muñoz, F; Muñoz-Valle, J F; Reynoso-Villalpando, G L; Flores-Salinas, H E; Padilla-Gutiérrez, J R

2017-09-27

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P ACE concentration levels; however, the polymorphism was not associated with ACS.

The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia.

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Muhammad Rauzan

Full Text Available Chronic myeloid leukemia (CML treatment has been improved by tyrosine kinase inhibitors (TKIs such as imatinib mesylate (IM but various factors can cause TKI resistance in patients with CML. One factor which contributes to TKI resistance is a germline intronic deletion polymorphism in the BCL2-like 11 (BIM gene which impairs the expression of pro-apoptotic splice isoforms of BIM. SB939 (pracinostat is a hydroxamic acid based HDAC inhibitor with favorable pharmacokinetic, physicochemical and pharmaceutical properties, and we investigated if this drug could overcome BIM deletion polymorphism-induced TKI resistance. We found that SB939 corrects BIM pre-mRNA splicing in CML cells with the BIM deletion polymorphism, and induces apoptotic cell death in CML cell lines and primary cells with the BIM deletion polymorphism. More importantly, SB939 both decreases the viability of CML cell lines and primary CML progenitors with the BIM deletion and restores TKI-sensitivity. Our results demonstrate that SB939 overcomes BIM deletion polymorphism-induced TKI resistance, and suggest that SB939 may be useful in treating CML patients with BIM deletion-associated TKI resistance.

STUDY OF A TREND IN THE FREQUENCY OF USING MAIN DRUG CLASSES INDICATED FOR THE TREATMENT OF PATIENTS WITH CHRONIC CORONARY HEART DISEASE IN 2004 TO 2014: DATA FROM THE CHD PROGNOSIS REGISTRY

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S. N. Tolpygina

2016-01-01

Full Text Available Objective: to estimate a trend in the frequency of using drugs with their proven effect on disease outcome in patients with chronic coronary heart disease (CHD in 2004–2014 within the CHD PROGNOSIS registry. Materials and methods. The investigation included data from the CHD PROGNOSIS registry on 303 patients with verified CHD during the 2004–2007 reference hospitalization at the National Research Center for Preventive Medicine, who made a control visit 4 years later, and those on 125 patients who had come following 7 years. Results. There was a low frequency of prescribing the drugs that were able to improve prognosis in patients with stable CHD prior to the 2004–2007 reference hospitalization with an increase at discharge and with a further reduction during outpatient treatment. 7.6 and 86.5% of the patients took statins; 68 and 96 % received disaggregants; 24.8 and 94 % used β-adrenoblockers (β-AB, and 19 and 83 % had angiotensin-converting enzyme (ACE inhibitors before hospitalization and at discharge, respectively (p < 0.001. Four and seven years after discharge, there were reductions in the frequency of using statins to 67 and 70 %, disaggregants to 80 and 90 %, β-AB to 80 and 75 %, and ACE inhibitors to 66 and 65 %, respectively (p < 0.01. At the same time, the above-mentioned drugs were taken by 15 and 69 % of patients on admission and at discharge, respectively (p < 0.001, by 41 and 35 % after 4 and 7 years (p < 0.01. In 2004 to 2014, most drugs were used at low and moderate doses with a gradual increase in the share of generics. Conclusion. The therapy in patients with stable CHD was characterized by a low frequency of using the drugs with their proven effect on prognosis prior to the 2004–2007 reference hospitalization with an increase and a decrease in the frequency of their use on discharge and after 4 and 7 years. During 10 years, β-AB, ACE inhibitors/angiotensin II receptor antagonists, and statins were used mainly at

Impact of medical treatment on lung diffusion capacity in elderly patients with heart failure. Baseline characteristics and 1-year follow up after medical treatment

DEFF Research Database (Denmark)

Petersen, Claus Leth; Kjaer, Andreas

2005-01-01

treatment (baseline) and after 1 year of treatment with diuretics and ACE-inhibitors/angiotensin-II receptor antagonists. Age- and gender-matched healthy volunteers were included as control group. RESULTS: (mean+/-S.E.M.): K(CO) at baseline was 0.95+/-0.06 and 1.25+/-0.04 mmol/min x kPa/l in HF patients......AIM: The aim of this investigation was (1) to study the effect of untreated chronic heart failure (CHF) on alveolar membrane diffusion capacity (transfer coefficient, K(CO)) in elderly patients and (2) to study the impact of the standard regime of medical treatment with diuretics and ACE......-inhibitor/angiotensin-II receptor antagonists on K(CO) in these patients. METHODS: Non-medicated patients (except for diuretics) with symptoms of heart failure (NYHA II-III) and echocardiographically estimated left ventricular ejection fraction (LVEF)

Etabloituminen Venäjän markkinoille : case: Ace Cafe

OpenAIRE

Airaksinen, Joni; Husu, Jukka

2013-01-01

Tämän tutkimuksen tarkoituksena oli selvittää Ace Cafe –kahvilaravintolaketjun etabloitumismahdollisuuksia Venäjän markkinoille. Tutkimuksen tavoitteena oli tuottaa kohdeyritykselle hyödyllinen entry plan ja tutkia Venäjän sekä erityisesti Pietarin alueen markkinoita ravintola- ja kahvila-alan näkökulmasta. Opinnäytetyö tehtiin toimeksiantona Ace Corner Finland Oy:lle. Tutkimus oli kvalitatiivinen eli laadullinen tutkimus, joka tehtiin haastatteluiden ja Venäjän markkinoita luotaavan PEST...

The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease

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A. Zatelli

2016-07-01

Full Text Available Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD; renal diets and angiotensin-converting enzyme (ACE-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4 were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22 received enalapril (0.5 mg/kg, q12h and in group B (n=22 benazepril (0.5 mg/kg, q24h; in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS, serum concentrations of creatinine, blood urea nitrogen (BUN, albumin and total proteins, and urine protein-to-creatinine (UPC ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001. Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05. In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

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

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

2015-10-05

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-1(R) allele), is already present. Furthermore, a duplicated allele (ace-1(D)) 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-1(D) confers less resistance than ace-1(R), the high fitness cost associated with ace-1(R) 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.

Differential diagnosis of depression and Alzheimer's disease with the Addenbrooke's Cognitive Examination-Revised (ACE-R).

Science.gov (United States)

Rotomskis, Augustinas; Margevičiūtė, Ramunė; Germanavičius, Arūnas; Kaubrys, Gintaras; Budrys, Valmantas; Bagdonas, Albinas

2015-04-17

One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer's disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer's Disease (AD). This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer's disease (AD), and 94 age, gender and education matched participants of control group. The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74). ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.

Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis.

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

2014-12-01

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.

Numerical analysis for simulation of condensing vapor bubble using CFD-ACE+

International Nuclear Information System (INIS)

Goyal, P.; Dutta, Anu; Singh, R.K.

2014-01-01

The motion of bubbles is very complex. They may be subject to break-up or coalescence and may appear to move with a spiraling, zigzagging or rocking behavior. Recently, many studies have been carried out to numerically simulate the rising bubble in various conditions by using VOF approach. However, all the above studies were limited to adiabatic bubble where heat and mass transfer between the phases were not considered. In the present work, an attempt was made to capture the behaviour of condensing bubble flowing in a channel, by using commercial CFD code CFD-ACE+ through VOF model. A User-Defined Function was developed to simulate interfacial heat and mass transfer during condensation. The effect of condensation on bubble behavior was analyzed by comparing the behavior of condensing bubble with that of adiabatic bubble. For validation of CFD-ACE UDF of bubble condensation, a comparison was made with the literature quoted experimental data and it agreed well. Through this work an emphasis was put on VOF module along with the development of an UDF for bubble condensation in CFD-ACE+ code. This theoretical study is motivated by the future CFD application and the intent to investigate the capabilities of the CFD-ACE+ package. (author)

BCR SIGNALING INHIBITORS: AN OVERVIEW OF TOXICITIES ASSOCIATED WITH IBRUTINIB AND IDELALISIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

OpenAIRE

Lorenzo Falchi; Jessica M Baron; Carrie Anne Orlikowski; Alessandra Ferrajoli

2016-01-01

The B-cell receptor signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment landscape of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in trea...

Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in Denmark: identification of viral resistance mutations.

Science.gov (United States)

Sølund, Christina; Krarup, Henrik; Ramirez, Santseharay; Thielsen, Peter; Røge, Birgit T; Lunding, Suzanne; Barfod, Toke S; Madsen, Lone G; Tarp, Britta; Christensen, Peer B; Gerstoft, Jan; Laursen, Alex L; Bukh, Jens; Weis, Nina

2014-01-01

The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.

Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

Science.gov (United States)

Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori

2017-08-31

Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (Phemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).

Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era

DEFF Research Database (Denmark)

Warlick, Erica; Ahn, Kwang Woo; Pedersen, Tanya L

2012-01-01

Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to...

Determination of association constants between steroid compounds and albumins by partial-filling ACE.

Science.gov (United States)

Amundsen, Lotta K; Sirén, Heli

2007-10-01

ACE is a popular technique for evaluating association constants between drugs and proteins. However, ACE has not previously been applied to study the association between electrically neutral biomolecules and plasma proteins. We studied the affinity between human and bovine serum albumins (HSA and BSA, respectively) and three neutral endogenous steroid hormones (testosterone, epitestosterone and androstenedione) and two synthetic analogues (methyltestosterone and fluoxymesterone) by applying the partial-filling technique in ACE (PF-ACE). From the endocrinological point of view, the distribution of endogenous steroids among plasma components is of great interest. Strong interactions with albumins suppress the biological activity of steroids. Notable differences in the association constants were observed. In the case of the endogenous steroids, the interactions between testosterone and the albumins were strongest, and those between androstenedione and the albumins were substantially weaker. The association constants, K(b), for testosterone, epitestosterone and androstenedione and HSA at 37 degrees C were 32 100 +/- 3600, 21 600 +/- 1500 and 13 300 +/- 1300 M(-1), respectively, while the corresponding values for the steroids and BSA were 18 800 +/- 1500, 14 000 +/- 400 and 7800 +/- 900 M(-1). Methyltestosterone was bound even more strongly than testosterone, while fluoxymesterone was only weakly bound by the albumins. Finally, the steroids were separated by PF-ACE with HSA and BSA used as resolving components.

Global distribution of upper tropospheric formic acid from the ACE-FTS

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G. González Abad

2009-10-01

Full Text Available We present the first near global upper tropospheric distribution of formic acid (HCOOH observed from space using solar occultation measurements from the Fourier transform spectrometer (FTS on board the Atmospheric Chemistry Experiment (ACE satellite. Using a new set of spectroscopic line parameters recently published for formic acid by Vander Auwera et al. (2007 and Perrin and Vander Auwera (2007, we have retrieved the concentrations of HCOOH between 5 km and the tropopause for ACE-FTS observations from February 2004 to September 2007. We observe a significant seasonal dependence for the HCOOH concentrations related to vegetation growth and biomass burning. We estimate an emission ratio of 0.0051±0.0015 for HCOOH relative to CO for tropical South American fires using a selected set of data for September 2004. Results from the balloon-borne MkIV Fourier transform spectrometer are also presented and compared with the ACE measurements.

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

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Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

2011-10-01

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing.

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de Almeida, Fernando G; Vanzolini, Kenia L; Cass, Quezia B

2017-01-05

Angiotensin converting enzyme (ACE) presents an important role in blood pressure regulation, since that converts angiotensin I to the vasoconstrictor angiotensin II. Some commercially available ACE inhibitors are captopril, lisinopril and enalapril; due to their side effects, naturally occurring inhibitors have been prospected. In order to endorse this research field we have developed a new tool for ACE ligand screening. To this end, ACE was extracted from bovine lung, purified and chemically immobilized in modified ferrite magnetic beads (ACE-MBs). The ACE-MBs have shown a Michaelian kinetic behavior towards hippuryl-histidyl-leucine. Moreover, as proof of concept, the ACE-MBs was inhibited by lisinopril with a half maximal inhibitory concentration (IC 50 ) of 10nM. At the fishing assay, ACE-MBs were able not only to fish out the reference inhibitor, but also one peptide from a pool of tryptic digested BSA. In conclusion, ACE-MBs emerge as new straightforward tool for ACE kinetics determination, inhibition and binder screening. Copyright © 2016 Elsevier B.V. All rights reserved.

Assertion checking environment (ACE) for formal verification of C programs

International Nuclear Information System (INIS)

Sharma, Babita; Dhodapkar, S.D.; Ramesh, S.

2003-01-01

In this paper we describe an Assertion Checking Environment (ACE) for compositional verification of programs, which are written in an industrially sponsored safe subset of C programming language called MISRA C [Guidelines for the Use of the C Language in Vehicle Based Software, 1998]. The theory is based on Hoare logic [Commun. ACM 12 (1969) 576] and the C programs are verified using static assertion checking technique. First the functional specifications of the program, captured in the form of pre- and post-conditions for each C function, are derived from the specifications. These pre- and post-conditions are then introduced as assertions (also called annotations or formal comments) in the program code. The assertions are then proved formally using ACE and theorem proving tool called Stanford Temporal Prover [The Stanford Temporal Prover User's Manual, 1998]. ACE has been developed by us and consists mainly of a translator c2spl, a GUI and some utility programs. The technique and tools developed are targeted towards verification of real-time embedded software

ACE-FTS ozone, water vapour, nitrous oxide, nitric acid, and carbon monoxide profile comparisons with MIPAS and MLS

Science.gov (United States)

Sheese, Patrick E.; Walker, Kaley A.; Boone, Chris D.; Bernath, Peter F.; Froidevaux, Lucien; Funke, Bernd; Raspollini, Piera; von Clarmann, Thomas

2017-01-01

The atmospheric limb sounders, ACE-FTS on the SCISAT satellite, MIPAS on ESA's Envisat satellite, and MLS on NASA's Aura satellite, take measurements used to retrieve atmospheric profiles of O3, N2O, H2O, HNO3, and CO. Each was taking measurements between February 2004 and April 2012 (ACE-FTS and MLS are currently operational), providing hundreds of profile coincidences in the Northern and Southern hemispheres, and during local morning and evening. Focusing on determining diurnal and hemispheric biases in the ACE-FTS data, this study compares ACE-FTS version 3.5 profiles that are collocated with MIPAS and MLS, and analyzes the differences between instrument retrievals for Northern and Southern hemispheres and for local morning and evening data. For O3, ACE-FTS is typically within ±5% of mid-stratospheric MIPAS and MLS data and exhibits a positive bias of 10 to 20% in the upper stratosphere - lower mesosphere. For H2O, ACE-FTS exhibits an average bias of -5% between 20 and 60 km. For N2O, ACE-FTS agrees with MIPAS and MLS within -20 to +10% up to 45 km and 35 km, respectively. For HNO3, ACE-FTS typically agrees within ±10% below 30 km, and exhibits a positive bias of 10 to 20% above 30 km. With respect to MIPAS CO, ACE-FTS exhibits an average -11% bias between 28 and 50 km, and at higher altitudes a positive bias on the order of 10% (>100%) in the winter (summer). With respect to winter MLS CO, ACE-FTS is typically within ±10% between 25 and 40 km, and has an average bias of -11% above 40 km.

Validation of Addenbrooke's cognitive examination (ACE) in a Persian-speaking population.

Science.gov (United States)

Pouretemad, Hamid Reza; Khatibi, Ali; Ganjavi, Anahita; Shams, Jamal; Zarei, Mojtaba

2009-01-01

Use of reliable screening and diagnostic tests for assessment of cognitive abilities in neurological patients is rapidly increasing in clinical practice. This is due to the increase in the prevalence of dementias and the raised awareness of cognitive impairment in neurological disorders. Two well-known bedside screening tests for dementias among the English-speaking population are the Mini Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination (ACE). However, such tests have not been developed for the Persian-speaking population, which is estimated at 120 million worldwide. In this study we developed the Persian ACE and MMSE, adopted from the English version. We also assessed the sensitivity and specificity of these tests in the identification of Alzheimer's disease (AD) and mild cognitive impairment (MCI). We found that the Persian ACE at a cutoff point of 84, has a sensitivity of 93% and a specificity of 91% in discriminating MCI from a normal population; at 78, the test has a sensitivity of 73% and a specificity of 93% in differentiating MCI from AD, and at a similar cutoff point has a sensitivity of 100% and specificity of 96% in discriminating AD from a normal population. We conclude that the Persian ACE is a valuable tool in clinical practice in the Persian-speaking population. 2009 S. Karger AG, Basel.

Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

Science.gov (United States)

Scheen, André J

2015-07-01

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin). These SGLT2 inhibitors share similar pharmacokinetic characteristics with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug. Pharmacokinetic parameters are slightly altered in the case of chronic kidney disease (CKD). While no dose adjustment is required in the case of mild CKD, SGLT2 inhibitors may not be used or only at a lower daily dose in patients with moderate CKD. Furthermore, the pharmacodynamic response to SGLT2 inhibitors as assessed by urinary glucose excretion declines with increasing severity of renal impairment as assessed by a reduction in the estimated glomerular filtration rate. Nevertheless, the glucose-lowering efficacy and safety of SGLT2 inhibitors are almost comparable in patients with mild CKD as in patients with normal kidney function. In patients with moderate CKD, the efficacy tends to be dampened and safety concerns may occur. In patients with severe CKD, the use of SGLT2 inhibitors is contraindicated. Thus, prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor. The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention because of preliminary favourable results

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

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Diana M Calderón-Noreña

2015-04-01

Full Text Available 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

The angiotensin converting enzyme inhibitor trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function

DEFF Research Database (Denmark)

Abdulla, Jawdat; Burchardt, Hans; Z Abildstrøm, Steen

2003-01-01

/day of furosemide was spared in trandolapril arm (P=0.001). CONCLUSIONS: Trandolapril had a mild diuretic-sparing effect. These results emphasis the importance of explaining to patients that ACE inhibitors provide protection against death and hospitalisation for heart failure but do not have any significant effect...

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

Science.gov (United States)

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.

Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS)

Science.gov (United States)

Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.

2018-01-01

The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

ACES MWL data analysis center at SYRTE

Science.gov (United States)

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

2017-12-01

The ACES-PHARAO mission aims at operating a cold-atom caesium clock on board the International Space Station, and performs two-way time transfer with ground terminals, in order to allow highly accurate and stable comparisons of its internal timescale with those found in various metrology institutes. Scientific goals in fundamental physics include tests of the gravitational redshift with unprecedented accuracy, and search for a violation of the Lorentz local invariance. As launch is coming closer we are getting ready to process the data expected to come from ACES Microwave Link (MWL) once on board the International Space Station. Several hurdles have been cleared in our software in the past months, as we managed to implement algorithms that reach target accuracy for ground/space desynchronisation measurement. I will present the current status of data analysis preparation, as well as the activities that will take place at SYRTE in order to set up its data processing center.

Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis

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Sang Wook Kang

2016-01-01

Full Text Available The relationship between polymorphism of the angiotensin I converting enzyme (ACE gene and chronic obstructive pulmonary disease (COPD has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR, and 95% confidence interval (95% CI were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p>0.05 in each model. In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population (codominant 2, OR = 3.126, 95% CI = 1.919–5.093, p0.05 in each model. In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample.

Chronic effects of fluoxetine, a selective inhibitor of serotonin uptake, on neurotransmitter receptors

International Nuclear Information System (INIS)

Wong, D.T.; Reid, L.R.; Bymaster, F.P.; Threlkeld, P.G.

1985-01-01

Fluoxetine administration to rats dose of 10mg/kg i.p. daily up to 12 or 24 days failed to change the concentration-dependent binding of [ 3 H]WB4101, [ 3 H]clonidine and [ 3 H]dihydroalprenolol to α 1 -, α 2 - and β-adrenergic receptors, respectively; [ 3 H]quinuclidinyl benzilate to muscarinic receptors; [ 3 H]pyrilamine to histamine H 1 receptors and [ 3 H]naloxone to opiate receptors. Persistent and significant decreases in receptor number (Bsub(max) value) without changes in the dissociation constant (Ksub(D) value) of [ 3 H]5-HT binding in cortical membranes were observed upon chronic treatment with fluoxetine administered either by intraperitoneal injection or incorporation in the diet. A detectable reduction of 5-HT 1 receptor number occured after once-daily injections of fluoxetine at 10mg/kg i.p. within 49 hours. After pretreatment for 3 days with p-chlorophenylalanine, an inhibitor of 5-HT synthesis, followed by repeated administration of fluoxetine, 5-HT 1 receptor numbers were higher than those of normal rats, suggesting a dependence on synaptic concentration of 5-HT for fluoxetine to affect a receptor down-regulation. These studies provide further evidence for the selectivity of fluoxetine as an inhibitor of 5-HT reuptake, resulting in a selective down-regulation of 5-HT 1 receptors in the cerebal cortex of rat brain. (Author)

The Utility of the Mini-Addenbrooke's Cognitive Examination as a Screen for Cognitive Impairment in Elderly Patients with Chronic Kidney Disease and Diabetes.

Science.gov (United States)

Hobson, Peter; Rohoma, Kamel H; Wong, Stephen P; Kumwenda, Mick J

2016-01-01

We tested the utility of the Mini-Addenbrooke's Cognitive Examination (M-ACE) in a cohort of older adults with chronic kidney disease (CKD) and diabetes. The M-ACE was administered to 112 CKD and diabetes patients attending a nephrology clinic. Cognitive impairment was based upon patient, informant, and case review, neuropsychological assessment, and application of criteria for mild cognitive impairment (MCI) and the Diagnostic and Statistical Manual of Mental Disorders, fifth edition for dementia. The M-ACE was also compared to the Mini-Mental State Examination (MMSE). Upon assessment, 52 patients had normal cognitive function, 33 had MCI, and 27 had dementia. The area under the receiver operating curve for the M-ACE was 0.96 (95% CI 0.95-1.00). The sensitivity and specificity for a dementia diagnosis were 0.96 and 0.84 at the cut point <25 and 0.70 and 1.00 at the cut point <21. Mean M-ACE scores differed significantly between normal, demented, and MCI groups ( p < 0.001), and compared to the MMSE, the M-ACE did not suffer from ceiling effects. The M-ACE is an easily administered test with good sensitivity and specificity to capture and assist in the diagnosis of MCI or dementia in patients with CKD and diabetes.

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

Science.gov (United States)

Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

2017-03-01

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Structural determinants for binding to angiotensin converting enzyme 2 (ACE2 and angiotensin receptors

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Daniel eClayton

2015-01-01

Full Text Available Angiotensin converting enzyme 2 (ACE2 is a zinc carboxypeptidase involved in the renin angiotensin system (RAS and inactivates the potent vasopressive peptide angiotensin II (Ang II by removing the C-terminal phenylalanine residue to yield Ang1-7. This conversion inactivates the vasoconstrictive action of Ang II and yields a peptide that acts as a vasodilatory molecule at the Mas receptor and potentially other receptors. Given the growing complexity of RAS and level of cross-talk between ligands and their corresponding enzymes and receptors, the design of molecules with selectivity for the major RAS binding partners to control cardiovascular tone is an on-going challenge. In previous studies we used single β-amino acid substitutions to modulate the structure of Ang II and its selectivity for ACE2, AT1R and angiotensin type 2 (AT2R receptor. We showed that modification at the C-terminus of Ang II generally resulted in more pronounced changes to secondary structure and ligand binding, and here we further explore this region for the potential to modulate ligand specificity. In this study, 1 a library of forty-seven peptides derived from the C-terminal tetra-peptide sequence (-IHPF of Ang II was synthesised and assessed for ACE2 binding, 2 the terminal group requirements for high affinity ACE2 binding were explored by and N- and C-terminal modification, 3 high affinity ACE2 binding chimeric AngII analogues were then synthesized and assessed, 4 the structure of the full-length Ang II analogues were assessed by circular dichroism, and 5 the Ang II analogues were assessed for AT1R/AT2R selectivity by cell-based assays. Studies on the C-terminus of Ang II demonstrated varied specificity at different residue positions for ACE2 binding and four Ang II chimeric peptides were identified as selective ligands for the AT2 receptor. Overall, these results provide insight into the residue and structural requirements for ACE2 binding and angiotensin receptor

Advanced Course in Engineering (ACE) - Cyber Security Boot Camp

National Research Council Canada - National Science Library

Older, Susan

2008-01-01

.... ACE achieved its stated objectives by completely immersing students in the cyber-security discipline for ten weeks, through a combination of intense coursework, open-ended problems, and internship...

Effects of exercise training on circulating and skeletal muscle renin-angiotensin system in chronic heart failure rats.

Science.gov (United States)

Gomes-Santos, Igor Lucas; Fernandes, Tiago; Couto, Gisele Kruger; Ferreira-Filho, Julio César Ayres; Salemi, Vera Maria Cury; Fernandes, Fernanda Barrinha; Casarini, Dulce Elena; Brum, Patricia Chakur; Rossoni, Luciana Venturini; de Oliveira, Edilamar Menezes; Negrao, Carlos Eduardo

2014-01-01

Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal

IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

Directory of Open Access Journals (Sweden)

Toshifumi Tezuka

Full Text Available Plasminogen activator inhibitor (PAI-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp. IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

Science.gov (United States)

Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

2015-01-01

Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

DAF: differential ACE filtering image quality assessment by automatic color equalization

Science.gov (United States)

Ouni, S.; Chambah, M.; Saint-Jean, C.; Rizzi, A.

2008-01-01

Ideally, a quality assessment system would perceive and measure image or video impairments just like a human being. But in reality, objective quality metrics do not necessarily correlate well with perceived quality [1]. Plus, some measures assume that there exists a reference in the form of an "original" to compare to, which prevents their usage in digital restoration field, where often there is no reference to compare to. That is why subjective evaluation is the most used and most efficient approach up to now. But subjective assessment is expensive, time consuming and does not respond, hence, to the economic requirements [2,3]. Thus, reliable automatic methods for visual quality assessment are needed in the field of digital film restoration. The ACE method, for Automatic Color Equalization [4,6], is an algorithm for digital images unsupervised enhancement. It is based on a new computational approach that tries to model the perceptual response of our vision system merging the Gray World and White Patch equalization mechanisms in a global and local way. Like our vision system ACE is able to adapt to widely varying lighting conditions, and to extract visual information from the environment efficaciously. Moreover ACE can be run in an unsupervised manner. Hence it is very useful as a digital film restoration tool since no a priori information is available. In this paper we deepen the investigation of using the ACE algorithm as a basis for a reference free image quality evaluation. This new metric called DAF for Differential ACE Filtering [7] is an objective quality measure that can be used in several image restoration and image quality assessment systems. In this paper, we compare on different image databases, the results obtained with DAF and with some subjective image quality assessments (Mean Opinion Score MOS as measure of perceived image quality). We study also the correlation between objective measure and MOS. In our experiments, we have used for the first image

Improvement of ACE inhibitory activity of casein hydrolysate by Maillard reaction with xylose.

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Hong, Xu; Meng, Jun; Lu, Rong-Rong

2015-01-01

The Maillard reaction is widely used to improve the functional properties or biological activities of food. The purpose of this study was to investigate the effect of the Maillard reaction on angiotensin I converting enzyme (ACE) inhibitory activity in a casein hydrolysate-xylose system. Two-step hydrolysis was used to prepare casein ACE inhibitory peptides. Maillard reaction products (MRPs) were prepared by heating hydrolyzed casein with xylose at pH 8.0, 110 °C for up to 16 h. The results showed that the content of free amino group decreased (P Maillard reaction (P reaction in the MRPs. The study shows that the Maillard reaction under appropriate conditions can improve the ACE inhibitory activity of casein hydrolysate effectively. © 2014 Society of Chemical Industry.

Validation of the Atmospheric Chemistry Experiment (ACE version 2.2 temperature using ground-based and space-borne measurements

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R. J. Sica

2008-01-01

Full Text Available An ensemble of space-borne and ground-based instruments has been used to evaluate the quality of the version 2.2 temperature retrievals from the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS. The agreement of ACE-FTS temperatures with other sensors is typically better than 2 K in the stratosphere and upper troposphere and 5 K in the lower mesosphere. There is evidence of a systematic high bias (roughly 3–6 K in the ACE-FTS temperatures in the mesosphere, and a possible systematic low bias (roughly 2 K in ACE-FTS temperatures near 23 km. Some ACE-FTS temperature profiles exhibit unphysical oscillations, a problem fixed in preliminary comparisons with temperatures derived using the next version of the ACE-FTS retrieval software. Though these relatively large oscillations in temperature can be on the order of 10 K in the mesosphere, retrieved volume mixing ratio profiles typically vary by less than a percent or so. Statistical comparisons suggest these oscillations occur in about 10% of the retrieved profiles. Analysis from a set of coincident lidar measurements suggests that the random error in ACE-FTS version 2.2 temperatures has a lower limit of about ±2 K.

The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample.

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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.

Association of plasminogen activator inhibitor-1 and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women

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Fatemeh Shakarami

2015-10-01

Full Text Available Background: Recurrent pregnancy loss (RPL defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1 and angiotensin converting enzyme (ACE genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%, and 5 controls (5% (p=0.006 so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84. In addition, 7 patients (7 %, and no one from the control group, were homozygote (I/I for ACE polymorphism (p=0.034, suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

NARCIS (Netherlands)

A. Persu (Alexandre); M. Lambert (Michael); J. Deinum (Jacob); M. Cossu (Marta); N. de Visscher (Nathalie); L. Irenge (Leonid); J. Ambroise (Jerôme); J.M. Minon (Jean-Marc); A.B. Nesterovitch (Andrew); A. Churbanov (Alexander); I.A. Popova (Isolda); S.M. Danilov (Sergei); A.H.J. Danser (Jan); J.L. Gala (Jean-Luc)

2013-01-01

textabstractBackground: Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and

A novel splice-site mutation in angiotensin I-converting enzyme (ACE) gene, c.3691+1G>A (IVS25+1G>A), causes a dramatic increase in circulating ace through deletion of the transmembrane anchor

NARCIS (Netherlands)

Persu, A.; Lambert, M.; Deinum, J.; Cossu, M.; Visscher, N. de; Irenge, L.; Ambroise, J.; Minon, J.M.; Nesterovitch, A.B.; Churbanov, A.; Popova, I.A.; Danilov, S.M.; Danser, A.H.; Gala, J.L.

2013-01-01

BACKGROUND: Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. METHODS AND RESULTS: Two

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

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Catalá-López, Ferrán; Macías Saint-Gerons, Diego; González-Bermejo, Diana; Rosano, Giuseppe M; Davis, Barry R; Ridao, Manuel; Zaragoza, Abel; Montero-Corominas, Dolores; Tobías, Aurelio; de la Fuente-Honrubia, César; Tabarés-Seisdedos, Rafael; Hutton, Brian

2016-03-01

Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

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Ferrán Catalá-López

2016-03-01

Full Text Available Medications aimed at inhibiting the renin-angiotensin system (RAS have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014. Interventions of interest were angiotensin-converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and direct renin (DR inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants, with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18, ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19, DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81, and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38. For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40, ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29, DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57, and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84. No significant differences were showed between ACE inhibitors and ARBs with

Strain differences in angiotensin-converting enzyme and angiotensin II type I receptor expression. Possible implications for experimental chronic renal transplant failure

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Smit-van Oosten, A; Henning, RH; van Goor, H

Background The Fisher to Lewis (F-L) model of renal transplantation (Rtx) is widely used. Rtx from F to L without immunosuppressive treatment results in 50% survival, whereas L to F results in survival rates similar to syngrafts. When treated with an angiotensin-converting enzyme (ACE) inhibitor or

Association between ACE gene I/D polymorphism and clinical presentation and prognosis of sarcoidosis.

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Alía, P; Mañá, J; Capdevila, O; Alvarez, A; Navarro, M A

2005-01-01

Serum angiotensin converting enzyme (SACE) concentration is considered a marker of sarcoidosis activity. This concentration is influenced by an insertion/deletion (I/D) polymorphism of the ACE gene, such that SACE levels follow the pattern DD>ID>II. The aim of our work was to study the relationship between I/D polymorphism and susceptibility to sarcoidosis, as well as the relation between this polymorphism and the clinical presentation and evolution of the disease in 177 sarcoidosis patients. A group of 104 individuals without sarcoidosis was included as control. Genotyping was done by a polymerase chain reaction (PCR) method, and SACE concentration at diagnosis was determined by a kinetic method. No differences were observed in genotype or allele distributions between patients and controls, nor between patients considering the type of presentation (Löfgren versus non-Löfgren) and evolution of the disease (acute versus chronic). As reported for healthy populations, SACE concentrations followed the pattern DD>ID>II in sarcoidosis patients, but significant differences between genotypes existed only in the Löfgren group (p = 0.003) and in acute patients (p = 0.02). SACE concentrations at diagnosis were lower in acute patients (p = 0.05) and in Löfgren's syndrome (p = 0.04), but this seemed to occur only in ID individuals (p = 0.02 and p = 0.01, respectively). No relation was thus found between I/D polymorphism and susceptibility to sarcoidosis, but ACE I/D genotyping may improve the assessment of disease activity, both at diagnosis and during the follow-up of treated and untreated patients.

ACE I/D polymorphism in Indian patients with hypertrophic cardiomyopathy and dilated cardiomyopathy

DEFF Research Database (Denmark)

Rai, Taranjit Singh; Dhandapany, Perundurai Subramaniam; Ahluwalia, Tarun Veer Singh

2008-01-01

The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM).......The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM)....

Polymorphism of the ACE gene and the risk of obstructive sleep apnoea.

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Chmielewska, Izabela; Mlak, Radosław; Krawczyk, Paweł; Czukiewska, Ewa; Milanowski, Janusz

2013-01-01

Obstructive sleep apnoea/hypopnea syndrome (OSA) is characterized by obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. Among the candidate genes affecting the risk of OSA, genes whose polymorphisms influence the development of diseases with similar pathogenesis such as OSA could be listed: APOE, genes for leptin and leptin receptor, TNFA1, ADRB2 and ACE (gene for angiotensin-converting enzyme). Until now there has been a confirmed relationship between ACE gene polymorphism and cardiovascular diseases, but its effect on the incidence of OSA is debatable. The aim of this study was to investigate the effect of ACE gene insertion/deletion (I/D) polymorphism on the risk of OSA. Fifty-five patients with confirmed diagnose of OSA and qualified to CPAP therapy entered the study. The control group included 50 subjects who did not complain of any sleep related symptoms. Diagnose of OSA was set on the basis of full overnight polysomnography together with Epworth Sleepiness Scale according to American Academy of Sleep Medicine guidelines. DNA was isolated from peripheral blood leukocytes with Qiagen DNA mini Kit. ACE gene polymorphism was determined in genomic DNA using allele specific polymerase chain reaction. Different sizes of PCR products were observed on agarose gel electrophoresis. There were non-significant differences in the frequency of ACE genotypes. However, allele D had significantly lower prevalence in the study group than in the control group. (χ(2) = 4.25 p = 0.04). Moreover, I allele carriers had a threefold greater risk of developing OSA (HR = 2.748, 95% CI = 1.029-7.340, p gene polymorphism might be useful to determine the risk of developing OSA in clinically predisposed patients.

SU-F-T-22: Clinical Implications When Using TG-186 (ACE) Heterogeneity Software

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Likhacheva, A; Grade, E; Sadeghi, A; Sokolowski, T [Arizona Cancer Specialists, Mesa, AZ (United States)

2016-06-15

Purpose: The purpose of this study is to compare dosimetric calculations using traditional TG-43 formalism and Oncentra Brachy Advanced Collapsed cone Engine (ACE) TG-186 calculation algorithm in clinical setting. Methods: We analyzed dosimetry of four patients treated with accelerated partial breast irradiation using a multi-channel intracavitary device (SAVI). All patients were treated to 34 Gy in 10 fractions using a high-dose-rate (192) Ir source. The plans were designed and treated using the TG-43 model. ACE was used to assess the effect heterogeneity correction on various dosimetric parameters. Mass density was estimated using Hounsfield units. Results: Compared to TG-43 formalism, ACE estimated lower doses to targets and organs at risk. The mean difference was 19.8% (range 15.3–24.1%) for PTV-eval V200, 12.0% (range 9.7–17.7%) for PTV-eval V150, 4.3% (range 3.3–6.5%) for PTV-eval D95, 3.3% (range 1.4–5.4%) for PTV-eval D90, 5.4% (range 2.9–9.9%) for maximum rib dose, and 5.7% (2.4–7.4%) for maximum skin dose. There was no correlation between the magnitude of the difference and the PTV-eval volume, air volume, or tissue-applicator conformance. Conclusion: Based on our preliminary study, the TG-43 algorithm appears to overestimate the dose to targets and organs at risk when compared to the ACE TG-186 software. We hypothesize that air adjacent to the SAVI struts contributes to lack of scatter thereby contributing a significant difference in dose calculation when using ACE. We believe that ACE calculation provides a more realistic isodose distribution than TG-43. We plan to further investigate the impact of heterogeneity correction on brachytherapy planning for a wide variety of clinical scenarios, include skin, cervix/uterus, prostate, and lung.

Equine protease inhibitor system as a marker for the diagnosis of chronic obstructive pulmonary disease (COPD

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Vinocur Myriam E.

2005-01-01

Full Text Available The protease inhibitor system (PI was investigated to ascertain if it can be used as a marker of chronic obstructive pulmonary disease (COPD in thoroughbred horses. Serum samples were taken from healthy thoroughbreds (n = 13 and those diagnosed as having COPD (n = 24 or inflammatory airway disease (IAD, n = 38 as well as from 3,600 undiagnosed thoroughbred horses. PI allelic and genotypic frequencies were estimated using protein electrophoresis on starch and polyacrylamide gels. The four groups of horses showed high genotypic similarity and none of the observed alleles or genotypes of the equine PI system were found to be associated with COPD.

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

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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.

Is the association between ACE genes and blood pressure mediated by postnatal growth during the first 3 years?

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Min, JungWon; Kim, Young Ju; Lee, Hwayoung; Park, Eun Ae; Cho, Su Jin; Hong, Young Mi; Oh, Se-Young; Ha, Eunhee; Kang, DukHee; Park, Hyesook

2012-06-01

Unlike the defined role of angiotensin-converting enzyme (ACE) gene in adult hypertension, ACE gene did not show direct influence on childhood blood pressure (BP), rather, seemed to be related to childhood growth with age-dependent characteristics. Thus, we examined intermediate effects of postnatal growth between the ACE polymorphisms and BP. We analyzed data from 257 children born in 2001-04 at Ewha Womans University Hospital in Seoul, Korea, and followed them up until 3 years of age. Children with excessive adiposity had higher BP, as rapid growers did to no-change and decelerated growers. The ACE II genotype was associated with greater growth acceleration than the DD genotype (II: 46.8% vs. DD: 23.9%), and with a higher BP. The interactions between ACE genotype and adiposity at age 3 were significant on the BP levels. The highest BP increase with the same degree of adiposity was observed in those with the II genotype [β (SE) for BMI: 1.9 (0.9), p=0.04]; particularly, only rapid grown II carriers demonstrated statistical significance on this linear association. These results suggested that ACE polymorphisms and BP association are mediated by postnatal growth. Further studies are required to determine the age-specific ACE genetic effects and its undefined biological mechanism. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pulmonary sarcoidosis : CT findings and correlation with sACE level and PFT

International Nuclear Information System (INIS)

Ji, Eun Kyung; Song, Koun Sik; Lee, Jin Seong; Kwon, Jin Sook; Park, Kwang Bo; Lim, Tae Whan

1997-01-01

To assess CT findings of pulmonary sarcoidosis and correlate these with sACE level and PFT Between 1989 and 1995, 14 patients (4 men and 10 women, aged between 28 and 55 years) with histologically confirmed pulmonary sarcoidosis were consecutively selected. HRCT scans were performed in 12 patients and conventional CT scans in two. CT findings were reviewed by three radiologists, and were correlated with the index of disease activity based on sACE level and pulmonary function test. Pulmonary parenchymal abnormalities were seen in all patients;small nodules of less than 3mm in diameter were seen in eight. Other abnormalities were nodules of more than 3mm in diameter (n=7), confluent nodules (n=5), ground glass opacity (n=5), patchy areas of consolidation with air bronchogram (n=5), and architectural distortion (n=3). The upper lung zone was more frequently involved than the middle or lower zone. In ten patients, the paripheral interstitum was predominantly involved, while only three patients showed predominant peribronchovascular involvement. Lymphadenopathy was noted in 13. There was no correlation between sACE level, the results of a pulmonary function test and the extent of parenchymal involvement. HRCT is valuable for the identification, characterization, and determination of the extent to which parenchymal lung is involved in sarcoidosis. The extent of this involvement does not correlate with sACE level and pulmonary function test results

Angiotensin-converting enzyme I/D polymorphism in chronic obstructive pulmonary disease

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Pabst S

2009-12-01

Full Text Available Abstract Study objective The etiology of chronic obstructive lung disease (COPD is unclear. It is supposed to be the product of an exogenous antigenic stimulus, such as tobacco smoke, and an endogenous genetic susceptibility. The angiotensin-converting enzyme (ACE gene contains a polymorphism based on the presence (insertion [I] or absence (deletion [D] of a 287-bp nonsense domain, resulting in three different genotypes (II, ID and DD. The aim of the study was to find out whether the ACE gene polymorphism can determine the course of COPD. Patients and design We genotyped 152 Caucasian patients with COPD and 158 healthy controls for the ACE (I/D polymorphism. We divided the COPD group into one group of 64 patients with a stable course of disease, defined as less than three hospitalizations over the last three years due to COPD, and another group of 88 patients with an instable course with more than three hospitalizations. Results The I-allele was significantly associated with an increased risk for COPD in a dominant model (OR 1.67 (95% CI 1.00 to 2.78, p = 0.048, but not in a recessive or co-dominant model. Moreover, the I-allele of ACE (I/D was significantly increased in patients with a stable course of COPD (p = 0.012 compared with controls. In a dominant model (II/ID v DD we found an even stronger association between the I-allele and a stable course of COPD (OR 3.24 (95% CI 1.44 to 7.31, p = 0.003. Conclusion These data suggest that the presence of an ACE I-allele determines a stable course of COPD.

Analysis of whey protein hydrolysates: peptide profile and ACE inhibitory activity

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Marialice Pinto Coelho Silvestre

2012-12-01

Full Text Available The aim of this study was to prepare enzymatic hydrolysates from whey protein concentrate with a nutritionally adequate peptide profile and the ability to inhibit angiotensin-converting enzyme (ACE activity. The effects of the type of enzyme used (pancreatin or papain, the enzyme:substrate ratio (E:S ratio=0.5:100, 1:100, 2:100 and 3:100 and the use of ultrafiltration (UF were investigated. The fractionation of peptides was performed by size-exclusion-HPLC, and the quantification of the components of the chromatographic fractions was carried out by a rapid Corrected Fraction Area method. The ACE inhibitory activity (ACE-IA was determined by Reverse Phase-HPLC. All parameters tested affected both the peptide profile and the ACE-IA. The best peptide profile was achieved for the hydrolysates obtained with papain, whereas pancreatin was more advantageous in terms of ACE-IA. The beneficial effect of using a lower E:S ratio on the peptide profile and ACE-IA was observed for both enzymes depending on the conditions used to prepare the hydrolysates. The beneficial effect of not using UF on the peptide profile was observed in some cases for pancreatin and papain. However, the absence of UF yielded greater ACE-IA only when using papain.O objetivo deste estudo foi preparar hidrolisados enzimáticos do concentrado proteico do soro de leite com perfil peptídico nutricionalmente adequado e com capacidade para inibir a atividade da enzima conversora da angiotensina (ECA. Os efeitos do tipo de enzima usado (pancreatina ou papaína, da relação enzima:substrato (E:S=0,5:100, 1:100, 2:100 e 3:100 e do uso da ultrafiltração (UF foram investigados. O fracionamento dos peptídeos foi feito por CLAE de exclusão molecular e a quantificação dos componentes das frações cromatográficas foi realizada pelo método da Área Corrigida da Fração. A atividade inibitória da ECA (AI-ECA foi determinada por CLAE de fase reversa. Todos os parâmetros testados afetaram

AMBULATORY BLOOD PRESSURE PATTERNS IN CHILDREN WITH CHRONIC KIDNEY DISEASE

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Samuels, Joshua; Ng, Derek; Flynn, Joseph T.; Mitsnefes, Mark; Poffenbarger, Tim; Warady, Bradley A.; Furth, Susan

2012-01-01

Ambulatory blood pressure monitoring (ABPM) is the best method of detecting abnormal blood pressure (BP) in patients with chronic kidney disease (CKD), whose hypertension may be missed with office BP measurements. We report ABPM findings in 332 children 1 year after entry in the Chronic Kidney Disease in Children (CKiD) cohort study. All subjects underwent casual and ambulatory BP measurement. BP was categorized based on casual and ABPM results into normal, white coat, masked, and ambulatory hypertension. Only half of the subjects had a normal ABPM. BP load was elevated (>25%) in 52% (n= 172) while mean BP was elevated in 32% (n= 105). In multivariate analysis, those using an ACE inhibitor (ACEi) were 89% more likely to have a normal ABPM than those who did not report using an ACEi (OR: 1.89, 95%CI: 1.17, 3.04). For every 20% faster decline in annualized GFR change, the odds of an abnormal ABPM increased 26% (OR: 1.26, 95%CI: 0.97, 1.64; p= 0.081). A 2.25 fold increase in urine protein:creatinine ratio annualized change was associated with a 39% higher odds of an abnormal ABPM (OR: 1.39, 95%CI: 1.06, 1.82; p= 0.019). Abnormalities on ABPM are common in children with CKD, and are strongly associated with known risk factors for end stage renal disease. Individuals on ACEi were less likely to have abnormal ABPM, suggesting a possible therapeutic intervention. ABPM should be used to monitor risk and guide therapy in children with CKD. PMID:22585950

The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model

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Chih-Che Lin

2014-01-01

Full Text Available Serine protease inhibitors reportedly attenuated airway inflammation and had antioxidant in multiorgan. However, the effects of the serine protease inhibitors nafamostat mesilate (FUT, gabexate mesilate (FOY, and ulinastatin (UTI on a long-term challenged mouse model of chronic asthma are unclear. BALB/c mice (6 mice/group were intratracheally inoculated with five doses of Dermatophagoides pteronyssinus (Der p; 50 μL, 1 mg/mL at one-week intervals. Therapeutic doses of FUT (0.0625 mg/kg, FOY (20 mg/kg, or UTI (10,000 U/kg were, respectively, injected intraperitoneally into these mice. Control mice received sterile PBS. At 3 days after the last challenge, mice were sacrificed to assess airway hyperresponsiveness (AHR, remodeling, and inflammation; lung histological features; and cytokine expression profiles. Compared with untreated controls, mice treated with FUT, FOY, and UTI had decreased AHR and goblet cell hyperplasia, decreased eosinophil and neutrophil infiltration, decreased Der p-induced IL-4 levels in serum and IL-5, IL-6, IL-13, and IL-17 levels in bronchoalveolar lavage fluid, and inhibited nuclear factor (NF-κB activity in lung tissues. The serine protease inhibitors FUT, FOY, and UTI have potential therapeutic benefits for treating asthma by downregulating Th2 cytokines and Th17 cell function and inhibiting NF-κB activation in lung tissue.

High serum ACE activity predicts severe hypoglycaemia over time in patients with type 1 diabetes

DEFF Research Database (Denmark)

Færch, Louise; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2011-01-01

High serum angiotensin-converting enzyme (ACE) activity is associated with increased risk of severe hypoglycaemia (SH) within 1 year in type 1 diabetes. We wanted to find out whether ACE activity is stable over time and predicts SH beyond 1 year, and if gender differences exist in the association...

Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography

International Nuclear Information System (INIS)

Sakaguchi, K.; Chai, S.Y.; Jackson, B.; Johnston, C.I.; Mendelsohn, F.A.

1988-01-01

Inhibition of angiotensin converting enzyme (ACE) in serum and tissues of rats was studied after administration of lisinopril, an ACE inhibitor. Tissue ACE was assessed by quantitative in vitro autoradiography using the ACE inhibitor [ 125 I]351A, as a ligand, and serum ACE was measured by a fluorimetric method. Following oral administration of lisinopril (10 mg/kg), serum ACE activity was acutely reduced but recovered gradually over 24 hours. Four hours after lisinopril administration, ACE activity was markedly inhibited in kidney (11% of control level), adrenal (8%), duodenum (8%), and lung (33%; p less than 0.05). In contrast, ACE in testis was little altered by lisinopril (96%). In brain, ACE activity was markedly reduced 4 hours after lisinopril administration in the circumventricular organs, including the subfornical organ (16-22%) and organum vasculosum of the lamina terminalis (7%; p less than 0.05). In other areas of the brain, including the choroid plexus and caudate putamen, ACE activity was unchanged. Twenty-four hours after administration, ACE activity in peripheral tissues and the circumventricular organs of the brain had only partially recovered toward control levels, as it was still below 50% of control activity levels. These results establish that lisinopril has differential effects on inhibiting ACE in different tissues and suggest that the prolonged tissue ACE inhibition after a single oral dose of lisinopril may reflect targets involved in the hypotensive action of ACE inhibitors

Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

DEFF Research Database (Denmark)

Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

2010-01-01

Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study.

Science.gov (United States)

Yaqoob, Irfan; Tramboo, Nisar A; Bhat, Irfan A; Pandith, Arshad; Beig, Jahangir R; Hafeez, Imran; Lone, Aijaz A; Shah, Tariq R; Samreen, Sumera

The role of polymorphism of Angiotensin converting enzyme (ACE) gene and ACE activity in etiopathogenesis, prognosis, and many other clinical parameters in the various form of the cardiovascular disease has been established to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy (PPCM) remains an area of active research. The main aim of our study was to see pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on left ventricular performance indices. This single-center case-control study included 45 cases and 70 controls. The diagnosis of PPCM was established clinically and echocardiographically. ACE genotyping was done by polymerase chain reaction (PCR) method in all subjects. The II, ID, and DD genotype was present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253 (95% CI=0.114-0.558; p=0.007), for that of II genotype was 1.93 (95% CI=0.86-4.3; p=0.107) and for DD genotype was 7.225 (95% CI; 1.88-27.6; p=0.0039). Overall frequency of D allele in cases was significantly higher than controls (odds=4.25; 95% CI=2.01-6.7; p=0.0001). Moreover, ejection fraction, left ventricular volume and linear dimensions were worse in patients with DD genotype. ACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically. Copyright © 2017. Published by Elsevier B.V.

Epidemiological patterns of chronic kidney disease in black African elders: A retrospective study in West Africa

Directory of Open Access Journals (Sweden)

Sidy Mohamed Seck

2013-01-01

Full Text Available Chronic kidney disease (CKD is frequently described in elders. This study describes the epidemiological patterns of patients ≥60 years old admitted in our department during one year. The prevalence of CKD was 10.8% (60/552. The mean age of the patients was 70.5 years (60-84 years and the sex ratio (male:female was 1.08. The mean serum creatinine level was 7.10 mg/dL (1.31-25.0 mg/dL and more than two-third of the patients presented CKD stage 4-5. Causes of CKD were dominated by hypertension (30% and diabetes (25%. Prevalence of inpatients aged 60-69 years old was higher than in those ≥80 years old but lower than that in patients aged 70-79 years. At admission, 83.3% of the patients were hypertensive, 75% were anemic and 13% presented proteinuria. The main co-morbidities associated with CKD were neoplasms (17% of cases, chronic heart disease (15% of cases and pneumonia (15% of cases. Furosemide was prescribed in 55% of the patients, calcium channel blockers in 23% of the patients and ACE inhibitors in 20% of the patients. Renal replacement therapy was not performed for any patient. Evolution was favorable in the majority of patients (77%, but 23% died mainly because of uremia and infections.

Development of Antennas for Subsurface Radars within ACE

DEFF Research Database (Denmark)

Yarovoy, Alexander; Meincke, Peter; Dauvignac, Jean-Yves

2007-01-01

The paper gives an overview of the joint activities of the ACE-2 partners in the area of antennas for surface penetrating radar. Main areas of joint research and development are discussed and main results of joint activities are presented. Special attention is given to experimental verification...

Effect of enalapril on the progression of chronic renal failure. A randomized controlled trial

DEFF Research Database (Denmark)

Kamper, A L; Strandgaard, S; Leyssac, P P

1992-01-01

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conve......In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril...... or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake.......18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower...

TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

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Belarbi Karim

2012-01-01

Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a

Silencing of HaAce1 gene by host-delivered artificial microRNA disrupts growth and development of Helicoverpa armigera.

Science.gov (United States)

Saini, Ravi Prakash; Raman, Venkat; Dhandapani, Gurusamy; Malhotra, Era Vaidya; Sreevathsa, Rohini; Kumar, Polumetla Ananda; Sharma, Tilak R; Pattanayak, Debasis

2018-01-01

The polyphagous insect-pest, Helicoverpa armigera, is a serious threat to a number of economically important crops. Chemical application and/or cultivation of Bt transgenic crops are the two strategies available now for insect-pest management. However, environmental pollution and long-term sustainability are major concerns against these two options. RNAi is now considered as a promising technology to complement Bt to tackle insect-pests menace. In this study, we report host-delivered silencing of HaAce1 gene, encoding the predominant isoform of H. armigera acetylcholinesterase, by an artificial microRNA, HaAce1-amiR1. Arabidopsis pre-miRNA164b was modified by replacing miR164b/miR164b* sequences with HaAce1-amiR1/HaAce1-amiR1* sequences. The recombinant HaAce1-preamiRNA1 was put under the control of CaMV 35S promoter and NOS terminator of plant binary vector pBI121, and the resultant vector cassette was used for tobacco transformation. Two transgenic tobacco lines expressing HaAce1-amiR1 was used for detached leaf insect feeding bioassays. Larval mortality of 25% and adult deformity of 20% were observed in transgenic treated insect group over that control tobacco treated insect group. The reduction in the steady-state level of HaAce1 mRNA was 70-80% in the defective adults compared to control. Our results demonstrate promise for host-delivered amiRNA-mediated silencing of HaAce1 gene for H. armigera management.